bluuebunny/crossref_metadata_2025 huggingface dataset:
Advancing head and neck cancer following the coronavirus disease 2019 pandemic
Authors: Flynn W , Maqsood R , Maseland T , Montgomery J , Douglas C
Published: April 2022

Objective

Delay in the diagnosis of head and neck cancer can result in significant excess morbidity and mortality. How the pandemic has affected patient presentation in Scotland is unknown.

Method

This retrospective cohort study compared all presentations of head and neck cancer between June and October of 2019 with the same period following the peak of the pandemic in 2020 in West Scotland, a region populated by 2.5 million people.

Results

A total of 528 patients met our inclusion criteria. Compared with 2019, patients in 2020 were more likely to present with a higher American Joint Committee on Cancer stage (odds ratio, 1.67 (95 per cent confidence interval = 1.20 to 2.31); p = 0.002), a longer preceding symptom duration (odds ratio, 2.03 (95 per cent confidence interval = 1.44 to 2.87; p < 0.001) and to have an emergency presentation (odds ratio, 2.53, (95 per cent confidence interval = 1.15 to 5.55; p = 0.017).

Conclusion

Patients are presenting later with more advanced head and neck cancer following the coronavirus disease 2019 pandemic.
Population growth ofGyrodactylus kobayashiiin goldfish (Carassius auratus) associated with host density
Authors: Jin Xiao , Zou Hong , Li Ming , Wu Shangong , Wang Guitang , Marcogliese David J. , Li Wenxiang
Published: April 2022

Host density is a key regulatory factor in parasite transmission. The goldfish (Carassius auratus)-Gyrodactylus kobayashiimodel was used to investigate effects of host density on population growth of gyrodactylids. A donor fish infected by five gravid gyrodactylids was mixed with 11 parasite-free goldfish at five host densities. There was a significant positive correlation between host density and mean abundance ofG. kobayashiithroughout the 58-day experiment. During early infection (days 15–24), mean abundance in medium high (0.5 fish L−1) and high host density groups (1 and 2 fish L−1) was significantly higher than that in the low host density groups (0.125 and 0.25 fish L−1). At high host density, prevalence increased more rapidly, and the peak prevalence was higher. Fitting of an exponential growth model showed that the population growth rate of the parasite increased with host density. A hypothesis was proposed that higher host density contributed to increased reinfection of detached gyrodactylids. A reinfection experiment was designed to test this hypothesis. Both mean abundance and prevalence at a host density of 1 fish L−1were significantly higher than those at 0.25 fish L−1on days 1 and 3, which suggested that more reinfections ofG. kobyashiioccurred at the higher host density. Density-dependent transmission during the early infection was an important contributor of population growth ofG. kobayashii, as well as density-dependent reinfection of the detached gyrodactylids.
Foreign Occupation and Support for International Cooperation
Authors: Aaskoven Lasse
Published: April 2022

A growing literature investigates how historical state repression affects later political outcomes, but little attention has been given to whether violence during foreign occupation affects support for international cooperation. This article investigates this issue by analyzing the 1972 Danish referendum on membership in the European Economic Community (eec)—an organization seen at the time as being dominated by Germany. The analysis shows that municipalities that experienced more German-inflicted violence during the German occupation of Denmark (1940–1945) in World War II had a higher rate of no votes in this referendum. This effect seems to have worked through increased support for Danish far-left parties that were associated with the Danish resistance movement and that actively used anti-German sentiment in their campaigns against eec membership. The results suggest that foreign-inflicted violence can be a substantial hindrance for popular support for international cooperation and that political parties play an important role in translating historical grievances into mass political behavior.
Norbert Schmitt's essential bookshelf: Formulaic language
Authors: Schmitt Norbert
Published: April 2022

In this series,Language Teachinginvites a well-established scholar to make a personal choice of 12 works that he or she regards as essential reading for those interested in an historical and contemporary overview of the key work in the area chosen for study.
Evaluation of the Early Childhood Music Education project’s influence on the development of 3- to 5-year-old children in Andalusia, Spain
Authors: Thapa Joseph , Rodríguez-Quiles José A.
Published: April 2022

In 2005, the Barenboim-Said Foundation launched the Early Childhood Music Education project in Andalusia (Spain) to promote music education for young children. Ten years later, an initial study was performed to evaluate the influence of the project on the development of the participating children. The results of this study form part of a broader ongoing research project, in collaboration with the University of Seville, aimed at investigating the influence of the Early Childhood Music Education project on general aspects of child development. This study has a quasi-experimental design, framed in Gardner’s Theory of Multiple Intelligences, consisting of an experimental and a control group (n = 1101) and the administration of a questionnaire, adapted to measure and compare means between the two groups, as the sole measurement tool. The results, analysed using an independent samples t-test for the comparison of means and Cohen’s d effect size, reveal statistically significant differences in the means of the dimensions of the experimental and control groups. This confirms the hypothesis that the Early Childhood Music Education project has a positive impact on the different dimensions, in accordance with Gardner’s Theory of Multiple Intelligences.
Dependence comparisons of order statistics in the proportional hazards model
Authors: Kochar Subhash
Published: April 2022

Let $X_1, \ldots, X_n$ be mutually independent exponential random variables with distinct hazard rates $\lambda _1, \ldots, \lambda _n$ and let $Y_1, \ldots, Y_n$ be a random sample from the exponential distribution with hazard rate $\bar \lambda = \sum _{i=1}^{n} \lambda _i/n$. Also let $X_{1:n} \lt \cdots \lt X_{n:n}$ and $Y_{1:n} \lt \cdots \lt Y_{n:n}$ be their associated order statistics. It is proved that for $1\le i \lt j \le n$, the generalized spacing $X_{j:n} - X_{i:n}$ is more dispersed than $Y_{j:n} - Y_{i:n}$ according to dispersive ordering and for $2\le i \le n$, the dependence of $X_{i:n}$ on $X_{1:n}$ is less than that of $Y_{i:n}$ on $Y_{1 :n}$, in the sense of the more stochastically increasing ordering. This dependence result is also extended to the proportional hazard rates (PHR) model. This extends the earlier work of Genest et al. [(2009)]. On the range of heterogeneous samples. Journal of Multivariate Analysis 100: 1587–1592] who proved this result for $i =n$.
Defining the role of the hypothalamic-pituitary-adrenal axis in the relationship between fetal growth and adult cardiometabolic outcomes
Authors: Martin Wrivu N. , Wang Carol A. , Lye Stephen J. , Reynolds Rebecca M. , Matthews Stephen G. , McLaughlin Carly E. , Oldmeadow Christopher , Mori Trevor A. , Beilin Lawrence , Smith Roger , Pennell Craig E.
Published: April 2022

Animal and human data demonstrate independent relationships between fetal growth, hypothalamic-pituitary-adrenal axis function (HPA-A) and adult cardiometabolic outcomes. While the association between fetal growth and adult cardiometabolic outcomes is well-established, the role of the HPA-A in these relationships is unclear. This study aims to determine whether HPA-A function mediates or moderates this relationship. Approximately 2900 pregnant women were recruited between 1989-1991 in the Raine Study. Detailed anthropometric data was collected at birth (per cent optimal birthweight [POBW]). The Trier Social Stress Test was administered to the offspring (Generation 2; Gen2) at 18 years; HPA-A responses were determined (reactive responders [RR], anticipatory responders [AR] and non-responders [NR]). Cardiometabolic parameters (BMI, systolic BP [sBP] and LDL cholesterol) were measured at 20 years. Regression modelling demonstrated linear associations between POBW and BMI and sBP; quadratic associations were observed for LDL cholesterol. For every 10% increase in POBW, there was a 0.54 unit increase in BMI (standard error [SE] 0.15) and a 0.65 unit decrease in sBP (SE 0.34). The interaction between participant’s fetal growth and HPA-A phenotype was strongest for sBP in young adulthood. Interactions for BMI and LDL-C were non-significant. Decomposition of the total effect revealed no causal evidence of mediation or moderation.
Can Policy Responses to Pandemics Reduce Mass Fear?
Authors: Bechtel Michael M. , O’Brochta William , Tavits Margit
Published: April 2022

To successfully address large-scale public health threats such as the novel coronavirus outbreak, policymakers need to limit feelings of fear that threaten social order and political stability. We study how policy responses to an infectious disease affect mass fear using data from a survey experiment conducted on a representative sample of the adult population in the USA (N = 5,461). We find that fear is affected strongly by the final policy outcome, mildly by the severity of the initial outbreak, and minimally by policy response type and rapidity. These results hold across alternative measures of fear and various subgroups of individuals regardless of their level of exposure to coronavirus, knowledge of the virus, and several other theoretically relevant characteristics. Remarkably, despite accumulating evidence of intense partisan conflict over pandemic-related attitudes and behaviors, we show that effective government policy reduces fear among Democrats, Republicans, and Independents alike.
Validierung einer Skala zur Erfassung der depressionsbezogenen Selbstwirksamkeitserwartung (DSW)
Authors: Hesse Savion , Heddaeus Daniela , Steinmann Maya , Wolf Markus , Härter Martin , Watzke Birgit
Published: April 2022

Zusammenfassung. Erste Befunde indizieren, dass Patientinnen und Patienten mit stark ausgeprägter depressionsbezogener Selbstwirksamkeitserwartung bessere Behandlungsergebnisse erzielen und ein geringeres Rückfallrisiko aufweisen. Bisher existieren jedoch nur englischsprachige validierte Instrumente zur Erfassung des Konstrukts. In der vorliegenden Studie erfolgte eine psychometrische Überprüfung der deutschsprachigen Adaptation (DSW-Skala) der Self-efficacy for Managing Depression Scale ( Bush et al., 2001 ) anhand von N = 377 primärärztlichen Patientinnen und Patienten mit depressiver Symptomatik, die zu Behandlungsbeginn sowie nach 3, 6 und 12 Monaten untersucht wurden. Die Ergebnisse belegten eine gute interne Konsistenz der Skala (Cronbachs α ≥ .85) und akzeptable Retest-Reliabilität ( rtt = .63). Die Responsivität der Skala sowie eine vergleichbare Messstruktur über alle Messzeitpunkte hinweg wurden nachgewiesen. Multiple Regressionsanalysen belegten die Vorhersagekraft der DSW-Skala bezüglich der depressiven Symptomatik über 6 Monate. Die Ergebnisse zeigen, dass die DSW-Skala gängige psychometrische Standards erfüllt, sodass die Skala als zeitökonomisches und reliables Messinstrument in der Praxis und Forschung eingesetzt werden kann.
Destabilization of Long‐Lived Hadean Protocrust and the Onset of Pervasive Hydrous Melting at 3.8 Ga
Authors: Drabon Nadja , Byerly Benjamin L. , Byerly Gary R. , Wooden Joseph L. , Wiedenbeck Michael , Valley John W. , Kitajima Kouki , Bauer Ann M. , Lowe Donald R.
Published: April 2022

The nature of Earth's earliest crust and crustal processes remain unresolved questions in Precambrian geology. While some hypotheses suggest that plate tectonics began in the Hadean, others suggest that the Hadean was characterized by long‐lived protocrust and an absence of significant plate tectonic processes. Recently proposed trace‐element proxies for the tectono‐magmatic settings in which zircons formed are a relatively novel tool to understand crustal processes in the past. Here, we present high‐spatial resolution zircon trace and rare earth element geochemical data along with Hf and O isotope data of a new location with Hadean materials, 4.1–3.3 Ga detrital zircons from the 3.31 Ga Green Sandstone Bed, Barberton Greenstone Belt. Together, the hafnium isotope and trace element geochemistry of the detrital zircons record a major transition in crustal processes. Zircons older than 3.8 Ga show evidence for isolated, long‐lived protocrust derived by reworking of relatively undepleted mantle sources with limited remelting of surface‐altered material. After 3.8 Ga, Hf isotopic evidence for this protocrust is muted while relatively juvenile source components for the zircon's parental magmas and flux‐like melting signatures become more prominent. This shift mirrors changes in Hf isotopes and trace element geochemistry in other Archean terranes between ∼3.8 and 3.6 Ga and supports the notion that the global onset of pervasive crustal instability and recycling—A possible sign for mobile‐lid tectonics—Occurred in that time period.
Olivine Morphology and Fabric During Diffusion Creep: Pure Shear Experiments
Authors: Kim N. , Ando A. , Yabe K. , Hiraga T.
Published: April 2022

We deformed aggregates of Fe‐free olivine +20 vol% diopside in pure shear to study olivine grain morphology and fabric during diffusion creep. Samples were each deformed to a strain of around 0.7 at different temperatures and experimental durations, which resulted in different grain sizes among the samples due to grain growth. The sample microstructures were observed from each of the three principal stress directions, which revealed various 3D grain morphologies among the samples. Samples with tabular grains displayed a crystallographic preferred orientation (CPO) in olivine, while samples with weakly anisotropic grains had uniform CPOs. The CPO patterns vary from AG‐type (i.e., a uniaxial [010] concentration in the direction of sample shortening) to A‐type (i.e [010] and [100] concentrations in the directions of sample shortening and stretching, respectively), with intermediate types being the most common. The transition from AG‐ to A‐type fabrics is accompanied by a change from oblate to prolate grain morphologies. We explain the direct correlation between the olivine morphology and fabrics based on preferential grain‐boundary sliding (GBS) at boundaries with fewer steps (ledges). Oblate morphologies with well‐developed grain boundaries oriented parallel to (010) provide easy GBS along (010) and [h0l] planes and directions, respectively, while relatively prolate morphologies with boundaries parallel to (010) that are elongated along [100] provide easy GBS along (010) and [100] planes and directions, respectively. Boundaries form parallel to a particular crystallographic plane through differential grain growth in the directions of the crystallographic axes. Such grain growth causes fabric transitions during diffusion creep.
Calibration and Application of Branched GDGTs to Tibetan Lake Sediments: The Influence of Temperature on the Fall of the Guge Kingdom in Western Tibet, China
Authors: Liang Jie , Guo Yanlong , Richter Nora , Xie Haichao , Vachula Richard S. , Lupien Rachel L. , Zhao Boyang , Wang Mingda , Yao Yuan , Hou Juzhi , Liu Jianbao , Russell James M.
Published: April 2022

Branched glycerol dialkyl glycerol tetraethers (brGDGTs) from lacustrine sediments have been widely used to reconstruct mean annual air temperature (MAAT). Although many proxy calibrations relating brGDGT characteristics have been put forth, these calibrations may produce warm biases when applied to lakes in cold regions. We present an expanded Chinese lake surface sediment brGDGT‐MAAT calibration with 29 new surface samples from cold regions along with 39 previously published from Chinese lakes. We deployed sediment traps in a meromictic lake, Dagze Co, and compared results with previously published data from a dimictic lake, Lake 578 in Greenland, to determine potential seasonal and depth‐dependence of brGDGTs. In the meromictic lake, brGDGTs are primarily produced in the lake bottom water, whereas in the dimictic lake, the brGDGTs are produced throughout the water column and mainly reflect the annual bottom water temperature or mixing season water column temperature. We applied our refined calibration to a sediment core from Western Tibet to examine how fluctuations in temperature influenced the Guge Kingdom over the last 2,000 years. Our record reveals relatively warm temperatures during the Medieval Climate Anomaly, cooling of 2°C to −2°C during the Little Ice Age, warming into the eighteenth century, and stabilization after 1800 CE. The temperature variations coincided with a transition of dynasties in Western Tibet. Temperature sensitivity tests on barley distribution, the principal cultivated cereal in Tibet, suggest that a decline in temperature led to a decreased crop yield that may have factored into the disappearance of the Guge Kingdom.
Regional Map of Molecular Water at High Southern Latitudes on the Moon Using 6 μm Data From the Stratospheric Observatory for Infrared Astronomy
Authors: Honniball C. I. , Lucey P. G. , Arredondo A. , Reach W. T. , Malaret E. R.
Published: April 2022

A map of surface molecular water was derived from long slit spectroscopy of the south polar region of the Moon using the Faint Object infraRed CAmera for the SOFIA Telescope spectrometer on the Stratospheric Observatory for Infrared Astronomy. Mean water abundances detected are about 250 μg/g over that of a mare reference surface at Mare Fecunditatis. Water abundances are locally anticorrelated with temperature. The distribution of water is consistent with derivation of water from pre‐existing hydroxyl subsequently trapped in impact glass, provided hydroxyl increases with latitude as some models and measurements suggest. The detected water cannot be in equilibrium with the exosphere because insufficient water is present in the exosphere to maintain the surface abundance. The data are consistent with a high latitude water‐bearing mineral host that may be a precursor to recently detected high latitude hematite.
Shear‐Wave Velocity Structure Beneath Northeast China From Joint Inversion of Receiver Functions and Rayleigh Wave Phase Velocities: Implications for Intraplate Volcanism
Authors: Tang Zheng , Julià Jordi , Mai P. Martin , Mooney Walter D. , Wu Yanqiang
Published: April 2022

A high‐resolution 3D crustal and upper‐mantle shear‐wave velocity model of Northeast China is established by joint inversion of receiver functions and fundamental‐mode Rayleigh wave phase velocities. The teleseismic data used to calculate receiver functions are collected from 107 CEA permanent sites and 118 NECESSArray portable stations. Rayleigh wave dispersion measurements are extracted from an independent tomographic study. Our model exhibits significant detail in S wave velocity structure. Particularly, we observe a nearly constant S wave velocity of 3.4–3.6 km/s from shallow to deep crystalline crust under the study area, which we attribute to a high thermal gradient. Some modestly positive S wave velocity anomalies in the crust beneath the Songliao basin are interpreted as solidified late‐Mesozoic mafic intrusions. In the upper mantle, we confirm the local presence of low‐velocity zones below the Changbai mountains and Lesser Xing'an mountain range, consistent with asthenospheric mantle upwelling models. Furthermore, moderately low shear velocities imaged beneath the Halaha and Abaga volcanoes indicate possible pathways of magma ascent through the lithospheric mantle from the asthenosphere. At a regional scale, the average lithosphere‐asthenosphere boundary depth increases from ∼70 km under the greater Changbai mountains to ∼100 km below the Songliao basin, and reaches ∼110–120 km beneath the Greater Xing'an mountain range in the west. The conjectured dense mantle lid under the Songliao basin, characterized by fast S velocities, may have prevented sublithospheric melts from migrating to the surface.
Mechanism of cancer stemness maintenance in human liver cancer
Authors: Liang Ning , Yang Tao , Huang Qian , Yu Pengfei , Liu Chaoxu , Chen Liusheng , Wang Qian , Wang Gang , He Xianli
Published: April 2022

Primary liver cancer mainly includes the following four types: hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), hepatoblastoma (HB), and combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CCA). Recent studies have indicated that there are differences in cancer stem cell (CSC) properties among different types of liver cancer. Liver cancer stem cells (LCSCs), also called liver tumor-initiating cells, have been viewed as drivers of tumor initiation and metastasis. Many mechanisms and factors, such as mitophagy, mitochondrial dynamics, epigenetic modifications, the tumor microenvironment, and tumor plasticity, are involved in the regulation of cancer stemness in liver cancer. In this review, we analyze cancer stemness in different liver cancer types. Moreover, we further evaluate the mechanism of cancer stemness maintenance of LCSCs and discuss promising treatments for eradicating LCSCs.
ORP5 promotes tumor metastasis via stabilizing c-Met in renal cell carcinoma
Authors: Song Li , Zhang Lin , Zhou Yun , Shao Xiaotong , Xu Yuting , Pei Dongsheng , Wang Qingling
Published: April 2022

ORP5, a lipid transporter, has been reported to increase the metastasis of several cancers. However, the potential mechanisms of ORP5 in renal cell carcinoma (RCC) remain unclear. In this study, we demonstrated that ORP5 was commonly overexpressed in tumor cells and tissues of RCC, and associated with tumor progression. Overexpression of ORP5 could promote RCC cells migration and invasion. In addition, the results suggested that the expression of ORP5 was favorably associated with c-Met expression, and ORP5 promoted RCC cells metastasis by upregulating c-Met in vitro and in vivo. Mechanistically, ORP5 facilitated the ubiquitination and degradation of c-Cbl (the E3 ligase of c-Met), and thus inhibited c-Met lysosomal degradation, which resulted in the stabilization of c-Met. In general, these findings revealed the role of ORP5 in contributing to tumorigenesis via upregulating c-Met in RCC.
Ferroptosis is involved in PGPS-induced otitis media in C57BL/6 mice
Authors: Yan Bin , Xie Daoli , Wu Yuancheng , Wang Shuli , Zhang Xiaolin , Zhao Tong , Liu Luying , Ma Peng , Li Guqiang , Yang Ying , Zhao Yucheng , Zheng Tihua , Geng Ruishuang , Li Bo , Zheng Qingyin
Published: April 2022

Otitis media (OM) is a common disease that can cause hearing loss in children. Currently, the main clinical treatment for OM is antibiotics, but the overuse of antibiotics might lead to bacterial resistance, which is a worldwide public health challenge. Studying the pathogenesis of OM will help us develop new effective treatments. Ferroptosis is one type of programmed cell death characterized by the occurrence of lipid peroxidation driven by iron ions. Many studies have shown that ferroptosis is associated with infectious diseases. It is presently unclear whether ferroptosis is involved in the pathogenesis of OM. In this study, we explored the relationship between ferroptosis and OM by PGPS-induced OM in C57BL/6 mice and treating the induced OM with ferroptosis inhibitors deferoxamine (DFO), Ferrostatin-1 (Fer-1), and Liperoxstatin-1 (Lip-1). We examined the expression of ferroptosis-related proteins acyl-CoA synthetase long chain family member 4 (ACSL4) and prostaglandin-endoperoxide synthase 2 (Cox2), glutathione peroxidase 4 (GPX4) protein as well as lipid peroxidation markers 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA). The results showed that in PGPS-induced OM model mice, several ferroptosis-related proteins including ACSL4 and Cox2 were up-regulated compared to mice treated with saline. Meanwhile, a ferroptosis-related protein GPX4 was down-regulated upon PGPS treatment. The DFO treatment in PGPS-inoculated mice effectively inhibited the development of OM. The inhibitors treatment caused a significant decrease in the expression of ACSL4, Cox2, 4 HNE, MDA, reduction in free iron. Meanwhile, the ferroptosis inhibitors treatment caused increase in the expression of inflammation-related factors tumor necrosis factor-α (TNF-α) and antioxidant protein GPX4. Our results suggest that there is a crosstalk between ferroptosis signaling pathway and the pathogenesis of OM. Ferroptosis inhibition can alleviate PGPS-induced OM.
Microscale carbon distribution around pores and particulate organic matter varies with soil moisture regime
Authors: Schlüter Steffen , Leuther Frederic , Albrecht Lukas , Hoeschen Carmen , Kilian Rüdiger , Surey Ronny , Mikutta Robert , Kaiser Klaus , Mueller Carsten W. , Vogel Hans-Jörg
Published: April 2022

Soil carbon sequestration arises from the interplay of carbon input and stabilization, which vary in space and time. Assessing the resulting microscale carbon distribution in an intact pore space, however, has so far eluded methodological accessibility. Here, we explore the role of soil moisture regimes in shaping microscale carbon gradients by a novel mapping protocol for particulate organic matter and carbon in the soil matrix based on a combination of Osmium staining, X-ray computed tomography, and machine learning. With three different soil types we show that the moisture regime governs C losses from particulate organic matter and the microscale carbon redistribution and stabilization patterns in the soil matrix. Carbon depletion around pores (aperture > 10 µm) occurs in a much larger soil volume (19–74%) than carbon enrichment around particulate organic matter (1%). Thus, interacting microscale processes shaped by the moisture regime are a decisive factor for overall soil carbon persistence.
Emergence of novel cephalopod gene regulation and expression through large-scale genome reorganization
Authors: Schmidbaur Hannah , Kawaguchi Akane , Clarence Tereza , Fu Xiao , Hoang Oi Pui , Zimmermann Bob , Ritschard Elena A. , Weissenbacher Anton , Foster Jamie S. , Nyholm Spencer V. , Bates Paul A. , Albertin Caroline B. , Tanaka Elly , Simakov Oleg
Published: April 2022

Coleoid cephalopods (squid, cuttlefish, octopus) have the largest nervous system among invertebrates that together with many lineage-specific morphological traits enables complex behaviors. The genomic basis underlying these innovations remains unknown. Using comparative and functional genomics in the model squid Euprymna scolopes, we reveal the unique genomic, topological, and regulatory organization of cephalopod genomes. We show that coleoid cephalopod genomes have been extensively restructured compared to other animals, leading to the emergence of hundreds of tightly linked and evolutionary unique gene clusters (microsyntenies). Such novel microsyntenies correspond to topological compartments with a distinct regulatory structure and contribute to complex expression patterns. In particular, we identify a set of microsyntenies associated with cephalopod innovations (MACIs) broadly enriched in cephalopod nervous system expression. We posit that the emergence of MACIs was instrumental to cephalopod nervous system evolution and propose that microsyntenic profiling will be central to understanding cephalopod innovations.
Single-layer spatial analog meta-processor for imaging processing
Authors: Wang Zhuochao , Hu Guangwei , Wang Xinwei , Ding Xumin , Zhang Kuang , Li Haoyu , Burokur Shah Nawaz , Wu Qun , Liu Jian , Tan Jiubin , Qiu Cheng-Wei
Published: April 2022

Computational meta-optics brings a twist on the accelerating hardware with the benefits of ultrafast speed, ultra-low power consumption, and parallel information processing in versatile applications. Recent advent of metasurfaces have enabled the full manipulation of electromagnetic waves within subwavelength scales, promising the multifunctional, high-throughput, compact and flat optical processors. In this trend, metasurfaces with nonlocality or multi-layer structures are proposed to perform analog optical computations based on Green’s function or Fourier transform, intrinsically constrained by limited operations or large footprints/volume. Here, we showcase a Fourier-based metaprocessor to impart customized highly flexible transfer functions for analog computing upon our single-layer Huygens’ metasurface. Basic mathematical operations, including differentiation and cross-correlation, are performed by directly modulating complex wavefronts in spatial Fourier domain, facilitating edge detection and pattern recognition of various image processing. Our work substantiates an ultracompact and powerful kernel processor, which could find important applications for optical analog computing and image processing.
High-entropy induced a glass-to-glass transition in a metallic glass
Authors: Luan Hengwei , Zhang Xin , Ding Hongyu , Zhang Fei , Luan J. H. , Jiao Z. B. , Yang Yi-Chieh , Bu Hengtong , Wang Ranbin , Gu Jialun , Shao Chunlin , Yu Qing , Shao Yang , Zeng Qiaoshi , Chen Na , Liu C. T. , Yao Ke-Fu
Published: April 2022

Glass-to-glass transitions are useful for us to understand the glass nature, but it remains difficult to tune the metallic glass into significantly different glass states. Here, we have demonstrated that the high-entropy can enhance the degree of disorder in an equiatomic high-entropy metallic glass NbNiZrTiCo and elevate it to a high-energy glass state. An unusual glass-to-glass phase transition is discovered during heating with an enormous heat release even larger than that of the following crystallization at higher temperatures. Dramatic atomic rearrangement with a short- and medium-range ordering is revealed by in-situ synchrotron X-ray diffraction analyses. This glass-to-glass transition leads to a significant improvement in the modulus, hardness, and thermal stability, all of which could promote their applications. Based on the proposed high-entropy effect, two high-entropy metallic glasses are developed and they show similar glass-to-glass transitions. These findings uncover a high-entropy effect in metallic glasses and create a pathway for tuning the glass states and properties.
Single-cell transcriptomics identifies Mcl-1 as a target for senolytic therapy in cancer
Authors: Troiani Martina , Colucci Manuel , D’Ambrosio Mariantonietta , Guccini Ilaria , Pasquini Emiliano , Varesi Angelica , Valdata Aurora , Mosole Simone , Revandkar Ajinkya , Attanasio Giuseppe , Rinaldi Andrea , Rinaldi Anna , Bolis Marco , Cippà Pietro , Alimonti Andrea
Published: April 2022

Cells subjected to treatment with anti-cancer therapies can evade apoptosis through cellular senescence. Persistent senescent tumor cells remain metabolically active, possess a secretory phenotype, and can promote tumor proliferation and metastatic dissemination. Removal of senescent tumor cells (senolytic therapy) has therefore emerged as a promising therapeutic strategy. Here, using single-cell RNA-sequencing, we find that senescent tumor cells rely on the anti-apoptotic gene Mcl-1 for their survival. Mcl-1 is upregulated in senescent tumor cells, including cells expressing low levels of Bcl-2, an established target for senolytic therapy. While treatment with the Bcl-2 inhibitor Navitoclax results in the reduction of metastases in tumor bearing mice, treatment with the Mcl-1 inhibitor S63845 leads to complete elimination of senescent tumor cells and metastases. These findings provide insights on the mechanism by which senescent tumor cells survive and reveal a vulnerability that can be exploited for cancer therapy.
Golgi apparatus-targeted aggregation-induced emission luminogens for effective cancer photodynamic therapy
Authors: Liu Minglun , Chen Yuncong , Guo Yan , Yuan Hao , Cui Tongxiao , Yao Shankun , Jin Suxing , Fan Huanhuan , Wang Chengjun , Xie Ran , He Weijiang , Guo Zijian
Published: April 2022

Golgi apparatus (GA) oxidative stress induced by in situ reactive oxygen species (ROS) could severely damage the morphology and function of GA, which may open up an avenue for effective photodynamic therapy (PDT). However, due to the lack of effective design strategy, photosensitizers (PSs) with specific GA targeting ability are in high demand and yet quite challenging. Herein, we report an aggregation-induced emission luminogen (AIEgen) based PS (TPE-PyT-CPS) that can effectively target the GA via caveolin/raft mediated endocytosis with a Pearson correlation coefficient up to 0.98. Additionally, the introduction of pyrene into TPE-PyT-CPS can reduce the energy gap between the lowest singlet state (S1) and the lowest triplet state (T1) (ΔEST) and exhibits enhanced singlet oxygen generation capability. GA fragmentation and cleavage of GA proteins (p115/GM130) are observed upon light irradiation. Meanwhile, the apoptotic pathway is activated through a crosstalk between GA oxidative stress and mitochondria in HeLa cells. More importantly, GA targeting TPE-T-CPS show better PDT effect than its non-GA-targeting counterpart TPE-PyT-PS, even though they possess very close ROS generation rate. This work provides a strategy for the development of PSs with specific GA targeting ability, which is of great importance for precise and effective PDT.
AI-enabled, implantable, multichannel wireless telemetry for photodynamic therapy
Authors: Kim Woo Seok , Khot M. Ibrahim , Woo Hyun-Myung , Hong Sungcheol , Baek Dong-Hyun , Maisey Thomas , Daniels Brandon , Coletta P. Louise , Yoon Byung-Jun , Jayne David G. , Park Sung Il
Published: April 2022

Photodynamic therapy (PDT) offers several advantages for treating cancers, but its efficacy is highly dependent on light delivery to activate a photosensitizer. Advances in wireless technologies enable remote delivery of light to tumors, but suffer from key limitations, including low levels of tissue penetration and photosensitizer activation. Here, we introduce DeepLabCut (DLC)-informed low-power wireless telemetry with an integrated thermal/light simulation platform that overcomes the above constraints. The simulator produces an optimized combination of wavelengths and light sources, and DLC-assisted wireless telemetry uses the parameters from the simulator to enable adequate illumination of tumors through high-throughput (<20 mice) and multi-wavelength operation. Together, they establish a range of guidelines for effective PDT regimen design. In vivo Hypericin and Foscan mediated PDT, using cancer xenograft models, demonstrates substantial suppression of tumor growth, warranting further investigation in research and/or clinical settings.
Effect of electrode and oxide properties on the filament kinetics during electroforming in metal-oxide-based memories
Authors: Zhang Kena , Ren Yao , Ganesh Panchapakesan , Cao Ye
Published: April 2022

We developed a physical model to fundamentally understand the conductive filament (CF) formation and growth behavior in the switching layer during electroforming process in the metal-oxide-based resistive random-access memories (RRAM). The effects of the electrode and oxide layer properties on the CF morphology evolution, current-voltage characteristic, local temperature, and electrical potential distribution have been systematically explored. It is found that choosing active electrodes with lower oxygen vacancy formation energy and oxides with small Lorenz number (ratio of thermal and electrical conductivity) enables CF formation at a smaller electroforming voltage and creates a CF with more homogeneous morphology. This work advances our understanding of the kinetic behaviors of the CF formation and growth during the electroforming process and could potentially guide the oxide and electrode materials selection to realize a more stable and functional RRAM.
Snapshots of actin and tubulin folding inside the TRiC chaperonin
Authors: Kelly John J. , Tranter Dale , Pardon Els , Chi Gamma , Kramer Holger , Happonen Lotta , Knee Kelly M. , Janz Jay M. , Steyaert Jan , Bulawa Christine , Paavilainen Ville O. , Huiskonen Juha T. , Yue Wyatt W.
Published: April 2022

The integrity of a cell’s proteome depends on correct folding of polypeptides by chaperonins. The chaperonin TCP-1 ring complex (TRiC) acts as obligate folder for >10% of cytosolic proteins, including he cytoskeletal proteins actin and tubulin. Although its architecture and how it recognizes folding substrates are emerging from structural studies, the subsequent fate of substrates inside the TRiC chamber is not defined. We trapped endogenous human TRiC with substrates (actin, tubulin) and cochaperone (PhLP2A) at different folding stages, for structure determination by cryo-EM. The already-folded regions of client proteins are anchored at the chamber wall, positioning unstructured regions toward the central space to achieve their native fold. Substrates engage with different sections of the chamber during the folding cycle, coupled to TRiC open-and-close transitions. Further, the cochaperone PhLP2A modulates folding, acting as a molecular strut between substrate and TRiC chamber. Our structural snapshots piece together an emerging model of client protein folding within TRiC.
Comparative analysis of long noncoding RNA and mRNA expression provides insights into adaptation to hypoxia in Tibetan sheep
Authors: Wang Fan , Liu Jianbin , Zeng Qiaoying , Zhuoga Deqing
Published: April 2022

Tibetan sheep have lived on the Qinghai-Tibetan Plateau for thousands of years and have good adaptability to the hypoxic environment and strong disease resistance. However, the molecular mechanism by which Tibetan sheep adapt to this extreme environment, especially the role of genetic regulation, is still unknown. Emerging evidence suggests that long noncoding RNAs (lncRNAs) participate in the regulation of a diverse range of biological processes. To explore the potential lncRNAs involved in the adaptation to high-altitude hypoxia of Tibetan sheep, we analysed the expression profile of lncRNAs and mRNAs in the liver and lung tissues of sheep using comparative transcriptome analysis between four Tibetan sheep populations (high altitude) and one Hu sheep population (low altitude). The results showed a total of 7848 differentially expressed (DE) lncRNA transcripts, and 22,971 DE mRNA transcripts were detected by pairwise comparison. The expression patterns of selected mRNAs and lncRNAs were validated by qRT-PCR, and the results correlated well with the transcriptome data. Moreover, the functional annotation analysis based on the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases showed that DE mRNAs and the target genes of the lncRNAs were significantly enriched in organ morphogenesis, response to stimulus, haem binding, the immune system, arginine and proline metabolism, and fatty acid biosynthesis. The prediction of mRNA–mRNA and lncRNA–mRNA interaction networks further revealed transcripts potentially involved in adaptation to high-altitude hypoxia, and the hub genes DDX24, PDCD11, EIF4A3, NDUFA11, SART1, PRPF8 and TCONS_00306477, TCONS_00306029, TCONS_00139593, TCONS_00293272, and TCONS_00313398 were selected. Additionally, a set of target genes, PIK3R1, IGF1R, FZD6, IFNB2, ATF3, MB, CYP2B4, PSMD13, and TGFB1, were also identified as candidate genes associated with high-altitude hypoxia adaptation. In conclusion, a collection of novel expressed lncRNAs, a set of target genes and biological pathways known to be relevant for altitude adaptation were identified by comparative transcriptome analysis between Tibetan sheep and Hu sheep. Our results are the first to identify the characterization and expression profile of lncRNAs between Tibetan sheep and Hu sheep and provide insights into the genetic regulation mechanisms by which Tibetan sheep adapt to high-altitude hypoxic environments.
Evaluating the job shop scheduling problem on a D-wave quantum annealer
Authors: Carugno Costantino , Ferrari Dacrema Maurizio , Cremonesi Paolo
Published: April 2022

Job Shop Scheduling is a combinatorial optimization problem of particular importance for production environments where the goal is to complete a production task in the shortest possible time given limitations in the resources available. Due to its computational complexity it quickly becomes intractable for problems of interesting size. The emerging technology of Quantum Annealing provides an alternative computational architecture that promises improved scalability and solution quality. However, several limitations as well as open research questions exist in this relatively new and rapidly developing technology. This paper studies the application of quantum annealing to solve the job shop scheduling problem, describing each step required from the problem formulation to the fine-tuning of the quantum annealer and compares the solution quality with various classical solvers. Particular attention is devoted to aspects that are often overlooked, such as the computational cost of representing the problem in the formulation required by the quantum annealer, the relative qubits requirements and how to mitigate chain breaks. Furthermore, the impact of advanced tools such as reverse annealing is presented and its effectiveness discussed. The results indicate several challenges emerging at various stages of the experimental pipeline which bring forward important research questions and directions of improvement.
Inhibitory effect of concomitantly administered rabies immunoglobulins on the immunogenicity of commercial and candidate human rabies vaccines in hamsters
Authors: Bernard Marie-Clotilde , Boudet Florence , Pineda-Peña Andrea-Clemencia , Guinet-Morlot Françoise
Published: April 2022

The World Health Organization protocol for rabies post-exposure prophylaxis (PEP) recommends extensive wound washing, immediate vaccination, and administration of rabies immunoglobulin (RIG) in severe category III exposures. Some studies have shown that RIG can interfere with rabies vaccine immunogenicity to some extent. We investigated the interference of RIG on a next generation highly purified Vero cell rabies vaccine candidate (PVRV-NG) versus standard-of-care vaccines in a previously described hamster model. The interference of either human (h) or equine (e) RIG on the immune response elicited by PVRV-NG, Verorab® (purified Vero cell rabies vaccine, PVRV), and Imovax® Rabies (human diploid cell rabies vaccine; HDCV) was evaluated using the 4-dose Essen PEP regimen. The anti-rabies seroneutralizing titers and specific serum IgM titers were measured by fluorescent antibody virus neutralization test and enzyme-linked immunosorbent assay, respectively, for the vaccines administered with or without RIG. The RIG interference on PVRV-NG, observed transiently at Day 7, was similar to that on PVRV and tended to be lower than that on HDCV using both read-outs. In summary, the results generated in the hamster model showed that RIG induced similar or less interference on PVRV-NG than the standard-of-care vaccines.
Data-driven computational intelligence applied to dengue outbreak forecasting: a case study at the scale of the city of Natal, RN-Brazil
Authors: Sanchez-Gendriz Ignacio , de Souza Gustavo Fontoura , de Andrade Ion G. M. , Neto Adrião Duarte Doria , de Medeiros Tavares Alessandre , Barros Daniele M. S. , de Morais Antonio Higor Freire , Galvão-Lima Leonardo J. , de Medeiros Valentim Ricardo Alexsandro
Published: April 2022

Dengue is recognized as a health problem that causes significant socioeconomic impacts throughout the world, affecting millions of people each year. A commonly used method for monitoring the dengue vector is to count the eggs that Aedes aegypti mosquitoes have laid in spatially distributed ovitraps. Given this approach, the present study uses a database collected from 397 ovitraps allocated across the city of Natal, RN—Brazil. The Egg Density Index for each neighborhood was computed weekly, over four complete years (from 2016 to 2019), and simultaneously analyzed with the dengue case incidence. Our results illustrate that the incidence of dengue is related to the socioeconomic level of the neighborhoods in the city of Natal. A deep learning algorithm was used to predict future dengue case incidence, either based on the previous weeks of dengue incidence or the number of eggs present in the ovitraps. The analysis reveals that ovitrap data allows earlier prediction (four to six weeks) compared to dengue incidence itself (one week). Therefore, the results validate that the quantification of Aedes aegypti eggs can be valuable for the early planning of public health interventions.
Tuning nanowire lasers via hybridization with two-dimensional materials
Authors: Eobaldt Edwin , Vitale Francesco , Zapf Maximilian , Lapteva Margarita , Hamzayev Tarlan , Gan Ziyang , Najafidehaghani Emad , Neumann Christof , George Antony , Turchanin Andrey , Soavi Giancarlo , Ronning Carsten
Published: April 2022

Hybrid structures composed of 1D nanowires and layered 2D materials are promising building blocks for advanced optoelectronic devices and they provide new knobs for the control of lasing at the nanoscale.
Water-responsive shape memory thermoplastic polyurethane scaffolds triggered at body temperature for bone defect repair
Authors: Shuai Cijun , Wang Zhicheng , Peng Shuping , Shuai Yang , Chen Yanwen , Zeng Da , Feng Pei
Published: April 2022

The water-responsive shape memory mechanism model of a TPU specimen was proposed, in which the reversible hydrogen bonding between the water molecules and hard segments formed after wetting and disappeared after drying.
Synergetic effect between Pd2+ and Ir4+ species promoting direct ethane dehydrogenation into ethylene over bimetallic PdIr/AC catalysts
Authors: Zhang Ling , Sun Jikai , Jiang Shuchao , He Huijie , Ren Guoqing , Zhai Dong , Tu Rui , Zhai Shengliang , Yu Tie
Published: April 2022

This work reported the efficient Pd–Ir pairs on the Pd7Ir2/AC-B catalyst achieved a TOF (C2H4) of 756.6 h−1 at 500 °C, and the direct ethane dehydrogenation (EDH) rationale and deactivation mechanism were proposed.
Effects of natural dihydrochalcones in sweet tea (Lithocarpus polystachyus) on diabetes: a systematical review and meta-analysis of animal studies
Authors: Chen Xue-Min , Yang Wei-Qi , Wang Xue , Chen Chong , Qian Zheng-Ming , Wang Shu-Mei , Tang Dan
Published: April 2022

Sweet tea (Lithocarpus polystachyus Rehd.), a natural functional food highly rich in dihydrochalcones including trilobatin, phlorizin and phloretin, is reported to possess numerous biological activities especially for treating diabetes.
Lupeol inhibits the proliferation and migration of MDA-MB-231 breast cancer cells via a novel crosstalk mechanism between autophagy and the EMT
Authors: Zhang Xin , Gao Zhanwang , Chen Kehan , Zhuo Qingyuan , Chen Meixian , Wang Jiansong , Lai Xiaoping , Wang Lingli
Published: April 2022

Lupeol could inhibit TNBC cells by inducing autophagy, and additionally suppressing the tumor migration and invasion.
Epitaxial growth of structure-tunable ZnO/ZnS core/shell nanowire arrays using HfO2 as the buffer layer
Authors: Ru Fan , Xia Jing , Li Xuanze , Liu Pei , Qiao Peiyu , Li Yuye , Cao Jianyu , Tian Lifeng , Zhang Wenjun , Meng Xiang-Min
Published: April 2022

A two-step thermal deposition method is developed to synthesize structure-tunable and single-crystalline ZnO/ZnS core/shell nanowire arrays using HfO2 as buffer layer, which can promote fabricating high-quality heterostructure based nanodevices.
Conformationally rigid, π-extended annulated porphyrinoids derived from the naphthobipyrrole motif
Authors: Shetti Vijayendra S.
Published: April 2022

This review article provides an up-to-date account of the developments in the field of naphthobipyrrole-derived annulated porphyrinoid chemistry.
Low-temperature water-assisted crystallization approach to MOF@TiO2 core–shell nanostructures for efficient dye removal
Authors: Bao Shouxin , Lv Mingyang , Zhao Chen , She Ping , Lei Zhenyu , Song Xiaowei , Jia Mingjun
Published: April 2022

A mild crystallization approach to MOF@TiO2 core–shell nanostructures for the efficient adsorption and photodegradation of anionic dyes.