bluuebunny/crossref_metadata_2025_split huggingface dataset:
CircRNA GFRA1 promotes hepatocellular carcinoma progression by modulating the miR-498/NAP1L3 axis
Authors: Lv Shuai , Li Yingxia , Ning Hanbing , Zhang Meihui , Jia Qiaoyu , Wang Xijuan 
Published: January 2021

AbstractCircular RNAs (circRNAs) play essential roles in tumorigenesis and tumor progression. CircRNA GFRA1 (circGFRA1) was dysregulated in many cancer samples and acted as an independent marker for prediction of survivals in various cancer patients. However, the functions and molecular mechanisms of circGFRA1 in hepatocellular carcinoma (HCC) remain unclear. We collected 62 HCC tissues and normal adjacent tissues to evaluate the expression of circGFRA1 and the relationship between circGFRA1 expression and HCC patients’ survival. We carried out a list of characterization experiments to investigate the roles and underling mechanisms of circGFRA1 and miR-498 in HCC progressions. CircGFRA1 was greatly increased in HCC tissues and cells, and the over-expression of circGFRA1 was intimately related with the advanced clinical stage and poor survival of HCC patients. The expression of circGFRA1 was negatively correlated with the expression of miR-498, but a positive correlation was found between circGFRA1 and NAP1L3 expression in HCC tissues. Silencing circGFRA1 inhibited the growth and invasion of hepatocellular carcinoma. Moreover, miR-498 over-expression or NAP1L3 inhibition could abrogate the oncogene role of circGFRA1 in HCC in vivo. Our findings indicated that circGFRA1 contributed to HCC progression by modulating the miR-498/NAP1L3 axis in HCC.
Polysaccharide hydrogel based 3D printed tumor models for chemotherapeutic drug screening
Authors: Gebeyehu Aragaw , Surapaneni Sunil Kumar , Huang John , Mondal Arindam , Wang Vivian Ziwen , Haruna Nana Fatima , Bagde Arvind , Arthur Peggy , Kutlehria Shallu , Patel Nil , Rishi Arun K. , Singh Mandip 
Published: January 2021

AbstractA series of stable and ready-to-use bioinks have been developed based on the xeno-free and tunable hydrogel (VitroGel) system. Cell laden scaffold fabrication with optimized polysaccharide-based inks demonstrated that Ink H4 and RGD modified Ink H4-RGD had excellent rheological properties. Both bioinks were printable with 25–40 kPa extrusion pressure, showed 90% cell viability, shear-thinning and rapid shear recovery properties making them feasible for extrusion bioprinting without UV curing or temperature adjustment. Ink H4-RGD showed printability between 20 and 37 °C and the scaffolds remained stable for 15 days at temperature of 37 °C. 3D printed non-small-cell lung cancer (NSCLC) patient derived xenograft cells (PDCs) showed rapid spheroid growth of size around 500 µm in diameter and tumor microenvironment formation within 7 days. IC50 values demonstrated higher resistance of 3D spheroids to docetaxel (DTX), doxorubicin (DOX) and erlotinib compared to 2D monolayers of NSCLC-PDX, wild type triple negative breast cancer (MDA-MB-231 WT) and lung adenocarcinoma (HCC-827) cells. Results of flow property, shape fidelity, scaffold stability and biocompatibility of H4-RGD suggest that this hydrogel could be considered for 3D cell bioprinting and also for in-vitro tumor microenvironment development for high throughput screening of various anti-cancer drugs.
Circulating adiponectin and leptin and risk of overall and aggressive prostate cancer: a systematic review and meta-analysis
Authors: Burton Anya J. , Gilbert Rebecca , Tilling Kate , Langdon Ryan , Donovan Jenny L. , Holly Jeff M. P. , Martin Richard M. 
Published: January 2021

AbstractObesity is associated with an increased risk of advanced, recurrent and fatal prostate cancer. Adipokines may mediate this relationship. We conducted a systematic review and meta-analysis of associations of leptin and adiponectin with overall and aggressive prostate cancer. Bibliographic databases were systematically searched up to 1st April 2017. Log Odds Ratios (ORs) per 2.5 unit increase in adiponectin or leptin levels were derived and pooled. All analyses were stratified by study type (cross-sectional/prospective). 746 papers were retrieved, 34 eligible studies identified, 31 of these could be included in the meta-analysis. Leptin was not consistently associated with overall prostate cancer (pooled OR 1.00, 95%CI 0.98–1.02, per 2.5 ng/ml increase, prospective study OR 0.97, 95%CI 0.95–0.99, cross-sectional study OR 1.19, 95%CI 1.13–1.26) and there was weak evidence of a positive association with aggressive disease (OR 1.03, 95%CI 1.00–1.06). There was also weak evidence of a small inverse association of adiponectin with overall prostate cancer (OR 0.96, 95%CI 0.93–0.99, per 2.5 µg/ml increase), but less evidence of an association with aggressive disease (OR 0.98, 95%CI 0.94–1.01). The magnitude of any effects are small, therefore levels of circulating adiponectin or leptin alone are unlikely to be useful biomarkers of risk or prognosis.
Spatiotemporal variation in cell proliferation patterns during arthropod axial elongation
Authors: Cepeda Rodrigo E. , Terraza John B. , Pardo Renato V. , Núñez-Pascual Valentina , Mundaca-Escobar Marco , Sarrazin Andres F. 
Published: January 2021

AbstractAn elongated and segmented body plan is a common morphological characteristic of all arthropods and is probably responsible for their high adaptation ability to diverse environments. Most arthropods form their bodies by progressively adding segments, resembling vertebrate somitogenesis. This sequential segmentation relies on a molecular clock that operates in the posterior region of the elongating embryo that combines dynamically with cellular behaviors and tissue rearrangements, allowing the extension of the developing body along its main embryonic axis. Even though the molecular mechanisms involved in elongation and segment formation have been found to be conserved in a considerable degree, cellular processes such as cell division are quite variable between different arthropods. In this study, we show that cell proliferation in the beetleTribolium castaneumhas a nonuniform spatiotemporal patterning during axial elongation. We found that dividing cells are preferentially oriented along the anterior–posterior axis, more abundant and posteriorly localized during thoracic segments formation and that this cell proliferation peak was triggered at the onset of axis elongation. This raise in cell divisions, in turn, was correlated with an increase in the elongation rate, but not with changes in cell density. When DNA synthesis was inhibited over this period, both the area and length of thoracic segments were significantly reduced but not of the first abdominal segment. We discuss the variable participation that different cell division patterns and cell movements may have on arthropod posterior growth and their evolutionary contribution.
Potentiality of multiple modalities for single-cell analyses to evaluate the tumor microenvironment in clinical specimens
Authors: Kashima Yukie , Togashi Yosuke , Fukuoka Shota , Kamada Takahiro , Irie Takuma , Suzuki Ayako , Nakamura Yoshiaki , Shitara Kohei , Minamide Tatsunori , Yoshida Taku , Taoka Naofumi , Kawase Tatsuya , Wada Teiji , Inaki Koichiro , Chihara Masataka , Ebisuno Yukihiko , Tsukamoto Sakiyo , Fujii Ryo , Ohashi Akihiro , Suzuki Yutaka , Tsuchihara Katsuya , Nishikawa Hiroyoshi , Doi Toshihiko 
Published: January 2021

AbstractSingle-cell level analysis is powerful tool to assess the heterogeneity of cellular components in tumor microenvironments (TME). In this study, we investigated immune-profiles using the single-cell analyses of endoscopically- or surgically-resected tumors, and peripheral blood mononuclear cells from gastric cancer patients. Furthermore, we technically characterized two distinct platforms of the single-cell analysis; RNA-seq-based analysis (scRNA-seq), and mass cytometry-based analysis (CyTOF), both of which are broadly embraced technologies. Our study revealed that the scRNA-seq analysis could cover a broader range of immune cells of TME in the biopsy-resected small samples of tumors, detecting even small subgroups of B cells or Treg cells in the tumors, although CyTOF could distinguish the specific populations in more depth. These findings demonstrate that scRNA-seq analysis is a highly-feasible platform for elucidating the complexity of TME in small biopsy tumors, which would provide a novel strategies to overcome a therapeutic difficulties against cancer heterogeneity in TME.
Topological data analysis (TDA) enhances bispectral EEG (BSEEG) algorithm for detection of delirium
Authors: Yamanashi Takehiko , Kajitani Mari , Iwata Masaaki , Crutchley Kaitlyn J. , Marra Pedro , Malicoat Johnny R. , Williams Jessica C. , Leyden Lydia R. , Long Hailey , Lo Duachee , Schacher Cassidy J. , Hiraoka Kazuaki , Tsunoda Tomoyuki , Kobayashi Ken , Ikai Yoshiaki , Kaneko Koichi , Umeda Yuhei , Kadooka Yoshimasa , Shinozaki Gen 
Published: January 2021

AbstractCurrent methods for screening and detecting delirium are not practical in clinical settings. We previously showed that a simplified EEG with bispectral electroencephalography (BSEEG) algorithm can detect delirium in elderly inpatients. In this study, we performed a post-hoc BSEEG data analysis using larger sample size and performed topological data analysis to improve the BSEEG method. Data from 274 subjects included in the previous study were analyzed as a 1st cohort. Subjects were enrolled at the University of Iowa Hospitals and Clinics (UIHC) between January 30, 2016, and October 30, 2017. A second cohort with 265 subjects was recruited between January 16, 2019, and August 19, 2019. The BSEEG score was calculated as a power ratio between low frequency to high frequency using our newly developed algorithm. Additionally, Topological data analysis (TDA) score was calculated by applying TDA to our EEG data. The BSEEG score and TDA score were compared between those patients with delirium and without delirium. Among the 274 subjects from the first cohort, 102 were categorized as delirious. Among the 206 subjects from the second cohort, 42 were categorized as delirious. The areas under the curve (AUCs) based on BSEEG score were 0.72 (1st cohort, Fp1-A1), 0.76 (1st cohort, Fp2-A2), and 0.67 (2nd cohort). AUCs from TDA were much higher at 0.82 (1st cohort, Fp1-A1), 0.84 (1st cohort, Fp2-A2), and 0.78 (2nd cohort). When sensitivity was set to be 0.80, the TDA drastically improved specificity to 0.66 (1st cohort, Fp1-A1), 0.72 (1st cohort, Fp2-A2), and 0.62 (2nd cohort), compared to 0.48 (1st cohort, Fp1-A1), 0.54 (1st cohort, Fp2-A2), and 0.46 (2nd cohort) with BSEEG. BSEEG has the potential to detect delirium, and TDA is helpful to improve the performance.
Exploring the biological role of postzygotic and germinal de novo mutations in ASD
Authors: Alonso-Gonzalez A. , Calaza M. , Amigo J. , González-Peñas J. , Martínez-Regueiro R. , Fernández-Prieto M. , Parellada M. , Arango C. , Rodriguez-Fontenla Cristina , Carracedo A. 
Published: January 2021

AbstractDe novo mutations (DNMs), including germinal and postzygotic mutations (PZMs), are a strong source of causality for Autism Spectrum Disorder (ASD). However, the biological processes involved behind them remain unexplored. Our aim was to detect DNMs (germinal and PZMs) in a Spanish ASD cohort (360 trios) and to explore their role across different biological hierarchies (gene, biological pathway, cell and brain areas) using bioinformatic approaches. For the majority of the analysis, a combined ASD cohort (N = 2171 trios) was created using previously published data by the Autism Sequencing Consortium (ASC). New plausible candidate genes for ASD such as FMR1 and NFIA were found. In addition, genes harboring PZMs were significantly enriched for miR-137 targets in comparison with germinal DNMs that were enriched in GO terms related to synaptic transmission. The expression pattern of genes with PZMs was restricted to early mid-fetal cortex. In contrast, the analysis of genes with germinal DNMs revealed a spatio-temporal window from early to mid-fetal development stages, with expression in the amygdala, cerebellum, cortex and striatum. These results provide evidence of the pathogenic role of PZMs and suggest the existence of distinct mechanisms between PZMs and germinal DNMs that are influencing ASD risk.
The role of the PIK3CA gene in the development and aging of the brain
Authors: Xie Shaozhen , Ni Jing , Guo Hanbing , Luu Victor , Wang Yanzhi , Zhao Jean J. , Roberts Thomas M. 
Published: January 2021

AbstractThe CLOVES syndrome is an overgrowth disease arising from mosaic activating somatic mutations in the PIK3CA gene. These mutations occur during fetal development producing malformation and overgrowth of a variety of tissues. It has recently been shown that treatment with low doses of a selective inhibitor of Class I PI3K catalytic subunit p110α, the protein product of the PIK3CA gene, can yield dramatic therapeutic benefits for patients with CLOVES and PROS (a spectrum of PIK3CA-related overgrowth syndromes). To assess the long-term effects of moderate loses of p110α activity, we followed development and growth of mice with heterozygous loss of p110α (Pik3ca+/−) over their entire lifetimes, paying particular attention to effects on the brain. While homozygous deletion of the Pik3ca gene is known to result in early embryonic lethality, these Pik3ca+/− mice displayed a longer lifespan compared to their wild-type littermates. These mice appeared normal, exhibited no obvious behavioral abnormalities, and no body weight changes. However, their brains showed a significant reduction in size and weight. Notably, mice featuring deletion of one allele of Pik3ca only in the brain also showed gradually reduced brain size and weight. Mechanistically, either deletion of p110α or pharmacological inhibition of p110α activity reduced neurosphere size, but not numbers, in vitro, suggesting that p110α activity is critical for neuronal stem cells. The phenotypes observed in our two genetically engineered mouse models suggest that the sustained pharmacological inhibition of the PIK3CA activity in human patients might have both beneficial and harmful effects, and future treatments may need to be deployed in a way to avoid or minimize adverse effects.
Bromelain reduced pro-inflammatory mediators as a common pathway that mediate antinociceptive and anti-anxiety effects in sciatic nerve ligated Wistar rats
Authors: Bakare Ahmed O. , Owoyele Bamidele V. 
Published: January 2021

AbstractThe involvement of pro-inflammatory mediators complicates the complex mechanism in neuropathic pain (NP). This study investigated the roles of bromelain against pro-inflammatory mediators as a mechanism that underpins its antinociceptive and anti-anxiety effects in the peripheral model of NP. Sixty-four male Wistar rats randomly divided into eight groups, were used for the study. A chronic constriction injury model of peripheral neuropathy was used to induce NP. Tail-immersion and von Frey filaments tests were used to assess hyperalgesia while open field and elevated plus mazes were used to assess anxiety-like behaviour. NF-кB, iNOS, nitrate, and pro-inflammatory cytokines were investigated in the plasma, sciatic nerve, and brain tissues using ELISA, spectrophotometer, and immunohistochemistry techniques after twenty-one days of treatment. Bromelain significantly (p < 0.05) improved the cardinal signs of NP and inhibited anxiety-like behaviours in ligated Wistar rats. It mitigated the increases in cerebral cortex interleukin (IL) -1β, IL-6, and PGE2 levels. Bromelain reduced NF-кB, IL-1β, IL-6, TNF-α, PGE2, and nitrate concentrations as well as the expression of iNOS in the sciatic nerve. Hence, the antinociceptive and anxiolytic effects of bromelain in the sciatic nerve ligation model of NP is in part due to its ability to reduce nitrosative and inflammatory activities.
Transcriptomic analysis of early stages of intestinal regeneration in Holothuria glaberrima
Authors: Quispe-Parra David J. , Medina-Feliciano Joshua G. , Cruz-González Sebastián , Ortiz-Zuazaga Humberto , García-Arrarás José E. 
Published: January 2021

AbstractEchinoderms comprise a group of animals with impressive regenerative capabilities. They can replace complex internal organs following injury or autotomy. In holothurians or sea cucumbers, cellular processes of intestinal regeneration have been extensively studied. The molecular machinery behind this faculty, however, remains to be understood. Here we assembled and annotated a de novo transcriptome using RNA-seq data consisting of regenerating and non-regenerating intestinal tissues from the sea cucumber Holothuria glaberrima. Comparisons of differential expression were made using the mesentery as a reference against 24 h and 3 days regenerating intestine, revealing a large number of differentially expressed transcripts. Gene ontology and pathway enrichment analysis showed evidence of increasing transcriptional activity. Further analysis of transcripts associated with transcription factors revealed diverse expression patterns with mechanisms involving developmental and cancer-related activity that could be related to the regenerative process. Our study demonstrates the broad and diversified gene expression profile during the early stages of the process using the mesentery as the focal point of intestinal regeneration. It also establishes the genes that are the most important candidates in the cellular processes that underlie regenerative responses.
Plasma and follicular fluid osteopontin levels during ovarian cycle and their correlation with follicular fluid vascular endothelial growth factor levels
Authors: Kuwabara Yoshimitsu , Ono Shuichi , Katayama Akira , Kurihara Sachiko , Oishi Yumiko , Takeshita Toshiyuki 
Published: January 2021

AbstractOsteopontin (OPN) is a multifunctional secreted glycoprotein. We evaluated OPN concentrations in blood and follicular fluid (FF) during the ovarian cycle and their relationship with the production of vascular endothelial growth factor (VEGF), which is involved in the pathophysiology of ovarian hyperstimulation syndrome (OHSS). Twenty-two women undergoing in vitro fertilization (minimal stimulation protocol with clomiphene citrate) were enrolled. Samples were collected (a) on the third day of withdrawal bleeding, (b) 2 days before oocyte retrieval, and (c) on the day of oocyte retrieval. FF was collected during oocyte retrieval. The OPN concentration in each specimen and the VEGF concentration in FF was measured by enzyme-linked immunosorbent assays. Plasma OPN concentrations were (in ng/mL): (a) 416 ± 37.2, (b) 378 ± 35.8, and (c) 390 ± 40.0, with no significant differences between the groups. The OPN concentration in FF was 106 ± 13.4 ng/mL. A positive correlation was found between OPN concentrations in FF and plasma samples. A positive correlation was also found between plasma OPN and FF VEGF concentrations, irrespective of the blood-sampling period. Plasma OPN concentration is suggested to reflect the FF VEGF level at oocyte retrieval and maybe a novel clinical marker for predicting the risk for OHSS.
Source dipole analysis reveals a new brain response to visual symmetry
Authors: Tyson-Carr John , Bertamini Marco , Rampone Giulia , Makin Alexis 
Published: January 2021

AbstractVisual regularity activates a network of brain regions in the extrastriate cortex. Previous EEG studies have found that this response scales parametrically with proportion of symmetry in symmetry + noise displays. The parametric symmetry response happens in many tasks, but it is enhanced during active regularity discrimination. However, the origins and time course of this selective enhancement are unclear. Here we answered remaining questions with new source dipole analysis. As assumed, the parametric symmetry response found at the sensor level was generated by a pair of dipoles in the left and right extrastriate cortex. This bilateral activity was itself enhanced during regularity discrimination. However, we identified a third, and later, symmetry response in the posterior cingulate during regularity discrimination. Unlike the extrastriate response, this previously unknown activation only indexes strong, task relevant regularity signals. This clarifies the neural circuits which mediate the perceptual and cognitive aspects of symmetry discrimination.
Quantitative proteomics analysis of Angiostrongylus vasorum-induced alterations in dog serum sheds light on the pathogenesis of canine angiostrongylosis
Authors: Tritten Lucienne , Gillis-Germitsch Nina , Kockmann Tobias , Schnyder Manuela 
Published: January 2021

AbstractBlood contains hundreds of proteins, reflecting ongoing cellular processes and immune reactions. Infections with the blood-dwelling cardiopulmonary nematode Angiostrongylus vasorum in dogs manifest with a broad spectrum of clinical signs including respiratory distress, bleeding diathesis and neurological signs, and are associated with a perturbed blood protein profile in dogs. However, current knowledge does not completely explain the observed pathologies induced by A. vasorum infections, including bleeding disorders. Using sera from experimentally infected dogs, dog serum proteome was analysed by quantitative mass spectrometry methods over several time points before and after inoculation. Following computational analysis, we identified 139 up- and downregulated proteins after infection (log2 ratio cut-off ≥ 1.0; q-value ≤ 0.05). Among upregulated proteins were chitinase 3-like 1 and pulmonary surfactant-associated protein B (log2 fold-changes ≥ 5). Pathway enrichment revealed the complement (especially the lectin pathway) and coagulation cascades as significantly affected upon analysis of downregulated proteins. Among them were mannan-binding lectin serine peptidases, ficolin, and coagulation factor XIII-B. These results bring new elements towards understanding the underlying pathomechanisms of bleeding diatheses observed in some A. vasorum-infected dogs.
A threshold mechanism ensures minimum-path flow in lightning discharge
Authors: Blanchini Franco , Casagrande Daniele , Fabiani Filippo , Giordano Giulia , Palma David , Pesenti Raffaele 
Published: January 2021

AbstractA well-known property of linear resistive electrical networks is that the current distribution minimizes the total dissipated power. When the circuit includes resistors with nonlinear monotonic characteristic, the current distribution minimizes in general a different functional. We show that, if the nonlinear characteristic is a threshold-like function and the current generator is concentrated in a single point, as in the case of lightning or dielectric discharge, then the current flow is concentrated along a single path, which is a minimum path to the ground with respect to the threshold. We also propose a dynamic model that explains and qualitatively reproduces the lightning transient behavior: initial generation of several plasma branches and subsequent dismissal of all branches but the one reaching the ground first, which is the optimal one.