bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on the Dynamic Stress Tracking Test Period of the Bogie Frame for Metro Vehicle
Authors: Li Cen , Yin Yi , Qian Nan , Wang Binjie , Sun Shouguang
Published: April 2024

Dynamic stress is one of the key indicators reflecting the fatigue characteristics of metro bogie frames. Considering the test costs, operation safety, and other factors, it is impossible to record all the dynamic stress data for the whole service period in the tracking test. Therefore, the overall stress spectrum is statistically deduced based on limited dynamic stress data samples, which can not only provide a basis for the fatigue reliability research of the bogie frame, but also save costs. In this paper, the typical fatigue control points in different areas of the frame with large equivalent stress are selected for research. The daily measured stress spectrum samples are obtained through the rainflow counting method, and the statistical stress spectrum is then compiled. Weibull distribution fitting of the stress spectrum is carried out to obtain the scale and shape parameter samples for different fatigue control parts. After sampling of the obtained parameter samples and conducting variance homogeneity tests as well as t-tests, the minimum sample size representing the overall distribution of the interval is obtained. Therefore, the shortest tracking test period reflecting the overall stress distribution of typical fatigue control parts can be obtained.
Multi-year study of environmental stability of Ti3C2Tx MXene films
Authors: Lee Asaph , Shekhirev Mikhail , Anayee Mark , Gogotsi Yury
Published: April 2024

MXenes are a family of two-dimensional (2D) carbides and nitrides with extraordinary electrical, optical, chemical, and electrochemical properties. There is a perception that MXenes are unstable and degrade quickly, limiting potential applications and requiring specific storage conditions to last for a long time. It primarily comes from studies on delaminated MXenes flakes in dilute dispersions and samples from defective or non-stoichiometric precursors when MXene research was in its infancy. In the years since then, significant developments in synthesis, processing, and understanding of their chemistry have led to dramatic increases in the environmental stability of many MXenes, especially the widely studied Ti3C2Tx. However, previous studies focused primarily on MXene dispersion, while in the majority of applications, MXenes are processed into films soon after synthesis. Herein, we analyze Ti3C2Tx free-standing films aged from 4 to 10 years through structural and morphological characterization along with electrical conductivity measurements to reveal the effect, or lack thereof, of prolonged storage under ambient conditions. Further, we show that the decrease in electronic conductivity over time is caused mainly by water uptake by the hydrophilic surfaces of MXenes, which can be removed by vacuum annealing. As a result, the conductivity of the films can be partially or almost completely recovered.
Hostility on Twitter in the aftermath of terror attacks
Authors: Czymara Christian S. , Gorodzeisky Anastasia
Published: April 2024

This study investigates the relationship between major Jihadist terror attacks and manifestations of ethno-religious hostility on social media. Analyzing approximately 4.5 million time-stamped Tweets from 1.2 million users across five European countries, the study focuses on content discussing migration and related topics in the weeks before and after ten significant terror attacks. The findings show a notable and robust increase in hostile Tweets after an attack. An interrupted time series analysis demonstrates a 10% point surge at the time of the attack, followed by a gradual decline. Accordingly, the impact of such attacks on online hostility diminishes approximately seven days after the event. Further analyses reveal that while attacks have the strongest effect on Tweets about Muslims and Islam, the attacks also increase hostility in Tweets about migration in general. We find that the overall attack effect is driven by both intra-user changes in Tweeting and changes in the composition of users posting after an attack. The findings underscore the importance of understanding the interplay between terrorist events and online discourse, shedding light on the dynamics of ethno-religious hostility in the digital realm.
Hydrogeochemical characterization and water quality evaluation for drinking and irrigation purposes of coastal aquifers of Middle Andaman
Authors: Kumar Pardeep , Vishwakarma Chandrashekhar Azad , Singh Priyadarshini , asthana Harshita , Rena Vikas , mate Carolyne chinneikim , Mukherjee Saumitra
Published: April 2024

A comprehensive study to characterize the hydrogeochemistry of the region and the impact of saltwater intrusion on groundwater was conducted along the eastern coast of Middle Andaman of Andaman and Nicobar (A&N) Islands. The escalating population growth and intensified tourism activities have resulted in the over-extraction of groundwater. Seismic activities led to the opening of lineaments to the sea and the dissolution of limestone in the influence of seawater. 24 groundwater samples and 1 reference sample from sea were taken from various locations of middle Andaman. The analysis involved the determination of major cations, anions, and heavy metals using Inductively Coupled Plasma Optical Emission spectroscopy (ICP), spectrophotometry, and flame photometry. Furthermore, X-ray diffraction analysis, binary diagrams, Chloro-alkaline indices (CAI), Gibbs Plot, correlation matrix, Piper plot, Chadha’s plot and Principal Component Analysis (PCA) to the major ions data indicated rock-water interactions, strong correlations among alkali and alkaline earth metals, and interactions between seawater and carbonate minerals respectively. The water quality index indicated “very poor to unsuitable for drinking purposes” in 24% of the samples. Additionally, indices for irrigation suitability; total hardness (TH), residual sodium carbonate (RSC), and Magnesium adsorption ratio (MAR) were found to be detrimental for irrigation in 80%, 08%, and 12% of the water samples, respectively. These results highlight the importance of implementing effective water resource management techniques, such as groundwater extraction rates, adopting appropriate water treatment technologies to mitigate the adverse impacts of heavy metals, saltwater intrusion and maintain water quality for human consumption and agricultural use in the region.
Which Explanation Should be Selected: A Method Agnostic Model Class Reliance Explanation for Model and Explanation Multiplicity
Authors: Gunasekaran Abirami , Mistry Pritesh , Chen Minsi
Published: April 2024

Feature importance techniques offer valuable insights into machine learning (ML) models by conducting quantitative assessments of the individual contributions of variables to the model’s predictive outcomes. This quantification differs across various explanation methods and multiple almost equally accurate models (Rashomon models), creating explanation and model multiplicities. This resulted in a novel framework called method agnostic model class reliance range (MAMCR) for identifying a unified explanation across methods for multiple models. This consensus explanation provides each feature’s importance range for a class of models. Using state-of-the-art feature importance methods, experiments on popular machine learning datasets are conducted with a$$\varepsilon -$$ε-threshold value of 0.1. The dataset-specific Rashomon set with 200 models, and the prediction accuracy of concerned reference models ($$m^*$$m∗) have produced encouraging results in obtaining a consensus model reliance explanation that is consistent across multiple methods. The experiment results ensure whether the prediction accuracy level of models has an impact on the importance range estimation of features. Also, the order of features suggested by MAMCR leads to better performance of models consistently in all the experimented datasets, than the state-of-the-art methods.
ISO 59000 Standards for the Circular Economy: a Call for Accuracy
Authors: Heras-Saizarbitoria Iñaki , Boiral Olivier , Testa Francesco
Published: April 2024

With the expressed aim of reducing uncertainty and lack of precision about the Circular Economy paradigm, several standards are being proposed by standard-setting bodies. The world’s most prominent body — the International Organization for Standardization — is developing the ISO 59000 family of standards to establish a common language and conceptual framework for the Circular Economy. In the light of the vigorous debate in the scientific literature about the Circular Economy, as well as criticism of the concepts involved, this perspective article calls for more precision in the definition of this type of standard.
A novel trusted hardware-based scalable security framework for IoT edge devices
Authors: Khan Mohd , Hatami Mohsen , Zhao Wenfeng , Chen Yu
Published: April 2024

The Internet of Things (IoT) devices are pervasively deployed and embedded into our daily lives. Over several years, the massive assimilation of IoT devices has given rise to smart cities, smart factories, smart farms, etc. While IoTs can collect immense amounts of user and environmental information, the lack of adequate security measures is among the major concerns about information security and privacy. With the ever-increasing presence of IoTs, information flow between IoT devices in a single or multi-layered network is becoming increasingly vulnerable to attacks. Although several software-based solutions have been developed over the years that improve the security of resource-constrained IoT devices, there are limited efforts on hardware-oriented IoT security solutions. This paper proposes a Trusted HArdware-based Scalable Secure Architecture (THASSA) for IoT Edge systems. Leveraging standard cryptographic algorithms, THASSA provides a secure mechanism for data transfer and off-loads cryptography operations to trusted hardware. The modularized THASSA architecture allows devices to be added or removed without user intervention. Also, THASSA could be scaled to multiple subsystems using multiple trusted hardware to form IoT clusters with secure data path(s) for mission-critical applications. An experimental study has verified the correctness and effectiveness of THASSA.
Survival of the Greenest
Authors: Lebdioui Amir
Published: April 2024

The pathways to economic development are changing. Environmental sustainability is no longer a choice but a necessity to maintain a competitive edge in the global economy. Just like in nature, where survival hinges on adaptation, this Element shows how nations adjust to -and take advantage of- the new dynamics of structural transformation induced by climate change.
First, by analysing the uneven industrial geography of decarbonisation, the inadequate state of climate financing and rise of green protectionism, it demonstrates that the low-carbon economy stands to increase economic disparities between nations, unless action is taken. Then, by examining green industrial policies and their varied success, it explains how governments can still join the green industrialisation race. Finally, it examines how to adapt green industrial policy to different starting points, market sizes, productive structures, state-business relations dynamics, institutional layouts, and ecological contexts. This title is also available as Open Access on Cambridge Core.
Understanding Ionospheric and Geomagnetic Effects on Residual Biases in Radio Occultation Data for Stratospheric Climate Monitoring
Authors: Liu Congliang , Danzer Julia , Kirchengast Gottfried , Haas Stephanie J. , Proschek Veronika , Schwaerz Marc , Sun Yueqiang , Wang Xi
Published: April 2024

Higher‐order residual ionospheric errors in Global Navigation Satellite System (GNSS) radio occultation (RO) data can induce a systematic residual ionospheric bias (RIB) in RO bending angles, which can impact stratospheric climate monitoring. The main RIB causes are the ray path splitting of dual‐frequency GNSS signals, the electron density distribution along the ray path and at the RO receiver location, and the geomagnetic field. In this study, we investigate the ionospheric and geomagnetic effects on RO‐retrieved stratospheric bending angle and temperature profiles by inspecting the kappa and bi‐local RIB correction methods, the current state‐of‐the‐art methods, using multiple RO satellite mission data in different ionospheric and geomagnetic conditions. We find that, globally, the layer mean/median RIBs of the kappa and bi‐local correction methods exhibit similar behaviors for different RO missions: the estimated bending angle RIBs reach about −0.025/−0.01 and −0.024/−0.008 μrad in the upper (40–45 km) and lower (30–35 km) stratosphere, respectively, while the temperature RIBs reach about −1.0/−0.3 and −0.2/−0.1 K in these layers. However, in the equatorial day time region, the RIB statistics of the mission results diverge. Both the kappa and bi‐local RIBs increase in magnitude with increasing ionization and geomagnetic field strength but show no increase with an increasing degree of ionospheric asymmetry. Overall, the more refined bi‐local method has higher capacity than the comparatively simple kappa method to represent the variability of the ionospheric and geomagnetic conditions that affect RO events. This is important for regional‐scale studies, where the geomagnetic term can be of key relevance.
Statistical Properties of Ion Upflow Associated With Subauroral Ion Drift (SAID) in the Northern and Southern Hemispheres
Authors: Zhang Qiang , Han De‐Sheng , Wang Zhi‐Wei , Teng Shang‐Chun , Ma Yu‐Zhang
Published: April 2024

The ion upflow has great significance for the transport and exchange of particles during magnetosphere‐ionosphere coupling process. Previous studies focus on the ion upflow in the polar region, and find that ion upflow has hemispheric asymmetries. In subauroral region, the ion upflow is closely related with subauroral ion drift (SAID). However, the characteristics of ion upflow associated with SAID in both northern and southern hemispheres are still unknown. Based on the observation of DMSP satellites F16‐F18 from 2010 to 2020, we investigate the north‐south hemisphere distributions of ion upflow associated with SAID during quiet and disturbed time. The ion upflow rate presents localized features in both hemispheres. The ion upflow rate in the southern hemisphere is slightly higher/lower than that in the northern hemisphere before/after 1900 MLT. The ion upflow velocity in the southern hemisphere shows a clear dependence on magnetic local time (MLT). Furthermore, We find that the hemispheric asymmetry of ion upflow is closely related to the asymmetric configuration of the ionospheric parameters such as plasma density, conductance and solar elevation angle during magnetosphere‐ionosphere coupling process. The result also indicates that SAID and sunlight condition play important roles in the ion upflow in subauroral region.
Modeling the Impact of Secondary Ice Production on the Charge Structure of a Mesoscale Convective System
Authors: Huang Shiye , Jing Xiaoqin , Yang Jing , Zhang Qilin , Guo Fengxia , Wang Zhien , Chen Baojun
Published: April 2024

The charge structure in thunderstorms may be strongly affected by different secondary ice production (SIP) processes, but has not been well understood. In this study, the impacts of three SIP mechanisms on microphysics and electrification in a squall line are investigated using model simulation, including the rime‐splintering, ice‐ice collisional breakup, and shattering of freezing drops. The parameterization of the three SIP mechanisms, a noninductive and an inductive charging parameterization are implemented in the spectral bin microphysics. The results show that with SIP processes included, the modeled radar reflectivity is more consistent with observation. It is found that both the mass and concentrations of graupel/hail are enhanced by SIP processes, while the diameter decreases. The mixing ratio of ice/snow decreases due to the rime‐splintering, and increases in mixing ratio are due to the shattering of freezing drops. Particle charging is significantly affected by SIP, leading to a dipole structure of the total charge density, which includes a lower negative and an upper positive charge region. With both the noninductive and inductive charging considered, the charge carried by graupel/hail changes from negative to a bipolar structure, and the charge sign carried by ice/snow is inverted due to the SIP. The modeled lightning activity is enhanced by implementing all three SIP processes, while if only considering the rime‐splintering process, the flash rate would be suppressed. The insights obtained from this study highlight the importance of considering different mechanisms of SIP in modeling the charge structure and lightning activity in thunderstorms.
Surface and Atmospheric Heating Responses to Spectrally Resolved Albedo of Frozen and Liquid Water Surfaces
Authors: Tolento Juan P. , Zender Charles S. , Whicker‐Clarke Chloe A.
Published: April 2024

Multiple Earth system models (ESMs) discretize surface albedo into two semi‐broadbands comprising the UV/visible and near‐infrared (NIR) wavelengths. Here, we use an offline single‐column radiative transfer model to investigate the radiative effects of spectrally resolving the surface albedo. We use the Snow, Ice, and Aerosol Radiative model, extended to simulate liquid water, to calculate snow, ice, and liquid water albedo. We flux‐weight the hyperspectral albedo into the coarser spectral bands used by the atmospheric shortwave radiative transfer model. We establish representative atmospheric profiles for the three surface types and compare their shortwave fluxes and atmospheric warming rates with the spectrally resolved albedo to those calculated with the semi‐broadband approximation. Spectrally resolved surface albedo over snow and ice reduces atmospheric warming by darkening the albedo of NIR bands, correcting the too‐strong surface absorption in visible bands, and too‐weak surface absorption in shortwave infrared bands caused by the semi‐broadband approximation. We explore the effects on surface and atmospheric warming rates of varying solar zenith angle, cloud cover, relative humidity, and snow grain/air bubble radii. The semi‐broadband albedo biases can exceed 10% and 2% for the surface and atmospheric net flux respectively, being particularly strong under conditions which alter the distributions of surface insolation (i.e., cloud cover or increased atmospheric water vapor). These results show that transmitting a higher resolution spectral radiation field between the atmosphere and surface reduces biases in surface absorption and atmospheric heating present in ESMs that currently use the semi‐broadband approximation.
Reconstructing Balloon‐Observed Gravity Wave Momentum Fluxes Using Machine Learning and Input From ERA5
Authors: Has Sothea , Plougonven Riwal , Fischer Aurélie , Rani Raj , Lott Francois , Hertzog Albert , Podglajen Aurélien , Corcos Milena
Published: April 2024

Global atmospheric models rely on parameterizations to capture the effects of gravity waves (GWs) on middle atmosphere circulation. As they propagate upwards from the troposphere, the momentum fluxes associated with these waves represent a crucial yet insufficiently constrained component. The present study employs three tree‐based ensemble machine learning (ML) techniques to probe the relationship between large‐scale flow and small‐scale GWs within the tropical lower stratosphere. The measurements collected by eight superpressure balloons from the Strateole 2 campaign, comprising a cumulative observation period of 680 days, provide valuable estimates of the gravity wave momentum fluxes (GWMFs). Multiple explanatory variables, including total precipitation, wind, and temperature, were interpolated from the ERA5 reanalysis at each balloon's location. The ML methods are trained on data from seven balloons and subsequently utilized to estimate reference GWMFs of the remaining balloon. We observed that parts of the GW signal are successfully reconstructed, with correlations typically around 0.54 and exceeding 0.70 for certain balloons. The models show significantly different performances from one balloon to another, whereas they show rather comparable performances for any given balloon. In other words, limitations from training data are a stronger constraint than the choice of the ML method. The most informative inputs generally include precipitation and winds near the balloons' level. However, different models highlight different informative variables, making physical interpretation uncertain. This study also discusses potential limitations, including the intermittent nature of GWMFs and data scarcity, providing insights into the challenges and opportunities for advancing our understanding of these atmospheric phenomena.
Solar Influences on Winter Atmospheric Circulation Over the Ural, North Atlantic and North Pacific Regions: Pitchfork‐Like Relationships
Authors: Li Dongdong , Zhang Renhe , Zhang Ruonan , Huang Jianping
Published: April 2024

Li's previous study found a one‐to‐two correspondence relationship between the total solar irradiance (TSI) and monthly anomalies of the Ural atmospheric circulation during winter months. This relationship roughly meets the so‐called supercritical pitchfork bifurcation model, hence termed a pitchfork‐like (PL) relationship. Here, we extend this study and provide more evidence to support previous findings. By analyzing data from 192 winter months and estimating the joint probability density function, we find that over the Ural, North Atlantic, and North Pacific regions, there are all PL relationships between the TSI and geopotential height anomalies at pressure levels no higher than 700 hPa. When the TSI gradually decreases and passes a critical threshold of 1360.9 W m−2, the preferred circulation patterns undergo a regime transition from one regime to two others. When TSI < 1360.9 W m−2, positive and negative geopotential height anomalies occur at nearly equal frequencies within the same TSI range. This quantitative relation is met in almost the whole troposphere in each region. We suggest that the occurrence of PL relationships may be associated with the interaction between the westerly flow and topographic barriers; The decrease in TSI can regulate this interaction by reducing the stability of background westerly flow over all three regions, via increasing the land‐ocean thermal contrast and altering the planetary wavenumber‐2 wave at the mid‐high latitudes. Our work highlights the same quantitative relation between the TSI and the monthly mean geopotential height anomalies of three regions in winter, which has important implications for seasonal climate prediction.
Projections of Peak Water Timing From the East Rongbuk Glacier, Mt. Everest, Using a Higher‐Order Ice Flow Model
Authors: Zhang Tong , Wang Yuzhe , Leng Wei , Zhao Hongyu , Colgan Willliam , Wang Che , Ding Minghu , Sun Weijun , Yang Wei , Li Xin , Ren Jiawen , Xiao Cunde
Published: April 2024

In this study, we apply a three‐dimensional (3D) thermomechanically coupled higher‐order ice flow model to simulate the East Rongbuk Glacier (ERG), Mt. Everest. We first diagnostically investigate its present‐day ice dynamic features in 2009 and then prognostically simulate the glacier during the time period 2010–2100. The ice flow model is initialized based on a Robin‐type inversion method by conducting six sensitivity experiments relating to glacier thermal boundary conditions. We apply two different surface mass balance parameterizations in the model, and both of them can reproduce the observed ice volume loss (around 0.1 km3) during 2010–2020. We find that ERG is likely to experience maximum meltwater runoff at the year 2030 under the SSP‐126 scenario, while under SSP‐370 and ‐585 scenarios, the peak water will both likely occur at around 2060. The ice dynamics may contribute more to ice loss as climate warms in time.
Middle-of-the-Road Mountains Form the Best Carbon Sinks
Authors: Kernan Martin
Published: April 2024

Silicate rock weathering has a sweet spot: erosion that isn’t too fast or too slow.
Machine Learning Predicts Earthquakes in the Continuum Model of a Rate‐And‐State Fault With Frictional Heterogeneities
Authors: Norisugi Reiju , Kaneko Yoshihiro , Rouet‐Leduc Bertrand
Published: April 2024

Machine learning (ML) has been used to study the predictability of laboratory earthquakes. However, the question remains whether or not this approach can be applied in a tectonic setting where one may have to rely on sparse earthquake catalogs, and where important timescales vary by orders of magnitude. Here, we apply ML to a synthetic seismicity catalog, generated by continuum models of a rate‐and‐state fault with frictional heterogeneities, which contains foreshocks, mainshocks, and aftershocks that nucleate in a similar manner. We develop a network representation of the seismicity catalog to calculate input features and find that the trained ML model can predict the time‐to‐mainshock with great accuracy, from the scale of decades to minutes. Our results offer clues as to why ML can predict laboratory earthquakes and how the developed approach could be applied to more complex problems where multiple timescales are at play.
In-silico prediction of dislodgeable foliar residues and regulatory implications for plant protection products
Authors: Shi Yi , Choudhury Kanak , Sopko Xiaoyi , Adham Sarah , Chikwana Edward
Published: April 2024

Background

When experimentally determined dislodgeable foliar residue (DFR) values are not available, regulatory agencies use conservative default DFR values as a first-tier approach to assess post-application dermal exposures to plant protection products (PPPs). These default values are based on a limited set of field studies, are very conservative, and potentially overestimate exposures from DFRs.

Objective

Use Random Forest to develop classification and regression-type ensemble models to predict DFR values after last application (DFR0) by considering experimentally-based variability due to differences in physical and chemical properties of PPPs, agronomic practices, crop type, and climatic conditions.

Methods

Random Forest algorithm was used to develop in-silico ensemble DFR0 prediction models using more than 100 DFR studies from Corteva AgriscienceTM. Several variables related to the active ingredient (a.i.) that was applied, crop, and climate conditions at the time of last application were considered as model parameters.

Results

The proposed ensemble models demonstrated 98% prediction accuracy that if a DFR0 is predicted to be less than the European Food Safety Authority (EFSA) default DFR0 value of 3 µg/cm2/kg a.i./ha, it is highly indicative that the measured DFR value will be less than the default if the study is conducted. If a value is predicted to be larger than or equal to the EFSA default, the model has an 83% prediction accuracy.

Impact statement

This manuscript is expected to have significant impact globally as it provides:

A framework for incorporating in silico DFR data into worker exposure assessment,

A roadmap for a tiered approach for conducting re-entry exposure assessment, and

A proof of concept for using existing DFR data to provide a read-across framework that can easily be harmonized across all regulatory agencies to provide more robust assessments for PPP exposures.
Direct breastfeeding frequency of late preterm and term infants in the neonatal intensive care unit and availability of mother’s own milk at six months of age. a retrospective cohort study
Authors: Smith Amanda E , Sweigart Erin , Falatic Kimberly , Stuart Dena , Szugye Heidi , Lam Suet Kam , Aly Hany , Das Anirudha
Published: April 2024

Background

Mother’s Own Milk (MOM) reduces the risk of complications in premature infants. Breastfeeding rates for late preterm and term infants in the neonatal intensive care unit (NICU) are significantly lower than that of breastfed healthy term newborns at 6 months of age.

Design

This was a retrospective cohort study of neonates born at 34 weeks 0 days or later. Infants who were directly breastfed in the NICU and were discharged on breast milk were included. Logistic regression modeling was used to determine the significance of association.

Results

171 mother-infant dyads were included. After adjusting for confounders, the number of breastfeeding attempts during the NICU stay was significantly associated with the availability of MOM at six months of age (p = 0.003, 95% CI 1.02 to 1.14).

Conclusion

This study is the first to show an association between the number of direct breastfeeding attempts in the NICU and availability of MOM at six months of age.
Long COVID: plasma levels of neurofilament light chain in mild COVID-19 patients with neurocognitive symptoms
Authors: Gutman Elisa Gouvea , Salvio Andreza Lemos , Fernandes Renan Amphilophio , Duarte Larissa Araujo , Raposo-Vedovi Jessica Vasques , Alcaraz Helena França , Teixeira Milene Ataíde , Passos Giselle Fazzioni , de Medeiros Karoline Queiroz Muniz , Hammerle Mariana Beiral , Pires Karina Lebeis , Vasconcelos Claudia Cristina Ferreira , Leon Luciane Almeida Amado , Figueiredo Cláudia Pinto , Alves-Leon Soniza Vieira
Published: April 2024

It is well known the potential of severe acute respiratory coronavirus type 2 (SARS-CoV-2) infection to induce post-acute sequelae, a condition called Long COVID. This syndrome includes several symptoms, but the central nervous system (CNS) main one is neurocognitive dysfunction. Recently it has been demonstrated the relevance of plasma levels of neurofilament light chain (pNfL), as a biomarker of early involvement of the CNS in COVID-19. The aim of this study was to investigate the relationship between pNfL in patients with post-acute neurocognitive symptoms and the potential of NfL as a prognostic biomarker in these cases. A group of 63 long COVID patients ranging from 18 to 59 years-old were evaluated, submitted to a neurocognitive battery assessment, and subdivided in different groups, according to results. Plasma samples were collected during the long COVID assessment and used for measurement of pNfL with the Single molecule array (SIMOA) assays. Levels of pNfL were significantly higher in long COVID patients with neurocognitive symptoms when compared to HC (p = 0.0031). Long COVID patients with cognitive impairment and fatigue symptoms presented higher pNfL levels when compared to long COVID patients without these symptoms, individually and combined (p = 0.0263, p = 0.0480, and 0.0142, respectively). Correlation analysis showed that levels of cognitive lost and exacerbation of fatigue in the neurocognitive evaluation had a significative correlation with higher pNfL levels (p = 0.0219 and 0.0255, respectively). Previous reports suggested that pNfL levels are related with higher risk of severity and predict lethality of COVID-19. Our findings demonstrate that SARS-CoV-2 infection seems to have a long-term impact on the brain, even in patients who presented mild acute disease. NfL measurements might be useful to identify CNS involvement in long COVID associated with neurocognitive symptoms and to identify who will need continuous monitoring and treatment support.
Psilocybin restrains activity-based anorexia in female rats by enhancing cognitive flexibility: contributions from 5-HT1A and 5-HT2A receptor mechanisms
Authors: Conn K. , Milton L. K. , Huang K. , Munguba H. , Ruuska J. , Lemus M. B. , Greaves E. , Homman-Ludiye J. , Oldfield B. J. , Foldi C. J.
Published: April 2024

Psilocybin has shown promise for alleviating symptoms of depression and is currently in clinical trials for the treatment of anorexia nervosa (AN), a condition that is characterised by persistent cognitive inflexibility. Considering that enhanced cognitive flexibility after psilocybin treatment is reported to occur in individuals with depression, it is plausible that psilocybin could improve symptoms of AN by breaking down cognitive inflexibility. A mechanistic understanding of the actions of psilocybin is required to tailor the clinical application of psilocybin to individuals most likely to respond with positive outcomes. This can only be achieved using incisive neurobiological approaches in animal models. Here, we use the activity-based anorexia (ABA) rat model and comprehensively assess aspects of reinforcement learning to show that psilocybin (post-acutely) improves body weight maintenance in female rats and facilitates cognitive flexibility, specifically via improved adaptation to the initial reversal of reward contingencies. Further, we reveal the involvement of signalling through the serotonin (5-HT) 1 A and 5-HT2A receptor subtypes in specific aspects of learning, demonstrating that 5-HT1A antagonism negates the cognitive enhancing effects of psilocybin. Moreover, we show that psilocybin elicits a transient increase and decrease in cortical transcription of these receptors (Htr2a and Htr1a, respectively), and a further reduction in the abundance of Htr2a transcripts in rats exposed to the ABA model. Together, these findings support the hypothesis that psilocybin could ameliorate cognitive inflexibility in the context of AN and highlight a need to better understand the therapeutic mechanisms independent of 5-HT2A receptor binding.
Turning anecdotal irradiation-induced anticancer immune responses into reproducible in situ cancer vaccines via disulfiram/copper-mediated enhanced immunogenic cell death of breast cancer cells
Authors: Guo Wei , Jia Lin , Xie Ling , Kiang Juliann G. , Wang Yangyang , Sun Fengfei , Lin Zunwen , Wang Enwen , Zhang Yida , Huang Peigen , Sun Ting , Zhang Xiao , Bian Zhengying , Tang Tiejun , Guo Jingtian , Ferrone Soldano , Wang Xinhui
Published: April 2024

Irradiation (IR) induces immunogenic cell death (ICD) in tumors, but it rarely leads to the abscopal effect (AE); even combining IR with immune checkpoint inhibitors has shown only anecdotal success in inducing AEs. In this study, we aimed to enhance the IR-induced immune response and generate reproducible AEs using the anti-alcoholism drug, disulfiram (DSF), complexed with copper (DSF/Cu) to induce tumor ICD. We measured ICD in vitro and in vivo. In mouse tumor models, DSF/Cu was injected intratumorally followed by localized tumor IR, creating an in situ cancer vaccine. We determined the anticancer response by primary tumor rejection and assessed systemic immune responses by tumor rechallenge and the occurrence of AEs relative to spontaneous lung metastasis. In addition, we analyzed immune cell subsets and quantified proinflammatory and immunosuppressive chemokines/cytokines in the tumor microenvironment (TME) and blood of the vaccinated mice. Immune cell depletion was investigated for its effects on the vaccine-induced anticancer response. The results showed that DSF/Cu and IR induced more potent ICD under hypoxia than normoxia in vitro. Low-dose intratumoral (i.t.) injection of DSF/Cu and IR(12Gy) demonstrated strong anti-primary and -rechallenged tumor effects and robust AEs in mouse models. These vaccinations also increased CD8+ and CD4+ cell numbers while decreasing Tregs and myeloid-derived suppressor cells in the 4T1 model, and increased CD8+, dendritic cells (DC), and decreased Treg cell numbers in the MCa-M3C model. Depleting both CD8+ and CD4+ cells abolished the vaccine’s anticancer response. Moreover, vaccinated tumor-bearing mice exhibited increased TNFα levels and reduced levels of immunosuppressive chemokines/cytokines. In conclusion, our novel approach generated an anticancer immune response that results in a lack of or low tumor incidence post-rechallenge and robust AEs, i.e., absence of or decreased spontaneous lung metastasis in tumor-bearing mice. This approach is readily translatable to clinical settings and may increase IR-induced AEs in cancer patients.
Circadian rhythm regulates the function of immune cells and participates in the development of tumors
Authors: Zeng Yuen , Guo Zichan , Wu Mengqi , Chen Fulin , Chen Lihua
Published: April 2024

Circadian rhythms are present in almost all cells and play a crucial role in regulating various biological processes. Maintaining a stable circadian rhythm is essential for overall health. Disruption of this rhythm can alter the expression of clock genes and cancer-related genes, and affect many metabolic pathways and factors, thereby affecting the function of the immune system and contributing to the occurrence and progression of tumors. This paper aims to elucidate the regulatory effects of BMAL1, clock and other clock genes on immune cells, and reveal the molecular mechanism of circadian rhythm’s involvement in tumor and its microenvironment regulation. A deeper understanding of circadian rhythms has the potential to provide new strategies for the treatment of cancer and other immune-related diseases.
The fusion gene LRP1–SNRNP25 drives invasion and migration by activating the pJNK/37LRP/MMP2 signaling pathway in osteosarcoma
Authors: Xing Peipei , Liu Haotian , Xiao Wanyi , Zhang Gengpu , Zhang Chao , Liao Zhichao , Li Ting , Yang Jilong
Published: April 2024

Through transcriptome sequencing, we previously identified a new osteosarcoma-specific, frequent fusion gene, LRP1–SNRNP25, and found that it played an important role in tumor cell invasion and migration. However, the specific mechanism remains unclear. In this article, whole-genome sequencing further confirmed that the LRP1–SNRNP25 fusion gene is formed by fusion of LRP1 exon 8 and SNRNP25 exon 2. In vitro, scratch and Transwell assays demonstrated that the migration and invasion abilities of LRP1–SNRNP25-overexpressing osteosarcoma cells were significantly increased. To explore the molecular mechanism of the LRP1–SNRNP25 fusion in affecting osteosarcoma cell migration and invasion, we evaluated the migration and invasion-related molecular signaling pathways by western blotting. Some migration- and invasion-related genes, including pJNK and MMP2, were upregulated. Coimmunoprecipitation–mass spectrometry showed that 37LRP can interact with pJNK. Western blotting confirmed that LRP1–SNRNP25 overexpression upregulates 37LRP protein expression. Immunofluorescence staining showed the intracellular colocalization of LRP1–SNRNP25 with pJNK and 37LRP proteins and that LRP1–SNRNP25 expression increased the pJNK and 37LRP levels. Coimmunoprecipitation (co-IP) confirmed that LRP1–SNRNP25 interacted with pJNK and 37LRP proteins. The pJNK inhibitor SP600125 dose-dependently decreased the pJNK/37LRP/MMP2 levels. After siRNA-mediated 37LRP knockdown, the MMP2 protein level decreased. These two experiments proved the upstream/downstream relationship among pJNK, 37LRP, and MMP2, with pJNK the farthest upstream and MMP2 the farthest downstream. These results proved that the LRP1–SNRNP25 fusion gene exerts biological effects through the pJNK/37LRP/MMP2 signaling pathway. In vivo, LRP1–SNRNP25 promoted osteosarcoma cell growth. Tumor growth was significantly inhibited after SP600125 treatment. Immunohistochemical analysis showed that the pJNK, MMP2, and Ki-67 protein levels were significantly increased in tumor tissues of LRP1–SNRNP25-overexpressing cell-injected nude mice. Furthermore, lung and liver metastasis were more prevalent in these mice. In a word, LRP1–SNRNP25 promotes invasion, migration, and metastasis via pJNK/37LRP/MMP2 pathway. LRP1–SNRNP25 is a potential therapeutic target for LRP1–SNRNP25-positive osteosarcoma.
Negotiating severity behind the scenes: prenatal testing in Germany
Authors: Nov-Klaiman Tamar , Bowman-Smart Hilary , Horn Ruth
Published: April 2024

Foetal-related severity is a key concept in policy and legislation relating to access to both reproductive technologies and selective abortions in many countries around the world, but not in Germany. This study sheds light on how ‘severity’ in the context of prenatal testing is understood and negotiated within the particular socio-cultural and legal context of Germany, where ‘severity’ relating to foetal clinical findings neither counts as a justification to implement population prenatal screening programs, nor as a legal ground to terminate pregnancy. This study explores the views of women who undergo prenatal testing, as well as of professionals who encounter them, through semi-structured interviews. It showcases how they frame severity and questions whether the existing legal and regulatory framework relating to prenatal testing and termination of pregnancy addresses their concerns and needs regarding reproductive decision-making. The interviews (n = 27) reveal that despite it being legally outside the explicit reasons for testing and termination of pregnancy, both women and professionals negotiate severity behind the scenes. Their interpretation of severity is highly context-dependent and relies on clinical, social and familial facets. Their perceptions of severity guide them in their handling of and decision-making around pregnancy management. Acknowledging the personal nature of severity assessment and providing professional or legal guidance which explicitly mentions foetal anomaly as a legitimate factor in pregnancy management could provide healthcare professionals and patients with the room needed to manage the pregnancy favourably.
A MTA2-SATB2 chromatin complex restrains colonic plasticity toward small intestine by retaining HNF4A at colonic chromatin
Authors: Gu Wei , Huang Xiaofeng , Singh Pratik N. P. , Li Sanlan , Lan Ying , Deng Min , Lacko Lauretta A. , Gomez-Salinero Jesus M. , Rafii Shahin , Verzi Michael P. , Shivdasani Ramesh A. , Zhou Qiao
Published: April 2024

Plasticity among cell lineages is a fundamental, but poorly understood, property of regenerative tissues. In the gut tube, the small intestine absorbs nutrients, whereas the colon absorbs electrolytes. In a striking display of inherent plasticity, adult colonic mucosa lacking the chromatin factor SATB2 is converted to small intestine. Using proteomics and CRISPR-Cas9 screening, we identify MTA2 as a crucial component of the molecular machinery that, together with SATB2, restrains colonic plasticity. MTA2 loss in the adult mouse colon activated lipid absorptive genes and functional lipid uptake. Mechanistically, MTA2 co-occupies DNA with HNF4A, an activating pan-intestinal transcription factor (TF), on colonic chromatin. MTA2 loss leads to HNF4A release from colonic chromatin, and accumulation on small intestinal chromatin. SATB2 similarly restrains colonic plasticity through an HNF4A-dependent mechanism. Our study provides a generalizable model of lineage plasticity in which broadly-expressed TFs are retained on tissue-specific enhancers to maintain cell identity and prevent activation of alternative lineages, and their release unleashes plasticity.
Current-sensitive Hall effect in a chiral-orbital-current state
Authors: Zhang Yu , Ni Yifei , Schlottmann Pedro , Nandkishore Rahul , DeLong Lance E. , Cao Gang
Published: April 2024

Chiral orbital currents (COC) underpin a novel colossal magnetoresistance in ferrimagnetic Mn3Si2Te6. Here we report the Hall effect in the COC state which exhibits the following unprecedented features: (1) A sharp, current-sensitive peak in the magnetic field dependence of the Hall resistivity, and (2) A current-sensitive scaling relation between the Hall conductivity σxy and the longitudinal conductivity σxx, namely, σxy ∝ σxxα with α reaching up to 5, which is exceptionally large compared to α ≤ 2 typical of all solids. The novel Hall responses along with a current-sensitive carrier density and a large Hall angle of 15% point to a giant, current-sensitive Hall effect that is unique to the COC state. Here, we show that a magnetic field induced by the fully developed COC combines with the applied magnetic field to exert the greatly enhanced transverse force on charge carriers, which dictates the COC Hall responses.
Staggered structural dynamic-mediated selective adsorption of H2O/D2O on flexible graphene oxide nanosheets
Authors: Futamura Ryusuke , Iiyama Taku , Ueda Takahiro , Bonnaud Patrick A. , Coudert François-Xavier , Furuse Ayumi , Tanaka Hideki , Pellenq Roland J. -M. , Kaneko Katsumi
Published: April 2024

Graphene oxide (GO) is the one of the most promising family of materials as atomically thin membranes for water-related molecular separation technologies due to its amphipathic nature and layered structure. Here, we show important aspects of GO on water adsorption from molecular dynamics (MD) simulations, in-situ X-ray diffraction (XRD) measurements, and ex-situ nuclear magnetic resonance (NMR) measurements. Although the MD simulations for GO and the reduced GO models revealed that the flexibility of the interlayer spacing could be attributed to the oxygen-functional groups of GO, the ultra-large GO model cannot well explain the observed swelling of GO from XRD experiments. Our MD simulations propose a realistic GO interlayer structure constructed by staggered stacking of flexible GO sheets, which can explain very well the swelling nature upon water adsorption. The transmission electron microscopic (TEM) observation also supports the non-regular staggered stacking structure of GO. Furthermore, we demonstrate the existence of the two distinct types of adsorbed water molecules in the staggered stacking: water bonded with hydrophilic functional groups and “free” mobile water. Finally, we show that the staggered stacking of GO plays a crucial role in H/D isotopic recognition in water adsorption, as well as the high mobility of water molecules.
Climate-forced Hg-remobilization associated with fern mutagenesis in the aftermath of the end-Triassic extinction
Authors: Bos Remco , Zheng Wang , Lindström Sofie , Sanei Hamed , Waajen Irene , Fendley Isabel M. , Mather Tamsin A. , Wang Yang , Rohovec Jan , Navrátil Tomáš , Sluijs Appy , van de Schootbrugge Bas
Published: April 2024

The long-term effects of the Central Atlantic Magmatic Province, a large igneous province connected to the end-Triassic mass-extinction (201.5 Ma), remain largely elusive. Here, we document the persistence of volcanic-induced mercury (Hg) pollution and its effects on the biosphere for ~1.3 million years after the extinction event. In sediments recovered in Germany (Schandelah-1 core), we record not only high abundances of malformed fern spores at the Triassic-Jurassic boundary, but also during the lower Jurassic Hettangian, indicating repeated vegetation disturbance and stress that was eccentricity-forced. Crucially, these abundances correspond to increases in sedimentary Hg-concentrations. Hg-isotope ratios (δ202Hg, Δ199Hg) suggest a volcanic source of Hg-enrichment at the Triassic-Jurassic boundary but a terrestrial source for the early Jurassic peaks. We conclude that volcanically injected Hg across the extinction was repeatedly remobilized from coastal wetlands and hinterland areas during eccentricity-forced phases of severe hydrological upheaval and erosion, focusing Hg-pollution in the Central European Basin.
Loss of NEDD8 in cancer cells causes vulnerability to immune checkpoint blockade in triple-negative breast cancer
Authors: Papakyriacou Irineos , Kutkaite Ginte , Rúbies Bedós Marta , Nagarajan Divya , Alford Liam P. , Menden Michael P. , Mao Yumeng
Published: April 2024

Immune checkpoint blockade therapy aims to activate the immune system to eliminate cancer cells. However, clinical benefits are only recorded in a subset of patients. Here, we leverage genome-wide CRISPR/Cas9 screens in a Tumor-Immune co-Culture System focusing on triple-negative breast cancer (TNBC). We reveal that NEDD8 loss in cancer cells causes a vulnerability to nivolumab (anti-PD-1). Genetic deletion of NEDD8 only delays cell division initially but cell proliferation is unaffected after recovery. Since the NEDD8 gene is commonly essential, we validate this observation with additional CRISPR screens and uncover enhanced immunogenicity in NEDD8 deficient cells using proteomics. In female immunocompetent mice, PD-1 blockade lacks efficacy against established EO771 breast cancer tumors. In contrast, we observe tumor regression mediated by CD8+ T cells against Nedd8 deficient EO771 tumors after PD-1 blockade. In essence, we provide evidence that NEDD8 is conditionally essential in TNBC and presents as a synergistic drug target for PD-1/L1 blockade therapy.