bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation of de novo mutations in a schizophrenia case-parent trio by induced pluripotent stem cell based in vitro disease-modeling: Convergence of schizophrenia and autism-related cellular phenotypes
Authors: Hathy Edit , Szabó Eszter , Varga Nóra , Erdei Zsuzsa , Tordai Csongor , Czehlár Boróka , Baradits Máté , Jezsó Bálint , Koller Júlia , Nagy László , Molnár Mária Judit , Homolya László , Nemoda Zsófia , Apáti Ágota , Réthelyi János M 
Published: October 2020

Abstract
Background: De novo mutations (DNMs) have been implicated in the etiology of schizophrenia (SZ), a chronic debilitating psychiatric disorder characterized by hallucinations, delusions, cognitive dysfunction and decreased community functioning. Several DNMs have been identified by examining SZ cases and their unaffected parents, however in most cases the biological significance of these mutations remains elusive. To overcome this limitation, we have developed an approach of using induced pluripotent stem cell (iPSC) lines from each member of a SZ case-parent trio, in order to investigate the effects of DNMs in cellular progenies of interest, particularly in dentate gyrus neuronal progenitors.Methods: We identified a male SZ patient characterized by early disease onset and negative symptoms, who is a carrier of 3 non-synonymous DNMs in genes LRRC7, KHSRP, and KIR2DL1. iPSC lines were generated from his and his parents’ peripheral blood mononuclear cells using Sendai virus-based reprogramming and differentiated into neuronal progenitor cells (NPCs) and hippocampal dentate gyrus granule cells. We used RNASeq to explore transcriptomic differences, and calcium (Ca2+) imaging, cell proliferation, migration, oxidative stress, and mitochondrial assays to characterize the investigated NPC lines. Results: NPCs derived from the SZ patient exhibited transcriptomic differences related to Wnt-signaling, neuronal differentiation, axonal guidance and synaptic function, and decreased Ca2+ reactivity to glutamate. Moreover, we could observe increased cellular proliferation, and alterations in mitochondrial quantity and morphology.Conclusions: The approach of reprograming case-parent trios represents an opportunity for investigating the molecular effects of disease-causing mutations, and comparing these in cell lines with reduced variation in genetic background. Our results are indicative of a partial overlap between schizophrenia and autism-related phenotypes in the investigated family.Limitations: Our study investigated only one family, therefore the generalizability of findings is limited. We could not derive iPSCs from two other siblings to test for possible genetic effects in the family that are not driven by DNMs. The transcriptomic and functional assays were limited to the NPC stage, although these variables should also be investigated at the mature neuronal stage.
Barriers and drivers to capacity-building in global mental health projects
Authors: Endale Tarik , Qureshi Onaiza , Ryan Grace Kathryn , Esponda Georgina Miguel , Verhey Ruth , Eaton Julian , De Silva Mary , Murphy Jill 
Published: October 2020

Abstract
BackgroundThe global shortage of mental health workers is a significant barrier to the implementation and scale-up of mental health services. Partially as a result of this shortage, approximately 85% of people with mental, neurological and substance-use disorders in low- and middle-income countries do not receive care. Consequently, developing and implementing scalable solutions for mental health capacity-building has been identified as a priority in global mental health. There remains limited evidence to inform best practices for capacity building in global mental health. As one in a series of four papers on factors affecting the implementation of mental health projects in low- and middle-income countries, this paper reflects on the experiences of Global Mental Health grantees funded by Grand Challenges Canada, focusing on the barriers to and drivers of capacity-building.MethodsBetween June 2014 and May 2017, current or former Grand Challenges Canada Global Mental Health grantees were recruited using purposive sampling. N=29 grantees participated in semi-structured qualitative interviews, representing projects in Central America and the Caribbean (n=4), South America (n=1), West Africa (n=4), East Africa (n=6), South Asia (n=11) and Southeast Asia (n=3). Based on the results of a quantitative analysis of project outcomes using a portfolio-level Theory of Change framework, six key themes were identified as important to implementation success. As part of a larger multi-method study, this paper utilized a framework analysis to explore the themes related to capacity-building.ResultsStudy participants described barriers and facilitators to capacity building within three broad themes: 1) training, 2) supervision, and 3) quality assurance. Running throughout these thematic areas were the crosscutting themes of contextual understanding, human resources, and sustainability. Additionally, participants described approaches and mechanisms for successful capacity building.ConclusionsThis study demonstrates the importance of capacity building to global mental health research and implementation, its relationship to stakeholder engagement and service delivery, and the implications for funders, implementers, and researchers alike. Investment in formative research, contextual understanding, stakeholder engagement, policy influence, and integration into existing systems of education and service delivery is crucial for the success of capacity building efforts.
Canopy airspace of riparian forest mitigates soil N2O emission during hot moments
Authors: Mander Ülo , Krasnova Alisa , Escuer-Gatius Jordi , Espenberg Mikk , Schindler Thomas , Machacova Katerina , Pärn Jaan , Maddison Martin , Megonigal Patrick , Pihlatie Mari , Kasak Kuno , Niinemets Ülo , Junninen Heikki , Soosaar Kaido 
Published: October 2020

Abstract
Riparian forests are known as hot spots of N cycling in landscapes and climate warming speeds up the cycle. Here we present results from the first multi-annual high temporal-frequency study of soil, stem and ecosystem (eddy covariance) fluxes of N2O from a typical riparian forest in Europe.Hot moments (extreme events of N2O emission) last a quarter of the study period but contribute more than a half of soil fluxes. For the first time we demonstrate that high soil emissions of N2O do not reach the ecosystem level. During the drought onset, soil N2O emission peaks at intermediate soil water content. Rapid water content change is the main determinant of the emissions. The freeze–thaw period is another hot moment. However, according to the eddy covariance measurements the riparian forest is a modest source of N2O. We propose photochemical reactions and dissolution in canopy-space water as consumption mechanisms.
Identification of FMRP target mRNAs in the developmental brain: FMRP might coordinate Ras/MAPK, Wnt/ß-catenin, and mTOR signaling during corticogenesis
Authors: Casingal Cristine R. , Kikkawa Takako , Inada Hitoshi , Sasaki Yukio , Osumi Noriko 
Published: October 2020

Abstract
Corticogenesis is one of the most critical and complicated processes during embryonic brain development. Any slight impairment in corticogenesis could cause neurodevelopmental disorders such as Fragile X syndrome (FXS), of which symptoms contain intellectual disability (ID) and autism spectrum disorder (ASD). Fragile X mental retardation protein (FMRP), an RNA-binding protein responsible for FXS, shows strong expression in neural stem/precursor cells (NPCs) during corticogenesis, although its function during brain development remains largely unknown. In this study, we attempted to identify the FMRP target mRNAs in the mouse cortical primordium using RNA immunoprecipitation sequencing analysis in the mouse embryonic brain. We identified 865 candidate genes as targets of FMRP involving 126 and 118 genes overlapped with ID and ASD-associated genes, respectively. These overlapped genes were enriched with those related to chromatin/chromosome organization and histone modifications, suggesting the involvement of FMRP in epigenetic regulation. We further identified a common set of 17 "core" genes involved in neurogenesis/FXS/ID/ASD, containing factors associated with Ras/mitogen-activated protein kinase, Wnt/ß-catenin, and mTOR pathways. We indeed showed overactivation of mTOR signaling via an increase in mTOR phosphorylation in the Fmr1 knockout (Fmr1 KO) neocortex. Our results provide further insight into the critical roles of FMRP in the developing brain, where dysfunction of FMRP may influence the regulation of its mRNA targets affecting signaling pathways and epigenetic modifications.
Identification of an RNA binding protein-related gene signature in hepatocellular carcinoma patients
Authors: Wang Li , Zhou Na , Qu Jialin , Jiang Man , Zhang Xiaochun 
Published: October 2020

Abstract
Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related morbidity and mortality among all human cancers. Studies have demonstrated that RNA binding proteins (RBPs) involved in the biological process of cancers including hepatocellular cancer. In this study, we aim to identify clinical value of RNA binding proteins for hepatocellular carcinoma.Methods: We analyses the data of HCC that downloaded from the Cancer Genome Atlas (TCGA) database and determined the differently expressed of RBPs between cancer and normal tissues. We further elucidate the function of RBPs by utilized Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Gene signature of SMG5, EZH2, FBLL1, ZNF239, IGF2BP3 were generated by performed the univariate and multivariate Cox regression and LASSO regression analysis. CIBERSORT analysis was used to evaluation of tumor-infiltrating immune cells in different group. We built and verify a prognosis nomogram base on RBPs-related genes. Gene signature was validated by the International Cancer Genome Consortium (ICGC) database. The expressions of RBPs-related genes were validated by using Oncomine database, and the Human Protein Atlas.Result: Most of RBPs-related genes were significantly different in cancer and normal tissue. The survival of patients in the different group was statistically different. The Gene signature showed good performance for predicting the survival of HCC patients by having a better area under the receiver operating characteristic curve than other clinicopathological parameters (AUC=0.758). The patients in the high-risk group were more likely to have a higher Macrophages M0. Conclusion: Gene signature constructed by RNA binding proteins can be independent risk factors for hepatocellular carcinoma patients.
Cardiac Tyrosine Hydroxylase Activation and MB-COMT in Dyskinetic Monkeys&nbsp;
Authors: Cuenca-Bermejo Lorena , Almela Pilar , Gallo-Soljancic Pablo , Yuste Jose E. , Pablos Vicente de , Bautista-Hernández Víctor , Fernández-Villalba Emiliano , Laorden María-Luisa , Herrero María-Trinidad 
Published: October 2020

Abstract
Background: The impact of age-associated disorders is increasing as the life expectancy of the population increments. Cardiovascular diseases and neurodegenerative disorders, such as Parkinson’s disease, have the highest social and economic burden and increasing evidence show interrelations between them. Particularly, dysfunction of the cardiovascular nervous system is part of the dysautonomic symptoms of Parkinson’s disease, although more studies are needed to elucidate the role of cardiac function on it . Methods: We analyzed the dopaminergic system in the nigrostriatal pathway of Parkinsonian and dyskinetic monkeys and the expression of some key proteins in the metabolism and synthesis of catecholamines in the heart: total and phosphorylated (phospho) tyrosine hydroxylase (TH), and membrane (MB) and soluble (S) isoforms of catechol-O-methyl transferase (COMT). Results: The number of dopaminergic neurons in the Substantia Nigra pars compacta and the optical density of TH+ fibers and dopamine transporter in the striatum were significantly decreased in all MPTP-intoxicated monkeys. MPTP- and MPTP+L-DOPA-treated animals also showed a decrease in total TH expression in both right (RV) and left ventricle (LV). We found a significant increase of phospho-TH in both groups (MPTP and MPTP+L-DOPA) in the LV, while this increase was only observed in MPTP-treated monkeys in the RV. MB-COMT analysis showed a very significant increase of this isoform in the LV of MPTP- and MPTP+L-DOPA-treated animals. However, we found no significant differences in S-COMT levels. These data suggest that MB-COMT is the main isoform implicated in the cardiac noradrenergic changes observed after MPTP treatment, suggesting an increase in NA metabolism. Moreover, the increase of TH activity indicates that cardiac noradrenergic neurons still respond despite MPTP treatment. Conclusions: These results could help to elucidate the possible role of alterations in the catecholaminergic system that can contribute to noradrenergic deficiency in the hearts of PD patients. Therefore, this information might be relevant to clinical field, contributing to the therapeutic design of the disease.
Reducing Drug-use Harms among Higher Education Students: X Contextual-Behaviour Change Digital Intervention Development Using the Behaviour Change Wheel
Authors: Vasiliou Vasilis S. , Dockray Samantha , Dick Samantha , Davoren Martin P. , Heavin Ciara , Linehan Conor , Byrne Michael 
Published: October 2020

Abstract
Background: Digital harm-reduction interventions typically focus on people with severe drug-use problems, yet, these interventions have a moderate effectiveness on drug-users with lower levels of risk of harm. The difference in effectiveness may be explained by differences in behavioural patterns between the two groupings. Harnessing behavioural theories to understand what is at the core of drug-use behaviours to map the content of new interventions can improve the effectiveness of interventions for lower-risk drug-users. This is the first study to systematically apply the Behaviour Change Wheel (BCW) to understand the components, influencing capabilities, opportunities, and motivations (COM-B) of higher education students to change their drug-use behaviour. This is also the first study which identifies specific patterns of behaviours likely to be most responsive to harm reduction practices through the use of the Theoretical Domain Framework (TDF). Methods: We first conducted an online survey and a Delphi exercise to understand the factors influencing COM-B components of higher education students to change drug-use. Subsequently, we mapped all evidence onto the COM-B and the TDF to identify clusters of behaviours to target for change using a pattern-based discourse analysis. Finally, a series of multidisciplinary group meetings identified the intervention functions- the means by which the intervention change targeted behaviours and the Behavioural Change Techniques (BCTs) involved using the behaviour change technique taxonomy (v.1). Results: Twenty nine BCTs relevant to harm-reduction practices were identified and mapped across five intervention functions (education, modelling, persuasion, incentivization, and training) and five policy categories (communication/marketing, guidelines, regulation, service provision and environmental/social planning). These BCTs were distributed across eight identified saturated clusters of behaviours this intervention attempts to change. Conclusions: The BCTs identified will inform the development of a digitally delivered behaviour change intervention that focuses on increasing mindful decision-making with respect to drug-use and promotes alternatives to drug-use activities. The findings can also inform implementation scientists in applying context-specific harm-reduction practices in higher education. Examples of how the eight identified clusters of target behaviours are mapped across the COM-B components and the TDF are provided, along with suggestions of implementation practices for harm -reduction targeting students in higher education.
Systematic analysis of the expression and prognosis relevance of FBXO family reveals the significance of FBXO1 in human breast cancer
Authors: Liu Yaqian , Pan Bo , Qu Weikun , Cao Yilong , Li Jun , Zhao Haidong 
Published: October 2020

Abstract
Background: Breast cancer (BC) remains a prevalent and common form of cancer with high heterogeneity. Making efforts to explore novel molecular biomarkers and serve as potential disease indicators, which is essential to effectively enhance the prognosis and individualized treatment of BC. FBXO proteins act as the core component of E3 ubiquitin ligase, which play essential regulators roles in multiple cellular processes. Recently, research has indicated that FBXOs also play significant roles in cancer development. However, the molecular functions of these family members in BC have not been fully elucidated.Methods: In this research, we investigated the expression data, survival relevance and mutation situation of 10 FBXO members (FBXO1, 2, 5, 6, 16, 17, 22, 28, 31 and 45) in patients with BC from the Oncomine, GEPIA, HPA, Kaplan-Meier Plotter, UALCAN and cBioPortal databases. The high transcriptional levels of FBXO1 in different subtypes of BC were verified by immunohistochemical staining and the specific mutations of FBXO1 were obtained from COSMIC database. Top 10 genes with the highest correlation to FBXO1 were identified through cBioPortal and COXPRESdb tools. Additionally, functional enrichment analysis, PPI network and survival relevance of FBXO1 and co-expressed genes in BC were obtained from DAVID, STRING, UCSC Xena, GEPIA, bc-GenExMiner and Kaplan-Meier Plotter databases.Results: We found that FBXO2, FBXO6, FBXO16 and FBXO17 were potential favorable prognostic factors for BC. FBXO1, FBXO5, FBXO22, FBXO28, FBXO31 and FBXO45 may be the independent poor prognostic factors for BC. All of them were correlated to clinicopathological staging. Moreover, we identified that FBXO1 was an excellent molecular biomarker and therapeutic target for BC. Conclusion: This study implies that FBXO1, FBXO2, FBXO5, FBXO6, FBXO16, FBXO17, FBXO22, FBXO28, FBXO31 and FBXO45 genes are potential clinical targets and prognostic biomarkers for patients with BC.
CAEV-Surrounding Objects Detection and&nbsp;Tracking for Autonomous Driving Using Lidar and Radar Fusion
Authors: Liu Ze , Cai Feng Ying 
Published: October 2020

Abstract
Radar and Lidar are two environmental sensors commonly used in autonomous vehicles，Lidars are accurate in determining objects’ positions but significantly less accurate on measuring their velocities. However, Radars are more accurate on measuring objects velocities but less accurate on determining their positions as they have a lower spatial resolution. In order to compensate for the low detection accuracy, incomplete target attributes and poor environmental adaptability of single sensors such as Radar and LIDAR, we proposed an effective method for high-precision detection and tracking of surrounding targets of autonomous vehicles. By employing the Unscented Kalman Filter, radar and LIDAR information is effectively fused to achieve high-precision detection of the position and speed information of targets around the autonomous vehicle. Finally, we do a variety of driving environment under the real car algorithm verification test. The experimental results show that the proposed sensor fusion method can effectively detect and track the vehicle peripheral targets with high accuracy. Compared with a single sensor, it has obvious advantages and can improve the intelligence level of driverless cars.
Crystal chemistry and high-temperature vibrational spectra of humite and norbergite: Fluorine and titanium in humite-group minerals
Authors: Liu Dan , Hirner Sarah M. , Smyth Joseph R. , Zhang Junfeng , Shi Xiaochao , Wang Xiang , Zhu Xi , Ye Yu 
Published: October 2020

AbstractThe humite-group minerals along the brucite-olivine join may be important dense hydrous magnesium silicate (DHMS) phases in the subducting slab. Fluorine and titanium can be incorporated into their structures through the substitutions (OH)– = F– and Mg2+ + 2(OH)– = Ti4+ + 2O2–. These substitutions have significant effects on the hydrogen bonding behavior in the structures. Structure refinements and in situ high-temperature Raman and Fourier transform infrared (FTIR) measurements were conducted on natural humite and norbergite crystals. Both minerals crystallize in space group Pbnm, and their isobaric Grüneisen parameters for the lattice and SiO4 internal vibrations are compared with those of chondrodite, clinohumite, brucite, and forsterite. For the humite-group minerals, the OH-stretching modes above 3450 cm–1 are affected by local H-H repulsion, whereas the behavior of those below 3450 cm–1 can be explained by F– and Ti4+ substitutions, either of which may relieve the H-H repulsion effect. The Raman-active OH bands below 3450 cm–1 are affected by Ti4+ substitution, while the IR-active bands can be affected by either F– or Ti4+ substitutions. Based on an analysis of the high-T Raman and FTIR spectra, the OH vibrations above and below 3450 cm–1 behave differently as a function of temperature, and similar behavior has also been observed for other dense hydrous silicate phases in the hydrous peridotite system. Hence, the lengths of the oxygen-oxygen edges in MgO6 octahedra where protonation can occur become similar to each other at elevated temperatures. This may provide an atomistic explanation for the electrical conductivity properties of DHMS phases at high temperatures.
The exploration of a Temporal Convolutional Network combined with Encoder-Decoder framework for runoff forecasting
Authors: Lin Kangling , Sheng Sheng , Zhou Yanlai , Liu Feng , Li Zhiyu , Chen Hua , Xu Chong-Yu , Chen Jie , Guo Shenglian 
Published: October 2020

Abstract
The Temporal Convolutional Network (TCN) and TCN combined with the Encoder-Decoder architecture (TCN-ED) are proposed to forecast runoff in this study. Both models are trained and tested using the hourly data in the Jianxi basin, China. The results indicate that the forecast horizon has a great impact on the forecast ability, and the concentration time of the basin is a critical threshold to the effective forecast horizon for both models. Both models perform poorly in the low flow and well in the medium and high flow at most forecast horizons, while it is subject to the forecast horizon in forecasting peak flow. TCN-ED has better performance than TCN in runoff forecasting, with higher accuracy, better stability, and insensitivity to fluctuations in the rainfall process. Therefore, TCN-ED is an effective deep learning solution in runoff forecasting within an appropriate forecast horizon.