bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pore‐Scale Modeling of Water and Ion Diffusion in Partially Saturated Clays
Authors: Yang Yuankai , Churakov Sergey V. , Patel Ravi A. , Prasianakis Nikolaos , Deissmann Guido , Bosbach Dirk , Poonoosamy Jenna 
Published: January 2024

AbstractAn accurate mechanistic understanding of solute diffusion in partially saturated clays is critical for assessing the safety of deep geological repositories for radioactive waste. In this study, a pore‐scale numerical framework is developed to simulate water and ion diffusion in partially saturated clays. First, the two‐phase Shan‐Chen Lattice Boltzmann method is employed to establish the liquid‐gas distribution in a reconstructed three‐dimensional pore geometry of a clay. An equivalent solute method is also developed and validated to improve the numerical stability of the solution at the liquid/gas interface corresponding to steep variations of the concentration and diffusion coefficient of the water tracer. By using a mobility‐distance relationship from molecular simulations, Fick's law is numerically solved to simulate water diffusion in nanopores, while the coupled Poisson‐Boltzmann‐Nernst‐Planck equations are solved to simulate ion diffusion under the influence of the electrical double layer (EDL). Our model reveals that the decrease of relative effective diffusion coefficients during the desaturation is more pronounced for ions than for water, due to the additional transport pathway of water tracers in the gas phase. The obtained effective diffusion coefficients of tritiated water and ions agree well with reported data from compacted sedimentary rocks. By comparing the local electric potential and the distribution of ion concentrations in single pores, the simulation results suggest that the EDL in unsaturated clays has a more complex influence on ion distribution than under fully water‐saturated conditions. This study provides critical insights into the coupled transport processes of solutes in partially saturated clays.
Reconstruction of the Pleistocene Paleoclimate From Deep Groundwater in Southern Germany From Noble Gas Temperatures Linked With Organic Radiocarbon Dating
Authors: Winter Theis , Aeschbach Werner , Einsiedl Florian 
Published: January 2024

AbstractThis study presents a 25 ka reconstruction of the Pleistocene paleoclimate in the South German Molasse Basin. Deep groundwater was sampled at 19 wells in the Upper Jurassic aquifer (UJA). Calculating gas temperatures (NGT) using the UA model with the noble gases Ar, Kr, and Xe led to groundwater recharge temperatures between 0.4 and 4.7°C. Combined with innovative 14CDOC groundwater dating, calculated NGTs revealed up to 8°C cooler soil temperatures during the Pleistocene compared with modern soil temperature. This interpretation agrees well with the observed depleted stable water isotope signature ranging from −83.3 to −86.1 for δ2H and from −10.66 to −11.77 for δ18O, which is characteristic of groundwater of Pleistocene origin in Southern Germany. The temperature differences (∆T) agree remarkably well with calculated NGTs within other European basins (∆T 6–9.5°C) and suggest widespread pronounced terrestrial cooling during the Last Glacial Maximum through the interior of the European continent.
Hybrid Discrete Fracture Network Inversion of Hydraulic Tomography Data From a Fractured‐Porous Field Site
Authors: Römhild Lukas , Ringel Lisa Maria , Liu Quan , Hu Linwei , Ptak Thomas , Bayer Peter 
Published: January 2024

AbstractThe accurate characterization of hydraulic conductivity heterogeneities in an aquifer is crucial for predicting flow and transport processes correctly. Hydraulic tomography (HT) experiments are often used to infer the hydraulically relevant features, but the correct inversion of the data remains a challenging task. We implemented a discrete fracture network (DFN) inversion approach that is expanded by considering a nonzero matrix permeability. The hybrid model allows the accurate characterization of fractured‐porous sites by taking into account both matrix and fracture flow. This novel inversion algorithm is successfully applied to HT data acquired at a field site in Goettingen (Germany), and the results are compared with those of a standard travel time inversion. Furthermore, we validate the inversion results by using them as the underlying material parameters for simulating heat tracer experiments and comparing the modeled temperature responses with those of heat tracer tests actually conducted at the site. It is shown that the DFN ensemble predicts the thermal response of the experiments correctly for the two major fractures in terms of location, amplitude, and time‐dependent behavior of the temperature anomaly, as long as the stochastic nature of the results is taken into account. We conclude that considering both matrix and fracture flow in a hybrid DFN inversion approach can lead to significant improvements in flow and transport modeling at fractured‐porous sites.
Stochastic Inversion of a Tomographic Pumping Test: Identifying Conductivity Horizontal Correlation and Longitudinal Macrodispersivity
Authors: Cheng Kan Bun , Rabinovich Avinoam , Dagan Gedeon 
Published: January 2024

AbstractTwo important properties for modeling flow and transport in heterogeneous aquifers are the horizontal integral scale (Ih) of hydraulic logconductivity (Y = ln K) and the longitudinal macrodispersivity (αL). Estimating the former generally requires K measurements in many wells, which are typically not available. In this work, we present a method for estimating Ih and αL from hydraulic tomography (HT) pumping tests. The approach is based on stochastic inversion, assuming head and K are stationary random space functions. Head variance and mean head gradient are calculated from measured head data at large distances from the pumping well and for large times from the start of pumping. These are then used in a theoretical formula for head variance in uniform mean flow to obtain Ih and subsequently αL, requiring only previous knowledge of the vertical integral scale (Iv) and the logconductivity variance . The method is applied to data from an HT pumping test at the Boise Hydrogeophysical Research site and results for Ih and αL are in the range previously reported in the literature. Particularly promising results are found for αL, which is seen to be robust, with relatively little variation for different values of Iv and .
An in vitro demonstration of a passive, acoustic metamaterial as a temperature sensor with mK resolution for implantable applications
Authors: Maini Lucrezia , Genovés Vicente , Furrer Roman , Cesarovic Nikola , Hierold Christofer , Roman Cosmin 
Published: January 2024

AbstractWireless medical sensors typically utilize electromagnetic coupling or ultrasound for energy transfer and sensor interrogation. Energy transfer and management is a complex aspect that often limits the applicability of implantable sensor systems. In this work, we report a new passive temperature sensing scheme based on an acoustic metamaterial made of silicon embedded in a polydimethylsiloxane matrix. Compared to other approaches, this concept is implemented without additional electrical components in situ or the need for a customized receiving unit. A standard ultrasonic transducer is used for this demonstration to directly excite and collect the reflected signal. The metamaterial resonates at a frequency close to a typical medical value (5 MHz) and exhibits a high-quality factor. Combining the design features of the metamaterial with the high-temperature sensitivity of the polydimethylsiloxane matrix, we achieve a temperature resolution of 30 mK. This value is below the current standard resolution required in infrared thermometry for monitoring postoperative complications (0.1 K). We fabricated, simulated, in vitro tested, and compared three acoustic sensor designs in the 29–43 °C (~302–316 K) temperature range. With this concept, we demonstrate how our passive metamaterial sensor can open the way toward new zero-power smart medical implant concepts based on acoustic interrogation.
High-resolution tracking of unconfined zebrafish behavior reveals stimulatory and anxiolytic effects of psilocybin
Authors: Braun Dotan , Rosenberg Ayelet M. , Rabaniam Elad , Haruvi Ravid , Malamud Dorel , Barbara Rani , Aiznkot Tomer , Levavi-Sivan Berta , Kawashima Takashi 
Published: January 2024

AbstractSerotonergic psychedelics are emerging therapeutics for psychiatric disorders, yet their underlying mechanisms of action in the brain remain largely elusive. Here, we developed a wide-field behavioral tracking system for larval zebrafish and investigated the effects of psilocybin, a psychedelic serotonin receptor agonist. Machine learning analyses of precise body kinematics identified latent behavioral states reflecting spontaneous exploration, visually-driven rapid swimming, and irregular swim patterns following stress exposure. Using this method, we found that acute psilocybin treatment has two behavioral effects: [i] facilitation of spontaneous exploration (“stimulatory”) and [ii] prevention of irregular swim patterns following stress exposure (“anxiolytic”). These effects differed from the effect of acute SSRI treatment and were rather similar to the effect of ketamine treatment. Neural activity imaging in the dorsal raphe nucleus suggested that psilocybin inhibits serotonergic neurons by activating local GABAergic neurons, consistent with psychedelic-induced suppression of serotonergic neurons in mammals. These findings pave the way for using larval zebrafish to elucidate neural mechanisms underlying the behavioral effects of serotonergic psychedelics.
Lung microbiome: new insights into the pathogenesis of respiratory diseases
Authors: Li Ruomeng , Li Jing , Zhou Xikun 
Published: January 2024

AbstractThe lungs were long thought to be sterile until technical advances uncovered the presence of the lung microbial community. The microbiome of healthy lungs is mainly derived from the upper respiratory tract (URT) microbiome but also has its own characteristic flora. The selection mechanisms in the lung, including clearance by coughing, pulmonary macrophages, the oscillation of respiratory cilia, and bacterial inhibition by alveolar surfactant, keep the microbiome transient and mobile, which is different from the microbiome in other organs. The pulmonary bacteriome has been intensively studied recently, but relatively little research has focused on the mycobiome and virome. This up-to-date review retrospectively summarizes the lung microbiome’s history, composition, and function. We focus on the interaction of the lung microbiome with the oropharynx and gut microbiome and emphasize the role it plays in the innate and adaptive immune responses. More importantly, we focus on multiple respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), fibrosis, bronchiectasis, and pneumonia. The impact of the lung microbiome on coronavirus disease 2019 (COVID-19) and lung cancer has also been comprehensively studied. Furthermore, by summarizing the therapeutic potential of the lung microbiome in lung diseases and examining the shortcomings of the field, we propose an outlook of the direction of lung microbiome research.
Cdk5-dependent rapid formation and stabilization of dendritic spines by corticotropin-releasing factor
Authors: Vandael Dorien , Vints Katlijn , Baatsen Pieter , Śliwińska Małgorzata A. , Gabarre Sergio , De Groef Lies , Moons Lieve , Rybakin Vasily , Gounko Natalia V. 
Published: January 2024

AbstractThe neuropeptide corticotropin-releasing factor (CRF) exerts a pivotal role in modulating neuronal activity in the mammalian brain. The effects of CRF exhibit notable variations, depending on factors such as duration of exposure, concentration, and anatomical location. In the CA1 region of the hippocampus, the impact of CRF is dichotomous: chronic exposure to CRF impairs synapse formation and dendritic integrity, whereas brief exposure enhances synapse formation and plasticity. In the current study, we demonstrate long-term effects of acute CRF on the density and stability of mature mushroom spines ex vivo. We establish that both CRF receptors are present in this hippocampal region, and we pinpoint their precise subcellular localization within synapses by electron microscopy. Furthermore, both in vivo and ex vivo data collectively demonstrate that a transient surge of CRF in the CA1 activates the cyclin-dependent kinase 5 (Cdk5)-pathway. This activation leads to a notable augmentation in CRF-dependent spine formation. Overall, these data suggest that upon acute release of CRF in the CA1-SR synapse, both CRF-Rs can be activated and promote synaptic plasticity via activating different downstream signaling pathways, such as the Cdk5-pathway.
Mode of progression in smoldering multiple myeloma: a study of 406 patients
Authors: Abdallah Nadine H. , Lakshman Arjun , Kumar Shaji K. , Cook Joselle , Binder Moritz , Kapoor Prashant , Dispenzieri Angela , Gertz Morie A. , Lacy Martha Q. , Hayman Suzanne R. , Buadi Francis K. , Dingli David , Lin Yi , Kourelis Taxiarchis , Warsame Rahma , Bergsagel Leif , Rajkumar S. Vincent 
Published: January 2024

AbstractThe approach to patients with high-risk smoldering multiple myeloma (SMM) varies among clinicians; while some advocate early intervention, others reserve treatment at progression to multiple myeloma (MM). We aimed to describe the myeloma-defining events (MDEs) and clinical presentations leading to MM diagnosis among SMM patients seen at our institution. We included 406 patients diagnosed with SMM between 2013–2022, seen at Mayo Clinic, Rochester, MN. The 2018 Mayo 20/2/20 criteria were used for risk stratification. Median follow-up was 3.9 years. Among high-risk patients who did not receive treatment in the SMM phase (n = 71), 51 progressed by last follow-up; the MDEs included: bone lesions (37%), anemia (35%), hypercalcemia (8%), and renal failure (6%); 24% met MM criteria based on marrow plasmacytosis (≥60%) and/or free light chain ratio (>100); 45% had clinically significant MDEs (hypercalcemia, renal insufficiency, and/or bone lesions). MM diagnosis was made based on surveillance labs/imaging(45%), testing obtained due to provider suspicion for progression (14%), bone pain (20%), and hospitalization/ED presentations due to MM complications/symptoms (4%). The presentation was undocumented in 14%. A high proportion (45%) of patients with high-risk SMM on active surveillance develop end-organ damage at progression. About a quarter of patients who progress to MM are not diagnosed based on routine interval surveillance testing.
Soluble lymphocyte activation gene-3 (sLAG3) and CD4/CD8 ratio dynamics as predictive biomarkers in patients undergoing immune checkpoint blockade for solid malignancies
Authors: Gorgulho Joao , Roderburg Christoph , Beier Fabian , Bokemeyer Carsten , Brümmendorf Tim H. , Loosen Sven H. , Luedde Tom 
Published: January 2024

Abstract
Background
The search for biomarkers to identify suitable candidates for immune checkpoint inhibitor (ICI) therapy remains ongoing. We evaluate how soluble levels of the next generation immune checkpoint Lymphocyte Activation Gene-3 (sLAG-3) and its association with circulating T lymphocyte subsets could pose as a novel biomarker to predict outcome to ICI therapy.

Methods
Circulating levels of sLAG3 were analyzed using multiplex immunoassay in n = 84 patients undergoing ICI therapy for advanced solid cancer, accompanied by flow cytometry analyses of peripheral blood mononuclear cells (PBMCs).

Results
Uni- and multivariate analysis shows that patients with higher sLAG3 concentrations before ICI therapy had a significantly impaired progression-free (PFS) and overall survival (OS) (HRPFS: 1.005 [95%CI: 1.000–1.009], p = 0.039; HROS: 1.006 [95%CI: 1.001–1.011], p = 0.015). The CD4/CD8 cell ratio and its dynamics during therapy were strong predictors of PFS and OS with patients with a decreasing ratio between baseline and after 1–2 cycles having an improved median OS compared to patients with increasing values (p = 0.012, HR: 3.32). An immunological score combining sLAG3 and the CD4/CD8 ratio showed the highest predictive potential (HROS: 10.3).

Conclusion
Pending prospective validation, sLAG3 and correlating circulating T-cell subsets can be used as a non-invasive predictive marker to predict outcome to ICI therapy to help identifying ideal ICI candidates in the future.
FKBP10 promotes clear cell renal cell carcinoma progression and regulates sensitivity to the HIF2α blockade by facilitating LDHA phosphorylation
Authors: Liu Ren , Zou Zhihao , Chen Lingwu , Feng Yuanfa , Ye Jianheng , Deng Yulin , Zhu Xuejin , Zhang Yixun , Lin Jundong , Cai Shanghua , Tang Zhenfeng , Liang Yingke , Lu Jianming , Zhuo Yangjia , Han Zhaodong , Ling Xiaohui , Liang Yuxiang , Wang Zongren , Zhong Weide 
Published: January 2024

AbstractRenal cell carcinoma (RCC) is one of the three major malignant tumors of the urinary system and originates from proximal tubular epithelial cells. Clear cell renal cell carcinoma (ccRCC) accounts for approximately 80% of RCC cases and is recognized as a metabolic disease driven by genetic mutations and epigenetic alterations. Through bioinformatic analysis, we found that FK506 binding protein 10 (FKBP10) may play an essential role in hypoxia and glycolysis pathways in ccRCC progression. Functionally, FKBP10 promotes the proliferation and metastasis of ccRCC in vivo and in vitro depending on its peptidyl-prolyl cis-trans isomerase (PPIase) domains. Mechanistically, FKBP10 binds directly to lactate dehydrogenase A (LDHA) through its C-terminal region, the key regulator of glycolysis, and enhances the LDHA-Y10 phosphorylation, which results in a hyperactive Warburg effect and the accumulation of histone lactylation. Moreover, HIFα negatively regulates the expression of FKBP10, and inhibition of FKBP10 enhances the antitumor effect of the HIF2α inhibitor PT2385. Therefore, our study demonstrates that FKBP10 promotes clear cell renal cell carcinoma progression and regulates sensitivity to HIF2α blockade by facilitating LDHA phosphorylation, which may be exploited for anticancer therapy.
Improving the marine biodegradability of poly(alkylene succinate)-based copolymers
Authors: Kumagai Sumito , Hayashi Senri , Katsuragi Atsushi , Imada Motosuke , Sato Kaoko , Abe Hideki , Asakura Noriyuki , Takenaka Yasumasa 
Published: January 2024

AbstractWe report the syntheses of novel marine biodegradable poly(ethylene succinate) (PES)- and poly(butylene succinate) (PBS)-based copolymers containing different dicarboxylic acid (DCA) units with various carbon numbers and different feed ratios. Biochemical oxygen demand tests demonstrated that some of the obtained PES- and PBS-based copolymers were biodegradable in seawater. Specifically, polymers with longer-chain DCA units, even at low contents, exhibited marine biodegradability. The thermomechanical properties of the copolymers, such as their thermal stabilities, melting points, glass transition temperatures, tensile moduli, strains at break, and stresses at break, also varied with the DCA contents. These results indicated that the thermomechanical properties and the marine biodegradabilities of the PES- and PBS-based copolymers were regulated by controlling their structures and DCA contents. The polymers obtained in this study may replace general-purpose polymers. Our approach may also be applicable to other polymeric materials. Furthermore, our findings pave the way for the rational design and preparation of polymeric materials that are biodegradable in environments other than oceans and have good thermomechanical properties.
Conserved chromatin and repetitive patterns reveal slow genome evolution in frogs
Authors: Bredeson Jessen V. , Mudd Austin B. , Medina-Ruiz Sofia , Mitros Therese , Smith Owen Kabnick , Miller Kelly E. , Lyons Jessica B. , Batra Sanjit S. , Park Joseph , Berkoff Kodiak C. , Plott Christopher , Grimwood Jane , Schmutz Jeremy , Aguirre-Figueroa Guadalupe , Khokha Mustafa K. , Lane Maura , Philipp Isabelle , Laslo Mara , Hanken James , Kerdivel Gwenneg , Buisine Nicolas , Sachs Laurent M. , Buchholz Daniel R. , Kwon Taejoon , Smith-Parker Heidi , Gridi-Papp Marcos , Ryan Michael J. , Denton Robert D. , Malone John H. , Wallingford John B. , Straight Aaron F. , Heald Rebecca , Hockemeyer Dirk , Harland Richard M. , Rokhsar Daniel S. 
Published: January 2024

AbstractFrogs are an ecologically diverse and phylogenetically ancient group of anuran amphibians that include important vertebrate cell and developmental model systems, notably the genus Xenopus. Here we report a high-quality reference genome sequence for the western clawed frog, Xenopus tropicalis, along with draft chromosome-scale sequences of three distantly related emerging model frog species, Eleutherodactylus coqui, Engystomops pustulosus, and Hymenochirus boettgeri. Frog chromosomes have remained remarkably stable since the Mesozoic Era, with limited Robertsonian (i.e., arm-preserving) translocations and end-to-end fusions found among the smaller chromosomes. Conservation of synteny includes conservation of centromere locations, marked by centromeric tandem repeats associated with Cenp-a binding surrounded by pericentromeric LINE/L1 elements. This work explores the structure of chromosomes across frogs, using a dense meiotic linkage map for X. tropicalis and chromatin conformation capture (Hi-C) data for all species. Abundant satellite repeats occupy the unusually long (~20 megabase) terminal regions of each chromosome that coincide with high rates of recombination. Both embryonic and differentiated cells show reproducible associations of centromeric chromatin and of telomeres, reflecting a Rabl-like configuration. Our comparative analyses reveal 13 conserved ancestral anuran chromosomes from which contemporary frog genomes were constructed.
High-content screening identifies a small molecule that restores AP-4-dependent protein trafficking in neuronal models of AP-4-associated hereditary spastic paraplegia
Authors: Saffari Afshin , Brechmann Barbara , Böger Cedric , Saber Wardiya Afshar , Jumo Hellen , Whye Dosh , Wood Delaney , Wahlster Lara , Alecu Julian E. , Ziegler Marvin , Scheffold Marlene , Winden Kellen , Hubbs Jed , Buttermore Elizabeth D. , Barrett Lee , Borner Georg H. H. , Davies Alexandra K. , Ebrahimi-Fakhari Darius , Sahin Mustafa 
Published: January 2024

AbstractUnbiased phenotypic screens in patient-relevant disease models offer the potential to detect therapeutic targets for rare diseases. In this study, we developed a high-throughput screening assay to identify molecules that correct aberrant protein trafficking in adapter protein complex 4 (AP-4) deficiency, a rare but prototypical form of childhood-onset hereditary spastic paraplegia characterized by mislocalization of the autophagy protein ATG9A. Using high-content microscopy and an automated image analysis pipeline, we screened a diversity library of 28,864 small molecules and identified a lead compound, BCH-HSP-C01, that restored ATG9A pathology in multiple disease models, including patient-derived fibroblasts and induced pluripotent stem cell-derived neurons. We used multiparametric orthogonal strategies and integrated transcriptomic and proteomic approaches to delineate potential mechanisms of action of BCH-HSP-C01. Our results define molecular regulators of intracellular ATG9A trafficking and characterize a lead compound for the treatment of AP-4 deficiency, providing important proof-of-concept data for future studies.