bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determining the Beaming of Io Decametric Emissions: A Remote Diagnostic to Probe the Io‐Jupiter Interaction
Authors: Lamy L. , Colomban L. , Zarka P. , Prangé R. , Marques M. S. , Louis C. K. , Kurth W. S. , Cecconi B. , Girard J. N. , Grießmeier J.‐M. , Yerin S. 
Published: March 2022

AbstractWe investigate the beaming of 11 Io‐Jupiter decametric (Io‐DAM) emissions observed by Juno/Waves, the Nançay Decameter Array, and NenuFAR. Using an up‐to‐date magnetic field model and three methods to position the active Io Flux Tube (IFT), we accurately locate the radiosources and determine their emission angle θ from the local magnetic field vector. These methods use (a) updated models of the IFT equatorial lead angle, (b) ultraviolet (UV) images of Jupiter's aurorae, and (c) multi‐point radio measurements. The kinetic energy Ee− of source electrons is then inferred from θ in the framework of the Cyclotron Maser Instability. The precise position of the active IFT achieved from methods (b and c) can be used to test the effective plasma density of the Io torus. Simultaneous radio/UV observations reveal that multiple Io‐DAM arcs are associated with multiple UV spots and provide the first direct evidence of an Io‐DAM arc associated with a trans‐hemispheric beam UV spot. Multi‐point radio observations probe the Io‐DAM sources at various altitudes, times and hemispheres. Overall, θ varies a function of frequency (altitude), by decreasing from 75°−80° to 70°−75° over 10−40 MHz with slightly larger values in the northern hemisphere, and independently varies as a function of time (or longitude of Io). Its uncertainty of a few degrees is dominated by the error on the longitude of the active IFT. The inferred values of Ee− also vary as a function of altitude and time. For the 11 investigated cases, they range from 3 to 16 keV, with a 6.6 ± 2.7 keV average.
Notch signaling pathway: architecture, disease, and therapeutics
Authors: Zhou Binghan , Lin Wanling , Long Yaling , Yang Yunkai , Zhang Huan , Wu Kongming , Chu Qian 
Published: March 2022

AbstractThe NOTCH gene was identified approximately 110 years ago. Classical studies have revealed that NOTCH signaling is an evolutionarily conserved pathway. NOTCH receptors undergo three cleavages and translocate into the nucleus to regulate the transcription of target genes. NOTCH signaling deeply participates in the development and homeostasis of multiple tissues and organs, the aberration of which results in cancerous and noncancerous diseases. However, recent studies indicate that the outcomes of NOTCH signaling are changeable and highly dependent on context. In terms of cancers, NOTCH signaling can both promote and inhibit tumor development in various types of cancer. The overall performance of NOTCH-targeted therapies in clinical trials has failed to meet expectations. Additionally, NOTCH mutation has been proposed as a predictive biomarker for immune checkpoint blockade therapy in many cancers. Collectively, the NOTCH pathway needs to be integrally assessed with new perspectives to inspire discoveries and applications. In this review, we focus on both classical and the latest findings related to NOTCH signaling to illustrate the history, architecture, regulatory mechanisms, contributions to physiological development, related diseases, and therapeutic applications of the NOTCH pathway. The contributions of NOTCH signaling to the tumor immune microenvironment and cancer immunotherapy are also highlighted. We hope this review will help not only beginners but also experts to systematically and thoroughly understand the NOTCH signaling pathway.
Pseudomonas aeruginosa polysaccharide Psl supports airway microbial community development
Authors: Stoner Sara N , Baty Joshua J , Scoffield Jessica A 
Published: March 2022

Abstract
Pseudomonas aeruginosa dominates the complex polymicrobial cystic fibrosis (CF) airway and is a leading cause of death in persons with CF. Oral streptococcal colonization has been associated with stable CF lung function. However, no studies have demonstrated how Streptococcus salivarius, the most abundant streptococcal species found in individuals with stable CF lung disease, potentially improves lung function or becomes incorporated into the CF airway biofilm. By utilizing a two-species biofilm model to probe interactions between S. salivarius and P. aeruginosa, we discovered that the P. aeruginosa exopolysaccharide Psl promoted S. salivarius biofilm formation. Further, we identified a S. salivarius maltose-binding protein (MalE) that is required for promotion of biofilm formation both in vitro and in a Drosophila melanogaster co-infection model. Finally, we demonstrate that promotion of dual biofilm formation with S. salivarius is common among environmental and clinical P. aeruginosa isolates. Overall, our data supports a model in which S. salivarius uses a sugar-binding protein to interact with P. aeruginosa exopolysaccharide, which may be a strategy by which S. salivarius establishes itself within the CF airway microbial community.
Sleep’s role in updating aversive autobiographical memories
Authors: Azza Yasmine , Wilhelm Frank H. , Seifritz Erich , Junghanns Klaus , Kleim Birgit , Wilhelm Ines 
Published: March 2022

AbstractAversive autobiographical memories play a key role in the development and maintenance of many mental disorders. Imagery rescripting is a well-established psychotherapeutic intervention aiming to create a more adaptive version of an aversive memory by modifying its interpretation. Sleep has been shown to support reconsolidation of updated neutral memories. Here, we investigated in healthy participants whether a 90-min nap compared to wake supports the adaptive reconsolidation of autobiographical memories. Forty-four university students received a single 50-min imagery rescripting session. Thereafter, half of the participants took a 90-min nap, whereas the other half stayed awake. Subjective (arousal ratings, reports of emotions and dysfunctional cognitions) and heart rate (HR) responses to individual memory scripts were measured before the intervention (pre), after the 90-min retention interval (post 1) and 7 days later (post 2). Results demonstrate a significant decrease in distress of aversive memories pre to post imagery rescripting. The nap group showed less distressing dysfunctional cognitions along with a lower HR in response to the negative memory script as compared to the wake group at post 1. These differences were no longer evident 1 week later (post 2). Central sleep spindle density during the nap was correlated with the reduction in HR in response to the negative memory script from pre to post 1. Our results provide first evidence for sleep benefitting adaptive reconsolidation of aversive autobiographical memories. Future research should expand this approach to clinical populations and investigate precise conditions under which sleep may benefit psychotherapeutic interventions utilizing reconsolidation mechanisms.
No increase in inflammation in late-life major depression screened to exclude physical illness
Authors: Luning Prak Eline T. , Brooks Thomas , Makhoul Walid , Beer Joanne C. , Zhao Ling , Girelli Tommaso , Skarke Carsten , Sheline Yvette I. 
Published: March 2022

AbstractDepression is a common and debilitating disorder in the elderly. Late-life depression (LLD) has been associated with inflammation and elevated levels of proinflammatory cytokines including interleukin (IL)-1β, tumor necrosis factor-alpha, and IL-6, but often depressed individuals have comorbid medical conditions that are associated with immune dysregulation. To determine whether depression has an association with inflammation independent of medical illness, 1120 adults were screened to identify individuals who had clinically significant depression but not medical conditions associated with systemic inflammation. In total, 66 patients with LLD screened to exclude medical conditions associated with inflammation were studied in detail along with 26 age-matched controls (HC). At baseline, circulating cytokines were low and similar in LLD and HC individuals. Furthermore, cytokines did not change significantly after treatment with either an antidepressant (escitalopram 20 mg/day) or an antidepressant plus a COX-2 inhibitor or placebo, even though depression scores improved in the non-placebo treatment arms. An analysis of cerebrospinal fluid in a subset of individuals for IL-1β using an ultrasensitive digital enzyme-linked immunosorbent assay revealed low levels in both LLD and HC at baseline. Our results indicate that depression by itself does not result in systemic or intrathecal elevations in cytokines and that celecoxib does not appear to have an adjunctive antidepressant role in older patients who do not have medical reasons for having inflammation. The negative finding for increased inflammation and the lack of a treatment effect for celecoxib in this carefully screened depressed population taken together with multiple positive results for inflammation in previous studies that did not screen out physical illness support a precision medicine approach to the treatment of depression that takes the medical causes for inflammation into account.
Disruption of 5-hydroxytryptamine 1A receptor and orexin receptor 1 heterodimer formation affects novel G protein-dependent signaling pathways and has antidepressant effects in vivo
Authors: Zhang Rumin , Li Dandan , Mao Huiling , Wei Xiaonan , Xu MingDong , Zhang Shengnan , Jiang Yunlu , Wang Chunmei , Xin Qing , Chen Xiaoyu , Li Guorong , Ji Bingyuan , Yan Maocai , Cai Xin , Dong Bo , Randeva Harpal S. , Liu Chuanxin , Chen Jing 
Published: March 2022

AbstractG protein-coupled receptor (GPCR) heterodimers are new targets for the treatment of depression. Increasing evidence supports the importance of serotonergic and orexin-producing neurons in numerous physiological processes, possibly via a crucial interaction between 5-hydroxytryptamine 1A receptor (5-HT1AR) and orexin receptor 1 (OX1R). However, little is known about the function of 5-HT1AR/OX1R heterodimers. It is unclear how the transmembrane domains (TMs) of the dimer affect its function and whether its modulation mediates antidepressant-like effects. Here, we examined the mechanism of 5-HT1AR/OX1R dimerization and downstream G protein-dependent signaling. We found that 5-HT1AR and OX1R form constitutive heterodimers that induce novel G protein-dependent signaling, and that this heterodimerization does not affect recruitment of β-arrestins to the complex. In addition, we found that the structural interface of the active 5-HT1AR/OX1R dimer transforms from TM4/TM5 in the basal state to TM6 in the active conformation. We also used mutation analyses to identify key residues at the interface (5-HT1AR R1514.40, 5-HT1AR Y1985.41, and OX1R L2305.54). Injection of chronic unpredictable mild stress (CUMS) rats with TM4/TM5 peptides improved their depression-like emotional status and decreased the number of endogenous 5-HT1AR/OX1R heterodimers in the rat brain. These antidepressant effects may be mediated by upregulation of BDNF levels and enhanced phosphorylation and activation of CREB in the hippocampus and medial prefrontal cortex. This study provides evidence that 5-HT1AR/OX1R heterodimers are involved in the pathological process of depression. Peptides including TMs of the 5-HT1AR/OX1R heterodimer interface are candidates for the development of compounds with fast-acting antidepressant-like effects.
Complex roles of nicotinamide N-methyltransferase in cancer progression
Authors: Wang Weixuan , Yang Changmei , Wang Tianxiang , Deng Haiteng 
Published: March 2022

AbstractNicotinamide N-methyltransferase (NNMT) is an intracellular methyltransferase, catalyzing the N-methylation of nicotinamide (NAM) to form 1-methylnicotinamide (1-MNAM), in which S-adenosyl-l-methionine (SAM) is the methyl donor. High expression of NNMT can alter cellular NAM and SAM levels, which in turn, affects nicotinamide adenine dinucleotide (NAD+)-dependent redox reactions and signaling pathways, and remodels cellular epigenetic states. Studies have revealed that NNMT plays critical roles in the occurrence and development of various cancers, and analysis of NNMT expression levels in different cancers from The Cancer Genome Atlas (TCGA) dataset indicated that NNMT might be a potential biomarker and therapeutic target for tumor diagnosis and treatment. This review provides a comprehensive understanding of recent advances on NNMT functions in different tumors and deciphers the complex roles of NNMT in cancer progression.
CircTHBS1 drives gastric cancer progression by increasing INHBA mRNA expression and stability in a ceRNA- and RBP-dependent manner
Authors: Qiu Shengkui , Li Bowen , Xia Yiwen , Xuan Zhe , Li Zheng , Xie Li , Gu Chao , Lv Jialun , Lu Chen , Jiang Tianlu , Fang Lang , Xu Penghui , Yang Jing , Li Ying , Chen Zetian , Zhang Lu , Wang Linjun , Zhang Diancai , Xu Hao , Wang Weizhi , Xu Zekuan 
Published: March 2022

AbstractCircular RNAs (circRNAs) play vital regulatory roles in the progression of multiple cancers. In our study, transcriptome analysis and self-organizing maps (SOM) were applied to screen backbone circRNAs in gastric cancer (GC). Upon validation of the expression patterns of screened circRNAs, gain- and loss-of-function assays were performed in vitro and in vivo. Underlying mechanisms were investigated using RNA pull-down, luciferase reporter assay and RNA immunoprecipitation. The expression of circTHBS1 was significantly increased in GC and associated with poor prognosis. CircTHBS1 facilitated the malignant behavior and epithelial-to-mesenchymal transition of GC cells. Mechanistically, circTHBS1 sponged miR-204-5p to promote the expression of Inhibin Subunit Beta A (INHBA). Moreover, circTHBS1 could enhance the HuR-mediated mRNA stability of INHBA, which subsequently activated the TGF-β pathway. Our research identified circTHBS1 as an oncogenic circRNA that enhances GC malignancy by elevating INHBA expression, providing new insight and a feasible target for the diagnosis and treatment of GC.
Detection of cracked teeth using a mechanoluminescence phosphor with a stretchable photodetector array
Authors: Kim Ha Jun , Ji Sangyoon , Han Ju Yeon , Cho Han Bin , Park Young-Geun , Choi Dongwhi , Cho Hoonsung , Park Jang-Ung , Im Won Bin 
Published: March 2022

AbstractCracked tooth syndrome (CTS) is an incomplete fracture of a human tooth that commonly arises from chewing hard foods. Although it is a very common syndrome, CTS is often difficult to diagnose owing to the common small size of tooth cracks. Conventional techniques for the detection of cracks, such as transillumination and radiographic methods, are inaccurate and have poor imaging resolution. In this study, we devise a novel method for the in vivo detection of tooth microcracks by exploiting the mechanoluminescence (ML) phenomenon. ZrO2:Ti4+ (ZRT) phosphor particles are pasted onto suspected regions of tooth cracks and emit cyan-colored light as a result of masticatory forces. Then, a stretchable and self-healable photodetector (PD) array laminated on top of the phosphor particles converts the emitted photons into a photocurrent, which facilitates the two-dimensional mapping of the tooth cracks. Because of the high photosensitivity of the PD, intense ML and small size of ZRT phosphor particles, it is possible to image submicron- to micron-sized cracks with high resolution. Furthermore, the uniqueness of this technique over the conventional techniques stems from the application of a simple optical phenomenon, i.e., ML, for obtaining precise information regarding the locations, depth, and length of tooth cracks.
Harnessing DSB repair to promote efficient homology-dependent and -independent prime editing
Authors: Peterka Martin , Akrap Nina , Li Songyuan , Wimberger Sandra , Hsieh Pei-Pei , Degtev Dmitrii , Bestas Burcu , Barr Jack , van de Plassche Stijn , Mendoza-Garcia Patricia , Šviković Saša , Sienski Grzegorz , Firth Mike , Maresca Marcello 
Published: March 2022

AbstractPrime editing recently emerged as a next-generation approach for precise genome editing. Here we exploit DNA double-strand break (DSB) repair to develop two strategies that install precise genomic insertions using an SpCas9 nuclease-based prime editor (PEn). We first demonstrate that PEn coupled to a regular prime editing guide RNA (pegRNA) efficiently promotes short genomic insertions through a homology-dependent DSB repair mechanism. While PEn editing leads to increased levels of by-products, it can rescue pegRNAs that perform poorly with a nickase-based prime editor. We also present a small molecule approach that yields increased product purity of PEn editing. Next, we develop a homology-independent PEn editing strategy, which installs genomic insertions at DSBs through the non-homologous end joining pathway (NHEJ). Lastly, we show that PEn-mediated insertions at DSBs prevent Cas9-induced large chromosomal deletions and provide evidence that continuous Cas9-mediated cutting is one of the mechanisms by which Cas9-induced large deletions arise. Altogether, this work expands the current prime editing toolbox by leveraging distinct DNA repair mechanisms including NHEJ, which represents the primary pathway of DSB repair in mammalian cells.
A genome-wide meta-analysis identifies 50 genetic loci associated with carpal tunnel syndrome
Authors: Skuladottir Astros Th. , Bjornsdottir Gyda , Ferkingstad Egil , Einarsson Gudmundur , Stefansdottir Lilja , Nawaz Muhammad Sulaman , Oddsson Asmundur , Olafsdottir Thorunn A. , Saevarsdottir Saedis , Walters G. Bragi , Magnusson Sigurdur H. , Bjornsdottir Anna , Sveinsson Olafur A. , Vikingsson Arnor , Hansen Thomas Folkmann , Jacobsen Rikke Louise , Erikstrup Christian , Schwinn Michael , Brunak Søren , Banasik Karina , Ostrowski Sisse Rye , Troelsen Anders , Henkel Cecilie , Pedersen Ole Birger ,   DBDS Genetic Consortium, Andersen Steffen , Burgdorf Kristoffer , Didriksen Maria , Dinh Khoa Manh , Hjalgrim Henrik , Jemec Gregor , Jennum Poul , Johansson Pär Ingemar , Larsen Margit Anita Hørup , Mikkelsen Susan , Nielsen Kasper Rene , Nyegaard Mette , Stefánsson Hreinn , Sækmose Susanne , Sørensen Erik , Thorsteinsdottir Unnur , Bruun Mie Topholm , Ullum Henrik , Werge Thomas , Jonsdottir Ingileif , Gudbjartsson Daniel F. , Sulem Patrick , Thorgeirsson Thorgeir E. , Stefansson Hreinn , Stefansson Kari 
Published: March 2022

AbstractCarpal tunnel syndrome (CTS) is the most common entrapment neuropathy and has a largely unknown underlying biology. In a genome-wide association study of CTS (48,843 cases and 1,190,837 controls), we found 53 sequence variants at 50 loci associated with the syndrome. The most significant association is with a missense variant (p.Glu366Lys) in SERPINA1 that protects against CTS (P = 2.9 × 10−24, OR = 0.76). Through various functional analyses, we conclude that at least 22 genes mediate CTS risk and highlight the role of 19 CTS variants in the biology of the extracellular matrix. We show that the genetic component to the risk is higher in bilateral/recurrent/persistent cases than nonrecurrent/nonpersistent cases. Anthropometric traits including height and BMI are genetically correlated with CTS, in addition to early hormonal-replacement therapy, osteoarthritis, and restlessness. Our findings suggest that the components of the extracellular matrix play a key role in the pathogenesis of CTS.
Automated multilabel diagnosis on electrocardiographic images and signals
Authors: Sangha Veer , Mortazavi Bobak J. , Haimovich Adrian D. , Ribeiro Antônio H. , Brandt Cynthia A. , Jacoby Daniel L. , Schulz Wade L. , Krumholz Harlan M. , Ribeiro Antonio Luiz P. , Khera Rohan 
Published: March 2022

AbstractThe application of artificial intelligence (AI) for automated diagnosis of electrocardiograms (ECGs) can improve care in remote settings but is limited by the reliance on infrequently available signal-based data. We report the development of a multilabel automated diagnosis model for electrocardiographic images, more suitable for broader use. A total of 2,228,236 12-lead ECGs signals from 811 municipalities in Brazil are transformed to ECG images in varying lead conformations to train a convolutional neural network (CNN) identifying 6 physician-defined clinical labels spanning rhythm and conduction disorders, and a hidden label for gender. The image-based model performs well on a distinct test set validated by at least two cardiologists (average AUROC 0.99, AUPRC 0.86), an external validation set of 21,785 ECGs from Germany (average AUROC 0.97, AUPRC 0.73), and printed ECGs, with performance superior to signal-based models, and learning clinically relevant cues based on Grad-CAM. The model allows the application of AI to ECGs across broad settings.
Ultrafast photothermoelectric effect in Dirac semimetallic Cd3As2 revealed by terahertz emission
Authors: Lu Wei , Fan Zipu , Yang Yunkun , Ma Junchao , Lai Jiawei , Song Xiaoming , Zhuo Xiao , Xu Zhaoran , Liu Jing , Hu Xiaodong , Zhou Shuyun , Xiu Faxian , Cheng Jinluo , Sun Dong 
Published: March 2022

AbstractThe thermoelectric effects of topological semimetals have attracted tremendous research interest because many topological semimetals are excellent thermoelectric materials and thermoelectricity serves as one of their most important potential applications. In this work, we reveal the transient photothermoelectric response of Dirac semimetallic Cd3As2, namely the photo-Seebeck effect and photo-Nernst effect, by studying the terahertz (THz) emission from the transient photocurrent induced by these effects. Our excitation polarization and power dependence confirm that the observed THz emission is due to photothermoelectric effect instead of other nonlinear optical effect. Furthermore, when a weak magnetic field (~0.4 T) is applied, the response clearly indicates an order of magnitude enhancement on transient photothermoelectric current generation compared to the photo-Seebeck effect. Such enhancement supports an ambipolar transport nature of the photo-Nernst current generation in Cd3As2. These results highlight the enhancement of thermoelectric performance can be achieved in topological Dirac semimetals based on the Nernst effect, and our transient studies pave the way for thermoelectric devices applicable for high field circumstance when nonequilibrium state matters. The large THz emission due to highly efficient photothermoelectric conversion is comparable to conventional semiconductors through optical rectification and photo-Dember effect.
BMP feed-forward loop promotes terminal differentiation in gastric glands and is interrupted by H. pylori-driven inflammation
Authors: Kapalczynska Marta , Lin Manqiang , Maertzdorf Jeroen , Heuberger Julian , Muellerke Stefanie , Zuo Xiangsheng , Vidal Ramon , Shureiqi Imad , Fischer Anne-Sophie , Sauer Sascha , Berger Hilmar , Kidess Evelyn , Mollenkopf Hans-Joachim , Tacke Frank , Meyer Thomas F. , Sigal Michael 
Published: March 2022

AbstractHelicobacter pylori causes gastric inflammation, gland hyperplasia and is linked to gastric cancer. Here, we studied the interplay between gastric epithelial stem cells and their stromal niche under homeostasis and upon H. pylori infection. We find that gastric epithelial stem cell differentiation is orchestrated by subsets of stromal cells that either produce BMP inhibitors in the gland base, or BMP ligands at the surface. Exposure to BMP ligands promotes a feed-forward loop by inducing Bmp2 expression in the epithelial cells themselves, enforcing rapid lineage commitment to terminally differentiated mucous pit cells. H. pylori leads to a loss of stromal and epithelial Bmp2 expression and increases expression of BMP inhibitors, promoting self-renewal of stem cells and accumulation of gland base cells, which we mechanistically link to IFN-γ signaling. Mice that lack IFN-γ signaling show no alterations of BMP gradient upon infection, while exposure to IFN-γ resembles H. pylori-driven mucosal responses.