bluuebunny/crossref_metadata_2025_split huggingface dataset:
Small changes in rhizosphere microbiome composition predict disease outcomes earlier than pathogen density variations
Authors: Gu Yian , Banerjee Samiran , Dini-Andreote Francisco , Xu Yangchun , Shen Qirong , Jousset Alexandre , Wei Zhong 
Published: July 2022

Abstract
Even in homogeneous conditions, plants facing a soilborne pathogen tend to show a binary outcome with individuals either remaining fully healthy or developing severe to lethal disease symptoms. As the rhizosphere microbiome is a major determinant of plant health, we postulated that such a binary outcome may result from an early divergence in the rhizosphere microbiome assembly that may further cascade into varying disease suppression abilities. We tested this hypothesis by setting up a longitudinal study of tomato plants growing in a natural but homogenized soil infested with the soilborne bacterial pathogen Ralstonia solanacearum. Starting from an originally identical species pool, individual rhizosphere microbiome compositions rapidly diverged into multiple configurations during the plant vegetative growth. This variation in community composition was strongly associated with later disease development during the later fruiting state. Most interestingly, these patterns also significantly predicted disease outcomes 2 weeks before any difference in pathogen density became apparent between the healthy and diseased groups. In this system, a total of 135 bacterial OTUs were associated with persistent healthy plants. Five of these enriched OTUs (Lysinibacillus, Pseudarthrobacter, Bordetella, Bacillus, and Chryseobacterium) were isolated and shown to reduce disease severity by 30.4–100% when co-introduced with the pathogen. Overall, our results demonstrated that an initially homogenized soil can rapidly diverge into rhizosphere microbiomes varying in their ability to promote plant protection. This suggests that early life interventions may have significant effects on later microbiome states, and highlights an exciting opportunity for microbiome diagnostics and plant disease prevention.
MicroRNA-mediated regulation of lipid metabolism in virus-infected Emiliania huxleyi
Authors: Zhang Enquan , Gao Jingjing , Wei Zehua , Zeng Jun , Li Jian , Li Guiling , Liu Jingwen 
Published: July 2022

Abstract
The interactions between Emiliania huxleyi and E. huxleyi virus (EhV) regulate marine carbon and sulfur biogeochemical cycles and play a prominent role in global climate change. As a large DNA virus, EhV has developed a novel “virocell metabolism” model to meet its high metabolic needs. Although it has been widely demonstrated that EhV infection can profoundly rewire lipid metabolism, the epigenetic regulatory mechanisms of lipid metabolism are still obscure. MicroRNAs (miRNAs) can regulate biological pathways by targeting hub genes in the metabolic processes. In this study, the transcriptome, lipidome, and miRNAome were applied to investigate the epigenetic regulation of lipid metabolism in E. huxleyi cells during a detailed time course of viral infection. Combined transcriptomic, lipidomic, and physiological experiments revealed reprogrammed lipid metabolism, along with mitochondrial dysfunction and calcium influx through the cell membrane. A total of 69 host miRNAs (including 1 known miRNA) and 7 viral miRNAs were identified, 27 of which were differentially expressed. Bioinformatic prediction revealed that miRNAs involved in the regulation of lipid metabolism and a dual-luciferase reporter assay suggested that phosphatidylinositol 3-kinase (PI3K) gene might be a target of ehx-miR5. Further qPCR and western blot analysis showed a significant negative correlation between the expression of ehx-miR5 and its target gene PI3K, along with the lower activity of its downstream components (p-Akt, p-TOR, SREBP), indicating that lipid metabolism might be regulated by ehx-miR5 through the PI3K-Akt-TOR signaling pathway. Our findings reveal several novel mechanisms of viral strategies to manipulate host lipid metabolism and provide evidence that ehx-miR5 negatively modulates the expression of PI3K and disturbs lipid metabolism in the interactions between E. huxleyi and EhV.
Factors affecting the quality of endodontic treatment in general dental practice in Scotland: a qualitative focus group study
Authors: Khamuani Sonia , Ross Alastair , Robertson Douglas 
Published: July 2022

AbstractIntroduction The quality of endodontic treatment worldwide is variable despite clear clinical guidelines being available.Aims Identify the factors that affect the quality of endodontic treatment in general dental practice in Scotland and how to overcome the barriers identified.Methods Four online focus group interview sessions were conducted in which a total of 16 participants were recruited, including general dental practitioners, endodontic specialists and educationalists. Topics for facilitated discussion were based on healthcare system theory and included education/training, patient factors, resources and equipment factors; themes were identified via template analysis.Results A number of themes and subthemes affecting the quality of care are reported, including aspects to do with remuneration, time, education, training, support from secondary care and the impact of COVID-19.Conclusion Findings support: increase practical experience for undergraduates; access to postgraduate mentoring and training; development of a managed clinical network to facilitate access to appropriately trained specialists; and increased remuneration to allow sufficient time and adequate equipment to achieve clinical standards.
Non-canonical EphA2 activation underpins PTEN-mediated metastatic migration and poor clinical outcome in prostate cancer
Authors: Sachdeva Ashwin , Hart Claire A. , Kim Kyungmin , Tawadros Thomas , Oliveira Pedro , Shanks Jonathan , Brown Mick , Clarke Noel 
Published: July 2022

Abstract
Background
The key process of mesenchymal to amoeboid transition (MAT), which enables prostate cancer (PCa) transendothelial migration and subsequent development of metastases in red bone marrow stroma, is driven by phosphorylation of EphA2S897 by pAkt, which is induced by the omega-6 polyunsaturated fatty acid arachidonic acid. Here we investigate the influence of EphA2 signalling in PCa progression and long-term survival.

Methods
The mechanisms underpinning metastatic biopotential of altered EphA2 signalling in relation to PTEN status were assessed in vitro using canonical (EphA2D739N) and non-canonical (EphA2S897G) PC3-M mutants, interrogation of publicly available PTEN-stratified databases and clinical validation using a PCa TMA (n = 177) with long-term follow-up data. Spatial heterogeneity of EphA2 was assessed using a radical prostatectomy cohort (n = 67).

Results
Non-canonical EphA2 signalling via pEphA2S897 is required for PCa transendothelial invasion of bone marrow endothelium. High expression of EphA2 or pEphA2S897 in a PTENlow background is associated with poor overall survival. Expression of EphA2, pEphA2S897 and the associated MAT marker pMLC2 are spatially regulated with the highest levels found within lesion areas within 500 µm of the prostate margin.

Conclusion
EphA2 MAT-related signalling confers transendothelial invasion. This is associated with a substantially worse prognosis in PTEN-deficient PCa.
SMOC2 promotes an epithelial-mesenchymal transition and a pro-metastatic phenotype in epithelial cells of renal cell carcinoma origin
Authors: Feng Daniel , Gao Peng , Henley Nathalie , Dubuissez Marion , Chen Nan , Laurin Louis-Philippe , Royal Virginie , Pichette Vincent , Gerarduzzi Casimiro 
Published: July 2022

AbstractRenal Cell Carcinoma (RCC) is the most common form of all renal cancer cases, and well-known for its highly aggressive metastatic behavior. SMOC2 is a recently described non-structural component of the extracellular matrix (ECM) that is highly expressed during tissue remodeling processes with emerging roles in cancers, yet its role in RCC remains elusive. Using gene expression profiles from patient samples, we identified SMOC2 as being significantly expressed in RCC tissue compared to normal renal tissue, which correlated with shorter RCC patient survival. Specifically, de novo protein synthesis of SMOC2 was shown to be much higher in the tubular epithelial cells of patients with biopsy-proven RCC. More importantly, we provide evidence of SMOC2 triggering kidney epithelial cells into an epithelial-to-mesenchymal transition (EMT), a phenotype known to promote metastasis. We found that SMOC2 induced mesenchymal-like morphology and activities in both RCC and non-RCC kidney epithelial cell lines. Mechanistically, treatment of RCC cell lines ACHN and 786-O with SMOC2 (recombinant and enforced expression) caused a significant increase in EMT-markers, -matrix production, -proliferation, and -migration, which were inhibited by targeting SMOC2 by siRNA. We further characterized SMOC2 activation of EMT to occur through the integrin β3, FAK and paxillin pathway. The proliferation and metastatic potential of SMOC2 overexpressing ACHN and 786-O cell lines were validated in vivo by their significantly higher tumor growth in kidneys and systemic dissemination into other organs when compared to their respective controls. In principle, understanding the impact that SMOC2 has on EMT may lead to more evidence-based treatments and biomarkers for RCC metastasis.
Mesenchymal/stromal stem cells: necessary factors in tumour progression
Authors: Li Xinyu , Fan Qing , Peng Xueqiang , Yang Shuo , Wei Shibo , Liu Jingang , Yang Liang , Li Hangyu 
Published: July 2022

AbstractMesenchymal/stromal stem cells (MSCs) are a crucial component of the tumour microenvironment (TME). They can be recruited from normal tissues into the TME and educated by tumour cells to transform into tumour-associated MSCs, which are oncogenic cells that promote tumour development and progression by impacting or transforming into various kinds of cells, such as immune cells and endothelial cells. Targeting MSCs in the TME is a novel strategy to prevent malignant processes. Exosomes, as communicators, carry various RNAs and proteins and thus link MSCs and the TME, which provides options for improving outcomes and developing targeted treatment.
ACSL4 is essential for radiation-induced intestinal injury by initiating ferroptosis
Authors: Ji Qian , Fu Shengqiao , Zuo Hao , Huang Yumeng , Chu Liangmei , Zhu Yanyan , Hu Jing , Wu Yuting , Chen Shuangwei , Wang Yue , Ren Yongfei , Pu Xi , Liu Na , Li Rongkun , Wang Xu , Dai Chunhua 
Published: July 2022

AbstractLipid peroxidation-induced ferroptosis is a newly recognized type of programmed cell death. With the method of RNA sequencing, we found that irradiation (IR) markedly increased the expression of ferroptosis promotive genes, whereas reduced the expression of ferroptosis suppressive genes in murine intestine tissues, when compared with those of liver and lung tissues. By using ferroptosis inducer RSL-3 and inhibitor liproxstatin-1, we found that ferroptosis is essential for IR-induced intestinal injury. Acyl-CoA Synthetase Long-Chain Family Member 4 (ACSL4) is an important component for ferroptosis execution, and we found that ACSL4 expression was significantly upregulated in irradiated intestine tissues, but not in liver or lung tissues. Antibacterial and antifungal regents reduced the expression of ASCL4 and protected against tissue injury in irradiated intestine tissues. Further studies showed that troglitazone, a ACSL4 inhibitor, succeeded to suppresses intestine lipid peroxidation and tissue damage after IR.
Implantable vision-enhancing devices and postoperative rehabilitation in advanced age-related macular degeneration
Authors: Borkenstein Andreas F. , Borkenstein Eva-Maria , Augustin Albert J. 
Published: July 2022

AbstractAge-related macular degeneration (AMD) results in progressive vision loss that significantly impacts patients’ quality of life and ability to perform routine daily activities. Although pharmaceutical treatments for AMD are available and in clinical development, patients with late-stage AMD are relatively underserved. Specialized rehabilitation programs and external low-vision aids are available to support visual performance for those with advanced AMD; but intraocular vision-improving devices, including implantable miniature telescope (IMT) and intraocular lens (IOL) implants, offer advantages regarding head motion, vestibular ocular reflex development, and depth perception. IMT and IOL technologies are rapidly evolving, and many patients who could benefit from them remain unidentified. This review of recent literature summarizes available information on implantable devices for improving vision in patients with advanced AMD. Furthermore, it discusses recent attempts of developing the quality of life tests including activities of daily life and objective assessments. This may offer the ophthalmologist but also the patient a better possibility to detect changes or improvements before and after surgery. It is evident that surgery with new implants/devices is no longer the challenge, but rather the more complex management of patients before and after surgery as well as the correct selection of cases.
Neurocomputational mechanisms of confidence in self and others
Authors: Bang Dan , Moran Rani , Daw Nathaniel D. , Fleming Stephen M. 
Published: July 2022

AbstractComputing confidence in one’s own and others’ decisions is critical for social success. While there has been substantial progress in our understanding of confidence estimates about oneself, little is known about how people form confidence estimates about others. Here, we address this question by asking participants undergoing fMRI to place bets on perceptual decisions made by themselves or one of three other players of varying ability. We show that participants compute confidence in another player’s decisions by combining distinct estimates of player ability and decision difficulty – allowing them to predict that a good player may get a difficult decision wrong and that a bad player may get an easy decision right. We find that this computation is associated with an interaction between brain systems implicated in decision-making (LIP) and theory of mind (TPJ and dmPFC). These results reveal an interplay between self- and other-related processes during a social confidence computation.
Accurate somatic variant detection using weakly supervised deep learning
Authors: Krishnamachari Kiran , Lu Dylan , Swift-Scott Alexander , Yeraliyev Anuar , Lee Kayla , Huang Weitai , Leng Sim Ngak , Skanderup Anders Jacobsen 
Published: July 2022

AbstractIdentification of somatic mutations in tumor samples is commonly based on statistical methods in combination with heuristic filters. Here we develop VarNet, an end-to-end deep learning approach for identification of somatic variants from aligned tumor and matched normal DNA reads. VarNet is trained using image representations of 4.6 million high-confidence somatic variants annotated in 356 tumor whole genomes. We benchmark VarNet across a range of publicly available datasets, demonstrating performance often exceeding current state-of-the-art methods. Overall, our results demonstrate how a scalable deep learning approach could augment and potentially supplant human engineered features and heuristic filters in somatic variant calling.
Emergency triage of brain computed tomography via anomaly detection with a deep generative model
Authors: Lee Seungjun , Jeong Boryeong , Kim Minjee , Jang Ryoungwoo , Paik Wooyul , Kang Jiseon , Chung Won Jung , Hong Gil-Sun , Kim Namkug 
Published: July 2022

AbstractTriage is essential for the early diagnosis and reporting of neurologic emergencies. Herein, we report the development of an anomaly detection algorithm (ADA) with a deep generative model trained on brain computed tomography (CT) images of healthy individuals that reprioritizes radiology worklists and provides lesion attention maps for brain CT images with critical findings. In the internal and external validation datasets, the ADA achieved area under the curve values (95% confidence interval) of 0.85 (0.81–0.89) and 0.87 (0.85–0.89), respectively, for detecting emergency cases. In a clinical simulation test of an emergency cohort, the median wait time was significantly shorter post-ADA triage than pre-ADA triage by 294 s (422.5 s [interquartile range, IQR 299] to 70.5 s [IQR 168]), and the median radiology report turnaround time was significantly faster post-ADA triage than pre-ADA triage by 297.5 s (445.0 s [IQR 298] to 88.5 s [IQR 179]) (all p < 0.001).
Personalized bacteriophage therapy to treat pandrug-resistant spinal Pseudomonas aeruginosa infection
Authors: Ferry T. , Kolenda C. , Laurent F. , Leboucher G. , Merabischvilli M. , Djebara S. , Gustave C.-A. , Perpoint T. , Barrey C. , Pirnay J.-P. , Resch G. 
Published: July 2022

AbstractBone and joint infections (BJI) are one of the most difficult-to-treat bacterial infection, especially in the era of antimicrobial resistance. Lytic bacteriophages (phages for short) are natural viruses that can selectively target and kill bacteria. They are considered to have a high therapeutic potential for the treatment of severe bacterial infections and especially BJI, as they also target biofilms. Here we report on the management of a patient with a pandrug-resistant Pseudomonas aeruginosa spinal abscess who was treated with surgery and a personalized combination of phage therapy that was added to antibiotics. As the infecting P. aeruginosa strain was resistant to the phages developed by private companies that were contacted, we set up a unique European academic collaboration to find, produce and administer a personalized phage cocktail to the patient in due time. After two surgeries, despite bacterial persistence with expression of small colony variants, the patient healed with local and intravenous injections of purified phages as adjuvant therapy.
Construction of the axolotl cell landscape using combinatorial hybridization sequencing at single-cell resolution
Authors: Ye Fang , Zhang Guodong , E. Weigao , Chen Haide , Yu Chengxuan , Yang Lei , Fu Yuting , Li Jiaqi , Fu Sulei , Sun Zhongyi , Fei Lijiang , Guo Qile , Wang Jingjing , Xiao Yanyu , Wang Xinru , Zhang Peijing , Ma Lifeng , Ge Dapeng , Xu Suhong , Caballero-Pérez Juan , Cruz-Ramírez Alfredo , Zhou Yincong , Chen Ming , Fei Ji-Feng , Han Xiaoping , Guo Guoji 
Published: July 2022

AbstractThe Mexican axolotl (Ambystoma mexicanum) is a well-established tetrapod model for regeneration and developmental studies. Remarkably, neotenic axolotls may undergo metamorphosis, a process that triggers many dramatic changes in diverse organs, accompanied by gradually decline of their regeneration capacity and lifespan. However, the molecular regulation and cellular changes in neotenic and metamorphosed axolotls are still poorly investigated. Here, we develop a single-cell sequencing method based on combinatorial hybridization to generate a tissue-based transcriptomic landscape of the neotenic and metamorphosed axolotls. We perform gene expression profiling of over 1 million single cells across 19 tissues to construct the first adult axolotl cell landscape. Comparison of single-cell transcriptomes between the tissues of neotenic and metamorphosed axolotls reveal the heterogeneity of non-immune parenchymal cells in different tissues and established their regulatory network. Furthermore, we describe dynamic gene expression patterns during limb development in neotenic axolotls. This system-level single-cell analysis of molecular characteristics in neotenic and metamorphosed axolotls, serves as a resource to explore the molecular identity of the axolotl and facilitates better understanding of metamorphosis.
A temperature-regulated circuit for feeding behavior
Authors: Qian Shaowen , Yan Sumei , Pang Ruiqi , Zhang Jing , Liu Kai , Shi Zhiyue , Wang Zhaoqun , Chen Penghui , Zhang Yanjie , Luo Tiantian , Hu Xianli , Xiong Ying , Zhou Yi 
Published: July 2022

AbstractBoth rodents and primates have evolved to orchestrate food intake to maintain thermal homeostasis in coping with ambient temperature challenges. However, the mechanisms underlying temperature-coordinated feeding behavior are rarely reported. Here we find that a non-canonical feeding center, the anteroventral and periventricular portions of medial preoptic area (apMPOA) respond to altered dietary states in mice. Two neighboring but distinct neuronal populations in apMPOA mediate feeding behavior by receiving anatomical inputs from external and dorsal subnuclei of lateral parabrachial nucleus. While both populations are glutamatergic, the arcuate nucleus-projecting neurons in apMPOA can sense low temperature and promote food intake. The other type, the paraventricular hypothalamic nucleus (PVH)-projecting neurons in apMPOA are primarily sensitive to high temperature and suppress food intake. Caspase ablation or chemogenetic inhibition of the apMPOA→PVH pathway can eliminate the temperature dependence of feeding. Further projection-specific RNA sequencing and fluorescence in situ hybridization identify that the two neuronal populations are molecularly marked by galanin receptor and apelin receptor. These findings reveal unrecognized cell populations and circuits of apMPOA that orchestrates feeding behavior against thermal challenges.
Functional data-driven framework for fast forecasting of electrode slurry rheology simulated by molecular dynamics
Authors: Duquesnoy Marc , Lombardo Teo , Caro Fernando , Haudiquez Florent , Ngandjong Alain C. , Xu Jiahui , Oularbi Hassan , Franco Alejandro A. 
Published: July 2022

AbstractThe computational simulation of the manufacturing process of lithium-ion battery composite electrodes based on mechanistic models allows capturing the influence of manufacturing parameters on electrode properties. However, ensuring that these properties match with experimental data is typically computationally expensive. In this work, we tackled this costly procedure by proposing a functional data-driven framework, aiming first to retrieve the early numerical values calculated from a molecular dynamics simulation to predict if the observable being calculated is prone to match with our range of experimental values, and in a second step, recover additional values of the ongoing simulation to predict its final result. We demonstrated this approach in the context of the calculation of electrode slurries viscosities. We report that for various electrode chemistries, the expected mechanistic simulation results can be obtained 11 times faster with respect to the complete simulations, while being accurate with a $${R}_{\rm{score}}^{2}$$

R

score

2

equals to 0.96.