bluuebunny/crossref_metadata_2025_split huggingface dataset:
Attention-deficit/hyperactivity disorder and other neurodevelopmental disorders in offspring of parents with depression and bipolar disorder
Authors: Propper L. , Sandstrom A. , Rempel S. , Howes Vallis E. , Abidi S. , Bagnell A. , Lovas D. , Alda M. , Pavlova B. , Uher R. 
Published: June 2021

Abstract

Background
Offspring of parents with major mood disorders (MDDs) are at increased risk for early psychopathology. We aim to compare the rates of neurodevelopmental disorders in offspring of parents with bipolar disorder, major depressive disorder, and controls.

Method
We established a lifetime diagnosis of neurodevelopmental disorders [attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, communication disorders, intellectual disabilities, specific learning disorders, and motor disorders] using the Kiddie Schedule for Affective Disorders and Schizophrenia, Present and Lifetime Version in 400 participants (mean age 11.3 + s.d. 3.9 years), including 93 offspring of parents with bipolar disorder, 182 offspring of parents with major depressive disorder, and 125 control offspring of parents with no mood disorder.

Results
Neurodevelopmental disorders were elevated in offspring of parents with bipolar disorder [odds ratio (OR) 2.34, 95% confidence interval (CI) 1.23–4.47, p = 0.010] and major depressive disorder (OR 1.87, 95% CI 1.03–3.39, p = 0.035) compared to controls. This difference was driven by the rates of ADHD, which were highest among offspring of parents with bipolar disorder (30.1%), intermediate in offspring of parents with major depressive disorder (24.2%), and lowest in controls (14.4%). There were no significant differences in frequencies of other neurodevelopmental disorders between the three groups. Chronic course of mood disorder in parents was associated with higher rates of any neurodevelopmental disorder and higher rates of ADHD in offspring.

Conclusions
Our findings suggest monitoring for ADHD and other neurodevelopmental disorders in offspring of parents with MDDs may be indicated to improve early diagnosis and treatment.
Lack of fit with the neighbourhood social environment as a risk factor for psychosis – a national cohort study
Authors: Schofield Peter , Das-Munshi Jayati , Webb Roger T. , Horsdal Henriette Thisted , Pedersen Carsten B. , Agerbo Esben 
Published: June 2021

AbstractBackgroundMany studies report an ethnic density effect whereby psychosis incidence among ethnic minority groups is higher in low co-ethnic density areas. It is unclear whether an equivalent density effect applies with other types of socioeconomic disadvantages.MethodsWe followed a population cohort of 2 million native Danes comprising all those born on 1st January 1965, or later, living in Denmark on their 15th birthday. Socioeconomic disadvantage, based on parents' circumstances at age 15 (low income, manual occupation, single parent and unemployed), was measured alongside neighbourhood prevalence of these indices.ResultsEach indicator was associated with a higher incidence of non-affective psychosis which remained the same, or was slightly reduced, if neighbourhood levels of disadvantage were lower. For example, for individuals from a low-income background there was no difference in incidence for those living in areas where a low-income was least common [incidence rate ratio (IRR) 1.01; 95% confidence interval (CI) 0.93–1.10 v. those in the quintile where a low income was most common. Typically, differences associated with area-level disadvantage were the same whether or not cohort members had a disadvantaged background; for instance, for those from a manual occupation background, incidence was lower in the quintile where this was least v. most common (IRR 0.83; 95% CI 0.71–0.97), as it was for those from a non-manual background (IRR 0.77; 95% CI 0.67–0.87).ConclusionWe found little evidence for group density effects in contrast to previous ethnic density studies. Further research is needed with equivalent investigations in other countries to see if similar patterns are observed.
Three plays and a shared socio-spiritual horizon in the modern Buddhist revivals in India and China
Authors: Zu Jessica 
Published: June 2021

AbstractThe current study reveals that the Buddhist egalitarian spiritual message found global resonance in an era of globalized inequality. By comparing three modern retellings of an ancient romance between an outcaste (untouchable/Dalit) maiden and the Buddha's attendant Ānanda, this study showcases a shared socio-spiritual horizon that emerged in the Indian and Chinese Buddhist revivals and that thwarted colonial epistemic domination and offered powerful social critiques. More specifically, this study shows that the Indian and Chinese afterlives of the romance display innovative formations of Buddhist social consciousness. The authors reinterpreted equality and freedom on Buddhist terms, creating a new standard of civilization. Employing this “already democratic” Buddhist civilization, they launched critiques of the Indian caste system and Chinese patriarchy. This socio-spiritual horizon subverts the typecast images of “spiritual India” and “rational China.” Whereas these images reflect the limits of the comparative lens based on political regimes – namely, Indian democracy and Chinese socialism – the current study goes beyond regime types by examining diverse formations of universal religion in the cultural sphere. More broadly, a critical strategy for provincializing Europe is to block the colonial gaze and instead showcase the vibrant cultural productions and meaning-making that circulated at the margins of empire.
Towards Wind Vector and Wave Height Retrievals Over Inland Waters Using CYGNSS
Authors: Loria Eric , O'Brien Andrew , Zavorotny Valery , Zuffada Cinzia 
Published: June 2021

AbstractGNSS Reflectometry (GNSS‐R) measurements over inland water bodies, such as lakes, rivers, and wetlands exhibit strong coherent signals. The strength of the coherent reflections is highly sensitive to small‐scale surface roughness. For inland waters, this roughness is primarily due to wind‐driven surface waves. The sensitivity of the coherent reflections to surface roughness can be leveraged to estimate wave height profiles across inland waters. Coupled with a wind wave model, an approach to retrieve a wind vector is described using a forward model, which is potentially able to predict scattered power profiles for different wind speeds and directions and choosing the minimum‐squared error solution. The ability for spaceborne or airborne GNSS‐R to measure an inland water wind vector and wave heights could contribute to scientific applications focused on understanding nearshore ecosystems, monitoring climate change effects on inland waters, sediment resuspension, biomass production, fish habitat, and others. This paper presents a novel approach to potentially retrieve wind vector and wave heights over inland waters using GNSS‐R and discusses the issues with performing such retrievals using simulation and very few available raw signals recorded from CYGNSS satellites.
Contrasting Response of West and East Antarctic Ice Sheets to Glacial Isostatic Adjustment
Authors: Coulon Violaine , Bulthuis Kevin , Whitehouse Pippa L. , Sun Sainan , Haubner Konstanze , Zipf Lars , Pattyn Frank 
Published: June 2021

AbstractThe Antarctic ice sheet (AIS) lies on a solid Earth that displays large spatial variations in rheological properties, with a thin lithosphere and low‐viscosity upper mantle (weak Earth structure) beneath West Antarctica and an opposing structure beneath East Antarctica. This contrast is known to have a significant impact on the ice‐sheet grounding‐line stability. Here, we embed within an ice‐sheet model a modified glacial‐isostatic Elastic Lithosphere‐Relaxing Asthenosphere model that considers a dual pattern for the Earth structure beneath West and East Antarctica supplemented with an approximation of gravitationally consistent geoid changes, allowing to approximate near‐field relative sea‐level changes. We show that this elementary GIA model captures the essence of global Self‐Gravitating Viscoelastic solid‐Earth Models (SGVEMs) and compares well with both SGVEM outputs and geodetic observations, allowing to capture the essential features and processes influencing Antarctic grounding‐line stability in a computationally efficient way. In this framework, we perform a probabilistic assessment of the impact of uncertainties in solid‐Earth rheological properties on the response of the AIS to future warming. Results show that on multicentennial‐to‐millennial timescales, spatial variability in solid‐Earth deformation plays a significant role in promoting the stability of the West Antarctic ice sheet (WAIS). However, WAIS collapse cannot be prevented under high‐emissions climate scenarios. On longer timescales and for unmitigated climate scenarios, continent‐wide mass loss projections may be underestimated because spatially uniform Earth models, as typically considered in numerical ice sheet models, will overestimate the stabilizing effect of GIA across East Antarctica, which is characterized by thick lithosphere and high upper‐mantle viscosity.
A Large Magma Reservoir Beneath the Tengchong Volcano Revealed by Ambient Noise Adjoint Tomography
Authors: Zhao Y. , Guo Z. , Wang K. , Yang Y. J. 
Published: June 2021

AbstractThe Tengchong volcano (TCV) is a large active volcano system in the southeastern Tibetan Plateau. It is characterized by large‐volume magmatic gas emission, active hydrothermal circulation, and intense volcanic and earthquake activities, posing a threat of near future eruptions. However, there is still no available model of the magmatic plumbing system beneath the volcano system, limiting the quantitative assessments of the eruption hazards. Here, we present a high‐resolution 3D model of the TCV constructed using ambient noise adjoint tomography. Our 3D model reveals a large basaltic magma reservoir with a volume of ∼7,000 km3 at depths of 20–35 km, which has a melt fraction of ∼2%–4.5%. Our results suggest that the deep crustal magma reservoir is fed by partial melting in the uppermost mantle and is recharging the shallow magma chambers beneath the TCV. Our results are key to understanding the volcanic activities and assessing future eruption hazards.
LncRNA MIR17HG promotes colorectal cancer liver metastasis by mediating a glycolysis-associated positive feedback circuit
Authors: Zhao Senlin , Guan Bingjie , Mi Yushuai , Shi Debing , Wei Ping , Gu Yanzi , Cai Sanjun , Xu Ye , Li Xinxiang , Yan Dongwang , Huang Mingzhu , Li Dawei 
Published: June 2021

AbstractGlycolysis plays a crucial role in reprogramming the metastatic tumor microenvironment. A series of lncRNAs have been identified to function as oncogenic molecules by regulating glycolysis. However, the roles of glycolysis-related lncRNAs in regulating colorectal cancer liver metastasis (CRLM) remain poorly understood. In the present study, the expression of the glycolysis-related lncRNA MIR17HG gradually increased from adjacent normal to CRC to the paired liver metastatic tissues, and high MIR17HG expression predicted poor survival, especially in patients with liver metastasis. Functionally, MIR17HG promoted glycolysis in CRC cells and enhanced their invasion and liver metastasis in vitro and in vivo. Mechanistically, MIR17HG functioned as a ceRNA to regulate HK1 expression by sponging miR-138-5p, resulting in glycolysis in CRC cells and leading to their invasion and liver metastasis. More interestingly, lactate accumulated via glycolysis activated the p38/Elk-1 signaling pathway to promote the transcriptional expression of MIR17HG in CRC cells, forming a positive feedback loop, which eventually resulted in persistent glycolysis and the invasion and liver metastasis of CRC cells. In conclusion, the present study indicates that the lactate-responsive lncRNA MIR17HG, acting as a ceRNA, promotes CRLM through a glycolysis-mediated positive feedback circuit and might be a novel biomarker and therapeutic target for CRLM.
The FLI portion of EWS/FLI contributes a transcriptional regulatory function that is distinct and separable from its DNA-binding function in Ewing sarcoma
Authors: Boone Megann A. , Taslim Cenny , Crow Jesse C. , Selich-Anderson Julia , Byrum Andrea K. , Showpnil Iftekhar A. , Sunkel Benjamin D. , Wang Meng , Stanton Benjamin Z. , Theisen Emily R. , Lessnick Stephen L. 
Published: June 2021

AbstractEwing sarcoma is an aggressive bone cancer of children and young adults defined by the presence of a chromosomal translocation: t(11;22)(q24;q12). The encoded protein, EWS/FLI, fuses the amino-terminal domain of EWS to the carboxyl-terminus of FLI. The EWS portion is an intrinsically disordered transcriptional regulatory domain, while the FLI portion contains an ETS DNA-binding domain and two flanking regions of unknown function. Early studies using non-Ewing sarcoma models provided conflicting information on the roles of each domain of FLI in EWS/FLI oncogenic function. We therefore sought to define the specific contributions of each FLI domain to EWS/FLI activity in a well-validated Ewing sarcoma model and, in doing so, to better understand Ewing sarcoma development mediated by the fusion protein. We analyzed a series of engineered EWS/FLI mutants with alterations in the FLI portion using a variety of assays. Fluorescence anisotropy, CUT&RUN, and ATAC-sequencing experiments revealed that the isolated ETS domain is sufficient to maintain the normal DNA-binding and chromatin accessibility function of EWS/FLI. In contrast, RNA-sequencing and soft agar colony formation assays revealed that the ETS domain alone was insufficient for transcriptional regulatory and oncogenic transformation functions of the fusion protein. We found that an additional alpha-helix immediately downstream of the ETS domain is required for full transcriptional regulation and EWS/FLI-mediated oncogenesis. These data demonstrate a previously unknown role for FLI in transcriptional regulation that is distinct from its DNA-binding activity. This activity is critical for the cancer-causing function of EWS/FLI and may lead to novel therapeutic approaches.
A comparison of genotyping arrays
Authors: Verlouw Joost A. M. , Clemens Eva , de Vries Jard H. , Zolk Oliver , Verkerk Annemieke J. M. H. , am Zehnhoff-Dinnesen Antoinette , Medina-Gomez Carolina , Lanvers-Kaminsky Claudia , Rivadeneira Fernando , Langer Thorsten , van Meurs Joyce B. J. , van den Heuvel-Eibrink Marry M. , Uitterlinden André G. , Broer Linda 
Published: June 2021

AbstractArray technology to genotype single-nucleotide variants (SNVs) is widely used in genome-wide association studies (GWAS), clinical diagnostics, and linkage studies. Arrays have undergone a tremendous growth in both number and content over recent years making a comprehensive comparison all the more important. We have compared 28 genotyping arrays on their overall content, genome-wide coverage, imputation quality, presence of known GWAS loci, mtDNA variants and clinically relevant genes (i.e., American College of Medical Genetics (ACMG) actionable genes, pharmacogenetic genes, human leukocyte antigen (HLA) genes and SNV density). Our comparison shows that genome-wide coverage is highly correlated with the number of SNVs on the array but does not correlate with imputation quality, which is the main determinant of GWAS usability. Average imputation quality for all tested arrays was similar for European and African populations, indicating that this is not a good criterion for choosing a genotyping array. Rather, the additional content on the array, such as pharmacogenetics or HLA variants, should be the deciding factor. As the research question of a study will in large part determine which class of genes are of interest, there is not just one perfect array for all different research questions. This study can thus help as a guideline to determine which array best suits a study’s requirements.
Improved prediction of solvation free energies by machine-learning polarizable continuum solvation model
Authors: Alibakhshi Amin , Hartke Bernd 
Published: June 2021

AbstractTheoretical estimation of solvation free energy by continuum solvation models, as a standard approach in computational chemistry, is extensively applied by a broad range of scientific disciplines. Nevertheless, the current widely accepted solvation models are either inaccurate in reproducing experimentally determined solvation free energies or require a number of macroscopic observables which are not always readily available. In the present study, we develop and introduce the Machine-Learning Polarizable Continuum solvation Model (ML-PCM) for a substantial improvement of the predictability of solvation free energy. The performance and reliability of the developed models are validated through a rigorous and demanding validation procedure. The ML-PCM models developed in the present study improve the accuracy of widely accepted continuum solvation models by almost one order of magnitude with almost no additional computational costs. A freely available software is developed and provided for a straightforward implementation of the new approach.
The extracellular contractile injection system is enriched in environmental microbes and associates with numerous toxins
Authors: Geller Alexander Martin , Pollin Inbal , Zlotkin David , Danov Aleks , Nachmias Nimrod , Andreopoulos William B. , Shemesh Keren , Levy Asaf 
Published: June 2021

AbstractThe extracellular Contractile Injection System (eCIS) is a toxin-delivery particle that evolved from a bacteriophage tail. Four eCISs have previously been shown to mediate interactions between bacteria and their invertebrate hosts. Here, we identify eCIS loci in 1,249 bacterial and archaeal genomes and reveal an enrichment of these loci in environmental microbes and their apparent absence from mammalian pathogens. We show that 13 eCIS-associated toxin genes from diverse microbes can inhibit the growth of bacteria and/or yeast. We identify immunity genes that protect bacteria from self-intoxication, further supporting an antibacterial role for some eCISs. We also identify previously undescribed eCIS core genes, including a conserved eCIS transcriptional regulator. Finally, we present our data through an extensive eCIS repository, termed eCIStem. Our findings support eCIS as a toxin-delivery system that is widespread among environmental prokaryotes and likely mediates antagonistic interactions with eukaryotes and other prokaryotes.
Emission impacts of China’s solid waste import ban and COVID-19 in the copper supply chain
Authors: Ryter John , Fu Xinkai , Bhuwalka Karan , Roth Richard , Olivetti Elsa A. 
Published: June 2021

AbstractClimate change will increase the frequency and severity of supply chain disruptions and large-scale economic crises, also prompting environmentally protective local policies. Here we use econometric time series analysis, inventory-driven price formation, dynamic material flow analysis, and life cycle assessment to model each copper supply chain actor’s response to China’s solid waste import ban and the COVID-19 pandemic. We demonstrate that the economic changes associated with China’s solid waste import ban increase primary refining within China, offsetting the environmental benefits of decreased copper scrap refining and generating a cumulative increase in CO2-equivalent emissions of up to 13 Mt by 2040. Increasing China’s refined copper imports reverses this trend, decreasing CO2e emissions in China (up to 180 Mt by 2040) and globally (up to 20 Mt). We test sensitivity to supply chain disruptions using GDP, mining, and refining shocks associated with the COVID-19 pandemic, showing the results translate onto disruption effects.
Structural basis for CSPG4 as a receptor for TcdB and a therapeutic target in Clostridioides difficile infection
Authors: Chen Peng , Zeng Ji , Liu Zheng , Thaker Hatim , Wang Siyu , Tian Songhai , Zhang Jie , Tao Liang , Gutierrez Craig B. , Xing Li , Gerhard Ralf , Huang Lan , Dong Min , Jin Rongsheng 
Published: June 2021

AbstractC. difficile is a major cause of antibiotic-associated gastrointestinal infections. Two C. difficile exotoxins (TcdA and TcdB) are major virulence factors associated with these infections, and chondroitin sulfate proteoglycan 4 (CSPG4) is a potential receptor for TcdB, but its pathophysiological relevance and the molecular details that govern recognition remain unknown. Here, we determine the cryo-EM structure of a TcdB–CSPG4 complex, revealing a unique binding site spatially composed of multiple discontinuous regions across TcdB. Mutations that selectively disrupt CSPG4 binding reduce TcdB toxicity in mice, while CSPG4-knockout mice show reduced damage to colonic tissues during C. difficile infections. We further show that bezlotoxumab, the only FDA approved anti-TcdB antibody, blocks CSPG4 binding via an allosteric mechanism, but it displays low neutralizing potency on many TcdB variants from epidemic hypervirulent strains due to sequence variations in its epitopes. In contrast, a CSPG4-mimicking decoy neutralizes major TcdB variants, suggesting a strategy to develop broad-spectrum therapeutics against TcdB.
Subtype-specific collaborative transcription factor networks are promoted by OCT4 in the progression of prostate cancer
Authors: Takayama Ken-ichi , Kosaka Takeo , Suzuki Takashi , Hongo Hiroshi , Oya Mototsugu , Fujimura Tetsuya , Suzuki Yutaka , Inoue Satoshi 
Published: June 2021

AbstractInteractive networks of transcription factors (TFs) have critical roles in epigenetic and gene regulation for cancer progression. It is required to clarify underlying mechanisms for transcriptional activation through concerted efforts of TFs. Here, we show the essential role of disease phase-specific TF collaboration changes in advanced prostate cancer (PC). Investigation of the transcriptome in castration-resistant PC (CRPC) revealed OCT4 as a key TF in the disease pathology. OCT4 confers epigenetic changes by promoting complex formation with FOXA1 and androgen receptor (AR), the central signals for the progression to CRPC. Meanwhile, OCT4 facilitates a distinctive complex formation with nuclear respiratory factor 1 (NRF1) to gain chemo-resistance in the absence of AR. Mechanistically, we reveal that OCT4 increases large droplet formations with AR/FOXA1 as well as NRF1 in vitro. Disruption of TF collaborations using a nucleoside analogue, ribavirin, inhibited treatment-resistant PC tumor growth. Thus, our findings highlight the formation of TF collaborations as a potent therapeutic target in advanced cancer.
Immunological imprinting of the antibody response in COVID-19 patients
Authors: Aydillo Teresa , Rombauts Alexander , Stadlbauer Daniel , Aslam Sadaf , Abelenda-Alonso Gabriela , Escalera Alba , Amanat Fatima , Jiang Kaijun , Krammer Florian , Carratala Jordi , García-Sastre Adolfo 
Published: June 2021

AbstractIn addition to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), humans are also susceptible to six other coronaviruses, for which consecutive exposures to antigenically related and divergent seasonal coronaviruses are frequent. Despite the prevalence of COVID-19 pandemic and ongoing research, the nature of the antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. Here we longitudinally profile the early humoral immune response against SARS-CoV-2 in hospitalized coronavirus disease 2019 (COVID-19) patients and quantify levels of pre-existing immunity to OC43, HKU1 and 229E seasonal coronaviruses, and find a strong back-boosting effect to conserved but not variable regions of OC43 and HKU1 betacoronaviruses spike protein. However, such antibody memory boost to human coronaviruses negatively correlates with the induction of IgG and IgM against SARS-CoV-2 spike and nucleocapsid protein. Our findings thus provide evidence of immunological imprinting by previous seasonal coronavirus infections that can potentially modulate the antibody profile to SARS-CoV-2 infection.