bluuebunny/crossref_metadata_2025 huggingface dataset:
Emerging Tools to Support DILI Assessment in Clinical Trials with Abnormal Baseline Serum Liver Tests or Pre-existing Liver Diseases
Authors: Amirzadegan Jasmine , Tesfaldet Bereket , Pei Y. Veronica , Navarro Almario Eileen , Avigan Mark I. , Hayashi Paul H.
Published: February 2025

Based on the late Dr. Hyman Zimmerman’s observation that hepatocellular drug-induced liver injury (DILI) leading to jaundice carries a ≥ 10% fatality risk (coined as Hy’s law by others), evaluation of Drug-Induced Serious Hepatotoxicity (eDISH) continues to play a central role in the assessment of a study drug’s liability for acute hepatocellular DILI. The eDISH identifies drugs in clinical trials with DILI fatality (death or transplant) risk that may be unacceptable in a post-market setting. As a two-dimensional graph that plots peak total bilirubin (TB) versus peak serum aminotransferase levels for each patient during study drug or comparator treatment, eDISH identifies potential cases of acute, modest, and serious hepatocellular DILI for in-depth analysis of liver tests (LT) and clinical course so that the likelihood of causal association with the study drug can be determined. Unfortunately, the generalizable utility of this tool only pertains to trials enrolling patients with normal or near normal (NNN) baseline (BL) serum LTs. The eDISH does not necessarily apply to trials of patients with abnormal baseline (ABN-BL) LTs that often coincide with underlying liver disorders. Because drug development programs being reviewed by the FDA increasingly target liver disorders, we are often challenged to evaluate DILI risk in trials of patients with ABN-BL LTs. Also, the high background prevalence of metabolic dysfunction associated steatotic liver disease (MASLD) means patients with LTs above NNN may need to be enrolled in trials treating non-liver disorders to reflect the target population. Such study populations create challenges for industry and regulators because eDISH may not reliably categorize or identify potential cases of DILI for further analysis, as it so efficiently does in NNN-BL trials. We describe the main functionalities of eDISH in NNN-BL trials to understand what should be emulated by new tools or eDISH modifications. We then discuss non-eDISH–based plots that may be useful in ABN-BL trials.
Predictive and Prognostic Factors in Epithelial Ovarian Cancer: A Review
Authors: Giro Alexia , Herrmann Tressie , Bauer Arthur , Pinard Céleste , Godiveau Mélanie , Passildas Judith , Abrial Catherine , Durando Xavier
Published: February 2025

Introduction

Ovarian cancer is the eighth most common cancer among women, accounting for 4.7% of all cancer-related deaths.

Objective

In this review, we aimed to describe both established and emerging, prognostic and predictive factors.

Results

Some established prognostic factors are clinical, such as age, ECOG, and Body Mass Index. Histological subtype, stage and grade are also prognostic factors, and optimal surgery is one of the main factors. Furthermore, the presence of ascites at diagnosis and cancer Antigen 125 assessment could help to predict patient outcomes. Nevertheless, median survival is less than 5 years. Among the emerging factors, tumor-infiltrating lymphocytes (TILs) have a proven prognostic value, although their predictive value has not been used in routine practice. Inflammatory response marker ratios, i.e., neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios, could have a prognostic value. Circulating tumor DNA is one of the most promising prognostic and predictive factors. Concerning predictive factors, the main one is homologous recombination deficiency, which is a marker for response to PARP inhibitors and platin-based chemotherapy. The KELIM score is also used to predict chemosensitivity. To be validated in routine practice, other predictive factors require further investigation.

Conclusion

Despite the poor prognosis in this pathology, some patients are still alive 10 years after diagnosis. A better understanding of this population’s characteristics could help to anticipate patient outcomes and thus adapt their management.
Highly porous hollow 3D devices obtained by a combined melt-wet processing for long-term controlled release
Authors: Balsamo Marta , Mistretta Maria Chiara , Scaffaro Roberto
Published: February 2025

The possibility to obtain resistant and reusable hollow devices with differentiated high porosity for storage and tunable long-term controlled release of substances is difficult to achieve efficiently. To solve this problem, we propose a combined melt-wet processing, which allows predictable and tunable morphologies. The process consists in combining Material Extrusion (MEX) with an eco-friendly salt leaching in distilled water, by using a biostable polymer and high percentages of saline porogen. Three blends with PA6/NaCl-30/70wt% composition were extruded, varying the salt particles size, that shows good dispersion in all the filaments, with a spontaneous tendency for bigger particles to accumulate in the central region of the cross-sections, attributable to fluid-dynamic reasons. Blends rheological and mechanical properties appeared suitable for the printing process. The hollow devices were then printed and successfully leached, resulting in homogeneously dispersed pores, with size ranges comparable to those of the porogen for each blend; therefore, the morphology of the pores can be directly predicted by the porogen and it was not altered during processing. Leaching occurred completely, in fact the real porosity for each device was consistent with the theoretical one. Despite the high percentage of voids, the hollow devices appeared to be mechanically resistant and therefore suitable for the application. Controlled release up to 11 days of a model molecule (methylene blue) was tested and predictable kinetics related to pore size were achieved so, therefore, they are easily tunable and versatile. Release data were fitted according to Peppas-Korsmeyer-model to describe the release mechanism related to porosity.
Crisis and crisis management in the Upper Franconian textile industry
Authors: Grötsch Margitta
Published: February 2025

Crises are becoming the new normal in the twenty-first century. This impression arises when one looks at the last decades’ political, economic, social, or ecological developments. Companies operating in this heterodox and dynamic environment are required to act quickly and in an adapted manner. The more closely companies are integrated into the macroeconomic context, the more they are affected by changes in the environment. Especially small and medium-sized enterprises, which are considered more vulnerable to crises (Detarsio et al. 2016), need appropriate strategies to survive them. The study examines which methods small and medium sized enterprises (SMEs) used to survive crises and if there were similar reactions to the same crisis scenarios. The textile industry in Upper Franconia is strongly integrated into the macroeconomic context and consists predominantly of small and medium-sized enterprises. This industry was hit by various crises between 1972 and 2008. The multiple crisis scenarios and the close link between the companies and their environment require a pluralistic perspective. Companies from other sectors that are confronted with similar crisis scenarios can use the study results to better position themselves against crises.
Starch Granule Evidence for Biscuitroot (Lomatium spp.) Processing at Upland Rock Art Sites in Warner Valley, Oregon
Authors: Wilks Stefania L. , Louderback Lisbeth A. , Simper Heidi M. , Cannon William J.
Published: February 2025

Geophytes are hardy, resilient plants that are tolerant of cold temperatures and drought and are well documented as a reliable food source for hunter-gatherers worldwide. Human settlement patterns and foraging behaviors have long been associated with the use of nutrient-dense geophytes rich in carbohydrates, fiber, vitamins, and minerals. Indigenous communities in the northern Great Basin developed cultural practices centered around gathering, preparing, and consuming important geophytic plants. These practices became deeply embedded in their cultural identity, forming rituals, stories, and traditions that persist today. Although there is strong ethnographic precedent for the significance of geophytes, finding evidence of their use in the archaeological record remains a challenge. This study analyzed archaeological starch residue extracted from bedrock metates in the uplands of Warner Valley, Oregon. Systematic studies of starch granules collected from extant plant communities growing near archaeological sites were applied to the identification of archaeological granules. Starch granules from geophytes, specifically Lomatium spp. (biscuitroot), were identified on metate surfaces at all sites, thus providing direct evidence for the collection and processing of geophyte vegetables. Evidence of geophyte plant processing on bedrock metates contributes to archaeological theories about subsistence strategies, food-processing technologies, social organization, and cultural practices in past human societies.
Isotypical components of the homology of ICIS and images of deformations of map germs
Authors: Conejero R. Giménez
Published: February 2025

We give a simple way to study the isotypical components of the homology of simplicial complexes with actions of finite groups and use it for Milnor fibres of isolated complete intersection singularity (icis). We study the homology of images of mappings ft that arise as deformations of complex map germs

$f:(\mathbb{C}^n,S)\to(\mathbb{C}^p,0)$

, with n < p, and the behaviour of singularities (instabilities) in this context. We study two generalizations of the notion of image Milnor number µI given by Mond and give a workable way of compute them, in corank one, with Milnor numbers of icis. We also study two unexpected traits when

$p \gt n+1$

: stable perturbations with contractible image and homology of

$\text{im} f_t$

in unexpected dimensions. We show that Houston’s conjecture, µI constant in a family implies excellency in Gaffney’s sense, is false, but we give a correct modification of the statement of the conjecture which we also prove.
The Horn of Enlightenment: Mozart's Operatic Use of the Clarinet
Authors: Pesic Peter
Published: February 2025

In his operas, Mozart followed contemporary practice by using the clarinet to set the mood for amorous scenes, but he adapted this into a new kind of topic that dramatises his characters’ changing self-knowledge and growing enlightenment. In so doing, he emphasised both their recognition of their true feelings and the political and moral implications for their subsequent actions. This is exemplified in La clemenza di Tito, in which a clarinet (or basset horn) serves as an important soloistic voice whose dialogue with the protagonist illuminates their inner struggles with conflicting emotional, social and political realities as they move towards new understanding.
Resilient forces of public amusement: the negotiation of ‘urban modernity’ in a peripheral port city (1880s–1930s)
Authors: Reimann Christina
Published: February 2025

This article studies public amusement in turn-of-the-twentieth-century Gothenburg, Sweden, and argues that historians of urban and popular culture need to take the hybrid character of modernity more seriously. The case of the small peripheral port city of Gothenburg, more clearly than large metropoles or rapidly growing urban centres, showcases how turn-of-the-century urban culture was negotiated through the confrontation of traditional and innovative forms of popular amusement. Hence, insights from Gothenburg can prompt a more critical, nuanced view of ‘urban modernity’, marked not only by the emergence of commercial mass entertainment but also by the resilience of itinerant performers, for example. The article draws on different types of source material that from different perspectives embrace the co-constitutive character of practices and representations of pleasure through which people in Gothenburg negotiated urban change.
Outward foreign direct investment and energy efficiency: firm-level evidence from China
Authors: Lin Xi , Liu Xinheng , He Ling-Yun
Published: February 2025

Energy inefficiency and environmental damages caused by this inefficiency are increasingly common in developing countries. As the largest developing country, China is experiencing a rapid growth in outward foreign direct investment (OFDI). Do OFDI firms have higher energy efficiency in the same sector? After OFDI, how does the energy efficiency of the firms change? In this study, we employ the data from Chinese industrial firms to empirically investigate these questions. Our results show that OFDI firms have higher energy efficiency and total factor energy efficiency (TFEE) relative to non-OFDI firms in the same sector. After OFDI, firms improve energy efficiency and TFEE through expanding output scale. In addition, these effects are found to be heterogeneous in terms of energy types as well as OFDI motivations and destinations. In general, this study provides some initial evidence for the relationship between OFDI and energy performance at the firm level.
Anxiety Reducing Effects of Physical Activity in Adolescents and Young Adults
Authors: Aumer Thierry , Vögele Claus
Published: February 2025

Abstract: This systematic review provides an overview of the current literature on the effects of physical activity (PA) as an intervention to treat anxiety symptoms in adolescents and young adults. Three searches (March and May 2022; July 2024) focusing on RCTs using a PA intervention of at least moderate intensity were carried out in PubMed, PsycInfo, SportDiscus, and Google Scholar. Studies were screened, and risk of bias was assessed for all included studies. In total 2,521 studies were retrieved, and 14 RCTs were retained. Studies were compared based on several criteria, such as type of exercise, intensity, delivery mode, PA alone or as add-on treatment. Results suggest that PA is more effective compared to inactive control conditions. Intensity (moderate or high) or type of exercise (aerobic or resistance training) requirements for anxiolytic effects are less clear. Participants with elevated anxiety scores benefit more from PA interventions than those with low anxiety scores. We conclude that PA is a promising intervention to treat anxiety in adolescents and young adults. Heterogeneity between studies is high, and many present methodological shortcomings. Little is known about the underlying mechanisms responsible for anxiety-reducing effects. To advance research, more high-quality studies are needed to develop effective and personalized PA interventions.
Magnetic Characteristics of Highly Serpentinized Peridotite in the Iberia Abyssal Plain and Implications for Marine Magnetic Anomalies
Authors: Zhang Yuzhen , Jiang Zhaoxia , Su Kai , Dekkers Mark J. , Li Sanzhong , Liu Qingsong
Published: February 2025

Serpentinization, a consequence of water‐rock interaction in mafic and ultramafic rocks, refers to the hydrothermal alteration of olivine and pyroxene with serpentine as the typical product. Magnetite is produced in variable amounts during this serpentinization process. Here, we conducted a systematic rock magnetic study on the serpentinite of Ocean Drilling Program (ODP) Hole 1070A from the Iberia Abyssal Plain. From bottom to top, three units are distinguished rock‐magnetically: (a) serpentinized peridotite dominated by single‐domain (SD) ± multidomain (MD) magnetite particles; (b) gabbro with SD ± vortex state magnetite; (c) breccia dominated by MD ± vortex and SD ± vortex state maghemite/hematite and magnetite. Samples of the three units are highly serpentinized with serpentinization degrees >60%. The magnetite content increases exponentially with the degree of serpentinization. Two phases of serpentinization are proposed: (a) massive serpentinization that occurred before mantle exhumation and (b) maghemitization‐serpentinization that occurred near or at the seafloor after the final exhumation of mantle peridotites. The latter reduces the magnetization of the breccia unit significantly. Serpentinized peridotite associated with strong magnetization is the dominant contributor to the marine magnetic anomalies in ocean to continent transition areas.
Forecasting Recurrent Large Earthquakes From Paleoearthquake and Fault Displacement Data
Authors: Griffin Jonathan D. , Wang Ting , Stirling Mark W. , Gerstenberger Matthew C.
Published: February 2025

Long recurrence intervals of large earthquakes relative to the historical record mean that geological data are often utilized to inform forecasts of future events. Geological data from any particular fault may constrain the timing of past earthquakes (paleoearthquake data), or simply the time period over which a certain amount of fault displacement has occurred due to one or more earthquakes. These data are typically subject to large uncertainties, and available records often only constrain the timing of a few events. Variability in earthquake inter‐event times (aperiodicity) has been observed for many faults, particularly in low seismicity regions, further hampering the utilisation of small data sets for developing forecasts. A challenge for earthquake forecasting therefore concerns how best to utilize all of the limited available data while fully considering uncertainties. Here we present a concise Bayesian model for developing time‐dependent earthquake forecasts from geological data. Using the additive property of the Brownian passage time distribution, we make inference on the model parameters jointly from paleoearthquake and fault displacement data. Monte Carlo Markov Chain methods are used to sample the posterior distribution of model parameters, which is subsequently used to forecast future earthquake probabilities. The method incorporates data uncertainties and does not rely on a priori assumptions of quasiperiodic earthquake recurrence, allowing application in a wide range of tectonic settings. We demonstrate the method using data from two reverse faults in Otago, southern Aotearoa New Zealand, a region in which aperiodic earthquake recurrence has previously been observed.
Spectral Analysis of Topography as Proxy for Lineament Analysis
Authors: Dichiarante A. M. , Torgersen E. , Redfield T. , Köhler A. , Torabi A. , Svendby K. , Oye V.
Published: February 2025

Spectral analysis (SA) for image processing, utilizing the Fast Fourier Transform (FFT), computes the 2D power spectrum to capture the amplitude of each frequency component of an image. Recent studies have applied SA on digital elevation models (DEMs) to characterize repetitive and spatially homogeneous landforms in terms of their orientation, frequency, and amplitude. Here, we advance the application of SA by introducing a new preprocessing step and an appropriate windowing function, tailored to analyze heterogenous and complex topographies and derive lineament spatial distributions. The validation of our approach involved two phases: (a) testing on synthetic images, and (b) application to a case study. The synthetic image validation illustrated the length‐weighted characteristics of SA‐derived rose diagrams and the robustness of the method, evidenced by a 99% similarity across 1,000 synthetically generated lineament networks. The case study consisted of three areas characterized by different topographic patterns within the Oslo region of Norway. The SA‐derived results were compared to lineaments automatically extracted using a conventional peak‐and‐valley seeking algorithm that mimics manual tracing of lineaments inside a 3D map domain. The comparison showed similarity better than 90%. Lastly, we addressed a key pitfall of SA by locating signatures observed in the power spectrum on the map through cross‐correlation (CC) of profiles. Although CC results are not consistently perfect, they provide a promising avenue for further development.
Alpine Crust and Mantle Structure From 3D Monte Carlo Surface‐ and Body‐Wave Tomography
Authors: Kästle E. D. , Paffrath M. , El‐Sharkawy A. ,   the AlpArray and Swath‐D working groups
Published: February 2025

An ongoing controversy revolves around the detailed structure of the subducting European and Adriatic plates under the Alps and the adjacent orogens. Mostly based on P‐wave travel time tomographic images, slab break‐off at different times, reversals of subduction polarity and segmentation of the slab into independent units have been proposed. These processes may have important geodynamic consequences such as rapid surface uplift, past magmatic events or changes in the style of continental collision. However, some of the tomographic results are contradictory, particularly evident in the uppermost mantle where teleseismic P waves traverse the medium almost vertically with few ray crossings and a stronger dependence on the crustal correction. In this work, we present the result of an innovative joint inversion approach using surface‐ and teleseismic body‐wave travel times to mitigate some of the shortcomings in both data types. Applying a reversible‐jump Markov chain Monte Carlo approach, we simultaneously constrain the and structure and their uncertainties in the crust and upper mantle. The results indicate a continuous slab structure from the crust‐mantle boundary down to at least 400 km depth under the western, central and eastern Alps. The results, however, also suggest that fitting the data within their respective measurement uncertainties may not be sufficient to reliably determine the presence of a shallow slab break‐off beneath the Alps.
Roles of Upwelling on the Dynamics and Freshwater Transport of a River Plume Over the Inner Shelf
Authors: Chen Zhaoyun , Zhang Lie , Zhang Shuwen , Zong Xiaolong , Jiang Yuwu
Published: February 2025

Apart from the influences of wind and tides, upwelling can also modulate the dispersal and dynamics of river plumes. However, the specific responses to upwelling processes over the inner shelf remain unclear. This study employs a numerical model to investigate the effects of upwelling over the northeastern shelf of the South China Sea and its barotropic influences on the dynamics and freshwater transport of a medium‐scale river plume. In a model experiment with extremely weakened upwelling (tiny upwelling case), plume water spreads across a wide coastal region driven by upwelling‐favorable winds. With the barotropic effects of upwelling, plume water occupies a much smaller area, and the alongshore geostrophic current is enhanced. In the Control Run, plume water disperses further offshore in a stratified seawater column, as the Ekman layer thins and the offshore Ekman current intensifies in the upwelling region. The upwelling process not only accelerates the downwind advection of offshore extended far‐field plume water due to the drop in coastal sea level but also continually upwells high‐salinity water from the lower layer to the upper layer, enhancing mixing with plume water and leading to a smaller river plume area. Under upwelling‐favorable wind conditions, freshwater is primarily transported offshore in tiny upwelling case, while the proportion of downwind freshwater transport increases in the Control Run or the barotropic case. In the tiny upwelling case, the contribution of advection and vertical shear to freshwater flux gradually decreases and increases, respectively, with the duration of upwelling‐favorable winds, while the tendency reverses in the Control Run.
Characteristics and Mechanisms of Ocean Fronts‐Induced Decomposition of Particulate Organic Matter and Its Implication for Marine Carbon Burial
Authors: Chen Fajin , Xu Renhao , Lao Qibin , Chen Chunqing , Liu Sihai , Cai Shangjun , Xu Jie , Jin Guangzhe
Published: February 2025

Ocean fronts are dynamic regions that significantly influence marine biogeochemical processes and climate change. Despite their importance, there is limited research on the dynamics of particulate organic matter (POM) at these fronts, limiting our understanding of carbon burial mechanisms in such environments. Here, we investigated the seasonal physicochemical parameters and stable isotopes of POM in the Beibu Gulf to explore how ocean fronts affect POM fate. During non‐frontal periods, notably summer and fall, microbial consumption of POM is minimal due to strong stratification, resulting in partial mineralization in middle and deep waters only. In contrast, frontal formations during winter enhance the decomposition of POM. In the northern frontal region with shallower water, intense vertical mixing induces upwelling of nutrient‐rich deeper water, stimulating phytoplankton growth and enhancing the production of fresh POM. This is accompanied by significant decomposition (94%) of fresh POM, driven by oxygen replenishment from photosynthesis and vertical mixing. In the eastern frontal region, with its deeper waters, restricted nutrient availability limits phytoplankton growth, resulting in more aging POM. However, decomposition still reaches 73% due to active vertical mixing. Therefore, regardless of the occurrence of phytoplankton blooms within frontal areas, decomposition is identified as a prevailing process, reducing the potential for marine carbon burial and challenging traditional theories that depict ocean fronts solely as carbon sinks. This comprehensive study sheds light on the biological pump mechanisms active within ocean fronts and highlights their potential role as significant carbon sources.
On the Timescales of the Response of the Brewer‐Dobson Circulation to an Abrupt Quadrupling of CO2
Authors: Calvo N. , Garcia R. R. , Chiodo G. , Marsh D. R. , Polvani L. M.
Published: February 2025

Changes in the Brewer‐Dobson circulation (BDC) in response to increasing CO2 concentrations can arise from the direct effect of radiative cooling in the stratosphere or the indirect effects induced by warmer sea surface temperatures (SSTs). This study aims to disentangle these two contributions in the Whole Atmosphere Community Climate Model (WACCM) by analyzing the timescales of the tropical upwelling response to an abrupt quadrupling of CO2. Transient atmosphere‐ocean climate model simulations of 100 years under 4xCO2 conditions are compared to preindustrial control simulations and to simulations with an atmosphere‐only version of WACCM that uses preindustrial SSTs. We find that most of the response in both shallow and deep branches of the BDC occurs on fast timescales (first 2‐3 decades). In the shallow branch of the BDC, the response is mainly driven by changes in SSTs in the well‐mixed shallow ocean, which cause tropospheric warming and an intensification and upward displacement of the subtropical jets, and alter wave forcing in their vicinity. The contribution from stratospheric radiative cooling is almost negligible. In the upper stratosphere, the response of tropical upwelling begins earlier and develops faster than in the shallow branch, owing to the larger contribution from the rapid adjustments. At 1 hPa, 70% of the fast response relates to stratospheric radiative cooling and 30% to warmer SSTs. The modulation of the filtering of non‐orographic gravity waves (mainly of frontal origin) in the subtropics explain most of the response in tropical upwelling in the deep branch, on both fast and slow timescales.
Exploring the Jau Crater Cluster, Gale Crater, Mars
Authors: Grant J. A. , Hoffman M. E. , Newsom posthumously H. E. , Kubacki T. , Juarez C. , Moore N. , Wilson S. A. , Parker T. J.
Published: February 2025

The Jau crater cluster on the north flank of Mt. Sharp in the Gale crater consists of 20–30 simultaneously formed impact structures. The craters are ∼2 to ∼25 m across (generally increasing in size from the ESE to WNW). Using Digital Terrain Models derived from orbital and rover orthomosaics of two of the larger craters, we evaluated the amount and processes of degradation based upon current versus expected original crater morphology. We conclude that the craters in the cluster are the result of a fragmenting primary impactor and that predominantly aeolian degradation at these two craters is responsible for ∼1–2 m wall back‐wasting, 10s of cm of infilling by aeolian drift, and 20–40 cm rim lowering. Other craters in the cluster experienced similar degradation whose expression varied according to crater size: smaller‐scale morphology at smaller craters is more modified by a given amount of erosion. Prevailing winds erode the downhill, NNE side of the craters more though raised rims persist at the larger craters. An estimated vertical erosion rate of 0.1 m/Myr and a horizontal erosion rate of several m/Myr predicted by others appear most consistent with the Jau crater morphology and setting relative to erosion estimates for elsewhere in Gale crater and other Mars landing sites. Factoring in uncertainties in our estimates, these rates are broadly consistent with the scale of erosion inferred for the evolution of larger, older features on Mt. Sharp and suggest that the cluster‐forming impact occurred one to a few and less than ∼5 Ma.
Solar Wind and Magnetospheric Conditions for Satellite Anomalies Attributed to Shallow Internal Charging
Authors: Rodriguez J. V. , Kress B. T. , Buzulukova N. Y. , Redmon R. J.
Published: February 2025

Satellite charging in Earth's magnetospheric plasma and radiation belts frequently causes operational anomalies. A recent study of a frequent Space Wire anomaly on GOES linked it to shallow internal charging by 100–300 keV electrons. Solar wind and magnetospheric conditions during a period spanning solar minimum (2017–2021) are analyzed to gain further insight into the anomalies. The anomalies are divided into two groups, with inter‐anomaly intervals shorter than 2 days (clustered) and longer (background). The clusters sometimes exhibit a clear 27‐day recurrence. The magnetic local time (MLT) distributions for background anomalies are statistically uniform, unlike those for clustered anomalies, which peak prior to local noon. The clustered anomaly distributions with respect to Kp are similar to those for surface charging, indicating enhanced plasma sheet access to geostationary orbit. The maximum 100–300 keV fluxes during injections are similar to published extreme fluxes. Through superposed epoch analysis and comparison with published lists of high‐speed streams, clustered anomalies are determined to occur during high‐speed streams with elevated solar wind speed, lower number density, and weakly negative interplanetary magnetic field . The MLT and Kp dependencies of the clustered anomalies may indicate charge accumulating in a thin dielectric with a time constant less than 1 day. The background anomalies, occurring uniformly in local time and varying slowly between solar rotation periods, may indicate a distinct charging location with a time constant greater than a solar rotation.
The Need for a Sub‐L1 Space Weather Research Mission: Current Knowledge Gaps on Coronal Mass Ejections
Authors: Lugaz Noé , Al‐Haddad Nada , Zhuang Bin , Möstl Christian , Davies Emma E. , Farrugia Charles J. , Banu Sahanaj Aktar , Weiler Eva , Galvin Antoinette B.
Published: February 2025

Over the past decades, missions at the L1 point have been providing solar wind and interplanetary magnetic field measurements that are necessary for forecasting space weather at Earth with high accuracy and a lead time of a few tens of minutes. Improving the lead time, while maintaining a relatively high level of accuracy, can be achieved with missions sunward of L1, so‐called sub‐L1 monitors. However, too much is unknown to plan for sub‐L1 monitors as operational missions: both the orbital requirements of such missions, and the achievable accuracy of forecasts based on their measurements have not been quantitatively defined. We review here some proposed mission concepts and explain the knowledge gaps related to coronal mass ejections (CMEs) that require a space weather research or science mission. We first show how STEREO‐A measurements in 2023 can be used as a proof of concept of the use of sub‐L1 monitor slightly off the Sun‐Earth line to forecast the Dst index. We then highlight that separations of are needed to ensure that CMEs measured by a sub‐L1 monitor impact Earth. Next, we show that measurements with angular separations of have negligible errors but separations of a few degrees can result in significant errors in lead time and in the forecasted magnetic field strength of CMEs. We also discuss how CME evolution over the last 0.05–0.2 au before impacting Earth is strongly under‐constrained and needs to be better understood before using measurements of sub‐L1 monitors for real‐time space weather forecasting.
Pressure‐Induced Change in Mechanical Anisotropy Within the Foliation Plane of Antigorite as an Indicator of the Brittle‒Ductile Transition
Authors: Shao Tongbin , Song Maoshuang , Li Jianfeng , Jiang Zhexuan
Published: February 2025

The response of antigorite deformation to preexisting fabrics in subduction zones is unclear. We deform antigorite schist with foliation and lineation (X is parallel to the lineation, Y is in the foliation and perpendicular to the lineation, and Z is normal to the foliation) at different angles to the maximum principal stress (σ1) via a Paterson gas‐medium apparatus under a confining pressure of 200 MPa, a temperature of 600°C, a strain rate of ∼10−5 s−1, and a preheating time of 6 hr. The mechanical results indicate that σ(Z) ≫ σ(X) ≈σ(Y), indicating nearly transverse isotropy. Observations of the recovered samples revealed that less ductile and more brittle deformation occurred simultaneously, indicative of a brittle‐to‐semibrittle regime. Microcracks formed parallel to the foliation likely increase anisotropy. The slightly greater strength, more kinks and/or occurrence of slow stick‐slip along the Y direction suggest that the a‐axis is in a hard‐friction direction, supporting the results of an atomic force microscopy (AFM) study by Campione and Capitani (2013, https://www.doi.org/10.1038/ngeo1905) on single‐crystal antigorite under ambient conditions. In contrast, our previous deformation at 1.3 GPa shows that the b‐axis is in a hard‐slip direction, consistent with the results from transmission electron microscopy (TEM) observations by Amiguet et al. (2014, https://www.doi.org/10.1002/2013jb010791) on antigorite deformed under 1 and 4 GPa. This comparison suggests that mechanical anisotropy within the foliation changes with pressure, likely reconciling the opposite results obtained by the two studies and indicating brittle‒ductile transitions near the mantle wedge corner where deep slow earthquakes related to antigorite may have occurred.
Associations between maternal pre-pregnancy BMI and mean diffusivity of the hippocampus and amygdala in infants
Authors: Rosberg Aylin , Merisaari Harri , Lewis John D. , Hashempour Niloofar , Lukkarinen Minna , Rasmussen Jerod M. , Scheinin Noora M. , Karlsson Linnea , Karlsson Hasse , Tuulari Jetro J.
Published: February 2025

Background

Maternal pre-pregnancy obesity may negatively affect offspring outcomes, including neurodevelopment. This study examined the relationship between maternal pre-pregnancy body mass index (MBMI) and the microstructure of the hippocampus and amygdala in neonates.

Methods

Diffusion tensor imaging was used to assess mean diffusivity (MD) in these brain regions in 122 infants (mean gestational age: 39.9 weeks, mean age at scan: 24.8 days) from the FinnBrain Birth Cohort Study (www.finnbrain.fi). Linear regression was applied to explore associations between MBMI and MD at the regional level, while non-parametric permutation analysis was used for voxelwise investigations.

Results

A positive association was found between MBMI and hippocampal MD, particularly in the right hippocampus. Voxelwise analyses showed stronger associations in distinct areas: posterior for the right hippocampus and anterior for the left. No significant association was found between MBMI and amygdala MD.

Conclusion

These findings suggest that in utero exposure to high MBMI may influence hippocampal microstructure in infants, underscoring the need for further research on the intergenerational effects of maternal obesity on early brain development.
Absence of TAAR1 function increases methamphetamine-induced excitability of dorsal raphe serotonin neurons and drives binge-level methamphetamine intake
Authors: Rios Samantha M. , Mootz John R. K. , Phillips Tamara J. , Ingram Susan L.
Published: February 2025

Methamphetamine (MA) is a potent psychostimulant capable of exerting both rewarding and aversive effects, the balance of which likely drives variation in voluntary MA intake. Understanding the genetic factors underlying sensitivity to these effects of MA is critical for developing effective treatments. The activity of dorsal raphe serotonin neurons is linked to reward processing. Here, we performed whole-cell patch-clamp electrophysiology in dorsal raphe serotonin neurons from mice with high or low MA intake corresponding with high or low MA reward sensitivity. The MA drinking (MADR) mice consist of the MA reward sensitive MA high drinking (MAHDR) and the MA reward insensitive MA low drinking (MALDR) lines. MA is a trace amine-associated receptor 1 (TAAR1) agonist, and MAHDR mice are homozygous for a mutation in the Taar1 gene, Taar1

m1J
, that encodes non-functional TAAR1, whereas MALDR mice possess at least one copy of the reference Taar1

+
allele that encodes functional TAAR1. Our previous research using CRISPR-Cas9-generated MAHDR-Taar1

+/+
knock-in mice in which Taar1

m1J
was replaced with Taar1

+
, and non-edited MAHDR-Taar1

m1J/m1J
controls demonstrated that lack of TAAR1 function is critical for heightened MA consumption and MA reward sensitivity. Here, electrophysiological recordings in the MADR lines demonstrate a MA-induced decrease in dorsal raphe serotonin neuron activity from MALDR, but not MAHDR mice. However, in the presence of serotonin autoreceptor antagonists, MA potentiates dorsal raphe serotonin neuron activity of MAHDR, but not MALDR mice. Importantly, potentiation in the presence of the antagonists is abolished in knock-in mice expressing functional TAAR1. The knock-in mice did not display binge-level MA intake, consistent with the loss of MA-reward sensitivity previously reported in mice with functional TAAR1. Finally, because MA is a substrate of the serotonin transporter, we evaluated whether the serotonin transporter is necessary for MA-induced potentiation of dorsal raphe serotonin neuron activity in mice with non-functional TAAR1. The serotonin transporter antagonist fluoxetine blocks MA-induced potentiation for both MAHDR and MAHDR-Taar1

m1J/m1J
mice. Thus, TAAR1 function directly impacts MA reward sensitivity and MA intake and serves as a critical regulator of MA-induced activity of dorsal raphe serotonin neurons through its interaction with the serotonin transporter.
Cryo-EM structure of the botulinum neurotoxin A/SV2B complex and its implications for translocation
Authors: Khanppnavar Basavraj , Leka Oneda , Pal Sushant K. , Korkhov Volodymyr M. , Kammerer Richard A.
Published: February 2025

Botulinum neurotoxin A1 (BoNT/A1) belongs to the most potent toxins and is used as a major therapeutic agent. Neurotoxin conformation is crucial for its translocation to the neuronal cytosol, a key process for intoxication that is only poorly understood. To gain molecular insights into the steps preceding toxin translocation, we determine cryo-EM structures of BoNT/A1 alone and in complex with its receptor synaptic vesicle glycoprotein 2B (SV2B). In solution, BoNT/A1 adopts a unique, semi-closed conformation. The toxin changes its structure into an open state upon receptor binding with the translocation domain (HN) and the catalytic domain (LC) remote from the membrane, suggesting translocation incompatibility. Under acidic pH conditions, where translocation is initiated, receptor-bound BoNT/A1 switches back into a semi-closed conformation. This conformation brings the LC and HN close to the membrane, suggesting that a translocation-competent state of the toxin is required for successful LC transport into the neuronal cytosol.
The neurobench framework for benchmarking neuromorphic computing algorithms and systems
Authors: Yik Jason , Van den Berghe Korneel , den Blanken Douwe , Bouhadjar Younes , Fabre Maxime , Hueber Paul , Ke Weijie , Khoei Mina A. , Kleyko Denis , Pacik-Nelson Noah , Pierro Alessandro , Stratmann Philipp , Sun Pao-Sheng Vincent , Tang Guangzhi , Wang Shenqi , Zhou Biyan , Ahmed Soikat Hasan , Vathakkattil Joseph George , Leto Benedetto , Micheli Aurora , Mishra Anurag Kumar , Lenz Gregor , Sun Tao , Ahmed Zergham , Akl Mahmoud , Anderson Brian , Andreou Andreas G. , Bartolozzi Chiara , Basu Arindam , Bogdan Petrut , Bohte Sander , Buckley Sonia , Cauwenberghs Gert , Chicca Elisabetta , Corradi Federico , de Croon Guido , Danielescu Andreea , Daram Anurag , Davies Mike , Demirag Yigit , Eshraghian Jason , Fischer Tobias , Forest Jeremy , Fra Vittorio , Furber Steve , Furlong P. Michael , Gilpin William , Gilra Aditya , Gonzalez Hector A. , Indiveri Giacomo , Joshi Siddharth , Karia Vedant , Khacef Lyes , Knight James C. , Kriener Laura , Kubendran Rajkumar , Kudithipudi Dhireesha , Liu Shih-Chii , Liu Yao-Hong , Ma Haoyuan , Manohar Rajit , Margarit-Taulé Josep Maria , Mayr Christian , Michmizos Konstantinos , Muir Dylan R. , Neftci Emre , Nowotny Thomas , Ottati Fabrizio , Ozcelikkale Ayca , Panda Priyadarshini , Park Jongkil , Payvand Melika , Pehle Christian , Petrovici Mihai A. , Posch Christoph , Renner Alpha , Sandamirskaya Yulia , Schaefer Clemens J. S. , van Schaik André , Schemmel Johannes , Schmidgall Samuel , Schuman Catherine , Seo Jae-sun , Sheik Sadique , Shrestha Sumit Bam , Sifalakis Manolis , Sironi Amos , Stewart Kenneth , Stewart Matthew , Stewart Terrence C. , Timcheck Jonathan , Tömen Nergis , Urgese Gianvito , Verhelst Marian , Vineyard Craig M. , Vogginger Bernhard , Yousefzadeh Amirreza , Zohora Fatima Tuz , Frenkel Charlotte , Reddi Vijay Janapa
Published: February 2025

Neuromorphic computing shows promise for advancing computing efficiency and capabilities of AI applications using brain-inspired principles. However, the neuromorphic research field currently lacks standardized benchmarks, making it difficult to accurately measure technological advancements, compare performance with conventional methods, and identify promising future research directions. This article presents NeuroBench, a benchmark framework for neuromorphic algorithms and systems, which is collaboratively designed from an open community of researchers across industry and academia. NeuroBench introduces a common set of tools and systematic methodology for inclusive benchmark measurement, delivering an objective reference framework for quantifying neuromorphic approaches in both hardware-independent and hardware-dependent settings. For latest project updates, visit the project website (neurobench.ai).
Lack of harmonisation of greenhouse gases reporting standards and the methane emissions gap
Authors: Cenci Simone , Biffis Enrico
Published: February 2025

Monitoring companies’ contributions to climate dynamics and their exposure to transition risks requires accurate measurements of their non-carbon dioxide greenhouse gas emissions (non-CO2 GHG). However, carbon accounting standards are not harmonised and allow for some discretion when converting emissions of different GHGs into CO2 equivalent units, the currency in which carbon footprints are expressed. Focusing on methane, we build counterfactual harmonised standards using the latest IPCC Global Warming Potential (GWP) values over 100 years and estimate a cumulative gap in reported methane emissions of 170MtCO2e ( ~6Tg) over a sample of 2864 companies. Changing the counterfactual from GWP100to GWP20, as recently codified in certain jurisdictions and initiatives, increases the cumulative gap to 3300MtCO2e ( ~40Tg). The gap only covers direct emissions and hence understates the extent of potential under-reporting across value chains. Overall, our study underscores the importance of global harmonisation of CO2-equivalence standards to coherently track corporate GHG emissions and their exposure to transition risks.
A comprehensive metabolomic study of three Egyptian Salsola species revealed their potential anti-inflammatory activity
Authors: Zakaria Abdelrhman , Kassem Fahima. F. , Ghareeb Doaa A. , Shams Eldin Safa M. , Selim Dina A.
Published: February 2025

Salsola plants are halophytic crops that are distributed worldwide, with more than 100 species figured out in Asia, the Mediterranean region and North Africa. Different Salsola species were reported to exert marked anti-inflammatory activities, whereas the potential anti-inflammatory activities of the three species, S. tetrandra, S. tetragona and S. vermiculata, have not been evaluated. This study provides a comprehensive metabolic study of the shoots and roots of those three species to identify potential anti-inflammatory candidates. An ultra-high performance liquid chromatography mass-mass spectrometry (UHPLC MS/MS) method in conjunction with multivariate analysis principles was utilized in an attempt to decipher their bio-active metabolites and their relevant anti-inflammatory activities. Eighty metabolites were identified in the tested extracts, where nitrogenous compounds and phenolics were highly detected in S. tetragona samples, meanwhile, saponins and phenolic acids were highly dominant in S. tetrendra sample and S. vermiculata samples have a similar chemical profile as S. tetrandra. Concerning the anti-inflammatory activity of the tested extracts, the safety margin of all the tested extracts was higher than that of the standard drug piroxicam. The shoots of the three species demonstrated more potent anti-inflammatory activities compared to the roots. The shoot extract of S. tetrandra was the most biologically active fraction. The obtained results revealed the shoots of the three Salosla species to be promising anti-inflammatory drug candidates of high safety and efficacy that could be used in the pharmaceutical industry.
Investigating brain activity at rest in patients with persistent genital arousal disorder (PGAD) using functional magnetic resonance imaging
Authors: Dalkeranidis Eleni , Kümpers Franziska M L M , Sinke Christopher , Krüger Tillmann H C
Published: February 2025

Persistent genital arousal disorder (PGAD) is a rare disease causing high emotional distress eminently impacting the individual’s quality of life. Experts in this field assume that the disease is caused by a multifaceted interplay of different etiologies which may share a common neurobiological basis. However, only one functional neuroimaging investigation exist, and a more in-depth comprehension of the neurobiological foundation is required. Therefore, this study aims to provide new insights into how the functional integration of brain regions may relate to PGAD. By using the functional magnetic resonance imaging (fMRI) technique, functional connectivity at rest (rs-FC) was compared between patients suffering PGAD (n = 26) and healthy controls (n = 26). Patients with PGAD showed different pattern in connectivity within brain structures putatively associated with the psychological and somatic dimensions of the disease including the right amygdala, left anterior cingulate cortex, right insula cortex, thalamic nuclei and prefrontal regions as seeds. The majority of these showed differences in brain connectivity pattern to the precuneus and prefrontal regions. The study offers preliminary insights into the characteristics and relevant neural mechanisms of PGAD. Nevertheless, since this study did not identify any peripheral correlates that would corroborate the interpretation of these findings, they were interpreted from a more theoretical perspective, thereby offering potential areas of focus for future research.