bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advances in seismic imaging of magma and crystal mush
Authors: Paulatto Michele , Hooft Emilie E. E. , Chrapkiewicz Kajetan , Heath Benjamin , Toomey Douglas R. , Morgan Joanna V. 
Published: October 2022

Seismic imaging methods have provided detailed three-dimensional constraints on the physical properties of magmatic systems leading to invaluable insight into the storage, differentiation and dynamics of magma. These constraints have been crucial to the development of our modern understanding of magmatic systems. However, there are still outstanding knowledge gaps resulting from the challenges inherent in seismic imaging of volcanoes. These challenges stem from the complex physics of wave propagation across highly heterogeneous low-velocity anomalies associated with magma reservoirs. Ray-based seismic imaging methods such as travel-time and surface-wave tomography lead to under-recovery of such velocity anomalies and to under-estimation of melt fractions. This review aims to help the volcanologist to fully utilize the insights gained from seismic imaging and account for the resolution limits. We summarize the advantages and limitations of the most common imaging methods and propose best practices for their implementation and the quantitative interpretation of low-velocity anomalies. We constructed and analysed a database of 277 seismic imaging studies at 78 arc, hotspot and continental rift volcanoes. Each study is accompanied by information about the seismic source, part of the wavefield used, imaging method, any detected low-velocity zones, and estimated melt fraction. Thirty nine studies attempted to estimate melt fractions at 22 different volcanoes. Only five studies have found evidence of melt storage at melt fractions above the critical porosity that separates crystal mush from mobile magma. The median reported melt fraction is 13% suggesting that magma storage is dominated by low-melt fraction crystal mush. However, due to the limits of seismic resolution, the seismological evidence does not rule out the presence of small (&lt;10 km3) and medium-sized (&lt;100 km3) high-melt fraction magma chambers at many of the studied volcanoes. The combination of multiple tomographic imaging methods and the wider adoption of methods that use more of the seismic wavefield than the first arriving travel-times, promise to overcome some of the limitations of seismic tomography and provide more reliable constraints on melt fractions. Wider adoption of these new methods and advances in data collection are needed to enable a revolution in imaging magma reservoirs.
Near-surface heat transfer at two gentle slope sites with differing aspects, Qinghai-Tibet Plateau
Authors: Fan Xingwen , Lin Zhanju , Niu Fujun , Lan Aiyu , Yao Miaomiao , Li Wenjiao 
Published: October 2022

The slope aspect effect is widely distributed on the Qinghai-Tibet Plateau and has an important impact on the permafrost environment. The differences in surface heat exchange characteristics of different slope aspects in the permafrost region of Gu Mountain in the Beiluhe Basin were compared and analyzed based on observations of the south slope (sunny slope) and north slope (shadowy slope) from 2019 to 2021. The air-ground heat transfer process on the slopes was simulated using the Monin-Obukhov similarity theory. Then, the simulation results of the sensible and latent heat fluxes on the slopes were corrected and analyzed using the Bowen ratio correction method. The results show that under the influence of the solar altitude angle and subsurface conditions, the downward shortwave radiation (DR), upward shortwave radiation (UR), and upward longwave radiation (ULR) were higher on the sunny slope than those on the shadowy slope, whereas the downward longwave radiation (DLR) was lower than that on the shadowy slope. Jointly, the net radiation energy on the sunny slope was smaller than that on the shadowy slope, and the annual average net radiation difference reached 16.7 W·m−2. The annual and daily variations in soil heat flux on the sunny slope were higher than those on the shadowy slope. The energy closure rate on the sunny slope was high with a confinement rate of 0.85, whereas that on the shadowy slope was poor with a confinement rate of 0.51. The air-ground energy transfer patterns on the sunny and shadowy slopes showed obvious seasonal differences. Both slopes are dominated by the sensible heat exchange transfer mode in the cold season, whereas the shadowy slope is dominated by latent heat exchange in the warm season. This study improves our understanding of the distribution, development, and environmental effects of permafrost, under the influence of local factors.
Stream nitrogen uptake associated with suspended sediments: A microcosm study
Authors: Bacmeister Eva , Peck E. , Bernasconi S. , Inamdar S. , Kan J. , Peipoch M. 
Published: October 2022

Despite significant advances in our understanding of nitrogen (N) removal pathways along river networks, the role of water column processes remains largely understudied. This knowledge gap not only limits our capacity to determine N transport and retention in mid-to-large rivers but also hampers our understanding of N removal processes in smaller streams during stormflow conditions, in which significant increases in suspended sediment concentrations (SSC) typically occur. High SSC in the water column can provide abundant substrate for microbial growth and water column N uptake. However, storms of different size mobilize different quantities of sediment of varying properties and sizes, which can ultimately modulate water column N uptake rates in the stream during stormflows. To assess water column N uptake associated with suspended sediment particles of different sources and sizes, we quantified assimilatory and dissimilatory N uptake rates in a set of microcosms representing a gradient of sediment properties (organic matter, N content, and microbial activity) and surface area (fine vs. coarse size) availability. Water column assimilatory uptake (Used) ranged from 12.7 to 187.8 µg N [g sediment]−1 d−1 across all sediment sources and size fractions, and was higher on average than denitrification rates (DNsed) in agricultural and stream bank sediments but not in streambed sediments (mean DNsed = 240.9 ± 99 µg·N [g sediment]−1·d−1). Sediment-bound C in suspended sediment varied among sediment sources and was directly related to Used rates, but not to DNsed rates, which were less predictable and more variable. Overall, our results showed a positive nonlinear relationship between water column N uptake and SSC, while indicating that water column N uptake may scale differently to SSC depending on sediment source, and to a lesser degree, particle size. Because low, moderate, and large storms can mobilize different quantities of sediment in the watershed of different sources and sizes, it is likely that storm size will ultimately modulate the contribution of water column uptake during storm events to whole-reach N retention.
Spatial distribution of benthic flora and fauna of coastal placentia bay, an ecologically and biologically significant area of the island of newfoundland, atlantic Canada
Authors: Mackin-McLaughlin Julia , Nemani Shreya , Misiuk Benjamin , Templeton Adam , Gagnon Patrick , Edinger Evan , Robert Katleen 
Published: October 2022

Coastal habitats have the potential to be biodiversity hotspots that provide important ecosystem services, but also hotspots for human development and exploitation. Continued use of coastal ecosystem services requires establishing baselines that capture the present state of the benthos. This study employs habitat mapping to establish a baseline describing the spatial distribution of benthic organisms along the western coast of Placentia Bay, an Ecologically and Biologically Significant Area (EBSA) in Newfoundland, Canada. The influence of seafloor characteristics on the distribution of four dominant epifaunal assemblages and two macrophyte species were modelled using two machine learning techniques: the well-established Random Forest and the newer Light Gradient Boosting Machine. When investigating model performance, the inclusion of fine-scale (&lt;1 m) substrate information from the benthic videos was found to consistently improve model accuracy. Predictive maps developed here suggest that the majority of the surveyed areas consisted of a species-rich epifaunal assemblage dominated by ophiuroids, porifera, and hydrozoans, as well as prominent coverage by Agarum clathratum and non-geniculate crustose coralline algae. These maps establish a baseline that enables future monitoring of Placentia Bay’s coastal ecosystem, helping to conserve the biodiversity and ecosystem services this area provides.
Association of smoking status with non-small cell lung cancer patients harboring uncommon epidermal growth factor receptor mutation
Authors: Ko How-Wen , Shie Shian-Sen , Wang Chih-Wei , Chiu Chi-Tsun , Wang Chih-Liang , Yang Tsung-Ying , Chou Shou-Chu , Liu Chien-Ying , Kuo Chih-Hsi Scott , Lin Yu-Ching , Li Li-Fu , Yang Cheng-Ta , Wang Chin-Chou 
Published: October 2022

IntroductionUncommon epidermal growth factor receptor (EGFR) mutations include single and complex mutations. However, the association of the smoking status of patients with uncommon and complex EGFR mutations remains unclear.MethodsThis retrospective study evaluates the spectrum of uncommon EGFR mutations and investigates the influence of smoking status on the frequency of various uncommon EGFR mutations using a multi-institutional medical database.ResultsBetween 2010 and 2019, 5,608 non-small cell lung cancer (NSCLC) patients were analyzed. EGFR mutations were detected in 3,155 (56.3%) patients. Among the 399 (12.6%) patients with uncommon mutations, 198 had single uncommon and 201 complex mutations, including 87 exon 20 insertions, 79 de novo T790M, 70 complex common, and 52 complex uncommon mutations. For comparison, we also included 402 patients with common EGFR mutations. The percentage of ever-smokers was significantly higher in patients with uncommon EGFR mutations than in patients with common EGFR mutations (25.8% vs. 17.4%, p = 0.005). Furthermore, the percentage of ever-smokers was higher in those with a complex mutation than in those with a single uncommon mutation (30.3% vs. 21.2%, p = 0.040). Among patients carrying uncommon EGFR mutations, ever-smokers had significantly more complex uncommon EGFR mutations than never-smokers (22.3% vs. 9.8%, p = 0.002). Among patients carrying G719X, L861Q, and S768I, ever-smokers tended to have complex EGFR mutations more frequently than never-smokers (64.7% vs. 28.7%, 50.0% vs. 18.7%, 88.9% vs. 81.2%, respectively).ConclusionsOur study demonstrates not only a comprehensive spectrum of uncommon EGFR mutations, but also a positive relationship between smoking status and uncommon EGFR mutation frequency, especially complex uncommon EGFR mutations. The results suggest that smoking contributes to the development of complex EGFR mutations.
CEACAM 1, 3, 5 and 6 -positive classical monocytes correlate with interstitial lung disease in early systemic sclerosis
Authors: Yokoyama Kana , Mitoma Hiroki , Kawano Shotaro , Yamauchi Yusuke , Wang Qiaolei , Ayano Masahiro , Kimoto Yasutaka , Ono Nobuyuki , Arinobu Yojiro , Akashi Koichi , Horiuchi Takahiko , Niiro Hiroaki 
Published: October 2022

BackgroundSystemic sclerosis (SSc) is a multiple-organ disease characterized by vascular damage, autoimmunity, and tissue fibrosis. Organ injuries such as interstitial lung diseases (ILD), resulting from inflammatory and fibrosis processes, lead to poor prognosis. Although autoantibodies are detected in the serum of patients with SSc, the mechanisms by which immune cells are involved in tissue inflammation and fibrosis is not fully understood. Recent studies have revealed carcinoembryonic antigen related cell adhesion molecule (CEACAM)-positive monocytes are involved in murine bleomycin-induced lung fibrosis. We investigated CEACAM-positive monocytes in patients with SSc to clarify the role of monocytes in the pathogenesis of SSc.MethodsThe proportion of of CEACAM-positive classical monocytes in healthy controls (HCs) and patients with rheumatoid arthritis (RA) and SSc was evaluated using flow cytometry. The correlation between the proportion of CEACAM-positive monocytes and clinical parameters was analyzed in patients with SSc. Gene expression microarrays were performed in CEACAM-positive and negative monocytes in patients with SSc. Infiltration of CEACAM-positive monocytes into scleroderma skin was evaluated by immunohistochemical staining.ResultsThe proportion of CEACAM-positive classical monocytes was increased in patients with early SSc within 2 years after diagnosis, which positively correlated with ESR, serum IgG, and serum KL-6 and negatively correlated with %forced vital capacity. The percentage of CEACAM-positive monocytes decreased after immunosuppressive therapy. CEACAM6-positive cells among classical monocytes were significantly increased in patients with SSc compared with HCs and patients with rheumatoid arthritis. SSc serum induced CEACAM6 expression on monocytes from HCs. Functionally, CEACAM-positive monocytes produced higher levels of TNF-α and IL-1β compared to CEACAM-negative cells and showed activation of the NF-κB pathway. Furthermore, CEACAM6-positive monocytes infiltrated the dermis of SSc.ConclusionsCEACAM-positive monocytes showed inflammatory phenotypes and may be involved in the tissue inflammation and fibrosis in early SSc. CEACAM-positive monocytes may be one of biomarkers to detect patients with progressive ILD, requiring therapeutic intervention.
Preclinical characterization and phase I clinical trial of CT053PTSA targets MET, AXL, and VEGFR2 in patients with advanced solid tumors
Authors: Ma Yu-Xiang , Liu Fu-Rong , Zhang Yang , Chen Qun , Chen Zhi-Qiang , Liu Qian-Wen , Huang Yan , Yang Yun-Peng , Fang Wen-Feng , Xi Ning , Kang Ning , Zhuang Yu-Lei , Zhang Qi , Jiang Ying-Zhi , Zhang Li , Zhao Hong-Yun 
Published: October 2022

BackgroundCT053PTSA is a novel tyrosine kinase inhibitor that targets MET, AXL, VEGFR2, FLT3 and MERTK. Here, we present preclinical data about CT053PTSA, and we conducted the first-in-human (FIH) study to evaluate the use of CT053PTSA in adult patients with pretreated advanced solid tumors.MethodsThe selectivity and antitumor activity of CT053PTSA were assessed in cell lines in vitro through kinase and cellular screening panels and in cell line-derived tumor xenograft (CDX) and patient-derived xenograft (PDX) models in vivo. The FIH, phase I, single-center, single-arm, dose escalation (3 + 3 design) study was conducted, patients received at least one dose of CT053PTSA (15 mg QD, 30 mg QD, 60 mg QD, 100 mg QD, and 150 mg QD). The primary objectives were to assess safety and tolerability, to determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and the recommended dose of CT053PTSA for further study. Secondary objectives included pharmacokinetics, antitumor activity.ResultsCT053 (free-base form of CT053PTSA) inhibited MET, AXL, VEGFR2, FLT3 and MERTK phosphorylation and suppressed tumor cell angiogenesis by blocking VEGF and HGF, respectively, in vitro. Moreover, cell lines with high MET expression exhibited strong sensitivity to CT053, and CT053 blocked the MET and AXL signaling pathways. In an in vivo study, CT053 significantly inhibited tumor growth in CDX and PDX models. Twenty eligible patients were enrolled in the FIH phase I trial. The most common treatment-related adverse events were transaminase elevation (65%), leukopenia (45%) and neutropenia (35%). DLTs occurred in 3 patients, 1/6 in the 100 mg group and 2/4 in the 150 mg group, so the MTD was set to 100 mg. CT053PTSA was rapidly absorbed after the oral administration of a single dose, and the Cmax and AUC increased proportionally as the dose increased. A total of 17 patients in this trial underwent tumor imaging evaluation, and 29.4% had stable disease.ConclusionsCT053PTSA has potent antitumor and antiangiogenic activity in preclinical models. In this FIH phase I trial, CT053PTSA was well tolerated and had a satisfactory safety profile. Further trials evaluating the clinical activity of CT053PTSA are ongoing.
Molecular profiling of core immune-escape genes highlights LCK as an immune-related prognostic biomarker in melanoma
Authors: Wang Fang , Zheng Anfu , Zhang Duoli , Zou Tao , Xiao Mintao , Chen Jie , Wen Bo , Wen Qinglian , Wu Xu , Li Mingxing , Du Fukuan , Chen Yu , Zhao Yueshui , Shen Jing , Xiang Shixin , Li Jing , Deng Shuai , Zhang Zhuo , Yi Tao , Xiao Zhangang 
Published: October 2022

The tumor microenvironment is complicated and continuously evolving. This study was devoted to the identification of potential prognostic biomarkers based on the tumor microenvironment associated with immunotherapy for melanoma. This study integrates a couple of melanoma single cell and transcriptome sequencing datasets and performs a series of silico analyses as nicely as validation of molecular biology techniques. A core set of immune escape related genes was identified through Lawson et al. and the ImmPort portal. The differential proteins were identified through the cBioPortal database. Regression analysis was used to profile independent prognostic factors. Correlation with the level of immune cell infiltration was evaluated by multiple algorithms. The capacity of LCK to predict response was assessed in two independent immunotherapy cohorts. High LCK expression is associated with better prognosis, high levels of TILs and better clinical staging. Pathway analysis showed that high expression of LCK was significantly associated with activation of multiple tumor pathways as well as immune-related pathways. LCK expression tends to be higher in immunotherapy-responsive patients and those with lower IC50s treated with chemotherapeutic agents. RT-qPCR detected that LCK expression was significantly upregulated in melanoma cell lines. Single-cell transcriptome analysis showed that LCK was specifically highly expressed on T cells. CellChat analysis confirmed that LCK in C2 subpopulations and T cell subpopulations exerted immune promotion between cells by binding to CD8 receptors. In conclusion, LCK is a reliable biomarker for melanoma and will contribute to its immunotherapy.
A CD8+ T cell-associated immune gene panel for prediction of the prognosis and immunotherapeutic effect of melanoma
Authors: Sun Shanwen , Zhi Zhengke , Su Yang , Sun Jingxian , Li Qianjun 
Published: October 2022

BackgroundSkin cutaneous melanoma (SKCM) is the most frequently encountered tumor of the skin. Immunotherapy has opened a new horizon in melanoma treatment. We aimed to construct a CD8+ T cell-associated immune gene prognostic model (CDIGPM) for SKCM and unravel the immunologic features and the benefits of immunotherapy in CDIGPM-defined SKCM groups.MethodSingle-cell SKCM transcriptomes were utilized in conjunction with immune genes for the screening of CD8+ T cell-associated immune genes (CDIGs) for succeeding assessment. Thereafter, through protein-protein interaction (PPI) networks analysis, univariate COX analysis, and multivariate Cox analysis, six genes (MX1, RSAD2, IRF2, GBP2, IFITM1, and OAS2) were identified to construct a CDIGPM. We detected cell proliferation of SKCM cells transfected with IRF2 siRNA. Then, we analyzed the immunologic features and the benefits of immunotherapy in CDIGPM-defined groups.ResultsThe overall survival (OS) was much better in low-CDIGPM group versus high CDIGPM group in TCGA dataset and GSE65904 dataset. On the whole, the results unfolded that a low CDIGPM showed relevance to immune response-correlated pathways, high expressions of CTLA4 and PD-L1, a high infiltration rate of CD8+ T cells, and more benefits from immunotherapy.ConclusionCDIGPM is an good model to predict the prognosis, the potential immune escape from immunotherapy for SKCM, and define immunologic and molecular features.
SDF-1 expression and tumor-infiltrating lymphocytes identify clinical subtypes of triple-negative breast cancer with different responses to neoadjuvant chemotherapy and survival
Authors: Wang Ruo-Xi , Ji Peng , Gong Yue , Shao Zhi-Ming , Chen Sheng 
Published: October 2022

BackgroundIn this study, we investigated the prediction and prognostic value of SDF-1 for triple-negative breast cancer (TNBC) patients who underwent neoadjuvant chemotherapy (NAC) following standard radical surgery.MethodsA total of 303 TNBC patients were included in this study. The NAC regimen was weekly paclitaxel plus carboplatin (PC) for all patients. SDF-1 and CXCR4 expression were measured at baseline and surgery via enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC), respectively. Correlations between variables and treatment response were studied, and Cox proportional hazards regression analysis was implemented for prognostic evaluation.ResultsOf the 303 patients, 103 (34.0%) experienced pathological complete response (pCR) after completion of NAC. Serum SDF-1 expression before NAC was significantly correlated with the abundance of TILs. A higher pCR rate was more likely to be observed in patients with lower serum SDF-1 levels before NAC (P=0.001, OR=0.997, 95% CI: 0.996-0.999) and higher levels of TILs (P=0.005). In the multivariate survival model for nonpCR patients, serum SDF-1 expression at surgery served as an independent prognostic value for survival (high level, HR=1.980, 95% CI: 1.170-3.350, low level was used as a reference; P=0.011). Additionally, the predictive and prognostic value of serum SDF-1 expression was significant in patients with high abundance of TILs but not in patients with low abundance of TILs.ConclusionsThis study contributes to the clarification of the value of serum SDF-1 to predict pCR and survival for TNBC patients who underwent NAC. This new serum marker, together with TILs, might help identify clinical subtypes of TNBC with different treatment responses and survival and play an important role in tailoring and modifying the NAC strategy for advanced TNBCs in the future.
Tidy up - The unfolded protein response in sepsis
Authors: Vivas Wolfgang , Weis Sebastian 
Published: October 2022

Pathogens, their toxic byproducts, and the subsequent immune reaction exert different forms of stress and damage to the tissue of the infected host. This stress can trigger specific transcriptional and post-transcriptional programs that have evolved to limit the pathogenesis of infectious diseases by conferring tissue damage control. If these programs fail, infectious diseases can take a severe course including organ dysfunction and damage, a phenomenon that is known as sepsis and which is associated with high mortality. One of the key adaptive mechanisms to counter infection-associated stress is the unfolded protein response (UPR), aiming to reduce endoplasmic reticulum stress and restore protein homeostasis. This is mediated via a set of diverse and complementary mechanisms, i.e. the reduction of protein translation, increase of protein folding capacity, and increase of polyubiquitination of misfolded proteins and subsequent proteasomal degradation. However, UPR is not exclusively beneficial since its enhanced or prolonged activation might lead to detrimental effects such as cell death. Thus, fine-tuning and time-restricted regulation of the UPR should diminish disease severity of infectious disease and improve the outcome of sepsis while not bearing long-term consequences. In this review, we describe the current knowledge of the UPR, its role in infectious diseases, regulation mechanisms, and further clinical implications in sepsis.