bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disentangling the Sources of Uncertainties in the Projection of Flood Risk Across the Central United States (Iowa)
Authors: Michalek Alexander T. , Villarini Gabriele , Kim Taereem , Quintero Felipe , Krajewski Witold F. 
Published: November 2023

AbstractWe explore the projected changes in flood impacts across Iowa (central United States) and the associated uncertainties by forcing a hydrologic model with downscaled global climate model outputs and four Shared Socioeconomic Pathways. Our results point to projected increasing magnitude and variability in flooding across the state, especially for high‐emission scenarios. Next, we partition the flood impacts' projections into: (a) the response of the global climate models to anthropogenic forcing, (b) scenario uncertainty due to emissions, and (c) internal climate variability. We find scenario uncertainty plays a small role, while climate model uncertainty and internal climate variability dominate the flood impacts' projections, with the contribution of model uncertainty increasing toward the end of this century. Insights from our work can be utilized by stakeholders to understand the current limitations of flood impact projections and provide suggestions about where modelers should focus efforts to reduce uncertainty.
A Climatology of Summer‐Time Arctic Cyclones Using a Modified Phase Space
Authors: Croad Hannah L. , Methven John , Harvey Ben , Keeley Sarah P. E. , Volonté Ambrogio , Hodges Kevin I. 
Published: November 2023

AbstractWe perform a climatological analysis of summer‐time Arctic cyclone structure in reanalysis data using a phase space approach. A classification scheme for Arctic cyclones is proposed, dependent on whether vorticity structure during development is low‐level‐dominant (LLD) or upper‐level‐dominant (ULD). During growth, LLD cyclones (65.5%) exhibit warm‐core asymmetric structures, whereas ULD cyclones (34.5%) have cold‐core asymmetric structures. LLD cyclones typically have greater thermal asymmetry during growth. However, a transition to a persistent cold‐core axisymmetric structure after maturity is characteristic of summer‐time Arctic cyclones, regardless of structure during growth. LLD cyclones are typically stronger and preferentially track on the Russian coastline where there is high baroclinicity, whereas ULD cyclones tend to be longer‐lived and preferentially track in the Pacific sector, where they can interact with tropopause polar vortices. This study provides a platform for further research into different classes of Arctic cyclones and associated hazardous weather, and ultimately for developing conceptual models.
Mantle Oxidation Induced by Recycled Carbonate: Insights From Mg‐Zn‐Fe‐Cu Isotopic Systematics of Intraplate Basalts
Authors: Wu Tian‐Hao , Liu Sheng‐Ao 
Published: November 2023

AbstractMantle oxidation plays an essential role in volatile cycling between Earth’s interior and exterior. However, the conceivable oxidizer remains enigmatic and needs to be explored by geochemical tools. Here, we examine the potential of recycled carbonates in inducing redox changes of the deep mantle through combined isotopic studies of Mg (δ26Mg), Zn (δ66Zn), Fe (δ56Fe), and Cu (δ65Cu) on a suite of intraplate alkaline basalts proposed to have originated from the mantle transition zone (∼440–660 km). Compared with mid‐ocean ridge basalts (MORB), these basalts have variably lower δ26Mg and higher δ66Zn, the typical features of marine carbonates, indicating the presence of various amounts of deeply recycled carbonates in their sources. As the estimated amounts of recycled carbonates in sources increase (i.e., lower δ26Mg and higher δ66Zn), the basalts have higher δ56Fe and lower δ65Cu compared with MORB. These correlations cannot be explained alone by binary mixing between recycled carbonates and the pristine mantle because of the much lower Fe and Cu contents of marine carbonates than those of the mantle and instead require redox‐driven isotope fractionation induced by mantle carbonate metasomatism. During partial melting of an oxidized mantle source, isotopically heavy ferric iron and isotopically light sulfide were preferentially incorporated/dissolved into the melts that are enriched in heavy Fe and light Cu isotopes. These observations highlight that recycled carbonates serve as an important oxidizer for the deep mantle and facilitate the extraction of mantle sulfides, which can be effectively tracked by Fe and Cu isotopic systematics of intraplate basalts.
The Anisotropic Behavior of a Clay Shale: Strength, Hydro‐Mechanical Couplings and Failure Processes
Authors: Winhausen L. , Khaledi K. , Jalali M. , Bretthauer M. , Amann F. 
Published: November 2023

AbstractMany rocks exhibit a structural composition, which leads to an anisotropic behavior of different properties. A proper understanding of the directional dependency of these properties is required to analyze and predict the failure behavior of the rock mass upon stress changes during many geo‐engineering applications. This study investigates the selected host rock for nuclear waste disposal in Switzerland, Opalinus Clay, for its anisotropic unconfined compressive and tensile strength, poromechanical response, and effective shear strength in an extensive laboratory testing campaign. The results show the lowest unconfined compressive strength at angles of 30°–45° between the bedding plane and the compressive load direction, whereby the lowest tensile strength is found to be normal to the bedding orientation. Triaxial consolidated‐undrained compression tests reveal an anisotropic poromechanical behavior as well as peak and residual effective strength values, which are largely controlled by the orientation of the bedding plane with respect to the maximum principal stress. The magnitude of excess pore water pressures and dilation are both functions of loading configuration. The comparison of peak strength values for different loading angles indicates that the lowest effective shear strength can be expected at a loading configuration of approximately 45° between bedding orientation and the loading axis. The variation in the hydro‐mechanical response is associated with the microstructure controlling the poroelasticity and the failure processes. The results provide a deeper understanding of failure in anisotropic rocks contributing to the development of constitutive models for predicting the rock mass response.
Winter Subtropical Highs, the Hadley Circulation and Baroclinic Instability
Authors: Qiu Weiteng , Collins Matthew , Scaife Adam A. 
Published: November 2023

AbstractSubtropical highs have a profound influence on the weather and climate of adjacent continents. In this study, we use reanalysis data to investigate the interannual variability and trends in winter subtropical highs from 1979 to 2021. We find dynamical relationships between subtropical high intensity, the Hadley and Ferrel Circulation intensity, and the Eady Growth Rate (EGR). A poleward shift of the maximum in EGR is associated with a strengthening of the descending branches of the Ferrel and Hadley Cells, with subtropical troposphere adiabatic warming and an increased intensity and poleward movement of the subtropical highs. Shifts in the poleward EGR are dominated by changes in vertical wind shear which, in turn, are in thermal wind balance with variations and trends in temperature. The mechanism for the intensification of the subtropical highs involves feedbacks from high‐frequency transient eddies. Strong North Pacific and South Pacific Subtropical highs are associated with La‐Niña conditions. We also show that the mechanisms for interannual variations are similar to those for trends in the highs.
Exploring Deposition Observations of Oxidized Sulfur and Nitrogen as a Constraint on Emissions in the United States
Authors: Dutta Ishir , Heald Colette L. 
Published: November 2023

AbstractEmissions of anthropogenic sulfur and nitrogen oxides form secondary pollutants that impact human health, ecosystems, and climate. Accurate estimates of emissions trends are needed to verify the effectiveness of the regulation of these species. We explore the utility of deposition measurements of SOx (=SO2 + SO42−) and TNO3 (=HNO3 + NO3−) as constraints on emissions trends of SOx and NOx in the conterminous United States (CONUS) from 1990 to 2021. The GEOS‐Chem model captures observed annual SOx and TNO3 wet deposition at NADP‐NTN sites in 2011 with a −15% and +15% normalized mean bias (NMB), respectively. The model overestimates the dry deposition of SOx and TNO3 estimated at CASTNET sites in 2011 (NMB >100%), however, this bias is substantially reduced when using an alternate derived dry deposition data set at the same sites, highlighting the uncertainty in dry deposition velocities. Despite this, we find that the model (driven by scaled NEI emissions) captures the relative trend in dry deposition of SOx (−93% observed and −94% simulated) and TNO3 (−66% observed and −68% simulated) from 1990 to 2021 and that these decreases closely reflect the trends in anthropogenic SO2 emissions (−93%) and anthropogenic NOx emissions (−71%), respectively. SOx and TNO3 wet deposition observations are dominated by soluble secondary products and are more influenced by natural and transboundary sources, and therefore have decreased more modestly over the same period (−78% and −52%). Natural sources of NOx are relatively constant during this time and therefore moderate the reduction in total NOx emissions (−55%).
Impact of age and comorbidities on the efficacy and tolerability of bosutinib in previously treated patients with chronic myeloid leukemia: results from the phase 4 BYOND study
Authors: Rosti Gianantonio , Brümmendorf Tim H. , Gjertsen Björn T. , Giraldo-Castellano Pilar , Castagnetti Fausto , Gambacorti-Passerini Carlo , Ernst Thomas , Zhao Huadong , Kuttschreuter Luke , Purcell Simon , Giles Francis J. , Hochhaus Andreas 
Published: November 2023

AbstractIn the phase 4 BYOND trial, patients with pretreated chronic myeloid leukemia (CML) received bosutinib (starting dose: 500 mg/day). Efficacy and safety after ≥3 years of follow-up in 156 patients with Philadelphia chromosome–positive chronic phase CML by age and Charlson Comorbidity Index scores (without the age component; mCCI) is reported. Cumulative major molecular response rates at any time on treatment were 73.6%, 64.5%, and 74.1% in patients <65, 65–74, and ≥75 years of age, and 77.9%, 63.0%, and 59.3% in patients with mCCI scores 2, 3, and ≥4, respectively. Patients <65, 65–74, and ≥75 years of age experienced grade 3/4 treatment-emergent adverse events (TEAEs) at rates of 74.7%, 78.8%, and 96.4% and permanent discontinuations due to AEs at rates of 22.1%, 39.4%, and 46.4%, respectively. In patients with mCCI 2, 3, and ≥4, respective rates of grade 3/4 TEAEs were 77.8%, 77.8%, and 86.7%, and permanent discontinuations due to AEs were 25.3%, 33.3%, and 43.3%. In conclusion, a substantial proportion of patients maintained/achieved cytogenetic and molecular responses across age groups and mCCI scores. Older patients (≥75 years) and those with high comorbidity burden (mCCI ≥4) may require more careful monitoring due to the increased risk of TEAEs. Clinicaltrials.gov: NCT02228382.
Prognostic implications of CD9 in childhood acute lymphoblastic leukemia: insights from a nationwide multicenter study in China
Authors: Leung Kam Tong , Cai Jiaoyang , Liu Yu , Chan Kathy Yuen Yee , Shao Jingbo , Yang Hui , Hu Qun , Xue Yao , Wu Xuedong , Guo Xia , Zhai Xiaowen , Wang Ningling , Li Xue , Tian Xin , Li Zheng , Xue Ning , Guo Yuxia , Wang Lingzhen , Zou Yao , Xiao Peifang , He Yingyi , Jin Runming , Tang Jingyan , Yang Jun J. , Shen Shuhong , Pui Ching-Hon , Li Chi Kong 
Published: November 2023

AbstractThe outcomes of children with acute lymphoblastic leukemia (ALL) have been incrementally improved with risk-directed chemotherapy but therapy responses remain heterogeneous. Parameters with added prognostic values are warranted to refine the current risk stratification system and inform appropriate therapies. CD9, implicated by our prior single-center study, holds promise as one such parameter. To determine its precise prognostic significance, we analyzed a nationwide, multicenter, uniformly treated cohort of childhood ALL cases, where CD9 status was defined by flow cytometry on diagnostic samples of 3781 subjects. CD9 was expressed in 88.5% of B-ALL and 27.9% of T-ALL cases. It conferred a lower 5-year EFS and a higher CIR in B-ALL but not in T-ALL patients. The prognostic impact of CD9 was most pronounced in the intermediate/high-risk arms and those with minimal residual diseases, particularly at day 19 of remission induction. The adverse impact of CD9 was confined to specific cytogenetics, notablyBCR::ABL1+rather thanKMT2A-rearranged leukemia. Multivariate analyses confirmed CD9 as an independent predictor of both events and relapse. The measurement of CD9 offers insights into patients necessitating intervention, warranting its seamless integration into the diagnostic marker panel to inform risk level and timely introduction of therapeutic intervention for childhood ALL.
Does decreased autophagy and dysregulation of LC3A in astrocytes play a role in major depressive disorder?
Authors: He Shen , Shi Yue , Ye Jinmei , Yin Jiahui , Yang Yufang , Liu Dan , Shen Ting , Zeng Duan , Zhang Min , Li Siyuan , Xu Feikang , Cai Yiyun , Zhao Faming , Li Huafang , Peng Daihui 
Published: November 2023

AbstractAstrocytic dysfunction contributes to the molecular pathogenesis of major depressive disorder (MDD). However, the astrocytic subtype that mainly contributes to MDD etiology and whether dysregulated autophagy in astrocytes is associated with MDD remain unknown. Using a single-nucleus RNA sequencing (snRNA-seq) atlas, three astrocyte subtypes were identified in MDD, while C2 State-1Q astrocytes showed aberrant changes in both cell proportion and most differentially expressed genes compared with other subtypes. Moreover, autophagy pathways were commonly inhibited in astrocytes in the prefrontal cortices (PFCs) of patients with MDD, especially in C2 State-1Q astrocytes. Furthermore, by integrating snRNA-seq and bulk transcriptomic data, we found significant reductions in LC3A expression levels in the PFC region of CUMS-induced depressed mice, as well as in postmortem PFC tissues and peripheral blood samples from patients with MDD. These results were further validated by qPCR using whole-blood samples from patients with MDD and healthy controls. Finally, LC3A expression in the whole blood of patients with MDD was negatively associated with the severity of depressive symptoms. Overall, our results underscore autophagy inhibition in PFC astrocytes as a common molecular characteristic in MDD and might reveal a novel potential diagnostic marker LC3A.
Negative modulation of mitochondrial calcium uniporter complex protects neurons against ferroptosis
Authors: Marmolejo-Garza Alejandro , Krabbendam Inge E. , Luu Minh Danh Anh , Brouwer Famke , Trombetta-Lima Marina , Unal Osman , O’Connor Shane J. , Majerníková Naďa , Elzinga Carolina R. S. , Mammucari Cristina , Schmidt Martina , Madesh Muniswamy , Boddeke Erik , Dolga Amalia M. 
Published: November 2023

AbstractFerroptosis is an iron- and reactive oxygen species (ROS)-dependent form of regulated cell death, that has been implicated in Alzheimer’s disease and Parkinson’s disease. Inhibition of cystine/glutamate antiporter could lead to mitochondrial fragmentation, mitochondrial calcium ([Ca2+]m) overload, increased mitochondrial ROS production, disruption of the mitochondrial membrane potential (ΔΨm), and ferroptotic cell death. The observation that mitochondrial dysfunction is a characteristic of ferroptosis makes preservation of mitochondrial function a potential therapeutic option for diseases associated with ferroptotic cell death. Mitochondrial calcium levels are controlled via the mitochondrial calcium uniporter (MCU), the main entry point of Ca2+ into the mitochondrial matrix. Therefore, we have hypothesized that negative modulation of MCU complex may confer protection against ferroptosis. Here we evaluated whether the known negative modulators of MCU complex, ruthenium red (RR), its derivative Ru265, mitoxantrone (MX), and MCU-i4 can prevent mitochondrial dysfunction and ferroptotic cell death. These compounds mediated protection in HT22 cells, in human dopaminergic neurons and mouse primary cortical neurons against ferroptotic cell death. Depletion of MICU1, a [Ca2+]m gatekeeper, demonstrated that MICU is protective against ferroptosis. Taken together, our results reveal that negative modulation of MCU complex represents a therapeutic option to prevent degenerative conditions, in which ferroptosis is central to the progression of these pathologies.
Peroxiredoxin 1 regulates crosstalk between pyroptosis and autophagy in oral squamous cell carcinoma leading to a potential pro-survival
Authors: Ye Meilin , Liu Ting , Liu Shanshan , Tang Rong , Liu Hongrui , Zhang Fan , Luo Shenglei , Li Minqi 
Published: November 2023

AbstractPeroxiredoxin 1 (Prdx1), a vital antioxidant enzyme, has been proven to play an important role in the occurrence and development of cancers, but its effects on oral squamous cell carcinoma (OSCC) remain unclear. Here, we performed bioinformatics analysis and immunohistochemical (IHC) staining to confirm that Prdx1 was higher in OSCC tissues than in normal tissues. Consistently, RT-PCR and Western blot showed elevated Prdx1 expression in OSCC cell lines compared to human oral keratinocytes (HOK), which could be knockdown by small interfering RNA (siRNA) and Lentiviral vector delivery of short hairpin RNA (shRNA). Prdx1 silencing significantly blocked OSCC cell proliferation and metastasis, as evidenced by the CCK8, colony formation, in vivo tumorigenesis experiment, wound healing, transwell assays, and changes in migration-related factors. siPrdx1 transfection increased intracellular reactive oxygen species (ROS) levels and provoked pyroptosis, proved by the upregulation of pyroptotic factors and LDH release. Prdx1 silencing ROS-independently blocked autophagy. Mature autophagosome failed to form in the siPrdx1 group. Up-regulated autophagy limited pyroptosis triggered by Prdx1 deficiency, and down-regulated pyroptosis partly reversed siPrdx1-induced autophagy defect. Collectively, Prdx1 regulated pyroptosis in a ROS-dependent way and modulated autophagy in a ROS-independent way, involving the crosstalk between pyroptosis and autophagy.
PDK4 rescues high-glucose-induced senescent fibroblasts and promotes diabetic wound healing through enhancing glycolysis and regulating YAP and JNK pathway
Authors: Ma Zhouji , Ding Youjun , Ding Xiaofeng , Mou Haining , Mo Ran , Tan Qian 
Published: November 2023

AbstractDuring the process of wound healing, fibroblasts migrate to the wound site and perform essential functions in promoting cell proliferation, as well as synthesizing and secreting the extracellular matrix (ECM). However, in diabetic wounds, senescent fibroblasts exhibit impaired proliferative capacity and fail to synthesize essential ECM components. Pyruvate dehydrogenase kinase 4 (PDK4), a key enzyme regulating energy metabolism, has been implicated in modulating cellular senescence and fibroblast function. However, its specific role in diabetic wounds remains poorly understood. In this study, we conducted a series of in vivo and in vitro experiments using STZ-induced diabetic mice and human dermal fibroblasts. We evaluated cellular senescence markers, including SA-β-gal, P53, P16, P21, and PAI-1, as well as senescence-associated secretory phenotype (SASP) factors. Finally, we observed that PDK4 increased in normal wound healing, but its expression was insufficient in diabetic wounds. Significantly, the overexpression of PDK4 demonstrated the potential to accelerate diabetic wound healing and improve the senescence phenotype both in vivo and in vitro. Furthermore, our study elucidated the underlying mechanism by which PDK4 improved the senescent phenotype through the enhancement of glycolysis and regulation of YAP and JNK pathway. The effect was dependent on metabolic reprogramming and subsequent reduction of reactive oxygen species (ROS), which was mediated by PDK4. Overall, our findings highlight the potential of PDK4 as a promising therapeutic target for addressing diabetic wounds.
Optimal free-surface pumping by an undulating carpet
Authors: Pandey Anupam , Chen Zih-Yin , Yuk Jisoo , Sun Yuming , Roh Chris , Takagi Daisuke , Lee Sungyon , Jung Sunghwan 
Published: November 2023

AbstractExamples of fluid flows driven by undulating boundaries are found in nature across many different length scales. Even though different driving mechanisms have evolved in distinct environments, they perform essentially the same function: directional transport of liquid. Nature-inspired strategies have been adopted in engineered devices to manipulate and direct flow. Here, we demonstrate how an undulating boundary generates large-scale pumping of a thin liquid near the liquid-air interface. Two dimensional traveling waves on the undulator, a canonical strategy to transport fluid at low Reynolds numbers, surprisingly lead to flow rates that depend non-monotonically on the wave speed. Through an asymptotic analysis of the thin-film equations that account for gravity and surface tension, we predict the observed optimal speed that maximizes pumping. Our findings reveal how proximity to free surfaces, which ensure lower energy dissipation, can be leveraged to achieve directional transport of liquids.
Cytolytic circumsporozoite-specific memory CD4+ T cell clones are expanded during Plasmodium falciparum infection
Authors: Furtado Raquel , Paul Mahinder , Zhang Jinghang , Sung Joowhan , Karell Paul , Kim Ryung S. , Caillat-Zucman Sophie , Liang Li , Felgner Philip , Bauleni Andy , Gama Syze , Buchwald Andrea , Taylor Terrie , Seydel Karl , Laufer Miriam , Delahaye Fabien , Daily Johanna P. , Lauvau Grégoire 
Published: November 2023

AbstractClinical immunity against Plasmodium falciparum infection develops in residents of malaria endemic regions, manifesting in reduced clinical symptoms during infection and in protection against severe disease but the mechanisms are not fully understood. Here, we compare the cellular and humoral immune response of clinically immune (0-1 episode over 18 months) and susceptible (at least 3 episodes) during a mild episode of Pf malaria infection in a malaria endemic region of Malawi, by analysing peripheral blood samples using high dimensional mass cytometry (CyTOF), spectral flow cytometry and single-cell transcriptomic analyses. In the clinically immune, we find increased proportions of circulating follicular helper T cells and classical monocytes, while the humoral immune response shows characteristic age-related differences in the protected. Presence of memory CD4+ T cell clones with a strong cytolytic ZEB2+ T helper 1 effector signature, sharing identical T cell receptor clonotypes and recognizing the Pf-derived circumsporozoite protein (CSP) antigen are found in the blood of the Pf-infected participants gaining protection. Moreover, in clinically protected participants, ZEB2+ memory CD4+ T cells express lower level of inhibitory and chemotactic receptors. We thus propose that clonally expanded ZEB2+ CSP-specific cytolytic memory CD4+ Th1 cells may contribute to clinical immunity against the sporozoite and liver-stage Pf malaria.