bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Unified Framework for Extreme Subdaily Precipitation Frequency Analyses Based on Ordinary Events
Authors: Marra Francesco , Borga Marco , Morin Efrat 
Published: September 2020

AbstractThe metastatistical extreme value approach proved promising in the frequency analysis of daily precipitation from ordinary events, outperforming traditional methods based on sampled extremes. However, subdaily applications are currently restrained by two knowledge gaps: It is not known if ordinary events can be consistently examined over durations, and it is not clear to what extent their entire distributions represent extremes. We propose here a unified definition of ordinary events across durations and suggest the simplified metastatistical extreme value formulation for dealing with extremes emerging from the tail, rather than the entire distributions, of ordinary events. This unified framework provides robust estimates of extreme quantiles (<10% error on the 100 yr from a 26 yr long record) and allows representations in which ordinary and extreme events share the scaling exponent. Future applications could improve our knowledge of subdaily extreme precipitation and help investigate the impact of local factors and climatic forcing on their frequency.
Deep Learning for Characterizing Paleokarst Collapse Features in 3‐D Seismic Images
Authors: Wu Xinming , Yan Shangsheng , Qi Jie , Zeng Hongliu 
Published: September 2020

AbstractPaleokarst systems are found extensively in carbonate‐prone basins worldwide. They can form large reservoirs and provide efficient pathways for hydrocarbon migration, but they can also create serious engineering geohazards. The full delineation of potentially buried paleokarst systems plays an important role for reservoir characterization, oil and gas production, and other engineering tasks. We propose a supervised convolutional neural network (CNN) to automatically and accurately characterize paleokarst and associated collapse features from 3‐D seismic images. To avoid time‐consuming manual labeling for training the CNN, we propose an efficient workflow to automatically generate numerous 3‐D training image pairs including synthetic seismic images and the corresponding label images of the collapsed paleokarst features simulated in the seismic images. With this workflow, we are able to simulate realistic and diverse geologic structures and collapsed paleokarst features in the training images from which the CNN can effectively learn to recognize the collapsed paleokarst features in real field seismic images. Two field examples from the Fort Worth Basin demonstrate that our CNN‐based method is superior to conventional automatic methods in delineating paleokarst collapse features from seismic images. From the CNN‐based paleokarst characterization, we can further automatically extract 3‐D collapsed paleokarst systems and quantitatively measure their geometric parameters. Our CNN‐based method is highly efficient and takes only seconds to classify collapsed paleokarst features a 3‐D seismic image with 320 × 1, 024 × 1, 024 samples (approximately 268 km2) by using one graphics processing unit.
Seismic Discrimination of Controlled Explosions and Earthquakes Near Mount St. Helens Using P/S Ratios
Authors: Wang Ruijia , Schmandt Brandon , Kiser Eric 
Published: September 2020

AbstractExplosions and earthquakes are effectively discriminated by P/S amplitude ratios for moderate magnitude events (M ≥ 4) observed at regional to teleseismic distances (≥200 km). It is less clear if P/S ratios are effective explosion discriminants for lower magnitudes observed at shorter distances. We report new tests of P/S discrimination using a dense seismic array in a continental volcanic arc setting near Mount St. Helens, with 23 single‐fired borehole explosions (ML 0.9–2.3) and 406 earthquakes (ML 1–3.3). The array provides up to 95 three‐component broadband seismographs, and most source‐receiver distances are <120 km. Additional insight is provided by ~3,000 vertical component geophone recordings of each explosion. Potential controls on local distance P/S ratios are investigated, including frequency range, distance, magnitude, source depth, number of seismographs, and site effects. A frequency band of about 10–18 Hz performs better than lower or narrower bands because explosion‐induced S wave amplitudes diminish relative to P for higher frequencies. Source depth and magnitude exhibited weak influences on P/S ratios. Site responses for earthquakes and explosions are correlated with each other and with shallow crustal Vp and Vs from traveltime tomography. Overall, the results indicate high potential for local distance P/S explosion discrimination in a continental volcanic arc setting, with ≥98% true positives and ≤6.3% false positives when using the array median from ≥16 stations. Performance is reduced for smaller arrays, especially those with ≤4 stations, thereby emphasizing the importance of array data for discrimination of low magnitude explosions.
Glutamine reliance in cell metabolism
Authors: Yoo Hee Chan , Yu Ya Chun , Sung Yulseung , Han Jung Min 
Published: September 2020

AbstractAs knowledge of cell metabolism has advanced, glutamine has been considered an important amino acid that supplies carbon and nitrogen to fuel biosynthesis. A recent study provided a new perspective on mitochondrial glutamine metabolism, offering mechanistic insights into metabolic adaptation during tumor hypoxia, the emergence of drug resistance, and glutaminolysis-induced metabolic reprogramming and presenting metabolic strategies to target glutamine metabolism in cancer cells. In this review, we introduce the various biosynthetic and bioenergetic roles of glutamine based on the compartmentalization of glutamine metabolism to explain why cells exhibit metabolic reliance on glutamine. Additionally, we examined whether glutamine derivatives contribute to epigenetic regulation associated with tumorigenesis. In addition, in discussing glutamine transporters, we propose a metabolic target for therapeutic intervention in cancer.
The role of lifestyle and non-modifiable risk factors in the development of metabolic disturbances from childhood to adolescence
Authors: Börnhorst Claudia , Russo Paola , Veidebaum Toomas , Tornaritis Michael , Molnár Dénes , Lissner Lauren , Mårild Staffan , De Henauw Stefaan , Moreno Luis A. , Floegel Anna , Ahrens Wolfgang , Wolters Maike 
Published: September 2020

Abstract
Background
The study aimed to identify the effects of lifestyle, C-reactive protein (CRP) and non-modifiable risk factors on metabolic disturbances in the transition from childhood to adolescence.

Methods
In 3889 children of the IDEFICS/I.Family cohort, latent transition analysis was applied to estimate probabilities of metabolic disturbances based on waist circumference, blood pressure, blood glucose, and lipids assessed at baseline and at 2- and 6-year follow-ups. Multivariate mixed-effects models were used to assess the age-dependent associations of lifestyle, non-modifiable risk factors and CRP, with the transformed probabilities of showing abdominal obesity, hypertension, dyslipidemia, or several metabolic disturbances (reference: being metabolically healthy).

Results
Higher maternal body mass index, familial hypertension as well as higher CRP z-score increased the risk for all four metabolic outcomes while low/medium parental education increased the risk of abdominal obesity and of showing several metabolic disturbances. Out of the lifestyle factors, the number of media in the bedroom, membership in a sports club, and well-being were associated with some of the outcomes. For instance, having at least one media in the bedroom increased the risk for showing several metabolic disturbances where the odds ratio (OR) markedly increased with age (1.30 [95% confidence interval 1.18; 1.43] at age 8; 1.18 [1.14; 1.23] for interaction with age; i.e., resulting in an OR of 1.30 × 1.18 = 1.53 at age 9 and so forth). Further, entering puberty at an early age was strongly associated with the risk of abdominal obesity (2.43 [1.60; 3.69] at age 8; 0.75 [0.69; 0.81] for interaction with age) and the risk of showing several metabolic disturbances (2.46 [1.53; 3.96] at age 8; 0.71 [0.65; 0.77] for interaction with age).

Conclusions
Various factors influence the metabolic risk of children revealing the need for multifactorial interventions. Specifically, removing media from children’s bedroom as well as membership in a sports club seem to be promising targets for prevention.
Relationship of leukaemias with long-term ambient air pollution exposures in the adult Danish population
Authors: Puett Robin C. , Poulsen Aslak Harbo , Taj Tahir , Ketzel Matthias , Geels Camilla , Brandt Jørgen , Christensen Jesper H. , Sørensen Mette , Roswall Nina , Hvidtfeldt Ulla , Raaschou-Nielsen Ole 
Published: September 2020

Abstract
Background
Few population-based epidemiological studies of adults have examined the relationship between air pollution and leukaemias.

Methods
Using Danish National Cancer Registry data and Danish DEHM-UBM-AirGIS system-modelled air pollution exposures, we examined whether particulate matter (PM2.5), black carbon (BC), nitrogen dioxide (NO2) and ozone (O3) averaged over 1, 5 or 10 years were associated with adult leukaemia in general or by subtype. In all, 14,986 adult cases diagnosed 1989–2014 and 51,624 age, sex and time-matched controls were included. Separate conditional logistic regression models, adjusted for socio-demographic factors, assessed exposure to each pollutant with leukaemias.

Results
Fully adjusted models showed a higher risk of leukaemia with higher 1-, 5- and 10-year-average exposures to PM2.5 prior to diagnosis (e.g. OR per 10 µg/m3 for 10-year average: 1.17, 95% CI: 1.03, 1.32), and a positive relationship with 1-year average BC. Results were driven by participants 70 years and older (OR per 10 µg/m3 for 10-year average: 1.35, 95% CI: 1.15–1.58). Null findings for younger participants. Higher 1-year average PM2.5 exposures were associated with higher risks for acute myeloid and chronic lymphoblastic leukaemia.

Conclusion
Among older adults, higher risk for leukaemia was associated with higher residential PM2.5 concentrations averaged over 1, 5 and 10 years prior to diagnosis.
Metaplastic breast cancers frequently express immune checkpoint markers FOXP3 and PD-L1
Authors: Kalaw Emarene , Lim Malcolm , Kutasovic Jamie R. , Sokolova Anna , Taege Lucinda , Johnstone Kate , Bennett James , Saunus Jodi M. , Niland Colleen , Ferguson Kaltin , Gresshoff Irma , Bettington Mark , Pathmanathan Nirmala , Tse Gary M. , Papadimos David , Pathmanathan Rajadurai , Harris Gavin , Yamaguchi Rin , Tan Puay Hoon , Fox Stephen , O’Toole Sandra A. , Simpson Peter T. , Lakhani Sunil R. , McCart Reed Amy E. 
Published: September 2020

Abstract
Background
Metaplastic breast carcinoma encompasses a heterogeneous group of tumours with differentiation into squamous and/or spindle, chondroid, osseous or rhabdoid mesenchymal-looking elements. Emerging immunotherapies targeting Programmed Death Ligand 1 (PD-L1) and immune-suppressing T cells (Tregs) may benefit metaplastic breast cancer patients, which are typically chemo-resistant and do not express hormone therapy targets.

Methods
We evaluated the immunohistochemical expression of PD-L1 and FOXP3, and the extent of tumour infiltrating lymphocytes (TILs) in a large cohort of metaplastic breast cancers, with survival data.

Results
Metaplastic breast cancers were significantly enriched for PD-L1 positive tumour cells, compared to triple-negative ductal breast cancers (P < 0.0001), while there was no significant difference in PD-L1 positive TILs. Metaplastic breast cancers were also significantly enriched for TILs expressing FOXP3, with FOXP3 positive intra-tumoural TILs (iTILs) associated with an adverse prognostic outcome (P = 0.0226). Multivariate analysis identified FOXP3 iTILs expression status as an important independent prognostic factor for patient survival.

Conclusions
Our findings indicate the clinical significance and prognostic value of FOXP3, PD-1/PD-L1 checkpoint and TILs in metaplastic breast cancer and confirm that a subset of metaplastics may benefit from immune-based therapies.
BCAT1 binds the RNA-binding protein ZNF423 to activate autophagy via the IRE1-XBP-1-RIDD axis in hypoxic PASMCs
Authors: Xin Wei , Zhang Min , Yu Yang , Li Songlin , Ma Cui , Zhang Junting , Jiang Yuan , Li Yiying , Zheng Xiaodong , Zhang Lixin , Zhao Xijuan , Pei Xuzhong , Zhu Daling 
Published: September 2020

AbstractAbnormal functional changes in pulmonary artery smooth muscle cells are the main causes of many lung diseases. Among, autophagy plays a crucial role. However, the specific molecular regulatory mechanism of autophagy in PASMCs remains unclear. Here, we first demonstrate that BCAT1 played a key role in the autophagy of hypoxic PASMCs and hypoxic model rats. BCAT1-induced activation and accumulation of the autophagy signaling proteins BECN1 and Atg5 by the endoplasmic reticulum (ER) stress pathway. Interestingly, we discovered that BCAT1 bound IRE1 on the ER to activate expression of its downstream pathway XBP-1-RIDD axis to activate autophagy. More importantly, we identified an RNA-binding protein, zinc finger protein 423, which promoted autophagy by binding adenylate/uridylate (AU)-rich elements in the BCAT1 mRNA 3′-untranslated region. Overall, our results identify BCAT1 as a potential therapeutic target for the clinical treatment of lung diseases and reveal a novel posttranscriptional regulatory mechanism and signaling pathway in hypoxia-induced PASMC autophagy.
Four-octyl itaconate activates Nrf2 cascade to protect osteoblasts from hydrogen peroxide-induced oxidative injury
Authors: Zheng Yuehuan , Chen Zhe , She Chang , Lin Yazhou , Hong Yuan , Shi Liqiang , Zhang Yingzi , Cao Peng , Xu Xiangyang 
Published: September 2020

AbstractFour-octyl itaconate (4-OI) is the cell-permeable derivative of itaconate that can activate Nrf2 signaling by alkylating Keap1’s cysteine residues. Here, we tested the potential effect of 4-OI on hydrogen peroxide (H2O2)-induced oxidative injury in osteoblasts. In OB-6 cells and primary murine osteoblasts, 4-OI was able to activate Nrf2 signaling cascade and cause Keap1–Nrf2 disassociation, Nrf2 protein stabilization, cytosol accumulation, and nuclear translocation. 4-OI also augmented antioxidant-response element reporter activity and promoted expression of Nrf2-dependent genes (HO1, NQO1, and GCLC). Pretreatment with 4-OI inhibited H2O2-induced reactive oxygen species production, cell death, and apoptosis in osteoblasts. Furthermore, 4-OI inhibited H2O2-induced programmed necrosis by suppressing mitochondrial depolarization, mitochondrial cyclophilin D-ANT1 (adenine nucleotide translocase 1)-p53 association, and cytosol lactate dehydrogenase release in osteoblasts. Ectopic overexpression of immunoresponsive gene 1 (IRG1) increased endogenous itaconate production and activated Nrf2 signaling cascade, thereby inhibiting H2O2-induced oxidative injury and cell death. In OB-6 cells, Nrf2 silencing or CRISPR/Cas9-induced Nrf2 knockout blocked 4-OI-induced osteoblast cytoprotection against H2O2. Conversely, forced Nrf2 activation, by CRISPR/Cas9-induced Keap1 knockout, mimicked 4-OI-induced actions in OB-6 cells. Importantly, 4-OI was ineffective against H2O2 in Keap1-knockout cells. Collectively, 4-OI efficiently activates Nrf2 signaling to inhibit H2O2-induced oxidative injury and death of osteoblasts.
Wnt/β-catenin signaling pathway induces autophagy-mediated temozolomide-resistance in human glioblastoma
Authors: Yun Eun-Jin , Kim Sangwoo , Hsieh Jer-Tsong , Baek Seung Tae 
Published: September 2020

AbstractTemozolomide (TMZ) is widely used for treating glioblastoma multiforme (GBM), however, the treatment of such brain tumors remains a challenge due to the development of resistance. Increasing studies have found that TMZ treatment could induce autophagy that may link to therapeutic resistance in GBM, but, the precise mechanisms are not fully understood. Understanding the molecular mechanisms underlying the response of GBM to chemotherapy is paramount for developing improved cancer therapeutics. In this study, we demonstrated that the loss of DOC-2/DAB2 interacting protein (DAB2IP) is responsible for TMZ-resistance in GBM through ATG9B. DAB2IP sensitized GBM to TMZ and suppressed TMZ-induced autophagy by negatively regulating ATG9B expression. A higher level of ATG9B expression was associated with GBM compared to low-grade glioma. The knockdown of ATG9B expression in GBM cells suppressed TMZ-induced autophagy as well as TMZ-resistance. Furthermore, we showed that DAB2IP negatively regulated ATG9B expression by blocking the Wnt/β-catenin pathway. To enhance the benefit of TMZ and avoid therapeutic resistance, effective combination strategies were tested using a small molecule inhibitor blocking the Wnt/β-catenin pathway in addition to TMZ. The combination treatment synergistically enhanced the efficacy of TMZ in GBM cells. In conclusion, the present study identified the mechanisms of TMZ-resistance of GBM mediated by DAB2IP and ATG9B which provides insight into a potential strategy to overcome TMZ chemo-resistance.
Macrophage migration inhibitory factor inhibition as a novel therapeutic approach against triple-negative breast cancer
Authors: Charan Manish , Das Subhadip , Mishra Sanjay , Chatterjee Nabanita , Varikuti Sanjay , Kaul Kirti , Misri Swati , Ahirwar Dinesh K. , Satoskar Abhay R. , Ganju Ramesh K. 
Published: September 2020

AbstractTriple-negative breast cancer (TNBC), defined as loss of estrogen, progesterone, and Her2 receptors, is a subtype of highly aggressive breast cancer with worse prognosis and poor survival rate. Macrophage migration inhibitory factor (MIF) is a pleiotropic pro-inflammatory cytokine aberrantly expressed in many solid tumors and known to promote tumor progression and metastasis. However, its role in TNBC progression and metastasis is unexplored. Here we have shown that in TNBC patients, MIF expression was significantly enriched in the tumor compared to adjacent normal tissue. Using publically available patient datasets, we showed that MIF overexpression correlates with worse survival in TNBC compared to other hormonal status. Orthotopic implantation of TNBC cells into MIF knockout mice showed reduced tumor growth compared to wild-type mice. In addition, we have shown that MIF downregulation inhibits TNBC growth and progression in a syngeneic mouse model. We further showed that CPSI-1306, a small-molecule MIF inhibitor, inhibits the growth of TNBC cells in vitro. Mechanistic studies revealed that CPSI-1306 induces intrinsic apoptosis by alteration in mitochondrial membrane potential, cytochrome c (Cyt c) release, and activation of different caspases. In addition, CPSI-1306 inhibits the activation of cell survival and proliferation-related molecules. CPSI-1306 treatment also reduced the tumor growth and metastasis in orthotopic mouse models of mammary carcinoma. CPSI-1306 treatment of tumor-bearing mice significantly inhibited TNBC growth and pulmonary metastasis in a dose-dependent manner. Histological analysis of xenograft tumors revealed a higher number of apoptotic cells in CPSI-1306-treated tumors compared to vehicle controls. Our studies, for the first time, show that MIF overexpression in TNBC enhances growth and metastasis. Taken together, our results indicate that using small molecular weight MIF inhibitors could be a promising strategy to inhibit TNBC progression and metastasis.
Oxidative stress-mediated mitochondrial dysfunction facilitates mesenchymal stem cell senescence in ankylosing spondylitis
Authors: Ye Guiwen , Xie Zhongyu , Zeng Huiqiong , Wang Peng , Li Jinteng , Zheng Guan , Wang Shan , Cao Qian , Li Ming , Liu Wenjie , Cen Shuizhong , Li Zhaofeng , Wu Yanfeng , Ye Zhizhong , Shen Huiyong 
Published: September 2020

AbstractAnkylosing spondylitis (AS) is a chronic inflammatory disease possessing a morbid serum microenvironment with enhanced oxidative stress. Long-term exposure to an oxidative environment usually results in cellular senescence alone with cellular dysfunction. Mesenchymal stem cells (MSCs) are a kind of stem cell possessing strong capabilities for immunoregulation, and senescent MSCs may increase inflammation and participate in AS pathogenesis. The objective of this study was to explore whether and how the oxidative serum environment of AS induces MSC senescence. Here, we found that AS serum facilitated senescence of MSCs in vitro, and articular tissues from AS patients exhibited higher expression levels of the cell cycle arrest-related proteins p53, p21 and p16. Importantly, the levels of advanced oxidative protein products (AOPPs), markers of oxidative stress, were increased in AS serum and positively correlated with the extent of MSC senescence induced by AS serum. Furthermore, MSCs cultured with AS serum showed decreased mitochondrial membrane potential and ATP production together with a reduced oxygen consumption rate. Finally, we discovered that AS serum-induced mitochondrial dysfunction resulted in elevated reactive oxygen species (ROS) in MSCs, and ROS inhibition successfully rescued MSCs from senescence. In conclusion, our data demonstrated that the oxidative serum environment of AS facilitated MSC senescence through inducing mitochondrial dysfunction and excessive ROS production. These results may help elucidate the pathogenesis of AS and provide potential targets for AS treatment.
Carbon pricing and planetary boundaries
Authors: Engström Gustav , Gars Johan , Krishnamurthy Chandra , Spiro Daniel , Calel Raphael , Lindahl Therese , Narayanan Badri 
Published: September 2020

AbstractHuman activities are threatening to push the Earth system beyond its planetary boundaries, risking catastrophic and irreversible global environmental change. Action is urgently needed, yet well-intentioned policies designed to reduce pressure on a single boundary can lead, through economic linkages, to aggravation of other pressures. In particular, the potential policy spillovers from an increase in the global carbon price onto other critical Earth system processes has received little attention to date. To this end, we explore the global environmental effects of pricing carbon, beyond its effect on carbon emissions. We find that the case for carbon pricing globally becomes even stronger in a multi-boundary world, since it can ameliorate many other planetary pressures. It does however exacerbate certain planetary pressures, largely by stimulating additional biofuel production. When carbon pricing is allied with a biofuel policy, however, it can alleviate all planetary pressures.