bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quasiperiodic Emissions and Related Particle Precipitation Bursts Observed by the DEMETER Spacecraft
Authors: Němec F. , Hajoš M. , Parrot M. , Santolík O. 
Published: September 2021

AbstractElectromagnetic waves observed in the inner magnetosphere at frequencies between about 0.5 and 4 kHz sometimes exhibit a quasiperiodic (QP) time modulation of the wave intensity with modulation periods from tens of seconds up to a few minutes. Such waves are typically termed “QP emissions” and their origin is still not fully understood. We use a large set of more than 2,000 of these events identified in the low‐altitude DEMETER spacecraft data to check for energetic electron flux variations matching the individual QP wave elements. Altogether, seven such events are identified and their detailed analysis is performed. Energetic electron fluxes are found to be modulated primarily at energies lower than about 250 keV. While the waves may propagate unducted across L‐shells, the energetic particles follow magnetic field lines from the interaction region down to the observation point. This is used to estimate the locations of anticipated generation regions to L‐shells between about 4 and 6, and the respective source radial dimensions to about 0.6–1.2 Earth radii. The frequencies of the events are confined below half of the equatorial electron gyrofrequency in the determined source regions. Finally, it is shown that individual QP elements exhibit a fine inner structure corresponding to the wave bouncing between the hemispheres.
Effect of Poroelastic Coupling and Fracture Dynamics on Solute Transport and Geomechanical Stability
Authors: Tran Minh , Jha Birendra 
Published: September 2021

AbstractThe coupling between solute transport and rock's geomechanical processes, for example, flow‐induced fracture activation, has emerged as an important hydrogeological challenge due to its role in applications such as underground waste disposal, carbon sequestration, contaminant remediation, enhanced oil recovery, and tracer‐based reservoir surveillance. Despite recent advances in modeling flow and geomechanics coupling, a holistic approach to capturing the synergy between fluid flow, solute transport, induced stresses, and fracture mechanics is lacking. This study investigates the rich interplay between these processes within a novel computational framework that is proposed to solve the coupled flow, transport, geomechanics, and fracture mechanics problem. The Embedded Discrete Fracture Modeling (EDFM) method is used to model the flow and transport processes in fractured porous media while an improved Bandis model is employed to capture the fracture mechanical response to flow‐induced stress perturbations. The role of transport‐geomechanics coupling in modulating the spreading and miscibility of a solute slug during viscously unstable flows is examined. We investigate how flow‐transport coupling, parameterized through the solute viscosity contrast and the fracture permeability, influences the stress state and fracture stability in the domain. A case study, inspired by a huff‐n‐puff tracer flowback study, is conducted to investigate the applicability of the proposed framework in the field. A sensitivity analysis is performed to evaluate the dependence of global transport characteristics, permeability evolution, and fracture stability on parameters dictating the strength of coupling between geomechanics, flow, and transport.
An unusual nicotinamide derivative, 4-pyridone-3-carboxamide ribonucleoside (4PYR), is a novel endothelial toxin and oncometabolite
Authors: Mierzejewska Paulina , Kunc Michal , Zabielska-Kaczorowska Magdalena Agnieszka , Kutryb-Zajac Barbara , Pelikant-Malecka Iwona , Braczko Alicja , Jablonska Patrycja , Romaszko Pawel , Koszalka Patrycja , Szade Jolanta , Smolenski Ryszard Tomasz , Slominska Ewa Maria 
Published: September 2021

AbstractOur recent studies identified a novel pathway of nicotinamide metabolism that involves 4-pyridone-3-carboxamide-1-β-D-ribonucleoside (4PYR) and demonstrated its endothelial cytotoxic effect. This study tested the effects of 4PYR and its metabolites in experimental models of breast cancer. Mice were divided into groups: 4T1 (injected with mammary 4T1 cancer cells), 4T1 + 4PYR (4PYR-treated 4T1 mice), and control, maintained for 2 or 21 days. Lung metastasis and endothelial function were analyzed together with blood nucleotides (including 4PYR), plasma amino acids, nicotinamide metabolites, and vascular ectoenzymes of nucleotide catabolism. 4PYR metabolism was also evaluated in cultured 4T1, MDA-MB-231, MCF-7, and T47D cells. An increase in blood 4PYR in 4T1 mice was observed at 2 days. 4PYR and its metabolites were noticed after 21 days in 4T1 only. Higher blood 4PYR was linked with more lung metastases in 4T1 + 4PYR vs. 4T1. Decreased L-arginine, higher asymmetric dimethyl-L-arginine, and higher vascular ecto-adenosine deaminase were observed in 4T1 + 4PYR vs. 4T1 and control. Vascular relaxation caused by flow-dependent endothelial activation in 4PYR-treated mice was significantly lower than in control. The permeability of 4PYR-treated endothelial cells was increased. Decreased nicotinamide but enhanced nicotinamide metabolites were noticed in 4T1 vs. control. Reduced N-methylnicotinamide and a further increase in Met2PY were observed in 4T1 + 4PYR vs. 4T1 and control. In cultured breast cancer cells, estrogen and progesterone receptor antagonists inhibited the production of 4PYR metabolites. 4PYR formation is accelerated in cancer and induces metabolic disturbances that may affect cancer progression and, especially, metastasis, probably through impaired endothelial homeostasis. 4PYR may be considered a new oncometabolite.
Frontal-posterior functional imbalance and aberrant function developmental patterns in schizophrenia
Authors: Sun Dandan , Guo Huiling , Womer Fay Y. , Yang Jingyu , Tang Jingwei , Liu Juan , Zhu Yue , Duan Jia , Peng Zhengwu , Wang Huaning , Tan Qingrong , Zhu Qiwen , Wei Yange , Xu Ke , Zhang Yanbo , Tang Yanqing , Zhang Xizhe , Xu Fuqiang , Wang Jie , Wang Fei 
Published: September 2021

AbstractSchizophrenia (SZ) is a neurodevelopmental disorder. There remain significant gaps in understanding the neural trajectory across development in SZ. A major research focus is to clarify the developmental functional changes of SZ and to identify the specific timing, the specific brain regions, and the underlying mechanisms of brain alterations during SZ development. Regional homogeneity (ReHo) characterizing brain function was collected and analyzed on humans with SZ (hSZ) and healthy controls (HC) cross-sectionally, and methylazoxymethanol acetate (MAM) rats, a neurodevelopmental model of SZ, and vehicle rats longitudinally from adolescence to adulthood. Metabolomic and proteomic profiling in adult MAM rats and vehicle rats was examined and bioanalyzed. Compared to HC or adult vehicle rats, similar ReHo alterations were observed in hSZ and adult MAM rats, characterized by increased frontal (medial prefrontal and orbitofrontal cortices) and decreased posterior (visual and associated cortices) ReHo. Longitudinal analysis of MAM rats showed aberrant ReHo patterns as decreased posterior ReHo in adolescence and increased frontal and decreased posterior ReHo in adulthood. Accordingly, it was suggested that the visual cortex was a critical locus and adolescence was a sensitive window in SZ development. In addition, metabolic and proteomic alterations in adult MAM rats suggested that central carbon metabolism disturbance and mitochondrial dysfunction were the potential mechanisms underlying the ReHo alterations. This study proposed frontal-posterior functional imbalance and aberrant function developmental patterns in SZ, suggesting that the adolescent visual cortex was a critical locus and a sensitive window in SZ development. These findings from linking data between hSZ and MAM rats may have a significant translational contribution to the development of effective therapies in SZ.
Histone acetyltransferase 1 promotes gemcitabine resistance by regulating the PVT1/EZH2 complex in pancreatic cancer
Authors: Sun Yan , Ren Dianyun , Zhou Yingke , Shen Jian , Wu Heshui , Jin Xin 
Published: September 2021

AbstractThe poor prognosis of pancreatic cancer is primarily due to the development of resistance to therapies, including gemcitabine. The long noncoding RNA PVT1 (lncRNA PVT1) has been shown to interact with enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2), promoting gemcitabine resistance in pancreatic cancer. In this study, we found histone acetyltransferase 1 (HAT1) enhanced the tolerance of pancreatic cancer cells to gemcitabine and HAT1-mediated resistance mechanisms were regulated by PVT1 and EZH2. Our results showed that the aberrant HAT1 expression promoted gemcitabine resistance, while silencing HAT1 restored gemcitabine sensitivity. Moreover, HAT1 depletion caused a notable increase of gemcitabine sensitivity in gemcitabine-resistant pancreatic cancer cell lines. Further research found that HAT1 increased PVT1 expression to induce gemcitabine resistance, which enhanced the binding of bromodomain containing 4 (BRD4) to the PVT1 promoter, thereby promoting PVT1 transcription. Besides, HAT1 prevented EZH2 degradation by interfering with ubiquitin protein ligase E3 component n-recognin 4 (UBR4) binding to the N-terminal domain of EZH2, thus maintaining EZH2 protein stability to elevate the level of EZH2 protein, which also promoted HAT1-mediated gemcitabine resistance. These results suggested that HAT1 induced gemcitabine resistance of pancreatic cancer cells through regulating PVT1/EZH2 complex. Given this, Chitosan (CS)-tripolyphosphate (TPP)-siHAT1 nanoparticles were developed to block HAT1 expression and improve the antitumor effect of gemcitabine. The results showed that CS-TPP-siHAT1 nanoparticles augmented the antitumor effects of gemcitabine in vitro and in vivo. In conclusion, HAT1-targeted therapy can improve observably gemcitabine sensitivity of pancreatic cancer cells. HAT1 is a promising therapeutic target for pancreatic cancer.
Fear-of-intimacy-mediated zinc transport controls fat body cell dissociation through modulating Mmp activity in Drosophila
Authors: Wei Tian , Ji Xiaowen , Yu Qunhui , Li Guangying , Wu Lei , Gao Yan , Xiao Guiran 
Published: September 2021

AbstractMatrix metalloproteinases (Mmps) are pivotal extracellular proteinases that have been implicated in tumour invasion and metastasis. Drosophila fat body is important for energy storage and utilization, as well as biosynthetic and metabolic activities. The fat body undergoes remodelling during metamorphosis which is characterized by the dissociation of the fat body into individual cells. Mmps play important roles in the regulation of fat body cell dissociation. Here we show that a zinc transporter fear-of-intimacy (foi) is necessary for the cell dissociation of fat body in Drosophila. The progression of fat body cell dissociation was delayed by fat body-specific foi knockdown while it was accelerated by foi overexpression (OE). In essence, these phenotypes are closely associated with intracellular zinc homeostasis, which can be modulated by dietary zinc intervention or genetic modulation of other zinc transporters. Further study indicated that Mmp1 and Mmp2 levels could be transcriptionally regulated by zinc in vivo. Consistently, the retarded fat body cell dissociation caused by Mmp1 or Mmp2 RNAi could be regulated by modulating the expression of foi. Further, by using Drosophila models of malignant tumour RafGOFscrib−/− and RasV12lgl−/−, we showed that the tumour growth, invasion and migration could be markedly inhibited by foi knockdown. These findings demonstrate a close connection between zinc levels and cell dissociation in vivo, and also suggest that manipulation of zinc levels may provide a novel therapeutic strategy for cancer.
CHPF promotes gastric cancer tumorigenesis through the activation of E2F1
Authors: Lin Xiaolin , Han Ting , Xia Qing , Cui Jiujie , Zhuo Meng , Liang Yiyi , Su Wenyu , Wang Lisha , Wang Liwei , Liu Zebing , Xiao Xiuying 
Published: September 2021

AbstractChondroitin polymerizing factor (CHPF) is an important glycosyltransferase involved in the biosynthesis of chondroitin sulfate. However, the relationship between CHPF and gastric cancer has not been fully investigated. CHPF expression in gastric cancer tissues was detected by immunohistochemistry and correlated with gastric cancer patient prognosis. Cultured gastric cancer cells and human gastric epithelial cell line GES1 were used to investigate the effects of shCHPF and shE2F1 on the development and progression of gastric cancer by MTT, western blotting, flow cytometry analysis of cell apoptosis, colony formation, transwell and gastric cancer xenograft mouse models, in vitro and in vivo. In gastric cancer tissues, CHPF was found to be significantly upregulated, and its expression correlated with tumor infiltration and advanced tumor stage and shorter patient survival in gastric cancer. CHPF may promote gastric cancer development by regulating cell proliferation, colony formation, cell apoptosis and cell migration, while knockdown induced the opposite effects. Moreover, the results from in vivo experiments demonstrated that tumor growth was suppressed by CHPF knockdown. Additionally, E2F1 was identified as a potential downstream target of CHPF in the regulation of gastric cancer, and its knockdown decreased the CHPF-induced promotion of gastric cancer. Mechanistic study revealed that CHPF may regulate E2F1 through affecting UBE2T-mediated E2F1 ubiquitination. This study showed, for the first time, that CHPF is a potential prognostic indicator and tumor promoter in gastric cancer whose function is likely carried out through the regulation of E2F1.
Negative regulation of TGFβ-induced apoptosis by RAC1B enhances intestinal tumourigenesis
Authors: Gudiño Victoria , Cammareri Patrizia , Billard Caroline V. , Myant Kevin B. 
Published: September 2021

AbstractRAC1B is a tumour-related alternative splice isoform of the small GTPase RAC1, found overexpressed in a large number of tumour types. Building evidence suggests it promotes tumour progression but compelling in vivo evidence, demonstrating a role in driving tumour invasion, is currently lacking. In the present study, we have overexpressed RAC1B in a colorectal cancer mouse model with potential invasive properties. Interestingly, RAC1B overexpression did not trigger tumour invasion, rather it led to an acceleration of tumour initiation and reduced mouse survival. By modelling early stages of adenoma initiation we observed a reduced apoptotic rate in RAC1B overexpressing tumours, suggesting protection from apoptosis as a mediator of this phenotype. RAC1B overexpressing tumours displayed attenuated TGFβ signalling and functional analysis in ex vivo organoid cultures demonstrated that RAC1B negatively modulates TGFβ signalling and confers resistance to TGFβ-driven cell death. This work defines a novel mechanism by which early adenoma cells can overcome the cytostatic and cytotoxic effects of TGFβ signalling and characterises a new oncogenic function of RAC1B in vivo.
An international comparison of age and sex dependency of COVID-19 deaths in 2020: a descriptive analysis
Authors: Bauer Peter , Brugger Jonas , König Franz , Posch Martin 
Published: September 2021

AbstractThe number of reported coronavirus disease (COVID-19) deaths per 100,000 persons observed so far in 2020 is described in 15 European countries and the USA as dependent on age groups and sex. It is compared with the corresponding historic all-cause mortality per year depending on age and sex observed in these countries. Some common features exist although substantial differences in age and sex dependency of COVID-19 mortality were noted between countries. An exponential increase with age is a good model to describe and analyze both COVID-19 and all-cause mortality above 40 years old, where almost all COVID-19 deaths occur. Moreover, age dependency is stronger for COVID-19 mortality than for all-cause mortality, and males have an excess risk compared with women, which is less pronounced in the higher age groups. Additionally, concerning calendar time, differences in the age and sex dependency between countries were noted with the common tendency that male excess risk for COVID-19 mortality was smaller in the second half of the year.
Weekly Paclitaxel given concurrently with Durvalumab has a favorable safety profile in triple-negative metastatic breast cancer
Authors: Ghebeh Hazem , Al-Sayed Adher , Eiada Riham , Cabangon Leilani , Ajarim Dahish , Suleman Kausar , Tulbah Asma , Al-Tweigeri Taher 
Published: September 2021

AbstractTherapeutic anti-PD-L1 antibodies are safe as a monotherapy, albeit with minimal efficacy in triple-negative breast cancer (TNBC). This trial aimed to test the safety and efficacy of Durvalumab and Paclitaxel in metastatic TNBC. In this open-label, one-arm trial, five cycles of weekly paclitaxel were delivered intravenously (IV) concurrent with Durvalumab that was given IV every 2 weeks. The combination was preceded by one cycle of paclitaxel alone, for immunological priming, followed by Durvalumab solo until disease progression or unacceptable toxicity. Between 2017 and 2019, 14 patients received at least one cycle of the combination therapy. The therapy was safe with no-dose limiting toxicity, except one case of skin lesions. Adverse events (AEs) were reported in 71% of patients, and there was no death due to the combination therapy. Regardless of grade, the most common AEs were headache and peripheral neuropathy, as each happened in four patients (29%), followed by fatigue and skin rash in three patients (21%) each. Grade 3/4 AEs were experienced by three patients (21%), with the most common being headache and anemia, which happened in two patients (14%). The confirmed objective response rate (ORR) was observed in five patients with a median duration of 10.0 months. Median Progression-free survival (PFS) and overall survival (OS) were 5 and 20.7 months, respectively. The combination of Durvalumab and Paclitaxel is safe, leaving room for additional agents. This is the first report on the combination of Durvalumab and Paclitaxel in the treatment of TNBC (NCT02628132).
Cone beam CT optimisation for detection of vertical root fracture with metal in the field of view or the exomass
Authors: Candemil Amanda P. , Salmon Benjamin , Vasconcelos Karla F. , Oenning Anne C. , Jacobs Reinhilde , Freitas Deborah Q. , Haiter-Neto Francisco , Mangione Francesca , Oliveira Matheus L. 
Published: September 2021

AbstractDose optimisation has been revisited in the literature due to the frequent use of cone beam computed tomography (CBCT). Although the reduction of the field-of-view (FOV) size has shown to be an effective strategy, this indirectly increases the negative effect from the exomass. The aim of this study was to evaluate the diagnostic accuracy of an optimised CBCT protocol in the detection of simulated vertical root fracture (VRF) in the presence of metal in the exomass and/or inside the FOV. Twenty teeth were endodontically instrumented and VRF was induced in half of them. All teeth were individually placed in a human mandible covered with a soft tissue equivalent material, metallic materials were placed at different dispositions in the exomass and/or endomass, and CBCT scans were obtained at two dose protocols: standard and optimised. Five radiologists evaluated the images and indicated the presence of VRF using a 5-point scale. Area under the ROC curve (AUC), sensitivity, and specificity were calculated and compared using ANOVA (α = 0.05). Overall, AUC, sensitivity, and specificity did not differ significantly (p > 0.05) between the dose protocols. In conclusion, optimised dose protocols should be considered in the detection of simulated VRF irrespective of the occurrence of artefacts from metallic materials in the exomass and/or inside the FOV.
Comparative transcriptome analysis revealed omnivorous adaptation of the small intestine of Melinae
Authors: Wang Lidong , Yang Xiufeng , Zhou Shengyang , Lyu Tianshu , Shi Lupeng , Dong Yuehuan , Zhang Honghai 
Published: September 2021

AbstractAs the main digestive organ, the small intestine plays a vital role in the digestion of animals. At present, most of the research on animal feeding habits focuses on carnivores and herbivores. However, the mechanism of feeding and digestion in omnivores remains unclear. This study aims to reveal the molecular basis of the omnivorous adaptive evolution of Melinae by comparing the transcriptome of the small intestines of Asian Badgers (Meles leucurus) and Northern Hog Badgers (Arctonyx albogularis). We obtained high-quality small intestinal transcriptome data from these two species. Key genes and signalling pathways were analysed through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and other databases. Research has mainly found that orthologous genes related to six enzymes have undergone adaptive evolution. In addition, the study also found three digestion-related pathways (cGMP-PKG, cAMP, and Hippo). They are related to the digestion and absorption of nutrients, the secretion of intestinal fluids, and the transport of food through the small intestine, which may help omnivorous animals adapt to an omnivorous diet. Our study provides insight into the adaptation of Melinae to omnivores and affords a valuable transcriptome resource for future research.
Prevalence of peripheral neuropathy defined by monofilament insensitivity in middle-aged and older adults in two US cohorts
Authors: Hicks Caitlin W. , Wang Dan , Windham B. Gwen , Matsushita Kunihiro , Selvin Elizabeth 
Published: September 2021

AbstractPeripheral neuropathy is associated with substantial morbidity, but risk factors other than diabetes are largely uncharacterized. The aim of this study was to describe the prevalence and risk factors for peripheral neuropathy in adults with and without diabetes from two different population-based studies in the US. We performed a cross-sectional analysis of 5200 black and white participants from NHANES (1999–2004, age 40–85 years) and 3362 black and white participants from the ARIC Study (2016–2017, age 70–89 years) who underwent monofilament testing for peripheral neuropathy using a shared protocol. We used logistic regression to quantify age, sex, and race-adjusted risk factor associations for peripheral neuropathy among middle-aged (40–69 years) and older (≥ 70 years) adults. The age, sex, and race-adjusted prevalence of peripheral neuropathy (decreased sensation on monofilament testing) was 10.4% for middle-aged adults in NHANES, 26.8% for older adults in NHANES, and 39.2% for older adults in ARIC. Diabetes was an important risk factor, but more strongly associated with peripheral neuropathy in middle-aged (OR ~ 5 for long-standing diabetes) compared to older adults (ORs ~ 1.5–2). Male sex (ORs ~ 2), black race (ORs ~ 1.3–1.5), and greater height (ORs ~ 1.5–3) were robust risk factors for peripheral neuropathy. Other risk factors included body mass index, education, and peripheral artery disease. The burden of peripheral neuropathy defined by abnormal monofilament testing among older adults is substantial, even among adults without diabetes. Studies are needed to understand the etiology and prognosis of peripheral neuropathy in the absence of diabetes.