bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hematopoietic stem cell transplantation in children and adolescents with GATA2-related myelodysplastic syndrome
Authors: Bortnick Rachel , Wlodarski Marcin , de Haas Valerie , De Moerloose Barbara , Dworzak Michael , Hasle Henrik , Masetti Riccardo , Starý Jan , Turkiewicz Dominik , Ussowicz Marek , Kozyra Emilia , Albert Michael , Bader Peter , Bordon Victoria , Cario Gunnar , Beier Rita , Schulte Johannes , Bresters Dorine , Müller Ingo , Pichler Herbert , Sedlacek Petr , Sauer Martin G. , Zecca Marco , Göhring Gudrun , Yoshimi Ayami , Noellke Peter , Erlacher Miriam , Locatelli Franco , Niemeyer Charlotte M. , Strahm Brigitte ,   for EWOG-MDS
Published: July 2021

AbstractGATA2 deficiency is a heterogeneous multi-system disorder characterized by a high risk of developing myelodysplastic syndrome (MDS) and myeloid leukemia. We analyzed the outcome of 65 patients reported to the registry of the European Working Group (EWOG) of MDS in childhood carrying a germlineGATA2mutation (GATA2mut) who had undergone hematopoietic stem cell transplantation (HSCT). At 5 years the probability of overall survival and disease-free survival (DFS) was 75% and 70%, respectively. Non-relapse mortality and relapse equally contributed to treatment failure. There was no evidence of increased incidence of graft-versus-host-disease or excessive rates of infections or organ toxicities. Advanced disease and monosomy 7 (−7) were associated with worse outcome. Patients with refractory cytopenia of childhood (RCC) and normal karyotype showed an excellent outcome (DFS 90%) compared to RCC and −7 (DFS 67%). Comparing outcome ofGATA2mutwithGATA2wtpatients, there was no difference in DFS in patients with RCC and normal karyotype. The same was true for patients with −7 across morphological subtypes. We demonstrate that HSCT outcome is independent ofGATA2germline mutations in pediatric MDS suggesting the application of standard MDS algorithms and protocols. Our data support considering HSCT early in the course of GATA2 deficiency in young individuals.
Re-evaluating diabetic papillopathy using optical coherence tomography and inner retinal sublayer analysis
Authors: Huemer Josef , Khalid Hagar , Ferraz Daniel , Faes Livia , Korot Edward , Jurkute Neringa , Balaskas Konstantinos , Egan Catherine A. , Petzold Axel , Keane Pearse A. 
Published: July 2021

AbstractBackground/ObjectivesTo re-evaluate diabetic papillopathy using optical coherence tomography (OCT) for quantitative analysis of the peripapillary retinal nerve fibre layer (pRNFL), macular ganglion cell layer (mGCL) and inner nuclear layer (mINL) thickness.Subjects/MethodsIn this retrospective observational case series between June 2008 and July 2019 at Moorfields Eye hospital, 24 eyes of 22 patients with diabetes and optic disc swelling with confirmed diagnosis of NAION or diabetic papillopathy by neuro-ophthalmological assessment were included for evaluation of the pRNFL, mGCL and mINL thicknesses after resolution of optic disc swelling.ResultsThe mean age of included patients was 56.5 (standard deviation (SD) ± 14.85) years with a mean follow-up duration of 216 days. Thinning of pRNFL (mean: 66.26, SD ± 31.80 µm) and mGCL (mean volume: 0.27 mm3, SD ± 0.09) were observed in either group during follow-up, the mINL volume showed no thinning with 0.39 ± 0.05 mm3. The mean decrease in visual acuity was 4.13 (SD ± 14.27) ETDRS letters with a strong correlation between mGCL thickness and visual acuity (rho 0.74,p < 0.001).ConclusionAfter resolution of acute optic disc swelling, atrophy of pRNFL and mGCL became apparent in all cases of diabetic papillopathy and diabetic NAION, with preservation of mINL volumes. Analysis of OCT did not provide a clear diagnostic distinction between both entities. We suggest a diagnostic overlay with the degree of pRNFL and mGCL atrophy of prognostic relevance for poor visual acuity independent of the semantics of terminology.
Genetic influences on hub connectivity of the human connectome
Authors: Arnatkeviciute Aurina , Fulcher Ben D. , Oldham Stuart , Tiego Jeggan , Paquola Casey , Gerring Zachary , Aquino Kevin , Hawi Ziarih , Johnson Beth , Ball Gareth , Klein Marieke , Deco Gustavo , Franke Barbara , Bellgrove Mark A. , Fornito Alex 
Published: July 2021

AbstractBrain network hubs are both highly connected and highly inter-connected, forming a critical communication backbone for coherent neural dynamics. The mechanisms driving this organization are poorly understood. Using diffusion-weighted magnetic resonance imaging in twins, we identify a major role for genes, showing that they preferentially influence connectivity strength between network hubs of the human connectome. Using transcriptomic atlas data, we show that connected hubs demonstrate tight coupling of transcriptional activity related to metabolic and cytoarchitectonic similarity. Finally, comparing over thirteen generative models of network growth, we show that purely stochastic processes cannot explain the precise wiring patterns of hubs, and that model performance can be improved by incorporating genetic constraints. Our findings indicate that genes play a strong and preferential role in shaping the functionally valuable, metabolically costly connections between connectome hubs.
mTORC1 activity regulates post-translational modifications of glycine decarboxylase to modulate glycine metabolism and tumorigenesis
Authors: Liu Rui , Zeng Lin-Wen , Gong Rong , Yuan Fanen , Shu Hong-Bing , Li Shu 
Published: July 2021

AbstractGlycine decarboxylase (GLDC) is a key enzyme of glycine cleavage system that converts glycine into one-carbon units. GLDC is commonly up-regulated and plays important roles in many human cancers. Whether and how GLDC is regulated by post-translational modifications is unknown. Here we report that mechanistic target of rapamycin complex 1 (mTORC1) signal inhibits GLDC acetylation at lysine (K) 514 by inducing transcription of the deacetylase sirtuin 3 (SIRT3). Upon inhibition of mTORC1, the acetyltransferase acetyl-CoA acetyltransferase 1 (ACAT1) catalyzes GLDC K514 acetylation. This acetylation of GLDC impairs its enzymatic activity. In addition, this acetylation of GLDC primes for its K33-linked polyubiquitination at K544 by the ubiquitin ligase NF-X1, leading to its degradation by the proteasomal pathway. Finally, we find that GLDC K514 acetylation inhibits glycine catabolism, pyrimidines synthesis and glioma tumorigenesis. Our finding reveals critical roles of post-translational modifications of GLDC in regulation of its enzymatic activity, glycine metabolism and tumorigenesis, and provides potential targets for therapeutics of cancers such as glioma.
Highly active and selective oxygen reduction to H2O2 on boron-doped carbon for high production rates
Authors: Xia Yang , Zhao Xunhua , Xia Chuan , Wu Zhen-Yu , Zhu Peng , Kim Jung Yoon , Bai Xiaowan , Gao Guanhui , Hu Yongfeng , Zhong Jun , Liu Yuanyue , Wang Haotian 
Published: July 2021

AbstractOxygen reduction reaction towards hydrogen peroxide (H2O2) provides a green alternative route for H2O2production, but it lacks efficient catalysts to achieve high selectivity and activity simultaneously under industrial-relevant production rates. Here we report a boron-doped carbon (B-C) catalyst which can overcome this activity-selectivity dilemma. Compared to the state-of-the-art oxidized carbon catalyst, B-C catalyst presents enhanced activity (saving more than 210 mV overpotential) under industrial-relevant currents (up to 300 mA cm−2) while maintaining high H2O2selectivity (85–90%). Density-functional theory calculations reveal that the boron dopant site is responsible for high H2O2activity and selectivity due to low thermodynamic and kinetic barriers. Employed in our porous solid electrolyte reactor, the B-C catalyst demonstrates a direct and continuous generation of pure H2O2solutions with high selectivity (up to 95%) and high H2O2partial currents (up to ~400 mA cm−2), illustrating the catalyst’s great potential for practical applications in the future.
Exchange catalysis by tapasin exploits conserved and allele-specific features of MHC-I molecules
Authors: Lan Huan , Abualrous Esam T. , Sticht Jana , Fernandez Laura Maria Arroyo , Werk Tamina , Weise Christoph , Ballaschk Martin , Schmieder Peter , Loll Bernhard , Freund Christian 
Published: July 2021

AbstractThe repertoire of peptides presented by major histocompatibility complex class I (MHC-I) molecules on the cell surface is tailored by the ER-resident peptide loading complex (PLC), which contains the exchange catalyst tapasin. Tapasin stabilizes MHC-I molecules and promotes the formation of stable peptide-MHC-I (pMHC-I) complexes that serve as T cell antigens. Exchange of suboptimal by high-affinity ligands is catalyzed by tapasin, but the underlying mechanism is still elusive. Here we analyze the tapasin-induced changes in MHC-I dynamics, and find the catalyst to exploit two essential features of MHC-I. First, tapasin recognizes a conserved allosteric site underneath the α2-1-helix of MHC-I, ‘loosening’ the MHC-I F-pocket region that accomodates the C-terminus of the peptide. Second, the scoop loop11–20of tapasin relies on residue L18 to target the MHC-I F-pocket, enabling peptide exchange. Meanwhile, tapasin residue K16 plays an accessory role in catalysis of MHC-I allotypes bearing an acidic F-pocket. Thus, our results provide an explanation for the observed allele-specificity of catalyzed peptide exchange.
Peta-bit-per-second optical communications system using a standard cladding diameter 15-mode fiber
Authors: Rademacher Georg , Puttnam Benjamin J. , Luís Ruben S. , Eriksson Tobias A. , Fontaine Nicolas K. , Mazur Mikael , Chen Haoshuo , Ryf Roland , Neilson David T. , Sillard Pierre , Achten Frank , Awaji Yoshinari , Furukawa Hideaki 
Published: July 2021

AbstractData rates in optical fiber networks have increased exponentially over the past decades and core-networks are expected to operate in the peta-bit-per-second regime by 2030. As current single-mode fiber-based transmission systems are reaching their capacity limits, space-division multiplexing has been investigated as a means to increase the per-fiber capacity. Of all space-division multiplexing fibers proposed to date, multi-mode fibers have the highest spatial channel density, as signals traveling in orthogonal fiber modes share the same fiber-core. By combining a high mode-count multi-mode fiber with wideband wavelength-division multiplexing, we report a peta-bit-per-second class transmission demonstration in multi-mode fibers. This was enabled by combining three key technologies: a wideband optical comb-based transmitter to generate highly spectral efficient 64-quadrature-amplitude modulated signals between 1528 nm and 1610 nm wavelength, a broadband mode-multiplexer, based on multi-plane light conversion, and a 15-mode multi-mode fiber with optimized transmission characteristics for wideband operation.
Multiplexed functional genomic analysis of 5’ untranslated region mutations across the spectrum of prostate cancer
Authors: Lim Yiting , Arora Sonali , Schuster Samantha L. , Corey Lukas , Fitzgibbon Matthew , Wladyka Cynthia L. , Wu Xiaoying , Coleman Ilsa M. , Delrow Jeffrey J. , Corey Eva , True Lawrence D. , Nelson Peter S. , Ha Gavin , Hsieh Andrew C. 
Published: July 2021

AbstractThe functional consequences of genetic variants within 5’ untranslated regions (UTRs) on a genome-wide scale are poorly understood in disease. Here we develop a high-throughput multi-layer functional genomics method called PLUMAGE (Pooled full-length UTR Multiplex Assay on Gene Expression) to quantify the molecular consequences of somatic 5’ UTR mutations in human prostate cancer. We show that 5’ UTR mutations can control transcript levels and mRNA translation rates through the creation of DNA binding elements or RNA-based cis-regulatory motifs. We discover that point mutations can simultaneously impact transcript and translation levels of the same gene. We provide evidence that functional 5’ UTR mutations in the MAP kinase signaling pathway can upregulate pathway-specific gene expression and are associated with clinical outcomes. Our study reveals the diverse mechanisms by which the mutational landscape of 5’ UTRs can co-opt gene expression and demonstrates that single nucleotide alterations within 5’ UTRs are functional in cancer.
Structural basis of the membrane intramolecular transacylase reaction responsible for lyso-form lipoprotein synthesis
Authors: Olatunji Samir , Bowen Katherine , Huang Chia-Ying , Weichert Dietmar , Singh Warispreet , Tikhonova Irina G. , Scanlan Eoin M. , Olieric Vincent , Caffrey Martin 
Published: July 2021

AbstractLipoproteins serve diverse functions in the bacterial cell and some are essential for survival. Some lipoproteins are adjuvants eliciting responses from the innate immune system of the host. The growing list of membrane enzymes responsible for lipoprotein synthesis includes the recently discovered lipoprotein intramolecular transacylase, Lit. Lit creates a lipoprotein that is less immunogenic, possibly enabling the bacteria to gain a foothold in the host by stealth. Here, we report the crystal structure of the Lit enzyme fromBacillus cereusand describe its mechanism of action. Lit consists of four transmembrane helices with an extracellular cap. Conserved residues map to the cap-membrane interface. They include two catalytic histidines that function to effect unimolecular transacylation. The reaction involves acyl transfer from thesn-2 position of the glyceryl moiety to the amino group on the N-terminal cysteine of the substrate via an 8-membered ring intermediate. Transacylation takes place in a confined aromatic residue-rich environment that likely evolved to bring distant moieties on the substrate into proximity and proper orientation for catalysis.
Upstream modes and antidots poison graphene quantum Hall effect
Authors: Moreau N. , Brun B. , Somanchi S. , Watanabe K. , Taniguchi T. , Stampfer C. , Hackens B. 
Published: July 2021

AbstractThe quantum Hall effect is the seminal example of topological protection, as charge carriers are transmitted through one-dimensional edge channels where backscattering is prohibited. Graphene has made its marks as an exceptional platform to reveal new facets of this remarkable property. However, in conventional Hall bar geometries, topological protection of graphene edge channels is found regrettably less robust than in high mobility semi-conductors. Here, we explore graphene quantum Hall regime at the local scale, using a scanning gate microscope. We reveal the detrimental influence of antidots along the graphene edges, mediating backscattering towards upstream edge channels, hence triggering topological breakdown. Combined with simulations, our experimental results provide further insights into graphene quantum Hall channels vulnerability. In turn, this may ease future developments towards precise manipulation of topologically protected edge channels hosted in various types of two-dimensional crystals.
A clinical deep learning framework for continually learning from cardiac signals across diseases, time, modalities, and institutions
Authors: Kiyasseh Dani , Zhu Tingting , Clifton David 
Published: July 2021

AbstractDeep learning algorithms trained on instances that violate the assumption of being independent and identically distributed (i.i.d.) are known to experience destructive interference, a phenomenon characterized by a degradation in performance. Such a violation, however, is ubiquitous in clinical settings where data are streamed temporally from different clinical sites and from a multitude of physiological sensors. To mitigate this interference, we propose a continual learning strategy, entitled CLOPS, that employs a replay buffer. To guide the storage of instances into the buffer, we propose end-to-end trainable parameters, termed task-instance parameters, that quantify the difficulty with which data points are classified by a deep-learning system. We validate the interpretation of these parameters via clinical domain knowledge. To replay instances from the buffer, we exploit uncertainty-based acquisition functions. In three of the four continual learning scenarios, reflecting transitions across diseases, time, data modalities, and healthcare institutions, we show that CLOPS outperforms the state-of-the-art methods, GEM1 and MIR2. We also conduct extensive ablation studies to demonstrate the necessity of the various components of our proposed strategy. Our framework has the potential to pave the way for diagnostic systems that remain robust over time.
Self-assembly using a retro Diels-Alder reaction
Authors: Park Jaeyoung , Heo Jung-Moo , Seong Sicheon , Noh Jaegeun , Kim Jong-Man 
Published: July 2021

AbstractDespite their great utility in synthetic and materials chemistry, Diels-Alder (DA) and retro Diels-Alder (rDA) reactions have been vastly unexplored in promoting self-assembly processes. Herein we describe the first example of a retro Diels-Alder (rDA) reaction-triggered self-assembly method. Release of the steric bulkiness associated with the bridged bicyclic DA adduct by the rDA reaction allowed generation of two building blocks that spontaneously self-assembled to form a supramolecular polymer. By employing photopolymerizable lipid building blocks, we demonstrated the efficiency of the rDA-based self-assembly strategy. Generation of reactive functional groups (maleimide and furan) that can be used for further modification of the supramolecular polymer is an additional meritorious feature of the rDA-based approach. Advantage was taken of reactive functional groups to fabricate stimulus-responsive selective and tunable colorimetric sensors. The strategy developed in this study should be useful for the design of systems that participate in triggered molecular assembly.
Higher socioeconomic status does not predict decreased prosocial behavior in a field experiment
Authors: Andreoni James , Nikiforakis Nikos , Stoop Jan 
Published: July 2021

AbstractDoes higher socioeconomic status predict decreased prosocial behavior? Methodological issues such as the reliance of survey studies on self-reported measures of prosociality, the insufficient control of relative incentives in experiments, and the use of non-random samples, have prevented researchers from ruling out that there is a negative association between socioeconomic status (SES) and prosociality. Here, we present results from a field experiment on the willingness of unaware individuals of different SES to undertake an effortful prosocial task—returning a misdelivered letter. Specifically, using the rental or sale value of homes as indicators of SES, we randomly selected households of high and low SES and misdelivered envelopes to them. Despite controlling for numerous covariates and performing a series of ancillary tests, we fail to find any evidence that higher SES predicts decreased prosocial behavior. Instead, we find that misdelivered letters are substantially more likely to be returned from high rather than low SES households.
A general charge transport picture for organic semiconductors with nonlocal electron-phonon couplings
Authors: Li Weitang , Ren Jiajun , Shuai Zhigang 
Published: July 2021

AbstractThe nonlocal electron-phonon couplings in organic semiconductors responsible for the fluctuation of intermolecular transfer integrals has been the center of interest recently. Several irreconcilable scenarios coexist for the description of the nonlocal electron-phonon coupling, such as phonon-assisted transport, transient localization, and band-like transport. Through a nearly exact numerical study for the carrier mobility of the Holstein-Peierls model using the matrix product states approach, we locate the phonon-assisted transport, transient localization and band-like regimes as a function of the transfer integral (V) and the nonlocal electron-phonon couplings (ΔV), and their distinct transport behaviors are analyzed by carrier mobility, mean free path, optical conductivity and one-particle spectral function. We also identify an “intermediate regime” where none of the established pictures applies, and the generally perceived hopping regime is found to be at a very limited end in the proposed regime paradigm.
Gene therapy for aromatic L-amino acid decarboxylase deficiency by MR-guided direct delivery of AAV2-AADC to midbrain dopaminergic neurons
Authors: Pearson Toni S. , Gupta Nalin , San Sebastian Waldy , Imamura-Ching Jill , Viehoever Amy , Grijalvo-Perez Ana , Fay Alex J. , Seth Neha , Lundy Shannon M. , Seo Youngho , Pampaloni Miguel , Hyland Keith , Smith Erin , de Oliveira Barbosa Gardenia , Heathcock Jill C. , Minnema Amy , Lonser Russell , Elder J. Bradley , Leonard Jeffrey , Larson Paul , Bankiewicz Krystof S. 
Published: July 2021

AbstractAromatic L-amino acid decarboxylase (AADC) deficiency is a rare genetic disorder characterized by deficient synthesis of dopamine and serotonin. It presents in early infancy, and causes severe developmental disability and lifelong motor, behavioral, and autonomic symptoms including oculogyric crises (OGC), sleep disorder, and mood disturbance. We investigated the safety and efficacy of delivery of a viral vector expressing AADC (AAV2-hAADC) to the midbrain in children with AADC deficiency (ClinicalTrials.gov Identifier NCT02852213). Seven (7) children, aged 4–9 years underwent convection-enhanced delivery (CED) of AAV2-hAADC to the bilateral substantia nigra (SN) and ventral tegmental area (VTA) (total infusion volume: 80 µL per hemisphere) in 2 dose cohorts: 1.3 × 1011 vg (n = 3), and 4.2 × 1011 vg (n = 4). Primary aims were to demonstrate the safety of the procedure and document biomarker evidence of restoration of brain AADC activity. Secondary aims were to assess clinical improvement in symptoms and motor function. Direct bilateral infusion of AAV2-hAADC was safe, well-tolerated and achieved target coverage of 98% and 70% of the SN and VTA, respectively. Dopamine metabolism was increased in all subjects and FDOPA uptake was enhanced within the midbrain and the striatum. OGC resolved completely in 6 of 7 subjects by Month 3 post-surgery. Twelve (12) months after surgery, 6/7 subjects gained normal head control and 4/7 could sit independently. At 18 months, 2 subjects could walk with 2-hand support. Both the primary and secondary endpoints of the study were met. Midbrain gene delivery in children with AADC deficiency is feasible and safe, and leads to clinical improvements in symptoms and motor function.
Phase management in single-crystalline vanadium dioxide beams
Authors: Shi Run , Chen Yong , Cai Xiangbin , Lian Qing , Zhang Zhuoqiong , Shen Nan , Amini Abbas , Wang Ning , Cheng Chun 
Published: July 2021

AbstractA systematic study of various metal-insulator transition (MIT) associated phases of VO2, including metallic R phase and insulating phases (T, M1, M2), is required to uncover the physics of MIT and trigger their promising applications. Here, through an oxide inhibitor-assisted stoichiometry engineering, we show that all the insulating phases can be selectively stabilized in single-crystalline VO2 beams at room temperature. The stoichiometry engineering strategy also provides precise spatial control of the phase configurations in as-grown VO2 beams at the submicron-scale, introducing a fresh concept of phase transition route devices. For instance, the combination of different phase transition routes at the two sides of VO2 beams gives birth to a family of single-crystalline VO2 actuators with highly improved performance and functional diversity. This work provides a substantial understanding of the stoichiometry-temperature phase diagram and a stoichiometry engineering strategy for the effective phase management of VO2.