bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiation-induced gliomas represent H3-/IDH-wild type pediatric gliomas with recurrent PDGFRA amplification and loss of CDKN2A/B
Authors: Deng Maximilian Y. , Sturm Dominik , Pfaff Elke , Sill Martin , Stichel Damian , Balasubramanian Gnana Prakash , Tippelt Stephan , Kramm Christof , Donson Andrew M. , Green Adam L. , Jones Chris , Schittenhelm Jens , Ebinger Martin , Schuhmann Martin U. , Jones Barbara C. , van Tilburg Cornelis M. , Wittmann Andrea , Golanov Andrey , Ryzhova Marina , Ecker Jonas , Milde Till , Witt Olaf , Sahm Felix , Reuss David , Sumerauer David , Zamecnik Josef , Korshunov Andrey , von Deimling Andreas , Pfister Stefan M. , Jones David T. W. 
Published: September 2021

AbstractLong-term complications such as radiation-induced second malignancies occur in a subset of patients following radiation-therapy, particularly relevant in pediatric patients due to the long follow-up period in case of survival. Radiation-induced gliomas (RIGs) have been reported in patients after treatment with cranial irradiation for various primary malignancies such as acute lymphoblastic leukemia (ALL) and medulloblastoma (MB). We perform comprehensive (epi-) genetic and expression profiling of RIGs arising after cranial irradiation for MB (n = 23) and ALL (n = 9). Our study reveals a unifying molecular signature for the majority of RIGs, with recurrentPDGFRAamplification and loss ofCDKN2A/Band an absence of somatic hotspot mutations in genes encoding histone 3 variants orIDH1/2, uncovering diagnostic markers and potentially actionable targets.
Comprehensive molecular characterization of pediatric radiation-induced high-grade glioma
Authors: DeSisto John , Lucas John T. , Xu Ke , Donson Andrew , Lin Tong , Sanford Bridget , Wu Gang , Tran Quynh T. , Hedges Dale , Hsu Chih-Yang , Armstrong Gregory T. , Arnold Michael , Bhatia Smita , Flannery Patrick , Lemma Rakeb , Hardie Lakotah , Schüller Ulrich , Venkataraman Sujatha , Hoffman Lindsey M. , Dorris Kathleen , Mulcahy Levy Jean M. , Hankinson Todd C. , Handler Michael , Liu Arthur K. , Foreman Nicholas , Vibhakar Rajeev , Jones Kenneth , Allen Sariah , Zhang Jinghui , Baker Suzanne J. , Merchant Thomas E. , Orr Brent A. , Green Adam L. 
Published: September 2021

AbstractRadiation-induced high-grade gliomas (RIGs) are an incurable late complication of cranial radiation therapy. We performed DNA methylation profiling, RNA-seq, and DNA sequencing on 32 RIG tumors and an in vitro drug screen in two RIG cell lines. We report that based on DNA methylation, RIGs cluster primarily with the pediatric receptor tyrosine kinase I high-grade glioma subtype. Common copy-number alterations include Chromosome (Ch.) 1p loss/1q gain, and Ch. 13q and Ch. 14q loss; focal alterations include PDGFRA and CDK4 gain and CDKN2A and BCOR loss. Transcriptomically, RIGs comprise a stem-like subgroup with lesser mutation burden and Ch. 1p loss and a pro-inflammatory subgroup with greater mutation burden and depleted DNA repair gene expression. Chromothripsis in several RIG samples is associated with extrachromosomal circular DNA-mediated amplification of PDGFRA and CDK4. Drug screening suggests microtubule inhibitors/stabilizers, DNA-damaging agents, MEK inhibition, and, in the inflammatory subgroup, proteasome inhibitors, as potentially effective therapies.
Generalized and scalable trajectory inference in single-cell omics data with VIA
Authors: Stassen Shobana V. , Yip Gwinky G. K. , Wong Kenneth K. Y. , Ho Joshua W. K. , Tsia Kevin K. 
Published: September 2021

AbstractInferring cellular trajectories using a variety of omic data is a critical task in single-cell data science. However, accurate prediction of cell fates, and thereby biologically meaningful discovery, is challenged by the sheer size of single-cell data, the diversity of omic data types, and the complexity of their topologies. We present VIA, a scalable trajectory inference algorithm that overcomes these limitations by using lazy-teleporting random walks to accurately reconstruct complex cellular trajectories beyond tree-like pathways (e.g., cyclic or disconnected structures). We show that VIA robustly and efficiently unravels the fine-grained sub-trajectories in a 1.3-million-cell transcriptomic mouse atlas without losing the global connectivity at such a high cell count. We further apply VIA to discovering elusive lineages and less populous cell fates missed by other methods across a variety of data types, including single-cell proteomic, epigenomic, multi-omics datasets, and a new in-house single-cell morphological dataset.
Profilin and Mical combine to impair F-actin assembly and promote disassembly and remodeling
Authors: Grintsevich Elena E. , Ahmed Giasuddin , Ginosyan Anush A. , Wu Heng , Rich Shannon K. , Reisler Emil , Terman Jonathan R. 
Published: September 2021

AbstractCellular events require the spatiotemporal interplay between actin assembly and actin disassembly. Yet, how different factors promote the integration of these two opposing processes is unclear. In particular, cellular monomeric (G)-actin is complexed with profilin, which inhibits spontaneous actin nucleation but fuels actin filament (F-actin) assembly by elongation-promoting factors (formins, Ena/VASP). In contrast, site-specific F-actin oxidation by Mical promotes F-actin disassembly and release of polymerization-impaired Mical-oxidized (Mox)-G-actin. Here we find that these two opposing processes connect with one another to orchestrate actin/cellular remodeling. Specifically, we find that profilin binds Mox-G-actin, yet these complexes do not fuel elongation factors’-mediated F-actin assembly, but instead inhibit polymerization and promote further Mox-F-actin disassembly. UsingDrosophilaas a model system, we show that similar profilin–Mical connections occur in vivo – where they underlie F-actin/cellular remodeling that accompanies Semaphorin–Plexin cellular/axon repulsion. Thus, profilin and Mical combine to impair F-actin assembly and promote F-actin disassembly, while concomitantly facilitating cellular remodeling and plasticity.
The relevance of rock shape over mass—implications for rockfall hazard assessments
Authors: Caviezel Andrin , Ringenbach Adrian , Demmel Sophia E. , Dinneen Claire E. , Krebs Nora , Bühler Yves , Christen Marc , Meyrat Guillaume , Stoffel Andreas , Hafner Elisabeth , Eberhard Lucie A. , Rickenbach Daniel von , Simmler Kevin , Mayer Philipp , Niklaus Pascal S. , Birchler Thomas , Aebi Tim , Cavigelli Lukas , Schaffner Michael , Rickli Stefan , Schnetzler Christoph , Magno Michele , Benini Luca , Bartelt Perry 
Published: September 2021

AbstractThe mitigation of rapid mass movements involves a subtle interplay between field surveys, numerical modelling, and experience. Hazard engineers rely on a combination of best practices and, if available, historical facts as a vital prerequisite in establishing reproducible and accurate hazard zoning. Full-scale field tests have been performed to reinforce the physical understanding of debris flows and snow avalanches. Rockfall dynamics are - especially the quantification of energy dissipation during the complex rock-ground interaction - largely unknown. The awareness of rock shape dependence is growing, but presently, there exists little experimental basis on how rockfall hazard scales with rock mass, size, and shape. Here, we present a unique data set of induced single-block rockfall events comprising data from equant and wheel-shaped blocks with masses up to 2670 kg, quantifying the influence of rock shape and mass on lateral spreading and longitudinal runout and hence challenging common practices in rockfall hazard assessment.
Exosome-mediated stable epigenetic repression of HIV-1
Authors: Shrivastava Surya , Ray Roslyn M. , Holguin Leo , Echavarria Lilliana , Grepo Nicole , Scott Tristan A. , Burnett John , Morris Kevin V. 
Published: September 2021

AbstractHuman Immunodeficiency Virus (HIV-1) produces a persistent latent infection. Control of HIV-1 using combination antiretroviral therapy (cART) comes at the cost of life-shortening side effects and development of drug-resistant HIV-1. An ideal and safer therapy should be deliverable in vivo and target the stable epigenetic repression of the virus, inducing a stable “block and lock” of virus expression. Towards this goal, we developed an HIV-1 promoter-targeting Zinc Finger Protein (ZFP-362) fused to active domains of DNA methyltransferase 3 A to induce long-term stable epigenetic repression of HIV-1. Cells were engineered to produce exosomes packaged with RNAs encoding this HIV-1 repressor protein. We find here that the repressor loaded anti-HIV-1 exosomes suppress virus expression and that this suppression is mechanistically driven by DNA methylation of HIV-1 in humanized NSG mouse models. The observations presented here pave the way for an exosome-mediated systemic delivery platform of therapeutic cargo to epigenetically repress HIV-1 infection.
Unwinding of a DNA replication fork by a hexameric viral helicase
Authors: Javed Abid , Major Balazs , Stead Jonathan A. , Sanders Cyril M. , Orlova Elena V. 
Published: September 2021

AbstractHexameric helicases are motor proteins that unwind double-stranded DNA (dsDNA) during DNA replication but how they are optimised for strand separation is unclear. Here we present the cryo-EM structure of the full-length E1 helicase from papillomavirus, revealing all arms of a bound DNA replication fork and their interactions with the helicase. The replication fork junction is located at the entrance to the helicase collar ring, that sits above the AAA + motor assembly. dsDNA is escorted to and the 5´ single-stranded DNA (ssDNA) away from the unwinding point by the E1 dsDNA origin binding domains. The 3´ ssDNA interacts with six spirally-arranged β-hairpins and their cyclical top-to-bottom movement pulls the ssDNA through the helicase. Pulling of the RF against the collar ring separates the base-pairs, while modelling of the conformational cycle suggest an accompanying movement of the collar ring has an auxiliary role, helping to make efficient use of ATP in duplex unwinding.
Profiling the inhibitory receptors LAG-3, TIM-3, and TIGIT in renal cell carcinoma reveals malignancy
Authors: Takamatsu Kimiharu , Tanaka Nobuyuki , Hakozaki Kyohei , Takahashi Ryohei , Teranishi Yu , Murakami Tetsushi , Kufukihara Ryohei , Niwa Naoya , Mikami Shuji , Shinojima Toshiaki , Sasaki Takashi , Sato Yusuke , Kume Haruki , Ogawa Seishi , Kakimi Kazuhiro , Kamatani Takashi , Miya Fuyuki , Tsunoda Tatsuhiko , Aimono Eriko , Nishihara Hiroshi , Sawada Kazuaki , Imamura Takeshi , Mizuno Ryuichi , Oya Mototsugu 
Published: September 2021

AbstractA cutting edge therapy for future immuno-oncology is targeting a new series of inhibitory receptors (IRs): LAG-3, TIM-3, and TIGIT. Both immunogenomic analyses and diagnostic platforms to distinguish candidates and predict good responders to these IR-related agents are vital in clinical pathology. By applying an automated single-cell count for immunolabelled LAG-3, TIM-3, and TIGIT, we reveal that individual IR levels with exclusive domination in each tumour can serve as valid biomarkers for profiling human renal cell carcinoma (RCC). We uncover the immunogenomic landscape associated with individual IR levels in human RCC tumours with metastases in various organs and histological subtypes. We then externally validate our results and devise a workflow with optimal biomarker cut-offs for discriminating the LAG-3, TIM-3, and TIGIT tumour profiles. The discrimination of LAG-3, TIM-3, and TIGIT profiles in tumours may have a broad impact on investigations of immunotherapy responses after targeting a new series of IRs.
Geolocated dataset of Chinese overseas development finance
Authors: Ray Rebecca , Gallagher Kevin P. , Kring William , Pitts Joshua , Simmons B. Alexander 
Published: September 2021

AbstractChina is now the world’s largest source of bilateral development finance and will likely continue to play a prominent role in sovereign lending through its multi-billion-dollar Belt and Road Initiative. This paper introduces major methodological enhancements in tracking this finance: the use of an original application programming interface (API) to gathers news in multiple languages; double-verification of every record to ensure every finance commitment has been formalized; and visual geo-location to trace the precise footprint of every project. The resulting dataset enables economic, environmental, and social analyses with high-precision spatial accuracy, as well as spatiotemporal monitoring by project stakeholders and enhanced planning by project managers. It covers the years 2008–2019 to enable analysis before and after the announcement of the Belt and Road Initiative. It includes 862 finance commitments, 669 of which have geographic location, to 94 countries across the world.
Loneliness, social isolation, and pain following the COVID-19 outbreak: data from a nationwide internet survey in Japan
Authors: Yamada Keiko , Wakaizumi Kenta , Kubota Yasuhiko , Murayama Hiroshi , Tabuchi Takahiro 
Published: September 2021

AbstractThe aim of cross-sectional study was to investigate the association between loneliness, increased social isolation, and pain following the COVID-19 outbreak. A total of 25,482 participants, aged 15–79 years, were assessed using an internet survey; the University of California, Los Angeles Loneliness Scale (Version 3), Short Form 3-item (UCLA-LS3-SF3) was used to assess loneliness, and a modified item of the UCLA-LS3-SF3 was used to measure the perception of increased social isolation during the pandemic. The outcome measures included the prevalence/incidence of pain (i.e., headache, neck or shoulder pain, upper limb pain, low back pain, and leg pain), pain intensity, and the prevalence of past/present chronic pain. Pain intensity was measured by the pain/discomfort item of the 5-level version of the EuroQol 5 Dimension scale. Odds ratios of pain prevalence/incidence and past/present chronic pain prevalence according to the UCLA-LS3-SF3 scoring groups (tertiles) and the frequency of the perceived increase in social isolation (categories 1–5) were calculated using multinomial logistic regression analysis. The mean pain intensity values among different loneliness and social isolation levels were tested using an analysis of covariance. Increased loneliness and the severity of the perceived social isolation were positively associated with the prevalence/incidence of pain, pain intensity, and the prevalence of past/present chronic pain.
A new approach to produce IgG4-like bispecific antibodies
Authors: Zhao Caizhi , Zhang Wei , Gong Guihua , Xie Liping , Wang Ming-Wei , Hu Youjia 
Published: September 2021

AbstractWhile achieving rapid developments in recent years, bispecific antibodies are still difficult to design and manufacture, due to mispair of both heavy and light chains. Here we report a novel technology to make bispecific molecules. The knob-into-hole method was used to pair two distinct heavy chains as a heterodimer. IgG4 S228P CH1-CL interface was then partially replaced by T-cell receptor α/β constant domain to increase the efficiency of cognate heavy and light chain pairing. Following expression and purification, the bispecific antibody interface exchange was confirmed by Western blotting and LC–MS/MS. To ensure its validity, we combined a monovalent bispecific antibody against PD-1 (sequence from Pembrolizumab) and LAG3 (sequence from Relatlimab). The results showed that the molecule could be assembled correctly at a ratio of 95% in cells. In vitro functional assay demonstrated that the purified bispecific antibody exhibits an enhanced agonist activity compared to that of the parental antibodies. Low immunogenicity was predicted by an open-access software and ADA test.
The Pisciarelli main fumarole mechanisms reconstructed by electrical resistivity and induced polarization imaging
Authors: Troiano A. , Isaia R. , Tramparulo F. D. A. , Di Giuseppe M. G. 
Published: September 2021

AbstractPisciarelli, together with the adjacent Solfatara maar-diatreme, represents the most active structure of the Campi Flegrei caldera (Italy) in terms of degassing and seismic activity. This paper aims to define the structure of the Pisciarelli hydrothermal system (down to a 20 m depth) through electrical resistivity and time-domain-induced polarization tomography and self-potential mapping. The retrieved 3D image of the area helps reconstruct the Pisciarelli subsurface in its area of maximum degassing, containing the main fumarole (“soffione”) and the mud pool. In particular, a channel has been identified in which fluids stored in a deeper reservoir rise toward the surface. Such a structure seems to be surmounted by a clay-cap formation that could govern the circulation of fluids and the abundance of gases/vapors emitted by the soffione. Based on this new reconstruction of the Pisciarelli fumarolic field structural setting, the first conceptual model has been suggested that is capable of simultaneously explaining the mechanisms governing soffione activity and elucidating the role played by the fluid/gas of deeper origin in the shallow fluid circulation system. The proposed model can potentially help to better monitor the processes occurring throughout the Pisciarelli fumarolic field and provide an evaluation of the associated hazards.
Inhaled sphingosine has no adverse side effects in isolated ventilated and perfused pig lungs
Authors: Carstens Henning , Kalka Katharina , Verhaegh Rabea , Schumacher Fabian , Soddemann Matthias , Wilker Barbara , Keitsch Simone , Sehl Carolin , Kleuser Burkhard , Wahlers Thorsten , Reiner Gerald , Koch Achim , Rauen Ursula , Gulbins Erich , Kamler Markus 
Published: September 2021

AbstractEx-vivo lung perfusion (EVLP) systems like XVIVO are more and more common in the setting of lung transplantation, since marginal donor-lungs can easily be subjected to a performance test or be treated with corticosteroids or antibiotics in high dose regimes. Donor lungs are frequently positive in bronchoalveolar lavage (BAL) bacterial cultures (46–89%) which leads to a donor-to-recipient transmission and after a higher risk of lung infection with reduced posttransplant outcome. We have previously shown that sphingosine very efficiently kills a variety of pathogens, including Pseudomonas aeruginosa, Staphylococcus aureus and epidermidis, Escherichia coli or Haemophilus influenzae. Thus, sphingosine could be a new treatment option with broadspectrum antiinfective potential, which may improve outcome after lung transplantation when administered prior to lung re-implantation. Here, we tested whether sphingosine has any adverse effects in the respiratory tract when applied into isolated ventilated and perfused lungs. A 4-h EVLP run using minipig lungs was performed. Functional parameters as well as perfusate measurements where obtained. Biopsies were obtained 30 min and 150 min after inhalation of sphingosine. Tissue samples were fixed in paraformaldehyde, embedded in paraffin and sectioned. Hemalaun, TUNEL as well as stainings with Cy3-coupled anti-sphingosine or anti-ceramide antibodies were implemented. We demonstrate that tube-inhalation of sphingosine into ex-vivo perfused and ventilated minipig lungs results in increased levels of sphingosine in the luminal membrane of bronchi and the trachea without morphological side effects up to very high doses of sphingosine. Sphingosine also did not affect functional lung performance. In summary, the inhalation of sphingosine results in an increase of sphingosine concentrations in the luminal plasma membrane of tracheal and bronchial epithelial cells. The inhalation has no local side effects in ex-vivo perfused and ventilated minipig lungs.
Real-time monitoring of Arundo donax response to saline stress through the application of in vivo sensing technology
Authors: Michela Janni , Claudia Cocozza , Federico Brilli , Sara Pignattelli , Filippo Vurro , Nicola Coppede , Manuele Bettelli , Davide Calestani , Loreto Francesco , Zappettini Andrea 
Published: September 2021

AbstractOne of the main impacts of climate change on agriculture production is the dramatic increase of saline (Na+) content in substrate, that will impair crop performance and productivity. Here we demonstrate how the application of smart technologies such as an in vivo sensor, termed bioristor, allows to continuously monitor in real-time the dynamic changes of ion concentration in the sap ofArundo donaxL. (common name giant reed or giant cane), when exposed to a progressive salinity stress. Data collected in vivo by bioristor sensors inserted at two different heights intoA. donaxstems enabled us to detect the early phases of stress response upon increasing salinity. Indeed, the continuous time-series of data recorded by the bioristor returned a specific signal which correlated with Na+content in leaves of Na-stressed plants, opening a new perspective for its application as a tool for in vivo plant phenotyping and selection of genotypes more suitable for the exploitation of saline soils.
Heat capacity anomalies of the molecular crystal 1-fluoro-adamantane at low temperatures
Authors: Szewczyk Daria , Gebbia Jonathan F. , Jeżowski Andrzej , Krivchikov Alexander I. , Guidi Tatiana , Cazorla Claudio , Tamarit Josep-Lluís 
Published: September 2021

AbstractDisorder–disorder phase transitions are rare in nature. Here, we present a comprehensive low-temperature experimental and theoretical study of the heat capacity and vibrational density of states of 1-fluoro-adamantane (C10H15F), an intriguing molecular crystal that presents a continuous disorder–disorder phase transition at T = 180 K and a low-temperature tetragonal phase that exhibits fractional fluorine occupancy. It is shown that fluorine occupancy disorder in the low-T phase of 1-fluoro-adamantane gives rise to the appearance of low-temperature glassy features in the corresponding specific heat (i.e., “boson peak” -BP-) and vibrational density of states. We identify the inflation of low-energy optical modes as the main responsible for the appearance of such glassy heat-capacity features and propose a straightforward correlation between the first localized optical mode and maximum BP temperature for disordered molecular crystals (either occupational or orientational). Thus, the present study provides new physical insights into the possible origins of the BP appearing in disordered materials and expands the set of molecular crystals in which “glassy-like” heat-capacity features have been observed.
Leveraging long short-term memory (LSTM)-based neural networks for modeling structure–property relationships of metamaterials from electromagnetic responses
Authors: Pillai Prajith , Pal Parama , Chacko Rinu , Jain Deepak , Rai Beena 
Published: September 2021

AbstractWe report a neural network model for predicting the electromagnetic response of mesoscale metamaterials as well as generate design parameters for a desired spectral behavior. Our approach entails treating spectral data as time-varying sequences and the inverse problem as a single-input multiple output model, thereby compelling the network architecture to learn the geometry of the metamaterial designs from the spectral data in lieu of abstract features.