bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Nappe des Marbres Unit of the Basque‐Cantabrian Basin: The Tectono‐thermal Evolution of a Fossil Hyperextended Rift Basin
Authors: Ducoux M. , Jolivet L. , Callot J.‐P. , Aubourg C. , Masini E. , Lahfid A. , Homonnay E. , Cagnard F. , Gumiaux C. , Baudin T. 
Published: September 2019

AbstractThe architecture of the Pyrenean‐Cantabrian belt results from the inversion of a series of former Cretaceous rift basins. A HT‐LP metamorphic event dated at 105 to 85 Ma ago is commonly associated with an Albo‐Cenomanian episode of hyperextension of the continental crust. This metamorphism is well known in the eastern Basque‐Cantabrian Basin within the Nappe des Marbres Unit (NMU) that is preserved from intense compressional deformation during the Pyrenean orogeny. Based on a structural study at the scale of the eastern Basque‐Cantabrian Basin and on a dense sampling for TRSCM estimates with the Raman spectroscopy of carbonaceous material (RSCM) method (Raman Spectrometry on Carbonaceous Material), we show following results: (1) the NMU has recorded two major phases of deformation, related to a localized extensional ductile foliation (S1) during the Cretaceous rifting and later by the regional N‐S shortening, recorded by a regional cleavage (S2) observed only in shale sediments. (2) The NMU is affected by early salt tectonics related to several diapirs and salt walls fed by the Upper Triassic evaporitic layer. (3) The NMU recorded maximum temperatures exceeding 550°C, which represent some of the highest temperatures along the Pyrenees. These new data demonstrate that there is no E‐W lateral metamorphic gradient across the belt and that hyperextension rifting occurred consistently within a high‐thermal regime; (4) metamorphic isograds are oblique in respect of the main structures, suggesting that the metamorphic event postdates most of the early salt‐related deformations prior to or coeval with early stages of rifting. As it represents one of the best preserved example of preorogenic hyperextended basin, the eastern Basque‐Cantabrian Basin record may be used regionally to better understand the rift to orogen evolution of the Pyrenean Internal Metamorphic Zone but also more generally as an analog of salt‐bearing hyperextended rift record.
Multiple‐Instance Superparameterization: 1. Concept, and Predictability of Precipitation
Authors: Jones Todd R. , Randall David A. , Branson Mark D. 
Published: September 2019

AbstractWe have investigated the predictability of precipitation using a new configuration of the superparameterized Community Atmosphere Model (SP‐CAM). The new configuration, called the multiple‐instance SP‐CAM, or MP‐CAM, uses the average heating and drying rates from 10 independent two‐dimensional cloud‐permitting models (CPMs) in each grid column of the global model, instead of a single CPM. The 10 CPMs start from slightly different initial conditions and simulate alternative realizations of the convective cloud systems. By analyzing the ensemble of possible realizations, we can study the predictability of the cloud systems and identify the weather regimes and physical mechanisms associated with chaotic convection. We explore alternative methods for quantifying the predictability of precipitation. Our results show that unpredictable precipitation occurs when the simulated atmospheric state is close to critical points as defined by Peters and Neelin (2006, https://doi.org/10.1038/nphys314). The predictability of precipitation is also influenced by the convective available potential energy and the degree of mesoscale organization. It is strongly controlled by the large‐scale circulation. A companion paper compares the global atmospheric circulations simulated by SP‐CAM and MP‐CAM.
Imagining Simpler Worlds to Understand the Complexity of Our Own
Authors: Gerber Edwin P. , DallaSanta Kevin , Gupta Aman 
Published: September 2019

AbstractThe atmospheric circulation response to global warming is important for accurate prediction of climate change on regional scales. For the midlatitudes, shifts in the extratropical jet streams have important consequences for precipitation, blocking, and extreme events. It has proven to be a challenge, however, to predict. For example, the North Atlantic jet stream plays a vital role in the climate of eastern North America and Europe; in the last intercomparison of state‐of‐the‐art climate models, the models did not even agree on the sign of its wintertime response to global warming. Perhaps this should not come as a surprise, as we also lack a comprehensive theory for the impact of warming on the midlatitude circulation. In a recent study, Tan et al. (2019, https://doi.org/10.1029/2018MS001492) constructed models of simpler atmospheres to explore the response of the midlatitude jet to global warming. Their idealized atmospheres highlight the difficulty of developing a comprehensive theory for the midlatitude circulation but also provide pathways to improve models of Earth's atmosphere. Models of simpler atmospheres allow one to isolate the impact of specific atmospheric processes and connect theoretical understanding with comprehensive climate prediction systems. Such models can also be used to explore very different atmospheric regimes, from Earth's past to distant planets.
Activation of mitogen-activated protein kinases in satellite glial cells of the trigeminal ganglion contributes to substance P-mediated inflammatory pain
Authors: Zhang Yanyan , Song Ning , Liu Fei , Lin Jiu , Liu Mengke , Huang Chaolan , Liao Daqing , Zhou Cheng , Wang Hang , Shen Jiefei 
Published: September 2019

Abstract
Inflammatory orofacial pain, in which substance P (SP) plays an important role, is closely related to the cross-talk between trigeminal ganglion (TG) neurons and satellite glial cells (SGCs). SGC activation is emerging as the key mechanism underlying inflammatory pain through different signalling mechanisms, including glial fibrillary acidic protein (GFAP) activation, phosphorylation of mitogen-activated protein kinase (MAPK) signalling pathways, and cytokine upregulation. However, in the TG, the mechanism underlying SP-mediated orofacial pain generated by SGCs is largely unknown. In this study, we investigated whether SP is involved in inflammatory orofacial pain by upregulating interleukin (IL)-1β and tumour necrosis factor (TNF)-α from SGCs, and we explored whether MAPK signalling pathways mediate the pain process. In the present study, complete Freund’s adjuvant (CFA) was injected into the whisker pad of rats to induce an inflammatory model in vivo. SP was administered to SGC cultures in vitro to confirm the effect of SP. Facial expression analysis showed that pre-injection of L703,606 (an NK-1 receptor antagonist), U0126 (an inhibitor of MAPK/extracellular signal-regulated kinase [ERK] kinase [MEK] 1/2), and SB203580 (an inhibitor of P38) into the TG to induce targeted prevention of the activation of the NK-1 receptor and the phosphorylation of MAPKs significantly suppressed CFA-induced inflammatory allodynia. In addition, SP promoted SGC activation, which was proven by increased GFAP, p-MAPKs, IL-1β and TNF-α in SGCs under inflammatory conditions. Moreover, the increase in IL-1β and TNF-α was suppressed by L703, 606, U0126 and SB203580 in vivo and in vitro. These present findings suggested that SP, released from TG neurons, activated SGCs through the ERK1/2 and P38 pathways and promoted the production of IL-1β and TNF-α from SGCs, contributing to inflammatory orofacial pain associated with peripheral sensitization.
Multi-omic biomarker identification and validation for diagnosing warzone-related post-traumatic stress disorder
Authors:   The PTSD Systems Biology Consortium, Dean Kelsey R. , Hammamieh Rasha , Mellon Synthia H. , Abu-Amara Duna , Flory Janine D. , Guffanti Guia , Wang Kai , Daigle Bernie J. , Gautam Aarti , Lee Inyoul , Yang Ruoting , Almli Lynn M. , Bersani F. Saverio , Chakraborty Nabarun , Donohue Duncan , Kerley Kimberly , Kim Taek-Kyun , Laska Eugene , Young Lee Min , Lindqvist Daniel , Lori Adriana , Lu Liangqun , Misganaw Burook , Muhie Seid , Newman Jennifer , Price Nathan D. , Qin Shizhen , Reus Victor I. , Siegel Carole , Somvanshi Pramod R. , Thakur Gunjan S. , Zhou Yong , Hood Leroy , Ressler Kerry J. , Wolkowitz Owen M. , Yehuda Rachel , Jett Marti , Doyle Francis J. , Marmar Charles 
Published: September 2019

AbstractPost-traumatic stress disorder (PTSD) impacts many veterans and active duty soldiers, but diagnosis can be problematic due to biases in self-disclosure of symptoms, stigma within military populations, and limitations identifying those at risk. Prior studies suggest that PTSD may be a systemic illness, affecting not just the brain, but the entire body. Therefore, disease signals likely span multiple biological domains, including genes, proteins, cells, tissues, and organism-level physiological changes. Identification of these signals could aid in diagnostics, treatment decision-making, and risk evaluation. In the search for PTSD diagnostic biomarkers, we ascertained over one million molecular, cellular, physiological, and clinical features from three cohorts of male veterans. In a discovery cohort of 83 warzone-related PTSD cases and 82 warzone-exposed controls, we identified a set of 343 candidate biomarkers. These candidate biomarkers were selected from an integrated approach using (1) data-driven methods, including Support Vector Machine with Recursive Feature Elimination and other standard or published methodologies, and (2) hypothesis-driven approaches, using previous genetic studies for polygenic risk, or other PTSD-related literature. After reassessment of ~30% of these participants, we refined this set of markers from 343 to 28, based on their performance and ability to track changes in phenotype over time. The final diagnostic panel of 28 features was validated in an independent cohort (26 cases, 26 controls) with good performance (AUC = 0.80, 81% accuracy, 85% sensitivity, and 77% specificity). The identification and validation of this diverse diagnostic panel represents a powerful and novel approach to improve accuracy and reduce bias in diagnosing combat-related PTSD.
Large-scale integrated analysis of ovarian cancer tumors and cell lines identifies an individualized gene expression signature for predicting response to platinum-based chemotherapy
Authors: Sun Jie , Bao Siqi , Xu Dandan , Zhang Yan , Su Jianzhong , Liu Jiaqi , Hao Dapeng , Zhou Meng 
Published: September 2019

AbstractHeterogeneity in chemotherapeutic response is directly associated with prognosis and disease recurrence in patients with ovarian cancer (OvCa). Despite the significant clinical need, a credible gene signature for predicting response to platinum-based chemotherapy and for guiding the selection of personalized chemotherapy regimens has not yet been identified. The present study used an integrated approach involving both OvCa tumors and cell lines to identify an individualized gene expression signature, denoted as IndividCRS, consisting of 16 robust chemotherapy-responsive genes for predicting intrinsic or acquired chemotherapy response in the meta-discovery dataset. The robust performance of this signature was subsequently validated in 25 independent tumor datasets comprising 2215 patients and one independent cell line dataset, across different technical platforms. The IndividCRS was significantly correlated with the response to platinum therapy and predicted the improved outcome. Moreover, the IndividCRS correlated with homologous recombination deficiency (HRD) and was also capable of discriminating HR-deficient tumors with or without platinum-sensitivity for guiding HRD-targeted clinical trials. Our results reveal the universality and simplicity of the IndividCRS as a promising individualized genomic tool to rapidly monitor response to chemotherapy and predict the outcome of patients with OvCa.
Lactate and pyruvate promote oxidative stress resistance through hormetic ROS signaling
Authors: Tauffenberger Arnaud , Fiumelli Hubert , Almustafa Salam , Magistretti Pierre J. 
Published: September 2019

AbstractL-lactate was long considered a glycolytic by-product but is now being recognized as a signaling molecule involved in cell survival. In this manuscript, we report the role of L-lactate in stress resistance and cell survival mechanisms using neuroblastoma cells (SH-SY5Y) as well as the C. elegans model. We observed that L-lactate promotes cellular defense mechanisms, including Unfolded Protein Response (UPR) and activation of nuclear factor erythroid 2–related factor 2 (NRF2), by promoting a mild Reactive Oxygen Species (ROS) burst. This increase in ROS triggers antioxidant defenses and pro-survival pathways, such as PI3K/AKT and Endoplasmic Reticulum (ER) chaperones. These results contribute to the understanding of the molecular mechanisms involved in beneficial effects of L-lactate, involving mild ROS burst, leading to activation of unfolded protein responses and detoxification mechanisms. We present evidence that this hormetic mechanism induced by L-lactate protects against oxidative stress in vitro and in vivo. This work contributes to the identification of molecular mechanisms, which could serve as targets for future therapeutic approaches for cell protection and aging-related disorders.
High throughput circRNA sequencing analysis reveals novel insights into the mechanism of nitidine chloride against hepatocellular carcinoma
Authors: Xiong Dan-dan , Feng Zhen-bo , Lai Ze-feng , Qin Yue , Liu Li-min , Fu Hao-xuan , He Rong-quan , Wu Hua-yu , Dang Yi-wu , Chen Gang , Luo Dian-zhong 
Published: September 2019

AbstractNitidine chloride (NC) has been demonstrated to have an anticancer effect in hepatocellular carcinoma (HCC). However, the mechanism of action of NC against HCC remains largely unclear. In this study, three pairs of NC-treated and NC-untreated HCC xenograft tumour tissues were collected for circRNA sequencing analysis. In total, 297 circRNAs were differently expressed between the two groups, with 188 upregulated and 109 downregulated, among which hsa_circ_0088364 and hsa_circ_0090049 were validated by real-time quantitative polymerase chain reaction. The in vitro experiments showed that the two circRNAs inhibited the malignant biological behaviour of HCC, suggesting that they may play important roles in the development of HCC. To elucidate whether the two circRNAs function as “miRNA sponges” in HCC, we identified circRNA-miRNA and miRNA-mRNA interactions by using the CircInteractome and miRwalk, respectively. Subsequently, 857 miRNA-associated differently expressed genes in HCC were selected for weighted gene co-expression network analysis. Module Eigengene turquoise with 423 genes was found to be significantly related to the survival time, pathology grade and TNM stage of HCC patients. Gene functional enrichment analysis showed that the 423 genes mainly functioned in DNA replication- and cell cycle-related biological processes and signalling cascades. Eighteen hubgenes (SMARCD1, CBX1, HCFC1, RBM12B, RCC2, NUP205, ECT2, PRIM2, RBM28, COPS7B, PRRC2A, GPR107, ANKRD52, TUBA1B, ATXN7L3, FUS, MCM8 and RACGAP1) associated with clinical outcomes of HCC patients were then identified. These findings showed that the crosstalk between hsa_circ_0088364 and hsa_circ_0090049 and their competing mRNAs may play important roles in HCC, providing interesting clues into the potential of circRNAs as therapeutic targets of NC in HCC.
Degraded neutrophil extracellular traps promote the growth of Actinobacillus pleuropneumoniae
Authors: de Buhr Nicole , Bonilla Marta C. , Pfeiffer Jessica , Akhdar Silke , Schwennen Cornelia , Kahl Barbara C. , Waldmann Karl-Heinz , Valentin-Weigand Peter , Hennig-Pauka Isabel , von Köckritz-Blickwede Maren 
Published: September 2019

AbstractActinobacillus pleuropneumoniae (A.pp) causes severe pneumonia associated with enormous economic loss in pigs. Peracute diseased pigs die in <24 h with pneumonia. Neutrophils are the prominent innate immune cell in this infection that massively infiltrate the infected lung. Here we show that neutrophils release neutrophil extracellular traps (NETs) as response to A.pp infection. Numerous NET-markers were identified in bronchoalveolar lavage fluid (BALF) of A.pp-infected piglets in vivo, however, most NET fibers are degraded. Importantly, A.pp is able to enhance its growth rate in the presence of NETs that have been degraded by nucleases efficiently. A.pp itself releases no nuclease, but we identified host nucleases as sources that degrade NETs after A.pp infection. Furthermore, the nucleases of co-infecting pathogens like Streptococcus suis increase growth of A.pp in presence of porcine NETs. Thus, A.pp is not only evading the antimicrobial activity of NETs, A.pp is rather additionally using parts of NETs as growth factor thereby taking advantage of host nucleases as DNase1 or nucleases of co-infecting bacteria, which degrade NETs. This effect can be diminished by inhibiting the bacterial adenosine synthase indicating that degraded NETs serve as a source for NAD, which is required by A.pp for its growth. A similar phenotype was found for the human pathogen Haemophilus (H.) influenzae and its growth in the presence of human neutrophils. H. influenzae benefits from host nucleases in the presence of neutrophils. These data shed light on the detrimental effects of NETs during host immune response against certain bacterial species that require and/or efficiently take advantage of degraded DNA material, which has been provided by host nuclease or nucleases of other co-infecting bacteria, as growth source.
Lung tumorspheres reveal cancer stem cell-like properties and a score with prognostic impact in resected non-small-cell lung cancer
Authors: Herreros-Pomares Alejandro , de-Maya-Girones Juan Diego , Calabuig-Fariñas Silvia , Lucas Rut , Martínez Alicia , Pardo-Sánchez José Miguel , Alonso Sergio , Blasco Ana , Guijarro Ricardo , Martorell Miguel , Escorihuela Eva , Chiara María Dolores , Duréndez Elena , Gandía Carolina , Forteza Jerónimo , Sirera Rafael , Jantus-Lewintre Eloísa , Farràs Rosa , Camps Carlos 
Published: September 2019

AbstractThe high resistance against current therapies found in non-small-cell lung cancer (NSCLC) has been associated to cancer stem-like cells (CSCs), a population for which the identification of targets and biomarkers is still under development. In this study, primary cultures from early-stage NSCLC patients were established, using sphere-forming assays for CSC enrichment and adherent conditions for the control counterparts. Patient-derived tumorspheres showed self-renewal and unlimited exponential growth potentials, resistance against chemotherapeutic agents, invasion and differentiation capacities in vitro, and superior tumorigenic potential in vivo. Using quantitative PCR, gene expression profiles were analyzed and NANOG, NOTCH3, CD44, CDKN1A, SNAI1, and ITGA6 were selected to distinguish tumorspheres from adherent cells. Immunoblot and immunofluorescence analyses confirmed that proteins encoded by these genes were consistently increased in tumorspheres from adenocarcinoma patients and showed differential localization and expression patterns. The prognostic role of genes significantly overexpressed in tumorspheres was evaluated in a NSCLC cohort (N = 661) from The Cancer Genome Atlas. Based on a Cox regression analysis, CDKN1A, SNAI1, and ITGA6 were found to be associated with prognosis and used to calculate a gene expression score, named CSC score. Kaplan–Meier survival analysis showed that patients with high CSC score have shorter overall survival (OS) in the entire cohort [37.7 vs. 60.4 months (mo), p = 0.001] and the adenocarcinoma subcohort [36.6 vs. 53.5 mo, p = 0.003], but not in the squamous cell carcinoma one. Multivariate analysis indicated that this gene expression score is an independent biomarker of prognosis for OS in both the entire cohort [hazard ratio (HR): 1.498; 95% confidence interval (CI), 1.167–1.922; p = 0.001] and the adenocarcinoma subcohort [HR: 1.869; 95% CI, 1.275–2.738; p = 0.001]. This score was also analyzed in an independent cohort of 114 adenocarcinoma patients, confirming its prognostic value [42.90 vs. not reached (NR) mo, p = 0.020]. In conclusion, our findings provide relevant prognostic information for lung adenocarcinoma patients and the basis for developing novel therapies. Further studies are required to identify suitable markers and targets for lung squamous cell carcinoma patients.
The emerging role of IMD 0354 on bone homeostasis by suppressing osteoclastogenesis and bone resorption, but without affecting bone formation
Authors: Chen Wenxiang , Xie Ziang , Tang Pan , Wang Yongli , Jie Zhiwei , Qin An , Jiang Xuesheng , Hu Zhijun , Fan Shunwu 
Published: September 2019

AbstractOsteoporosis is caused by an imbalance between bone formation and bone resorption. Receptor activator of nuclear factor-κB ligand (RANKL) promotes the activity and differentiation of osteoclasts via activating the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. IMD 0354 is a selective molecular inhibitor of inhibitor of NF-κB kinase subunit beta (IKKβ) and effective for treatment of acute and subacute inflammatory diseases through the suppression of NF-κB activation. However, the effect of IMD 0354 on bone homeostasis is unknown. In this study, we demonstrated that IMD 0354 significantly attenuated ovariectomy-induced bone loss and inhibited osteoclastogenesis in mice, whereas bone formation was not affected. Additionally, IMD 0354 dramatically inhibited osteoclast differentiation and function induced by RANKL and macrophage colony-stimulating factor in bone marrow monocytes as verified by tartrate-resistant acid phosphatase (TRAP) staining as well as bone resorption assay in vitro. Subsequently, we found that activation of NF-κB signaling and the ERK/c-Fos axis were blunted during osteoclast formation induced by RANKL. Transcription factors nuclear factor of activated T cells c1 (NFATc1) and c-Fos were suppressed with the decreased expression of osteoclast-related genes by IMD 0354. Our findings suggest that IMD 0354 could be a potential preventive and therapeutic drug for osteoporosis.
Epidemiology of genitourinary foreign bodies in the united states emergency room setting and its association with mental health disorders
Authors: Rodríguez Dayron , Thirumavalavan Nannan , Pan Shu , Apoj Michel , Butaney Mohit , Gross Martin S. , Munarriz Ricardo 
Published: September 2019

Abstract
The epidemiology of genitourinary foreign bodies (GUFB) has been mainly described through case reports and small series. The aim of this study is to investigate the epidemiologic, medical, and socioeconomic factors associated with GUFB, along with the resultant costs of care in emergency departments (EDs) nationwide. ED visits with the primary diagnosis of a GUFB between 2010 and 2014 were abstracted from the Nationwide Emergency Department Sample database. Between 2010 and 2014, a weighted estimate of 102,333 visits to the ED with GUFB were recorded in the US, representing a national incidence of 7.6 ED visits per 100,000 persons. Of these visits, 4.7% resulted in admission and males were more likely to be admitted (24.8% vs. 2.1%, p < 0.01). A third of patients had low income, 30% had no medical insurance, and a third of patients had Medicaid. Urethra/bladder and penile foreign bodies had a significant association with mental health disorders (35.6%). Vulvar/vaginal foreign bodies had a lower prevalence of mental health disorders (6.1%). Costs of managing patients in the ED averaged $3769. More importantly, penile or urethra/bladder foreign bodies incurred a higher cost ($30,071). This is the largest population-based study investigating the epidemiology of GUFB. GUFB are more common in young women and the majority of them are vulvar/vaginal. Urethral and bladder foreign bodies occurred in older male patients and are associated with longer hospital stays and costs. Over one third of male patients with urethra/bladder had significant mental health disorders.