bluuebunny/crossref_metadata_2025 huggingface dataset:
The Paradigm Shift in the Disciplining of Village Cadres in China: From Mao to Xi
Authors: Wang Juan , Mou Yu
Published: October 2021

Village cadres are important agents for the state yet disciplining them has been difficult. There are few disciplinary tools that can easily hold them to account. Prior to 2018, Party discipline did not apply to non-Party cadres. Legislation was ambiguous in relation to these grassroots agents and had to rely heavily on legal interpretation. The impact of the cadre evaluation system on village cadres, who are not considered to be public servants on the state payroll, was limited. This situation has changed since 2018. The party-state has consolidated and institutionalized ways in which grassroots cadres are checked and disciplined. Instead of relying on policy regulation, which had been the dominant disciplinary method since 1949, village cadres are now fully subject to Party rules and state laws. These changes have been accomplished through the application of three measures. First, village Party secretaries are to serve concurrently as village heads, and members of village and Party committees are to overlap, thereby making them subject to Party discipline. Second, village cadres are now considered to be “public agents” and are on an equal legal footing with other state agents. Finally, a campaign waged by the criminal justice apparatus cleaned up village administration and prepared it for upcoming village elections in a new era.
Recycled water reuse: what factors affect public acceptance?
Authors: Nkhoma Peter R , Alsharif Kamal , Ananga Erick , Eduful Michael , Acheampong Michael
Published: October 2021

Globally, water resources are under immense and increasing pressure. This, coupled with the threat of climate change, has increased global interest in water reuse. However, global water reuse remains limited because of public opposition. This paper thus examines public perceptions and attitudes to water reuse across the world. It finds that results from studies of water reuse acceptance have tended to be context specific, although claims can be made about the universal relevance of some predictors, underscoring the need for individual water reuse schemes to carefully consider their local context. Disgust remains a constant in the public psyche, while public trust in delivery agents as well as how water reuse is communicated vis-à-vis perceptions about the quality and safety of recycled water are also critical. The latter particularly highlights public concerns about the indeterminate health risks associated with water reuse.
Prenatal substance exposure and maternal hostility from pregnancy to toddlerhood: Associations with temperament profiles at 16 months of age
Authors: Ostlund Brendan D. , Pérez-Edgar Koraly E. , Shisler Shannon , Terrell Sarah , Godleski Stephanie , Schuetze Pamela , Eiden Rina D.
Published: October 2021

We investigated whether infant temperament was predicted by level of and change in maternal hostility, a putative transdiagnostic vulnerability for psychopathology, substance use, and insensitive parenting. A sample of women (N= 247) who were primarily young, low-income, and had varying levels of substance use prenatally (69 nonsmokers, 81 tobacco-only smokers, and 97 tobacco and marijuana smokers) reported their hostility in the third trimester of pregnancy and at 2, 9, and 16 months postpartum, and their toddler's temperament and behavior problems at 16 months. Maternal hostility decreased from late pregnancy to 16 months postpartum. Relative to pregnant women who did not use substances, women who used both marijuana and tobacco prenatally reported higher levels of hostility while pregnant and exhibited less change in hostility over time. Toddlers who were exposed to higher levels of prenatal maternal hostility were more likely to be classified in temperament profiles that resemble either irritability or inhibition, identified via latent profile analysis. These two profiles were each associated with more behavior problems concurrently, though differed in their association with competence. Our results underscore the utility of transdiagnostic vulnerabilities in understanding the intergenerational transmission of psychopathology risk and are discussed in regards to the Research Domain Criteria (RDoC) framework.
SUCCESS IN ACADEMIC PHILOSOPHY: WHAT FEMALE STUDENTS AND JUNIOR ACADEMICS NEED TO KNOW
Authors: Roache Rebecca
Published: October 2021

Despite some important progress over the past decade, academic philosophy remains a male-dominated discipline. This raises questions about how established philosophers can best support and advise female students and junior academics in philosophy. We need to avoid encouraging them to adopt a fatalistic attitude to their success (‘Philosophy is sexist, I'll never make it’), while also avoiding encouraging them to believe that their success lies in their own hands and that therefore it must be their own fault if they don't succeed. I argue that we can do this by reflecting on what success in a misogynistic culture looks like, and by guiding young female philosophers to distinguish between the changes that it is possible for them, as individuals, to make, and those that require action by many individuals.
Need, demand, supply in health care: working definitions, and their implications for defining access
Authors: Rodriguez Santana Idaira , Mason Anne , Gutacker Nils , Kasteridis Panagiotis , Santos Rita , Rice Nigel
Published: October 2021

Effective policymaking in health care systems begins with a clear typology of the terminology – need, demand, supply and access to care – and their interrelationships. However, the terms are contested and their meaning is rarely stated explicitly. This paper offers working definitions of need, demand and supply. We draw on the international literature and use a Venn diagram to explain the terms. We then define access to care, reviewing alternative and competing definitions from the literature. We conclude by discussing potential applications of our conceptual framework to help to understand the interrelationships and trade-offs between need, demand, supply and access in health care.
State Responsibility for COVID-19: Does International Contagion Constitute Transboundary Harm?
Authors: CAPICCHIANO YOUNG Sophie
Published: October 2021

As the damage caused by COVID-19 has increased exponentially, so too has the insistence that China bears some international responsibility for the unquantifiable damage sustained as a direct result of the state having failed to contain the virus, and to notify the international community of its existence. Some have suggested that the international contagion of the virus may be classified as transboundary harm. The current article analyses the law of transboundary harm, and proposes a set of criteria based on treaty and precedent that may be relied on to properly classify an event as such. It concludes that it is not only incorrect to classify international contagion as transboundary harm, but that to do so would pose a significant risk to the position and treatment of the individual in international law.
Heterogeneous Interseismic Coupling Along the Xianshuihe‐Xiaojiang Fault System, Eastern Tibet
Authors: Li Yanchuan , Nocquet Jean‐Mathieu , Shan Xinjian , Jian Huizi
Published: October 2021

We use Global Positioning System (GPS) and Interferometric Synthetic Aperture Radar (InSAR) data to quantify the interseismic coupling along the Xianshuihe‐Xiaojiang fault system (XXFS). Our results confirm 7–11 mm/a of left‐lateral strike‐slip motion along the XXFS. South of the Shimian County, high interseismic coupling is found down to 20 km‐depth along the Anninghe‐Zemuhe fault. A second 130 km‐long section, highly coupled down to 10–15 km‐depth, is identified along the northern Xiaojiang fault. North of the Kangding County, the Xianshuihe fault appears to be predominantly creeping at depth. Previously identified long‐lasting surface creep following the 1973 M 7.6 Luhuo earthquake has now ended, possibly marking the initiation of a new period of stress accumulation and progressive relocking of the fault. Farther south along the fault, we identify a ∼30 km‐long section (∼30.2°–30.4°N) creeping at ∼7 mm/yr. Furthermore, creep accelerated by ∼2 mm/yr during the 2008–2014 period, possibly as a result of the static Coulomb failure stress increment induced by the 2008 Mw 7.9 Wenchuan earthquake, that occurred ∼200 km northeast of it. The 2014 Mw 5.9 Kangding earthquake occurred along the creeping section at the end of the period of accelerated creep. Finally, taking advantage of the long historical records of past large earthquakes available since 1327, we quantitatively compare the moment budget along the XXFS. Results highlight that along the Anninghe, Zemuhe, and Xiaojiang faults, moment deficit for Mw > 7 earthquakes has now accumulated.
Forecasting the Indian Ocean Dipole With Deep Learning Techniques
Authors: Liu Jun , Tang Youmin , Wu Yanling , Li Tang , Wang Qiang , Chen Dake
Published: October 2021

In the present research, Indian Ocean Dipole (IOD) prediction was explored using statistical methods based on deep learning techniques. First, convolutional neural network (CNN) models were trained using sea‐surface temperature anomaly (SSTA) maps of the Indian Ocean from 1854 to 1989, and the properly trained CNN models were then validated with the period from 1991 to 2019. The results indicate that the deep learning approach is capable of forecasting the IOD at lead times up to 7 months. The forecast skills of CNN are superior to those of the dynamic models in the North American Multi‐Model Ensemble (NMME). The CNN outperforms the NMME with lower sensitivity to predictability barriers and fewer systematic errors. Moreover, the gradient heat map analysis demonstrates that the triggering precursors selected by CNN models for IOD events are novel and physically sensible. These results suggest the CNN to be a new and effective tool for both IOD prediction and comprehension.
Lagrangian Measurements of Orbital Velocities in the Surf Zone
Authors: Bjørnestad M. , Buckley M. , Kalisch H. , Streßer M. , Horstmann J. , Frøysa H. G. , Ige O. E. , Cysewski M. , Carrasco‐Alvarez R.
Published: October 2021

Eulerian and Lagrangian measurements of orbital velocities in waves approaching a beach are analyzed with the goal of understanding the relative influence of wave‐by‐wave variations in mean‐water level, wave height and incipient wave breaking on mass transport properties of waves in the surf zone. It is shown quantitatively that elevated local mean‐water level correlates positively with increased Lagrangian mass transport at the free surface. Eulerian ADV measurements in the fluid column suggest that the depth‐integrated wave‐by‐wave mass transport also correlates positively with the local mean‐water level, and is only weakly linked to wave height and wave‐breaking events.
Effective Polytropic Index of Small‐Scale and Force‐Free Magnetic Flux Ropes in the Solar Wind
Authors: Teh Wai‐Leong
Published: October 2021

The effective polytropic index, , of small‐scale magnetic flux ropes in the solar wind is investigated using the Wind observations near 1 AU. A total of 59 flux ropes were selected with a good estimation on and divided into two categories, namely, CAT1 for flux ropes accompanied with torsional Alfvén waves and CAT2 for those without. These 59 flux ropes were satisfied the constant‐alpha, force‐free flux rope model. It is found that the index ranges between 1.05 and 2.34, with a mean of 1.68  0.43, for CAT1, while it ranges between 0.71 and 2.42, with a mean of 1.52  0.44, for CAT2. Apparently, the mean of CAT1 flux ropes is closer to the adiabatic condition ( = 5/3), as compared to CAT2 ones. No clear correlation of the index with the solar wind speed and flux rope size is found for these 59 flux ropes. For each flux rope category, the flux ropes are further distinguished by the presence of counterstreaming suprathermal electrons (CSEs) inside it. For both CAT1 and CAT2 flux ropes, it seems that the median and mean of are <5/3 for flux ropes associated with CSEs but greater than 5/3 for those without. Since the index spreads over a wide range of values, it is suggested that various polytropic processes may happen within the flux ropes during their propagation in the solar wind.
Improving the Constraint on theMw7.1 2016 Off‐Fukushima Shallow Normal‐Faulting Earthquake With the High Azimuthal Coverage Tsunami Data From the S‐Net Wide and Dense Network: Implication for the Stress Regime in the Tohoku Overriding Plate
Authors: Kubota Tatsuya , Kubo Hisahiko , Yoshida Keisuke , Chikasada Naotaka Y. , Suzuki Wataru , Nakamura Takeshi , Tsushima Hiroaki
Published: October 2021

Tsunamis with amplitudes of up to 40 cm, related to theMw7.1 normal‐faulting earthquake off Fukushima, Japan, on November 21, 2016, were clearly recorded by a new offshore wide and dense ocean‐bottom pressure gauge network, S‐net, with high azimuthal coverage located closer to the focal area. We processed the S‐net data and found some stations included the tsunami‐irrelevant drift and step signals. We analyzed the S‐net data to infer the tsunami source distribution. A subsidence region with a narrow spatial extent (∼40 km) and a large peak (∼200 cm) was obtained. The other near‐coastal waveforms not used for the inversion analysis were also reproduced very well. Our fault model suggests the maximum stress drop across the fault plane of >∼10 MPa and the average of 4.2 MPa, whereas the shear stress increase along the fault caused by the 2011 Tohoku earthquake was only ∼2 MPa. Past studies have suggested that horizontal compressional stress around this region switched to horizontal extensional stress after the Tohoku earthquake due to its stress perturbation. The present result, however, suggests that the horizontal extensional stress was locally predominant at the shallowest surface around the focal area even before 2011. The present study demonstrates that the S‐net high‐azimuthal‐coverage pressure data provide a significant constraint on the fault modeling, which enables us to discuss the stress regime within the overriding plate at the offshore. Our analysis provides an implication for crustal stress states, which is important for understanding generation mechanisms of intraplate earthquakes.
ROME: A Pseudo‐Spectral Algorithm for Time‐Dependent Shear Flows in Stratified Environments
Authors: Brown Justin M. , Radko Timour
Published: October 2021

Parameterizations of small‐scale mixing are important in modeling the behavior of the World Ocean. These microstructure mixing processes do not exist in isolation, however, and larger‐scale processes can affect their fluxes, which is an important consideration for general circulation models. We have developed a new pseudo‐spectral hydrodynamic model, the “Rocking Ocean Modeling Environment,” which is able to simulate the effects of some large‐scale processes, such as shear and internal waves. The code induces a time‐dependent shear forcing across a small domain that can accurately resolve the micro‐scale. This configuration presents a challenge for modeling via Fourier‐based algorithms because the typical evolution of such a flow is incompatible with the periodic boundary conditions at the vertical extremities of the computational domain. This complication is addressed by reformulating the governing equations in a new, temporally varying “tilting” coordinate system associated with the background flow as has been done in the past in the field of homogenous turbulence. The code is applied to one such process which is known to show substantial differences in turbulent environments: salt fingers. We simulate salt fingers in the presence of constant and oscillating shear in order to quantify the mixing of heat and salt by these systems under the impacts of large‐scale internal waves. Generally, it is shown that the application of shear can reduce fluxes by a factor of 2 or 3 for typical amplitudes of near‐inertial waves and that the impact of shear decreases as the frequency of the applied shear increases.
Human kidney organoids reveal the role of glutathione in Fabry disease
Authors: Kim Jin Won , Kim Hyung Wook , Nam Sun Ah , Lee Jong Young , Cho Hae Jin , Kim Tae-Min , Kim Yong Kyun
Published: October 2021

Fabry disease is an X-linked lysosomal storage disease caused by a mutation in the galactosidase alpha (GLA) gene. Despite advances in therapeutic technologies, the lack of humanized experimental models of Fabry disease has limited the development of new therapies to cure the disease. Herein, we modeled Fabry disease using human inducible pluripotent stem cell (iPSC)-derived kidney organoids and the CRISPR–Cas9 genome-editing system. GLA-mutant human kidney organoids revealed deformed podocytes and tubular cells with accumulation of globotriaosylceramide (Gb3). Ultrastructural analysis showed abundant electron-dense granular deposits and electron-dense lamellate lipid-like deposits that formed concentric bodies (zebra bodies) in the cytoplasm of podocytes and tubules. The oxidative stress level was increased in GLA-mutant kidney organoids, and the increase was accompanied by apoptosis. Enzyme replacement treatment (ERT) with recombinant human α-Gal A decreased the Gb3 accumulation and oxidative stress, which resulted in amelioration of the deformed cellular structure of the GLA-mutant kidney organoids. Transcription profile analyses showed decreased glutathione (GSH) metabolism in GLA-mutant kidney organoids. GSH replacement treatment decreased oxidative stress and attenuated the structural deformity of the GLA-mutant kidney organoids. GSH treatment also increased the expression of podocyte and tubular markers and decreased apoptosis. In conclusion, GLA-mutant kidney organoids derived from human iPSCs are valuable tools for studying the mechanisms and developing novel therapeutic alternatives for Fabry disease.
A needle tip CCEA microfluidic device based on enhanced Dean flow for cell washing
Authors: Shi Xin , Tan Wei , Lu Yuwen , Cao Wenfeng , Zhu Guorui
Published: October 2021

Particle/cell washing is an essential technique in biological and clinical manipulations. Herein, we propose a novel circular contraction–expansion array (CCEA) microdevice. It can be directly connected to a needle tip without connection tubes. Its small size and centrosymmetric structure are beneficial to low sample consumption, high connection stability, and a wide application range. Computational fluid dynamics (CFD) simulation results show that the CCEA structure can produce a stronger Dean flow and lead to faster particle/cell focusing than the circle structure and CEA structure with the same length. Experimentally, an optimal flow rate ratio of 1:3 and an optimal total flow rate of 120 μL/min were found to ensure a stable fluid distribution. Under these conditions, rapid focusing of 10–20 μm particles with high efficiencies was achieved. Compared with a normal CEA device using tubes, the particle loss rate could be reduced from 64 to 7% when washing 500 μL of a rare sample. Cell suspensions with concentrations from 3 × 105/mL to 1 × 103/mL were tested. The high cell collection efficiency (>85% for three cell lines) and stable waste removal efficiency (>80%) reflected the universality of the CCEA microfluidic device. After the washing, the cell activities of H1299 cells and MCF-7 cells were calculated to be 93.8 and 97.5%, respectively. This needle-tip CCEA microfluidic device showed potential in basic medical research and clinical diagnosis.
The atypical Rho GTPase Rnd2 is critical for dentate granule neuron development and anxiety-like behavior during adult but not neonatal neurogenesis
Authors: Kerloch Thomas , Farrugia Fanny , Bouit Lou , Maître Marlène , Terral Geoffrey , Koehl Muriel , Mortessagne Pierre , Heng Julian Ik-Tsen , Blanchard Mylène , Doat Hélène , Leste-Lasserre Thierry , Goron Adeline , Gonzales Delphine , Perrais David , Guillemot François , Abrous Djoher Nora , Pacary Emilie
Published: October 2021

Despite the central role of Rho GTPases in neuronal development, their functions in adult hippocampal neurogenesis remain poorly explored. Here, by using a retrovirus-based loss-of-function approach in vivo, we show that the atypical Rho GTPase Rnd2 is crucial for survival, positioning, somatodendritic morphogenesis, and functional maturation of adult-born dentate granule neurons. Interestingly, most of these functions are specific to granule neurons generated during adulthood since the deletion ofRnd2in neonatally-born granule neurons only affects dendritogenesis. In addition, suppression ofRnd2in adult-born dentate granule neurons increases anxiety-like behavior whereas its deletion in pups has no such effect, a finding supporting the adult neurogenesis hypothesis of anxiety disorders. Thus, our results are in line with the view that adult neurogenesis is not a simple continuation of earlier processes from development, and establish a causal relationship between Rnd2 expression and anxiety.
A novel function of NLRP3 independent of inflammasome as a key transcription factor of IL-33 in epithelial cells of atopic dermatitis
Authors: Zheng Jie , Yao Lu , Zhou Yijing , Gu Xiaoqun , Wang Can , Bao Kaifan , Sun Yang , Hong Min
Published: October 2021

Atopic dermatitis (AD) is a common chronic pruritic inflammatory skin disorder characterized by recurrent eczematous lesions. Interleukin (IL)−33, a cytokine of the IL-1 family, was found to play an important role in the pathogenesis of AD. As a key component of the inflammasome, NLRP3 has been mostly described in myeloid cells that to mediate inflammasome activation conducted proinflammatory cytokine production of the IL-1 family. However, the role of NLRP3 inflammasome in the pathogenesis of AD, as well as IL-33 processing are highly controversial. Whether NLRP3 can mediate IL-33 expression and secretion independently of the inflammasome in the epithelium of AD has remained unclear. In this article, we found the mRNA expression ofIl33andNlrp3were notably increased in the lesional skin of AD patients compared to healthy controls. We then found a significant positive correlation between the expression ofNlrp3andIl33in the epithelium of MC903-mediated AD mice model, but no changes were observed forIl36α,Il36γ,Il1β, orIl18mRNA expression, as well as IL-1β or IL-18 production. Overexpression of NLRP3 in human immortalized epithelial cells increased IL-33 expression, whereas siRNA targeting NLRP3 abolished IL-33 expression. In addition, inhibition of NLRP3 inflammasome activation or caspase-1 activity with MCC950 or VX-765 showed no effect on the expression and secretion of IL-33 in AD mice. Unlike myeloid cells, NLRP3 predominantly located in the nucleus of epithelial cells, which could directly bind toIl33specific-promoters and transactivate it through an interaction with transcription factor IRF4. Furthermore, NLRP3 deficient mice exhibited a significant alleviated epidermis inflammation and decreased mRNA expression and secretion of IL-33 in MC903-mediated AD mice without interfering with TSLP and IL-1β production. Our results demonstrate a novel ability of NLRP3 to function as a crucial transcription factor of IL-33 in epithelium independently of inflammasome that to mediate the pathological process of AD.
Multiband charge density wave exposed in a transition metal dichalcogenide
Authors: Pásztor Árpád , Scarfato Alessandro , Spera Marcello , Flicker Felix , Barreteau Céline , Giannini Enrico , Wezel Jasper van , Renner Christoph
Published: October 2021

In the presence of multiple bands, well-known electronic instabilities may acquire new complexity. While multiband superconductivity is the subject of extensive studies, the possibility of multiband charge density waves (CDWs) has been largely ignored so far. Here, combining energy dependent scanning tunnelling microscopy (STM) topography with a simple model of the charge modulations and a self-consistent calculation of the CDW gap, we find evidence for a multiband CDW in 2H-NbSe2. This CDW not only involves the opening of a gap on the inner band around the K-point, but also on the outer band. This leads to spatially out-of-phase charge modulations from electrons on these two bands, which we detect through a characteristic energy dependence of the CDW contrast in STM images.
Genetic investigation of fibromuscular dysplasia identifies risk loci and shared genetics with common cardiovascular diseases
Authors: Georges Adrien , Yang Min-Lee , Berrandou Takiy-Eddine , Bakker Mark K. , Dikilitas Ozan , Kiando Soto Romuald , Ma Lijiang , Satterfield Benjamin A. , Sengupta Sebanti , Yu Mengyao , Deleuze Jean-François , Dupré Delia , Hunker Kristina L. , Kyryachenko Sergiy , Liu Lu , Sayoud-Sadeg Ines , Amar Laurence , Brummett Chad M. , Coleman Dawn M. , d’Escamard Valentina , de Leeuw Peter , Fendrikova-Mahlay Natalia , Kadian-Dodov Daniella , Li Jun Z. , Lorthioir Aurélien , Pappaccogli Marco , Prejbisz Aleksander , Smigielski Witold , Stanley James C. , Zawistowski Matthew , Zhou Xiang , Zöllner Sebastian ,   FEIRI investigators, de Leeuw Peter ,   International Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group,   MEGASTROKE, Amouyel Philippe , De Buyzere Marc L. , Debette Stéphanie , Dobrowolski Piotr , Drygas Wojciech , Gornik Heather L. , Olin Jeffrey W. , Piwonski Jerzy , Rietzschel Ernst R. , Ruigrok Ynte M. , Vikkula Miikka , Warchol Celinska Ewa , Januszewicz Andrzej , Kullo Iftikhar J. , Azizi Michel ,   ARCADIA Investigators, Jeunemaitre Xavier , Persu Alexandre , Kovacic Jason C. , Ganesh Santhi K. , Bouatia-Naji Nabila
Published: October 2021

Fibromuscular dysplasia (FMD) is an arteriopathy associated with hypertension, stroke and myocardial infarction, affecting mostly women. We report results from the first genome-wide association meta-analysis of six studies including 1556 FMD cases and 7100 controls. We find an estimate of SNP-based heritability compatible with FMD having a polygenic basis, and report four robustly associated loci (PHACTR1, LRP1, ATP2B1, and LIMA1). Transcriptome-wide association analysis in arteries identifies one additional locus (SLC24A3). We characterize open chromatin in arterial primary cells and find that FMD associated variants are located in arterial-specific regulatory elements. Target genes are broadly involved in mechanisms related to actin cytoskeleton and intracellular calcium homeostasis, central to vascular contraction. We find significant genetic overlap between FMD and more common cardiovascular diseases and traits including blood pressure, migraine, intracranial aneurysm, and coronary artery disease.
Rational design of mechanically robust Ni-rich cathode materials via concentration gradient strategy
Authors: Liu Tongchao , Yu Lei , Lu Jun , Zhou Tao , Huang Xiaojing , Cai Zhonghou , Dai Alvin , Gim Jihyeon , Ren Yang , Xiao Xianghui , Holt Martin V. , Chu Yong S. , Arslan Ilke , Wen Jianguo , Amine Khalil
Published: October 2021

Mechanical integrity issues such as particle cracking are considered one of the leading causes of structural deterioration and limited long-term cycle stability for Ni-rich cathode materials of Li-ion batteries. Indeed, the detrimental effects generated from the crack formation are not yet entirely addressed. Here, applying physicochemical and electrochemical ex situ and in situ characterizations, the effect of Co and Mn on the mechanical properties of the Ni-rich material are thoroughly investigated. As a result, we successfully mitigate the particle cracking issue in Ni-rich cathodes via rational concentration gradient design without sacrificing the electrode capacity. Our result reveals that the Co-enriched surface design in Ni-rich particles benefits from its low stiffness, which can effectively suppress the formation of particle cracking. Meanwhile, the Mn-enriched core limits internal expansion and improve structural integrity. The concentration gradient design also promotes morphological stability and cycling performances in Li metal coin cell configuration.
Damaged brain accelerates bone healing by releasing small extracellular vesicles that target osteoprogenitors
Authors: Xia Wei , Xie Jing , Cai Zhiqing , Liu Xuhua , Wen Jing , Cui Zhong-Kai , Zhao Run , Zhou Xiaomei , Chen Jiahui , Mao Xinru , Gu Zhengtao , Zou Zhimin , Zou Zhipeng , Zhang Yue , Zhao Ming , Mac Maegele , Song Qiancheng , Bai Xiaochun
Published: October 2021

Clinical evidence has established that concomitant traumatic brain injury (TBI) accelerates bone healing, but the underlying mechanism is unclear. This study shows that after TBI, injured neurons, mainly those in the hippocampus, release osteogenic microRNA (miRNA)-enriched small extracellular vesicles (sEVs), which targeted osteoprogenitors in bone to stimulate bone formation. We show that miR-328a-3p and miR-150-5p, enriched in the sEVs after TBI, promote osteogenesis by directly targeting the 3′UTR of FOXO4 or CBL, respectively, and hydrogel carrying miR-328a-3p-containing sEVs efficiently repaires bone defects in rats. Importantly, increased fibronectin expression on sEVs surface contributes to targeting of osteoprogenitors in bone by TBI sEVs, thereby implying that modification of the sEVs surface fibronectin could be used in bone-targeted drug delivery. Together, our work unveils a role of central regulation in bone formation and a clear link between injured neurons and osteogenitors, both in animals and clinical settings.
Three chromosome-scale Papaver genomes reveal punctuated patchwork evolution of the morphinan and noscapine biosynthesis pathway
Authors: Yang Xiaofei , Gao Shenghan , Guo Li , Wang Bo , Jia Yanyan , Zhou Jian , Che Yizhuo , Jia Peng , Lin Jiadong , Xu Tun , Sun Jianyong , Ye Kai
Published: October 2021

For millions of years, plants evolve plenty of structurally diverse secondary metabolites (SM) to support their sessile lifestyles through continuous biochemical pathway innovation. While new genes commonly drive the evolution of plant SM pathway, how a full biosynthetic pathway evolves remains poorly understood. The evolution of pathway involves recruiting new genes along the reaction cascade forwardly, backwardly, or in a patchwork manner. With three chromosome-scale Papaver genome assemblies, we here reveal whole-genome duplications (WGDs) apparently accelerate chromosomal rearrangements with a nonrandom distribution towards SM optimization. A burst of structural variants involving fusions, translocations and duplications within 7.7 million years have assembled nine genes into the benzylisoquinoline alkaloids gene cluster, following a punctuated patchwork model. Biosynthetic gene copies and their total expression matter to morphinan production. Our results demonstrate how new genes have been recruited from a WGD-induced repertoire of unregulated enzymes with promiscuous reactivities to innovate efficient metabolic pathways with spatiotemporal constraint.
High-dimensional neural network potentials for magnetic systems using spin-dependent atom-centered symmetry functions
Authors: Eckhoff Marco , Behler Jörg
Published: October 2021

Machine learning potentials have emerged as a powerful tool to extend the time and length scales of first-principles quality simulations. Still, most machine learning potentials cannot distinguish different electronic spin arrangements and thus are not applicable to materials in different magnetic states. Here we propose spin-dependent atom-centered symmetry functions as a type of descriptor taking the atomic spin degrees of freedom into account. When used as an input for a high-dimensional neural network potential (HDNNP), accurate potential energy surfaces of multicomponent systems can be constructed, describing multiple collinear magnetic states. We demonstrate the performance of these magnetic HDNNPs for the case of manganese oxide, MnO. The method predicts the magnetically distorted rhombohedral structure in excellent agreement with density functional theory and experiment. Its efficiency allows to determine the Néel temperature considering structural fluctuations, entropic effects, and defects. The method is general and is expected to be useful also for other types of systems such as oligonuclear transition metal complexes.
CAR T cells with dual targeting of CD19 and CD22 in pediatric and young adult patients with relapsed or refractory B cell acute lymphoblastic leukemia: a phase 1 trial
Authors: Cordoba Shaun , Onuoha Shimobi , Thomas Simon , Pignataro Daniela Soriano , Hough Rachael , Ghorashian Sara , Vora Ajay , Bonney Denise , Veys Paul , Rao Kanchan , Lucchini Giovanna , Chiesa Robert , Chu Jan , Clark Liz , Fung Mei Mei , Smith Koval , Peticone Carlotta , Al-Hajj Muhammad , Baldan Vania , Ferrari Mathieu , Srivastava Saket , Jha Ram , Arce Vargas Frederick , Duffy Kevin , Day William , Virgo Paul , Wheeler Lucy , Hancock Jeremy , Farzaneh Farzin , Domning Sabine , Zhang Yiyun , Khokhar Nushmia Z. , Peddareddigari Vijay G. R. , Wynn Robert , Pule Martin , Amrolia Persis J.
Published: October 2021

Chimeric antigen receptor (CAR) T cells targeting CD19 or CD22 have shown remarkable activity in B cell acute lymphoblastic leukemia (B-ALL). The major cause of treatment failure is antigen downregulation or loss. Dual antigen targeting could potentially prevent this, but the clinical safety and efficacy of CAR T cells targeting both CD19 and CD22 remain unclear. We conducted a phase 1 trial in pediatric and young adult patients with relapsed or refractory B-ALL (n = 15) to test AUTO3, autologous transduced T cells expressing both anti-CD19 and anti-CD22 CARs (AMELIA trial, EUDRA CT 2016-004680-39). The primary endpoints were the incidence of grade 3–5 toxicity in the dose-limiting toxicity period and the frequency of dose-limiting toxicities. Secondary endpoints included the rate of morphological remission (complete response or complete response with incomplete bone marrow recovery) with minimal residual disease-negative response, as well as the frequency and severity of adverse events, expansion and persistence of AUTO3, duration of B cell aplasia, and overall and event-free survival. The study endpoints were met. AUTO3 showed a favorable safety profile, with no dose-limiting toxicities or cases of AUTO3-related severe cytokine release syndrome or neurotoxicity reported. At 1 month after treatment the remission rate (that is, complete response or complete response with incomplete bone marrow recovery) was 86% (13 of 15 patients). The 1 year overall and event-free survival rates were 60% and 32%, respectively. Relapses were probably due to limited long-term AUTO3 persistence. Strategies to improve CAR T cell persistence are needed to fully realize the potential of dual targeting CAR T cell therapy in B-ALL.
A text-mining based analysis of 100,000 tumours affecting dogs and cats in the United Kingdom
Authors: Rodríguez José , Killick David R. , Ressel Lorenzo , Espinosa de los Monteros Antonio , Santana Angelo , Beck Samuel , Cian Francesco , McKay Jenny S. , Noble P. J. , Pinchbeck Gina L. , Singleton David A. , Radford Alan D.
Published: October 2021

Cancer is a major reason for veterinary consultation, especially in companion animals. Cancer surveillance plays a key role in prevention but opportunities for such surveillance in companion animals are limited by the lack of suitable veterinary population health infrastructures. In this paper we describe a pathology-based animal tumour registry (PTR) developed within the Small Animal Veterinary Surveillance Network (SAVSNET) built from electronic pathology records (EPR) submitted to this network. From an original collection of 180232 free text (non-structured) EPRs reported between April 2018 and June 2019, we used specific text-mining methodologies to identify 109895 neoplasias. These data were normalized to describe both the tumour (type and location) and the animal (breed, neutering status and veterinary practice postcode). The resulting PTR, the largest of its kind for companion animals to date, is an important research resource being able to facilitate a wide array of research in areas including surveillance, clinical decision making and comparative cancer biology.
Task-evoked simultaneous FDG-PET and fMRI data for measurement of neural metabolism in the human visual cortex
Authors: Jamadar Sharna D. , Zhong Shenjun , Carey Alexandra , McIntyre Richard , Ward Phillip G. D. , Fornito Alex , Premaratne Malin , Jon Shah N , O’Brien Kieran , Stäb Daniel , Chen Zhaolin , Egan Gary F.
Published: October 2021

Understanding how the living human brain functions requires sophisticated in vivo neuroimaging technologies to characterise the complexity of neuroanatomy, neural function, and brain metabolism. Fluorodeoxyglucose positron emission tomography (FDG-PET) studies of human brain function have historically been limited in their capacity to measure dynamic neural activity. Simultaneous [18 F]-FDG-PET and functional magnetic resonance imaging (fMRI) with FDG infusion protocols enable examination of dynamic changes in cerebral glucose metabolism simultaneously with dynamic changes in blood oxygenation. The Monash vis-fPET-fMRI dataset is a simultaneously acquired FDG-fPET/BOLD-fMRI dataset acquired from n = 10 healthy adults (18–49 yrs) whilst they viewed a flickering checkerboard task. The dataset contains both raw (unprocessed) images and source data organized according to the BIDS specification. The source data includes PET listmode, normalization, sinogram and physiology data. Here, the technical feasibility of using opensource frameworks to reconstruct the PET listmode data is demonstrated. The dataset has significant re-use value for the development of new processing pipelines, signal optimisation methods, and to formulate new hypotheses concerning the relationship between neuronal glucose uptake and cerebral haemodynamics.
Diagnostic and prognostic value of FDG PET-CT in patients with suspected recurrent thymic epithelial tumors
Authors: Hou Guozhu , Jiang Yuanyuan , Li Fang , Cheng Wuying
Published: October 2021

This study aimed to evaluate the diagnostic and prognostic value of FDG PET/CT in patients with suspected recurrent thymic epithelial tumors (TETs). We retrospectively reviewed 83 patients with histopathologically proven TETs (50 thymomas; 33 thymic carcinomas) who underwent FDG PET/CT after surgery. The sensitivity and specificity of FDG PET/CT in detecting recurrence were calculated. The progression-free survival rate (PFS) was calculated by the Kaplan–Meier method. FDG PET/CT results were positive in 50 patients and negative in 33. Recurrent TETs were confirmed in 40 of 50 patients with positive PET/CT findings. The sensitivity and specificity of FDG PET/CT were 100% and 76.7%, respectively. Disease progression occurred in 28 patients during the follow-up. FDG PET/CT showed added prognostic value over the Masaoka stage and histopathology. Among patients with the same Masaoka stage, negative PET/CT was significantly associated with better PFS (P < 0.001). Similarly, among patients with the same histopathology, negative PET/CT was also associated with a significantly longer PFS (P < 0.001). FDG PET/CT demonstrated a good diagnostic performance in patients with recurrent TETs and had an important prognostic value in assessing the risk of disease progression.
Free-moving Quantitative Gamma-ray Imaging
Authors: Hellfeld Daniel , Bandstra Mark S. , Vavrek Jayson R. , Gunter Donald L. , Curtis Joseph C. , Salathe Marco , Pavlovsky Ryan , Negut Victor , Barton Paul J. , Cates Joshua W. , Quiter Brian J. , Cooper Reynold J. , Vetter Kai , Joshi Tenzing H. Y.
Published: October 2021

The ability to map and estimate the activity of radiological source distributions in unknown three-dimensional environments has applications in the prevention and response to radiological accidents or threats as well as the enforcement and verification of international nuclear non-proliferation agreements. Such a capability requires well-characterized detector response functions, accurate time-dependent detector position and orientation data, a digitized representation of the surrounding 3D environment, and appropriate image reconstruction and uncertainty quantification methods. We have previously demonstrated 3D mapping of gamma-ray emitters with free-moving detector systems on a relative intensity scale using a technique called Scene Data Fusion (SDF). Here we characterize the detector response of a multi-element gamma-ray imaging system using experimentally benchmarked Monte Carlo simulations and perform 3D mapping on an absolute intensity scale. We present experimental reconstruction results from hand-carried and airborne measurements with point-like and distributed sources in known configurations, demonstratingquantitativeSDF in complex 3D environments.
High-speed camera recordings uncover previously unidentified elements of zebrafish mating behaviors integral to successful fertilization
Authors: Zempo Buntaro , Tanaka Natsuko , Daikoku Eriko , Ono Fumihito
Published: October 2021

The mating behavior of teleost fish consists of a sequence of stereotyped actions. By observing mating of zebrafish under high-speed video, we analyzed and characterized a behavioral cascade leading to successful fertilization. When paired, a male zebrafish engages the female by oscillating his body in high frequency (quivering). In response, the female pauses swimming and bends her body (freezing). Subsequently, the male contorts his trunk to enfold the female’s trunk. This behavior is known as wrap around. Here, we found that wrap around behavior consists of two previously unidentified components. After both sexes contort their trunks, the male adjusts until his trunk compresses the female’s dorsal fin (hooking). After hooking, the male trunk slides away from the female’s dorsal fin, simultaneously sliding his pectoral fin across the female’s gravid belly, stimulating egg release (squeezing/spawning). Orchestrated coordination of spawning presumably increases fertilization success. Surgical removal of the female dorsal fin inhibited hooking and the transition to squeezing. In a neuromuscular mutant where males lack quivering, female freezing and subsequent courtship behaviors were absent. We thus identified traits of zebrafish mating behavior and clarified their roles in successful mating.
Dosimetry and radioprotection evaluations of very high energy electron beams
Authors: Masilela Thongchai A. M. , Delorme Rachel , Prezado Yolanda
Published: October 2021

Very high energy electrons (VHEEs) represent a promising alternative for the treatment of deep-seated tumors over conventional radiotherapy (RT), owing to their favourable dosimetric characteristics. Given the high energy of the electrons, one of the concerns has been the production of photoneutrons. In this article we explore the consequence, in terms of neutron yield in a water phantom, of using a typical electron applicator in conjunction with a 2 GeV and 200 MeV VHEE beam. Additionally, we evaluate the resulting ambient neutron dose equivalent at various locations between the phantom and a concrete wall. Through Monte Carlo (MC) simulations it was found that an applicator acts to reduce the depth of the dose build-up region, giving rise to lower exit doses but higher entrance doses. Furthermore, neutrons are injected into the entrance region of the phantom. The highest dose equivalent found was approximately 1.7 mSv/Gy in the vicinity of the concrete wall. Nevertheless, we concluded that configurations of VHEEs studied in this article are similar to conventional proton therapy treatments in terms of their neutron yield and ambient dose equivalent. Therefore, a clinical implementation of VHEEs would likely not warrant additional radioprotection safeguards compared to conventional RT treatments.
Seasonality of tuberculosis in intermediate endemicity setting dominated by reactivation diseases in Hong Kong
Authors: Lau Leonia Hiu Wan , Wong Ngai Sze , Leung Chi Chiu , Chan Chi Kuen , Lau Alexis K. H. , Tian Linwei , Lee Shui Shan
Published: October 2021

Summer-spring predominance of tuberculosis (TB) has been widely reported. The relative contributions of exogenous recent infection versus endogenous reactivation to such seasonality remains poorly understood. Monthly TB notifications data between 2005 and 2017 in Hong Kong involving 64,386 cases (41% aged ≥ 65; male-to-female ratio 1.74:1) were examined for the timing, amplitude, and predictability of variation of seasonality. The observed seasonal variabilities were correlated with demographics and clinical presentations, using wavelet analysis coupled with dynamic generalised linear regression models. Overall, TB notifications peaked annually in June and July. No significant annual seasonality was demonstrated for children aged ≤ 14 irrespective of gender. The strongest seasonality was detected in the elderly (≥ 65) among males, while seasonal pattern was more prominent in the middle-aged (45–64) and adults (30–44) among females. The stronger TB seasonality among older adults in Hong Kong suggested that the pattern has been contributed largely by reactivation diseases precipitated by defective immunity whereas seasonal variation of recent infection was uncommon.
RETRACTED ARTICLE: Chemical, electrochemical and surface studies of new metal–organic frameworks (MOF) as corrosion inhibitors for carbon steel in sulfuric acid environment
Authors: Fouda Abd El-Aziz S. , Etaiw Safaa Eldin H. , Hassan Gannat S.
Published: October 2021

The effects of [Co2(SCN) 4(hmt)2(H2O)6. H2O] (SC1) and [Co (CN)6(Me3Sn)3(H2O). (qox)] (SCP2) MOF as corrosion inhibitors on C-steel in 0.5 M sulfuric acid solutions are illustrated utilizing mass reduction (MR), electrochemical [potentiodynamic polarization (PP), andACelectrochemical impedance (EIS)].The experiments revealed that as the dose of these compounds rose, the inhibition efficacy (IE percent) of C-steel corrosion improved, reaching 80.7–93.1% at dose 25 × 10−6 M for SC1 and SCP2, respectively.IEpercent, on the other hand, dropped as the temperature range grew. SC1was adsorbed physically and chemically (mixed adsorption) but SCP2 was adsorbed physically on the surface of C-steel and conformed to the Langmuir adsorption isotherm equation. ThePPstudies revealed that these compounds act as mixed kind inhibitors. To establish the morphology of the inhibited C-steel surface, scanning electron microscopy (SEM), energy transmittedX-ray (EDX),and atomic force microscopy (AFM) studies were used. All tested experiments were in good agreement.
Prognostic impact of lingual lymph node metastasis in patients with squamous cell carcinoma of the tongue: a retrospective study
Authors: Kuroshima Takeshi , Onozato Yusuke , Oikawa Yu , Ohsako Toshimitsu , Kugimoto Takuma , Hirai Hideaki , Tomioka Hirofumi , Michi Yasuyuki , Miura Masahiko , Yoshimura Ryoichi , Harada Hiroyuki
Published: October 2021

Squamous cell carcinoma (SCC) of the tongue rarely metastasizes to the lingual lymph nodes (LLNs), which are inconstant nodes and often situated outside the areas of basic tongue tumor surgery. The current study evaluated the clinicopathological features and prognostic impact of LLN metastasis (LLNM), compared to that of cervical lymph node metastasis, in patients with tongue SCC. A total of 608 patients underwent radical surgery for tongue SCC at our department between January 2001 and December 2016. During neck dissection, we scrutinized and resected lateral LLNs, when present. Of the 128 patients with lymph node metastasis, 107 had cervical lymph node metastasis and 21 had both cervical lymph node metastasis and LLNM. Univariate analysis demonstrated that LLNM was significantly associated with the adverse features of cervical lymph node metastasis. The 5-year disease-specific survival (5y-DSS) was significantly lower in patients with LLNMs than in those without LLNMs (49.0% vs. 88.4%, P < 0.01). Moreover, Cox proportional hazards model analyses revealed that cervical lymph node metastasis at level IV or V and LLNM were independent prognostic factors for 5y-DSS. LLNM has a strong negative impact on survival in patients with tongue SCC. An advanced status of cervical lymph node metastasis may predict LLNM.