bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness and safety of ranibizumab in patients with central retinal vein occlusion: results from the real-world, global, LUMINOUS study
Authors: Lotery Andrew , Clemens Andreas , Tuli Raman , Xu Xun , Shimura Masahiko , Nardi Marco , Ziemssen Focke , Dunger-Baldauf Cornelia , Tadayoni Ramin ,   on behalf of the LUMINOUS™ study group
Published: July 2021

Abstract
Objective
To evaluate the effectiveness, treatment patterns and long-term safety of ranibizumab 0.5 mg in treatment-naïve patients with central retinal vein occlusion (CRVO) in a real-world setting.

Methods
LUMINOUS, a 5-year, global, prospective, multicentre, multi-indication, observational, open-label study, recruited treatment naïve or prior treated patients who were treated as per the local ranibizumab label. Here, we report the mean change in visual acuity (VA; Early Treatment Diabetic Retinopathy Study [ETDRS] letters), treatment exposure over year (Y) 1 and 5-year safety in treatment-naïve CRVO patients.

Results
At baseline, the mean age of treatment-naïve CRVO patients (n = 327) was 68.9 years, with a mean (Standard deviation [SD]) VA of 40.6 (23.9) letters. At Y1, patients (n = 144) had a mean (SD) VA gain from baseline of 10.8 (19.66) letters, with a mean (SD) of 5.4 (2.65) ranibizumab injections. Patients demonstrated mean (SD) VA gains of 2.7 (19.35), 11.6 (20.56), 13.9 (18.08), 11.1 (18.46) and 8.2 (24.86) letters with 1, 2–3, 4–5, 6–8 and >8 ranibizumab injections, respectively. Mean (SD) VA gains at Y1 in patients receiving loading (67.4%) and no loading dose (32.6%) was 11.9 (20.42) and 8.4 (17.99) letters, respectively. Over five years, the incidence of ocular/non-ocular adverse events (AEs) and serious AEs was 11.3%/8.6% and 1.2%/6.7%, respectively.

Conclusions
These results demonstrate the effectiveness of ranibizumab in treatment-naïve CRVO patients at Y1 with clinically meaningful VA gains and no new safety findings over five years. These findings may help inform routine practice and enable better clinical management to achieve optimal visual outcomes.
20th century cooling of the deep ocean contributed to delayed acceleration of Earth’s energy imbalance
Authors: Bagnell A. , DeVries T. 
Published: July 2021

AbstractThe historical evolution of Earth’s energy imbalance can be quantified by changes in the global ocean heat content. However, historical reconstructions of ocean heat content often neglect a large volume of the deep ocean, due to sparse observations of ocean temperatures below 2000 m. Here, we provide a global reconstruction of historical changes in full-depth ocean heat content based on interpolated subsurface temperature data using an autoregressive artificial neural network, providing estimates of total ocean warming for the period 1946-2019. We find that cooling of the deep ocean and a small heat gain in the upper ocean led to no robust trend in global ocean heat content from 1960-1990, implying a roughly balanced Earth energy budget within −0.16 to 0.06 W m−2 over most of the latter half of the 20th century. However, the past three decades have seen a rapid acceleration in ocean warming, with the entire ocean warming from top to bottom at a rate of 0.63 ± 0.13 W m−2. These results suggest a delayed onset of a positive Earth energy imbalance relative to previous estimates, although large uncertainties remain.
MuSyC is a consensus framework that unifies multi-drug synergy metrics for combinatorial drug discovery
Authors: Wooten David J. , Meyer Christian T. , Lubbock Alexander L. R. , Quaranta Vito , Lopez Carlos F. 
Published: July 2021

AbstractDrug combination discovery depends on reliable synergy metrics but no consensus exists on the correct synergy criterion to characterize combined interactions. The fragmented state of the field confounds analysis, impedes reproducibility, and delays clinical translation of potential combination treatments. Here we present a mass-action based formalism to quantify synergy. With this formalism, we clarify the relationship between the dominant drug synergy principles, and present a mapping of commonly used frameworks onto a unified synergy landscape. From this, we show how biases emerge due to intrinsic assumptions which hinder their broad applicability and impact the interpretation of synergy in discovery efforts. Specifically, we describe how traditional metrics mask consequential synergistic interactions, and contain biases dependent on the Hill-slope and maximal effect of single-drugs. We show how these biases systematically impact synergy classification in large combination screens, potentially misleading discovery efforts. Thus the proposed formalism can provide a consistent, unbiased interpretation of drug synergy, and accelerate the translatability of synergy studies.
Highly efficient and robust noble-metal free bifunctional water electrolysis catalyst achieved via complementary charge transfer
Authors: Oh Nam Khen , Seo Jihyung , Lee Sangjin , Kim Hyung-Jin , Kim Ungsoo , Lee Junghyun , Han Young-Kyu , Park Hyesung 
Published: July 2021

AbstractThe operating principle of conventional water electrolysis using heterogenous catalysts has been primarily focused on the unidirectional charge transfer within the heterostructure. Herein, multidirectional charge transfer concept has been adopted within heterostructured catalysts to develop an efficient and robust bifunctional water electrolysis catalyst, which comprises perovskite oxides (La0.5Sr0.5CoO3–δ, LSC) and potassium ion-bonded MoSe2 (K-MoSe2). The complementary charge transfer from LSC and K to MoSe2 endows MoSe2 with the electron-rich surface and increased electrical conductivity, which improves the hydrogen evolution reaction (HER) kinetics. Excellent oxygen evolution reaction (OER) kinetics of LSC/K-MoSe2 is also achieved, surpassing that of the noble metal (IrO2), attributed to the enhanced adsorption capability of surface-based oxygen intermediates of the heterostructure. Consequently, the water electrolysis efficiency of LSC/K-MoSe2 exceeds the performance of the state-of-the-art Pt/C||IrO2 couple. Furthermore, LSC/K-MoSe2 exhibits remarkable chronopotentiometric stability over 2,500 h under a high current density of 100 mA cm−2.
BRCA2 binding through a cryptic repeated motif to HSF2BP oligomers does not impact meiotic recombination
Authors: Ghouil Rania , Miron Simona , Koornneef Lieke , Veerman Jasper , Paul Maarten W. , Le Du Marie-Hélène , Sleddens-Linkels Esther , van Rossum-Fikkert Sari E. , van Loon Yvette , Felipe-Medina Natalia , Pendas Alberto M. , Maas Alex , Essers Jeroen , Legrand Pierre , Baarends Willy M. , Kanaar Roland , Zinn-Justin Sophie , Zelensky Alex N. 
Published: July 2021

AbstractBRCA2 and its interactors are required for meiotic homologous recombination (HR) and fertility. Loss of HSF2BP, a BRCA2 interactor, disrupts HR during spermatogenesis. We test the model postulating that HSF2BP localizes BRCA2 to meiotic HR sites, by solving the crystal structure of the BRCA2 fragment in complex with dimeric armadillo domain (ARM) of HSF2BP and disrupting this interaction in a mouse model. This reveals a repeated 23 amino acid motif in BRCA2, each binding the same conserved surface of one ARM domain. In the complex, two BRCA2 fragments hold together two ARM dimers, through a large interface responsible for the nanomolar affinity — the strongest interaction involving BRCA2 measured so far. Deleting exon 12, encoding the first repeat, frommBrca2disrupts BRCA2 binding to HSF2BP, but does not phenocopy HSF2BP loss. Thus, results herein suggest that the high-affinity oligomerization-inducing BRCA2-HSF2BP interaction is not required for RAD51 and DMC1 recombinase localization in meiotic HR.
SARS-CoV-2 specific T cell responses are lower in children and increase with age and time after infection
Authors: Cohen Carolyn A. , Li Athena P. Y. , Hachim Asmaa , Hui David S. C. , Kwan Mike Y. W. , Tsang Owen T. Y. , Chiu Susan S. , Chan Wai Hung , Yau Yat Sun , Kavian Niloufar , Ma Fionn N. L. , Lau Eric H. Y. , Cheng Samuel M. S. , Poon Leo L. M. , Peiris Malik , Valkenburg Sophie A. 
Published: July 2021

AbstractSARS-CoV-2 infection of children leads to a mild illness and the immunological differences with adults are unclear. Here, we report SARS-CoV-2 specific T cell responses in infected adults and children and find that the acute and memory CD4+ T cell responses to structural SARS-CoV-2 proteins increase with age, whereas CD8+ T cell responses increase with time post-infection. Infected children have lower CD4+ and CD8+ T cell responses to SARS-CoV-2 structural and ORF1ab proteins when compared with infected adults, comparable T cell polyfunctionality and reduced CD4+ T cell effector memory. Compared with adults, children have lower levels of antibodies to β-coronaviruses, indicating differing baseline immunity. Total T follicular helper responses are increased, whilst monocyte numbers are reduced, indicating rapid adaptive co-ordination of the T and B cell responses and differing levels of inflammation. Therefore, reduced prior β-coronavirus immunity and reduced T cell activation in children might drive milder COVID-19 pathogenesis.
Proton switching molecular magnetoelectricity
Authors: Hu Yong , Broderick Scott , Guo Zipeng , N’Diaye Alpha T. , Bola Jaspal S. , Malissa Hans , Li Cheng , Zhang Qiang , Huang Yulong , Jia Quanxi , Boehme Christoph , Vardeny Z. Valy , Zhou Chi , Ren Shenqiang 
Published: July 2021

AbstractThe convergence of proton conduction and multiferroics is generating a compelling opportunity to achieve strong magnetoelectric coupling and magneto-ionics, offering a versatile platform to realize molecular magnetoelectrics. Here we describe machine learning coupled with additive manufacturing to accelerate the design strategy for hydrogen-bonded multiferroic macromolecules accompanied by strong proton dependence of magnetic properties. The proton switching magnetoelectricity occurs in three-dimensional molecular heterogeneous solids. It consists of a molecular magnet network as proton reservoir to modulate ferroelectric polarization, while molecular ferroelectrics charging proton transfer to reversibly manipulate magnetism. The magnetoelectric coupling induces a reversible 29% magnetization control at ferroelectric phase transition with a broad thermal hysteresis width of 160 K (192 K to 352 K), while a room-temperature reversible magnetic modulation is realized at a low electric field stimulus of 1 kV cm−1. The findings of electrostatic proton transfer provide a pathway of proton mediated magnetization control in hierarchical molecular multiferroics.
Stroboscopic high-order nonlinearity for quantum optomechanics
Authors: Rakhubovsky Andrey A. , Filip Radim 
Published: July 2021

AbstractHigh-order quantum nonlinearity is an important prerequisite for the advanced quantum technology leading to universal quantum processing with large information capacity of continuous variables. Levitated optomechanics, a field where motion of dielectric particles is driven by precisely controlled tweezer beams, is capable of attaining the required nonlinearity via engineered potential landscapes of mechanical motion. Importantly, to achieve nonlinear quantum effects, the evolution caused by the free motion of mechanics and thermal decoherence have to be suppressed. For this purpose, we devise a method of stroboscopic application of a highly nonlinear potential to a mechanical oscillator that leads to the motional quantum non-Gaussian states exhibiting nonclassical negative Wigner function and squeezing of a nonlinear combination of mechanical quadratures. We test the method numerically by analyzing highly instable cubic potential with relevant experimental parameters of the levitated optomechanics, prove its feasibility within reach, and propose an experimental test. The method paves a road for experiments instantaneously transforming a ground state of mechanical oscillators to applicable nonclassical states by nonlinear optical force.
Early visual processing relevant to the reduction of adaptation-induced perceptual bias
Authors: Urakawa Tomokazu , Tanaka Motoyoshi , Suzuki Yuta , Araki Osamu 
Published: July 2021

AbstractVisual perception is biased by the preceding visual environment. A well-known perceptual bias is the negative bias where a current percept is biased away from the preceding image (adaptor). The preceding adaptor induces augmentation of early visual evoked potential (the P1 enhancement) of the following test image; the adaptor may invoke certain visual processing for the subsequent test image. However, the visual mechanism underlying P1 enhancement remains unclear. The present study assessed what the P1 alteration reflects in relation to the occurrence of the negative bias. In terms of inter-individual differences, we report that the P1 enhancement of the Necker lattice significantly correlated with the reduction of the reverse-bias effect. Further analyses revealed that the P1 enhancement was insusceptible to neural adaptation to the adaptor at the level of perceptual configuration. The present study suggests that prolonged exposure to a visual image induces modulatory visual processing for the subsequent image (reflected in the P1 enhancement), which is relevant to counteraction of the negative bias.
RETRACTED ARTICLE: Discovery of nanoscale sanal flow choking in cardiovascular system: exact prediction of the 3D boundary-layer-blockage factor in nanotubes
Authors: Kumar V. R. Sanal , Sankar Vigneshwaran , Chandrasekaran Nichith , Rafic Sulthan Ariff Rahman Mohamed , Sukumaran Ajith , Radhakrishnan Pradeep Kumar , Choudhary Shiv Kumar 
Published: July 2021

AbstractEvidences are escalating on the diverse neurological-disorders and asymptomatic cardiovascular-diseases associated with COVID-19 pandemic due to the Sanal-flow-choking. Herein, we established the proof of the concept of nanoscale Sanal-flow-choking in real-world fluid-flow systems using a closed-form-analytical-model. This mathematical-model is capable of predicting exactly the 3D-boundary-layer-blockage factor of nanoscale diabatic-fluid-flow systems (flow involves the transfer of heat) at the Sanal-flow-choking condition. As the pressure of the diabatic nanofluid and/or non-continuum-flows rises, average-mean-free-path diminishes and thus, the Knudsen-number lowers heading to a zero-slip wall-boundary condition with the compressible-viscous-flow regime in the nanoscale-tubes leading to Sanal-flow-choking due to the sonic-fluid-throat effect. At the Sanal-flow-choking condition the total-to-static pressure ratio (ie., systolic-to-diastolic pressure ratio) is a unique function of the heat-capacity-ratio of the real-world flows. The innovation of the nanoscale Sanal-flow-choking model is established herein through the entropy relation, as it satisfies all the conservation-laws of nature. The physical insight of the boundary-layer-blockage persuaded nanoscale Sanal-flow-choking in diabatic flows presented in this article sheds light on finding solutions to numerous unresolved scientific problems in physical, chemical and biological sciences carried forward over the centuries because the mathematical-model describing the phenomenon of Sanal-flow-choking is a unique scientific-language of the real-world-fluid flows. The 3D-boundary-layer-blockage factors presented herein for various gases are universal-benchmark-data for performing high-fidelity in silico, in vitro and in vivo experiments in nanotubes.
Epigenetic regulation of triple negative breast cancer (TNBC) by TGF-β signaling
Authors: Vishnubalaji Radhakrishnan , Alajez Nehad M. 
Published: July 2021

AbstractTGFβ signaling plays crucial role during development and cancer, however the role for TGFβ signaling in regulating the noncoding part of the human genome in triple negative breast cancer (TNBC) is still being unraveled. Herein, we provide the transcriptional landscape of TNBC in response to TGFβ activation and subsequent inhibition employing SB431542, selective TGFβ1 Receptor ALK5 Inhibitor. Our data revealed 72 commonly upregulated [fold change (FC) ≥ 2.0], including PLAU, TPM1, TAGLN, COL1A1, TGFBI, and SNAI1, and 53 downregulated (FC ≤ 2.0) protein coding genes in BT-549 and MDA-MB-231 models in response to TGFβ1 activation. Alignment to the geocode (V33) identified 41 upregulated (FC ≥ 2.0) and 22 downregulated (FC ≤ 2.0) long non-coding RNA (lncRNA) in response to TGFβ1 activation, which were inhibited by concurrent treatment with SB431542. To place our data from the in vitro models into their clinical context, we identified AC015909.1, AC013451.1, CYP1B1-AS1, AC004862.1, LINC01824, AL138828.1, B4GALT1-AS1, AL353751.1, AC090826.3, AC104695.4, ADORA2A-AS1, PTPRG-AS1, LINC01943, AC026954.3, TPM1-AS, ZFPM2-AS1, AC007362.1, AC112721.2, MALAT1, AL513314.2, AC112721.1, AC010343.3, LINC01711, and MAP3K2-DT lncRNA expression to positively correlate with TGFβ1 expression in a cohort of 360 TNBC patients. To provide mechanistic insight into lncRNA regulation by TGFβ signaling, SMAD2/3 ChIp-Seq data from BT-549 TNBC model retrieved from Gene Expression Omnibus (GEO) revealed direct binding of SMAD2/SMAD3 to the promoter of AC112721.1, AC112721.2, MALAT1, HHIP-AS1, LINC00472, and SLC7A11, suggesting their direct regulation by TGFβ1/SMAD2/SMAD3 pathway. Interestingly, AC112721.1, AC112721.2 exhibited higher expression in TNBC compared to normal breast tissue suggesting a possible role for those lncRNA in TNBC biology. Our miRNA analysis in the BT-549 model in response to exogenous TGFB1 revealed several affected miRNAs (2.0 ≤ FC ≤ 2.0), whose expression pattern was reversed in the presence of SB431542, suggesting those miRNA as plausible targets for TGFβ regulation. In particular, we observed hsa-miR-1275 to be downregulated in response to TGFB1 which was highly predicted to regulate PCDH1, FIBCD1, FXYD7, GDNF, STC1, EDN1, ZSWIM4, FGF1, PPP1R9B, NUAK1, PALM2AKAP2, IGFL3, and SPOCK1 whose expression were upregulated in response to TGFβ1 stimulus. On the other hand, hsa-miR-181b-5p was among the top upregulated miRNAs in response to TGFB1, which is also predicted to regulate CDKN1B, TNFRSF11B, SIM1, and ARSJ in the BT-549 model. Taken together, our data is the first to provide such in depth analysis of lncRNA and miRNA epigenetic changes in response to TGFβ signaling in TNBC.
A framework for quantifying uncertainty in DFT energy corrections
Authors: Wang Amanda , Kingsbury Ryan , McDermott Matthew , Horton Matthew , Jain Anubhav , Ong Shyue Ping , Dwaraknath Shyam , Persson Kristin A. 
Published: July 2021

AbstractIn this work, we demonstrate a method to quantify uncertainty in corrections to density functional theory (DFT) energies based on empirical results. Such corrections are commonly used to improve the accuracy of computational enthalpies of formation, phase stability predictions, and other energy-derived properties, for example. We incorporate this method into a new DFT energy correction scheme comprising a mixture of oxidation-state and composition-dependent corrections and show that many chemical systems contain unstable polymorphs that may actually be predicted stable when uncertainty is taken into account. We then illustrate how these uncertainties can be used to estimate the probability that a compound is stable on a compositional phase diagram, thus enabling better-informed assessments of compound stability.
Muscle synergy differences between voluntary and reactive backward stepping
Authors: Wang Shuaijie , Varas-Diaz Gonzalo , Bhatt Tanvi 
Published: July 2021

AbstractReactive stepping responses are essential to prevent falls after a loss of balance. It has previously been well described that both voluntary and reactive step training could improve the efficacy of reactive stepping in different populations. However, the effect of aging on neuromuscular control during voluntary and reactive stepping remains unclear. Electromyography (EMG) signals during both backward voluntary stepping in response to an auditory cue and backward reactive stepping elicited by a forward slip-like treadmill perturbation during stance were recorded in ten healthy young adults and ten healthy older adults. Using muscle synergy analysis, we extracted the muscle synergies for both voluntary and reactive stepping. Our results showed that fewer muscle synergies were used during reactive stepping than during voluntary stepping in both young and older adults. Minor differences in the synergy structure were observed for both voluntary and reactive stepping between age groups. Our results indicate that there is a low similarity of muscle synergies between voluntary stepping and reactive stepping and that aging had a limited effect on the structure of muscle synergies. This study enhances our understanding of the neuromuscular basis of both voluntary and reactive stepping as well as the potential effect of aging on neuromuscular control during balance tasks.
Gas–liquid mass transfer characteristics of aviation fuel scrubbing in an aircraft fuel tank
Authors: Chaoyue Li , Shiyu Feng , Lei Xu , Xiaotian Peng , Yan Yan 
Published: July 2021

AbstractDissolved oxygen evolving from aviation fuel leads to an increase in the oxygen concentration in an inert aircraft fuel tank ullage that may increase the flammability of the tank. Aviation fuel scrubbing with nitrogen-enriched air (NEA) can largely reduce the amount of dissolved oxygen and counteract the adverse effect of oxygen evolution. The gas–liquid mass transfer characteristics of aviation fuel scrubbing are investigated using the computational fluid dynamics method, which is verified experimentally. The effects of the NEA bubble diameter, NEA superficial velocity and fuel load on oxygen transfer between NEA and aviation fuel are discussed. Findings from this work indicate that the descent rate of the average dissolved oxygen concentration, gas holdup distribution and volumetric mass transfer coefficient increase with increasing NEA superficial velocity but decrease with increasing bubble diameter and fuel load. When the bubble diameter varies from 1 to 4 mm, the maximum change of descent rate of dissolved oxygen concentration is 18.46%, the gas holdup is 8.73%, the oxygen volumetric mass transfer coefficient is 81.45%. When the NEA superficial velocities varies from 0.04 to 0.10 m/s, the maximum change of descent rate of dissolved oxygen concentration is 146.77%, the gas holdup is 77.14%, the oxygen volumetric mass transfer coefficient is 175.38%. When the fuel load varies from 35 to 80%, the maximum change of descent rate of dissolved oxygen concentration is 21.15%, the gas holdup is 49.54%, the oxygen volumetric mass transfer coefficient is 44.57%. These results provide a better understanding of the gas and liquid mass transfer characteristics of aviation fuel scrubbing in aircraft fuel tanks and can promote the optimal design of fuel scrubbing inerting systems.