bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cholenic acid derivative UniPR1331 impairs tumor angiogenesis via blockade of VEGF/VEGFR2 in addition to Eph/ephrin
Authors: Rusnati Marco , Paiardi Giulia , Tobia Chiara , Urbinati Chiara , Lodola Alessio , D’Ursi Pasqualina , Corrado Miriam , Castelli Riccardo , Wade Rebecca C. , Tognolini Massimiliano , Chiodelli Paola 
Published: August 2021

AbstractAngiogenesis, the formation of new blood vessels from preexisting ones, is crucial for tumor growth and metastatization, and is considered a promising therapeutic target. Unfortunately, drugs directed against a specific proangiogenic growth factor or receptor turned out to be of limited benefit for oncology patients, likely due to the high biochemical redundancy of the neovascularization process. In this scenario, multitarget compounds that are able to simultaneously tackle different proangiogenic pathways are eagerly awaited. UniPR1331 is a 3β-hydroxy-Δ5-cholenic acid derivative, which is already known to inhibit Eph–ephrin interaction. Here, we employed an analysis pipeline consisting of molecular modeling and simulation, surface plasmon resonance spectrometry, biochemical assays, and endothelial cell models to demonstrate that UniPR1331 directly interacts with the vascular endothelial growth factor receptor 2 (VEGFR2) too. The binding of UniPR1331 to VEGFR2 prevents its interaction with the natural ligand vascular endothelial growth factor and subsequent autophosphorylation, signal transduction, and in vitro proangiogenic activation of endothelial cells. In vivo, UniPR1331 inhibits tumor cell-driven angiogenesis in zebrafish. Taken together, these data shed light on the pleiotropic pharmacological effect of UniPR1331, and point to Δ5-cholenic acid as a promising molecular scaffold for the development of multitarget antiangiogenic compounds.
What colour are your eyes? Teaching the genetics of eye colour & colour vision. Edridge Green Lecture RCOphth Annual Congress Glasgow May 2019
Authors: Mackey David A. 
Published: August 2021

AbstractEye colour and colour perception are excellent examples to use when teaching genetics as they encompass not simply the basic Mendelian genetics of dominant, recessive and X-linked disorders, but also many of the new concepts such as non-allelic diseases, polygenic disease, phenocopies, genome-wide association study (GWAS), founder effects, gene-environment interaction, evolutionary drivers for variations, copy number variation, insertions deletions, methylation and gene inactivation. Beyond genetics, colour perception touches on concepts involving optics, physics, physiology and psychology and can capture the imagination of the population, as we saw with social media trend of “#the dress”. Television shows such as Game of Thrones focused attention on the eye colour of characters, as well as their Dire-wolves and Dragons. These themes in popular culture can be leveraged as tools to teach and engage everyone in genetics, which is now a key component in all eye diseases. As the explosion of data from genomics, big data and artificial intelligence transforms medicine, ophthalmologists need to be genetically literate. Genetics is relevant, not just for Inherited Retinal Diseases and congenital abnormalities but also for the leading causes of blindness: age-related macular degeneration, glaucoma, myopia, diabetic retinopathy and cataract. Genetics should be part of the armamentarium of every practicing ophthalmologist. We need to ask every patient about their family history. In the near future, patients will attend eye clinics with genetic results showing they are at high risk of certain eye diseases and ophthalmologists will need to know how to screen, follow and treat these patients.
Real-space observations of 60-nm skyrmion dynamics in an insulating magnet under low heat flow
Authors: Yu Xiuzhen , Kagawa Fumitaka , Seki Shinichiro , Kubota Masashi , Masell Jan , Yasin Fehmi S. , Nakajima Kiyomi , Nakamura Masao , Kawasaki Masashi , Nagaosa Naoto , Tokura Yoshinori 
Published: August 2021

AbstractThermal-current induced electron and spin dynamics in solids –dubbed “caloritronics”– have generated widespread interest in both fundamental physics and spintronics applications. Here, we examine the dynamics of nanometric topological spin textures, skyrmions driven by a temperature gradient ∇T or heat flow, that are evaluated through in-situ real-space observations in an insulating helimagnet Cu2OSeO3. We observe increases of the skyrmion velocity and the Hall angle with increasing ∇T above a critical value of ~ 13 mK/mm, which is two orders of magnitude lower than the ∇T required to drive ferromagnetic domain walls. A comparable magnitude of ∇T is also observed to move the domain walls between a skyrmion domain and the non-topological conical-spin domain from cold to hot regions. Our results demonstrate the efficient manipulation of skyrmions by temperature gradients, a promising step towards energy-efficient “green” spintronics.
The paraventricular thalamus provides a polysynaptic brake on limbic CRF neurons to sex-dependently blunt binge alcohol drinking and avoidance behavior in mice
Authors: Levine Olivia B. , Skelly Mary Jane , Miller John D. , Rivera-Irizarry Jean K. , Rowson Sydney A. , DiBerto Jeffrey F. , Rinker Jennifer A. , Thiele Todd E. , Kash Thomas L. , Pleil Kristen E. 
Published: August 2021

AbstractBed nucleus of the stria terminalis (BNST) neurons that synthesize corticotropin-releasing factor (CRF) drive binge alcohol drinking and anxiety. Here, we found that female C57BL/6J mice binge drink more than males and have greater basal BNSTCRFneuron excitability and synaptic excitation. We identified a dense VGLUT2 + synaptic input from the paraventricular thalamus (PVT) that releases glutamate directly onto BNSTCRFneurons but also engages a large BNST interneuron population to ultimately inhibit BNSTCRFneurons, and this polysynaptic PVTVGLUT2-BNSTCRFcircuit is more robust in females than males. Chemogenetic inhibition of the PVTBNSTprojection promoted binge alcohol drinking only in female mice, while activation reduced avoidance behavior in both sexes. Lastly, repeated binge drinking produced a female-like phenotype in the male PVT-BNSTCRFexcitatory synapse without altering the function of PVTBNSTneurons per se. Our data describe a complex, feedforward inhibitory PVTVGLUT2-BNSTCRFcircuit that is sex-dependent in its function, behavioral roles, and alcohol-induced plasticity.
Unveiling the additive-assisted oriented growth of perovskite crystallite for high performance light-emitting diodes
Authors: Zhu Lin , Cao Hui , Xue Chen , Zhang Hao , Qin Minchao , Wang Jie , Wen Kaichuan , Fu Zewu , Jiang Tao , Xu Lei , Zhang Ya , Cao Yu , Tu Cailing , Zhang Ju , Liu Dawei , Zhang Guangbin , Kong Decheng , Fan Ning , Li Gongqiang , Yi Chang , Peng Qiming , Chang Jin , Lu Xinhui , Wang Nana , Huang Wei , Wang Jianpu 
Published: August 2021

AbstractSolution-processed metal halide perovskites have been recognized as one of the most promising semiconductors, with applications in light-emitting diodes (LEDs), solar cells and lasers. Various additives have been widely used in perovskite precursor solutions, aiming to improve the formed perovskite film quality through passivating defects and controlling the crystallinity. The additive’s role of defect passivation has been intensively investigated, while a deep understanding of how additives influence the crystallization process of perovskites is lacking. Here, we reveal a general additive-assisted crystal formation pathway for FAPbI3 perovskite with vertical orientation, by tracking the chemical interaction in the precursor solution and crystallographic evolution during the film formation process. The resulting understanding motivates us to use a new additive with multi-functional groups, 2-(2-(2-Aminoethoxy)ethoxy)acetic acid, which can facilitate the orientated growth of perovskite and passivate defects, leading to perovskite layer with high crystallinity and low defect density and thereby record-high performance NIR perovskite LEDs (~800 nm emission peak, a peak external quantum efficiency of 22.2% with enhanced stability).
Rational design of chemically complex metallic glasses by hybrid modeling guided machine learning
Authors: Zhou Z. Q. , He Q. F. , Liu X. D. , Wang Q. , Luan J. H. , Liu C. T. , Yang Y. 
Published: August 2021

AbstractThe compositional design of metallic glasses (MGs) is a long-standing issue in materials science and engineering. However, traditional experimental approaches based on empirical rules are time consuming with a low efficiency. In this work, we successfully developed a hybrid machine learning (ML) model to address this fundamental issue based on a database containing ~5000 different compositions of metallic glasses (either bulk or ribbon) reported since 1960s. Unlike the prior works relying on empirical parameters for featurization of data, we designed modeling guided data descriptors in line with the recent theoretical models on amorphization in chemically complex alloys for the development of the hybrid classification-regression ML algorithms. Our hybrid ML modeling was validated both numerically and experimentally. Most importantly, it enabled the discovery of MGs (either bulk or ribbon) through the ML-aided deep search of a multitude of quaternary to scenery alloy compositions. The computational framework herein established is expected to accelerate the design of MG compositions and expand their applications by probing the complex and multi-dimensional compositional space that has never been explored before.
LOXL2 attenuates osteoarthritis through inactivating Integrin/FAK signaling
Authors: Zhang Caixia , Zhu Mengjiao , Wang Huijuan , Wen Juan , Huang Ziwei , Chen Sheng , Zhao Hongting , Li Huang 
Published: August 2021

AbstractTemporomandibular joint OA (TMJOA) is a common degenerative joint disease, leads to structural damage and ultimately loss of function. Matrix degradation is one of the first pathogenesis during the progression of OA, it was effective to inhibit matrix degradation to block the development of OA. In this study, an in vivo model (compressive mechanical force) and an in vitro model (IL-1β) were used to induce OA-like changes in TMJ cartilage and chondrocytes. We revealed lysyl oxidase like-2 (LOXL2) play a critical role in TMJOA. LOXL2 expression decreased in mechanical stress/IL-β induced TMJOA-like lesions in both in vivo models and in vitro models. Furthermore, recombinant LOXL2 (rhLOXL2) treatment ameliorated the degenerative changes induced by mechanical stress in vivo, including the thinning cartilage, down-expression of collagen II and proteoglycan, and over-expression of TNF-a, while LOXL2 antibody (anti-LOXL2) treatment exacerbated these changes. Mechanistically, the protection of LOXL2 in chondrocytes was induced partly through activation of the Integrin/FAK pathway. The inhibition of the Integrin/FAK pathway could neutralized the effects caused by rhLOXL2. Collectively, our study suggests that the LOXL2 plays a protective role in mechanical stress induced TMJOA-like changes, and the Integrin/FAK pathway may be a key downstream pathway in this process.
Investigating relationship between water production and interfacial activity of γ-oryzanol, ethyl ferulate, and ferulic acid during peroxidation of bulk oil
Authors: Toorani Mohamad Reza , Golmakani Mohammad-Taghi 
Published: August 2021

AbstractIn this study, lecithin (as a surfactant) was added to promote the inhibitory-mechanism of γ-oryzanol, ethyl-ferulate and ferulic acid (based on the interfacial phenomena) so as to inhibit the oxidation of stripped sunflower oil. Monitoring the amount of water production as a byproduct of oxidation showed that the water content of the lipid system increased remarkably through the oxidation progress. Lecithin enhanced the critical concentration of hydroperoxides in reverse micelles, compared to the basic state (14.8 vs. 9.2 mM), thereby improving the hydrogen-donating mechanism of antioxidants. The size of reverse micelles increased progressively during the oxidation, while two breakpoints were pointed out in the micelles growth, i.e. at the end of the initiation and the propagation phases. Based on the kinetic data, ferulic acid showed the highest antioxidant activity (23.4), compared to ethyl-ferulate (15.5) and γ-oryzanol (13.7). Generally, lecithin enhanced antioxidant activity (~ 65%) by improving the interfacial performance of antioxidants.
Biological correlates before esophageal cancer screening and after diagnosis
Authors: Zhu Juan , Ma Shanrui , Chen Ru , Xie Shuanghua , Liu Zhengkui , Li Xinqing , Wei Wenqiang 
Published: August 2021

AbstractAlmost 50% of the world’s esophageal cancer (EC) cases occur in China, and the impact of cancer screening has long been a controversial topic. The study was designed to evaluate the biological correlates of EC screening and subsequent diagnosis in China. Based on the national cohort of esophageal cancer program, a prospective multicenter study in high-risk regions was conducted from 2017 to 2019. 61 participants received twice esophageal endoscopy screening and pathological biopsy successively (with a mean follow-up of 14.03 months). Box–Cox-power transformation and two-way repeated measures ANOVA were used to evaluate hormone cortisol and immunoglobulin (IgA, IgG, IgM) levels in plasma, reflecting their stress, immune function, and biological correlates before screening and after knowing the diagnosis. The median of cortisol, IgA, IgG, and IgM in pre-screening was 15.46 ug/dL, 1.86 g/L, 12.14 g/L, and 0.91 g/L, corresponding value at post-diagnosis was 15.30 ug/dL, 2.00 g/L, 12.79 g/L, and 0.94 g/L, respectively. No significant differences in biological indicators were found between normal and esophagitis and low-grade intraepithelial neoplasia before screening and after diagnosis. After normality transformation, cortisol, IgA, IgG and IgM levels were (0.25 ± 0.04) U/mL, (0.72 ± 0.13) (g/L), (2.44 ± 0.22) (g/L) and (0.98 ± 0.25) (g/L) before screening, (0.25 ± 0.05) U/mL, (0.70 ± 0.13) (g/L), (2.48 ± 0.21) (g/L) and (1.00 ± 0.25) (g/L) after diagnosis, respectively. Repeated Measures ANOVA showed that the main effects were significant on IgA levels between pre-screening and post-diagnosis (P = 0.019). No interaction effects on biological levels between pre-post screening and esophageal pathology, anxiety states (all P > 0.05). Little biological correlates were found both before screening and after diagnosis. Cortisol and IgA dropped less significantly, while IgM and IgA were increased slightly after diagnosis. Further multi-round longitudinal studies are needed to validate these results.
The Chinese pond mussel Sinanodonta woodiana demographically outperforms European native mussels
Authors: Urbańska Maria , Kamocki Andrzej , Kirschenstein Małgorzata , Ożgo Małgorzata 
Published: August 2021

AbstractUnionid mussels are essential for the integrity of freshwater ecosystems but show rapid worldwide declines. The large-sized, thermophilic Chinese pond mussel Sinanodonta woodiana s.l., however, is a successful global invader, spread with commercially traded fish encysted with mussel larvae; its negative impacts on native mussels are expected. Here, we exploit a natural experiment provided by a simultaneous introduction of S. woodiana and four species of native unionids for water filtration to a pond in north-eastern Poland. Sinanodonta woodiana established a self-sustaining population and persisted for 19 years in suboptimal thermal conditions (mean annual temperature, 7.4 °C; mean temperature of the coldest month, − 3.7 °C, 73-day mean yearly ice-formation), extending the known limits of its cold tolerance. Over four study years, its frequency increased, and it showed higher potential for population growth than the native mussels, indicating possible future dominance shifts. Outbreaks of such sleeper populations are likely to be triggered by increasing temperatures. Additionally, our study documents the broad tolerance of S. woodiana concerning bottom sediments. It also points to the importance of intentional introductions of adult individuals and the bridgehead effect facilitating its further spread. We argue that S. woodiana should be urgently included in invasive species monitoring and management programmes.
Low-count whole-body PET with deep learning in a multicenter and externally validated study
Authors: Chaudhari Akshay S. , Mittra Erik , Davidzon Guido A. , Gulaka Praveen , Gandhi Harsh , Brown Adam , Zhang Tao , Srinivas Shyam , Gong Enhao , Zaharchuk Greg , Jadvar Hossein 
Published: August 2021

AbstractMore widespread use of positron emission tomography (PET) imaging is limited by its high cost and radiation dose. Reductions in PET scan time or radiotracer dosage typically degrade diagnostic image quality (DIQ). Deep-learning-based reconstruction may improve DIQ, but such methods have not been clinically evaluated in a realistic multicenter, multivendor environment. In this study, we evaluated the performance and generalizability of a deep-learning-based image-quality enhancement algorithm applied to fourfold reduced-count whole-body PET in a realistic clinical oncologic imaging environment with multiple blinded readers, institutions, and scanner types. We demonstrate that the low-count-enhanced scans were noninferior to the standard scans in DIQ (p < 0.05) and overall diagnostic confidence (p < 0.001) independent of the underlying PET scanner used. Lesion detection for the low-count-enhanced scans had a high patient-level sensitivity of 0.94 (0.83–0.99) and specificity of 0.98 (0.95–0.99). Interscan kappa agreement of 0.85 was comparable to intrareader (0.88) and pairwise inter-reader agreements (maximum of 0.72). SUV quantification was comparable in the reference regions and lesions (lowest p-value=0.59) and had high correlation (lowest CCC = 0.94). Thus, we demonstrated that deep learning can be used to restore diagnostic image quality and maintain SUV accuracy for fourfold reduced-count PET scans, with interscan variations in lesion depiction, lower than intra- and interreader variations. This method generalized to an external validation set of clinical patients from multiple institutions and scanner types. Overall, this method may enable either dose or exam-duration reduction, increasing safety and lowering the cost of PET imaging.
Pulmonary immune cell trafficking promotes host defense against alcohol-associated Klebsiella pneumonia
Authors: Samuelson Derrick R. , Gu Min , Shellito Judd E. , Molina Patricia E. , Taylor Christopher M. , Luo Meng , Welsh David A. 
Published: August 2021

AbstractThe intestinal microbiota generates many different metabolites which are critical for the regulation of host signaling pathways. In fact, a wide-range of diseases are associated with increased levels of local or systemic microbe-derived metabolites. In contrast, certain bacterial metabolites, such as tryptophan metabolites, are known to contribute to both local and systemic homeostasis. Chronic alcohol consumption is accompanied by alterations to intestinal microbial communities, and their functional capacities. However, little is known about the role of alcohol-associated dysbiosis on host defense against bacterial pneumonia. Our previous work using fecal transplantation demonstrated that alcohol-associated intestinal dysbiosis, independent of ethanol consumption, increased susceptibility toKlebsiellapneumonia. Here, we demonstrate that intestinal microbiota treatments mitigate the increased risk of alcohol-associated pneumonia. Treatment with the microbial metabolite indole or with probiotics reduced pulmonary and extrapulmonary bacterial burden, restored immune responses, and improved cellular trafficking required for host defense. Protective effects were, in part, mediated by aryl hydrocarbon receptors (AhR), as inhibition of AhR diminished the protective effects. Thus, alcohol appears to impair the production/processing of tryptophan catabolites resulting in immune dysregulation and impaired cellular trafficking. These data support microbiota therapeutics as novel strategies to mitigate the increased risk for alcohol-associated bacterial pneumonia.
Ultra-deep optical cooling of coupled nuclear spin-spin and quadrupole reservoirs in a GaAs/(Al,Ga)As quantum well
Authors: Kotur Mladen , Tolmachev Daniel O. , Litvyak Valentina M. , Kavokin Kirill V. , Suter Dieter , Yakovlev Dmitri R. , Bayer Manfred 
Published: August 2021

AbstractThe physics of interacting nuclear spins in solids is well interpreted within the nuclear spin temperature concept. A common approach to cooling the nuclear spin system is adiabatic demagnetization of the initial, optically created, nuclear spin polarization. Here, the selective cooling of 75As spins by optical pumping followed by adiabatic demagnetization in the rotating frame is realized in a nominally undoped GaAs/(Al,Ga)As quantum well. The lowest nuclear spin temperature achieved is 0.54 μK. The rotation of 6 kG strong Overhauser field at the 75As Larmor frequency of 5.5 MHz is evidenced by the dynamic Hanle effect. Despite the presence of the quadrupole induced nuclear spin splitting, it is shown that the rotating 75As magnetization is uniquely determined by the spin temperature of coupled spin-spin and quadrupole reservoirs. The dependence of heat capacity of these reservoirs on the external magnetic field direction with respect to crystal and structure axes is investigated.
Beam-induced surface modifications as a critical source of heat loads in the Large Hadron Collider
Authors: Petit Valentine , Taborelli Mauro , Zanin Danilo Andrea , Himmerlich Marcel , Neupert Holger , Chiggiato Paolo , Iadarola Giovanni 
Published: August 2021

AbstractBeam-induced heat loads on the cryogenic regions of the Large Hadron Collider (LHC) exhibit a wide and unexpected dispersion along the accelerator, with potential impact on the performance of its High-Luminosity upgrade. Studies related the heat load source to the avalanche multiplication of electrons at the surface of the beam vacuum chamber, a phenomenon known as electron could build-up. Here, we demonstrate that the topmost copper surface of beam pipes extracted from a low heat load region of the LHC consists of native Cu2O, while the pipe surface from a high heat load region had been oxidized to CuO during LHC operation and maintenance cycles. Experiments show that this process increases the secondary electron yield and inhibits efficient surface conditioning, thus enhancing the electron cloud intensity during LHC operation. This study relates the abnormal LHC heat loads to beam-induced surface modifications of its beam pipes, enabling the development of curative solutions to overcome this critical limitation.
The Kuroshio flowing over seamounts and associated submesoscale flows drive 100-km-wide 100-1000-fold enhancement of turbulence
Authors: Nagai Takeyoshi , Hasegawa Daisuke , Tsutsumi Eisuke , Nakamura Hirohiko , Nishina Ayako , Senjyu Tomoharu , Endoh Takahiro , Matsuno Takeshi , Inoue Ryuichiro , Tandon Amit 
Published: August 2021

AbstractAlthough previous studies reported that currents over topographic features, such as seamounts and ridges, cause strong turbulence in close proximity, it has been elusive how far intense turbulence spreads toward the downstream. Here, we conducted a series of intensive in-situ turbulence observations using a state-of-the-art tow-yo microstructure profiler in the Kuroshio flowing over the seamounts of the Tokara Strait, south of Kyusyu Japan, in November 2017, June 2018, and November 2019, and employed a high-resolution numerical model to elucidate the turbulence generation mechanisms. We find that the Kuroshio flowing over seamounts generates streaks of negative potential vorticity and near-inertial waves. With these long-persisting mechanisms in addition to other near-field mixing processes, intense mixing hotspots are formed over a 100-km scale with the elevated energy dissipation by 100- to 1000-fold. The observed turbulence could supply nutrients to sunlit layers, promoting phytoplankton primary production and CO2uptake.