bluuebunny/crossref_metadata_2025_split huggingface dataset:
A New Adaptive Absolute Method for Homogenizing GNSS‐Derived Precipitable Water Vapor Time Series
Authors: Zhu Dantong , Zhang Kefei , Shen Zhen , Wu Suqin , Liu Zhiping , Tong Laga 
Published: June 2021

AbstractThe inhomogeneities, the so‐called changepoints, inevitably occur in the precipitable water vapor (PWV) time series derived from Global Navigation Satellite Systems (GNSS‐PWV). Currently, the two predominant types of homogenization methods, that is, absolute and relative methods, are limited in the poor performance and dependency on reference time series. In this study, a new absolute approach named adaptive absolute homogenization test (AAHT) by combining Seasonal‐Trend decomposition based on LOESS (STL) and Penalized Maximal F‐test to account for the red noise (PMFred) is proposed. The performance of the new approach was validated using Monte Carlo simulations. Results showed the success rate and false alarm rate were better than 74.9% and 12.2%; the detection accuracy of the changepoint epochs and the offset magnitudes were 8.0 days and 0.153 mm. AAHT was also applied to homogenizing the real GNSS‐PWV time series over 91 International GNSS Service stations, from which 63 time series were identified as inhomogeneous containing 126 changepoints. Based on a comparison with the PWV time series from the fifth‐generation European center for medium‐range weather forecasts (ECMWF) reanalysis (ERA5), 43 changepoints were connected to climatic drivers, leaving 83 artificial changepoints at 48 stations. The offset magnitudes at these artificial changepoints were estimated and corrected in the inhomogeneous time series. The long‐term trends of those homogenized time series were compared with that of the PWV time series derived from ERA5 data sets (ERA‐PWV) and the correlation coefficient between the two sets of trends was 0.75, which was significantly larger than 0.23 before homogenization.
Time‐Dependent Probabilistic Tsunami Inundation Assessment Using Mode Decomposition to Assess Uncertainty for an Earthquake Scenario
Authors: Fukutani Yo , Moriguchi Shuji , Terada Kenjiro , Otake Yu 
Published: June 2021

AbstractThis study presents an innovative probabilistic tsunami inundation assessment for an earthquake scenario to randomly generate tsunami inundation depth distributions by quantitatively evaluating the spatial correlation of tsunami inundation depths using singular value decomposition (SVD) derived from proper orthogonal decomposition and to evaluate the tsunami inundation depths considering the imminent occurrence of an earthquake. We found a good agreement between the evaluation results of the proposed surrogate model and the numerical results of the nonlinear long wave equations for the tsunami inundation depth distribution in Kamakura city, Japan, due to the Sagami Trough megathrust earthquake. Evaluating the spatial correlation using SVD has the advantage that the covariance matrix does not need to be defined in advance but can be defined from the data itself. We also achieved a significant reduction in the number of required tsunami propagation simulations for the probabilistic assessment and attained higher computational efficiency by extracting spatial correlations with SVD. Furthermore, we conducted a probabilistic tsunami inundation assessment focusing on a relatively short period (i.e., 50 years) considering the time‐dependent occurrence probability of the target earthquake. The proposed probabilistic assessment method with mode decomposition is applicable to the general probabilistic tsunami hazard assessment by integrating it with physical stochastic slip models.
Psychobiotic interventions for anxiety in young people: a systematic review and meta-analysis, with youth consultation
Authors: Cohen Kadosh Kathrin , Basso Melissa , Knytl Paul , Johnstone Nicola , Lau Jennifer Y. F. , Gibson Glenn R. 
Published: June 2021

AbstractThe human gut microbiome influence on brain function and mental health is an emerging area of intensive research. Animal and human research indicates adolescence as a sensitive period when the gut-brain axis is fine-tuned, where dietary interventions to change the microbiome may have long-lasting consequences for mental health. This study reports a systematic review and meta-analysis of microbiota-targeted (psychobiotics) interventions on anxiety in youth, with discussion of a consultation on the acceptability of psychobiotic interventions for mental health management amongst youth with lived experience. Six databases were searched for controlled trials in human samples (age range: 10–24 years) seeking to reduce anxiety. Post intervention outcomes were extracted as standard mean differences (SMDs) and pooled based on a random-effects model. 5416 studies were identified: 14 eligible for systematic review and 10 eligible for meta-analysis (total of 324 experimental and 293 control subjects). The meta-analysis found heterogeneity I2 was 12% and the pooled SMD was −0.03 (95% CI: −0.21, 0.14), indicating an absence of effect. One study presented with low bias risk, 5 with high, and 4 with uncertain risk. Accounting for risk, sensitivities analysis revealed a SMD of −0.16 (95% CI: −0.38, 0.07), indicative of minimal efficacy of psychobiotics for anxiety treatment in humans. There is currently limited evidence for use of psychobiotics to treat anxiety in youth. However, future progress will require a multidisciplinary research approach, which gives priority to specifying mechanisms in the human models, providing causal understanding, and addressing the wider context, and would be welcomed by anxious youths.
Convergent and distributed effects of the 3q29 deletion on the human neural transcriptome
Authors: Sefik Esra , Purcell Ryan H. ,   The Emory 3q29 Project, Aberizk Katrina , Averbach Hallie , Black Emily , Burrell T. Lindsey , Cambala Shanthi , Carlock Grace , Caspary Tamara , Cubells Joseph F. , Cutler David , Dawson Paul A. , Epstein Michael T. , Espana Roberto , Gambello Michael J. , Goines Katrina , Guest Ryan M. , Johnston Henry R. , Klaiman Cheryl , Koh Sookyong , Leslie Elizabeth J. , Li Longchuan , Mak Bryan , Malone Tamika , Mosley Trenell , Murphy Melissa M. , Papetti Ava , Pollak Rebecca M. , Russo Rossana Sanchez , Saulnier Celine A. , Shultz Sarah , Sisodoya Nikisha , Sloan Steven , Warren Stephen T. , Weinshenker David , Wen Zhexing , White Stormi Pulver , Zwick Mike , Walker Elaine F. , Bassell Gary J. , Mulle Jennifer G. 
Published: June 2021

AbstractThe 3q29 deletion (3q29Del) confers high risk for schizophrenia and other neurodevelopmental and psychiatric disorders. However, no single gene in this interval is definitively associated with disease, prompting the hypothesis that neuropsychiatric sequelae emerge upon loss of multiple functionally-connected genes. 3q29 genes are unevenly annotated and the impact of 3q29Del on the human neural transcriptome is unknown. To systematically formulate unbiased hypotheses about molecular mechanisms linking 3q29Del to neuropsychiatric illness, we conducted a systems-level network analysis of the non-pathological adult human cortical transcriptome and generated evidence-based predictions that relate 3q29 genes to novel functions and disease associations. The 21 protein-coding genes located in the interval segregated into seven clusters of highly co-expressed genes, demonstrating both convergent and distributed effects of 3q29Del across the interrogated transcriptomic landscape. Pathway analysis of these clusters indicated involvement in nervous-system functions, including synaptic signaling and organization, as well as core cellular functions, including transcriptional regulation, posttranslational modifications, chromatin remodeling, and mitochondrial metabolism. Top network-neighbors of 3q29 genes showed significant overlap with known schizophrenia, autism, and intellectual disability-risk genes, suggesting that 3q29Del biology is relevant to idiopathic disease. Leveraging “guilt by association”, we propose nine 3q29 genes, including one hub gene, as prioritized drivers of neuropsychiatric risk. These results provide testable hypotheses for experimental analysis on causal drivers and mechanisms of the largest known genetic risk factor for schizophrenia and highlight the study of normal function in non-pathological postmortem tissue to further our understanding of psychiatric genetics, especially for rare syndromes like 3q29Del, where access to neural tissue from carriers is unavailable or limited.
ZFP36L2 regulates myocardial ischemia/reperfusion injury and attenuates mitochondrial fusion and fission by LncRNA PVT1
Authors: Wu Fang , Huang Weifeng , Tan Qin , Guo Yong , Cao Yongmei , Shang Jiawei , Ping Feng , Wang Wei , Li Yingchuan 
Published: June 2021

AbstractAmong several leading cardiovascular disorders, ischemia–reperfusion (I/R) injury causes severe manifestations including acute heart failure and systemic dysfunction. Recently, there has been increasing evidence suggesting that alterations in mitochondrial morphology and dysfunction also play an important role in the prognosis of cardiac disorders. Long non-coding RNAs (lncRNAs) form major regulatory networks altering gene transcription and translation. While the role of lncRNAs has been extensively studied in cancer and tumor biology, their implications on mitochondrial morphology and functions remain to be elucidated. In this study, the functional roles of Zinc finger protein 36-like 2 (ZFP36L2) and lncRNA PVT1 were determined in cardiomyocytes under hypoxia/reoxygenation (H/R) injury in vitro and myocardial I/R injury in vivo. Western blot and qRT-PCR analysis were used to assess the levels of ZFP36L2, mitochondrial fission and fusion markers in the myocardial tissues and cardiomyocytes. Cardiac function was determined by immunohistochemistry, H&E staining, and echocardiogram. Ultrastructural analysis of mitochondrial fission was performed using transmission electron microscopy. The mechanistic model consisting of PVT1 with ZFP36L2 and microRNA miR-21-5p with E3 ubiquitin ligase MARCH5 was assessed by subcellular fraction, RNA pull down, FISH, and luciferase reporter assays. These results identified a novel regulatory axis involving PVT1, miR-21-5p, and MARCH5 that alters mitochondrial morphology and function during myocardial I/R injury. Using an in vivo I/R injury mouse model and in vitro cardiomyocytes H/R model, we demonstrated that ZFP36L2 directly associates with PVT1 and alters mitochondrial fission and fusion. PVT1 also interactes with miR-21-5p and suppresses its expression and activity. Furthermore, we identified MARCH5 as a modifier of miR-21-5p, and its effect on mitochondrial fission and fusion are directly proportional to PVT1 expression during H/R injury. Our findings show that manipulation of PVT1-miR-21-5p-MARCH5-mediated mitochondrial fission and fusion via ZFP36L2 may be a novel therapeutic approach to regulate myocardial I/R injury.
ISL1 promoted tumorigenesis and EMT via Aurora kinase A-induced activation of PI3K/AKT signaling pathway in neuroblastoma
Authors: Li Mengzhen , Sun Chengtao , Bu Xiaoyun , Que Yi , Zhang Lian , Zhang Yu , Zhang Li , Lu Suying , Huang Junting , Zhu Jia , Wang Juan , Sun Feifei , Zhang Yizhuo 
Published: June 2021

AbstractNeuroblastoma (NB) is the most common extracranial solid malignancy in children and its mortality rate is relatively high. However, driver genes of NB are not clearly identified. Using bioinformatics analysis, we determined the top 8 differentially expressed genes (DEGs) in NB, including GFAP, PAX6, FOXG1, GAD1, PTPRC, ISL1, GRM5, and GATA3. Insulin gene enhancer binding protein 1 (ISL1) is a LIM homeodomain transcription factor which has been found to be highly expressed in a variety of malignant tumors, but the function of ISL1 in NB has not been fully elucidated. We identified ISL1 as an oncogene in NB. ISL1 is preferentially upregulated in NB tissues compared with normal tissues. High ISL1 expression is significantly associated with poor outcome of NB patients. Knockdown of ISL1 markedly represses proliferation and induces cell apoptosis in vitro, and suppresses tumorigenicity in vivo, while overexpression of ISL1 has the opposite effects. Mechanistically, we demonstrate that ISL1 promotes cell proliferation and EMT transformation through PI3K/AKT signaling pathway by upregulating Aurora kinase A (AURKA), a serine-threonine kinase that is essential for the survival of NB cells. The blockade of AURKA attenuates the function of ISL1 overexpression in the regulation of cell proliferation and migration, Conclusively, this study showed that ISL1 targeted AURKA to facilitate the development of NB, which provided new insights into the tumorigenesis of NB. Thus, ISL1 may be a promising therapeutic target in the future.
RTP801/REDD1 contributes to neuroinflammation severity and memory impairments in Alzheimer’s disease
Authors: Pérez-Sisqués Leticia , Sancho-Balsells Anna , Solana-Balaguer Júlia , Campoy-Campos Genís , Vives-Isern Marcel , Soler-Palazón Ferran , Anglada-Huguet Marta , López-Toledano Miguel-Ángel , Mandelkow Eva-Maria , Alberch Jordi , Giralt Albert , Malagelada Cristina 
Published: June 2021

AbstractRTP801/REDD1 is a stress-regulated protein whose upregulation is necessary and sufficient to trigger neuronal death. Its downregulation in Parkinson’s and Huntington’s disease models ameliorates the pathological phenotypes. In the context of Alzheimer’s disease (AD), the coding gene for RTP801, DDIT4, is responsive to Aβ and modulates its cytotoxicity in vitro. Also, RTP801 mRNA levels are increased in AD patients’ lymphocytes. However, the involvement of RTP801 in the pathophysiology of AD has not been yet tested. Here, we demonstrate that RTP801 levels are increased in postmortem hippocampal samples from AD patients. Interestingly, RTP801 protein levels correlated with both Braak and Thal stages of the disease and with GFAP expression. RTP801 levels are also upregulated in hippocampal synaptosomal fractions obtained from murine 5xFAD and rTg4510 mice models of the disease. A local RTP801 knockdown in the 5xFAD hippocampal neurons with shRNA-containing AAV particles ameliorates cognitive deficits in 7-month-old animals. Upon RTP801 silencing in the 5xFAD mice, no major changes were detected in hippocampal synaptic markers or spine density. Importantly, we found an unanticipated recovery of several gliosis hallmarks and inflammasome key proteins upon neuronal RTP801 downregulation in the 5xFAD mice. Altogether our results suggest that RTP801 could be a potential future target for theranostic studies since it could be a biomarker of neuroinflammation and neurotoxicity severity of the disease and, at the same time, a promising therapeutic target in the treatment of AD.
Influence of maternal and paternal pre-conception overweight/obesity on offspring outcomes and strategies for prevention
Authors: Hieronimus Bettina , Ensenauer Regina 
Published: June 2021

AbstractOverweight, obesity, and their comorbidities remain global health challenges. When established early in life, overweight is often sustained into adulthood and contributes to the early onset of non-communicable diseases. Parental pre-conception overweight and obesity is a risk factor for overweight and obesity in childhood and beyond. This increased risk likely is based on an interplay of genetic alterations and environmental exposures already at the beginning of life, although mechanisms are still poorly defined. In this narrative review, potential routes of transmission of pre-conceptional overweight/obesity from mothers and fathers to their offspring as well as prevention strategies are discussed. Observational evidence suggests that metabolic changes due to parental overweight/obesity affect epigenetic markers in oocytes and sperms alike and may influence epigenetic programming and reprogramming processes during embryogenesis. While weight reduction in overweight/obese men and women, who plan to become pregnant, seems advisable to improve undesirable outcomes in offspring, caution might be warranted. Limited evidence suggests that weight loss in men and women in close proximity to conception might increase undesirable offspring outcomes at birth due to nutritional deficits and/or metabolic disturbances in the parent also affecting gamete quality. A change in the dietary pattern might be more advisable. The data reviewed here suggest that pre-conception intervention strategies should shift from women to couples, and future studies should address possible interactions between maternal and paternal contribution to longitudinal childhood outcomes. Randomized controlled trials focusing on effects of pre-conceptional diet quality on long-term offspring health are warranted.
Cross-border climate vulnerabilities of the European Union to drought
Authors: Ercin Ertug , Veldkamp Ted I. E. , Hunink Johannes 
Published: June 2021

AbstractEuropean Union’s vulnerability to climate change stretches far beyond its borders because many of its economic sectors, such as meat and dairy, use raw materials sourced from far afield. Cross-border climate vulnerability is a relatively new subject in scientific literature, while of high societal and economic relevance. We quantify these climate vulnerabilities with a focus on drought risk and assessed them for 2030, 2050, 2085 and for RCP 2.6 and 6.0 climate scenarios. Here we find that more than 44% of the EU agricultural imports will become highly vulnerable to drought in future because of climate change. The drought severity in production locations of the agricultural imports in 2050 will increase by 35% compared to current levels of drought severity. This is particularly valid for imports that originate from Brazil, Indonesia, Vietnam, Thailand, India and Turkey. At the same time, imports from Russia, Nigeria, Peru, Ecuador, Uganda and Kenya will be less vulnerable in future. We also report that the climate vulnerabilities of meat and dairy, chocolate (cocoa), coffee, palm oil-based food and cosmetic sectors mainly lie outside the EU borders rather than inside.
Integrated analysis of Xist upregulation and X-chromosome inactivation with single-cell and single-allele resolution
Authors: Pacini Guido , Dunkel Ilona , Mages Norbert , Mutzel Verena , Timmermann Bernd , Marsico Annalisa , Schulz Edda G. 
Published: June 2021

AbstractTo ensure dosage compensation between the sexes, one randomly chosen X chromosome is silenced in each female cell in the process of X-chromosome inactivation (XCI). XCI is initiated during early development through upregulation of the long non-coding RNA Xist, which mediates chromosome-wide gene silencing. Cell differentiation, Xist upregulation and gene silencing are thought to be coupled at multiple levels to ensure inactivation of exactly one out of two X chromosomes. Here we perform an integrated analysis of all three processes through allele-specific single-cell RNA-sequencing. Specifically, we assess the onset of random XCI in differentiating mouse embryonic stem cells, and develop dedicated analysis approaches. By exploiting the inter-cellular heterogeneity of XCI onset, we identify putative Xist regulators. Moreover, we show that transient Xist upregulation from both X chromosomes results in biallelic gene silencing right before transitioning to the monoallelic state, confirming a prediction of the stochastic model of XCI. Finally, we show that genetic variation modulates the XCI process at multiple levels, providing a potential explanation for the long-known X-controlling element (Xce) effect, which leads to preferential inactivation of a specific X chromosome in inter-strain crosses. We thus draw a detailed picture of the different levels of regulation that govern the initiation of XCI. The experimental and computational strategies we have developed here will allow us to profile random XCI in more physiological contexts, including primary human cells in vivo.
Tailoring Dzyaloshinskii–Moriya interaction in a transition metal dichalcogenide by dual-intercalation
Authors: Zheng Guolin , Wang Maoyuan , Zhu Xiangde , Tan Cheng , Wang Jie , Albarakati Sultan , Aloufi Nuriyah , Algarni Meri , Farrar Lawrence , Wu Min , Yao Yugui , Tian Mingliang , Zhou Jianhui , Wang Lan 
Published: June 2021

AbstractDzyaloshinskii–Moriya interaction (DMI) is vital to form various chiral spin textures, novel behaviors of magnons and permits their potential applications in energy-efficient spintronic devices. Here, we realize a sizable bulk DMI in a transition metal dichalcogenide (TMD) 2H-TaS2 by intercalating Fe atoms, which form the chiral supercells with broken spatial inversion symmetry and also act as the source of magnetic orderings. Using a newly developed protonic gate technology, gate-controlled protons intercalation could further change the carrier density and intensely tune DMI via the Ruderman–Kittel–Kasuya–Yosida mechanism. The resultant giant topological Hall resistivity $${\rho }_{{xy}}^{T}$$

ρ

x
y

T

of $$1.41{\mathrm{\mu}} \Omega \cdot {{\mathrm{cm}}}$$
1.41
μ
Ω
⋅
cm
at $${V}_{g}=-5.2{\mathrm{V}}$$

V

g

=
−
5.2
V
(about $$424 \%$$
424
%
larger than the zero-bias value) is larger than most known chiral magnets. Theoretical analysis indicates that such a large topological Hall effect originates from the two-dimensional Bloch-type chiral spin textures stabilized by DMI, while the large anomalous Hall effect comes from the gapped Dirac nodal lines by spin–orbit interaction. Dual-intercalation in 2H-TaS2 provides a model system to reveal the nature of DMI in the large family of TMDs and a promising way of gate tuning of DMI, which further enables an electrical control of the chiral spin textures and related electromagnetic phenomena.