bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mapping the genetic architecture of cortical morphology through neuroimaging: progress and perspectives
Authors: van der Meer Dennis , Kaufmann Tobias 
Published: October 2022

AbstractCortical morphology is a key determinant of cognitive ability and mental health. Its development is a highly intricate process spanning decades, involving the coordinated, localized expression of thousands of genes. We are now beginning to unravel the genetic architecture of cortical morphology, thanks to the recent availability of large-scale neuroimaging and genomic data and the development of powerful biostatistical tools. Here, we review the progress made in this field, providing an overview of the lessons learned from genetic studies of cortical volume, thickness, surface area, and folding as captured by neuroimaging. It is now clear that morphology is shaped by thousands of genetic variants, with effects that are region- and time-dependent, thereby challenging conventional study approaches. The most recent genome-wide association studies have started discovering common genetic variants influencing cortical thickness and surface area, yet together these explain only a fraction of the high heritability of these measures. Further, the impact of rare variants and non-additive effects remains elusive. There are indications that the quickly increasing availability of data from whole-genome sequencing and large, deeply phenotyped population cohorts across the lifespan will enable us to uncover much of the missing heritability in the upcoming years. Novel approaches leveraging shared information across measures will accelerate this process by providing substantial increases in statistical power, together with more accurate mapping of genetic relationships. Important challenges remain, including better representation of understudied demographic groups, integration of other ‘omics data, and mapping of effects from gene to brain to behavior across the lifespan.
My tongue hurts
Authors: Porter Stephen , Escudier Michael , Fedele Stefano 
Published: October 2022

AbstractThis series of articles comprise of short reviews of clinical problems relevant to oral health care in the twenty-first century. The present article uses a composite of presenting case symptoms to hypothetically illustrate differential diagnoses of pain of the tongue and why there may, or may not be, links to aspects of infection of SARS-CoV-2 (COVID-19).
Drug toxicity assessment: cell proliferation versus cell death
Authors: Sazonova Elena V. , Chesnokov Mikhail S. , Zhivotovsky Boris , Kopeina Gelina S. 
Published: October 2022

AbstractAnalysis of the toxicity of chemotherapeutic drugs is one of the main tasks of clinical pharmacology. Decreased viability of tumor cells may reflect two important physiological processes, namely the arrest of proliferation associated with disturbances in cellular metabolism or actual cell death. Elucidation of the exact processes mediating a reduction in the number of cells is fundamentally important to establish the mechanisms of drug action. Only the use of a combination of cell biological and biochemical approaches makes it possible to understand these mechanisms. Here, using various lines of tumor cells and a set of methodological approaches, we carried out a detailed comparative analysis and demonstrated the possible ways to overcome the uncertainties in establishing the mechanisms of cell response to the action of chemotherapeutic drugs and their toxicity.
A novel protein RASON encoded by a lncRNA controls oncogenic RAS signaling in KRAS mutant cancers
Authors: Cheng Rongjie , Li Fanying , Zhang Maolei , Xia Xin , Wu Jianzhuang , Gao Xinya , Zhou Huangkai , Zhang Zhi , Huang Nunu , Yang Xuesong , Zhang Yaliang , Shen Shunli , Kang Tiebang , Liu Zexian , Xiao Feizhe , Yao Hongwei , Xu Jianbo , Yan Chao , Zhang Nu 
Published: October 2022

AbstractMutations of the RAS oncogene are found in around 30% of all human cancers yet direct targeting of RAS is still considered clinically impractical except for the KRASG12C mutant. Here we report that RAS-ON (RASON), a novel protein encoded by the long intergenic non-protein coding RNA 00673 (LINC00673), is a positive regulator of oncogenic RAS signaling. RASON is aberrantly overexpressed in pancreatic ductal adenocarcinoma (PDAC) patients, and it promotes proliferation of human PDAC cell lines in vitro and tumor growth in vivo. CRISPR/Cas9-mediated knockout of Rason in mouse embryonic fibroblasts inhibits KRAS-mediated tumor transformation. Genetic deletion of Rason abolishes oncogenic KRAS-driven pancreatic and lung cancer tumorigenesis in LSL-KrasG12D; Trp53R172H/+ mice. Mechanistically, RASON directly binds to KRASG12D/V and inhibits both intrinsic and GTPase activating protein (GAP)-mediated GTP hydrolysis, thus sustaining KRASG12D/V in the GTP-bound hyperactive state. Therapeutically, deprivation of RASON sensitizes KRAS mutant pancreatic cancer cells and patient-derived organoids to EGFR inhibitors. Our findings identify RASON as a critical regulator of oncogenic KRAS signaling and a promising therapeutic target for KRAS mutant cancers.
Reprogramming of cancer-associated fibroblasts by apoptotic cancer cells inhibits lung metastasis via Notch1-WISP-1 signaling
Authors: Kim Hee Ja , Yang Kyungwon , Kim Kiyoon , Lee Ye‐Ji , Lee Sieun , Ahn Sung Yong , Ahn Young‐Ho , Kang Jihee Lee 
Published: October 2022

AbstractThe interplay between apoptotic cancer cells and the tumor microenvironment modulates cancer progression and metastasis. Cancer-associated fibroblasts (CAFs) play a crucial role in promoting these events through paracrine communication. Here, we demonstrate that conditioned medium (CM) from lung CAFs exposed to apoptotic cancer cells suppresses TGF-β1-induced migration and invasion of cancer cells and CAFs. Direct exposure of CAFs to apoptotic 344SQ cells (ApoSQ) inhibited CAF migration and invasion and the expression of CAF activation markers. Enhanced secretion of Wnt‐induced signaling protein 1 (WISP-1) by CAFs exposed to ApoSQ was required for these antimigratory and anti-invasive effects. Pharmacological inhibition of Notch1 activation or siRNA-mediated Notch1 silencing prevented WISP-1 production by CAFs and reversed the antimigratory and anti-invasive effects. Enhanced expression of the Notch ligand delta-like protein 1 on the surface of ultraviolet-irradiated apoptotic lung cancer cells triggered Notch1-WISP-1 signaling. Phosphatidylserine receptor brain-specific angiogenesis inhibitor 1 (BAI1)-Rac1 signaling, which facilitated efferocytosis by CAFs, participated in crosstalk with Notch1 signaling for optimal production of WISP-1. In addition, a single injection of ApoSQ enhanced WISP-1 production, suppressed the expression of CAF activation markers in isolated Thy1+ CAFs, and inhibited lung metastasis in syngeneic immunocompetent mice via Notch1 signaling. Treatment with CM from CAFs exposed to ApoSQ suppressed tumor growth and lung metastasis, whereas treatment with WISP-1-immunodepleted CM from CAFs exposed to ApoSQ reversed the antitumorigenic and antimetastatic effects. Therefore, treatment with CM from CAFs exposed to apoptotic lung cancer cells could be therapeutically applied to suppress CAF activation, thereby preventing cancer progression and metastasis.
High strength and damage-tolerance in echinoderm stereom as a natural bicontinuous ceramic cellular solid
Authors: Yang Ting , Jia Zian , Wu Ziling , Chen Hongshun , Deng Zhifei , Chen Liuni , Zhu Yunhui , Li Ling 
Published: October 2022

AbstractDue to their low damage tolerance, engineering ceramic foams are often limited to non-structural usages. In this work, we report that stereom, a bioceramic cellular solid (relative density, 0.2–0.4) commonly found in the mineralized skeletal elements of echinoderms (e.g., sea urchin spines), achieves simultaneous high relative strength which approaches the Suquet bound and remarkable energy absorption capability (ca. 17.7 kJ kg−1) through its unique bicontinuous open-cell foam-like microstructure. The high strength is due to the ultra-low stress concentrations within the stereom during loading, resulted from their defect-free cellular morphologies with near-constant surface mean curvatures and negative Gaussian curvatures. Furthermore, the combination of bending-induced microfracture of branches and subsequent local jamming of fractured fragments facilitated by small throat openings in stereom leads to the progressive formation and growth of damage bands with significant microscopic densification of fragments, and consequently, contributes to stereom’s exceptionally high damage tolerance.
Immunopeptidomics-based design of mRNA vaccine formulations against Listeria monocytogenes
Authors: Mayer Rupert L. , Verbeke Rein , Asselman Caroline , Aernout Ilke , Gul Adillah , Eggermont Denzel , Boucher Katie , Thery Fabien , Maia Teresa M. , Demol Hans , Gabriels Ralf , Martens Lennart , Bécavin Christophe , De Smedt Stefaan C. , Vandekerckhove Bart , Lentacker Ine , Impens Francis 
Published: October 2022

AbstractListeria monocytogenesis a foodborne intracellular bacterial pathogen leading to human listeriosis. Despite a high mortality rate and increasing antibiotic resistance no clinically approved vaccine againstListeriais available. AttenuatedListeriastrains offer protection and are tested as antitumor vaccine vectors, but would benefit from a better knowledge on immunodominant vector antigens. To identify novel antigens, we screen forListeriapeptides presented on the surface of infected human cell lines by mass spectrometry-based immunopeptidomics. In between more than 15,000 human self-peptides, we detect 68Listeriaimmunopeptides from 42 different bacterial proteins, including several known antigens. Peptides presented on different cell lines are often derived from the same bacterial surface proteins, classifying these antigens as potential vaccine candidates. Encoding these highly presented antigens in lipid nanoparticle mRNA vaccine formulations results in specific CD8+ T-cell responses and induces protection in vaccination challenge experiments in mice. Our results can serve as a starting point for the development of a clinical mRNA vaccine againstListeriaand aid to improve attenuatedListeriavaccines and vectors, demonstrating the power of immunopeptidomics for next-generation bacterial vaccine development.
Induction of the hepatic aryl hydrocarbon receptor by alcohol dysregulates autophagy and phospholipid metabolism via PPP2R2D
Authors: Kim Yun Seok , Ko Bongsub , Kim Da Jung , Tak Jihoon , Han Chang Yeob , Cho Joo-Youn , Kim Won , Kim Sang Geon 
Published: October 2022

AbstractDisturbed lipid metabolism precedes alcoholic liver injury. Whether and how AhR alters degradation of lipids, particularly phospho-/sphingo-lipids during alcohol exposure, was not explored. Here, we show that alcohol consumption in mice results in induction and activation of aryl hydrocarbon receptor (AhR) in the liver, and changes the hepatic phospho-/sphingo-lipids content. The levels of kynurenine, an endogenous AhR ligand, are elevated with increased hepatic tryptophan metabolic enzymes in alcohol-fed mice. Either alcohol or kynurenine treatment promotes AhR activation with autophagy dysregulation via AMPK. Protein Phosphatase 2 Regulatory Subunit-Bdelta (Ppp2r2d) is identified as a transcriptional target of AhR. Consequently, PPP2R2D-dependent AMPKα dephosphorylation causes autophagy inhibition and mitochondrial dysfunction. Hepatocyte-specific AhR ablation attenuates steatosis, which is associated with recovery of phospho-/sphingo-lipids content. Changes of AhR targets are corroborated using patient specimens. Overall, AhR induction by alcohol inhibits autophagy in hepatocytes through AMPKα, which is mediated by Ppp2r2d gene transactivation, revealing an AhR-dependent metabolism of phospho-/sphingo-lipids.
Tidewater-glacier response to supraglacial lake drainage
Authors: Stevens Laura A. , Nettles Meredith , Davis James L. , Creyts Timothy T. , Kingslake Jonathan , Hewitt Ian J. , Stubblefield Aaron 
Published: October 2022

AbstractThe flow speed of the Greenland Ice Sheet changes dramatically in inland regions when surface meltwater drains to the bed. But ice-sheet discharge to the ocean is dominated by fast-flowing outlet glaciers, where the effect of increasing surface melt on annual discharge is unknown. Observations of a supraglacial lake drainage at Helheim Glacier, and a consequent velocity pulse propagating down-glacier, provide a natural experiment for assessing the impact of changes in injected meltwater, and allow us to interrogate the subglacial hydrological system. We find a highly efficient subglacial drainage system, such that summertime lake drainage has little net effect on ice discharge. Our results question the validity of common remote-sensing approaches for inferring subglacial conditions, knowledge of which is needed for improved projections of sea-level rise.
Zinc isotopic evidence for recycled carbonate in the deep mantle
Authors: Zhang Xiao-Yu , Chen Li-Hui , Wang Xiao-Jun , Hanyu Takeshi , Hofmann Albrecht W. , Komiya Tsuyoshi , Nakamura Kentaro , Kato Yasuhiro , Zeng Gang , Gou Wen-Xian , Li Wei-Qiang 
Published: October 2022

AbstractCarbonate, the major carbon reservoir on Earth’s surface, can enter into the mantle by subduction. However, evidence for recycled surficial carbonates in the deep mantle is still scarce. Ocean island basalts from Cook-Austral islands and St. Helena Island, widely called HIMU basalts because of their high μ = 238U/204Pb sources, are thought to be fed by mantle plumes originating in the lower mantle. Here we report exceptionally high δ66Zn values (δ66Zn = 0.38 ± 0.03‰) of these HIMU lavas relative to most published data for oceanic basalts (δ66Zn = 0.31 ± 0.10‰), which requires a source contributed by isotopically heavy recycled surficial carbonates. During subduction of the oceanic lithosphere, melting of mixed surficial carbonates and basaltic crust in the deep mantle generates carbonatite melts, which metasomatizes the nearby mantle and the resultant carbonated mantle ultimately evolves into a high-δ66Zn HIMU source. High-δ66Zn signatures of HIMU basalts, therefore, demonstrate that carbonates can be transported into Earth’s deep mantle.
The gut microbe Bacteroides fragilis ameliorates renal fibrosis in mice
Authors: Zhou Wei , Wu Wen-hui , Si Zi-lin , Liu Hui-ling , Wang Hanyu , Jiang Hong , Liu Ya-fang , Alolga Raphael N. , Chen Cheng , Liu Shi-jia , Bian Xue-yan , Shan Jin-jun , Li Jing , Tan Ning-hua , Zhang Zhi-hao 
Published: October 2022

AbstractRenal fibrosis is an inevitable outcome of various manifestations of progressive chronic kidney diseases (CKD). The need for efficacious treatment regimen against renal fibrosis can therefore not be overemphasized. Here we show a novel protective role of Bacteroides fragilis (B. fragilis) in renal fibrosis in mice. We demonstrate decreased abundance of B. fragilis in the feces of CKD patients and unilateral ureteral obstruction (UUO) mice. Oral administration of live B. fragilis attenuates renal fibrosis in UUO and adenine mice models. Increased lipopolysaccharide (LPS) levels are decreased after B. fragilis administration. Results of metabolomics and proteomics studies show decreased level of 1,5-anhydroglucitol (1,5-AG), a substrate of SGLT2, which increases after B. fragilis administration via enhancement of renal SGLT2 expression. 1,5-AG is an agonist of TGR5 that attenuates renal fibrosis by inhibiting oxidative stress and inflammation. Madecassoside, a natural product found via in vitro screening promotes B. fragilis growth and remarkably ameliorates renal fibrosis. Our findings reveal the ameliorative role of B. fragilis in renal fibrosis via decreasing LPS and increasing 1,5-AG levels.
Genetic map of regional sulcal morphology in the human brain from UK biobank data
Authors: Sun Benjamin B. , Loomis Stephanie J. , Pizzagalli Fabrizio , Shatokhina Natalia , Painter Jodie N. , Foley Christopher N. ,   Biogen Biobank Team, Sun Benjamin , Tsai Ellen , Bronson Paola , Sexton David , John Sally , Marshall Eric , Patel Mehool , Duraisamy Saranya , Swan Timothy , Baird Dennis , Chen Chia-Yen , Eaton Susan , Gagnon Jake , Gao Feng , Gubbels Cynthia , Huang Yunfeng , Kupelian Varant , Li Kejie , Liu Dawei , Loomis Stephanie , McLaughlin Helen , Mitchell Adele , Jensen Megan E. , McLaren Donald G. , Chintapalli Sai Spandana , Zhu Alyssa H. , Dixon Daniel , Islam Tasfiya , Ba Gari Iyad , Runz Heiko , Medland Sarah E. , Thompson Paul M. , Jahanshad Neda , Whelan Christopher D. 
Published: October 2022

AbstractGenetic associations with macroscopic brain structure can provide insights into brain function and disease. However, specific associations with measures of local brain folding are largely under-explored. Here, we conducted large-scale genome- and exome-wide associations of regional cortical sulcal measures derived from magnetic resonance imaging scans of 40,169 individuals in UK Biobank. We discovered 388 regional brain folding associations across 77 genetic loci, with genes in associated loci enriched for expression in the cerebral cortex, neuronal development processes, and differential regulation during early brain development. We integrated brain eQTLs to refine genes for various loci, implicated several genes involved in neurodevelopmental disorders, and highlighted global genetic correlations with neuropsychiatric phenotypes. We provide an interactive 3D visualisation of our summary associations, emphasising added resolution of regional analyses. Our results offer new insights into the genetic architecture of brain folding and provide a resource for future studies of sulcal morphology in health and disease.
Flexible active antenna arrays
Authors: Gal-Katziri Matan , Fikes Austin , Hajimiri Ali 
Published: October 2022

AbstractComplex and dynamic control of radiated fields are advantageous for flexible radio systems, which naturally move, roll, bend, twist, deform, and vibrate. Practical challenges hinder the proliferation of these antenna arrays. This work shows how using radio-frequency microchips reduces system component count, decreases mass to ~0.1 g cm−2, and increases functionality and mechanical flexibility. We develop a general platform for large scale flexible arrays and demonstrate two different 256-elements, 30 × 30 cm2 flexible arrays. By varying supply distribution methods and radiators we show how performance can be optimized for maximum power delivery or physical flexibility. The demonstrated systems conform to curved surfaces with radii of curvatures as low as 23 cm and wirelessly deliver ~ 80 mW of DC power to a 6.7 cm × 11 cm-receiver over one meter away. This paves the way towards the integration of smart arrays in flexible wearables and deployable lightweight airborne systems.
Machine learning to predict the development of recurrent urinary tract infection related to single uropathogen, Escherichia coli
Authors: Jeng Shuen-Lin , Huang Zi-Jing , Yang Deng-Chi , Teng Ching-Hao , Wang Ming-Cheng 
Published: October 2022

AbstractRecurrent urinary tract infection (RUTI) can damage renal function and has impact on healthcare costs and patients’ quality of life. There were 2 stages for development of prediction models for RUTI. The first stage was a scenario in the clinical visit. The second stage was a scenario after hospitalization for urinary tract infection caused by Escherichia coli. Three machine learning models, logistic regression (LR), decision tree (DT), and random forest (RF) were built for the RUTI prediction. The RF model had higher prediction accuracy than LR and DT (0.700, 0.604, and 0.654 in stage 1, respectively; 0.709, 0.604, and 0.635 in stage 2, respectively). The decision rules constructed by the DT model could provide high classification accuracy (up to 0.92 in stage 1 and 0.94 in stage 2) in certain subgroup patients in different scenarios. In conclusion, this study provided validated machine learning models and RF could provide a better accuracy in predicting the development of single uropathogen (E. coli) RUTI. Both host and bacterial characteristics made important contribution to the development of RUTI in the prediction models in the 2 clinical scenarios, respectively. Based on the results, physicians could take action to prevent the development of RUTI.
Prediction of prognosis, immune infiltration and immunotherapy response with N6-methyladenosine-related lncRNA clustering patterns in cervical cancer
Authors: Jia Haixia , Cao Meiting , Hao Suhua , Wang Jiahao , Wang Jintao 
Published: October 2022

AbstractLncRNAs and tumor microenvironment (TME) exert an important effect in antitumor immunity. Nonetheless, the role of m6A-related lncRNA clustering patterns in prognosis, TME and immunotherapy of cervical cancer (CC) remains unknown. Here, based on 7 m6A-related prognostic lncRNAs obtained from TCGA-CC dataset, two m6AlncRNA clustering patterns were determined. m6AlncRNA clusterA was characterized by immune cell infiltrates and immune activation. m6AlncRNA clusterB was characterized by enrichment of immune evasion and tumorigenic activation pathways as well as survival and clinical stage disadvantage. Then, principal component analysis algorithms were used to construct m6AlncRNAscore based on prognostic differentially expressed genes between two m6AlncRNA clusters to quantify m6AlncRNA clustering patterns. m6AlncRNAscore was an independent prognostic protective factor. Higher Th2 and Treg cells and enrichment of immunosuppressive pathways were observed in the low-m6AlncRNAscore group, with poorer survival. High-m6AlncRNAscore was characterized by increased infiltration of activated CD8 T cell, enrichment of immune activation pathways, lower IL-10 and TGF-beta1 levels, and higher immunophenscore values, indicating inflamed TME and better anti-tumor immunotherapy efficacy. Quantitative Real-Time Polymerase Chain Reaction was used for detection of m6A-related prognostic lncRNAs. Collectively, we identified two m6AlncRNA clustering patterns which play a nonnegligible role in the prognosis, TME heterogeneity and immunotherapy of CC patients.
MHD micropolar hybrid nanofluid flow over a flat surface subject to mixed convection and thermal radiation
Authors: Lone Showkat Ahmad , Alyami Maryam Ahmed , Saeed Anwar , Dawar Abdullah , Kumam Poom , Kumam Wiyada 
Published: October 2022

AbstractHybrid nanofluids play a significant role in the advancement of thermal characteristics of pure fluids both at experimental and industrial levels. This work explores the mixed convective MHD micropolar hybrid nanofluid flow past a flat surface. The hybrid nanofluid flow is composed of alumina and silver nanoparticles whereas water is used as a base fluid. The plate has placed vertical in a permeable medium with suction and injection effects. Furthermore, viscous dissipation, thermal radiation and Joule heating effects are taken into consideration. Specific similarity variables have been used to convert the set of modeled equations to dimension-free form and then has solved by homotopy analysis method (HAM). It has revealed in this investigation that, fluid motion upsurge with growth in magnetic field effects and mixed convection parameter and decline with higher values of micropolar factor. Micro-rotational velocity of fluid is upsurge with higher values of micropolar factor. Thermal flow behavior is augmenting for expended values of magnetic effects, radiation factor, Eckert number and strength of heat source. The intensification in magnetic strength and mixed convection factors has declined the skin friction and has upsurge with higher values of micropolar parameter. The Nusselt number has increased with the intensification in magnetic effects, radiation factor and Eckert number.