bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can gesture input support toddlers’ fast mapping?
Authors: FORAN Lori G. , BEVERLY Brenda L. , SHELLEY-TREMBLAY John , ESTIS Julie M. 
Published: April 2022

AbstractForty-eight toddlers participated in a word-learning task to assess gesture input on mapping nonce words to unfamiliar objects. Receptive fast mapping and expressive naming for target object-word pairs were tested in three conditions – with a point, with a shape gesture, and in a no-gesture, word-only condition. No statistically significant effect of gesture for receptive fast-mapping was found but age was a factor. Two year olds outperformed one year olds for both measures. Only one girl in the one-year-old group correctly named any items. There was a significant interaction between gesture and gender for expressive naming. Two-year-old girls were six times more likely than two-year-old boys to correctly name items given point and shape gestures; whereas, boys named more items taught with the word only than with a point or shape gesture. The role of gesture input remains unclear, particularly for children under two years and for toddler boys.
‘Irrational Nuances’: Interpreting Stockhausen'sKlavierstück I
Authors: JONES GABRIEL 
Published: April 2022

AbstractThe performance practice of European serial music has long been misunderstood. This article uses Stockhausen'sKlavierstück I(1952–3) as a lens through which to view the realities of this practice, drawing on close contextual analysis of the affordances of the score and the now significant corpus of recordings. These findings are used to extend M. J. Grant's view of serial aesthetics and to provide a practical basis for what she calls ‘serial listening’. Three principal styles of performance are identified and attendant modes of listening suggested, relating to the non-thematic principles and hermeneutic contexts of serial music, which include the embodied response of the performer to defamiliarized musical material and the nascent dialectic of instrumental and electronic composition. This investigation – informing serious judgements of value and taste – has broader implications for the development of Stockhausen's notation and temporal theory in the 1950s and for the performance practice of new music.
Magnesium Isotope Fractionation During Silicate Weathering: Constrains From Riverine Mg Isotopic Composition in the Southeastern Coastal Region of China
Authors: Zhao Tong , Liu Wenjing , Xu Zhifang 
Published: April 2022

AbstractMg isotopic composition of river water is dominantly controlled by the dissolution of both silicate and carbonate sources and a series of biogeochemical processes. However, the relative importance of source and isotopic fractionation control at basin/global scale is poorly constrained. This study presents the Mg isotopic composition of river water and suspended load in river draining silicate rocks in the southeastern coastal region of China. The fractionation effect of silicate weathering on Mg isotopes is documented in both dissolved and solid phases. Mg isotopic composition of rivers draining silicate rocks exhibit ∼0.3‰ δ26Mg difference, the release of Mg from Mg‐rich minerals and formation of clays are the dominant processes controlling Mg isotopic composition of river water. The variation of Mg isotopic compositions of suspended load is closely related to the species of secondary clays (illite and chlorite); the fractionation direction during illite and chlorite formation contrasts, isotopically heavy Mg preferentially incorporates into illite while light Mg incorporates into chlorite. Furthermore, the negative correlation between 1/Mg and Mg isotopic compositions of river water indicates the Mg re‐distribution and isotope fractionation between weathering solutions and secondary clays during silicate weathering. Such isotope fractionation‐induced Mg isotope variations could be employed to estimate the contribution of Mg from silicate weathering at basin/continental scale.
Modeling Subsurface Hydrogen Storage With Transport Properties From Entropy Scaling Using the PC‐SAFT Equation of State
Authors: Eller Johannes , Sauerborn Tim , Becker Beatrix , Buntic Ivan , Gross Joachim , Helmig Rainer 
Published: April 2022

AbstractHydrogen is a promising alternative to carbon based energy carriers and may be stored in large quantities in subsurface storage deposits. This work assesses the impact of static (density and phase equilibria) and dynamic (viscosity and diffusion coefficients) properties on the pressure field during the injection and extraction of hydrogen in the porous subsurface. In a first step, we derive transport properties for water, hydrogen and their mixture using the Perturbed‐Chain Statistical Associating Fluid Theory equation of state in combination with an entropy scaling approach and compare model predictions to alternative models from the literature. Our model compares excellently to experimental transport coefficients and models from literature with a higher number of adjustable parameters, such as GERG2008, and shows a clear improvement over empirical correlations for transport coefficients of hydrogen. In a second step, we determine the effect of further model reduction by comparing our against a much simpler model applying empirical transport coefficients from the literature. For this purpose, hydrogen is periodically injected into and extracted out of a dome‐shaped porous aquifer under a caprock. Our results show that density and viscosity of hydrogen have the highest impact on the pressure field, and that a thermodynamic model like the new model presented here is essential for modeling the storage aquifer, while keeping the number of coefficients at a minimum. In diffusion‐dominated settings such as the diffusion of hydrogen through the caprock, our developed diffusion coefficients show a much improved dependence on temperature and pressure, leading to a more accurate approximation of the diffusive fluxes.
Realization of quantum secure direct communication over 100 km fiber with time-bin and phase quantum states
Authors: Zhang Haoran , Sun Zhen , Qi Ruoyang , Yin Liuguo , Long Gui-Lu , Lu Jianhua 
Published: April 2022

AbstractRapid progress has been made in quantum secure direct communication in recent years. For practical application, it is important to improve the performances, such as the secure information rate and the communication distance. In this paper, we report an elaborate physical system design and protocol with much enhanced performance. This design increased the secrecy capacity greatly by achieving an ultra-low quantum bit error rate of <0.1%, one order of magnitude smaller than that of existing systems. Compared to previous systems, the proposed scheme uses photonic time-bin and phase states, operating at 50 MHz of repetition rate, which can be easily upgraded to over 1 GHz using current on-the-shelf technology. The results of our experimentation demonstrate that the proposed system can tolerate more channel loss, from 5.1 dB, which is about 28.3 km in fiber in the previous scheme, to 18.4 dB, which corresponds to fiber length of 102.2 km. Thus, the experiment shows that intercity quantum secure direct communication through fiber is feasible with present-day technology.
Convergent selective signaling impairment exposes the pathogenicity of latrophilin-3 missense variants linked to inheritable ADHD susceptibility
Authors: Moreno-Salinas Ana L. , Holleran Brian J. , Ojeda-Muñiz Estefania Y. , Correoso-Braña Kerlys G. , Ribalta-Mena Sheila , Ovando-Zambrano José-Carlos , Leduc Richard , Boucard Antony A. 
Published: April 2022

AbstractLatrophilin-3 (Lphn3; also known as ADGRL3) is a member of the adhesion G Protein Coupled Receptor subfamily, which participates in the stabilization and maintenance of neuronal networks by mediating intercellular adhesion through heterophilic interactions with transmembrane ligands. Polymorphisms modifying the Lphn3 gene are associated with attention-deficit/hyperactivity disorder (ADHD) in children and its persistence into adulthood. How these genetic alterations affect receptor function remains unknown. Here, we conducted the functional validation of distinct ADHD-related Lphn3 variants bearing mutations in the receptor’s adhesion motif-containing extracellular region. We found that all variants tested disrupted the ability of Lphn3 to stabilize intercellular adhesion in a manner that was distinct between ligands classes, but which did not depend on ligand-receptor interaction parameters, thus pointing to altered intrinsic receptor signaling properties. Using G protein signaling biosensors, we determined that Lphn3 couples to Gαi1, Gαi2, Gαs, Gαq, and Gα13. However, all ADHD-related receptor variants consistently lacked intrinsic as well as ligand-dependent Gα13 coupling efficiency while maintaining unaltered coupling to Gαi, Gαs, and Gαq. Consistent with these alterations, actin remodeling functions as well as actin-relevant RhoA signaling normally displayed by the constitutively active Lphn3 receptor were impeded by select receptor variants, thus supporting additional signaling defects. Taken together, our data point to Gα13 selective signaling impairments as representing a disease-relevant pathogenicity pathway that can be inherited through Lphn3 gene polymorphisms. This study highlights the intricate interplay between Lphn3 GPCR functions and the actin cytoskeleton in modulating neurodevelopmental cues related to ADHD etiology.
Neural responses to reward anticipation and feedback in adult and adolescent cannabis users and controls
Authors: Skumlien Martine , Mokrysz Claire , Freeman Tom P. , Wall Matthew B. , Bloomfield Michael , Lees Rachel , Borissova Anna , Petrilli Kat , Carson James , Coughlan Tiernan , Ofori Shelan , Langley Christelle , Sahakian Barbara J. , Curran H. Valerie , Lawn Will 
Published: April 2022

AbstractChronic use of drugs may alter the brain’s reward system, though the extant literature concerning long-term cannabis use and neural correlates of reward processing has shown mixed results. Adolescents may be more vulnerable to the adverse effects of cannabis than adults; however, this has not been investigated for reward processing. As part of the ‘CannTeen’ study, in the largest functional magnetic resonance imaging study of reward processing and cannabis use to date, we investigated reward anticipation and feedback in 125 adult (26–29 years) and adolescent (16–17 years) cannabis users (1–7 days/week cannabis use) and gender- and age-matched controls, using the Monetary Incentive Delay task. Blood-oxygen-level-dependent responses were examined using region of interest (ROI) analyses in the bilateral ventral striatum for reward anticipation and right ventral striatum and left ventromedial prefrontal cortex for feedback, and exploratory whole-brain analyses. Results showed no User-Group or User-Group × Age-Group effects during reward anticipation or feedback in pre-defined ROIs. These null findings were supported by post hoc Bayesian analyses. However, in the whole-brain analysis, cannabis users had greater feedback activity in the prefrontal and inferior parietal cortex compared to controls. In conclusion, cannabis users and controls had similar neural responses during reward anticipation and in hypothesised reward-related regions during reward feedback. The whole-brain analysis revealed tentative evidence of greater fronto-parietal activity in cannabis users during feedback. Adolescents showed no increased vulnerability compared with adults. Overall, reward anticipation and feedback processing appear spared in adolescent and adult cannabis users, but future longitudinal studies are needed to corroborate this.
eccDNAdb: a database of extrachromosomal circular DNA profiles in human cancers
Authors: Peng Li , Zhou Nan , Zhang Chao-Yang , Li Guan-Cheng , Yuan Xiao-Qing 
Published: April 2022

AbstractExtrachromosomal circular DNA (eccDNA) elements are circular DNA molecules that are derived from but are independent of chromosomal DNA. EccDNA is emerging as a rising star because of its ubiquitous existence in cancers and its crucial role in oncogene amplification and tumor progression. In the present study, whole-genome sequencing (WGS) data of cancer samples were downloaded from public repositories. Afterwards, eccDNAs were identified from WGS data via bioinformatic analyses. To leverage database coverage, eccDNAs were also collected by manual curation of literatures. Gene expression and clinical data were downloaded from TCGA and CCLE and then used to investigate the roles of eccDNAs in cancers. Finally, the first integrated database of eccDNAs, eccDNAdb, was developed. eccDNAdb currently includes 1270 eccDNAs, which were identified in 480 samples (of 42 cancers) after analyzing a total number of 3395 tumor samples (of 57 cancers) including patient tissues, patient-derived xenografts, and cancer cell lines. A total number of 54,901 eccDNA genes were annotated and included in the database as well. With the integration of gene expression, clinical information and chromatin accessibility data, eccDNAdb enables users to easily determine the biological function and clinical relevance of eccDNAs in human cancers. In conclusion, eccDNAdb is freely accessible at http://www.eccdnadb.org. To our knowledge, eccDNAdb is the first database in the eccDNA research field. It is expected to provide insight for novel cancer therapies.
Cannabis suppresses antitumor immunity by inhibiting JAK/STAT signaling in T cells through CNR2
Authors: Xiong Xinxin , Chen Siyu , Shen Jianfei , You Hua , Yang Han , Yan Chao , Fang Ziqian , Zhang Jianeng , Cai Xiuyu , Dong Xingjun , Kang Tiebang , Li Wende , Zhou Penghui 
Published: April 2022

AbstractThe combination of immune checkpoint blockade (ICB) with chemotherapy significantly improves clinical benefit of cancer treatment. Since chemotherapy is often associated with adverse events, concomitant treatment with drugs managing side effects of chemotherapy is frequently used in the combination therapy. However, whether these ancillary drugs could impede immunotherapy remains unknown. Here, we showed that ∆9-tetrahydrocannabinol (THC), the key ingredient of drugs approved for the treatment of chemotherapy-caused nausea, reduced the therapeutic effect of PD-1 blockade. The endogenous cannabinoid anandamide (AEA) also impeded antitumor immunity, indicating an immunosuppressive role of the endogenous cannabinoid system (ECS). Consistently, high levels of AEA in the sera were associated with poor overall survival in cancer patients. We further found that cannabinoids impaired the function of tumor-specific T cells through CNR2. Using a knock-in mouse model expressing a FLAG-tagged Cnr2 gene, we discovered that CNR2 binds to JAK1 and inhibits the downstream STAT signaling in T cells. Taken together, our results unveiled a novel mechanism of the ECS-mediated suppression on T-cell immunity against cancer, and suggest that cannabis and cannabinoid drugs should be avoided during immunotherapy.
Maternal levels of acute phase proteins in early pregnancy and risk of autism spectrum disorders in offspring
Authors: Brynge Martin , Gardner Renee , Sjöqvist Hugo , Karlsson Håkan , Dalman Christina 
Published: April 2022

AbstractPrevious research supports a contribution of early-life immune disturbances in the etiology of autism spectrum disorders (ASD). Biomarker studies of the maternal innate (non-adaptive) immune status related to ASD risk have focused on one of the acute phase proteins (APP), C-reactive protein (CRP), with conflicting results. We evaluated levels of eight different APP in first-trimester maternal serum samples, from 318 mothers to ASD cases and 429 mothers to ASD-unaffected controls, nested within the register-based Stockholm Youth Cohort. While no overall associations between high levels of APP and ASD were observed, associations varied across diagnostic sub-groups based on co-occurring conditions. Maternal levels of CRP in the lowest compared to the middle tertile were associated with increased risk of ASD without ID or ADHD in offspring (OR = 1.92, 95% CI 1.08–3.42). Further, levels of maternal ferritin in the lowest (OR = 1.78, 95% CI 1.18–2.69) and highest (OR = 1.64, 95% CI 1.11–2.43) tertiles were associated with increased risk of any ASD diagnosis in offspring, with stronger associations still between the lowest (OR = 3.81, 95% CI 1.91–7.58) and highest (OR = 3.36, 95% CI 1.73–6.53) tertiles of ferritin and risk of ASD with ID. The biological interpretation of lower CRP levels among mothers to ASD cases is not clear but might be related to the function of the maternal innate immune system. The finding of aberrant levels of ferritin conferring risk of ASD-phenotypes indicates a plausibly important role of iron during neurodevelopment.
Exosomal HMGA2 protein from EBV-positive NPC cells destroys vascular endothelial barriers and induces endothelial-to-mesenchymal transition to promote metastasis
Authors: Li Deng-Ke , Chen Xing-Rui , Wang Li-Na , Wang Jia-Hong , Li Ji-Ke , Zhou Zi-Ying , Li Xin , Cai Lin-Bo , Zhong Shui-Sheng , Zhang Jing-Jing , Zeng Yu-Mei , Zhang Qian-Bing , Fu Xiao-Yan , Lyu Xiao-Ming , Li Min-Ying , Huang Zhong-Xi , Yao Kai-Tai 
Published: April 2022

AbstractIncreased vascular permeability facilitates metastasis. Cancer-secreted exosomes are emerging mediators of cancer-host crosstalk. Epstein-Barr virus (EBV), identified as the first human tumor-associated virus, plays a crucial role in metastatic tumors, especially in nasopharyngeal carcinoma (NPC). To date, whether and how exosomes from EBV-infected NPC cells affect vascular permeability remains unclear. Here, we show that exosomes from EBV-positive NPC cells, but not exosomes from EBV-negative NPC cells, destroy endothelial cell tight junction (TJ) proteins, which are natural barriers against metastasis, and promote endothelial-to-mesenchymal transition (EndMT) in endothelial cells. Proteomic analysis revealed that the level of HMGA2 protein was higher in exosomes derived from EBV-positive NPC cells compared with that in exosomes derived from EBV-negative NPC cells. Depletion of HMGA2 in exosomes derived from EBV-positive NPC cells attenuates endothelial cell dysfunction and tumor cell metastasis. In contrast, exosomes from HMGA2 overexpressing EBV-negative NPC cells promoted these processes. Furthermore, we showed that HMGA2 upregulates the expression of Snail, which contributes to TJ proteins reduction and EndMT in endothelial cells. Moreover, the level of HMGA2 in circulating exosomes is significantly higher in NPC patients with metastasis than in those without metastasis and healthy negative controls, and the level of HMGA2 in tumor cells is associated with TJ and EndMT protein expression in endothelial cells. Collectively, our findings suggest exosomal HMGA2 from EBV-positive NPC cells promotes tumor metastasis by targeting multiple endothelial TJ and promoting EndMT, which highlights secreted HMGA2 as a potential therapeutic target and a predictive marker for NPC metastasis.
Harnessing Rift Valley fever virus NSs gene for cancer gene therapy
Authors: Davis Alicia M. , Scott Tristan A. , Morris Kevin V. 
Published: April 2022

AbstractOne of the greatest challenges in the treatment of cancer is tumor heterogeneity which results in differential responses to chemotherapy and drugs that work through a single pathway. A therapeutic agent that targets cancer cells for death through multiple mechanisms could be advantageous as a broad inhibitor for many types of cancers and the heterogeneous alterations they possess. Several viral proteins have been exploited for antiproliferative and apoptotic effect in cancer cells by disrupting critical survival pathways. Here, we report the use of the non-structural protein on the S segment (NSs) gene from the Rift Valley fever virus (RVFV) to induce cancer cell death. NSs has immune evasion functions in the context of RVFV with many of these functions affecting proliferation pathways and DNA damage signaling, which could be leveraged against cancer cells. We find that expression of NSs in multiple cancer cell lines leads to a rapid decline in cell viability and induction of apoptosis. Interestingly, we observed reduced toxicity in normal cells suggesting cancer cells may be more susceptible to NSs-mediated cell death. To enhance specificity of NSs for use in hepatocellular carcinoma, we incorporated four miR-122 binding sites in the 3’ untranslated region (UTR) of the NSs mRNA to achieve cell type specific expression. Observations presented here collectively suggest that delivery of the NSs gene may provide a unique therapeutic approach in a broad range of cancers.
NrCAM secreted by endometrial stromal cells enhances the progestin sensitivity of endometrial cancer cells through epigenetic modulation of PRB
Authors: Cheng Yali , Xie Liying , Xu Zhiying , Hao Mengxin , Yang Bingyi , Shan Weiwei , Wang Yiqin , Lv Qiaoying , Chen Xiaojun 
Published: April 2022

AbstractProgestin is one of the main hormone treatment regimens for early-stage estrogen receptor- and progesterone receptor (PR)-positive endometrial cancer (EC). However, the response rate of EC to progestins is unsatisfactory. Investigating the mechanisms related to progestin treatment could help improve treatment efficacy. Studies have demonstrated that normal endometrial stromal cells (ESCs) increase the inhibitory effect of progestin on EC cell proliferation via paracrine signaling, but the mechanisms involved remain unclear. In this study, we found that ESCs had different morphological features between progestin-sensitive and -insensitive EC tissues. ESCs presented typical decidualization changes in progestin-sensitive cases, while they remained slim in progestin-insensitive EC lesions, indicating no response. Furthermore, ESCs enhanced the inhibitory effect of medroxyprogesterone acetate (MPA) on EC cell proliferation by secreting neuron cell adhesion molecule (NrCAM). MPA treatment enhanced NrCAM secretion by ESCs. EC xenografts in BALB/C nude mice demonstrated that MPA combined with NrCAM had an increased tumor inhibitory effect compared with MPA or NrCAM alone. Mechanistically, MPA upregulated NrCAM expression in ESCs through PR. Specifically, NrCAM increased PR expression in EC cells through TET1-induced hydroxymethylation of the PRB gene promoter region. These findings indicate that NrCAM or NrCAM combined with progestins could be a new EC treatment.
Spontaneous activity of the mitochondrial apoptosis pathway drives chromosomal defects, the appearance of micronuclei and cancer metastasis through the Caspase-Activated DNAse
Authors: Haimovici Aladin , Höfer Christoph , Badr Mohamed Tarek , Bavafaye Haghighi Elham , Amer Tarek , Boerries Melanie , Bronsert Peter , Glavynskyi Ievgen , Fanfone Deborah , Ichim Gabriel , Thilmany Nico , Weber Arnim , Brummer Tilman , Spohr Corinna , Öllinger Rupert , Janssen Klaus-Peter , Rad Roland , Häcker Georg 
Published: April 2022

AbstractMicronuclei are DNA-containing structures separate from the nucleus found in cancer cells. Micronuclei are recognized by the immune sensor axis cGAS/STING, driving cancer metastasis. The mitochondrial apoptosis apparatus can be experimentally triggered to a non-apoptotic level, and this can drive the appearance of micronuclei through the Caspase-activated DNAse (CAD). We tested whether spontaneously appearing micronuclei in cancer cells are linked to sub-lethal apoptotic signals. Inhibition of mitochondrial apoptosis or of CAD reduced the number of micronuclei in tumor cell lines as well as the number of chromosomal misalignments in tumor cells and intestinal organoids. Blockade of mitochondrial apoptosis or deletion of CAD reduced, while experimental activation CAD, STING-dependently, enhanced aggressive growth of tumor cells in vitro. Deletion of CAD from human cancer cells reduced metastasis in xenograft models. CAD-deficient cells displayed a substantially altered gene-expression profile, and a CAD-associated gene expression ‘signature’ strongly predicted survival in cancer patients. Thus, low-level activity in the mitochondrial apoptosis apparatus operates through CAD-dependent gene-induction and STING-activation and has substantial impact on metastasis in cancer.