bluuebunny/crossref_metadata_2025 huggingface dataset:
Selenium efficiency in protecting sperm quality and testicular parameters of South African indigenous Zulu rams exposed to heat stress
Authors: Lekola Khomotso P. M. , Ngcobo Mthobisi S. , Lehloenya Khoboso C.
Published: October 2024

The study investigated selenium’s (Se) efficiency in preserving South African Zulu rams’ sperm quality and testicular parameters when they were exposed to heat stress. Indigenous Zulu rams (20) between 2 and 5 years old were allocated into four groups, namely the Se, testicular heat stress (THS), selenium plus testicular heat stress (SeTHS), and control. Each group comprised five rams; the groups were balanced according to the rams’ body weight and scrotal circumference. The Se and SeTHS groups received sodium selenite orally bi-weekly for 5 months. To induce heat stress, testicular heat insulation bags were wrapped around the testes of the rams receiving the THS and SeTHS treatments for 49 days. Semen was collected from the rams weekly from the third month onward; the first two months were for Se & THS acclimatization. In addition, testicular measurements were taken bi-weekly. Analysis of variance was used to analyze the sperm quality data. Duncan’s multiple range test was used to compare the groups’ data for significant differences. The results showed that the Se-supplemented rams’ scrotal circumference was smaller (p < 0.05) compared with the other groups. The Se, SeTHS, and control groups demonstrated similar total sperm motility; in contrast, the THS and SeTHS groups recorded low and high total sperm motility, respectively, compared with other treatment groups (p < 0.05). The semen from the rams that received THS without Se displayed a significantly higher number of immotile sperm cells (p < 0.05) and poor sperm quality, including total and progressive motility, and kinematic parameters when compared with other treatments, suggesting that Se protects sperm against THS. We concluded that selenium protected some sperm parameters (TSM, PSM, MV, VCL, VSL) of THS- treated rams while others did not improve (RV, NSM, C, STR).
Insider trading in discrete time Kyle games
Authors: Kühn Christoph , Lorenz Christopher
Published: October 2024

We present a new discrete time version of Kyle’s (Econometrica 53(6):1315–1335, 1985) classic model of insider trading, formulated as a generalised extensive form game. The model has three kinds of traders: an insider, random noise traders, and a market maker. The insider aims to exploit her informational advantage and maximise expected profits while the market maker observes the total order flow and sets prices accordingly. First, we show how the multi-period model with finitely many pure strategies can be reduced to a (static) social system in the sense of Debreu (Proc Natl Acad Sci 38(10):886–893, 1952) and prove the existence of a sequential Kyle equilibrium, following Kreps and Wilson (Econometrica 50(4):863–894, 1982). This works for any probability distribution with finite support of the noise trader’s demand and the true value, and for any finite information flow of the insider. In contrast to Kyle (1985) with normal distributions, equilibria exist in general only in mixed strategies and not in pure strategies. In the single-period model we establish bounds for the insider’s strategy in equilibrium. Finally, we prove the existence of an equilibrium for the game with a continuum of actions, by considering an approximating sequence of games with finitely many actions. Because of the lack of compactness of the set of measurable price functions, standard infinite-dimensional fixed point theorems are not applicable.
Clinical usefulness of four-dimensional dynamic ventilation CT for borderline resectable locally advanced esophageal cancer
Authors: Oda Shioto , Kuno Hirofumi , Fujita Takeo , Hiyama Takashi , Kotani Daisuke , Kadota Tomohiro , Sakashita Shingo , Kobayashi Tatsushi
Published: October 2024

Purpose

This study aimed to evaluate the clinical significance of four-dimensional dynamic ventilation CT (4DCT) for assessing resectability in borderline resectable locally advanced esophageal cancer (BR-LAEC) and confirmed the pathological validity of the 4DCT results in surgery without prior treatment.

Materials and methods

We retrospectively reviewed 128 patients (107 men; median age, 68 [range, 43–89] years) diagnosed with BR-LAEC on initial conventional CT (i-CT). These patients were initially classified into three categories: BR1 (closer to resectable), BR2 (resectability not assessable), or BR3 (closer to unresectable). Subsequent 4DCT reclassified patients as either resectable or unresectable within 1 week of i-CT. We analyzed the diagnostic shift induced by 4DCT. Additionally, 18 patients who underwent surgery without prior treatment were evaluated using 4DCT and pathological outcomes.

Results

4DCT reclassified patients with BR-LAEC as resectable (57.0%; 73/128) and unresectable (43.0%; 55/128). Of 53 patients initially classified as BR1, 32.1% (17/53) were reclassified as unresectable, and of 47 patients initially classified as BR3, 46.8% (22/47) were reclassified as resectable. Among 28 patients initially classified as BR2, 53.6% (15/27) were reclassified as resectable and 46.4% (13/27) as unresectable. In the surgery-only cohort of 18 patients, 9 were initially classified as BR1 and 9 as BR2, and all were reclassified as resectable. These patients were pathologically confirmed to have resectable disease.

Conclusions

4DCT may provide information complementary to that provided by initial conventional CT in assessing resectability among patients with BR-LAEC, and could be a useful adjunct tool for guiding clinical decisions in this patient population.
Maintenance Therapy Post-Stem Cell Transplantation for Patients with T-Cell Lymphomas
Authors: Braunstein Zachary , Brammer Jonathan E.
Published: October 2024

Purpose of Review

Given the poor outcomes for peripheral T-cell lymphomas (PTCL), stem cell transplant (SCT) remains an important therapeutic approach. Post-SCT relapse is common and maintenance therapy post-SCT is increasingly being utilized. Here we review the use of post-SCT maintenance therapy for PTCL patients.

Recent Findings

Maintenance therapy is increasingly utilized to decrease post-SCT relapse and improve outcomes in PTCL. Ongoing and completed post-SCT maintenance trials utilizing agents such as romidepsin, brentuximab vedotin, duvelisib, and pembrolizumab have shown efficacy in decreasing relapse. Further, additional agents with efficacy in PTCL have emerged that may inform future maintenance approaches.

Maintenance therapy is a promising approach to maintain response after SCT in PTCL. While several trials are ongoing to evaluate maintenance therapy in PTCL, current data suggests this may be an effective method to decrease post-SCT relapse.
Pathophysiology of Bullous Pemphigoid: Role of Type 2 Inflammation and Emerging Treatment Strategies (Narrative Review)
Authors: Werth Victoria P. , Murrell Dédée F. , Joly Pascal , Heck Renata , Orengo Jamie M. , Ardeleanu Marius , Hultsch Verena
Published: October 2024

Bullous pemphigoid (BP) is an autoimmune blistering disease that most often affects elderly individuals and has a significant negative impact on quality of life. The disease is characterized primarily by autoantibodies to hemidesmosomal proteins BP180 and/or BP230, and an inflammatory reaction with notable features of type 2 inflammation, including elevated serum IgE, increased numbers of eosinophils in lesions and peripheral blood, and elevated expression of type 2 cytokines and chemokines in skin lesions. In this review, we present what is known about BP pathophysiology, including the role of type 2 inflammation, and discuss how findings from studies of biologics targeting type 2 immune mediators have helped to clarify the biological mechanisms driving BP pathophysiology. Future studies of these targeted therapies and others in development will help to further elucidate the mechanisms underlying BP pathophysiology and potentially provide better treatment options for patients.
Potential role of heteroplasmic mitochondrial DNA mutations in modulating the subtype-specific adaptation of oral squamous cell carcinoma to cisplatin therapy
Authors: Aminuddin Amnani , Ng Pei Yuen , Leong Chee Onn , Makpol Suzana , Chua Eng Wee
Published: October 2024

Cancer cells are constantly evolving to adapt to environmental changes, particularly during exposure to drug treatment. In this work, we aimed to characterize genetic and epigenetic changes in mitochondrial DNA (mtDNA) that may increase the resistance of oral squamous cell carcinoma (OSCC) to cisplatin. We first derived drug-resistant cells from two human OSCC cell lines, namely SAS and H103, by continual cisplatin treatments for about 4 months. To determine mtDNA changes induced by cisplatin, we performed nanopore sequencing and quantitative polymerase chain reaction analysis of mtDNA extracted from the cells pre- and post-treatment. We also assessed the mitochondrial functions of the cells and their capacity to generate intracellular reactive oxygen species (ROS). We found that in the cisplatin-resistant cells derived from SAS, there was a reduction in mtDNA content and significant enrichment of a m.3910G > C mutation in the MT-ND1 gene. However, such changes were not detected in cisplatin-resistant H103 cells. The cisplatin treatment also altered methylation patterns in both SAS and H103 cells and decreased their sensitivity to ROS-induced cytotoxicity. We suggest that the sequence alterations and epigenetic changes in mtDNA and the reduction in mtDNA content could be key drivers of cisplatin resistance in OSCC. These mtDNA alterations may participate in cellular adaptation that serves as a response to adverse changes in the environment, particularly exposure to cytotoxic agents. Importantly, the observed mtDNA changes may be influenced by the distinct genetic landscapes of various cancer subtypes. Overall, this study reveals significant insights into cisplatin resistance driven by complex mtDNA dynamics, particularly in OSCC. This underscores the need for targeted therapies tailored to the genetic profiles of individual OSCC patients to improve disease prognosis.
Geodesign to advance boundary work in urban planning: A study in Stockholm focused on nature-based solutions
Authors: Adem Esmail Blal , Anderson Cyrus Carl , Bast Sigvard , Cortinovis Chiara , Suleiman Lina , Kato-Huerta Jarumi , Högström Johan , Balfors Berit , Arciniegas Gustavo , Geneletti Davide , Mörtberg Ulla , Albert Christian
Published: October 2024

Geodesign supports collaborative urban planning by managing ‘boundaries’ between diverse knowledge holders. However, there is a paucity of empirical evidence of its contribution to ‘boundary work’. This paper aims to evaluate how a geodesign process facilitates knowledge co-production through boundary work and to assess the scientific credibility, political saliency, and procedural legitimacy of its outputs in urban planning. We propose a replicable geodesign framework to assess boundary work, and test it in a case study on urban transformations with nature-based solutions in the Skarpnäck district of Stockholm, Sweden. Findings indicate that all geodesign steps facilitated communication by promoting collective reasoning. Participants acknowledged contributions to knowledge co-production and decision-making by mediating between different perspectives. However, data quality and modeling simplicity were identified as critical factors affecting the outputs’ perceived credibility. Future applications should include co-designing the geodesign process, improving capacity and skills, and facilitating more integrated planning.
Juvenile Dermatomyositis: Updates in Pathogenesis and Biomarkers, Current Treatment, and Emerging Targeted Therapies
Authors: Kim Hanna
Published: October 2024

Juvenile dermatomyositis is a rare systemic inflammatory autoimmune disease involving muscle, skin, and vessels. Most patients do not fully respond to initial therapy, instead having a chronic refractory or polycyclic disease course. Pathogenesis is not completely understood, but immune cell dysregulation, particularly of B cells, mitochondrial dysfunction, changes in neutrophils and neutrophil extracellular traps (NETs), and increased type I and type II interferon (IFN) signaling have been described. There are limited randomized controlled trials of drugs in juvenile dermatomyositis (JDM), and treatment is largely based on lower-quality data such as case series, retrospective studies, and open-label prospective studies. These data have been compiled into expert recommendations or consensus treatment plans, which help guide therapy. While initial therapy is more standard with most including corticosteroids (high-dose oral and/or pulse intravenous methylprednisolone) and methotrexate, for refractory patients, guidelines are more varied with multiple options or combinations, including biologic therapies. There is a clear need for more efficacious and personalized therapy in JDM. Emerging treatment options worthy of further study in JDM include targeting IFN-signaling (JAK, IFNAR1, IFN beta), B-cells (CD20, CD19, BAFF, TACI, CD38, BCMA) including Chimeric Antigen Receptor (CAR)-T cell therapy, mitochondrial dysfunction, and NETs.
Clinical characteristics and predictors of complications and mortality in hospitalized octogenarian patients with COVID-19: an ambispective study
Authors: Arroyo-Huidobro Marta , Fontanet Natàlia Pallarès , Cordomí Cristian Tebé , Simonetti Antonella F. , Pérez-López Carlos , Abelenda-Alonso Gabriela , Rombauts Alexander , Bermudez Isabel Oriol , Izquierdo Elisenda , Díaz-Brito Vicente , Molist Gemma , Melis Guadalupe Gómez , Videla Sebastian , Soto Alfons López , Carratalà Jordi , Molinero Alejandro Rodriguez ,   On behalf of MetroSud and Divine Study Group, Gudiol Carlota , Aranda-Lobo Judit , Sanmartí Montserrat , Moreno Encarna , Alvarez Maria C. , Faura Ana , González Martha , Cruz Paula , Colom Mireia , Perez Andrea , Serrano Laura , Videla Sebastià , Besalú Mireia , Cobo Erik , Cortés Jordi , Fernández Daniel , Garmendia Leire , Gómez Guadalupe , Hereu Pilar , Langohr Klaus , Pérez-Álvarez Núria , Piulachs Xavier , Pallares Natàlia , Tebé Cristian , Besalú Mireia , Cobo Erik , Cortés Jordi , Fernández Daniel , Langohr Klaus , Pérez-Álvarez Núria , Piulachs Xavier , Gómez Guadalupe
Published: October 2024

Objective

This study aimed to describe the clinical presentation of COVID-19 in hospitalized patients aged 80 or above and to identify predictors for death and complications throughout the epidemic waves of the disease.

Methods

This was an observational, multicenter, ambispective study conducted between March 2020 and August 2021 using data collected in five centers from southern metropolitan area of Barcelona (COVID-MetroSud cohort). Patients were grouped based on the pandemic waves of inclusion in the registry. We conducted a descriptive analysis, followed by bivariate and multivariate analyses (binary logistic regression) to identify predictors of risk for death or complications.

Results

A total of 1192 patients (mean [SD] age 85.7 [4.22] years and 46.8% female) were included. The most frequently reported symptoms in all waves were fever (63.1%), cough (56.5%), dyspnea (48.2%), and asthenia (27.5%). Laboratory and radiological findings consistently showed abnormal bilateral chest X-ray results (72.5% of patients) and elevated inflammatory markers such as lactate dehydrogenase (mean [SD] 335 [188] U/L), C-reactive protein (CRP) (mean [SD] 110 [88.4] U/L), and ferritin (mean [SD] 842 [1561] U/L). Acute respiratory distress syndrome (43.7%), renal failure (19.2%), and delirium (17.5%) were the most frequent complications. The overall mortality rate was 41.4% and declined across the epidemic waves. Age, diabetes mellitus, heart failure, dyspnea, and higher baseline levels of creatinine were identified as risk factors for complications, while a higher Barthel index and presence of cough were found to be protective. Age, dyspnea, abnormal bilateral chest X-ray, CRP, and sodium were identified as risk factors for death.

Conclusions

This study demonstrates the clinical presentation of COVID-19 (fever, cough, dyspnea, and asthenia) and the different risk factors for mortality and complications in octogenarian hospitalized patients throughout the pandemic. These findings could be highly valuable for managing future virus pandemics.
Edward A. Tenenbaum and the Deutschmark
Authors: Holtfrerich Carl-Ludwig
Published: October 2024

German industry had survived Allied bombing largely unscathed. Currency reform was necessary to provide incentives for capital owners and labor to produce. The abundance of old Reichsmarks had to be curtailed to a scarce supply of Deutschmarks that users would expect to retain value. It was Edward A. Tenenbaum, currency expert of US military government in Berlin since 1946, who managed the exceptionally successful currency reform in West Germany 1948, which was implemented by the legislative powers of the three Western Allies against opposition from West German financial experts. It was the foundation of West Germany's 'economic miracle.' The West German currency conversion is part of the founding myth of the Federal Republic of Germany. Yet Tenenbaum's pivotal role is largely unknown among the German public. Besides providing a full-blown biography of the true father of the currency reform, this book elevates Tenenbaum to his proper place in German history.
A Cloud-Based Solution to a Radar Data Deluge
Authors: Shriver Sargent , Meyer Franz , Lewandowski Alex , Lundell Eric , Palmieri Dylan
Published: October 2024

An open-science tool built to support NASA missions is making synthetic aperture radar, once the domain only of subject matter experts, more accessible for nonspecialists and real-world applications.
A Close Asteroid Encounter May Have Once Given Earth a Ring
Authors: Cartier Kimberly
Published: October 2024

An unusual concentration of impact craters suggests that they may have been caused by the breakup of an asteroid that created a temporary debris ring around Earth.
Enhancement of Green Ghosts Due To Recurrence of Sprite Element
Authors: Huang Xin , Lu Gaopeng , Liu Feifan , Cheng Zhengwei , Lucena Frankie , Liu Yu , Xue Xianghui , Wang Yongping , Cohen Morris B. , Ashcraft Thomas , Smith Paul , Schyma Hank
Published: October 2024

We examined three observations of green emission events (labeled as event A, B and C, respectively) associated with red sprites as captured by amateurs. In all cases, the green emissions were recorded atop of red sprite. Based on the location of causative strokes and background star fields for events A and B, their altitudes are confined between 88 and 100 km, with the maximum brightness at 90.7 and 95.5 km, respectively. Events B and C were lit up for a second time after the recurrence of a sprite element, extending their duration to approximately 1,084 ms and 732.6 ms, much longer than that (about 500 ms) for event A; the intensity of green emissions was also enhanced due to sprite recurrence. It is inferred that the recurrence of sprite elements could affect the ambient condition by further increasing electron density and strengthening the electric field for the ghost production.
A Composite Fault Model for the 2024 MW 7.4 Hualien Earthquake Sequence in Eastern Taiwan Inferred From GNSS and InSAR Data
Authors: Cheloni D. , Famiglietti N. A. , Caputo R. , Tolomei C. , Vicari A.
Published: October 2024

On 2 April 2024, an MW 7.4 earthquake struck the northern Longitudinal Valley in eastern Taiwan, about 18 km SSW of Hualien, causing damage and casualties. In this study, we investigated a comprehensive geodetic data set, employing Global Navigation Satellite Systems (GNSS) and Interferometric Synthetic Aperture Radar (InSAR) measurements to assess the rupture geometry associated with earthquake sequence. Although geodetic data can be satisfactorily reproduced by simple single‐fault models (i.e., a high‐angle E‐dipping plane related to the Longitudinal Valley Fault (LVF), or a gentle W‐dipping surface associated with the Central Range Fault, CRF), a composite model involving the rupture of different fault segments (a major CRF‐related W‐dipping fault, a deep segment of the E‐dipping LVF, and the Milun Fault) is able to explain the observations, the distribution of seismicity, and the complex structural arrangement of the northernmost sector of the Longitudinal Valley.
Implications of a Pervasive Climate Model Bias for Low‐Cloud Feedback
Authors: Ceppi P. , Myers T. A. , Nowack P. , Wall C. J. , Zelinka M. D.
Published: October 2024

How low clouds respond to warming constitutes a key uncertainty for climate projections. Here we observationally constrain low‐cloud feedback through a controlling factor analysis based on ridge regression. We find a moderately positive global low‐cloud feedback (0.45 W , 90% range 0.18–0.72 W ), about twice the mean value (0.22 W ) of 16 models from the Coupled Model Intercomparison Project. We link this discrepancy to a pervasive model mean‐state bias: models underestimate the low‐cloud response to warming because (a) they systematically underestimate present‐day tropical marine low‐cloud amount, and (b) the low‐cloud sensitivity to warming is proportional to this present‐day low‐cloud amount. Our results hence highlight the importance of reducing model biases in both the mean state of clouds and their sensitivity to environmental factors for accurate climate change projections.
Drivers of Cold Frontal Hourly Extreme Precipitation: A Climatological Study Over Europe
Authors: Schaffer Armin , Lichtenegger Tobias , Truhetz Heimo , Ossó Albert , Martínez‐Alvarado Oscar , Maraun Douglas
Published: October 2024

In the mid‐latitudes extreme precipitation events are strongly associated with cold fronts. By exploring drivers across different scales and relating them to precipitation, we aim to improve our understanding of processes influencing cold frontal extremes. Using hourly ERA5 data over Europe and the North Atlantic, cold fronts are detected and the associated conditions are identified. Quantile regression models are employed to find drivers of frontal precipitation and to quantify these relations. Additionally, we use composites to study the synoptic conditions and meso‐scale structure of extreme events. We find that humidity close to the detected fronts, convergence and the low level jet speed contribute most to the formation of extreme precipitation. Synoptic conditions favoring the formation of extreme events are also identified. These results improve our understanding of cold frontal processes leading to precipitation. Additionally, they provide the foundation for a process‐based evaluation of frontal dynamics in climate models.
Spatial Variability of Dropsonde‐Derived Moist Static Energy in North Atlantic Tropical Cyclones
Authors: Kopelman Michael V. , Wing Allison A. , Carstens Jacob D.
Published: October 2024

The spatial variability of moist static energy (MSE) and its column‐integral (CMSE) around tropical cyclones (TCs) are known to help prognose TC development. Though limited in number and spatial coverage per TC, modeling work suggests that dropsondes, when strategically deployed, can reliably capture radial MSE and CMSE variability. This study uses North Atlantic upper‐level reconnaissance dropsondes from 1996 to 2021 to produce the most extensive observational analysis of MSE structure in TCs to date. MSE and CMSE decrease with distance from the TC center. MSE spatial variability is larger in Category 1 and 2 hurricanes compared to tropical storms, and generally largest after a TC's lifetime maximum intensity. Moisture dominates the MSE spatial variability but temperature contributes in the upper levels near the TC center. While differences in MSE spatial variability between weakening and intensifying TCs are less clear, raw MSE tends to be greater in intensifying TCs at most radii and vertical levels.
Magnetostratigraphy of the Niubao Formation in the Bangong‐Nujiang Suture Zone: Constraints on the Amount of Crustal Shortening of the Tibetan Plateau Since 60 Ma
Authors: Li Shuai , Han Zhongpeng , Li Yalin , Tan Xiaodong , Todrani Alessandro , Ma Xingduo , Li Zijian , Wang Xinhang , Dai Jie , Wang Chengshan
Published: October 2024

The Early Cenozoic sedimentary archives of Tibet are crucial for elucidating the geodynamic processes related to continental collision, particularly crustal deformation and shortening. However, the lack of a reliable chronostratigraphic framework for the Cenozoic sedimentary basins in central Tibet has hindered a comprehensive understanding of the influence of the continuous India‐Asia convergence process on the tectonic evolution of the Tibetan hinterland. Here, we report new magnetostratigraphic ages and paleomagnetic results for the Niubao Formation exposed in the northern bank of the Siling Co. Positive field tests and microscopic observations suggest that the remanence is primary. We determine that the depositional age of the measured section was between 59.2 and 48.6 Ma. Our results reveal that the paleogeographic location of the Bangong‐Nujiang Suture Zone during the Late Paleocene–Early Eocene was 25.4 ± 2.1°N, thus supporting the model of two‐stage collision between India and Asia.
The Non‐Migrating DE3 Tide Response to the MJO Phenomenon at the MLT Altitudes
Authors: Li Xing , Ren Zhipeng , Cao Jinbin
Published: October 2024

Based on TIMED/SABER temperature observations and the Real‐Time Multivariate Madden‐Julian Oscillation (MJO) Index, for the first time, we discussed the daily resolution non‐migrating DE3 temperature tide response to the MJO phenomenon during MJO phases between ±45° latitude from 2003 to 2012 in the Mesosphere and Lower Thermosphere (MLT) region. We found: (a) The DE3 tide significantly depends on different MJO phases in the four seasons above 100 km altitude. The DE3 tidal phase exhibits varying responses to the different MJO phases. (b) The DE3 tide response to the MJO phenomenon is stronger at the solstices than at the equinoxes, and the response at the June solstices is stronger. (c) The symmetric component of the DE3 response to the MJO phenomenon is stronger than the asymmetric component. In summary, the daily resolved DE3 tide response to the MJO phenomenon, especially the DE3 tidal phase dominates certain seasonal characteristics and symmetry in the MLT region.
Latitudinal Characteristics of the Post‐Sunset Enhancements in Ionospheric Electron Density During the Geomagnetic Quiet Period in May 2021 Over East‐Asian Region
Authors: Hao Honglian , Zhao Biqiang , Yue Xinan , Ding Feng , Li Guozhu , Sun Wenjie , Ren Zhipeng , Liu Libo
Published: October 2024

This study investigated the latitudinal variations of post‐sunset enhancements in the ionospheric electron density during the geomagnetic quiet period in May 2021 with a combination of high‐precision ionospheric parameters obtained from four ionosondes, Beidou geostationary satellite (BD‐GEO) receiver network and Sanya incoherent scatter radar (SYISR). We identified four categories of post‐sunset enhancement phenomena (Types 1–4), each with unique spatial and temporal evolutions, yet uniformly accompanied by a decrease in hmF2. Measurements of plasma drift vector velocities from SYISR and hmF2 gradients across various latitudes provided pivotal insights, confirming that the ionospheric post‐sunset enhancements can result from downward plasma motion due to westward electric field, downward field‐aligned drift, or a combination of both. For Type 1, dominated by field‐aligned drift, plasma density enhancements not only intensify at low latitudes but may also extend to mid‐latitudes, exhibiting a distinct temporal delay with increasing latitude. In contrast, Type 4, primarily driven by the westward electric field, is characterized by modest increases in plasma density confined to localized low‐latitude regions, with no observable latitudinal time delay in the peak of enhancements. Types 2 and 3, which are subject to the combined influence of the westward electric field and field‐aligned drift, exhibit plasma density increases at certain low‐latitude areas, with Type 2 presenting a delayed pattern and Type 3 showing none with rising latitude. Meanwhile, neutral winds can partially account for the observed post‐sunset enhancement from low to middle latitudes. These findings offer new insights into the factors influencing ionospheric behavior after sunset.
Methods to Evaluate Subcolumn Profiles Based on Two‐Point Diagnostics
Authors: Stephens Benjamin A. , Larson Vincent E. , Newsom Rob , Gustafson William I. , Dikta Gerhard
Published: October 2024

In atmospheric models, stochastic generation of subgrid‐scale profiles or “subcolumns” has been used for a variety of purposes. Such subcolumns can be generated from subgrid probability density functions (PDFs) at different vertical levels, when such PDFs are available. To do so, the generator needs to decide how strongly points should be correlated in the vertical, that is, how much the values should be overlapped. This is sometimes called “PDF overlap.” To assess vertical correlation in a simplified, observable setting, here the vertical correlation of vertical velocity in subcloud layers is examined. Doppler lidar is used to evaluate the vertical profiles of vertical velocity produced by a large‐eddy simulation (LES) model and the Subgrid Importance Latin Hypercube Sampler (SILHS) subcolumn generator. In order to diagnose unrealistic features in subcolumn profiles, various statistical diagnostics are examined here, including the bivariate PDF of vertical velocity at two separated points (i.e., altitudes), the two‐point velocity correlation, the integral correlation length, the PDF of two‐point velocity differences, and the skewness and kurtosis of two‐point velocity differences. The profiles produced by LES match lidar well, except that they are too smooth at small scales. The profiles produced by SILHS exhibit sharp jumps from updraft to downdraft that are not observed in the lidar data. To reduce the generation of these unrealistically sharp jumps, the SILHS sampling method is revised. The diagnostics confirm that the revised sampling method reduces the overprediction of sharp jumps.
Equation of State, Structure, and Transport Properties of Iron Hydride Melts at Planetary Interior Conditions
Authors: Stoutenburg Emma R. , Caracas Razvan , Solomatova Natalia V. , Campbell Andrew J.
Published: October 2024

Iron hydrides are a potentially dominant component of the metallic cores of planets, primarily because of hydrogen's ubiquity in the universe and affinity for iron. Using ab initio molecular dynamics, we examine iron hydrides with 0.1, 0.33, 0.5, and 0.6 mol fraction hydrogen up to 100 GPa between 3,000 and 5,000 K to describe how hydrogen content affects the melt structure, hydrogen speciation, equation of state (EOS), atomic diffusivity, and melt viscosity. We find that the addition of hydrogen decreases the average Fe–Fe coordination number and lengthens Fe–Fe bonds, while Fe–H coordination number increases. The pair distribution function of hydrogen at low pressure indicates the presence of molecular hydrogen. By tracking chemical speciation, we show that the amount of molecular hydrogen increases and the number of iron in Hx≥1Fey≥0 clusters decreases as the hydrogen concentration increases. We parameterize a pressure, volume, temperature, and composition EOS and show that the molar volume and Grüneisen parameter of the melts decrease while the compressibility and thermal expansivity increase as a function of hydrogen concentration. We find that hydrogen acts as a lubricant in the melts as the iron and hydrogen become more diffusive and the melts become more inviscid as the hydrogen concentration increases. We estimate 2.7 wt% hydrogen in the Martian core and 0.49–1.1 wt% hydrogen in Earth's outer core based on comparisons to seismic models, with the assumption that the cores are pure liquid iron‐hydrogen alloy, and we compare the small exoplanet population with mass‐radius curves of iron hydride planets.
Picturing Global Substorm Dynamics in the Magnetotail Using Low‐Altitude ELFIN Measurements and Data Mining‐Based Magnetic Field Reconstructions
Authors: Shi Xiaofei , Stephens Grant K. , Artemyev Anton V. , Sitnov Mikhail I. , Angelopoulos Vassilis
Published: October 2024

A global reconfiguration of the magnetotail characterizes substorms. Current sheet thinning, intensification, and magnetic field stretching are defining features of the substorm growth phase and their spatial distributions control the timing and location of substorm onset. Presently, sparse in‐situ observations cannot resolve these distributions. A promising approach is to use new substorm magnetic field reconstruction methods based on data mining, termed SST19. Here we compare the SST19 reconstructions to low‐altitude electron losses and fields investigation (ELFIN) measurements of energetic particle precipitations to probe the radial profile of the equatorial magnetic field curvature during a 19 August 2022 substorm. ELFIN and SST19 yield a consistent dynamical picture of the magnetotail during the growth phase and capture its key features such as the formation of a thin current sheet and its earthward motion. Furthermore, they resolve a “checkmark” pattern of isotropic electron precipitation boundaries in the time‐energy plane, consistent with earlier observations but now over a broad energy range. It is shown that in the growth phase, the mismatch between SST19 and ELFIN latitudes is much less than one degree, the capability unattainable for any other empirical or first‐principles model.
O-GlcNAcylation inhibition redirects the response of colon cancer cells to chemotherapy from senescence to apoptosis
Authors: Loison Ingrid , Pioger Adrien , Paget Sonia , Metatla Inès ,   OrgaRES Consortium, Mariette Christophe , Piessen Guillaume , Corfiotti François , Eveno Clarisse , Pruvot François-René , Truant Stéphanie , El Amrani Mehdi , Leteurtre Emmanuelle , Renaud Florence , Dufour Charlotte , Gnemmi Viviane , Wicquart Laurence , Escande Fabienne , Leclerc Julie , Van Seuningen Isabelle , Vincent Audrey , Abbadie Corinne , Dehennaut Vanessa
Published: October 2024

The potential use of pro-senescence therapies, known as TIS (Therapy-Induced Senescence), for the treatment of colorectal cancer (CRC) generated significant interest since they require lower doses compared to those required for inducing apoptosis. However, the senescent cell cycle-arrested cancer cells are long-lived, and studies have revealed escape mechanisms contributing to tumor recurrence. To deepen our understanding of the survival pathways used by senescent cancer cells, we delved into the potential involvement of the hexosamine biosynthetic pathway (HBP). HBP provides UDP-GlcNAc, the substrate for O-GlcNAc transferase (OGT), which catalyzes O-GlcNAcylation, a post-translational modification implicated in regulating numerous cellular functions and aberrantly elevated in CRC. In this study, we demonstrated, in the p53-proficient colon cancer cell lines HCT116 and LS174T, that TIS induced by low-dose SN38 or etoposide treatment was accompanied with a decrease of GFAT (the rate limiting enzyme of the HBP), OGT and O-GlcNAcase (OGA) expression correlated with a slight reduction in O-GlcNAcylation levels. Further decreasing this level of O-GlcNAcylation by knocking-down GFAT or OGT redirected the cellular response to subtoxic chemotherapy doses from senescence to apoptosis, in correlation with an enhancement of DNA damages. Pharmacological inhibition of OGT with OSMI-4 in HCT116 and LS174T cells and in a patient-derived colon tumoroid model supported these findings. Taken together, these results suggest that combing O-GlcNAcylation inhibitors to low doses of conventional chemotherapeutic drugs could potentially reduce treatment side effects while preserving efficacy. Furthermore, this approach may increase treatment specificity, as CRC cells exhibit higher O-GlcNAcylation levels compared to normal tissues.
Slowly progressive autosomal dominant Alport Syndrome due to COL4A3 splicing variant
Authors: Daga Sergio , Loberti Lorenzo , Rollo Giulia , Adamo Loredaria , Colavecchio Olga Lorenza , Brunelli Giulia , Zguro Kristina , Tripodi Sergio Antonio , Guarnieri Andrea , Garosi Guido , D’Aurizio Romina , Ariani Francesca , Tita Rossella , Renieri Alessandra , Pinto Anna Maria
Published: October 2024

Alport syndrome is a rare genetic kidney disease caused by variants in the COL4A3/A4/A5 genes. It’s characterised by progressive kidney failure, though therapies targeting Renin-Angiotensin System can delay its progression. Additionally, extrarenal manifestations may sometimes coexist. Recent advances in genetic analysis and the necessity to better clarify genotype-phenotype correlations in affected patients raises the importance of detecting even cryptic splicing variants, lying in both canonical and non-canonical splice sites variants such as last exonic nucleotide variants. These variants, often, do not cause an amino acid change but alter the snRNP proteins binding. We studied a big Italian family with Alport syndrome showing a clear dominant pattern of transmission with younger family members having only haematuria and older individuals presenting with End-Stage Kidney Failure (ESKF). Kidney biopsy showed the typical disease hallmarks. We deeply mined the data for SNV and CNV through exome sequencing on DNA from both peripheral blood samples and patients’ podocytes-lineage cells. We identified an already reported synonymous variant, c.765G>A (p.(Thr255Thr)), in the last exonic nucleotide of exon 13 of the COL4A3 gene. Employing the patient’s podocytes we demonstrated that this variant results in exon skipping leading to an in-frame deletion of 28 amino acids without leaky effect. According to the pattern of transmission, to the kidney biopsy and to the exome data analysis we provided further evidence that autosomal dominant Alport syndrome is a well-defined clinical entity. We also confirmed the pathogenicity of the synonymous COL4A3 variant for the first time demonstrating its role in a dominant pattern of transmission.
The key role of sufficiency for low demand-based carbon neutrality and energy security across Europe
Authors: Wiese Frauke , Taillard Nicolas , Balembois Emile , Best Benjamin , Bourgeois Stephane , Campos José , Cordroch Luisa , Djelali Mathilde , Gabert Alexandre , Jacob Adrien , Johnson Elliott , Meyer Sébastien , Munkácsy Béla , Pagliano Lorenzo , Quoilin Sylvain , Roscetti Andrea , Thema Johannes , Thiran Paolo , Toledano Adrien , Vogel Bendix , Zell-Ziegler Carina , Marignac Yves
Published: October 2024

A detailed assessment of a low energy demand, 1.5 ∘C compatible pathway is provided for Europe from a bottom-up, country scale modelling perspective. The level of detail enables a clear representation of the potential of sufficiency measures. Results show that by 2050, 50% final energy demand reduction compared to 2019 is possible in Europe, with at least 40% of it attributable to various sufficiency measures across all sectors. This reduction enables a 77% renewable energy share in 2040 and 100% in 2050, with very limited need for imports from outside of Europe and no carbon sequestration technologies. Sufficiency enables increased fairness between countries through the convergence towards a more equitable share of energy service levels. Here we show, that without sufficiency measures, Europe misses the opportunity to transform energy demand leaving considerable pressure on supply side changes combined with unproven carbon removal technologies.
Serum metabolite and metal ions profiles for breast cancer screening
Authors: Wojtowicz Wojciech , Tarkowski R. , Olczak A. , Szymczycha-Madeja A. , Pohl P. , Maciejczyk A. , Trembecki Ł. , Matkowski R. , Młynarz Piotr
Published: October 2024

Enhancing early-stage breast cancer detection requires integrating additional screening methods with current diagnostic imaging. Omics screening, using easily collectible serum samples, could serve as an initial step. Alongside biomarker identification capabilities, omics analysis allows for a comprehensive analysis of prevalent histological types—DCIS and IDC. Employing metabolomics, metallomics, and machine learning, could yield accurate screening models with valuable insights into organism responses. Serum samples of confirmed breast cancer patients were utilized to analyze metabolite and metal ion profiles, using two distinct analysis methods, proton NMR for metabolomics and ICP-OES for metallomics. The resulting responses were then subjected to discriminant analysis, progression biomarker exploration, examination of correlations between patients’ metabolites and metal ions, and the impact of age and menopause status. Measured NMR spectra and metabolite relative integrals were used to achieve statistically significant discrimination through MVA between breast cancer and control groups. The analysis identified 24 metabolites and 4 metal ions crucial for discrimination. Furthermore, four metabolites were associated with disease progression. Additionally, there were important correlations and relationships between metabolite relative integrals, metal ion concentrations, and age/menopausal status subgroups. Quantified relative integrals allowed for discrimination between studied subgroups, validated with a holdout set. Feature importance and statistical analysis for metabolomics and metallomics extracted a set of common entities which in combination provides valuable insights into ongoing molecular disturbances and disease progression.
eBryoSoil: a citizen science application to monitor changes in soil ecosystems
Authors: Mira André F. , Hortal Joaquín , Portela Ana Paula , Albertos Belén , Estébanez Belén , Branquinho Cristina , Vieira Cristiana , Hespanhol Helena , Draper Isabel , Marques Joana , Monteiro Juliana , Leo María , Hurtado Pilar , Ochoa-Hueso Raúl , Varela Zulema , Medina Nagore G.
Published: October 2024

Biological soil covers (BSCs) play a pivotal role in ecosystem functioning by enhancing soil stability, mediating nutrient cycling, and influencing soil hydrology. Recognized as ecosystem engineers, they can physically modify, maintain, or create habitats, facilitating plant community development. Through these intricate interactions, BSCs contribute significantly to ecological processes, highlighting their importance in the overall health and functionality of the ecosystems of the Iberian Peninsula. Here we present the results obtained from the contributions of the citizen scientists uploaded from November 2019 to January 2021 with eBryoSoil, an app that allows citizens to participate in mapping the BSC communities across the Iberian Peninsula. Here, we emphasize the importance of habitats and consequently, their interaction with climatic variables for the persistence of BSCs (lichens and bryophytes). Conservation efforts targeted at preserving diverse habitats are essential to ensure the continued presence of lichen and bryophyte communities. Despite challenges posed by the SARS-CoV-2 outbreak, this citizen science project demonstrated success in utilizing a specifically tailored app to gather valuable information on BSC communities, providing insights into their vulnerability to climate change. This program serves as an illustrative example of how citizen science can effectively identify and study vulnerable habitats, offering a blueprint for future studies focused on understudied organisms.
Sensory cues, behavior and fur-based drying in the rat wetness response
Authors: Attah Augustine Triumph , Negrón-Moreno Paola N. , Amigo-Duran Macarena , Zhang Linghua , Kenngott Max , Brecht Michael , Clemens Ann M.
Published: October 2024

It never rains in standard lab-confinements; thus we have limited understanding of animal reactions to water and wetness. To address this issue, we sprayed water on different body parts of rats and measured drying and fur temperature by thermal imaging while manipulating behavior, sensory cues and fur. Spraying water on rats resulted in fur changes (hair clumping, apex formation), grooming, shaking, and scratching. Anesthesia abolished behavioral responses, interfered with fur changes, and slowed drying. Spraying water on different body parts resulted in differential behavioral drying responses. Spraying the head resulted in grooming and shaking responses; water evaporated from the head twice as fast as water sprayed on the animal’s back or belly. We observed no effect of whisker removal on post-water-spraying behavior. In contrast, local anesthesia of dorsal facial skin reduced post-water-spraying behavioral responses. Shaving of head fur drastically enhanced post-water-spraying behaviors, but reduced water loss during drying; indicating that fur promotes evaporation, acting in tandem with behavior to mediate drying. Excised wet fur patches dried and cooled faster than shaved excised wet skin. Water was sucked into distal hair tips, where it evaporated. We propose the wet-fur-heat-pump-hypothesis; fur might extract heat required for drying by cooling ambient air.
Spatial-temporal graph neural networks for groundwater data
Authors: Taccari Maria Luisa , Wang He , Nuttall Jonathan , Chen Xiaohui , Jimack Peter K.
Published: October 2024

This paper introduces a novel application of spatial-temporal graph neural networks (ST-GNNs) to predict groundwater levels. Groundwater level prediction is inherently complex, influenced by various hydrological, meteorological, and anthropogenic factors. Traditional prediction models often struggle with the nonlinearity and non-stationary characteristics of groundwater data. Our study leverages the capabilities of ST-GNNs to address these challenges in the Overbetuwe area, Netherlands. We utilize a comprehensive dataset encompassing 395 groundwater level time series and auxiliary data such as precipitation, evaporation, river stages, and pumping well data. The graph-based framework of our ST-GNN model facilitates the integration of spatial interconnectivity and temporal dynamics, capturing the complex interactions within the groundwater system. Our modified Multivariate Time Graph Neural Network model shows significant improvements over traditional methods, particularly in handling missing data and forecasting future groundwater levels with minimal bias. The model’s performance is rigorously evaluated when trained and applied with both synthetic and measured data, demonstrating superior accuracy and robustness in comparison to traditional numerical models in long-term forecasting. The study’s findings highlight the potential of ST-GNNs in environmental modeling, offering a significant step forward in predictive modeling of groundwater levels.