bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-Term Spatial and Temporal Variation of Near Surface Air Temperature in Southwest China During 1969–2018
Authors: Zhou Jia , Lu Tao 
Published: December 2021

Near surface air temperature (NSAT) is one of the most important climatic parameters and its variability plays a vital role in natural processes associated with climate. Based on an improved ANUSPLIN (short for Australian National University Spline) model which considers more terrain-related factors, this study analyzed the trends, anomalies, change points, and variations of NSAT in Southwest China from 1969 to 2018. The results revealed that the improved approach performed the best in terms of Mean Absolute Error (MAE), Root Mean Square Error (RMSE) and R-squared (R2) comparing to the conventional ANUSPLIN and co-kriging methods. It has great potential for future meteorological and climatological research, especially in mountainous regions with diverse topography. In addition, Southwest China experienced an overall warming trend of 0.21°C/decade for annual mean NSAT in the period 1969–2018. The warming rate was much higher than mainland China and global averages, and statistically significant warming began in the late 1990s. Moreover, consistent warming and significant elevation-dependent warming (EDW) were observed in most parts of Southwest China, and the hiatus or slowdown phenomenon after the 1997/1998 EL Niño event was not observed as expected. Furthermore, the remarkable increase in winter and minimum NSATs contributed more to the whole warming than summer and maximum NSATs. These findings imply that Southwest China responds to global warming more sensitively than generally recognized, and climate change in mountainous regions like Southwest China should be of particular concern.
A Machine Learning Approach to Predict Groundwater Levels in California Reveals Ecosystems at Risk
Authors: Rohde Melissa M. , Biswas Tanushree , Housman Ian W. , Campbell Leah S. , Klausmeyer Kirk R. , Howard Jeanette K. 
Published: December 2021

Groundwater dependent ecosystems (GDEs) are increasingly threatened worldwide, but the shallow groundwater resources that they are reliant upon are seldom monitored. In this study, we used satellite-based remote sensing to predict groundwater levels under groundwater dependent ecosystems across California, USA. Depth to groundwater was modelled for a 35-years period (1985–2019) within all groundwater dependent ecosystems across the state (n = 95,135). Our model was developed within Google Earth Engine using Landsat satellite imagery, climate data, and field-based groundwater data [n = 627 shallow (&lt; 30 m) monitoring wells] as predictors in a Random Forest model. Our findings show that 1) 44% of groundwater dependent ecosystems have experienced a significant long-term (1985–2019) decline in groundwater levels compared to 28% with a significant increase; 2) groundwater level declines have intensified during the most recent two decades, with 39% of groundwater dependent ecosystems experiencing declines in the 2003–2019 period compared to 27% in the 1985–2002 period; and 3) groundwater declines are most prevalent within GDEs existing in areas of the state where sustainable groundwater management is absent. Our results indicate that declining shallow groundwater levels may be adversely impacting California’s groundwater dependent ecosystems. Particularly where groundwater levels have fallen beneath plant roots or streams thereby affecting key life processes, such as forest recruitment/succession, or hydrological processes, such as streamflow that affects aquatic habitat. In the absence of groundwater monitoring well data, our model and findings can be used to help state and local water agencies fill in data gaps of shallow groundwater conditions, evaluate potential effects on GDEs, and improve sustainable groundwater management policy in California.
Brain Permeable AMP-Activated Protein Kinase Activator R481 Raises Glycaemia by Autonomic Nervous System Activation and Amplifies the Counterregulatory Response to Hypoglycaemia in Rats
Authors: Cruz Ana M. , Partridge Katie M. , Malekizadeh Yasaman , Vlachaki Walker Julia M. , Weightman Potter Paul G. , Pye Katherine R. , Shaw Simon J. , Ellacott Kate L. J. , Beall Craig 
Published: December 2021

AimWe evaluated the efficacy of a novel brain permeable “metformin-like” AMP-activated protein kinase activator, R481, in regulating glucose homeostasis.Materials and MethodsWe used glucose sensing hypothalamic GT1-7 neuronal cells and pancreatic αTC1.9 α-cells to examine the effect of R481 on AMPK pathway activation and cellular metabolism. Glucose tolerance tests and hyperinsulinemic-euglycemic and hypoglycemic clamps were used in Sprague-Dawley rats to assess insulin sensitivity and hypoglycemia counterregulation, respectively.ResultsIn vitro, we demonstrate that R481 increased AMPK phosphorylation in GT1-7 and αTC1.9 cells. In Sprague-Dawley rats, R481 increased peak glucose levels during a glucose tolerance test, without altering insulin levels or glucose clearance. The effect of R481 to raise peak glucose levels was attenuated by allosteric brain permeable AMPK inhibitor SBI-0206965. This effect was also completely abolished by blockade of the autonomic nervous system using hexamethonium. During hypoglycemic clamp studies, R481 treated animals had a significantly lower glucose infusion rate compared to vehicle treated controls. Peak plasma glucagon levels were significantly higher in R481 treated rats with no change to plasma adrenaline levels. In vitro, R481 did not alter glucagon release from αTC1.9 cells, but increased glycolysis. Non brain permeable AMPK activator R419 enhanced AMPK activity in vitro in neuronal cells but did not alter glucose excursion in vivo.ConclusionsThese data demonstrate that peripheral administration of the brain permeable “metformin-like” AMPK activator R481 increases blood glucose by activation of the autonomic nervous system and amplifies the glucagon response to hypoglycemia in rats. Taken together, our data suggest that R481 amplifies the counterregulatory response to hypoglycemia by a central rather than a direct effect on the pancreatic α-cell. These data provide proof-of-concept that central AMPK could be a target for future drug development for prevention of hypoglycemia in diabetes.
Tolerance of Electromagnetic Relay to Voltage Sags and Short Interruptions
Authors: Zhang Huaying , Wang Qing , You Yihong 
Published: December 2021

This paper studies the tolerance of electromagnetic relay (EMR) under voltage sag and short interruptions on the basis of response mechanism analysis and the extensive tests. First, it introduces the structure of EMR and proposes response mechanism of EMR under voltage sag. Then, a detailed test plan is presented, including the information of test platform, testing condition, EMRs used in test, list of test, test procedure, and the measured waveforms. Magnitude and duration of the sags are not only the characteristics to be considered to investigate EMR’s tolerance. The other factors, which may have significance influence on tolerance of EMR, are considered here, including point-on-wave (POW), phase angle jump (PAJ), harmonic, magnitude variation in pre- and post-sag segments, two-stage sag, and slow recovery sag. Extensive tests results are presented in the form of voltage-tolerance curves (VTCs). Besides magnitude and duration, POW, PAJ, and two-stage sag have a significant influence on the tolerance of EMR. Other factors only have a tiny impact on the tolerance of EMR. The results show that the magnitude tolerance of EMR is 48–74% of Unom, and duration tolerance is 5–28 ms; they are useful for the technical assessment of EMR’s tolerance to voltage sags and short interruptions, and for the economic assessment of the industry process trip due to its disengagement. Test results also benefit for choosing proper EMR and mitigation device in the complicated operating environment.
Using RNA-Seq to Investigate Immune-Metabolism Features in Immunocompromised Patients With Sepsis
Authors: Cheng Po-Liang , Chen Hsin-Hua , Jiang Yu-Han , Hsiao Tzu-Hung , Wang Chen-Yu , Wu Chieh-Liang , Ko Tai-Ming , Chao Wen-Cheng 
Published: December 2021

Objective:Sepsis is life threatening and leads to complex inflammation in patients with immunocompromised conditions, such as cancer, and receiving immunosuppressants for autoimmune diseases and organ transplant recipients. Increasing evidence has shown that RNA-Sequencing (RNA-Seq) can be used to define subendotype in patients with sepsis; therefore, we aim to use RNA-Seq to identify transcriptomic features among immunocompromised patients with sepsis.Methods:We enrolled patients who were admitted to medical intensive care units (ICUs) for sepsis at a tertiary referral centre in central Taiwan. Whole blood on day-1 and day-8 was obtained for RNA-Seq. We used Gene Set Enrichment Analysis (GSEA) to identify the enriched pathway of day-8/day-1 differentially expressed genes and MiXCR to determine the diversity of T cell repertoire.Results:A total of 18 immunocompromised subjects with sepsis and 18 sequential organ failure assessment (SOFA) score-matched immunocompetent control subjects were enrolled. The ventilator-day, ICU-stay, and hospital-day were similar between the two groups, whereas the hospital mortality was higher in immunocompromised patients than those in immunocompetent patients (50.0 vs. 5.6%,p&lt; 0.01). We found that the top day-8/day-1 upregulated genes in the immunocompetent group were mainly innate immunity and inflammation relevant genes, namely,PRSS33, HDC, ALOX15, FCER1A, andOLR1, whereas a blunted day-8/day-1 dynamic transcriptome was found among immunocompromised patients with septic. Functional pathway analyses of day-8/day-1 differentially expressed genes identified the upregulated functional biogenesis and T cell-associated pathways in immunocompetent patients recovered from sepsis, whereas merely downregulated metabolism-associated pathways were found in immunocompromised patients with septic. Moreover, we used MiXCR to identify a higher diversity of T cell receptor (TCR) in immunocompetent patients both on day-1 and on day-8 than those in immunocompromised patients.Conclusions:Using RNA-Seq, we found compromised T cell function, altered metabolic signalling, and decreased T cell diversity among immunocompromised patients with septic, and more mechanistic studies are warranted to elucidate the underlying mechanism.
Sedation, Analgesia, and Muscle Relaxation During VV-ECMO Therapy in Patients With Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2): A Single-Center, Retrospective, Observational Study
Authors: Wu Fang , Li Mingna , Zhang Zhongwei , Shang Jiawei , Guo Yong , Li Yingchuan 
Published: December 2021

Objective: The pharmacokinetics and pharmacodynamics of ECMO-supported sedative, analgesic, and muscle relaxants have changed, but there are insufficient data to determine the optimal dosing strategies for these agents. Sedation, analgesia and muscle relaxation therapy for patients with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) receiving ECMO support are more specific and have not been fully reported. This study observed and evaluated the use of sedative and analgesic drugs and muscle relaxants in SARS-CoV-2 patients treated with VV-ECMO.Methods: This study was a single-center, retrospective and observational study. Our study includes 8 SARS-CoV-2 patients treated with VV-ECMO in an intensive care unit at Shanghai Public Health Center from February to June 2020. We collected the demographic data from these patients and the dose and course of sedation, analgesia, and muscle relaxants administered during ECMO treatment.Results: The doses of sedative, analgesic and muscle relaxant drugs used in patients with VV-ECMO were significant. Over time, the doses of drugs that were used were increased, and the course of muscle relaxant treatment was extended.Conclusion: Sedation, analgesia, and muscle relaxant use require individualized titration in patients with SARS-CoV-2 who have respiratory failure and who are receiving VV-ECMO.
Construction and Validation of a Combined Ferroptosis and Hypoxia Prognostic Signature for Hepatocellular Carcinoma
Authors: Wen Kai , Yan Yongcong , Shi Juanyi , Hu Lei , Wang Weidong , Liao Hao , Li Huoming , Zhu Yue , Mao Kai , Xiao Zhiyu 
Published: December 2021

Background: Ferroptosis, as a unique programmed cell death modality, has been found to be closely related to the occurrence and development of hepatocellular carcinoma (HCC). Hypoxia signaling pathway has been found to be extensively involved in the transformation and growth of HCC and to inhibit anti-tumor therapy through various approaches. However, there is no high-throughput study to explore the potential link between ferroptosis and hypoxia, as well as their combined effect on the prognosis of HCC.Methods: We included 370 patients in The Cancer Genome Atlas (TCGA) database and 231 patients in the International Cancer Genome Consortium (ICGC) database. Univariate COX regression and Least Absolute Shrinkage and Selection Operator approach were used to construct ferroptosis-related genes (FRGs) and hypoxia-related genes (HRGs) prognostic signature (FHPS). Kaplan–Meier method and Receiver Operating Characteristic curves were analyzed to evaluate the predictive capability of FHPS. CIBERSOR and single-sample Gene Set Enrichment Analysis were used to explore the connection between FHPS and tumor immune microenvironment. Immunohistochemical staining was used to compare the protein expression of prognostic FRGs and HRGs between normal liver tissue and HCC tissue. In addition, the nomogram was established to facilitate the clinical application of FHPS.Results: Ten FRGs and HRGs were used to establish the FHPS. We found consistent results in the TCGA training cohort, as well as in the independent ICGC validation cohort, that patients in the high-FHPS subgroup had advanced tumor staging, shorter survival time, and higher mortality. Moreover, patients in the high-FHPS subgroup showed ferroptosis suppressive, high hypoxia, and immunosuppression status. Finally, the nomogram showed a strong prognostic capability to predict overall survival (OS) for HCC patients.Conclusion: We developed a novel prognostic signature combining ferroptosis and hypoxia to predict OS, ferroptosis, hypoxia, and immune status, which provides a new idea for individualized treatment of HCC patients.
The Correlation Among the Immunoglobulin G Synthesis Rate, IgG Index and Albumin Quotient in Guillain-Barré Syndrome and Chronic Inflammatory Demyelinating Polyradiculoneuropathy: A Retrospective Case–Control Study
Authors: Tu Yu , Gong Xuan , Zhang Yuanyuan , Peng Jiewei , Zhuo Wenyan , Yu Xueying 
Published: December 2021

Background: The immunoglobulin G synthesis rate (IgG SR) and immunoglobulin G (IgG) index are indicators of abnormal intrathecal humoural immune responses, and the albumin quotient (QALB) is an indicator used to evaluate the completeness of the blood-cerebrospinal fluid barrier (BCB). No systematic reports regarding differences in Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are available. We assessed differences in the IgG SR, IgG index and QALB between GBS and CIDP patients in a Chinese cohort.Methods: A total of 234 patients were retrospectively enrolled in this study, and 167 clinically confirmed GBS and CIDP patients were selected. Meanwhile, 67 non-GBS and non-CIDP patients requiring cerebrospinal fluid (CSF) examination were enrolled as the control group. The IgG SR, IgG index and QALB were calculated using formulas. The relevant clinical data were subjected to statistical analysis.Results: Among the GBS and CIDP study groups and the control group, the QALB had the highest positive rate (80.00%) in the CIDP group (P &lt; 0.01). The QALB stratification analysis showed that the ranges of 10 &lt; QALB ≤ 30 were dominant in the GBS and CIDP groups, and the positive rate of CIDP was higher than that of GBS. Furthermore, a QALB ≤ 7 was dominant in the control group, and a QALB &gt; 30 was dominant in the CIDP group. In receiver operating characteristic (ROC) curve analysis with the CIDP group as the trial group and the GBS group as the control group, the differences in the QALB were statistically significant (P &lt; 0.01). To achieve a high specificity of 98~99%, the diagnostic cut-off value for the QALB was above 57.37 (sensitivity: 9.33%) or below 0.60 (sensitivity: 4.35%). Multivariate logistic regression analysis showed that the CIDP patients had a QALB higher than 57.37, and compared with that in the GBS patients, the difference in the QALB was statistically significant (P &lt; 0.01).Conclusion: QALB elevation was associated with CIDP, while QALB values above 57.37 or below 0.60 had high specificity in differentiating between GBS and CIDP. In CIDP, the BCB is generally moderately to severely damaged; in GBS, the BCB is generally moderately damaged.
Mechanical Thrombectomy With and Without Intravenous Tissue Plasminogen Activator for Acute Ischemic Stroke: A Systematic Review and Meta-Analysis Using Nested Knowledge
Authors: Adusumilli Gautam , Pederson John M. , Hardy Nicole , Kallmes Kevin M. , Hutchison Kristen , Kobeissi Hassan , Heiferman Daniel M. , Heit Jeremy J. 
Published: December 2021

Background: Mechanical thrombectomy (MT) is now the standard-of-care treatment for acute ischemic stroke (AIS) of the anterior circulation and may be performed irrespective of intravenous tissue plasminogen activator (IV-tPA) eligibility prior to the procedure. This study aims to understand better if tPA leads to higher rates of reperfusion and improves functional outcomes in AIS patients after MT and to simultaneously evaluate the functionality and efficiency of a novel semi-automated systematic review platform.Methods: The Nested Knowledge AutoLit semi-automated systematic review platform was utilized to identify randomized control trials published between 2010 and 2021 reporting the use of mechanical thrombectomy and IV-tPA (MT+tPA) vs. MT alone for AIS treatment. The primary outcome was the rate of successful recanalization, defined as thrombolysis in cerebral infarction (TICI) scores ≥2b. Secondary outcomes included 90-day modified Rankin Scale (mRS) 0–2, 90-day mortality, distal embolization to new territory, and symptomatic intracranial hemorrhage (sICH). A separate random effects model was fit for each outcome measure.Results: We subjectively found Nested Knowledge to be highly streamlined and effective at sourcing the correct literature. Four studies with 1,633 patients, 816 in the MT+tPA arm and 817 in the MT arm, were included in the meta-analysis. In each study, patient populations consisted of only tPA-eligible patients and all imaging and clinical outcomes were adjudicated by an independent and blinded core laboratory. Compared to MT alone, patients treated with MT+tPA had higher odds of eTICI ≥2b (OR = 1.34 [95% CI: 1.10; 1.63]). However, there were no statistically significant differences in the rates of 90-day mRS 0-2 (OR = 0.98 [95% CI: 0.77; 1.24]), 90-day mortality (OR = 0.94 [95% CI: 0.67; 1.32]), distal emboli (OR = 0.94 [95% CI: 0.25; 3.60]), or sICH (OR = 1.17 [95% CI: 0.80; 1.72]).Conclusions: Administering tPA prior to MT may improve the rates of recanalization compared to MT alone in tPA-eligible patients being treated for AIS, but a corresponding improvement in functional and safety outcomes was not present in this review. Further studies looking at the role of tPA before mechanical thrombectomy in different cohorts of patients could better clarify the role of tPA in the treatment protocol for AIS.
High ATF4 Expression Is Associated With Poor Prognosis, Amino Acid Metabolism, and Autophagy in Gastric Cancer
Authors: Wang Mingliang , Lu Yida , Wang Huizhen , Wu Youliang , Xu Xin , Li Yongxiang 
Published: December 2021

BackgroundThe role of activating transcription factor 4 (ATF4) underlying gastric cancer (GC) remains unclear. The purpose of this study was to investigate the expression levels and biological functions of ATF4 in GC.MethodsExpression of ATF4 was detected by quantitative PCR (qPCR), Western blotting, and immunohistochemistry. Cox regression was used for survival analysis and the construction of the nomogram. Immunofluorescence was used to identify the intracellular localization of ATF4. Knockdown and overexpression of ATF4 in GC cells followed by wound healing and Transwell assays, EdU and Calcein-AM/propidium iodide (PI) staining, and cell cycle detection were performed to examine its function in vitro. Transmission electron microscopy was performed to assess the autophagy levels upon ATF4 silencing. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and gene set enrichment analysis (GSEA) were used to determine gene enrichment. SPSS 22.0 software, GraphPad Prism 7.0, and R version 3.6.1 were used for statistical analysis.ResultsATF4 expression was upregulated in GC cells and tissues compared with corresponding normal tissues. Survival analysis suggested that a high ATF4 expression was strongly associated with worse overall survival (OS) of GC patients (p &lt; 0.001). The nomogram and the receiver operating characteristic (ROC) curves demonstrated that ATF4 was a highly sensitive and specific prognostic marker of GC [C-index = 0.797, area under the ROC curve (AUC) of 3-year OS = 0.855, and AUC of 5-year OS = 0.863]. In addition, ATF4 knockdown inhibited the cell proliferation, migration, invasion, and cell cycle progression of GC cells in vitro, while overexpression of ATF4 exerted the opposite effects. Bioinformatics analysis showed that ATF4 could promote GC progression possibly by regulating asparagine (Asn) metabolism and autophagy pathways. Further experiments indicated that ATF4 expression was significantly positively correlated with ASNS expression. The inhibition of cell clone formation in Asn-deprived conditions was more significant in the shATF4 group. Finally, we found that ATF4 promoted autophagy through regulating the mTORC1 pathway in GC cells.ConclusionThese findings suggested that ATF4 can significantly promote GC development and serve as an independent prognostic factor for GC.
SIPL1, Regulated by MAZ, Promotes Tumor Progression and Predicts Poor Survival in Human Triple-Negative Breast Cancer
Authors: He Juanjuan , Wang Jing , Li Teng , Chen Kunlun , Li Songchao , Zhang Shaojin 
Published: December 2021

BackgroundTriple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer owing to a lack of effective targeted therapy and acquired chemoresistance. Here, we explored the function and mechanism of shank-interacting protein-like 1 (SIPL1) in TNBC progression.MethodsSIPL1 expression was examined in human TNBC tissues and cell lines by quantitative reverse transcription PCR, western blot, and immunohistochemistry. SIPL1 overexpression and silenced cell lines were established in BT-549 and MDA-MB-231 cells. The biological functions of SIPL1 in TNBC were studied in vitro using the CCK-8 assay, CellTiter-Glo Luminescent Cell Viability assay, caspase-3/8/9 assay, wound healing assay, and transwell assay and in vivo using a nude mouse model. The potential mechanisms underlying the effects of SIPL1 on TNBC progression were explored using bioinformatics analysis, luciferase reporter assays, and chromatin immunoprecipitation followed by qPCR.ResultsSIPL1 expression was higher in human TNBC tissues and cell lines than in adjacent normal tissues and a breast epithelial cell line (MCF10A). High expression of SIPL1 was positively correlated with poor overall and disease-free survival in patients with TNBC. SIPL1 overexpression elevated and SIPL1 silencing repressed the malignant phenotypes of TNBC cells in vitro. SIPL1 overexpression promoted xenograft tumor growth in vivo. Myc-associated zinc-finger protein (MAZ) transcriptionally activated SIPL1. Finally, we found that SIPL1 promoted TNBC malignant phenotypes via activation of the AKT/NF-κB signaling pathways.ConclusionsThese results indicate that the MAZ/SIPL1/AKT/NF-κB axis plays a crucial role in promoting the malignant phenotypes of TNBC cells.