bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations between levels of oxidative nucleoside damage and cardiovascular risk in patients newly diagnosed with bipolar disorder and their unaffected relatives
Authors: Bøgh Helena Lykke , Stanislaus Sharleny , Kjærstad Hanne Lie , Sletved Kimie Stefanie Ormstrup , Forman Julie Lyng , Poulsen Henrik Enghusen , Vinberg Maj , Kessing Lars Vedel , Coello Klara 
Published: August 2022

AbstractEnhanced oxidative stress-generated nucleoside damage may contribute to the increased cardiovascular disease mortality in patients with bipolar disorder (BD) but the association has never been investigated. We investigated the associations between oxidative stress-generated damage to DNA (8-oxodG) and RNA (8-oxoGuo), respectively, and three measures reflecting cardiovascular risk; namely, the Framingham 30-year risk score of cardiovascular diseases, the metabolic syndrome, and the insulin resistance index in 360 patients newly diagnosed with BD, 102 of their unaffected relatives (UR) and 197 healthy control individuals (HC). In sex- and age-adjusted models, the 30-year cardiovascular risk score increased by 20.8% (CI = 7.4–35.9%, p = 0.002) for every one nM/mM creatinine increase in 8-oxoGuo and by 15.6% (95% CI = 5.8–26.4%, p = 0.001) for every one nM/mM creatinine increase in 8-oxodG, respectively. Further, insulin resistance index increased by 24.1% (95% CI = 6.7–43%, p = 0.005) when 8-oxoGuo increased one nM/mM creatinine. The associations between cardiovascular measures and oxidative nucleoside damage were more pronounced in patients with BD compared with UR, and HC. Metabolic syndrome was not associated with nucleoside damage. Overall, higher oxidative stress-generated nucleoside damage was associated with a higher cardiovascular risk score and a higher degree of insulin resistance index, and having BD impacted the associations. Further, within patients, treatment with psychotropics seemed to enhance the associations between 30-year CVD risk score and insulin resistance index, respectively, and oxidatively stress-generated nucleoside damage. Our findings support enhanced oxidative stress-generated nucleoside damage as a putative pathophysiological mechanism that may mediate the higher cardiovascular risk observed in patients with BD already at the time of diagnosis.
Acute and long-term effects of psilocybin on energy balance and feeding behavior in mice
Authors: Fadahunsi Nicole , Lund Jens , Breum Alberte Wollesen , Mathiesen Cecilie Vad , Larsen Isabella Beck , Knudsen Gitte Moos , Klein Anders Bue , Clemmensen Christoffer 
Published: August 2022

AbstractPsilocybin and other serotonergic psychedelics have re-emerged as therapeutics for neuropsychiatric disorders, including addiction. Psilocybin induces long-lasting effects on behavior, likely due to its profound ability to alter consciousness and augment neural connectivity and plasticity. Impaired synaptic plasticity in obesity contributes to ‘addictive-like’ behaviors, including heightened motivation for palatable food, and excessive food seeking and consumption. Here, we evaluate the effects of psilocybin on feeding behavior, energy metabolism, and as a weight-lowering agent in mice. We demonstrate that a single dose of psilocybin substantially alters the prefrontal cortex transcriptome but has no acute or long-lasting effects on food intake or body weight in diet-induced obese mice or in genetic mouse models of obesity. Similarly, sub-chronic microdosing of psilocybin has no metabolic effects in obese mice and psilocybin does not augment glucagon-like peptide-1 (GLP-1) induced weight loss or enhance diet-induced weight loss. A single high dose of psilocybin reduces sucrose preference but fails to counter binge-like eating behavior. Although these preclinical data discourage clinical investigation, there may be nuances in the mode of action of psychedelic drugs that are difficult to capture in rodent models, and thus require human evaluation to uncover.
Transcription-coupled and epigenome-encoded mechanisms direct H3K4 methylation
Authors: Oya Satoyo , Takahashi Mayumi , Takashima Kazuya , Kakutani Tetsuji , Inagaki Soichi 
Published: August 2022

AbstractMono-, di-, and trimethylation of histone H3 lysine 4 (H3K4me1/2/3) are associated with transcription, yet it remains controversial whether H3K4me1/2/3 promote or result from transcription. Our previous characterizations of Arabidopsis H3K4 demethylases suggest roles for H3K4me1 in transcription. However, the control of H3K4me1 remains unexplored in Arabidopsis, in which no methyltransferase for H3K4me1 has been identified. Here, we identify three Arabidopsis methyltransferases that direct H3K4me1. Analyses of their genome-wide localization using ChIP-seq and machine learning reveal that one of the enzymes cooperates with the transcription machinery, while the other two are associated with specific histone modifications and DNA sequences. Importantly, these two types of localization patterns are also found for the other H3K4 methyltransferases in Arabidopsis and mice. These results suggest that H3K4me1/2/3 are established and maintained via interplay with transcription as well as inputs from other chromatin features, presumably enabling elaborate gene control.
Ultra-deep sequencing validates safety of CRISPR/Cas9 genome editing in human hematopoietic stem and progenitor cells
Authors: Cromer M. Kyle , Barsan Valentin V. , Jaeger Erich , Wang Mengchi , Hampton Jessica P. , Chen Feng , Kennedy Drew , Xiao Jenny , Khrebtukova Irina , Granat Ana , Truong Tiffany , Porteus Matthew H. 
Published: August 2022

AbstractAs CRISPR-based therapies enter the clinic, evaluation of safety remains a critical and active area of study. Here, we employ a clinical next generation sequencing (NGS) workflow to achieve high sequencing depth and detect ultra-low frequency variants across exons of genes associated with cancer, all exons, and genome wide. In three separate primary human hematopoietic stem and progenitor cell (HSPC) donors assessed in technical triplicates, we electroporated high-fidelity Cas9 protein targeted to three loci (AAVS1, HBB, and ZFPM2) and harvested genomic DNA at days 4 and 10. Our results demonstrate that clinically relevant delivery of high-fidelity Cas9 to primary HSPCs and ex vivo culture up to 10 days does not introduce or enrich for tumorigenic variants and that even a single SNP in a gRNA spacer sequence is sufficient to eliminate Cas9 off-target activity in primary, repair-competent human HSPCs.
Comparative immunogenicity and reactogenicity of heterologous ChAdOx1-nCoV-19-priming and BNT162b2 or mRNA-1273-boosting with homologous COVID-19 vaccine regimens
Authors: Klemis Verena , Schmidt Tina , Schub David , Mihm Janine , Marx Stefanie , Abu-Omar Amina , Ziegler Laura , Hielscher Franziska , Guckelmus Candida , Urschel Rebecca , Wagenpfeil Stefan , Schneitler Sophie , Becker Sören L. , Gärtner Barbara C. , Sester Urban , Sester Martina 
Published: August 2022

AbstractComparative analyses of the immunogenicity and reactogenicity of homologous and heterologous SARS-CoV-2 vaccine-regimens will inform optimized vaccine strategies. Here we analyze the humoral and cellular immune response following heterologous and homologous vaccination strategies in a convenience cohort of 331 healthy individuals. All regimens induce immunity to the vaccine antigen. Immunity after vaccination with ChAdOx1-nCoV-19 followed by either BNT162b2 (n = 66) or mRNA-1273 (n = 101) is equivalent to or more pronounced than homologous mRNA-regimens (n = 43 BNT162b2, n = 59 mRNA-1273) or homologous ChAdOx1-nCoV-19 vaccination (n = 62). We note highest levels of spike-specific CD8 T-cells following both heterologous regimens. Among mRNA-containing combinations, spike-specific CD4 T-cell levels in regimens including mRNA-1273 are higher than respective combinations with BNT162b2. Polyfunctional T-cell levels are highest in regimens based on ChAdOx1-nCoV-19-priming. All five regimens are well tolerated with most pronounced reactogenicity upon ChAdOx1-nCoV-19-priming, and ChAdOx1-nCoV-19/mRNA-1273-boosting. In conclusion, we present comparative analyses of immunogenicity and reactogenicity for heterologous vector/mRNA-boosting and homologous mRNA-regimens.
Circular RNA circTmem241 drives group III innate lymphoid cell differentiation via initiation of Elk3 transcription
Authors: Liu Nian , He Jiacheng , Fan Dongdong , Gu Yang , Wang Jianyi , Li Huimu , Zhu Xiaoxiao , Du Ying , Tian Yong , Liu Benyu , Fan Zusen 
Published: August 2022

AbstractInnate lymphoid cells (ILCs) exert important roles in host defense, tissue repair and inflammatory diseases. However, how ILC lineage specification is regulated remains largely elusive. Here we identify that circular RNA circTmem241 is highly expressed in group III innate lymphoid cells (ILC3s) and their progenitor cells. CircTmem241 deficiency impairs ILC3 commitment and attenuates anti-bacterial immunity. Mechanistically, circTmem241 interacts with Nono protein to recruit histone methyltransferase Ash1l onto Elk3 promoter in ILC progenitor cells (ILCPs). Ash1l-mediated histone modifications on Elk3 promoter enhance chromatin accessibility to initiate Elk3 transcription. Of note, circTmem241−/−, Nono−/− and Ash1l−/− ILCPs display impaired ILC3 differentiation, while Elk3 overexpression rescues ILC3 commitment ability. Finally, circTmem241−/−Elk3−/− mice show lower numbers of ILC3s and are more susceptible to bacterial infection. We reveal that the circTmem241-Nono-Ash1l-Elk3 axis is required for the ILCP differentiation into ILC3P and ILC3 maturation, which is important to manipulate this axis for ILC development on treatment of infectious diseases.
Rational highly dispersed ruthenium for reductive catalytic fractionation of lignocellulose
Authors: Liu Zhenzhen , Li Helong , Gao Xueying , Guo Xuan , Wang Shuizhong , Fang Yunming , Song Guoyong 
Published: August 2022

AbstractProducing monomeric phenols from lignin biopolymer depolymerization in a detachable and efficient manner comes under the spotlight on the fullest utilization of sustainable lignocellulosic biomass. Here, we report a low-loaded and highly dispersed Ru anchored on a chitosan-derived N-doped carbon catalyst (RuN/ZnO/C), which exhibits outstanding performance in the reductive catalytic fractionation of lignocellulose. Nearly theoretical maximum yields of phenolic monomers from lignin are achieved, corresponding to TON as 431 molphenols molRu−1, 20 times higher than that from commercial Ru/C catalyst; high selectivity toward propyl end-chained guaiacol and syringol allow them to be readily purified. The RCF leave high retention of (hemi)cellulose amenable to enzymatic hydrolysis due to the successful breakdown of biomass recalcitrance. The RuN/ZnO/C catalyst shows good stability in recycling experiments as well as after a harsh hydrothermal treatment, benefiting from the coordination of Ru species with N atoms. Characterizations of the RuN/ZnO/C imply a transformation from Ru single atoms to nanoclusters under current reaction conditions. Time-course experiment, as well as reactivity screening of a series of lignin model compounds, offer insight into the mechanism of current RCF over RuN/ZnO/C. This work opens a new opportunity for achieving the valuable aromatic products from lignin and promoting the industrial economic feasibility of lignocellulosic biomass.
Adenosine triphosphate-activated prodrug system for on-demand bacterial inactivation and wound disinfection
Authors: Weng Yuhao , Chen Huihong , Chen Xiaoqian , Yang Huilin , Chen Chia-Hung , Tan Hongliang 
Published: August 2022

AbstractThe prodrug approach has emerged as a promising solution to combat bacterial resistance and enhance treatment efficacy against bacterial infections. Here, we report an adenosine triphosphate (ATP)-activated prodrug system for on-demand treatment of bacterial infection. The prodrug system benefits from the synergistic action of zeolitic imidazolate framework-8 and polyacrylamide hydrogel microsphere, which simultaneously transports indole-3-acetic acid and horseradish peroxidase in a single carrier while preventing the premature activation of indole-3-acetic acid. The ATP-responsive characteristic of zeolitic imidazolate framework-8 allows the prodrug system to be activated by the ATP secreted by bacteria to generate reactive oxygen species (ROS), displaying exceptional broad-spectrum antimicrobial ability. Upon disruption of the bacterial membrane by ROS, the leaked intracellular ATP from dead bacteria can accelerate the activation of the prodrug system to further enhance antibacterial efficiency. In vivo experiments in a mouse model demonstrates the applicability of the prodrug system for wound disinfection with minimal side effects.
Restructured membrane contacts rewire organelles for human cytomegalovirus infection
Authors: Cook Katelyn C. , Tsopurashvili Elene , Needham Jason M. , Thompson Sunnie R. , Cristea Ileana M. 
Published: August 2022

AbstractMembrane contact sites (MCSs) link organelles to coordinate cellular functions across space and time. Although viruses remodel organelles for their replication cycles, MCSs remain largely unexplored during infections. Here, we design a targeted proteomics platform for measuring MCS proteins at all organelles simultaneously and define functional virus-driven MCS alterations by the ancient beta-herpesvirus human cytomegalovirus (HCMV). Integration with super-resolution microscopy and comparisons to herpes simplex virus (HSV-1), Influenza A, and beta-coronavirus HCoV-OC43 infections reveals time-sensitive contact regulation that allows switching anti- to pro-viral organelle functions. We uncover a stabilized mitochondria-ER encapsulation structure (MENC). As HCMV infection progresses, MENCs become the predominant mitochondria-ER contact phenotype and sequentially recruit the tethering partners VAP-B and PTPIP51, supporting virus production. However, premature ER-mitochondria tethering activates STING and interferon response, priming cells against infection. At peroxisomes, ACBD5-mediated ER contacts balance peroxisome proliferation versus membrane expansion, with ACBD5 impacting the titers of each virus tested.
A resonant electro-physical transmutation method for water purification
Authors: Lee McKane B. , Ward Nicholas D. , Leach Michael , Kent Randy 
Published: August 2022

AbstractWe present an electro-transmutation (ET) method of water purification using the Quantum Kinetic Fusor™. Electrolysis experiments were performed with residential well water and seawater coupled with two different electrode materials—stainless steel and aluminum—to test the effectiveness of ET in removing contaminants and altering the physiochemistry (e.g., pH, alkalinity) and isotopic composition of water. ET effectively removed contaminants at power inputs as low 0.142 mA cm−2, i.e., 1.9–4.2 watts, which is substantially lower than other electrochemical techniques. The ET process also reduces, and in some cases eliminates, electrode surface area degradation. This outcome is outside the field of traditional Faraday electrolysis, further distinguishing the ET process as potentially more cost-effective than other water purification methods. Importantly, the experiments reveal ET is an exceptionally low input energy generator. This finding is based on the presence of exotic x-rays (Bremsstrahlung) emissions during operation (1–20 KeV).
Context-specific emergence and growth of the SARS-CoV-2 Delta variant
Authors: McCrone John T. , Hill Verity , Bajaj Sumali , Pena Rosario Evans , Lambert Ben C. , Inward Rhys , Bhatt Samir , Volz Erik , Ruis Christopher , Dellicour Simon , Baele Guy , Zarebski Alexander E. , Sadilek Adam , Wu Neo , Schneider Aaron , Ji Xiang , Raghwani Jayna , Jackson Ben , Colquhoun Rachel , O’Toole Áine , Peacock Thomas P. , Twohig Kate , Thelwall Simon , Dabrera Gavin , Myers Richard ,   The COVID-19 Genomics UK (COG-UK) Consortium, Faria Nuno R. , Huber Carmen , Bogoch Isaac I. , Khan Kamran , du Plessis Louis , Barrett Jeffrey C. , Aanensen David M. , Barclay Wendy S. , Chand Meera , Connor Thomas , Loman Nicholas J. , Suchard Marc A. , Pybus Oliver G. , Rambaut Andrew , Kraemer Moritz U. G. 
Published: August 2022

AbstractThe SARS-CoV-2 Delta (Pango lineage B.1.617.2) variant of concern spread globally, causing resurgences of COVID-19 worldwide1,2. The emergence of the Delta variant in the UK occurred on the background of a heterogeneous landscape of immunity and relaxation of non-pharmaceutical interventions. Here we analyse 52,992 SARS-CoV-2 genomes from England together with 93,649 genomes from the rest of the world to reconstruct the emergence of Delta and quantify its introduction to and regional dissemination across England in the context of changing travel and social restrictions. Using analysis of human movement, contact tracing and virus genomic data, we find that the geographic focus of the expansion of Delta shifted from India to a more global pattern in early May 2021. In England, Delta lineages were introduced more than 1,000 times and spread nationally as non-pharmaceutical interventions were relaxed. We find that hotel quarantine for travellers reduced onward transmission from importations; however, the transmission chains that later dominated the Delta wave in England were seeded before travel restrictions were introduced. Increasing inter-regional travel within England drove the nationwide dissemination of Delta, with some cities receiving more than 2,000 observable lineage introductions from elsewhere. Subsequently, increased levels of local population mixing—and not the number of importations—were associated with the faster relative spread of Delta. The invasion dynamics of Delta depended on spatial heterogeneity in contact patterns, and our findings will inform optimal spatial interventions to reduce the transmission of current and future variants of concern, such as Omicron (Pango lineage B.1.1.529).
Substantial somatic genomic variation and selection for BCOR mutations in human induced pluripotent stem cells
Authors: Rouhani Foad J. , Zou Xueqing , Danecek Petr , Badja Cherif , Amarante Tauanne Dias , Koh Gene , Wu Qianxin , Memari Yasin , Durbin Richard , Martincorena Inigo , Bassett Andrew R. , Gaffney Daniel , Nik-Zainal Serena 
Published: August 2022

AbstractWe explored human induced pluripotent stem cells (hiPSCs) derived from different tissues to gain insights into genomic integrity at single-nucleotide resolution. We used genome sequencing data from two large hiPSC repositories involving 696 hiPSCs and daughter subclones. We find ultraviolet light (UV)-related damage in ~72% of skin fibroblast-derived hiPSCs (F-hiPSCs), occasionally resulting in substantial mutagenesis (up to 15 mutations per megabase). We demonstrate remarkable genomic heterogeneity between independent F-hiPSC clones derived during the same round of reprogramming due to oligoclonal fibroblast populations. In contrast, blood-derived hiPSCs (B-hiPSCs) had fewer mutations and no UV damage but a high prevalence of acquired BCOR mutations (26.9% of lines). We reveal strong selection pressure for BCOR mutations in F-hiPSCs and B-hiPSCs and provide evidence that they arise in vitro. Directed differentiation of hiPSCs and RNA sequencing showed that BCOR mutations have functional consequences. Our work strongly suggests that detailed nucleotide-resolution characterization is essential before using hiPSCs.
Statistically enriched geospatial datasets of Brazilian municipalities for data-driven modeling
Authors: Abdalla Livia , Augusto Douglas A. , Chame Marcia , Dufek Amanda S. , Oliveira Leonardo , Krempser Eduardo 
Published: August 2022

AbstractThe lack of georeferencing in geospatial datasets hinders the accomplishment of scientific studies that rely on accurate data. This is particularly concerning in the field of health sciences, where georeferenced data could lead to scientific results of great relevance to society. The Brazilian health systems, especially those for Notifiable Diseases, in practice do not register georeferenced data; instead, the records indicate merely the municipality in which the event occurred. Typically in data-driven modeling, accurate disease prediction models based on occurrence requires socioenvironmental characteristics of the exact location of each event, which is often unavailable. To enrich the expressiveness of data-driven models when the municipality of the event is the best available information, we produced datasets with statistical characterization of all 5,570 Brazilian municipalities in 642 layers of thematic data that represent the natural and artificial characteristics of the municipalities’ landscapes over time. This resulted in a collection of datasets comprising a total of 11,556 descriptive statistics attributes for each municipality.
A new Cretaceous thyreophoran from Patagonia supports a South American lineage of armoured dinosaurs
Authors: Riguetti Facundo J. , Apesteguía Sebastián , Pereda-Suberbiola Xabier 
Published: August 2022

AbstractThe early evolution of thyreophoran dinosaurs is thought to have occurred primarily in northern continents since most evidence comes from the Lower and Middle Jurassic of Europe and North America. The diversification into stegosaurs and ankylosaurs is obscured by a patchy fossil record comprising only a handful of fragmentary fossils, most with uncertain phylogenetic affinities. Here we report the discovery of a new armoured dinosaur from the early Late Cretaceous of Argentina, recovered phylogenetically using various datasets either as a basal thyreophoran or a stem ankylosaur, closely related to Scelidosaurus. It bears unusual anatomical features showing that several traits traditionally associated with the heavy Cretaceous thyreophorans did not occur universally. Jakapil kaniukura gen. et sp. nov. is the first definitive thyreophoran species from the Argentinian Patagonia. Unlike most thyreophorans, it seems to show a bipedal stance, as in Scutellosaurus. Jakapil also shows that early thyreophorans had a much broader geographic distribution than previously thought. It is a member of an ancient basal thyreophoran lineage that survived until the Late Cretaceous in South America.
Convolutional neural networks for approximating electrical and thermal conductivities of Cu-CNT composites
Authors: Ejaz Faizan , Hwang Leslie K. , Son Jangyup , Kim Jin-Sang , Lee Dong Su , Kwon Beomjin 
Published: August 2022

AbstractThis article explores the deep learning approach towards approximating the effective electrical and thermal conductivities of copper (Cu)-carbon nanotube (CNT) composites with CNTs aligned to the field direction. Convolutional neural networks (CNN) are trained to map the two-dimensional images of stochastic Cu-CNT networks to corresponding conductivities. The CNN model learns to estimate the Cu-CNT composite conductivities for various CNT volume fractions, interfacial electrical resistances, Rc = 20 Ω–20 kΩ, and interfacial thermal resistances, R″t,c = 10−10–10−7 m2K/W. For training the CNNs, the hyperparameters such as learning rate, minibatch size, and hidden layer neurons are optimized. Without iteratively solving the physical governing equations, the trained CNN model approximates the electrical and thermal conductivities within a second with the coefficient of determination (R2) greater than 98%, which may take longer than 100 min for a convectional numerical simulation. This work demonstrates the potential of the deep learning surrogate model for the complex transport processes in composite materials.