bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Hydro‐Mechanical Properties of Fracture Intersections: Pressure‐Dependant Permeability and Effective Stress Law
Authors: Stanton‐Yonge Ashley , Mitchell Thomas M. , Meredith Philip G. 
Published: February 2023

AbstractFluid flow through the brittle crust is primarily controlled by the capability of fracture networks to provide pathways for fluid transport. The dominant permeability orientation within fractured rock masses has been consistently correlated with the development of fracture intersections; an observation also made at the meso‐regional scale. Despite the importance attributed to fracture intersections in promoting fluid flow, the magnitude of their enhancement of fractured rock permeability has not yet been quantified. Here, we characterize the hydro‐mechanical properties of intersections in samples of Seljadalur Basalt by generating two orthogonal, tensile fractures produced by two separate loadings using a Brazilian test apparatus, and measuring their permeability as a function of hydrostatic pressure. We observe that intersecting fractures are significantly more permeable and less compliant than two independent macro‐fractures. We formulate a model for fracture intersection permeability as a function of pressure by adding the contributions of two independent fractures plus a tube‐like cavity with an effective elastic compressibility determined by its geometry. Permeability measurements during cyclic loading allowed determination of the effective stress coefficient (α in pe = pc − αpp) for fracture and intersection permeability. We observe a trend of lower αintersection values with respect to αfracture, which suggests that the channels controlling fluid flow have a higher aspect ratio (are more tubular) for the intersections relative to independent fractures. Our results suggest that fracture intersections play a critical role in maintaining permeability at depth, which has significant implications for the quantification and upscaling of fracture permeability toward reservoir‐scale simulations.
Tectonic Controls on Magmatic Tempo in an Active Continental Margin: Insights From the Early Cretaceous Syn‐Tectonic Magmatism in the Changle‐Nan’ao Belt, South China
Authors: Wei Wei , Lin Wei , Chen Yan , Faure Michel , Ji Wenbin , Hou Quanlin , Yan Quanren , Wang Qingchen 
Published: February 2023

AbstractThe cause of magmatic tempo in an active plate margin remains controversial, partly due to lack of structural analysis. During 130–105 Ma, the magmatism in the South China Block (SCB) was significantly reduced (lull) and restricted around the Changle‐Nan'ao Belt (CNB) while the magmatism was highly active (flare‐up) in North China. For unveiling the tectonic role on magmatism, a multidisciplinary study including field and microscopic structural observations, magnetic fabric measurement (AMS), and zircon/monazite dating was conducted on the plutons with oriented minerals in the CNB. Structural analysis and AMS results show a highly clustered NE‐striking vertical foliation developed during the emplacement indicating a syn‐emplacement NW‐SE shortening regime. The geochronology results confirm that the emplacement occurred during 130–105 Ma. Regional geologic correlation indicates that the collision between the Dangerous Grounds‐West Philippines Block and SCB was responsible for this shortening regime. The collected depleted zircon εHf(t) data suggest that a possible collision‐triggered slab break‐off caused the syn‐collisional magmatic activity around the CNB. This study shows that the magmatic lull in the SCB was coeval with a crustal shortening regime due to the arrival of a microcontinent carried by the subduction slab, while the magmatic flare‐up was coeval with an extensional regime due to the subduction roll‐back and retreat as evidenced by the Cretaceous evolution of the SCB before and after the collision and that of North China which is unaffected by the collision. The cause of magmatic tempo in the continental margin is largely due to the tectonic evolution of underlain subduction slabs.
Convectively Transported Water Vapor Plumes in the Midlatitude Lower Stratosphere
Authors: Wang Xun , Huang Yi , Qu Zhipeng , Vaillancourt Paul A. , Yau Man‐Kong , Feng Jing , Langille Jeffery , Bourassa Adam 
Published: February 2023

AbstractDeep convective overshooting has been shown to transport water vapor into the midlatitude lower stratosphere. However, it has not been demonstrated how the convective water vapor plumes evolve after the overshoots collapse. Furthermore, there is a lack of characterization of the convective water vapor plumes, nor is it clear whether satellite instruments can observe the characteristics. We use a high‐resolution numerical weather prediction model to study a convective system over North America. Multiple overshoots transport water vapor in the overworld stratosphere, forming a moist layer between 16.2 and 16.8 km (389.8–399.7 K), with horizontal diameters of about 300–400 km, and a maximum water vapor mixing ratio of 10.0 ppmv (4.3 ppmv anomaly). Lagrangian trajectories and mass integrations show the overworld water vapor plumes are maintained after the convective system weakens. In the lowermost stratosphere (LMS), water vapor plumes are less stable and ice is present, because there is perturbation by ongoing convection. Lagrangian trajectories and mass integrations show the LMS parcels partly return to the troposphere, and that the LMS water vapor mass is reduced by half after the convection weakens. On average, the LMS moistening is between 15.0 and 15.8 km (362.6–382.0 K), with horizontal diameters of about 150 km, and a maximum water vapor mixing ratio of 31.1 ppmv (18.4 ppmv anomaly). Although current satellites have difficulty observing the fine structure of the convective water vapor plumes, a new satellite instrument under development (SHOW) with 1‐km vertical and 100‐km horizontal resolution will be able to verify the plume characteristics.
Cloud Condensation Nuclei Closure Study Using Airborne Measurements Over the Southern Great Plains
Authors: Kulkarni Gourihar , Mei Fan , Shilling John E. , Wang Jian , Reveggino Renato Pinto , Flynn Connor , Zelenyuk Alla , Fast Jerome 
Published: February 2023

AbstractAirborne measurements of non‐refractory bulk aerosol chemical composition, aerosol size distributions, and cloud condensation nuclei (CCN) were conducted onboard a research aircraft during the Holistic Interactions of Shallow Clouds, Aerosols and Land Ecosystems field campaign in the spring and summer of 2016. A CCN closure study for the entire campaign period was performed where measured CCN concentrations at 0.24% and 0.46% supersaturation were compared with the predicted CCN concentrations calculated using κ‐Köhler theory, three different assumptions of aerosol mixing state, and various assumptions about hygroscopicity, density, and the insoluble fraction of organic particles. We found that the Closure Ratio (CR), calculated as the ratio of predicted to measured CCN concentrations, was equal to one under two different aerosol mixing state assumptions: (a) all particles are composed of 100% organic particles, and (b) particles are externally mixed and composed of pure sulfates, nitrates, and organic particles assuming hygroscopicity values for organic particles () between 0.04 and 0.17. The use of internal mixing state assumption often led to overprediction of CCN concentrations but the agreement within ±20% with the measured CCN concentrations was observed under certain closure permutations. A similar agreement, that is, within ±20%, was also observed using permuted parameters concerning density (1 and 1.5 g cm−3) and an insoluble fraction (0% and 20%) of organic particles. These findings may provide constraints on to predict CCN concentrations at a remote continental Southern Great Plains site.
Effect of Slope Aspect on Plant Above‐ and Belowground Functional Traits of Alpine Meadow on the Qinghai‐Tibet Plateau, China
Authors: Pan Yingping , Ren Liang , Xiang Xiang , Huo Jiaxuan , Meng Dehui , Wang Yuanyuan , Yu Cheng , Huang Yongmei 
Published: February 2023

AbstractSlope aspects could cause significant differences in microclimate (e.g., radiation and moisture) and edaphic properties (e.g., soil nutrients content) in rugged landscapes. Therefore, understanding the variations of the above‐ and belowground functional traits on hillslope scales and their driving factors are essential for disentangling the plant adaptive strategies to local environmental factors. Based on the measurements of community weighted mean traits of alpine meadow from 15 hillslopes (eight south‐facing and seven north‐facing) in the Qinghai Lake watershed, northeastern Qinghai‐Tibet Plateau, China, we found that the aboveground morphological traits that is, specific leaf area and leaf dry matter content, and belowground stoichiometric traits, that is, root carbon content (RCC), root nitrogen content (RNC), root phosphorus content (RPC) and RCC: RNC, varied significantly between slope aspects. Hierarchical partitioning indicated that the slope aspect contributed the most to the variations of aboveground morphological and belowground stoichiometric traits, whereas soil properties were the major contributor to aboveground phosphorous‐related traits and belowground morphological traits. Both above‐ and belowground traits displayed a two‐dimensional variation on the hillslope scale. Additionally, the above‐ and belowground traits were weakly coordinated. In general, alpine meadow on the south‐facing slopes tended to adopt the conservative strategy, while acquisitive strategy was preferred by that on the north‐facing slopes. These findings can improve our understanding of spatial variations of functional traits at fine scales, and we highlighted that it is helpful to integrate both above‐ and belowground traits dimensions in disentangling the ecological process and predicting ecosystem function under changing climate.
Cre recombinase expression cooperates with homozygous FLT3 internal tandem duplication knockin mouse model to induce acute myeloid leukemia
Authors: Straube Jasmin , Eifert Theresa , Vu Therese , Janardhanan Yashaswini , Haldar Rohit , von Eyss Björn , Cooper Leanne , Bruedigam Claudia , Ling Victoria Y. , Cooper Emily , Patch Ann-Marie , Bullinger Lars , Schnoeder Tina M. , Bywater Megan , Heidel Florian H. , Lane Steven W. 
Published: February 2023

AbstractMurine models offer a valuable tool to recapitulate genetically defined subtypes of AML, and to assess the potential of compound mutations and clonal evolution during disease progression. This is of particular importance for difficult to treat leukemias such as FLT3 internal tandem duplication (ITD) positive AML. While conditional gene targeting by Cre recombinase is a powerful technology that has revolutionized biomedical research, consequences of Cre expression such as lack of fidelity, toxicity or off-target effects need to be taken into consideration. We report on a transgenic murine model of FLT3-ITD induced disease, where Cre recombinase expression alone, and in the absence of a conditional allele, gives rise to an aggressive leukemia phenotype. Here, expression of various Cre recombinases leads to polyclonal expansion of FLT3ITD/ITD progenitor cells, induction of a differentiation block and activation of Myc-dependent gene expression programs. Our report is intended to alert the scientific community of potential risks associated with using this specific mouse model and of unexpected effects of Cre expression when investigating cooperative oncogenic mutations in murine models of cancer.
Mitochondrial fusion is a therapeutic vulnerability of acute myeloid leukemia
Authors: Larrue Clement , Mouche Sarah , Lin Shan , Simonetta Federico , Scheidegger Nastassja K. , Poulain Laury , Birsen Rudy , Sarry Jean-Emmanuel , Stegmaier Kimberly , Tamburini Jerome 
Published: February 2023

AbstractMitochondrial metabolism recently emerged as a critical dependency in acute myeloid leukemia (AML). The shape of mitochondria is tightly regulated by dynamin GTPase proteins, which drive opposing fusion and fission forces to consistently adapt bioenergetics to the cellular context. Here, we showed that targeting mitochondrial fusion was a new vulnerability of AML cells, when assayed in patient-derived xenograft (PDX) models. Genetic depletion of mitofusin 2 (MFN2) or optic atrophy 1 (OPA1) or pharmacological inhibition of OPA1 (MYLS22) blocked mitochondrial fusion and had significant anti-leukemic activity, while having limited impact on normal hematopoietic cells ex vivo and in vivo. Mechanistically, inhibition of mitochondrial fusion disrupted mitochondrial respiration and reactive oxygen species production, leading to cell cycle arrest at the G0/G1 transition. These results nominate the inhibition of mitochondrial fusion as a promising therapeutic approach for AML.
Spindle function and Wnt pathway inhibition by PBX1 to suppress tumor progression via downregulating DCDC2 in colorectal cancer
Authors: Dai Weigang , Liu Yinan , Zhang Tianhao , Huang Zhixin , Xu Xiang , Zhao Zeyu , Liu Jianqiu , Zhai Ertao , Cai Shirong , Chen Jianhui 
Published: February 2023

AbstractPBX1 is a transcription factor that regulates a variety of genes, involved in intracellular lipid metabolism, cell proliferation, and other pathways. The promoting and inhibiting function of PBX1 in various cancer types was extensively discussed, however, there have been no studies on PBX1 proteins in colorectal cancer (CRC). This study aimed to reveal the anti-tumor function of PBX1 in CRC and the underlying molecular mechanism. Bioinformatics analysis revealed that PBX1 is downregulated in CRC, indicating that is a potential antioncogene in CRC. Overexpression of PBX1 suppresses tumor growth and metastasis in vitro and in vivo. Mechanistically, we found that PBX1 acted as a transcription factor that suppressed DCDC2 expression and inhibited spindle function. Moreover, the PBX1-DCDC2 axis controlled the Wnt pathway in CRC cells. Overexpression of DCDC2 restored CRC proliferation, metastasis abilities and Wnt pathway. In conclusion, this study suggests that PBX1 acts as a transcription factor to suppress DCDC2 expression and inhibit cell proliferation and metastasis by disrupting spindle function and the Wnt pathway in CRC.
Blood glutamate scavenging as a novel glutamate-based therapeutic approach for post-traumatic brain injury anxiety and social impairment
Authors: Frank Dmitry , Gruenbaum Benjamin F. , Shelef Ilan , Zvenigorodsky Vladislav , Severynovska Olena , Fleidervish Ilya , Knyazer Boris , Frenkel Amit , Zlotnik Alexander , Kofman Ora , Boyko Matthew 
Published: February 2023

AbstractTraumatic brain injury (TBI) is a serious condition that is associated with an increased risk of severe, long-term psychiatric consequences. Drugs that target the glutamatergic system have proven successful in treating both TBI and many of its psychiatric sequelae. Blood glutamate scavengers (BGS) cause a decrease in blood glutamate levels, leading to a reduction in glutamate’s concentration gradient from the brain to the blood and decreased levels of brain glutamate. This study evaluated the BGS pyruvate as a treatment for TBI-related neuropsychiatric conditions in a rat model. 213 rats were divided into four groups in a 2 × 2 design: Sham or TBI rats treated with pyruvate or control treatment. Magnetic resonance imaging, neurological status, brain glutamate and blood glutamate levels were assessed following the injury. Four weeks after the start of treatment, all rats underwent behavioral tests to assess anxious behavior and social impairment (aggressive and hierarchical behavior). Rats responded positively to pyruvate in several tasks, lowering brain glutamate levels and reducing anxiety and depression, as well as modulating TBI-related changes in social behavior. Glutamate scavenging with pyruvate may be an effective therapeutic option for post-TBI behavioral changes by reducing associated elevations in brain glutamate levels.
Oxytocin vs. placebo effects on intrusive memory consolidation using a trauma film paradigm: a randomized, controlled experimental study in healthy women
Authors: Maslahati Tolou , Wingenfeld Katja , Hellmann-Regen Julian , Kraft Julia , Lyu Jing , Keinert Marie , Voß Aline , Cho An Bin , Ripke Stephan , Otte Christian , Schultebraucks Katharina , Roepke Stefan 
Published: February 2023

AbstractOxytocin administration during a trauma analogue has been shown to increase intrusive memories, which are a core symptom of post-traumatic stress disorder (PTSD). However, it is unknown whether oxytocin influences the acquisition or the consolidation of the trauma. The current study investigates the effect of the activation of the oxytocin system during the consolidation of an analogue trauma on the formation of intrusive memories over four consecutive days and whether this effect is influenced by individual neurobiological, genetic, or psychological factors. We conducted a randomized double-blind placebo-controlled study in 217 healthy women. They received either a single dose of intranasal oxytocin (24 IU) or placebo after exposure to a trauma film paradigm, which reliably induces intrusive memories. We used a general random forest to examine a potential heterogeneous treatment effect of oxytocin on the consolidation of intrusive memories. Furthermore, we used a poisson regression to examine whether salivary alpha amylase activity (sAA) as a marker of noradrenergic activity and cortisol response to the film, polygenic risk score (PRS) for psychiatric disorders, and psychological factors influence the number of intrusive memories. We found no significant effect of oxytocin on the formation of intrusive memories (F(2, 543.16) = 0.75, p = 0.51, ηp2 = 0.00) and identified no heterogeneous treatment effect. We replicated previous associations of the PRS for PTSD, sAA and the cortisol response on intrusive memories. We further found a positive association between high trait anxiety and intrusive memories, and a negative association between the emotion regulation strategy reappraisal and intrusive memories. Data of the present study suggest that the consolidation of intrusive memories in women is modulated by genetic, neurobiological and psychological factors, but is not influenced by oxytocin. Trial registration: NCT03875391.
Use of methotrexate and risk of skin cancer: a nationwide case–control study
Authors: Polesie Sam , Gillstedt Martin , Schmidt Sigrún Alba Jóhannesdóttir , Egeberg Alexander , Pottegård Anton , Kristensen Kasper 
Published: February 2023

Abstract
Background
Methotrexate (MTX) use has been suspected of increasing the risk of skin cancer. The aim of this investigation was to examine the association between the use of MTX and the risk of basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC) and cutaneous malignant melanoma (CMM).

Methods
In a nationwide Danish case–control study, we identified incident, histologically verified cases of BCC (n = 131,447), cSCC (n = 18,661) or CMM (26,068) from 2004 to 2018. We matched 10 controls to each case on sex and birth year using risk-set sampling and computed crude and adjusted odds ratios (ORs) using conditional logistic regression for the use of MTX (≥2.5 g) compared with never-use.

Results
Use of MTX was associated with increased risk of BCC, cSCC and CMM with adjusted ORs of (95% confidence interval) 1.29 (1.20–1.38), 1.61 (1.37–1.89) and 1.35 (1.13–1.61), respectively. For BCC and cSCC, ORs increased with higher cumulative doses. When restricting the study population to patients with psoriasis, the ORs were 1.43 (1.23–1.67), 1.18 (0.80–1.74) and 1.15 (0.77–1.72), respectively.

Conclusions
We observed an increased risk of BCC and cSCC associated with the use of MTX with evidence of a dose–response pattern; however, the association was not consistent when restricting the study population to patients with psoriasis.
Different pathways for engulfment and endocytosis of liquid droplets by nanovesicles
Authors: Ghosh Rikhia , Satarifard Vahid , Lipowsky Reinhard 
Published: February 2023

AbstractDuring endocytosis of nanoparticles by cells, the cellular membranes engulf the particles, thereby forming a closed membrane neck that subsequently undergoes fission. For solid nanoparticles, these endocytic processes have been studied in some detail. Recently, such processes have also been found for liquid and condensate droplets, both in vitro and in vivo. These processes start with the spreading of the droplet onto the membrane followed by partial or complete engulfment of the droplet. Here, we use molecular dynamics simulations to study these processes at the nanoscale, for nano-sized droplets and vesicles. For both partial and complete engulfment, we observe two different endocytic pathways. Complete engulfment leads to a closed membrane neck which may be formed in a circular or strongly non-circular manner. A closed circular neck undergoes fission, thereby generating two nested daughter vesicles whereas a non-circular neck hinders the fission process. Likewise, partial engulfment of larger droplets leads to open membrane necks which can again have a circular or non-circular shape. Two key parameters identified here for these endocytic pathways are the transbilayer stress asymmetry of the vesicle membrane and the positive or negative line tension of the membrane-droplet contact line.
Evolutionary route of nasopharyngeal carcinoma metastasis and its clinical significance
Authors: Lin Mei , Zhang Xiao-Long , You Rui , Liu You-Ping , Cai Hong-Min , Liu Li-Zhi , Liu Xue-Fei , Zou Xiong , Xie Yu-Long , Zou Ru-Hai , Zhang Yi-Nuan , Sun Rui , Feng Wei-Yi , Wang Hai-Yan , Tao Gui-Hua , Li Hao-Jiang , Huang Wen-Jie , Zhang Chao , Huang Pei-Yu , Wang Jin , Zhao Qi , Yang Qi , Zhang Hong-Wan , Liu Ting , Li Hui-Feng , Jiang Xiao-Bing , Tang Jun , Gu Yang-Kui , Yu Tao , Wang Zhi-Qiang , Feng Lin , Kang Tie-Bang , Zuo Zhi-Xiang , Chen Ming-Yuan 
Published: February 2023

AbstractIt is critical to understand factors associated with nasopharyngeal carcinoma (NPC) metastasis. To track the evolutionary route of metastasis, here we perform an integrative genomic analysis of 163 matched blood and primary, regional lymph node metastasis and distant metastasis tumour samples, combined with single-cell RNA-seq on 11 samples from two patients. The mutation burden, gene mutation frequency, mutation signature, and copy number frequency are similar between metastatic tumours and primary and regional lymph node tumours. There are two distinct evolutionary routes of metastasis, including metastases evolved from regional lymph nodes (lymphatic route, 61.5%, 8/13) and from primary tumours (hematogenous route, 38.5%, 5/13). The hematogenous route is characterised by higher IFN-γ response gene expression and a higher fraction of exhausted CD8+ T cells. Based on a radiomics model, we find that the hematogenous group has significantly better progression-free survival and PD-1 immunotherapy response, while the lymphatic group has a better response to locoregional radiotherapy.