bluuebunny/crossref_metadata_2025_split huggingface dataset:
FTO promotes clear cell renal cell carcinoma progression via upregulation of PDK1 through an m6A dependent pathway
Authors: Shen Haixiang , Ying Yufan , Ma Xueyou , Xie Haiyun , Chen Shiming , Sun Jiazhu , Liu Zixiang , Wen Chao , Yang Zitong , Wang Xiao , Xu Mingjie , Luo Jindan , Liu Ben , Li Jiangfeng , Zheng Xiangyi , Xie Liping 
Published: August 2022

AbstractFTO, as an m6A mRNA demethylase, is involved in various cancers. However, the role of FTO in clear cell renal cell carcinoma (ccRCC) remains unclear. In the present study, we discovered FTO is upregulated in ccRCC. Functionally, knockdown of FTO significantly impairs the proliferation and migration ability of ccRCC cells. Mechanistically, our data suggest FTO promotes the proliferation and migration of ccRCC through preventing degradation of PDK1 mRNA induced by YTHDF2 in an m6A-dependent mechanism. Overall, our results identify the protumorigenic role of FTO through the m6A/YTHDF2/PDK1 pathway, which could be a promising therapeutic target for ccRCC.
Virus-like particle vaccinology, from bench to bedside
Authors: Mohsen Mona O. , Bachmann Martin F. 
Published: August 2022

AbstractVirus-like particles (VLPs) have become key tools in biology, medicine and even engineering. After their initial use to resolve viral structures at the atomic level, VLPs were rapidly harnessed to develop antiviral vaccines followed by their use as display platforms to generate any kind of vaccine. Most recently, VLPs have been employed as nanomachines to deliver pharmaceutically active products to specific sites and into specific cells in the body. Here, we focus on the use of VLPs for the development of vaccines with broad fields of indications ranging from classical vaccines against viruses to therapeutic vaccines against chronic inflammation, pain, allergy and cancer. In this review, we take a walk through time, starting with the latest developments in experimental preclinical VLP-based vaccines and ending with marketed vaccines, which earn billions of dollars every year, paving the way for the next wave of prophylactic and therapeutic vaccines already visible on the horizon.
Tumor-associated macrophage (TAM)-derived CCL22 induces FAK addiction in esophageal squamous cell carcinoma (ESCC)
Authors: Chen Jie , Zhao Di , Zhang Lingyuan , Zhang Jing , Xiao Yuanfan , Wu Qingnan , Wang Yan , Zhan Qimin 
Published: August 2022

AbstractTumor cell dependence on activated oncogenes is considered a therapeutic target, but protumorigenic microenvironment-mediated cellular addiction to specific oncogenic signaling molecules remains to be further defined. Here, we showed that tumor-associated macrophages (TAMs) produced an abundance of C-C motif chemokine 22 (CCL22), whose expression in the tumor stroma was positively associated with the level of intratumoral phospho-focal adhesion kinase (pFAK Tyr397), tumor metastasis and reduced patient survival. Functionally, CCL22-stimulated hyperactivation of FAK was correlated with increased malignant progression of cancer cells. CCL22-induced addiction to FAK was demonstrated by the persistent suppression of tumor progression upon FAK-specific inhibition. Mechanistically, we identified that diacylglycerol kinase α (DGKα) acted as a signaling adaptor to link the CCL22 receptor C-C motif chemokine receptor 4 (CCR4) and FAK and promoted CCL22-induced activation of the FAK/AKT pathway. CCL22/CCR4 signaling activated the intracellular Ca2+/phospholipase C-γ1 (PLC-γ1) axis to stimulate the phosphorylation of DGKα at a tyrosine residue (Tyr335) and promoted the translocation of DGKα to the plasma membrane to assemble the DGKα/FAK signalosome, which critically contributed to regulating sensitivity to FAK inhibitors in cancer cells. The identification of TAM-driven intratumoral FAK addiction provides opportunities for utilizing the tumor-promoting microenvironment to achieve striking anticancer effects.
The role of natural gas in reaching net-zero emissions in the electric sector
Authors: Bistline John E. T. , Young David T. 
Published: August 2022

AbstractReplacing coal with natural gas has contributed to recent emissions reductions in the electric sector, but there are questions about the near- and long-term roles for gas under deep decarbonization. In this study, we assess the potential role for natural gas and carbon removal in deeply decarbonized electricity systems in the U.S. and evaluate the robustness of these insights to key technology and policy assumptions. We find that natural-gas-fired generation can lower the cost of electric sector decarbonization, a result that is robust to a range of sensitivities, when carbon removal is allowed under policy. Accelerating decarbonization to reach net-zero in 2035 entails greater contributions from natural gas than in 2050. Nonetheless, wind and solar have higher generation shares than natural gas for most regions and scenarios (52-66% variable renewables for net-zero scenarios versus 0-19% for gas), suggesting that natural gas generation can be substituted more easily than its capacity.
Molecular ensemble junctions with inter-molecular quantum interference
Authors: Li Ping’an , Selzer Yoram 
Published: August 2022

AbstractWe report of a high yield method to form nanopore molecular ensembles junctions containing ~40,000 molecules, in which the semimetal bismuth (Bi) is a top contact. Conductance histograms of these junctions are double-peaked (bi-modal), a behavior that is typical for single molecule junctions but not expected for junctions with thousands of molecules. This unique observation is shown to result from a new form of quantum interference that is inter-molecular in nature, which occurs in these junctions since the very long coherence length of the electrons in Bi enables them to probe large ensembles of molecules while tunneling through the junctions. Under such conditions, each molecule within the ensembles becomes an interference path that modifies via its tunneling phase the electronic structure of the entire junction. This new form of quantum interference holds a great promise for robust novel conductance effects in practical molecular junctions.
Generation of a CRISPR activation mouse that enables modelling of aggressive lymphoma and interrogation of venetoclax resistance
Authors: Deng Yexuan , Diepstraten Sarah T. , Potts Margaret A. , Giner Göknur , Trezise Stephanie , Ng Ashley P. , Healey Gerry , Kane Serena R. , Cooray Amali , Behrens Kira , Heidersbach Amy , Kueh Andrew J. , Pal Martin , Wilcox Stephen , Tai Lin , Alexander Warren S. , Visvader Jane E. , Nutt Stephen L. , Strasser Andreas , Haley Benjamin , Zhao Quan , Kelly Gemma L. , Herold Marco J. 
Published: August 2022

AbstractCRISPR technologies have advanced cancer modelling in mice, but CRISPR activation (CRISPRa) methods have not been exploited in this context. We establish a CRISPRa mouse (dCas9a-SAMKI) for inducing gene expression in vivo and in vitro. UsingdCas9a-SAMKIprimary lymphocytes, we induce B cell restricted genes in T cells and vice versa, demonstrating the power of this system. There are limited models of aggressive double hit lymphoma. Therefore, we transactivate pro-survival BCL-2 inEµ-MycT/+;dCas9a-SAMKI/+haematopoietic stem and progenitor cells. Mice transplanted with these cells rapidly develop lymphomas expressing high BCL-2 and MYC. Unlike standardEµ-Myclymphomas, BCL-2 expressing lymphomas are highly sensitive to the BCL-2 inhibitor venetoclax. We perform genome-wide activation screens in these lymphoma cells and find a dominant role for the BCL-2 protein A1 in venetoclax resistance. Here we show the potential of our CRISPRa model for mimicking disease and providing insights into resistance mechanisms towards targeted therapies.
Variational quantum eigensolver with reduced circuit complexity
Authors: Zhang Yu , Cincio Lukasz , Negre Christian F. A. , Czarnik Piotr , Coles Patrick J. , Anisimov Petr M. , Mniszewski Susan M. , Tretiak Sergei , Dub Pavel A. 
Published: August 2022

AbstractThe variational quantum eigensolver (VQE) is one of the most promising algorithms to find eigenstates of a given Hamiltonian on noisy intermediate-scale quantum devices (NISQ). The practical realization is limited by the complexity of quantum circuits. Here we present an approach to reduce quantum circuit complexity in VQE for electronic structure calculations. Our ClusterVQE algorithm splits the initial qubit space into clusters which are further distributed on individual (shallower) quantum circuits. The clusters are obtained based on mutual information reflecting maximal entanglement between qubits, whereas inter-cluster correlation is taken into account via a new “dressed” Hamiltonian. ClusterVQE therefore allows exact simulation of the problem by using fewer qubits and shallower circuit depth at the cost of additional classical resources, making it a potential leader for quantum chemistry simulations on NISQ devices. Proof-of-principle demonstrations are presented for several molecular systems based on quantum simulators as well as IBM quantum devices.
Formation of magnetic biskyrmions mediated by an intrinsic emergent monopole-antimonopole pair
Authors: Wang Cheng-Jie , Wang Pengfei , Zhou Yan , Wang Wenhong , Shi Fazhan , Du Jiangfeng 
Published: August 2022

AbstractVarious properties and potential technological applications of magnetic skyrmions have stimulated a flourishing interest in topological spin textures. Among them, biskyrmions with a rare topological charge of two are observed but their existence is still under debate. In this work, we present the formation of biskyrmion bubbles mediated by emergent monopoles via micromagnetic simulations. We find that biskyrmion bubbles and trivial bubbles share a unified three-dimensional structure, in which the relative position of an intrinsic emergent monopole-antimonopole pair dominates the two-dimensional topological property at the middle plane of magnetic uniaxial films. Biskyrmion bubbles can be transformed from trivial bubbles by the motion of emergent monopoles in confined geometry, paving the way for developing devices. These results highlight the three-dimensional aspect of skyrmion-related nanostructures and the versatile roles of emergent monopoles in topological spin textures.
Retrospective detection of asymptomatic monkeypox virus infections among male sexual health clinic attendees in Belgium
Authors: De Baetselier Irith , Van Dijck Christophe , Kenyon Chris , Coppens Jasmine , Michiels Johan , de Block Tessa , Smet Hilde , Coppens Sandra , Vanroye Fien , Bugert Joachim Jakob , Girl Philipp , Zange Sabine , Liesenborghs Laurens , Brosius Isabel , van Griensven Johan , Selhorst Philippe , Florence Eric , Van den Bossche Dorien , Ariën Kevin K. , Rezende Antonio Mauro , Vercauteren Koen , Van Esbroeck Marjan ,   for the ITM Monkeypox study group, Ramadan Kadrie , Platteau Tom , Van Looveren Karin , Baeyens Jolien , Van Hoyweghen Cindy , Mangelschots Marianne , Heyndrickx Leo , Hauner Anne , Willems Betty , Bottieau Emmanuel , Soentjens Patrick , Berens Nicole , Van Henten Saskia , Bracke Stefanie , Vanbaelen Thibaut , Vandenhove Leen , Verschueren Jacob , Ariën Kevin K. , Laga Marie , Vanhamel Jef , Vuylsteke Bea 
Published: August 2022

AbstractThe magnitude of the 2022 multi-country monkeypox virus (MPXV) outbreak has surpassed any preceding outbreak. It is unclear whether asymptomatic or otherwise undiagnosed infections are fuelling this epidemic. In this study, we aimed to assess whether undiagnosed infections occurred among men attending a Belgian sexual health clinic in May 2022. We retrospectively screened 224 samples collected for gonorrhea and chlamydia testing using an MPXV PCR assay and identified MPXV-DNA-positive samples from four men. At the time of sampling, one man had a painful rash, and three men had reported no symptoms. Upon clinical examination 21–37 days later, these three men were free of clinical signs, and they reported not having experienced any symptoms. Serology confirmed MPXV exposure in all three men, and MPXV was cultured from two cases. These findings show that certain cases of monkeypox remain undiagnosed and suggest that testing and quarantining of individuals reporting symptoms may not suffice to contain the outbreak.
Nine out of ten samples were mistakenly switched by The Orang-utan Genome Consortium
Authors: Banes Graham L. , Fountain Emily D. , Karklus Alyssa , Fulton Robert S. , Antonacci-Fulton Lucinda , Nelson Joanne O. 
Published: August 2022

AbstractThe Sumatran orang-utan (Pongo abelii) reference genome was first published in 2011, in conjunction with ten re-sequenced genomes from unrelated wild-caught individuals. Together, these published data have been utilized in almost all great ape genomic studies, plus in much broader comparative genomic research. Here, we report that the original sequencing Consortium inadvertently switched nine of the ten samples and/or resulting re-sequenced genomes, erroneously attributing eight of these to the wrong source individuals. Among them is a genome from the recently identified Tapanuli (P. tapanuliensis) species: thus, this genome was sequenced and published a full six years prior to the species’ description. Sex was wrongly assigned to five known individuals; the numbers in one sample identifier were swapped; and the identifier for another sample most closely resembles that of a sample from another individual entirely. These errors have been reproduced in countless subsequent manuscripts, with noted implications for studies reliant on data from known individuals.
Absolute protein quantitation of the mouse macrophage Toll-like receptor and chemotaxis pathways
Authors: Manes Nathan P. , Calzola Jessica M. , Kaplan Pauline R. , Fraser Iain D. C. , Germain Ronald N. , Meier-Schellersheim Martin , Nita-Lazar Aleksandra 
Published: August 2022

AbstractThe Toll-like receptor (TLR) and chemotaxis pathways are key components of the innate immune system. Subtle variation in the concentration, timing, and molecular structure of the ligands are known to affect downstream signaling and the resulting immune response. Computational modeling and simulation at the molecular interaction level can be used to study complex biological pathways, but such simulations require protein concentration values as model parameters. Here we report the development and application of targeted mass spectrometry assays to measure the absolute abundance of proteins of the mouse macrophage Toll-like receptor 4 (TLR4) and chemotaxis pathways. Two peptides per protein were quantified, if possible. The protein abundance values ranged from 1,332 to 227,000,000 copies per cell. They moderately correlated with transcript abundance values from a previously published mouse macrophage RNA-seq dataset, and these two datasets were combined to make proteome-wide abundance estimates. The datasets produced during this investigation can be used for pathway modeling and simulation, as well as for other studies of the TLR and chemotaxis pathways.
Semi-supervised learning framework for oil and gas pipeline failure detection
Authors: Alobaidi Mohammad H. , Meguid Mohamed A. , Zayed Tarek 
Published: August 2022

AbstractQuantifying failure events of oil and gas pipelines in real- or near-real-time facilitates a faster and more appropriate response plan. Developing a data-driven pipeline failure assessment model, however, faces a major challenge; failure history, in the form of incident reports, suffers from limited and missing information, making it difficult to incorporate a persistent input configuration to a supervised machine learning model. The literature falls short on the development of appropriate solutions to utilize incomplete databases and incident reports in the pipeline failure problem. This work proposes a semi-supervised machine learning framework which mines existing oil and gas pipeline failure databases. The proposed cluster-impute-classify (CIC) approach maps a relevant subset of the failure databases through which missing information in the incident report is reconstructed. A classifier is then trained on the fly to learn the functional relationship between the descriptors from a diverse feature set. The proposed approach, presented within an ensemble learning architecture, is easily scalable to various pipeline failure databases. The results show up to 91% detection accuracy and stable generalization ability against increased rate of missing information.
Humoral and cellular response in convalescent COVID-19 lupus patients
Authors: Solé Cristina , Domingo Sandra , Vidal Xavier , Cortés-Hernández Josefina 
Published: August 2022

AbstractIn SLE, underlying immune dysregulation and immunosuppression may increase the susceptibility to COVID-19 and impair the humoral and adaptive response. We aimed to characterize COVID-19 infection, identifying susceptibility and severity risk factors, assessing the presence of SARS-CoV-2 IgG antibodies and analyzing the cellular response. We established a prospective cohort of lupus patients to estimate the COVID-19 incidence compared to the reference general population. Data were collected via telephone interviews and medical record review. SARS-CoV-2 IgG antibodies were measured cross-sectionally as part of routine surveillance. Longitudinal changes in antibody titers and immunological profile from convalescent COVID-19 patients were evaluated at 6, 12 and 24 week after symptom onset. From immunological studies, PBMCs from convalescent patients were extracted and analyzed by flow cytometry and gene expression analysis. We included 725 patients, identifying 29 with PCR-confirmed COVID-19 infection and 16 with COVID-19-like symptoms without PCR-testing. Of the 29 confirmed cases, 7 had severe disease, 8 required hospital admission (27.6%), 4 intensive care, and 1 died. COVID-19 accumulated incidence was higher in lupus patients. Health care workers and anti-SSA/Ro52 antibody positivity were risk factors for COVID-19 susceptibility, and hypocomplementemia for severity. SARS-CoV-2 IgG antibodies were detected in 8.33% of patients. Three fourths of confirmed COVID-19 cases developed antibodies. High prednisone doses were associated with lack of antibody response. Antibody titers declined over time (39%). Convalescent patients at week 12 after symptom onset displayed a CD8+T cell reduction and predominant Th17 with a mild Th2 response, more pronounced in severe COVID-19 disease. Longitudinal immune response analysis showed a progressive sustained increase in CD8+ T and B memory cells with a decrease of Th17 signaling. Lupus patients are at higher risk of COVID-19 infection and new susceptibility and severity risk factors were identified. Lupus patients were able to mount humoral and cellular responses despite immunosuppressive therapy.
The impact of users’ cognitive function on evaluator perceptions of usability
Authors: Martins Ana Isabel , Silva Anabela G. , Pais Joana , Cruz Vítor Tedim , Rocha Nelson P. 
Published: August 2022

AbstractTo explore the association between the user’s cognitive function and usability reported by the evaluator. A cross-sectional study was conducted with a community-based sample. Data about participants’ age, sex, education, sleep quantity, subjective memory complaints, and cognitive function were collected. A usability session was conducted to evaluate a digital solution called Brain on Track. Independent linear-regression analyses were used to explore univariable and multivariable associations between evaluator-reported usability assessment and the users’ cognitive function, age, sex, education, sleep quantity, and subjective memory complaints. A total of 238 participants entered this study, of which 161 (67.6%) were females and the mean age was 42 (SD 12.9) years old. All variables (age, education, sleep quantity, subjective memory complaints and cognitive function) except sex were significantly associated with evaluator-reported usability in the univariable analysis (p < 0.05). Cognitive function, age, education, and subjective memory complaints remained significant in the multivariable model (F = 38.87, p < 0.001) with an adjusted R2 of 0.391. Cognition scores alone showed an adjusted R2 of 0.288. This work suggests that cognitive function impacts evaluator reported usability, alongside other users’ characteristics and needs to be considered in the usability evaluation.
Serotonin modulates asymmetric learning from reward and punishment in healthy human volunteers
Authors: Michely Jochen , Eldar Eran , Erdman Alon , Martin Ingrid M. , Dolan Raymond J. 
Published: August 2022

AbstractInstrumental learning is driven by a history of outcome success and failure. Here, we examined the impact of serotonin on learning from positive and negative outcomes. Healthy human volunteers were assessed twice, once after acute (single-dose), and once after prolonged (week-long) daily administration of the SSRI citalopram or placebo. Using computational modelling, we show that prolonged boosting of serotonin enhances learning from punishment and reduces learning from reward. This valence-dependent learning asymmetry increases subjects’ tendency to avoid actions as a function of cumulative failure without leading to detrimental, or advantageous, outcomes. By contrast, no significant modulation of learning was observed following acute SSRI administration. However, differences between the effects of acute and prolonged administration were not significant. Overall, these findings may help explain how serotonergic agents impact on mood disorders.
Marine sediment as a likely source of methyl and ethyl iodides in subpolar and polar seas
Authors: Ooki Atsushi , Minamikawa Keita , Meng Fanxing , Miyashita Naoya , Hirawake Toru , Ueno Hiromichi , Nosaka Yuichi , Takatsu Tetsuya 
Published: August 2022

AbstractThe surface ocean is an important source of longer-lived volatile organic iodine compounds, such as methyl and ethyl iodide. However, their production in deep waters is poorly constrained. Here, we combine shipborne seawater and sediment core analyses to investigate the temporal and vertical distribution of methyl and ethyl iodide concentrations in the Bering and Chukchi Seas in July 2017 and 2018, and Funka Bay, Japan, between March 2018 and December 2019. We find the highest methyl and ethyl iodide concentrations in sediment porewaters and at the sediment surface. In Funka Bay, concentrations in the sediment and bottom waters strongly increased following the spring bloom and subsequent settling of phytodetritus to the seafloor. Dark incubation experiments suggest that diatom aggregates are a source of methyl and ethyl iodide to the ambient water. Our findings suggest that phytodetritus at the seafloor is a potential source of volatile organic iodine compounds to the water column in polar and subpolar coastal oceans.