bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical characteristics and outcomes in leptomeningeal disease with or without brain metastasis: insights from an explorative data analysis of the Charité LMD registry
Authors: Wasilewski David , Eitner Chiara , Ates Rober , Murad Selin , Shaked Zoe , Steinle Julia Alexandra , Wetzel-Yalelis Andreas , Sargut Tarik Alp , Rösler Judith , Samman Majd Abdulhamid , Truckenmüller Peter , Mertens Robert , Kroneberg Daniel , Kowski Alexander , Radbruch Helena , Capper David , Ehret Felix , Roohani Siyer , Frost Nikolaj , Nawabi Jawed , Onken Julia , Schlaak Maximilian , Blohmer Jens-Uwe , Pelzer Uwe , Keller Ulrich , Sehouli Jalid , Vajkoczy Peter , Keilholz Ulrich , Misch Martin
Published: February 2025

Introduction and objectives

Leptomeningeal disease (LMD) involves disseminating cancer cells to the leptomeninges and cerebrospinal fluid. The impact of intracranial parenchymal brain metastases and extracranial disease burden at LMD diagnosis remains unclear. This study evaluates these factors alongside local and systemic therapies before and after LMD diagnosis.

Methods

A retrospective analysis was conducted on 188 patients diagnosed with LMD between 2011 and 2024. Data on demographics, imaging findings, and treatments were collected. Kaplan–Meier estimates were used for survival analysis, and independent prognostic factors were identified using a backward-stepwise Cox regression model.

Results

Primary cancers included breast cancer (34.0%), non-small cell lung cancer (22.3%), and melanoma (14.4%). LMD was diagnosed via MRI in 56.4% of cases, cerebrospinal fluid (CSF) cytology in 2.7%, and both in 41.0%. Median overall survival was 2.8 months [95% CI: 2.4 – 3.7]. Independent prognostic factors for improved survival included male sex (HR: 0.61 [95% CI: 0.40 – 0.93], p = 0.020), absence of hydrocephalus at LMD diagnosis (HR: 0.42 [95% CI: 0.22 – 0.79], p = 0.007), and targeted therapy post-diagnosis (HR: 0.33 [95% CI: 0.20 – 0.55], p < 0.001). Two or more lines of systemic therapy before LMD diagnosis increased mortality risk (HR: 1.73 [95% CI: 1.16 – 2.59], p = 0.007). Lack of CNS parenchymal disease at LMD diagnosis also increased risk (HR: 0.51 [95% CI: 0.30 – 0.89], p = 0.017). Pre-diagnosis radiation therapy showed no survival benefit, while post-diagnosis radiation improved outcomes (HR: 0.47 [95% CI: 0.32 – 0.70], p < 0.001).

Conclusion

Absence of hydrocephalus and use of targeted therapy post-diagnosis are favorable prognostic factors, while extensive prior systemic therapy and CNS parenchymal disease worsen outcomes. Tailored therapies addressing intracranial disease are crucial for improving survival in LMD patients.
Exploring the predictors of the populist vote using random forests
Authors: Benati Stefano , Bon Matteo , Nardi Filippo
Published: February 2025

In this paper, we use random forests to determine what individual attitudes and opinions are the best predictors of the vote for a populist party. We used data from the European Value Survey, Wave 7, and after coding European parties as populist or not, we carried out a preliminary analysis on two peculiar nations, France and Poland, highlighting the basic steps of a random forests application. The analysis reveals that populist voters have different attitudes. In Poland, the populist vote is mostly predicted by the adherence to religious and traditional values. In France, vote is mostly predicted by strong discontent on the actual practice of democracy. However, we show that predictions can be biased when imbalanced data are used, that is, data in which the minority class contains few observations. We discuss how to obtain a balanced dataset and we show that in this way the predictive power of the random forests is improved. Next, we extend the analysis of the populist vote to all the European nations available in the survey, to determine what are the most important predictors both at supranational and national level. The use of the random forest allows determining what are the most common global predictors, and the role of some local predictors as well.
A2B adenosine receptor-triggered intracellular calcium mobilization: Cell type-dependent involvement of Gi, Gq, Gs proteins and protein kinase C
Authors: Gao Zhan-Guo , Gao Ray R. , Meyer Clayton K. , Jacobson Kenneth A.
Published: February 2025

Activation of PLCβ enzymes by Giβγ and Gαq/11 proteins is a common mechanism to trigger cytosolic Ca2+ increase. We and others reported that Gαq/11 inhibitor FR900359 (FR) can inhibit both Gαq- and, surprisingly, Giβγ-mediated intracellular Ca2+ mobilization. Thus, the Gαi-Gβγ-PLCβ-Ca2+ signaling axis depends entirely on the presence of active Gαq, which reasonably explained FR-inhibited Giβγ-induced Ca2+ release. However, the conclusion that Giβγ signaling is controlled by Gαq derives mostly from HEK293 cells. Here we show that indeed in HEK293 cells both Gαq/11 siRNA and Gαq/11 inhibitors diminished Ca2+ increase triggered by native Gq-coupled P2Y1 receptors, or by transfected Gi-coupled A1- or Gs-coupled A2B adenosine receptors (ARs). However, in T24 bladder cancer cells, Gi inhibitor PTX, but not Gαq/11 inhibitors, FR, YM254890 (YM) or Gq/11 siRNA, inhibited Ca2+ increase triggered by native A2BAR activation. Simultaneous inactivation of Gi and Gs further suppressed A2BAR-triggered Ca2+ increase in T24 cells. The Gαq/11 inhibitor YM fully and partially inhibited endogenous P2Y1- and β2-adrenergic receptor-induced Ca2+ increase in T24 cells, respectively. PKC activator PMA partially diminished A2BAR-triggered but completely diminished β2-adrenergic receptor-triggered Ca2+ increase in T24 cells. Neither β-arrestin1 nor β-arrestin2 siRNA affected A2BAR-mediated Ca2+ increase. Unlike in T24 cells, YM inhibited native A2BAR-triggered calcium mobilization in MDA-MB-231 breast cancer cells. Thus, Gαq/11 is vital for Ca2+ increase in some cell types, but Giβγ-mediated Ca2+ signaling can be Gαq/11-dependent or independent based on cell type and receptor activated. Besides G proteins, PKC also modulates cytosolic Ca2+ increase depending on cell type and receptor.
How curriculum materials can contribute to implementing instructional innovations: the case of enactment of strategy instruction
Authors: Dröse Jennifer , Ahlemeyer Leonie , Prediger Susanne
Published: February 2025

Although curriculum materials are essential for implementing instructional innovations, little is known about how exactly they support teachers’ enactment of innovative approaches and how explicitly they must integrate their key components. The paper contributes to reducing this research gap for one instructional innovation: explicit strategy instruction for word problem comprehension strategies. In our qualitative video study, teachers participated in a professional development on explicit strategy instruction and experimented with it in their classrooms. We compared the teachers’ enactment of strategy instruction in two implementation conditions: in the strong material support condition, teachers received curriculum materials in which components of strategy instruction were explicitly integrated. In the weak material support condition, the curriculum materials only provided the sequence of word problems, but the teachers had to implement explicit strategy instruction themselves. In the qualitative analysis of four cases of teachers’ videorecorded enactment, we unpacked how one teacher with weak support provided only limited learning opportunities by non-targeted enactment, with limited measurable student strategic learning gains. However, in the same condition, another teacher provided productive learning opportunities by explicit and targeted strategy instruction in spite of weak material support. In the strong material support condition, learning opportunities were assured even in a case of partially non-targeted enactment (yet high measurable student strategic learning gains). The findings bear consequences for combining curriculum materials with strong support and professional development.
INIA 333 – CHUGAYNA new Potato Variety Resilient to Climate Change for the Family Farming System with Tolerance to Frost, Resistant to Late Blight and high Quality for Fresh Consumption
Authors: Cabrera Héctor , Otiniano Ronal , Pando Rosemeri , Garcia Henry Sánchez , Rodriguez Willian Huamanchay , Pérez Juan M. , de Haan Stef , Gastelo Manuel
Published: February 2025

The new potato variety INIA 333–CHUGAYNA, is the result of the joint work of the NGO Asociación Pataz, INIA and the International Potato Center, it was generated through traditional breeding and the use of the participatory varietal selection methodology, as a variety resilient to climate change with frost tolerance, resistance to late blight, compared to the improved variety INIA 302-Amarilis and the native varieties, Huevo de Indio. This new variety is also resilient to climate change, tolerant to frost, with field resistance to late blight, high tuber yield, low glycoalkaloid content and high quality for fresh consumption, adapted up to 4000 m above sea level. It was released in 2023 and officially registered in the national registry of commercial varieties of Peru. The new variety INIA 333-CHUGAYNA requires minimal use of fungicides and has a high economic profitability that will improve the living standards of small and medium-sized farmers in Peru. It can also be used as a parent in breeding programs in other countries in development, to confront climate change, especially frost.
Chemical analysis of the 5th and 12th century metal doors in the Lateran, Rome
Authors: Mödlinger Marianne , Fera M. , Utz J.
Published: February 2025

For the first time, the three bronze doors of the Lateran Baptistery and Cloister of the Archbasilica of St John Lateran in Rome have been studied to determine their chemical composition and to obtain further information about their manufacture. The doors studied include two made at the end of the twelfth century by Pietro and Uberto from Piacenza, Italy, and one made by an unknown master in the fifth century. This door now leads to the Oratory of St John the Baptist in the Lateran Baptistery. One of the 12th-century doors is now in the Chapel of St. John the Evangelist, and the second 12th-century door is in the cloister of the Archbasilica. High-resolution photographic documentation and a 3D model of one of the door wings complete the detailed documentation of the three medieval doors. The chemical analysis of the doors permits a detailed reconstruction of the alloys used in their manufacture. All doors were made of leaded tin bronze, and the resulting data provides a valuable contribution to the history of their construction and the processes employed in their manufacture.
Open-Source InSAR Data to Detect Ground Displacement Induced by Underground Gas Storage Reservoirs
Authors: Fibbi Gabriele , Landini Neri , Intrieri Emanuele , Ventisette Chiara Del , Soldato Matteo Del
Published: February 2025

This study investigates ground displacement in Underground Gas Storage (UGS) areas using Interferometric Synthetic Aperture Radar (InSAR) techniques applied to free and open-source Sentinel-1 data extracted from the European Ground Motion Service (EGMS). Three UGS facilities in Lower Saxony, Germany, are examined to understand how reservoir type plays a key role in surface deformation. In pore storage reservoirs, such as those at Uelsen and Rehden, UGS operations cause pressure changes propagating to the surface and resulting in observable seasonal uplift and subsidence. Conversely, in the Etzel salt caverns, subsidence is inherent, with deformation rates influenced by the balance of gas withdrawal and injection. The analysis includes mapping the displacement velocity in both ascending and descending geometries, as well as the vertical and horizontal components of the displacement. The extracted time series of ground displacement reveal temporal relationships between UGS operations and surface fluctuations. By integrating InSAR data with the UGS operational records, this study highlights significant differences in ground displacement behaviours between geological settings. The Etzel site exhibited the most significant deformations, while the Uelsen and Rehden sites showed seasonal ‘breathing’ patterns. This work represents a novel application, filling a significant gap in the literature by using free and open-source data to investigate UGS activities over different geological contexts. The results highlight the complexity of the interactions between UGS operations and the environment, emphasising the need for further research to improve the sustainable management of subsurface resources.
Context Matters: Soil Ecosystem Status Varies across Diverse Conservation Agriculture Systems
Authors: Preez Gerhard du , Loggenberg Ané , Fourie Driekie , Marcelo-Silva João , Martin Tvisha , Ramphisa-Nghondzweni Dimakatso , Smith Hendrik , Sprunger Christine
Published: February 2025

Conservation agriculture promotes soil health across different management and environmental contexts. While soil ecosystem status (health and functioning) serves as a key indicator of soil health, it remains understudied, with most evidence coming from long-term trials that may not reflect on-farm conditions. Therefore, this study evaluated and compared the long-term soil ecosystem status (health and functioning) of farmer croplands practicing conservation agriculture under two distinct management and environmental contexts. Two sites near Vrede and Reitz (South Africa) were investigated, focusing on conservation agriculture systems, with conventional agriculture and grazed grassland as references systems. Selected ecological indicators (nematode-based indices, organic matter, permanganate-oxidizable carbon, and soil respiration) and physico-chemical properties (particle size distribution, pH, electrical conductivity, and macro- and micronutrients) were assessed to measure soil ecosystem status and the environmental context. At Vrede, pasture and conservation agriculture systems presented elevated organic matter content and microbial activity due to continuous organic cover and minimal physical disturbance. Furthermore, the nematode Maturity Index in these systems was higher, indicating more balanced and healthier soil ecosystems. In contrast, at Reitz, differences between conservation agriculture systems were strongly associated with soil texture differences, influencing organic matter and respiration rates. Additionally, fine-textured soils consistently exhibited greater permanganate-oxidizable carbon values, reflecting the role of soil texture in carbon retention and ecosystem functioning. This study underscores the relevance of both agricultural management and environmental contexts, particularly soil texture, when implementing conservation agriculture systems. It highlights the need for tailored agricultural systems to complement on-farm options and local conditions.
Shocks and Politics
Authors: Bussell Jennifer
Published: February 2025

When will government elites prepare for natural hazards? Existing research posits that governments will respond to disasters, but rarely have incentives to prepare for them. This Element argues that disaster preparedness can, and does, occur in the context of both motivated ruling elites and a capable state. Ruling elites can be mobilized to lead preparedness efforts when there is a risk that past exposure to hazards will lead to political instability in the face of a future hazard. Where elites anticipate a threat to their rule in the face of a future hazard, due to substantial past exposure and significant opposition strength, they will be motivated to engage in disaster preparedness. The quality and character of these efforts subsequently depend on the government's capacity to coordinate the design and implementation of preparedness plans. The Element tests this argument using a medium-N, country case study approach, drawing on evidence from ten countries in Africa and three in South Asia, as well as subnational analysis in India.
THE CURIOUS CASE OF THE NATIONAL FUND
Authors: Ellison Martin
Published: February 2025

Changing attitudes to government debt influenced a recent High Court judgement on the National Fund, a British charity set up in 1928 with donations left to accumulate until they grew sufficient to repay in full the National Debt of the United Kingdom. Based on a belief that the Fund would never become large enough, the Attorney General in 2018 applied under cy-près jurisdiction to allow the charity to repay only part of the National Debt. The argument was that changing attitudes to debt have rendered the charity’s aim impracticable, even though it was at the time it was set up.
“These Are not Ordinary Criminals!” The First War Crimes Trial at the People's Tribunal and Its Implications in Post-Holocaust Romania
Authors: Ionescu Stefan Cristian
Published: February 2025

This article examines the neglected war crimes trials of Holocaust perpetrators that took place at the People's Tribunal in early postwar Romania, focusing especially on the first trial (the “Macici group”). The article shows that in spite of the political interferences by the new pro-communist regime and the USSR, the Macici group trial in particular, and the first war crimes trials in general, were not Stalinist show trials or fake trials and they sentenced real war criminals and accurately captured Romania's participation in the Holocaust. Unlike the Antonescu group trial – that indicted the former pro-Nazi dictator and his closest collaborators – the first war crimes trial was not a typical political trial. In general, it respected the rule of law of the era. Resembling the cases of other trials of Nazi perpetrators and collaborators in postwar Europe, the Romanian perpetrators invoked superior orders as their main line of defense. In spite of the public perception and the communist regime's propaganda, the primary sources show that the People's Tribunal proved rather lenient and inefficient. Additionally, these trials had an important political-social role in postwar Romania and helped the communist regime discredit political adversaries, purge the judiciary, gain legitimacy, and increase its control of local society.
The impact of intermittent energy restriction on women’s health
Authors: Harvie Michelle , Haiba Mai
Published: February 2025

Intermittent energy restricted diets are used amongst women with overweight and obesity and a healthy weight. For those with overweight and obesity weight control is typically achieved through daily energy restriction (DER) which has reduced adherence and attenuated metabolic benefits over time. Several intermittent energy restriction (IER) regimens have been developed aiming to promote maintained weight loss and additional weight independent metabolic benefits including the 5:2 diet, alternate day fasting (ADF) and time restricted eating (TRE). This review summarises the potential benefits or harms of these regimens for managing women’s health. 5:2 and ADF diets have equivalent long term (≥6-month) adherence, weight loss and metabolic benefits to DER. Current limited evidence suggests IER is a safe weight loss intervention for women which does not affect reproductive or bone health, increase eating disorders or disturb sleep. Adherence and weight loss with both IER and DER are lower amongst younger women compared to older women and men. Weight loss with ADF and TRE have respectively improved symptoms of polycystic ovarian syndrome and premenstrual syndrome but there is no evidence of weight independent effects of IER on these conditions. There is little evidence of the benefits and/or harms of IER amongst healthy weight women in whom there is a greater potential for adverse effects on reproductive and bone health, fat free mass, eating disorders and sleep. Further research benefits of IER for weight control and metabolic health as well as harms is required.
Neural correlates of emotional processing in trauma-related narratives
Authors: Cao Minne , Zhu Shengnan , Tang Enze , Xue Chuang , Li Kun , Yu Hua , Zhong Tao , Li Tao , Chen Hui , Deng Wei
Published: February 2025

Background

Post-traumatic stress disorder (PTSD) is a mental health condition caused by the dysregulation or overgeneralization of memories related to traumatic events. Investigating the interplay between explicit narrative and implicit emotional memory contributes to a better understanding of the mechanisms underlying PTSD.

Methods

This case–control study focused on two groups: unmedicated patients with PTSD and a trauma-exposed control (TEC) group who did not develop PTSD. Experiments included real-time measurements of blood oxygenation changes using functional near-infrared spectroscopy during trauma narration and processing of emotional and linguistic data through natural language processing (NLP).

Results

Real-time fNIRS monitoring showed that PTSD patients (mean [SD] Oxy-Hb activation, 0.153 [0.084], 95% CI 0.124 to 0.182) had significantly higher brain activity in the left anterior medial prefrontal cortex (L-amPFC) within 10 s after expressing negative emotional words compared with the control group (0.047 [0.026], 95% CI 0.038 to 0.056; p < 0.001). In the control group, there was a significant time-series correlation between the use of negative emotional memory words and activation of the L-amPFC (latency 3.82 s, slope = 0.0067, peak value = 0.184, difference = 0.273; Spearman’s r = 0.727, p < 0.001). In contrast, the left anterior cingulate prefrontal cortex of PTSD patients remained in a state of high activation (peak value = 0.153, difference = 0.084) with no apparent latency period.

Conclusions

PTSD patients display overactivity in pathways associated with rapid emotional responses and diminished regulation in cognitive processing areas. Interventions targeting these pathways may alleviate symptoms of PTSD.
Implicit neural sensitivity for negatively valued social and non-social visual scenes in young adults exposed to childhood adversity
Authors: Qiao Zhiling , Van der Donck Stephanie , Mazereel Victor , Jennen Lise , Samaey Celine , Vancampfort Davy , van Winkel Ruud , Boets Bart
Published: February 2025

Background

Based on facial expression experiments, childhood adversity may be associated with threat-related information processing bias. Yet, it is unclear whether this generalizes to other threat-related stimuli, such as social and non-social visual scenes.

Methods

We combined fast periodic visual stimulation with frequency-tagging electroencephalography (EEG) and eye-tracking to assess automatic and implicit neural discrimination, neural salience and preferential looking towards negative versus neutral social and non-social visual scenes in young adults aged 16–24 years (51 with childhood adversity and psychiatric symptoms and 43 controls).

Results

Controls showed enhanced negative-neutral neural discrimination within a social versus non-social context. However, this facilitating effect of social content was absent in those with adversity, suggesting a selective alteration in social threat processing. Moreover, individual differences in adversity severity, and more specifically threat experiences (but not neglect experiences), were associated with decreased neural discrimination of negative versus neutral social scenes, corresponding to similar findings in facial expression processing, indicating the robustness of adversity-related deficits in threat-safety discrimination across social visual stimuli.

Conclusions

The adversity-related decreased threat-safety discrimination might impact individuals’ perception of social cues in daily life and relate to poor social functioning and future development of psychopathology.
Overcoming the agglomeration paradox: skill-dependent FDI and urbanization in China
Authors: Vortherms Samantha A.
Published: February 2025

The influx of foreign capital into cities in developing countries creates new labor demands, triggering significant internal migration as workers move for opportunities. But this mobilization creates a management problem for local governments. How do local officials manage competing interests in developing their labor market while preventing governance problems from excessive demand on public resources? Using the highly institutionalized case of China, I argue that local governments encourage long-term migration of “desirable” migrants by integrating them into social services while keeping others out. Variation in locally invested FDI skill dependence drives variation in inclusivity towards internal migrants. Policies that facilitate the integration of internal migrants into local urban welfare systems correlate with investment in firms with greater dependence on high-skilled workers, especially when investment flows to firms established more than one year previously. These trends are strongest in eastern municipalities where market forces play a larger role in local development policies.
Empirical Models of Shallow Groundwater and Multi‐Hazard Flood Forecasts as Sea‐Levels Rise
Authors: Cox Simon C. , Ettema Marc H. J. , Chambers Lee A. , Stephens Scott A. , Bodeker Gregory E. , Nguyen Quyen , Diaz‐Rainey Ivan , Moore Antoni B.
Published: February 2025

Knowledge of coastal hydrogeology and hazards as groundwater responds to sea‐level rise (SLR) can be improved through installation of shallow groundwater monitoring piezometers and continuous observations. Interpolation of site data enables mapping of the present‐day state of groundwater elevation, depth to groundwater (DTW), their temporal statistical variation, and differing spatial responses to tides and rainfall. Future DTW and its variability can be projected under increments of SLR, with assumptions and caveats, to show where and when episodic and/or permanent inundation can be expected. This methodology is outlined in a case study of Dunedin, New Zealand, which enabled comparison of rising groundwater's contribution to pluvial flooding and groundwater emergence with coastal inundation. Changes in relative land exposure with SLR shows evolution in flood hazard from current pluvial‐dominated events, into “flooding from below” and groundwater emergence, in advance of any overland coastal inundation. Dunedin exemplifies how groundwater transfers effects of SLR surprisingly far inland, but the lowest‐lying or shoreline‐proximal suburbs are not necessarily the most vulnerable. Unlike coastal inundation, rising groundwater is unconstrained by protective topography and presents as a creeping hazard, or contributor to hazards such as pluvial flooding, which can be widespread, occurring already and difficult to defend against. The empirical models contain assumptions and uncertainties important to the veracity of results and application. While conservative (“risk averse”) and a compromise from computationally expensive numerical solutions, their value is in providing the spatial and temporal precision needed for multi‐source hazard assessment and holistic adaptive planning.
En‐échelon Rifting and Origin of the Volcanism in the Comoros
Authors: Boymond P. , Feuillet N. , Thinon I. , Scholtès L. , Zaragosi S. , Leroy S. , Lemoine A.
Published: February 2025

Two volcanic provinces have been recently discovered during the SISMAORE oceanographic cruise in the Comoros archipelago in the North Mozambique Channel between Madagascar and East Africa: N’Droundé, along the North‐eastern insular slopes of Grande Comores Island and Mwezi, in the abyssal plain, north‐east of Mayotte and Anjouan islands. By combining bathymetry and backscatter data, high‐resolution seismic reflection and sub‐bottom profiles, we have identified and mapped various tectonic (faults, forced folds) and volcanic structures (lava flows, edifices, sills, dykes) at several spatial scales on the seabed and in cross‐section within the sedimentary cover. We have characterized the volcano‐tectonic structures (geometry, segmentation, and kinematics) to better understand the link (geometry, chronology) between tectonic and volcanic processes. We show that volcanic and tectonic features are controlled by tectonic processes and vice‐versa. Ridges, volcanic cones and lava flows are set up along fissures and dikes during main rifting events to accommodate a N40°E regional extension within an E‐W right lateral shear transfer zone. The volcano tectonic features are Plio‐Pleistocene. This transfer zone lies between the offshore branch of the East African rift system and Malagasy grabens and may have formed when the East African rifts propagated offshore. We evidence a major rifting episode in the last Ma. The estimated volume and flux of extruded lavas show that the volcanism of the Comoros could be related to shallow tectonic processes.
Short‐Period Flapping Motion of Current Sheet in Saturn's Magnetosphere
Authors: Xu S. B. , Huang S. Y. , Yuan Z. G. , Jiang K. , Wu H. H. , Zhang J. , Wang Z. , Xiong Q. Y. , Lin R. T.
Published: February 2025

The flapping motion of the current sheet is a common dynamic phenomenon in the planetary magnetosphere and plays an important role in the transportation of energy and disturbances. Based on the measurements from the Cassini spacecraft, we investigate the short‐period flapping motions of the current sheet characterized by periods significantly much smaller than the planetary rotation cycle in Saturn's magnetosphere. Employing the Minimum Variance Analysis (MVA) method, a new technique is developed to distinguish the propagation of current sheet flapping in the radial and azimuthal directions. A total of 105 short‐period current sheet flapping events have been detected in Saturn's magnetosphere. The global spatial distribution of these events is provided, and their respective propagation directions have been identified. Further discussions are conducted on the potential sources of the short‐period current sheet flapping in Saturn's magnetosphere, including magnetic reconnection, Titan, fast plasma flow, planetary period oscillations, and instabilities near the magnetopause.
Diverse Altitudinal Patterns and Drivers of Greenhouse Gas Dynamics in Southwest China Alpine Streams and Rivers
Authors: Wang Ying , Li Yuhao , Wang Genxu , Li Yang , Sun Xiangyang , Wang Wenzhi , Song Chunlin
Published: February 2025

Streams and rivers are globally significant sources of greenhouse gases (GHGs) to the atmosphere. However, GHG evasion from mountain streams remains poorly constrained due to scarce data. In this study, we measured concentrations and estimated fluxes of riverine carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O) across three alpine catchments in Southwest China. GHG concentrations in these turbulent streams and rivers are slightly oversaturated but much lower than the global average, likely due to high gas transfer velocities that rapidly deplete GHGs. Headwater streams (first‐order) exhibited higher gas evasion rates than large rivers (fourth‐order), despite having lower CO2 and N2O concentrations. The partial pressure of CO2 and dissolved N2O concentrations decreased linearly with elevation, likely linked to the altitudinal patterns of forest cover and groundwater table depth. Dissolved CH4 concentrations and the three GHGs fluxes showed weak relationships with elevation. We observed significant seasonal differences in GHG fluxes, with higher evasion rates during the wet season. The seasonal and spatial heterogeneity in stream GHG concentrations and fluxes was primarily controlled by hydrology, climate, and geomorphology. Our analyses also revealed that GHG fluxes were positively correlated with stream water temperature, velocity, and channel slope. This study demonstrates that these alpine streams are underestimated net sources of GHGs, particularly CO2 and N2O, highlighting the importance of mountain headwater systems in regional and global GHG budgets. The diverse altitudinal patterns of GHG dynamics also suggest complex controls of GHG in alpine streams and rivers.
A Buried Columbia‐Forming Orogen Front Located in the Northwestern North China Craton
Authors: Tian Gang , Yang Minghui , Ma Li , Song Lijun , Wen Xiaogang , Xue Haijun , Jia Huichong , Pu Renhai , Chen Jie , Chen Shuo
Published: February 2025

The Inner Mongolia Suture Zone (IMSZ) in the North China Craton is an important component of the Colombia‐forming orogen, and its southern may have preserved the deformation relics of the ancient orogen front due to being prolonged buried beneath the Ordos Basin. Here we used the high‐resolution seismic profiles in the North Ordos Basin and U‐Pb zircon age data from the borehole basement samples to discover the existence of wedge tectonics consisting of thrust belt and ramp structure within the basement and to fingerprint markedly different basement ages on both sides of the Thrust Front Belt (TFB). The footwall rocks (∼2.2–1.95 Ga) have a dominant affinity with the south‐central Ordos Block (OB), while the hanging wall rocks (∼2.51–2.46 Ga) have no immediate affinity with the OB, possibly representing a set of late Neoarchean‐early Paleoproterozoic island arc formations developed in the northern margin of the OB (termed the Hangjinqi Terrane). So our preferred interpretation posits that the wedge tectonics was formed by wedging the OB into the underthrusting Hangjinqi Terrane during the ∼1.95 Ga collision between the Yinshan Block and OB, with the TFB demarcated as the tectonic boundary separating the OB and IMSZ. This wedge tectonics in the late Paleoproterozoic orogen flank bears a striking resemblance to crustal structures in Phanerozoic orogenic settings, suggesting that this orogenesis mode of crustal deformation has been initiated at least in the Orosirian and may have been a significant orogen mode for the assembly of the Columbia supercontinent.
NF-κB RelB suppresses the inflammatory gene expression programs of dendritic cells by competing with RelA for binding to target gene promoters
Authors: Navarro Héctor I. , Daly Allison E. , Rodriguez Benancio , Wu Sunny , Ngo Kim A. , Fraser Anna , Schiffman Allison , Liu Yi , Smale Stephen T. , Chia Jennifer J. , Hoffmann Alexander
Published: February 2025

A group of autoinflammatory disorders termed relopathies arise as a consequence of NF-κB dysregulation. Genetic loss of the NF-κB subunit RelB in humans and mice leads to autoimmunity and lethal multi-organ inflammatory pathology. Our recent study showed that this inflammatory pathology is independent of type I interferon signaling, and further identified dysregulation of a set of pro-inflammatory NF-κB target genes. However, it remains unknown how the loss of RelB leads to the dysregulation of these NF-κB motif-containing pro-inflammatory genes. Here, we report epigenome profiling studies revealing that RelB is associated with pro-inflammatory genes in dendritic cells. While these genes recruit RelA binding upon exposure to a maturation stimulus, we observed substantially more RelA recruitment in the absence of RelB. For these genes, we found that elevated RelA recruitment is correlated with elevated gene expression. To test whether RelB may compete with RelA for binding to NF-κB-regulated gene promoters via competition for κB sites, we generated a new mouse strain (RelB

DB/DB
) that harbors targeted point mutations in the RelB DNA binding domain that eliminates high-affinity DNA binding. We found that this targeted mutation in the RelB DNA binding domain is sufficient to drive multi-organ inflammatory pathology. These results provide insights into the biological mechanism of RelB as a suppressor of pro-inflammatory gene expression and autoimmune pathology.
Accelerated epigenetic aging in Huntington’s disease involves polycomb repressive complex 1
Authors: Brulé Baptiste , Alcalá-Vida Rafael , Penaud Noémie , Scuto Jil , Mounier Coline , Seguin Jonathan , Khodaverdian Sina Vincent , Cosquer Brigitte , Birmelé Etienne , Le Gras Stéphanie , Decraene Charles , Boutillier Anne-Laurence , Merienne Karine
Published: February 2025

Loss of epigenetic information during physiological aging compromises cellular identity, leading to de-repression of developmental genes. Here, we assessed the epigenomic landscape of vulnerable neurons in two reference mouse models of Huntington neurodegenerative disease (HD), using cell-type-specific multi-omics, including temporal analysis at three disease stages via FANS-CUT&Tag. We show accelerated de-repression of developmental genes in HD striatal neurons, involving histone re-acetylation and depletion of H2AK119 ubiquitination and H3K27 trimethylation marks, which are catalyzed by polycomb repressive complexes 1 and 2 (PRC1 and PRC2), respectively. We further identify a PRC1-dependent subcluster of bivalent developmental transcription factors that is re-activated in HD striatal neurons. This mechanism likely involves progressive paralog switching between PRC1-CBX genes, which promotes the upregulation of normally low-expressed PRC1-CBX2/4/8 isoforms in striatal neurons, alongside the down-regulation of predominant PRC1-CBX isoforms in these cells (e.g., CBX6/7). Collectively, our data provide evidence for PRC1-dependent accelerated epigenetic aging in HD vulnerable neurons.
Double-strand break repair pathways differentially affect processing and transduction by dual AAV vectors
Authors: Maurer Anna C. , Benyamini Brian , Whitney Oscar N. , Fan Vinson B. , Cattoglio Claudia , Kissiov Djem U. , Dailey Gina M. , Darzacq Xavier , Weitzman Matthew D. , Tjian Robert
Published: February 2025

Recombinant adeno-associated viral vectors (rAAV) are a powerful tool for gene delivery but have a limited DNA carrying capacity. Efforts to expand this genetic payload have focused on engineering the vector components, such as dual trans-splicing vectors which double the delivery size by exploiting the natural concatenation of rAAV genomes in host nuclei. We hypothesized that inefficient dual vector transduction could be improved by modulating host factors which affect concatenation. Since factors mediating concatenation are not well defined, we performed a genome-wide screen to identify host cell regulators. We discover that Homologous Recombination (HR) is inhibitory to dual vector transduction. We demonstrate that depletion or inhibition of HR factors BRCA1 and Rad51 significantly increase reconstitution of a large split transgene by increasing both concatenation and expression from rAAVs. Our results define roles for DNA damage repair in rAAV transduction and highlight the potential for pharmacological intervention to increase genetic payload of rAAV vectors.
Holographic tomographic volumetric additive manufacturing
Authors: Álvarez-Castaño Maria Isabel , Madsen Andreas Gejl , Madrid-Wolff Jorge , Sgarminato Viola , Boniface Antoine , Glückstad Jesper , Moser Christophe
Published: February 2025

Several 3D light-based printing technologies have been developed that rely on the photopolymerization of liquid resins. A recent method, so-called Tomographic Volumetric Additive Manufacturing, allows the fabrication of microscale objects within tens of seconds without the need for support structures. This method works by projecting intensity patterns, computed via a reverse tomography algorithm, into a photocurable resin from different angles to produce a desired 3D shape when the resin reaches the polymerization threshold. Printing using incoherent light patterning has been previously demonstrated. In this work, we show that a light engine with holographic phase modulation unlocks new potential for volumetric printing. The light projection efficiency is improved by at least a factor 20 over amplitude coding with diffraction-limited resolution and its flexibility allows precise light control across the entire printing volume. We show that computer-generated holograms implemented with tiled holograms and point-spread-function shaping mitigates the speckle noise which enables the fabrication of millimetric 3D objects exhibiting negative features of 31 μm in less than a minute with a 40 mW light source in acrylates and scattering materials, such as soft cell-laden hydrogels, with a concentration of 0.5 million cells per mL.
Numerical modeling of oxygen diffusion in tissue spheroids undergoing fusion using function representation and finite volumes
Authors: Vilinski-Mazur Katherine , Kirillov Bogdan , Rogozin Oleg , Kolomenskiy Dmitry
Published: February 2025

A three-dimensional cell culture called a spheroid serves as a foundational entity in a wide variety of modern tissue engineering applications, including 3D-bioprinting and preclinical drug testing. Lack of oxygen within tissue spheroids hinders metabolism of cells and eventually leads to cell death. Prevention of necrosis is crucial to success of tissue engineering methods and such prevention requires estimation of cell viability in the spheroid. We propose a novel approach for numerical modeling of diffusion in tissue spheroids during their fusion. The approach is based on numerical solutions of partial differential equations and the application of Function Representation (FRep) framework for geometric modeling. We present modeling of oxygen diffusion based on meshes derived from the geometry of fusing spheroids, a method for selecting optimal spheroid size, and several statistics for estimating cellular viability. Our findings provide insights into oxygen diffusion in three-dimensional cell cultures thus improving the robustness of biotechnological methods that employ tissue spheroids.
Effects of combined application of slow-release nitrogen fertilizer and urea on nitrogen uptake, utilization and yield of maize under two tillage methods
Authors: Fan Mingyuan , Chen Pei , Zhang Chang , Liang Min , Xie Guangming , Zhao Li , Wang Chuangyun
Published: February 2025

Corn is one of the important food crops in the world, in order to pursue high yield and high efficiency, the input of chemical fertilizer has been continuously increased, which has led to the decline of fertilizer utilization rate, environmental pollution and other problems, and the slow-release fertilizer has attracted much attention because of its nutrient characteristics, but the high price limits its wide application;On the other hand, long-term rotary tillage will lead to the shallowness of the soil tillage layer and the increase of the bulk density of the deep soil, and subsoiling can effectively break the bottom layer of the soil plough and reduce the bulk density of the soil. Therefore, in this study, Qiangsheng 388 was used as the experimental material, and under rotary tillage (R) and rotary tillage + subsoiling (R+S), CK (no fertilization), U (100% nitrogen fertilizer), S (100% slow-release fertilizer) and different UNS ratios (nitrogen fertilizer and slow-release fertilizer) were used for two years in field experiments to explore the effects of slow-release fertilizer and urea on soil water use efficiency, dry matter accumulation, nitrogen uptake and utilization, operation and yield under the two tillage methods. The results showed that compared with CK, U and S, UNS significantly improved water use efficiency, dry matter accumulation, nitrogen uptake, operation and yield. Among them, UNS2 (the ratio of S and U was 7:3) was the best. In 2022, R UNS2 had the best water use efficiency, dry matter accumulation, nitrogen uptake, operation and yield, which were 5.05%, 2.0%, 3.88%, 6.18% and 4.06% higher than those of R + S UNS2, respectively. In 2023, R + S UNS2 had the best treatment, which was 1.98%, 2.52%, 1.85%, 2.60% and 2.20% higher than that of R UNS2, respectively. R + S tillage can effectively improve maize yield, nitrogen uptake and utilization, water use and dry matter accumulation; Nitrogen application treatment UNS2 treatment was the best. In summary, R + S UNS2 is the best coordination strategy.
Clinical effectiveness of Finger gliding Exercise for patients with trigger fingers receiving steroid injection: a Randomized Clinical Trial
Authors: Choi Yue Kwan , Sit Regina Wing-Shan , Wang Bo , Cheuk Christina , Lee Man Kei , Leung Kwan Wa Maria
Published: February 2025

Finger gliding exercises are believed to enhance flexor tendons excursion. This study assesses the effectiveness of finger gliding exercises in patients after receiving steroid injections for trigger fingers. Patients with trigger fingers who received corticosteroid injection were randomly assigned (1:1) to control and intervention group. The intervention group was required to do finger exercises and submit online exercise log regularly. The clinical outcomes of trigger fingers at 24 weeks and compliance with finger gliding exercises were assessed via online surveys. A total of 38 participants were allocated to each group. Baseline characteristics were similar, except for a longer duration of symptoms in the intervention group (5.2 ± 2.9 vs. 3.6 ± 2.6 months, P = 0.002). At 24 weeks, 34 (89.5%) control and 33 (86.8%) intervention group participants responded to online survey. No statistical significant differences were observed in Numerical Pain Rating Score, Quinelle grading, finger improvement rate, recurrence of triggering, need for repeated injection and occurrence of new trigger finger sites. The exercise log response rate and compliance rate were 85.6% and 68.6%. In conclusion, our study did not establish the clinical effectiveness of finger gliding exercise for trigger finger patients following steroid injections compared to usual care.
Long QT syndrome type 3 gain-of-function of Nav1.5 increases ventricular fibroblasts proliferation and pro-fibrotic factors
Authors: Castro Claire , Patin Justine , Jajkiewicz Cyrielle , Chizelle Franck , Cerpa Cynthia Ore , Tessier Agnès , Le Pogam Eva , Fellah Imen , Baró Isabelle , Charpentier Flavien , Derangeon Mickaël
Published: February 2025

The long QT syndrome type 3 (LQT3) is a cardiac channelopathy caused by gain-of-function mutations in the SCN5A gene, encoding the sodium channel Nav1.5. As Nav1.5 is expressed in cardiomyocytes but also in cardiac fibroblasts, we investigated whether the LQT3-causing p.ΔQKP1507-1509 (ΔQKP) SCN5A mutation alters cardiac fibroblast phenotype. Primary cultured ventricular fibroblasts from Scn5a
+/ΔQKP knock-in mice showed increased proliferation, survival, expression of transforming growth factor-β (TGF-β) and activation of its canonical pathway, and reduced α-smooth muscle actin expression. Ventricular tissue from Scn5a
+/ΔQKP mice exhibited augmented fibroblast populations and fibrosis. Inhibiting TGF-β receptor, sodium current or Scn5a expression decreased Scn5a
+/ΔQKP fibroblast proliferation, while veratridine increased proliferation of control fibroblasts, mimicking Nav1.5 gain-of-function. Lastly, abnormal calcium signaling underlied the increased proliferation of Scn5a
+/ΔQKP fibroblasts. Our study shows that cardiac fibroblasts carrying the ΔQKP-SCN5A mutation exhibit an abnormal, proliferative phenotype, paving the way for better understanding the role of cardiac fibroblasts in LQT3.
Cytochrome b5 occurrence in giant and other viruses belonging to the phylum Nucleocytoviricota
Authors: Lamb David C. , Goldstone Jared V. , Belhaouari Djamal Brahim , Andréani Julien , Farooqi Ayesha , Allen Michael J. , Kelly Steven L. , La Scola Bernard , Stegeman John J.
Published: February 2025

Cytochrome b5 is an electron transport protein found in eukaryotes and bacteria, and plays roles in energy production, lipid biosynthesis and cytochrome P450 biochemistry. Here we report that genes for cytochrome b5 occur broadly among viruses in the class Megaviricetes isolated from the deep ocean, freshwater and terrestrial sources, and human patients. Transcriptional analysis showed that Mimivirus bradfordmassiliense cytochrome b5 is expressed in the host and has characteristic spectral properties. Viral cytochrome b5s have either a unique N-terminal transmembrane anchor or are predicted to be soluble proteins. Virus cytochrome b5 proteins share 45–95% sequence identity with one another but no more than 25% identity with that in Acanthamoeba castellanii, a host for many giant viruses. Thus, the origin of cytochrome b5 genes in giant viruses remains unknown. Our findings raise questions regarding the evolution and diversity of cytochrome b5, and about the origin of viral haemoproteins in general.