bluuebunny/crossref_metadata_2025_split huggingface dataset:
AR420626, a selective agonist of GPR41/FFA3, suppresses growth of hepatocellular carcinoma cells by inducing apoptosis via HDAC inhibition
Authors: Mikami Daisuke , Kobayashi Mamiko , Uwada Junsuke , Yazawa Takashi , Kamiyama Kazuko , Nishimori Kazuhisa , Nishikawa Yudai , Nishikawa Sho , Yokoi Seiji , Taniguchi Takanobu , Iwano Masayuki 
Published: March 2020

Background: Hepatocellular carcinoma (HCC) is a major cause of cancer death worldwide and establishment of new chemotherapies for HCC is urgently needed. GPR41 [free fatty acid receptor 3 (FFA3)] is a G protein-coupled receptor for short chain fatty acids, including acetate, propionate, and butyrate. In our previous study, we showed that propionate enhances the cytotoxic effect of cisplatin in HCC cells and that this mechanism is dependent on inhibition of histone deacetylases (HDACs) via GPR41/FFA3. However, the antitumor action of GPR41/FFA3 has not been elucidated. Methods: In this study, we examined AR420626 as a GPR41-selective agonist in HepG2 and HLE cells. Nude mice were used for HepG2 xenograft studies. The apoptotic effect of AR420626 was evaluated using flow cytometry analysis. Expression of apoptosis-related proteins and HDACs was evaluated by Western immunoblot. Gene silencing of HDAC 3/5/7 and GPR41 was performed using small interfering RNA. Expression of TNF-α mRNA was evaluated by TaqMan real-time polymerase chain reaction. Results: We found that AR420626, a selective GPR41/FFA3 agonist, suppressed growth of HepG2 xenografts and inhibited proliferation of HCC cells by inducing apoptosis. AR420626 induced proteasome activation through mTOR phosphorylation, which reduced HDAC proteins, and then increased expression of TNF-α. Conclusion: AR420626, a selective GPR41/FFA3 agonist, may be a candidate as a therapeutic agent for HCC.
The Concurrent Effect of Financial Development and Trade Openness on Private Investment in India
Authors: Boachie Micheal Kofi , Ruzima Martin , Immurana Mustapha 
Published: March 2020

This article examines the role of financial development and trade openness in promoting private investment in India. We use data (1960– 2013) from the World Development Indicators database. After checking the time series properties of the data, we employ auto-regressive distributed lag (ARDL) estimation technique to investigate the impact of the concurrent existence of financial development and trade openness on private investment and whether the effect of financial development is dependent on the level of openness. The results show that, independently, financial development and trade openness have significant positive effects on India’s private sector investment, in both the long run and the short run. However, the effect of the interaction between financial development and trade openness on private investment is significantly negative, suggesting that the effect of financial development on private investment depends on the level of openness. Therefore, we conclude that care should be taken in the design of policies that allow for the coexistence of financial development and trade openness if India aims at promoting private sector capital formation for job creation. JEL Classification: E22, E44, F10, F60
Proteomic profiling of HTLV-1 carriers and ATL patients reveals sTNFR2 as a novel diagnostic biomarker for acute ATL
Authors: Guerrero Carmina Louise Hugo , Yamashita Yoshiko , Miyara Megumi , Imaizumi Naoki , Kato Megumi , Sakihama Shugo , Hayashi Masaki , Miyagi Takashi , Karimata Kaori , Uchihara Junnosuke , Ohshiro Kazuiku , Todoroki Junpei , Nakachi Sawako , Morishima Satoko , Karube Kennosuke , Tanaka Yuetsu , Masuzaki Hiroaki , Fukushima Takuya 
Published: March 2020

Abstract
Adult T-cell leukemia/lymphoma (ATL) is a human T-cell leukemia virus type 1 (HTLV-1)–associated T-cell malignancy with generally poor prognosis. Although only ∼5% of HTLV-1 carriers progress to ATL, early diagnosis is challenging because of the lack of ATL biomarkers. In this study, we analyzed blood plasma profiles of asymptomatic HTLV-1 carriers (ACs); untreated ATL patients, including acute, lymphoma, smoldering, and chronic types; and ATL patients in remission. Through SOMAscan, expression levels of 1305 plasma proteins were analyzed in 85 samples (AC, n = 40; ATL, n = 40; remission, n = 5). Using gene set enrichment analysis and gene ontology, overrepresented pathways in ATL vs AC included angiogenesis, inflammation by cytokines and chemokines, interleukin-6 (IL-6)/JAK/STAT3, and notch signaling. In selecting candidate biomarkers, we focused on soluble tumor necrosis factor receptor 2 (sTNFR2) because of its active role in enriched pathways, extreme significance (Welch’s t test P &lt; .00001), high discrimination capacity (area under the curve &gt;0.90), and novelty in ATL research. Quantification of sTNFR2 in 102 plasma samples (AC, n = 30; ATL, n = 68; remission, n = 4) using enzyme-linked immunosorbent assay showed remarkable elevations in acute ATL, at least 10 times those of AC samples, and return of sTNFR2 to AC state levels after achieving remission. Flow cytometry and immunostaining validated the expression of TNFR2 in ATL cells. No correlation between sIL-2 and sTNFR2 levels in acute ATL was found, suggesting the possibility of sTNFR2 as an independent biomarker. Our findings represent the first extensive blood-based proteomic analysis of ATL, suggesting the potential clinical utility of sTNFR2 in diagnosing acute ATL.
Paleoenvironmental changes across the Paleocene–Eocene boundary in West Central Sinai, Egypt: geochemical proxies
Authors: Ghandour Ibrahim Mohamed 
Published: March 2020

AbstractA geochemical analysis has been conducted on twenty-six sediment samples spanning the P–E boundary interval collected from the Esna Shale in three well-dated stratigraphic sections in west-central Sinai, Egypt to interpret paleoenvironmental changes associated with the P–E boundary events. The Esna Shale consists of hemipelagic marine shales and marls and it is subdivided stratigraphically into the uppermost Paleocene Hanadi Member unconformably overlain by the lowermost Eocene Dababiya Quarry Bed (DQB) and El-Mahmiya members. A variety of geochemical proxies including the Al-normalized elemental concentrations and redox-related elemental ratios and parameter (V/Cr, V/V + Ni and Mn*) and productivity indicators (Porg and Babio) were employed for paleoceanographic interpretations. Across the P–E transition, the concentrations of SiO2, TiO2, Al2O3 Fe2O3, MgO, V, Cr, Ni, Cu, Rb, and Zr notably increased, whereas the concentrations of CaO, MnO, Sr, and Zn abruptly decreased. The variation in the elemental concentrations is attributed to the carbonate dissolution because of increased ocean acidification as well as a brief increase in the detrital influx associated with the brief humid interval at the base of the Eocene. The Al-normalized detrital-related elements (Ti, Zr, and Rb) values show a relatively homogeneous profile suggesting a uniform detrital input from an unchanged source rock. The simultaneous significant increase in the V/Cr and V/V + Ni ratios and enrichment of Ni, Cu, and Zn in the sediments of the DQB suggest that the depositional basin experienced dysoxic to slightly anoxic bottom conditions. The coeval increase in the Porg and Babio in the sediments of the DQB suggests an increase in nutrients availability and consequently primary productivity possibly due to enhanced upwelling during early Eocene.
2D electrophoresis image brightness correction based on gradient interval histogram
Authors: Ou Qiaofeng , Xiao Jiabing , Yu Lei , Wu Kaizhi , Xiong Bangshu 
Published: March 2020

Abstract
Background
Two-dimensional electrophoresis (2DE) is one of the most widely applied techniques in comparative proteomics. The basic task of 2DE is to identify differential protein expression by quantitative analysis of 2DE images. To reduce the errors of spot quantification in 2DE images, a novel brightness correction method based on gradient interval histogram (GIH) is proposed in this paper.

Results
First, GIH equalization is proposed to enhance the protein spot edges, especially the weak protein spots in the 2DE image. Second, to eliminate the overall brightness shift, GIH matching is applied to the 2DE images that need to be compared. Finally, the proposed method is verified by subjective quality evaluation and quantitative analysis of protein spots in real 2DE images.

Conclusions
The experimental results show that the average error of the quantification of corresponding protein spots in the resulting image pairs is less than 3%, which is significantly superior to that of the existing methods.
Comparison of RNA isolation methods on RNA-Seq: implications for differential expression and meta-analyses
Authors: Scholes Amanda N. , Lewis Jeffrey A. 
Published: March 2020

Abstract
Background
The increasing number of transcriptomic datasets has allowed for meta-analyses, which can be valuable due to their increased statistical power. However, meta-analyses can be confounded by so-called “batch effects,” where technical variation across different batches of RNA-seq experiments can clearly produce spurious signals of differential expression and reduce our power to detect true differences. While batch effects can sometimes be accounted for, albeit with caveats, a better strategy is to understand their sources to better avoid them. In this study, we examined the effects of RNA isolation method as a possible source of batch effects in RNA-seq design.

Results
Based on the different chemistries of “classic” hot phenol extraction of RNA compared to common commercial RNA isolation kits, we hypothesized that specific mRNAs may be preferentially extracted depending upon method, which could masquerade as differential expression in downstream RNA-seq analyses. We tested this hypothesis using the Saccharomyces cerevisiae heat shock response as a well-validated environmental response. Comparing technical replicates that only differed in RNA isolation method, we found over one thousand transcripts that appeared “differentially” expressed when comparing hot phenol extraction with the two kits. Strikingly, transcripts with higher abundance in the phenol-extracted samples were enriched for membrane proteins, suggesting that indeed the chemistry of hot phenol extraction better solubilizes those species of mRNA.

Conclusions
Within a self-contained experimental batch (e.g. control versus treatment), the method of RNA isolation had little effect on the ability to identify differentially expressed transcripts. However, we suggest that researchers performing meta-analyses across different experimental batches strongly consider the RNA isolation methods for each experiment.
Whole-genome sequencing of Puccinia striiformis f. sp. tritici mutant isolates identifies avirulence gene candidates
Authors: Li Yuxiang , Xia Chongjing , Wang Meinan , Yin Chuntao , Chen Xianming 
Published: March 2020

AbstractBackgroundThe stripe rust pathogen,Puccinia striiformisf. sp.tritici(Pst), threats world wheat production. Resistance toPstis often overcome by pathogen virulence changes, but the mechanisms of variation are not clearly understood. To determine the role of mutation inPstvirulence changes, in previous studies 30 mutant isolates were developed from a least virulent isolate using ethyl methanesulfonate (EMS) mutagenesis and phenotyped for virulence changes. The progenitor isolate was sequenced, assembled and annotated for establishing a high-quality reference genome. In the present study, the 30 mutant isolates were sequenced and compared to the wide-type isolate to determine the genomic variation and identify candidates for avirulence (Avr) genes.ResultsThe sequence reads of the 30 mutant isolates were mapped to the wild-type reference genome to identify genomic changes. After selecting EMS preferred mutations, 264,630 and 118,913 single nucleotide polymorphism (SNP) sites and 89,078 and 72,513 Indels (Insertion/deletion) were detected among the 30 mutant isolates compared to the primary scaffolds and haplotigs of the wild-type isolate, respectively. Deleterious variants including SNPs and Indels occurred in 1866 genes. Genome wide association analysis identified 754 genes associated with avirulence phenotypes. A total of 62 genes were found significantly associated to 16 avirulence genes after selection through six criteria for putative effectors and degree of association, including 48 genes encoding secreted proteins (SPs) and 14 non-SP genes but with high levels of association (P ≤ 0.001) to avirulence phenotypes. Eight of the SP genes were identified as avirulence-associated effectors with high-confidence as they met five or six criteria used to determine effectors.ConclusionsGenome sequence comparison of the mutant isolates with the progenitor isolate unraveled a large number of mutation sites along the genome and identified high-confidence effector genes as candidates for avirulence genes inPst.Since the avirulence gene candidates were identified from associated SNPs and Indels caused by artificial mutagenesis, these avirulence gene candidates are valuable resources for elucidating the mechanisms of the pathogen pathogenicity, and will be studied to determine their functions in the interactions between the wheat host and thePstpathogen.
A combination of the activation marker CD86 and the immune checkpoint marker B and T lymphocyte attenuator (BTLA) indicates a putative permissive activation state of B cell subtypes in healthy blood donors independent of age and sex
Authors: Axelsson Susanne , Magnuson Anders , Lange Anna , Alshamari Aseel , Hörnquist Elisabeth Hultgren , Hultgren Olof 
Published: March 2020

Abstract
Background
The use of anti-B cell based therapies in immune-mediated diseases targeting general B cell markers or molecules important for B cell function has increased the clinical needs of monitoring B cell subpopulations.

Results
We analyzed the expression profile of cell surface markers CD86 and B and T lymphocyte attenuator (BTLA) in B cell subtypes using flow cytometry, including naïve, transitional, switched memory, non-switched memory and double-negative memory B cells and plasmablasts, and investigated the dependence of age and sex in a healthy adult blood donor population. The switched memory B cell subtype displayed a divergent expression of the markers, with increased CD86 and decreased BTLA as compared to non-switched and double negative memory cells, as well as compared to naïve B cells. Plasmablasts expressed highly increased CD86 compared to all other subtypes and a decreased expression of BTLA compared to naïve cells, but still higher compared to the memory cell populations. Transitional B cells had CD86 and BTLA expression similar to the other naïve cells.

Conclusions
We show divergent expression of CD86 and BTLA in memory cells and plasmablasts compared to naïve B cells independent of age and sex. Furthermore, a similarly divergent difference of expression pattern was seen between the memory cell subtypes, altogether indicating that the combination of CD86 and BTLA might be markers for a permissive activation state. We suggest the combination of CD86 and BTLA expression on B cell subtypes as a potentially important tool in monitoring the status of B cell subtypes before and after treatments influencing the B cell compartment.
Phosphate transporters, PnPht1;1 and PnPht1;2 from Panax notoginseng enhance phosphate and arsenate acquisition
Authors: Cao Guan-Hua , Li Ze-Dong , Wang Xi-Fu , Zhang Xue , Zhao Rong-Hua , Gu Wen , Chen Di , Yu Jie , He Sen 
Published: March 2020

Abstract
Background
Panax notoginseng is a medicinally important Chinese herb with a long history of cultivation and clinical application. The planting area is mainly distributed in Wenshan Prefecture, where the quality and safety of P. notoginseng have been threatened by high concentration of arsenic (As) from the soil. The roles of phosphate (Pi) transporters involved in Pi acquisition and arsenate (AsV) tolerance were still unclear in this species.

Results
In this study, two open reading frames (ORFs) of PnPht1;1 and PnPht1;2 separated from P. notoginseng were cloned based on RNA-seq, which encoded 527 and 541 amino acids, respectively. The results of relative expression levels showed that both genes responded to the Pi deficiency or As exposure, and were highly upregulated. Heterologous expression in Saccharomyces cerevisiae MB192 revealed that PnPht1;1 and PnPht1;2 performed optimally in complementing the yeast Pi-transport defect, particularly in PnPht1;2. Cells expressing PnPht1;2 had a stronger AsV tolerance than PnPht1;1-expressing cells, and accumulated less As in cells under a high-Pi concentration. Combining with the result of plasma membrane localization, these data confirmed that transporters PnPht1;1 and PnPht1;2 were putative high-affinity H+/H2PO4− symporters, mediating the uptake of Pi and AsV.

Conclusion
PnPht1;1 and PnPht1;2 encoded functional plasma membrane-localized transporter proteins that mediated a putative high-affinity Pi/H+ symport activity. Expression of PnPht1;1 or PnPht1;2 in mutant strains could enhance the uptake of Pi and AsV, that is probably responsible for the As accumulation in the roots of P. notoginseng.
Anemia risk factors among people living with HIV across the United States in the current treatment era: a clinical cohort study
Authors: Harding B. N. , Whitney B. M. , Nance R. M. , Ruderman S. A. , Crane H. M. , Burkholder G. , Moore R. D. , Mathews W. C. , Eron J. J. , Hunt P. W. , Volberding P. , Rodriguez B. , Mayer K. H. , Saag M. S. , Kitahata M. M. , Heckbert S. R. , Delaney J. A. C. 
Published: March 2020

AbstractBackgroundAnemia is common among people living with HIV infection (PLWH) and is associated with adverse health outcomes. Information on risk factors for anemia incidence in the current antiretroviral therapy (ART) era is lacking.MethodsWithin a prospective clinical cohort of adult PLWH receiving care at eight sites across the United States between 1/2010–3/2018, Cox proportional hazards regression analyses were conducted among a) PLWH free of anemia at baseline and b) PLWH free of severe anemia at baseline to determine associations between time-updated patient characteristics and development of anemia (hemoglobin < 10 g/dL), or severe anemia (hemoglobin < 7.5 g/dL). Linear mixed effects models were used to examine relationships between patient characteristics and hemoglobin levels during follow-up. Hemoglobin levels were ascertained using laboratory data from routine clinical care. Potential risk factors included: age, sex, race/ethnicity, body mass index, smoking status, hazardous alcohol use, illicit drug use, hepatitis C virus (HCV) coinfection, estimated glomerular filtration rate (eGFR), CD4 cell count, viral load, ART use and time in care at CNICS site.ResultsThis retrospective cohort study included 15,126 PLWH. During a median follow-up of 6.6 (interquartile range [IQR] 4.3–7.6) years, 1086 participants developed anemia and 465 participants developed severe anemia. Factors that were associated with incident anemia included: older age, female sex, black race, HCV coinfection, lower CD4 cell counts, VL ≥400 copies/ml and lower eGFR.ConclusionBecause anemia is a treatable condition associated with increased morbidity and mortality among PLWH, hemoglobin levels should be monitored routinely, especially among PLWH who have one or more risk factors for anemia.
Prognostic value of the bone scan index in patients with metastatic castration-resistant prostate cancer: a systematic review and meta-analysis
Authors: Song Hualin , Jin Song , Xiang Peng , Hu Shuai , Jin Jie 
Published: March 2020

Abstract
Background
Many studies have reported the prognostic significance of the bone scan index (BSI) for metastatic castration-resistant prostate cancer (mCRPC); however, these reports are controversial. This study investigated the BSI in mCRPC and its relationship with prognosis.

Methods
The PubMed, Cochrane, and Embase databases were searched systematically for relevant articles published before September 1, 2019. Hazard ratios (HRs) were used to investigate the prognostic value.

Results
This study finally identified 9 eligible studies. The results suggested that high baseline BSI predicted poor OS (HR = 1.331, 95% CI: 1.081–1.640) and that elevated ΔBSI also predicted poor OS (HR = 1.220, 95% CI: 1.015–1.467). The subgroup analysis stratified by ethnicity showed that the baseline BSI and ΔBSI predicted poor OS in the Asian population but not in the Caucasian population. We also performed a subgroup analysis based on the different cut-off values of baseline BSI. The subgroup of ≤1 showed a significant association with OS in mCRPC patients.

Conclusion
Our study demonstrated that high baseline BSI and elevated ΔBSI predicted poor OS in patients with mCRPC. Hence, the BSI can serve as a prognostic indicator for mCRPC patients and may therefore guide clinical treatment in the future.
Neck lymph node metastasis detection in patients with differentiated thyroid carcinoma (DTC) in long-term follow-up: a 131I-SPECT/CT study
Authors: Spanu Angela , Nuvoli Susanna , Marongiu Andrea , Gelo Ilaria , Mele Luciana , Piras Bastiana , Madeddu Giuseppe 
Published: March 2020

AbstractBackgroundThe identification of neck lymph node (LN) metastases represents a very important issue in the management of patients with differentiated thyroid carcinoma (DTC). To this purpose, in the present study, we used 131I-SPECT/CT as a diagnostic imaging procedure.MethodsA consecutive series of 224 DTC patients with ascertained neck radioiodine-avid foci at131I-SPECT/CT during long-term follow-up was evaluated. All patients had already undergone total thyroidectomy and radioiodine therapy and had been classified as follows: 62 at high risk (H), 64 at low risk (L) and 98 at very low risk (VL).131I-Whole body scan (WBS) followed by SPECT/CT was performed in all cases.ResultsIn the 224 patients, 449 neck iodine avid foci were ascertained at SPECT/CT, while 322 were evidenced at WBS in 165/224 patients. WBS classified as residues 263/322 foci and as unclear 59/322 foci; among the former foci SPECT/CT correctly characterized 8 LN metastases and 3 physiologic uptakes and among the latter, it pinpointed 26 LN metastases, 18 residues, and 15 physiologic uptakes. SPECT/CT also classified 127 foci occult at WBS as 59 LN metastases and 68 residues. Globally, SPECT/CT identified 93 LN metastases in 59 patients (26 H, 20 L, 13 VL), while WBS evidenced 34 in 25 cases. All 13 VL patients, T1aN0M0, 5 of whom with LN near sub-mandibular glands, had thyroglobulin undetectable or < 2.5 ng/ml. Globally, SPECT/CT obtained an incremental value than WBS in 45.5% of patients, a more correct patient classification changing therapeutic approach in 30.3% of cases and identified WBS false-positive findings in 8% of cases.Conclusions131I-SPECT/CT proved to correctly detect and characterize neck LN metastases in DTC patients in long-term follow-up, improving the performance of planar WBS. SPECT/CT routine use is thus suggested; its role is particularly relevant in patients with WBS inconclusive, VL, T1aN0M0 and with undetectable or very low thyroglobulin levels.