bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activating Adenosine Monophosphate–Activated Protein Kinase Mediates Fibroblast Growth Factor 1 Protection From Nonalcoholic Fatty Liver Disease in Mice
Authors: Lin Qian , Huang Zhifeng , Cai Genxiang , Fan Xia , Yan Xiaoqing , Liu Zhengshuai , Zhao Zehua , Li Jingya , Li Jia , Shi Hongxue , Kong Maiying , Zheng Ming‐Hua , Conklin Daniel J. , Epstein Paul N. , Wintergerst Kupper A. , Mohammadi Moosa , Cai Lu , Li Xiaokun , Li Yu , Tan Yi 
Published: September 2020

Background and Aims
Fibroblast growth factor (FGF) 1 demonstrated protection against nonalcoholic fatty liver disease (NAFLD) in type 2 diabetic and obese mice by an uncertain mechanism. This study investigated the therapeutic activity and mechanism of a nonmitogenic FGF1 variant carrying 3 substitutions of heparin‐binding sites (FGF1△HBS) against NAFLD.

Approach and Results
FGF1△HBS administration was effective in 9‐month‐old diabetic mice carrying a homozygous mutation in the leptin receptor gene (db/db) with NAFLD; liver weight, lipid deposition, and inflammation declined and liver injury decreased. FGF1△HBS reduced oxidative stress by stimulating nuclear translocation of nuclear erythroid 2 p45‐related factor 2 (Nrf2) and elevation of antioxidant protein expression. FGF1△HBS also inhibited activity and/or expression of lipogenic genes, coincident with phosphorylation of adenosine monophosphate–activated protein kinase (AMPK) and its substrates. Mechanistic studies on palmitate exposed hepatic cells demonstrated that NAFLD‐like oxidative damage and lipid accumulation could be reversed by FGF1△HBS. In palmitate‐treated hepatic cells, small interfering RNA (siRNA) knockdown of Nrf2 abolished only FGF1△HBS antioxidative actions but not improvement of lipid metabolism. In contrast, AMPK inhibition by pharmacological agent or siRNA abolished FGF1△HBS benefits on both oxidative stress and lipid metabolism that were FGF receptor (FGFR) 4 dependent. Further support of these in vitro findings is that liver‐specific AMPK knockout abolished therapeutic effects of FGF1△HBS against high‐fat/high‐sucrose diet–induced hepatic steatosis. Moreover, FGF1△HBS improved high‐fat/high‐cholesterol diet–induced steatohepatitis and fibrosis in apolipoprotein E knockout mice.

Conclusions
These findings indicate that FGF1△HBS is effective for preventing and reversing liver steatosis and steatohepatitis and acts by activation of AMPK through hepatocyte FGFR4.
Reminders activate the prefrontal‐medial temporal cortex and attenuate forgetting of event memory
Authors: Sekeres Melanie J. , Moscovitch Morris , Winocur Gordon , Pishdadian Sara , Nichol Dan , Grady Cheryl L. 
Published: September 2020

AbstractReplicas of an aspect of an experienced event can serve as effective reminders, yet little is known about the neural basis of such reminding effects. Here we examined the neural activity underlying the memory‐enhancing effect of reminders 1 week after encoding of naturalistic film clip events. We used fMRI to determine differences in network activity associated with recently reactivated memories relative to comparably aged, non‐reactivated memories. Reminders were effective in facilitating overall retrieval of memory for film clips, in an all‐or‐none fashion. Prefrontal cortex and hippocampus were activated during both reminders and retrieval. Peak activation in ventro‐lateral prefrontal cortex (vPFC) preceded peak activation in the right hippocampus during the reminders. For film clips that were successfully retrieved after 7 days, pre‐retrieval reminders did not enhance the quality of the retrieved memory or the number of details retrieved, nor did they more strongly engage regions of the recollection network than did successful retrieval of a non‐reminded film clip. These results suggest that reminders prior to retrieval are an effective means of boosting retrieval of otherwise inaccessible episodic events, and that the inability to recall certain events after a delay of a week largely reflects a retrieval deficit, rather than a storage deficit for this information. The results extend other evidence that vPFC drives activation of the hippocampus to facilitate memory retrieval and scene construction, and show that this facilitation also occurs when reminder cues precede successful retrieval attempts. The time course of vPFC‐hippocampal activity during the reminder suggests that reminders may first engage schematic information meditated by vPFC followed by a recollection process mediated by the hippocampus.
Causal relationships between body mass index, smoking and lung cancer: Univariable and multivariable Mendelian randomization
Authors: Zhou Wen , Liu Geoffrey , Hung Rayjean J. , Haycock Philip C. , Aldrich Melinda C. , Andrew Angeline S. , Arnold Susanne M. , Bickeböller Heike , Bojesen Stig E. , Brennan Paul , Brunnström Hans , Melander Olle , Caporaso Neil E. , Landi Maria Teresa , Chen Chu , Goodman Gary E. , Christiani David C. , Cox Angela , Field John K. , Johansson Mikael , Kiemeney Lambertus A. , Lam Stephen , Lazarus Philip , Le Marchand Loïc , Rennert Gad , Risch Angela , Schabath Matthew B. , Shete Sanjay S. , Tardón Adonina , Zienolddiny Shanbeh , Shen Hongbing , Amos Christopher I. 
Published: September 2020

AbstractAt the time of cancer diagnosis, body mass index (BMI) is inversely correlated with lung cancer risk, which may reflect reverse causality and confounding due to smoking behavior. We used two‐sample univariable and multivariable Mendelian randomization (MR) to estimate causal relationships of BMI and smoking behaviors on lung cancer and histological subtypes based on an aggregated genome‐wide association studies (GWASs) analysis of lung cancer in 29 266 cases and 56 450 controls. We observed a positive causal effect for high BMI on occurrence of small‐cell lung cancer (odds ratio (OR) = 1.60, 95% confidence interval (CI) = 1.24‐2.06, P = 2.70 × 10−4). After adjustment of smoking behaviors using multivariable Mendelian randomization (MVMR), a direct causal effect on small cell lung cancer (ORMVMR = 1.28, 95% CI = 1.06‐1.55, PMVMR = .011), and an inverse effect on lung adenocarcinoma (ORMVMR = 0.86, 95% CI = 0.77‐0.96, PMVMR = .008) were observed. A weak increased risk of lung squamous cell carcinoma was observed for higher BMI in univariable Mendelian randomization (UVMR) analysis (ORUVMR = 1.19, 95% CI = 1.01‐1.40, PUVMR = .036), but this effect disappeared after adjustment of smoking (ORMVMR = 1.02, 95% CI = 0.90‐1.16, PMVMR = .746). These results highlight the histology‐specific impact of BMI on lung carcinogenesis and imply mediator role of smoking behaviors in the association between BMI and lung cancer.
Association between selective serotonin reuptake inhibitors and kidney cancer risk: A nationwide population‐based cohort study
Authors: Lee Min‐Jing , Huang Chien‐Wei , Chen Yi‐Lung , Yang Yao‐Hsu , Chen Vincent Chin‐Hung 
Published: September 2020

AbstractThe association between selective serotonin reuptake inhibitor (SSRI) exposure and cancer incidence has been investigated; however, no epidemiological study has investigated the association between exposure to individual SSRIs and kidney cancer incidence. The aim of this study is to examine whether SSRI use affected the risk of kidney cancer. We conducted a population‐based retrospective cohort study using data from Taiwan's National Health Insurance Research Database. After adjusting for sex, age, urbanization level, comorbidity and medication use through propensity score matching, we identified 222 024 SSRI users and 221 361 SSRI nonusers. A robust Cox proportional hazards model was used to examine the associations between use of individual SSRIs and the risk of kidney cancer with 1‐ and 2‐year induction periods. The result showed that SSRI users tended to be associated with a lower risk of kidney cancer with a 2‐year induction period than nonusers; however, the association was not statistically significant (adjusted hazards ratio [aHR] = 0.88, 95% confidence interval [CI] = 0.77‐1.01). We further examined the effects of individual SSRIs and observed a significantly lower risk of kidney cancer associated with the use of citalopram (aHR = 0.67, 95% CI = 0.47‐0.96) and paroxetine (aHR = 0.75, 95% CI = 0.58‐0.97) with the 2‐year induction period. These findings support that SSRIs are associated with decreased kidney cancer risk and indicate that citalopram and paroxetine have protective effects in depressed patients with kidney cancer.
Family ownership and M&A payment method
Authors: Teti Emanuele , Dallocchio Maurizio , Currao Tancredi 
Published: September 2020

AbstractWe investigate the effects of family ownership on the choice between cash and stock payment in M&A operations. On a sample of 269 M&A transactions performed by Italian listed bidders over the period 2008–2015, we demonstrate that families are more inclined to pay in cash in order to avoid dilution. We also find that the influence of family ownership on the choice of the payment method is stronger for intermediate levels of control than for other levels. Furthermore, we document that financial structure considerations, bidder growth opportunities and deal specific characteristics influence the choice of payment method.
Hybrid compression of biomedical ECG and EEG signals based on differential clustering and encoding techniques
Authors: Angeline M , Suja Priyadharsini S 
Published: September 2020

AbstractSignal processing techniques incorporated with data compression processes enrich the signals and boost up storage efficiency and transmission reliability. Transmitting uncompressed original data consume wide bandwidth, which increases transmission time and leads to data hammering. These limitations enforce to look for strategic data compression techniques. Lossless compression techniques are requisite where it is important that the original and the decompressed data should be identical or where deviations from the original data would lead to catastrophic consequences, especially in biomedical signal analysis and diagnostics. For which, the input signal preprocessed with differential pulse code modulation (DPCM) reduces the interchannel dependencies to get the desired output. A whole array of unique compression techniques are being utilized in the compression process. The combination of (K‐means clustering, arithmetic encoding [AE], Huffman encoding [HE]) clustering and coding compression techniques are analyzed using electro cardiogram (ECG) and electroencephalogram (EEG) signals. The proposed method employs k‐means clustering combined with Huffman encoding (DiKHE) and k‐means clustering combined with arithmetic encoding (DiKAE) individually. Compression ratio (CR) is analyzed with these combinations of compression techniques for various cluster size K (K = 2,3,4,5,6). A maximum CR of 6.03144 and 4.54126 is obtained for ECG and EEG signals respectively. The compressions based on these techniques are efficient since the compressed signal is reconstructed perfectly as it matches exactly with the original signal.
Role of silica in mitigation of Cd, Pb and Cr toxicities in rice under irrigation with drainage water in the Egypt Nile delta*
Authors: El‐Habet Howida B.I. 
Published: September 2020

AbstractThis work targeted investigation of the efficiency of silica application on anatomical structures of the root system after 45 days from sowing and grain yield at maturity of the five rice varieties, Sakha104 (V1), Egyptian hybrid rice1 (EHR1) (V2), Sakha105 (V3), Giza178 (V4) and Giza179 (V5) under irrigation with drainage water (DW), having varied concentrations of Cd, Pb and Cr. Potassium silicate, potassium sulphate and silicon dioxide were sprayed individually as an aqueous solution at a concentration of 2% silica, applied twice 15 and 30 days after sowing. The collected results for the anatomical characteristics indicated that the highest values of cortex (650 length and 650 width μm), vascular bundle (750 length and 750 width μm), epidermis (241 μm) and xylem (175 length and 160 width μm) were recorded with application of Si as potassium silicate or silicon dioxide under the two types of irrigation water and in two consecutive growing seasons. Si application significantly increased shoots and root weight and length, and grain yield, compared to the Si‐untreated counterparts. The concentrations of Cd, Pb and Cr in harvested grains with application of potassium silicate or silicon dioxide under irrigation by DW were below the safety limits of 0.40, 0.20 and 1.00 ppm respectively.
Interim Analysis of a Phase 2 Open-Label Trial Assessing Burosumab Efficacy and Safety in Patients With Tumor-Induced Osteomalacia
Authors: Imanishi Yasuo , Ito Nobuaki , Rhee Yumie , Takeuchi Yasuhiro , Shin Chan Soo , Takahashi Yutaka , Onuma Hiroki , Kojima Masahiro , Kanematsu Masanori , Kanda Hironori , Seino Yoshiki , Fukumoto Seiji 
Published: September 2020

ABSTRACT
Patients with tumor-induced osteomalacia (TIO), an acquired paraneoplastic condition characterized by osteomalacia due to hypophosphatemia, exhibit a similar clinical picture to those with X-linked hypophosphatemic rickets/osteomalacia (XLH). The human monoclonal anti-fibroblast growth factor 23 (FGF23) antibody burosumab (KRN23) increases serum phosphate and improves bone turnover, fracture healing, pain, and physical function in XLH patients by inhibiting circulating FGF23; thus, burosumab is expected to be an effective treatment for TIO. We report here an interim analysis of a multicenter, open-label, intraindividual dose-adjustment study of burosumab (0.3 to 2.0 mg/kg every 4 weeks) in Japanese and Korean TIO patients. The primary endpoint was the fasting serum phosphate level at each visit. Key secondary endpoints were changes over time in bone biomarkers, pharmacodynamic markers, bone histomorphometric parameters, motor function, and patient-reported outcomes. Safety was assessed based on treatment-emergent adverse events (TEAEs). Thirteen patients received burosumab treatment, of whom 4 underwent bone biopsy. The mean dose after week 112 was approximately 1.0 mg/kg. After the first burosumab administration, mean serum phosphate levels increased and remained above the lower limit of normal and in the normal range from weeks 14 to 112. Bone biomarkers initially increased, reaching maximum values at week 16 or 24, and then gradually decreased. After burosumab treatment, patients were able to walk further (evaluated by the 6-minute walk test), reported decreased pain levels, and showed a tendency toward healing of baseline fractures and pseudofractures. Two patients discontinued, one each due to disease progression and consent withdrawal. Burosumab was generally well tolerated, with no treatment-related TEAEs of grade ≥3 and no treatment-related serious AEs. In conclusion, the interim results of this first study of burosumab to treat TIO patients indicate that this drug has the potential to provide clinical benefit for patients with unresectable tumors. The full study results are eagerly anticipated. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)..
Downregulation of SOX11 in fetal heart tissue, under hyperglycemic environment, mediates cardiomyocytes apoptosis
Authors: Su Dongmei , Gao Qianqian , Guan Lina , Sun Peng , Li Qian , Shi Cuige , Ma Xu 
Published: September 2020

AbstractGestational diabetes mellitus is one of the causes of abnormal embryonic heart development, but the mechanism is still poor. This study investigated the regulatory mechanism and role of SOX11 in congenital heart abnormality in a hyperglycemic environment. Immunohistochemistry, Western blotting, and quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) showed decreased SOX11 protein and messenger RNA (mRNA) levels in the heart tissue of diabetic offspring compared with the control group. A Sequenom EpiTYPER MassArray showed that methylation sites upstream in SOX11 region 1 were increased in the diabetic group compared with the control group. Luciferase reporter assays and qRT‐PCR showed that Dnmt3b overexpression decreased SOX11 promoter activity and its mRNA level, whereas Dnmt3a had little effect on regulating SOX11 expression. Furthermore, we found that Dnmt3L cooperated with Dnmt3b to regulate SOX11 gene expression. Additionally, the function of SOX11 silencing was analyzed by using small interfering RNA‐mediated knockdown. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide and apoptotic assays showed that SOX11 downregulation inhibited cell viability and induced apoptosis in cardiomyocytes. Overexpression of the SOX11 gene suppressed cardiomyocytes apoptosis after high glucose treatment. We identified a novel epigenetic regulatory mechanism of SOX11 during heart development in a hyperglycemic environment and revealed a distinct role of SOX11 in mediating cardiomyocytes viability and apoptosis.
REST‐repressed lncRNA NPPA‐AS1 regulates cervical cancer progression by modulating miR‐302e/DKK1/Wnt/β‐catenin signaling pathway
Authors: Luan Yanan , Xie Bin , Wei Wenbin 
Published: September 2020

AbstractLong noncoding RNAs (lncRNAs), a group of transcripts, have been revealed to be critical participants in regulating multiple biological processes of malignant tumors. The knowledge of NPPA‐AS1 (a new lncRNA) in cancer research is hardly known. Thus, it is of urgent need to study the underlying role of NPPA antisense RNA 1 (NPPA‐AS1) in cervical cancer (CC). In this study, NPPA‐AS1 was discovered to be lowly expressed and upregulation of it impaired cell proliferation and migration in CC. Besides, downregulation of it led to opposite results. Molecular mechanism assays uncovered that increased expression of NPPA‐AS1 could inactivate Wnt/β‐catenin signaling pathway in CC. In addition, NPPA‐AS1 was found to negatively interact with miR‐302e whereas positively correlate with dickkopf‐1 (DKK1, an inhibitor of Wnt pathway) in CC. Besides, loss of function assay illuminated that miR‐302e inhibition restrained cell proliferation and migration in CC. Subsequent rescue assays confirmed that NPPA‐AS1 acted as a competing endogenous RNA in CC by sponging miR‐302e to upregulate DKK1 expression. Finally, the RE‐1 silencing transcription factor (REST) was testified to function as a transcription suppressor of NPPA‐AS1 in CC. In brief, REST‐repressed NPPA‐AS1 regulates CC progression by modulating miR‐302e/DKK1/Wnt/β‐catenin signaling pathway.
Comprehensive landscape of STEAP family functions and prognostic prediction value in glioblastoma
Authors: Chen Huaijun , Xu Chaoran , Yu Qian , Zhong Chen , Peng Yucong , Chen Jingyin , Chen Gao 
Published: September 2020

AbstractGlioblastoma (GBM) is the most common, malignant, and deadly primary glioma. Six‐transmembrane epithelial antigen of prostate (STEAP) family is involved in tumorigenesis; here, we have explored the biological function and the prognostic value of the STEAP family in GBM. Differentially expressed STEAP genes in tumor and normal samples were screened by using The Cancer Genome Atlas (TCGA) database. Univariate and multivariate Cox regression identified the prognosis‐related genes: STEAP2 and STEAP3, which were involved in the regulation of immune response and cell cycle. Finally, a prognostic nomogram combining age, gender, chemotherapy, radiotherapy, IDH1 status, and the risk score model based on STEAP2 and STEAP3 was built and further validated in TCGA and Chinese Glioma Genome Atlas (CGGA) cohorts via concordance index and calibration plot, which suggested a favorable value for prognosis prediction. In conclusion, our results provided a comprehensive analysis of the STEAP family and a model for the prognosis prediction of GBM.
Population Pharmacokinetics of Phenobarbital in Neonates and Infants on Extracorporeal Membrane Oxygenation and the Influence of Concomitant Renal Replacement Therapy
Authors: Thibault Céline , Massey Shavonne L. , Abend Nicholas S. , Naim Maryam Y. , Zoraian Alexandra , Zuppa Athena F. 
Published: September 2020

AbstractThe objective of this study was to describe the pharmacokinetics (PK) of intravenous phenobarbital in neonates and infants on extracorporeal membrane oxygenation (ECMO) and to provide dosing recommendations in this population. We performed a retrospective single‐center PK study of phenobarbital in neonates and infants on ECMO between January 1, 2014, and December 31, 2018. We developed a population PK model using nonlinear mixed‐effects modeling, performed simulations using the final PK parameters, and determined optimal dosing based on attainment of peak and trough concentrations between 20 and 40 mg/L. We included 35 subjects with a median (range) age and weight of 14 days (1–154 days) and 3.4 kg (1.6–8.1 kg), respectively. A total of 194 samples were included in the analysis. Five children (14%) contributing 30 samples (16%) were supported by continuous venovenous hemodiafiltration (CVVHDF). A 1‐compartment model best described the data. Typical clearance and volume of distribution for a 3.4–kg infant were 0.038 L/h and 3.83 L, respectively. Clearance increased with age and CVVHDF. Although on ECMO, phenobarbital clearance in children on CVVHDF was 6‐fold higher than clearance in children without CVVHDF. In typical subjects, a loading dose of 30 mg/kg/dose followed by maintenance doses of 6–7 mg/kg/day administered as divided doses every 12 hours reached goal concentrations. Age did not impact dosing recommendations. However, higher doses were needed in children on CVVHDF. We strongly recommend therapeutic drug monitoring in children on renal replacement therapy (excluding slow continuous ultrafiltration) while on ECMO.
Effect of Pregnancy and Concomitant Antiretrovirals on the Pharmacokinetics of Tenofovir in Women With HIV Receiving Tenofovir Disoproxil Fumarate‐Based Antiretroviral Therapy Versus Women With HBV Receiving Tenofovir Disoproxil Fumarate Monotherapy
Authors: Bukkems Vera E. , Smolders Elise J. , Jourdain Gonzague , Burger David M. , Colbers Angela P. , Cressey Tim R. ,   PANNA Network and iTAP Study Group
Published: September 2020

AbstractTenofovir disoproxil fumarate (TDF) is recommended as part of antiretroviral therapy (ART) for pregnant women with HIV and as monotherapy for pregnant women with hepatitis B virus (HBV) monoinfection at high risk of transmitting infection to their infants. Tenofovir (TFV) plasma exposures are reduced during pregnancy; however, concomitant antiretrovirals and the viral infection itself can also influence TFV pharmacokinetics. Our aim was to compare TFV pharmacokinetics in pregnant women receiving TDF‐based ART, with or without a ritonavir‐boosted protease inhibitor (r/PI), to pregnant women with HBV receiving TDF monotherapy. Non‐r/PI regimens were primarily integrase strand transfer inhibitors or nonnucleoside reverse transcriptase inhibitor–based regimens. Data were combined from a pharmacokinetic study of pregnant women with HIV on ART (PANNA), and a study assessing TFV pharmacokinetics in pregnant women with HBV (iTAP). A total of 196 pregnant women, 59 with HIV (32 receiving r/PIs) and 137 with HBV monoinfection were included. Intraindividual TFV area under the plasma concentration–time curve from time 0 to 24 hours was 25%, 26%, and 21% lower during the third trimester compared to 1 month postpartum in women with HIV using TDF and an r/PI or TDF and non‐r/PI and women with HBV receiving TDF monotherapy, respectively. TFV area under the plasma concentration–time curve from time 0 to 24 hours was similar in pregnant women receiving non‐r/PI to pregnant women with HBV receiving TDF monotherapy (1.84 vs 1.86 µg • h/mL); however, pregnant women receiving TDF with an r/PI had higher exposures (2.41 µg • h/mL; P < .01). Pregnancy reduces TFV exposure and the relative size was not impacted by concomitant antiretroviral drugs or viral infection, but a drug‐drug interaction between TDF and r/PI remains during pregnancy, leading to higher exposures than those on TDF and non‐r/PI or TDF monotherapy.