bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transplanting neurofibromatosis-1 gene knockout neural stem cells improve functional recovery in rats with spinal cord injury by enhancing the mTORC2 pathway
Authors: Chen Guoliang , Li Xianlong , Zhu Hongzhang , Wu Huachuan , He Dacheng , Shi Liangyu , Wei Fuxin , Liu Xizhe , Chen Ningning , Liu Shaoyu 
Published: October 2022

AbstractThe poor survival and low efficiency of neuronal differentiation limits the therapeutic effects of transplanted neural stem cells in the treatment of spinal cord injury. Neurofibromatosis-1 (NF-1) is a tumor suppressor gene that restricts the rapid and abnormal growth and differentiation of neural cells. In the present study, lentiviral vectors were used to knock out NF-1, Ricotr (the core member of mTORC2) or NF-1+Ricotr in neural stem cells in vitro, and the NF-1, Ricotr or NF-1+Ricotr knockout neural stem cells were transplanted at the lesion site in a rat model of spinal cord injury (SCI). We first demonstrated that targeted knockout of NF-1 had an antiapoptotic effect and improved neuronal differentiation by enhancing the mTORC2/Rictor pathway of neural stem cells in vitro. Subsequently, transplanting NF-1 knockout neural stem cells into the injured site sufficiently promoted the tissue repair and functional recovery of rats with spinal cord injury by enhancing the survival and neuronal differentiation of grafted neural stem cells. Collectively, these findings reveal a prominent role of NF-1 in neural stem cell biology, which is an invaluable step forward in enhancing the benefit of neural stem cell-mediated regenerative cell therapy for spinal cord injury and identifies the transplantation of NF-1 knockout neural stem cells as a promising strategy for spinal cord injury.
DDX41 coordinates RNA splicing and transcriptional elongation to prevent DNA replication stress in hematopoietic cells
Authors: Shinriki Satoru , Hirayama Mayumi , Nagamachi Akiko , Yokoyama Akihiko , Kawamura Takeshi , Kanai Akinori , Kawai Hidehiko , Iwakiri Junichi , Liu Rin , Maeshiro Manabu , Tungalag Saruul , Tasaki Masayoshi , Ueda Mitsuharu , Tomizawa Kazuhito , Kataoka Naoyuki , Ideue Takashi , Suzuki Yutaka , Asai Kiyoshi , Tani Tokio , Inaba Toshiya , Matsui Hirotaka 
Published: October 2022

AbstractMyeloid malignancies withDDX41mutations are often associated with bone marrow failure and cytopenia before overt disease manifestation. However, the mechanisms underlying these specific conditions remain elusive. Here, we demonstrate that loss of DDX41 function impairs efficient RNA splicing, resulting in DNA replication stress with excess R-loop formation. Mechanistically, DDX41 binds to the 5′ splice site (5′SS) of coding RNA and coordinates RNA splicing and transcriptional elongation; loss of DDX41 prevents splicing-coupled transient pausing of RNA polymerase II at 5ʹSS, causing aberrant R-loop formation and transcription-replication collisions. Although the degree of DNA replication stress acquired in S phase is small, cells undergo mitosis with under-replicated DNA being remained, resulting in micronuclei formation and significant DNA damage, thus leading to impaired cell proliferation and genomic instability. These processes may be responsible for disease phenotypes associated withDDX41mutations.
AKT-mTORC1 reactivation is the dominant resistance driver for PI3Kβ/AKT inhibitors in PTEN-null breast cancer and can be overcome by combining with Mcl-1 inhibitors
Authors: Dunn Shanade , Eberlein Cath , Yu Jason , Gris-Oliver Albert , Ong Swee Hoe , Yelland Urs , Cureton Natalie , Staniszewska Anna , McEwen Robert , Fox Millie , Pilling James , Hopcroft Philip , Coker Elizabeth A. , Jaaks Patricia , Garnett Mathew J. , Isherwood Beverley , Serra Violeta , Davies Barry R. , Barry Simon T. , Lynch James T. , Yusa Kosuke 
Published: October 2022

AbstractThe PI3K pathway is commonly activated in breast cancer, with PI3K-AKT pathway inhibitors used clinically. However, mechanisms that limit or enhance the therapeutic effects of PI3K-AKT inhibitors are poorly understood at a genome-wide level. Parallel CRISPR screens in 3 PTEN-null breast cancer cell lines identified genes mediating resistance to capivasertib (AKT inhibitor) and AZD8186 (PI3Kβ inhibitor). The dominant mechanism causing resistance is reactivated PI3K-AKT-mTOR signalling, but not other canonical signalling pathways. Deletion of TSC1/2 conferred resistance to PI3Kβi and AKTi through mTORC1. However, deletion of PIK3R2 and INPPL1 drove specific PI3Kβi resistance through AKT. Conversely deletion of PIK3CA, ERBB2, ERBB3 increased PI3Kβi sensitivity while modulation of RRAGC, LAMTOR1, LAMTOR4 increased AKTi sensitivity. Significantly, we found that Mcl-1 loss enhanced response through rapid apoptosis induction with AKTi and PI3Kβi in both sensitive and drug resistant TSC1/2 null cells. The combination effect was BAK but not BAX dependent. The Mcl-1i + PI3Kβ/AKTi combination was effective across a panel of breast cancer cell lines with PIK3CA and PTEN mutations, and delivered increased anti-tumor benefit in vivo. This study demonstrates that different resistance drivers to PI3Kβi and AKTi converge to reactivate PI3K-AKT or mTOR signalling and combined inhibition of Mcl-1 and PI3K-AKT has potential as a treatment strategy for PI3Kβi/AKTi sensitive and resistant breast tumours.
Cumulative muscle mass and blood pressure but not fat mass drives arterial stiffness and carotid intima-media thickness progression in the young population and is unrelated to vascular organ damage
Authors: Agbaje Andrew O. , Barker Alan R. , Tuomainen Tomi-Pekka 
Published: October 2022

AbstractWe examined the longitudinal associations of fat mass, lean mass, and blood pressure (BP) from childhood through young adulthood with changes in carotid-femoral pulse wave velocity (cfPWV), a measure of arterial stiffness, and carotid intima-media thickness (cIMT). We included 3863 participants from the Avon Longitudinal Study of Parents and Children birth cohort. Fat mass and lean mass, measured by dual-energy X-ray absorptiometry, and BP were measured at ages 9, 17 and 24 years and classified into low, moderate, and high tertiles. cfPWV and cIMT were measured at 17 and 24 years of age. Associations were examined via linear mixed effect models and adjusted for cardiometabolic and lifestyle factors. Among 1720 [44.5%] male and 2143 [55.5%] female participants, cumulative high exposures to lean mass (effect estimate 0.006 m/s [95% CI 0.001 to 0.010; p = 0.022]), systolic BP (0.013 m/s [0.009 to 0.017; p < 0.0001]) and diastolic BP (0.023 m/s [0.019 to 0.027; p < 0.0001]) from 9–24 years of age were positively associated with the 7-year increase in cfPWV. Persistent high exposures to lean mass (0.012 mm; [0.008 to 0.016; p < 0.0001]), body mass index (0.007 mm [0.003 to 0.011; p = 0.001]), and systolic BP (0.010 mm; [0.006 to 0.014; p < 0.0001]) from ages 9–24 years were positively associated with thicker cIMT at 17–24 years of age. Total fat and trunk fat mass from childhood had no association with cfPWV or cIMT progression. In conclusion, increased lean mass and BP but not fat mass from childhood drives arterial remodeling in young adulthood.
Alignment of single-cell trajectory trees with CAPITAL
Authors: Sugihara Reiichi , Kato Yuki , Mori Tomoya , Kawahara Yukio 
Published: October 2022

AbstractGlobal alignment of complex pseudotime trajectories between different single-cell RNA-seq datasets is challenging, as existing tools mainly focus on linear alignment of single-cell trajectories. Here we present CAPITAL (comparative analysis of pseudotime trajectory inference with tree alignment), a method for comparing single-cell trajectories with tree alignment whereby branching trajectories can be automatically compared. Computational tests on synthetic datasets and authentic bone marrow cells datasets indicate that CAPITAL has achieved accurate and robust alignments of trajectory trees, revealing various gene expression dynamics including gene–gene correlation conservation between different species.
TLCD1 and TLCD2 regulate cellular phosphatidylethanolamine composition and promote the progression of non-alcoholic steatohepatitis
Authors: Petkevicius Kasparas , Palmgren Henrik , Glover Matthew S. , Ahnmark Andrea , Andréasson Anne-Christine , Madeyski-Bengtson Katja , Kawana Hiroki , Allman Erik L. , Kaper Delaney , Uhrbom Martin , Andersson Liselotte , Aasehaug Leif , Forsström Johan , Wallin Simonetta , Ahlstedt Ingela , Leke Renata , Karlsson Daniel , González-King Hernán , Löfgren Lars , Nilsson Ralf , Pellegrini Giovanni , Kono Nozomu , Aoki Junken , Hess Sonja , Sienski Grzegorz , Pilon Marc , Bohlooly-Y Mohammad , Maresca Marcello , Peng Xiao-Rong 
Published: October 2022

AbstractThe fatty acid composition of phosphatidylethanolamine (PE) determines cellular metabolism, oxidative stress, and inflammation. However, our understanding of how cells regulate PE composition is limited. Here, we identify a genetic locus on mouse chromosome 11, containing two poorly characterized genes Tlcd1 and Tlcd2, that strongly influences PE composition. We generated Tlcd1/2 double-knockout (DKO) mice and found that they have reduced levels of hepatic monounsaturated fatty acid (MUFA)-containing PE species. Mechanistically, TLCD1/2 proteins act cell intrinsically to promote the incorporation of MUFAs into PEs. Furthermore, TLCD1/2 interact with the mitochondria in an evolutionarily conserved manner and regulate mitochondrial PE composition. Lastly, we demonstrate the biological relevance of our findings in dietary models of metabolic disease, where Tlcd1/2 DKO mice display attenuated development of non-alcoholic steatohepatitis compared to controls. Overall, we identify TLCD1/2 proteins as key regulators of cellular PE composition, with our findings having broad implications in understanding and treating disease.
Introducing the FAIR Principles for research software
Authors: Barker Michelle , Chue Hong Neil P. , Katz Daniel S. , Lamprecht Anna-Lena , Martinez-Ortiz Carlos , Psomopoulos Fotis , Harrow Jennifer , Castro Leyla Jael , Gruenpeter Morane , Martinez Paula Andrea , Honeyman Tom 
Published: October 2022

AbstractResearch software is a fundamental and vital part of research, yet significant challenges to discoverability, productivity, quality, reproducibility, and sustainability exist. Improving the practice of scholarship is a common goal of the open science, open source, and FAIR (Findable, Accessible, Interoperable and Reusable) communities and research software is now being understood as a type of digital object to which FAIR should be applied. This emergence reflects a maturation of the research community to better understand the crucial role of FAIR research software in maximising research value. The FAIR for Research Software (FAIR4RS) Working Group has adapted the FAIR Guiding Principles to create the FAIR Principles for Research Software (FAIR4RS Principles). The contents and context of the FAIR4RS Principles are summarised here to provide the basis for discussion of their adoption. Examples of implementation by organisations are provided to share information on how to maximise the value of research outputs, and to encourage others to amplify the importance and impact of this work.
OSeMOSYS Global, an open-source, open data global electricity system model generator
Authors: Barnes Trevor , Shivakumar Abhishek , Brinkerink Maarten , Niet Taco 
Published: October 2022

AbstractThis paper describes OSeMOSYS Global, an open-source, open-data model generator for creating global electricity system models for an active global modelling community. This version of the model generator is freely available and can be used to create interconnected electricity system models for both the entire globe and for any geographically diverse subset of the globe. Compared to other existing global models, OSeMOSYS Global allows for full user flexibility in determining the time slice structure and geographic scope of the model and datasets, and is built using the widely used fully open-source OSeMOSYS energy system model. This paper describes the data sources, structure and use of OSeMOSYS Global, and provides illustrative workflow results.
Brain oscillatory activity in adolescent idiopathic scoliosis
Authors: Formaggio Emanuela , Bertuccelli Margherita , Rubega Maria , Di Marco Roberto , Cantele Francesca , Gottardello Federica , De Giuseppe Michela , Masiero Stefano 
Published: October 2022

AbstractPathophysiology of Adolescent Idiopathic Scoliosis (AIS) is not yet completely understood. This exploratory study aims to investigate two aspects neglected in clinical practice: a defective postural central nervous system control in AIS, and alterations of body schema due to scoliosis spinal deformities. We recorded EEG data and balance data in four different standing positions in 14 adolescents with AIS and in 14 controls. A re-adaptation of the Image Marking Procedure (IMP) assessed body schema alterations on the horizontal (Body Perception Indices (BPIs)) and vertical direction (interacromial and bisiliac axes inclinations). Our results revealed no differences in balance control between groups; higher EEG alpha relative power over sensorimotor areas ipsilateral to the side of the curve and a significant increase of theta relative power localized over the central areas in adolescents with AIS. The difference in BPI shoulder and BPI waist significantly differed between the two groups. The inclinations of the perceived interacromial axes in adolescents with AIS was opposite to the real inclination. Increased theta activity and alpha lateralization observed may be a compensatory strategy to overcome sensorimotor dysfunction mirrored by altered body schema. Scoliosis onset might be preceded by sensorimotor control impairments that last during curve progression.
Pore types, genesis, and evolution model of lacustrine oil-prone shale: a case study of the Cretaceous Qingshankou Formation, Songliao Basin, NE China
Authors: He Wenyuan , Liu Bo , Sun Mengdi , Wang Liu , Zhang Jinyou , Yasin Qamar , Tian Shansi , Gao Shuo , Ukaomah Chima Finnian 
Published: October 2022

AbstractA comprehensive characterisation of the pore structure in shale oil reservoirs is essential for forecasting oil production and exploration risks. This study forecasted these risks in the oil-rich Songliao Basin using combination of high-resolution field emission scanning electron microscopy and quantitative X-ray diffraction to analyze the pore genesis and evolution mode within the first member of the Cretaceous Qingshankou Formation (K2qn1). The results showed the dominance of inorganic pores over organic pores, wherein diagenetic processes, such as compaction, pressure solution, and cementation, were responsible for the destruction of pore structure in the formation. Notably, the pores formed by dissolution and shrinkage cracks resulting from clay mineral transformation improved the oil storage space. Furthermore, according to the geochemical data and clay composition, the K2qn1 shale is in the middle diagenetic stage A, which can be further subdivided into A1 and A2 stages from top to bottom. The porosity slowly decreased in both sub-stages A1 and A2, wherein the decrease was stable in the latter. The diagenetic observations in this study are significant for the exploration of unconventional shale oil in petroliferous basins worldwide.
Canopy arthropod declines along a gradient of olive farming intensification
Authors: Vasconcelos Sasha , Pina Sílvia , Herrera José M. , Silva Bruno , Sousa Pedro , Porto Miguel , Melguizo-Ruiz Nereida , Jiménez-Navarro Gerardo , Ferreira Sónia , Moreira Francisco , Heleno Ruben , Jonsson Mattias , Beja Pedro 
Published: October 2022

AbstractArthropod declines have been linked to agricultural intensification. However, information about the impacts of intensification is still limited for many crops, as is our understanding of the responses of different arthropod taxa and trophic groups, thus hindering the development of effective mitigation measures. We investigated the impacts of olive farming intensification on canopy-dwelling arthropods in the Mediterranean region. Intensification involves the increased use of agrochemicals, mechanisation and irrigation, but also structural changes from traditional orchards with low densities of large and old trees, to intensive and superintensive orchards with high to very high densities of smaller and younger trees, respectively. Canopy arthropods were vacuum-sampled at 53 sites representing the three orchard intensification levels, in spring, summer and autumn 2017. We evaluated how the arthropod community varied across intensification levels, and in response to orchard structure, management and landscape context. We found no changes in the diversity of arthropod taxa across intensification levels after correcting for sample coverage, but arthropod abundance declined markedly along the intensification gradient. Decreased abundance was associated with changes in orchard structure, lower herbaceous cover, and higher herbicide and insecticide use. The abundance of a specialized olive pest was lower in landscapes with higher woodland cover. The negative effects of intensification were stronger in spring and summer than in autumn, and parasitoids and predators were particularly affected. Overall, results suggest that retaining herbaceous cover, reducing agrochemical inputs and preserving natural woody elements in the landscape, may contribute to mitigate impacts of olive farming intensification on canopy arthropods, particularly on beneficial species.
Overcoming the non-kinetic activity of EGFR1 using multi-functionalized mesoporous silica nanocarrier for in vitro delivery of siRNA
Authors: Parnian Javad , Ma’mani Leila , Bakhtiari Mohamad Reza , Safavi Maliheh 
Published: October 2022

AbstractTriple-negative breast cancer (TNBC) does not respond to HER2-targeted and hormone-based medicines. Epidermal growth factor receptor 1 (EGFR1) is commonly overexpressed in up to 70% of TNBC cases, so targeting cancer cells via this receptor could emerge as a favored modality for TNBC therapy due to its target specificity. The development of mesoporous silica nanoparticles (MSNs) as carriers for siRNAs remains a rapidly growing area of research. For this purpose, a multi-functionalized KIT-6 containing the guanidinium ionic liquid (GuIL), PEI and PEGylated folic acid (FA-PEG) was designed. Accordingly, KIT-6 was fabricated and modified with FA-PEG and PEI polymers attached on the surface and the GuIL placed in the mesopores. Subsequent to confirming the structure of this multi-functionalized KIT-6- based nanocarrier using TEM, SEM, AFM, BET, BJH, DLS and Zeta Potential, it was investigated for uploading and transferring the anti-EGFR1 siRNAs to the MD-MBA-231 cell line. The rate of cellular uptake, cellular localization and endolysosomal escape was evaluated based on the fluorescent intensity of FAM-labelled siRNA using flowcytometry analysis and confocal laser scanning microscopy (CLSM). The 64% cellular uptake after 4 h incubation, clearly suggested the successful delivery of siRNA into the cells and, CLSM demonstrated that siRNA@[FA-PEGylated/PEI@GuIL@KIT-6] may escape endosomal entrapment after 6 h incubation. Using qPCR, quantitative evaluation of EGFR1 gene expression, a knockdown of 82% was found, which resulted in a functional change in the expression of EGFR1 targets. Co-treatment of chemotherapy drug “carboplatin” in combination with siRNA@[FA-PEGylated/PEI@GuIL@KIT-6] exhibited a remarkable cytotoxic effect in comparison to carboplatin alone.
A comparison of the ClotPro system with rotational thromboelastometry in cardiac surgery: a prospective observational study
Authors: Yoshii Ryogo , Sawa Teiji , Kawajiri Hidetake , Amaya Fumimasa , Tanaka Kenichi A. , Ogawa Satoru 
Published: October 2022

AbstractViscoelastic coagulation tests have been increasingly used for hemostasis management in cardiac surgery. The ClotPro system is a novel viscoelastic device based on principles of rotational thromboelastometry. We aimed to compare ClotPro with ROTEM and plasma coagulation assays in cardiopulmonary bypass (CPB) patients. Blood samples were collected from 25 CPB patients at (1) baseline, (2) start of CPB, (3) end of CPB, and (4) end of surgery. The EX-test, IN-test, HI-test, FIB-test parameters on ClotPro were compared with corresponding ROTEM assay (EXTEM, INTEM, HEPTEM, and FIBTEM). Standard plasma coagulation assays and endogenous thrombin generation (TG) were simultaneously evaluated. Pearson correlation analyses showed moderate correlations between clotting times (CTs) (r = 0.63–0.67; p < 0.001, respectively), and strong correlations with maximal clot firmness (MCF) (r = 0.93–0.98; p < 0.001, respectively) between ClotPro and ROTEM. EX-test and IN-test MCF parameters were interchangeable with acceptable percentage errors (EX-test MCF: 7.3%, IN-test MCF: 8.3%), but FIB-test MCF (27.0%) and CT results were not (EX-test CT: 44.7%, IN-test CT: 31.4%). The correlations of PT/INR or peak TG with EX-test CTs were higher than with EXTEM CTs (PT/INR: r = 0.80 and 0.41, peak TG: 0.43 and 0.18, respectively). FIB-test MCF has strong correlation with plasma fibrinogen and factor XIII level (r = 0.84 and 0.66, respectively). ROC analyses showed that ClotPro was capable of emulating well-established ROTEM thresholds (area under curves: 0.83–1.00). ClotPro demonstrated strong correlations in MCF parameters of ROTEM in CPB patients. It may be reasonable to modify ROTEM-based transfusion algorithm pertaining to MCF parameters to establish cut-off values for ClotPro device.
A meta-analysis of the relationship between bullying and non-suicidal self-injury among children and adolescents
Authors: Huang Haitao , Ding Yueming , Wan Xiao , Liang Yipei , Zhang Yiming , Lu Guangli , Chen Chaoran 
Published: October 2022

AbstractNon-suicidal self-injury (NSSI) has attracted increasing attention due to its high detection rate, high risk and high repeatability. There is a need for the early identification of preventable occurrence factors, which is necessary to facilitate screening and intervention, especially to facilitate the early detection of high-risk individuals. This research aims to investigate the relationship between bullying behaviour and non-suicidal self-injury among children and adolescents by means of meta-analysis. The PubMed, Embase, Web of Science, SCOPUS, PsycINFO, CKNI and WAN FANG databases were searched from inception to 14 December 2021 for studies that explored the relationship between bullying behaviour and NSSI among children and adolescents. A total of 29 articles met the inclusion criteria of the meta-analysis, and 54 independent effect sizes were obtained, including 53,501 subjects. Victims [OR 2.46 (95% CI 2.14–2.83);p < 0.001], bullies [OR 2.12 (95% CI 1.37–3.27);p < 0.001], and bully-victims [OR: 2.98 (95% CI 1.85–4.82);p < 0.001] were more likely to have NSSI than uninvolved children or adolescents. In addition, analyses showed the absence of publication bias. In the victim group, the older the age was, the lower the risk of NSSI (z = − 3.74,p = 0.00). Gender does not play a moderating effect on the association between bullying behaviour and non-suicidal self-injury. The relationship between involvement in bullying and NSSI was demonstrated. By taking measures to prevent bullying, the incidence of NSSI in children and adolescents can be potentially reduced.