bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic Significance of Apparent Diffusion Coefficient in Hepatocellular Carcinoma Patients treated with Stereotactic Ablative Radiotherapy
Authors: Lo Cheng-Hsiang , Huang Wen-Yen , Hsiang Chih-Weim , Lee Meei-Shyuan , Lin Chun-Shu , Yang Jen-Fu , Hsu Hsian-He , Chang Wei-Chou 
Published: October 2019

AbstractThe role of diffusion-weighted magnetic resonance imaging (DW MRI) in assessing durable tumor control for patients with hepatocellular carcinoma (HCC) treated with stereotactic ablative radiotherapy (SABR) was not defined. This retrospective study included 34 HCC patients with 45 lesions who had DW MRI data at baseline and within 6 months post-SABR. On the first post-SABR MRI, 13 lesions (28.9%) had a complete response (CR), 12 (26.7%) had a partial response (PR), 17 (37.8%) had stable disease, and 3 (6.7%) had progressive disease by modified Response Evaluation Criteria in Solid Tumors (mRECIST). On subsequent imaging, the response rate improved from 55.6% to 75.6%. The apparent diffusion coefficients (ADCs) (mean ± standard deviation) pre- and post-SABR were 1.43 ± 0.28 and 1.72 ± 0.34 (×10−3 mm2/s), respectively (p < 0.001). An ADC change ≥25% (DW[+]) was identified as a predictor of favorable in-field control (IFC) (1-year IFC, 93.3% vs. 50.0% for DW[−], p = 0.004), but an mRECIST-based positive response (CR and PR) at the first MRI was not (p = 0.130). In conclusion, ADC change on early MRI is closely related to IFC in HCCs treated with SABR. Standardization of the DW MRI protocol, as well as prospective validation studies, are warranted.
Assessing trends of breast cancer and carcinoma in situ to monitor screening policies in developing settings
Authors: Brito Érika de Abreu Costa , Lima Marcela Sampaio , Siqueira Hianga Fayssa Fernandes , Marques Adriane Dórea , Moura Alex Rodrigues , Hora Evânia Curvelo , Lima Carlos Anselmo , Santos Marceli de Oliveira , de Souza Mirian Carvalho , da Silva Angela Maria , Brito Hugo Leite de Farias , Cipolotti Rosana 
Published: October 2019

AbstractThere have been arguments about the role of breast cancer screening at the population level, and some points of controversy have arisen, such the establishment of organized screening policies and the age at which to begin screening. The real benefit of screening has been questioned because the results of this practice may increase the diagnosis of indolent lesions without decreasing mortality due to breast cancer. The authors have proposed a study of incidence and mortality trends for breast cancer in a developing setting in Brazil to monitor the effectiveness of the official recommendations that prioritize the age group from 50 to 69 years. The database of the Cancer Registry and the Mortality Information System was used to calculate age-standardized and age-specific rates, which were then used to calculate incidence and mortality trends using the Joinpoint Regression Program. The results showed stability in trends across all ages and age-specific groups in both incidence and mortality. In conclusion, we found that incidence and mortality rates are compatible with those in regions with similar human development indexes, and trends have demonstrated stabilization. Thus, we do not endorse changes in the official recommendations to conduct screening for ages other than 50 to 69 years, nor should policy makers implement organized screening strategies.
Associations between Peripheral Thromboembolic Vascular Disease and Androgen Deprivation Therapy in Asian Prostate Cancer Patients
Authors: Lu Yu-Chuan , Huang Chao-Yuan , Yeh Huei-Ming , Hong Jian-Hua , Chang Chao-Hsiang , Muo Chih-Hsin , Chung Shiu-Dong , Yang Teng-Kai , Jaw Fu-Shan , Chung Chi-Jung 
Published: October 2019

AbstractThis study aimed to investigate the risks of thromboembolic vascular disease following androgen deprivation therapy (ADT) administered to prostate cancer (PCa) patients. A total of 24,464 men with newly diagnosed PCa during 2000–2008 were recruited through a longitudinal health insurance database in Taiwan. All PCa patients were stratified into two: ADT and non-ADT groups. Patients with ADT treatment were grouped into three: surgical castration, chemical castration, and anti-androgen alone. The risks of pulmonary embolism (PE), peripheral arterial occlusion disease (PAOD), and deep vein thrombosis (DVT) were assessed in multiple Cox proportional-hazards regression with time-dependent covariates. During the 12-year follow-up period, incidence rates per 1000 person-years in ADT and non-ADT groups were 2.87 and 1.62 for DVT, 1.00 and 0.52 for PE, and 1.03 and 0.70 for PAOD, respectively. The DVT and PE risks were significantly increased in patients receiving combined androgen blockade (CAB) compared with the counterpart ADT non-recipients. After adjusting for potential risk factors, PCa patients receiving CAB had the highest PE risk (HR = 3.11), followed by DVT risk (HR = 2.53). The DVT risk remained elevated throughout the entire duration of chemical castration. However, high PE risk was observed in patients with ≤720-day treatment duration. No association was found between ADT and PAOD risks. Overall, the risks of PE and DVT were considerably heightened in Asian men subjected to CAB for PCa, whereas PAOD risk was unrelated to such treatments.
RNA Sequencing revealed differentially expressed genes functionally associated with immunity and tumor suppression during latent phase infection of a vv + MDV in chickens
Authors: Dong Kunzhe , Chang Shuang , Xie Qingmei , Zhao Peng , Zhang Huanmin 
Published: October 2019

AbstractVery virulent plus Marek’s disease (MD) virus (vv + MDV) induces tumors in relatively resistant lines of chickens and early mortality in highly susceptible lines of chickens. The vv + MDV also triggers a series of cellular responses in both types of chickens. We challenged birds sampled from a highly inbred chicken line (line 63) that is relatively resistant to MD and from another inbred line (line 72) that is highly susceptible to MD with a vv + MDV. RNA-sequencing analysis was performed with samples extracted from spleen tissues taken at 10-day and 21-day post infection (dpi). A total of 64 and 106 differentially expressed genes was identified in response to the vv + MDV challenge at latent phase in the resistant and susceptible lines of chickens, respectively. Direct comparisons between samples of the two lines identified 90 and 126 differentially expressed genes for control and MDV challenged groups, respectively. The differentially expressed gene profiles illustrated that intensive defense responses were significantly induced by vv + MDV at 10 dpi and 21 dpi but with slight changes in the resistant line. In contrast, vv + MDV induced a measurable suppression of gene expression associated with host defense at 10 dpi but followed by an apparent activation of the defense response at 21 dpi in the susceptible line of chickens. The observed difference in gene expression between the two genetic lines of chickens in response to MDV challenge during the latent phase provided a piece of indirect evidence that time points for MDV reactivation differ between the genetic lines of chickens with different levels of genetic resistance to MD. Early MDV reactivation might be necessary and potent to host defense system readiness for damage control of tumorigenesis and disease progression, which consequently results in measurable differences in phenotypic characteristics including early mortality (8 to 20 dpi) and tumor incidence between the resistant and susceptible lines of chickens. Combining differential gene expression patterns with reported GO function terms and quantitative trait loci, a total of 27 top genes was selected as highly promising candidate genes for genetic resistance to MD. These genes are functionally involved with virus process (F13A1 and HSP90AB1), immunity (ABCB1LB, RGS5, C10ORF58, OSF-2, MMP7, CXCL12, GAL1, GAL2, GAL7, HVCN1, PDE4D, IL4I1, PARP9, EOMES, MPEG1, PDK4, CCLI10, K60 and FST), and tumor suppression (ADAMTS2, LXN, ARRDC3, WNT7A, CLDN1 and HPGD). It is anticipated that these findings will facilitate advancement in the fundamental understanding on mechanisms of genetic resistance to MD. In addition, such advancement may also provide insights on tumor virus-induced tumorigenesis in general and help the research community recognize MD study may serve as a good model for oncology study involving tumor viruses.
Genome-wide association study and whole-genome sequencing identify a deletion in LRIT3 associated with canine congenital stationary night blindness
Authors: Das Rueben G. , Becker Doreen , Jagannathan Vidhya , Goldstein Orly , Santana Evelyn , Carlin Kendall , Sudharsan Raghavi , Leeb Tosso , Nishizawa Yuji , Kondo Mineo , Aguirre Gustavo D. , Miyadera Keiko 
Published: October 2019

AbstractCongenital stationary night blindness (CSNB), in the complete form, is caused by dysfunctions in ON-bipolar cells (ON-BCs) which are secondary neurons of the retina. We describe the first disease causative variant associated with CSNB in the dog. A genome-wide association study using 12 cases and 11 controls from a research colony determined a 4.6 Mb locus on canine chromosome 32. Subsequent whole-genome sequencing identified a 1 bp deletion in LRIT3 segregating with CSNB. The canine mutant LRIT3 gives rise to a truncated protein with unaltered subcellular expression in vitro. Genetic variants in LRIT3 have been associated with CSNB in patients although there is limited evidence regarding its apparently critical function in the mGluR6 pathway in ON-BCs. We determine that in the canine CSNB retina, the mutant LRIT3 is correctly localized to the region correlating with the ON-BC dendritic tips, albeit with reduced immunolabelling. The LRIT3-CSNB canine model has direct translational potential enabling studies to help understand the CSNB pathogenesis as well as to develop new therapies targeting the secondary neurons of the retina.
Validation of a Miniaturized Permeability Assay Compatible with CRISPR-Mediated Genome-Wide Screen
Authors: Simonneau Claire , Yang Junning , Kong Xianguo , Kilker Robert , Edelstein Leonard , Fortina Paolo , Londin Eric , Horowitz Arie 
Published: October 2019

AbstractThe impermeability of the luminal endothelial cell monolayer is crucial for the normal performance of the vascular and lymphatic systems. A key to this function is the integrity of the monolayer’s intercellular junctions. The known repertoire of junction-regulating genes is incomplete. Current permeability assays are incompatible with high-throughput genome-wide screens that could identify these genes. To overcome these limitations, we designed a new permeability assay that consists of cell monolayers grown on ~150 μm microcarriers (MCs). Each MC functions as a miniature individual assay of permeability (MAP). We demonstrate that false-positive results can be minimized, and that MAP sensitivity to thrombin-induced increase in monolayer permeability is similar to the sensitivity of impedance measurement. We validated the assay by showing that the expression of single guide RNAs (sgRNAs) that target genes encoding known thrombin signaling proteins blocks effectively thrombin-induced junction disassembly, and that MAPs carrying such cells can be separated effectively by fluorescence-assisted sorting from those that carry cells expressing non-targeting sgRNAs. These results indicate that MAPs are suitable for high-throughput experimentation and for genome-wide screens for genes that mediate the disruptive effect of thrombin on endothelial cell junctions.
Polymorphisms in the P2X7 receptor, and differential expression of Toll-like receptor-mediated cytokines and defensins, in a Canadian Indigenous group
Authors: Semple Catlin , Choi Ka-Yee Grace , Kroeker Andrea , Denechezhe Lizette , Orr Pamela , Mookherjee Neeloffer , Larcombe Linda 
Published: October 2019

AbstractCanadian Indigenous peoples (First Nations and Inuit) exhibit a high burden of infectious diseases including tuberculosis influenced by societal factors, and biological determinants. Toll-like receptor (TLR)-mediated innate immune responses are the first line of defence against infections. We examined the production of a panel of 30 cytokines in peripheral blood-derived mononuclear cells (PBMC) isolated from Indigenous and non-Indigenous participants, following stimulation with five different TLR ligands. The levels of TLR-induced pro-inflammatory cytokines such as IL-12/23p40, IL-16, and IFN-γ, and chemokines (MCP-4, MDC and eotaxin) were different between Indigenous compared to non-Indigenous participants. Antimicrobial cationic host defence peptides (CHDP) induced by TLR activation are critical for resolution of infections and modulate the TLR-to-NFκB pathway to alter downstream cytokine responses. Therefore, we examined the expression of human CHDP defensins and cathelicidin in PBMC. mRNA expression of genes encoding fordef-A1anddef-B1were significantly higher following stimulation with TLR ligands in Indigenous compared to non-Indigenous participants. The purinergic receptor P2X7 known to be activated by ATP released following TLR stimulation, is a receptor for CHDP. Therefore, we further examined single nucleotide polymorphisms (SNP) in P2X7. Indigenous participants had a significantly higher percentage of a P2X7 SNP which is associated with reduced function and lower ability to clear infections. These results suggest that a higher frequency of non-functional P2X7 receptors may influence the activity of downstream immune mediators required for resolution of infections such as pro-inflammatory cytokines and CHDP defensins, thus contributing to higher burden of infections in Indigenous population.
The complete chloroplast genome of Stryphnodendron adstringens (Leguminosae - Caesalpinioideae): comparative analysis with related Mimosoid species
Authors: Souza Ueric José Borges de , Nunes Rhewter , Targueta Cíntia Pelegrineti , Diniz-Filho José Alexandre Felizola , Telles Mariana Pires de Campos 
Published: October 2019

AbstractStryphnodendron adstringensis a medicinal plant belonging to the Leguminosae family, and it is commonly found in the southeastern savannas, endemic to the Cerrado biome. The goal of this study was to assemble and annotate the chloroplast genome ofS. adstringensand to compare it with previously known genomes of the mimosoid clade within Leguminosae. The chloroplast genome was reconstructed usingde novoand referenced-based assembly of paired-end reads generated by shotgun sequencing of total genomic DNA. The size of theS. adstringenschloroplast genome was 162,169 bp. This genome included a large single-copy (LSC) region of 91,045 bp, a small single-copy (SSC) region of 19,014 bp and a pair of inverted repeats (IRa and IRb) of 26,055 bp each. TheS. adstringenschloroplast genome contains a total of 111 functional genes, including 77 protein-coding genes, 30 transfer RNA genes, and 4 ribosomal RNA genes. A total of 137 SSRs and 42 repeat structures were identified inS. adstringenschloroplast genome, with the highest proportion in the LSC region. A comparison of theS. adstringenschloroplast genome with those from other mimosoid species indicated that gene content and synteny are highly conserved in the clade. The phylogenetic reconstruction using 73 conserved coding-protein genes from 19 Leguminosae species was supported to be paraphyletic. Furthermore, the noncoding and coding regions with high nucleotide diversity may supply valuable markers for molecular evolutionary and phylogenetic studies at different taxonomic levels in this group.
Deciphering Dynamical Nonlinearities in Short Time Series Using Recurrent Neural Networks
Authors: Nagarajan Radhakrishnan 
Published: October 2019

AbstractSurrogate testing techniques have been used widely to investigate the presence of dynamical nonlinearities, an essential ingredient of deterministic chaotic processes. Traditional surrogate testing subscribes to statistical hypothesis testing and investigates potential differences in discriminant statistics between the given empirical sample and its surrogate counterparts. The choice and estimation of the discriminant statistics can be challenging across short time series. Also, conclusion based on a single empirical sample is an inherent limitation. The present study proposes a recurrent neural network classification framework that uses the raw time series obviating the need for discriminant statistic while accommodating multiple time series realizations for enhanced generalizability of the findings. The results are demonstrated on short time series with lengths (L = 32, 64, 128) from continuous and discrete dynamical systems in chaotic regimes, nonlinear transform of linearly correlated noise and experimental data. Accuracy of the classifier is shown to be markedly higher than ≫50% for the processes in chaotic regimes whereas those of nonlinearly correlated noise were around ~50% similar to that of random guess from a one-sample binomial test. These results are promising and elucidate the usefulness of the proposed framework in identifying potential dynamical nonlinearities from short experimental time series.
Biological importance of podoplanin expression in chorionic villous stromal cells and its relationship to placental pathologies
Authors: Onak Kandemir Nilufer , Barut Figen , Barut Aykut , Birol İsmail Eren , Dogan Gun Banu , Ozdamar Sukru Oguz 
Published: October 2019

AbstractPodoplanin, a reliable marker of lymphatic endothelium, is a mucin-type transmembrane protein. Although the human placenta is devoid of a lymphatic system, chorionic villous stromal (CVS) cells express podoplanin. In this study, the pattern of podoplanin expression in normal and pathological placental tissues and the biological role of podoplanin were investigated. In total, 198 placental tissues belonging to 184 patients, seen at the Department of Pathology of Bulent Ecevit University Education and Research Hospital, Zonguldak, Turkey, were evaluated histopathologically and determined to meet the study criteria. The tissues were assigned to control, cisternal placental disorders, inflammation and hypoxic-ischemic pathology groups. Podoplanin expression in CVS cells was graded from 0 to 3 depending on the staining intensity, as determined by an immunohistochemical evaluation of chorionic villi in the most intensively stained tissue region. Podoplanin levels in control CVS cells increased in parallel with placental maturation, whereas in molar pregnancies podoplanin expression was lower than in control tissues. In the acute placental inflammation group, podoplanin immunoreactivity was similar to that in the control group, whereas in the preeclampsia group, podoplanin expression was higher than in all other groups. Our study showed an increase in podoplanin expression in CVS cells during pregnancy. In preeclamptic patients, the increase in podoplanin expression may be a response to hypoxic-ischemic conditions, whereas in molar pregnancies the decrease in podoplanin levels may cause villous swelling by disrupting intercellular fluid homeostasis.
Anti-inflammatory and antioxidant effects of muscarinic acetylcholine receptor (mAChR) activation in the rat hippocampus
Authors: Frinchi Monica , Nuzzo Domenico , Scaduto Pietro , Di Carlo Marta , Massenti Maria F. , Belluardo Natale , Mudò Giuseppa 
Published: October 2019

AbstractRecently we found that acute treatment with Oxotremorine (Oxo), a non-selective mAChRs agonist, up-regulates heat shock proteins and activates their transcription factor heat shock factor 1 in the rat hippocampus. Here we aimed to investigate: a) if acute treatment with Oxo may regulate pro-inflammatory or anti-inflammatory cytokines and oxidative stress in the rat hippocampus; b) if chronic restraint stress (CRS) induces inflammatory or oxidative alterations in the hippocampus and whether such alterations may be affected by chronic treatment with Oxo. In the acute experiment, rats were injected with single dose of Oxo (0.4 mg/kg) and sacrificed at 24 h, 48 h and 72 h. In the CRS experiment, the rats were exposed for 21 days to the CRS and then were treated with Oxo (0.2 mg/kg) for further 10 days. The acute Oxo treatment showed an ability to significantly reduce reactive oxygen species (ROS), singlet oxygen (1O2), pro-inflammatory cytokines levels (IL-1β and IL-6) and phosphorylated NF-κB-p65. Acute Oxo treatment also increased superoxide dismutase (SOD)-2 protein levels and stimulated SOD activity. No differences were detected in the anti-inflammatory cytokine levels, including IL-10 and TGF-β1. In the group of rats exposed to the CRS were found increased hippocampal IL-1β and IL-6 levels, together with a reduction of SOD activity level. These changes produced by CRS were counteracted by chronic Oxo treatment. In contrast, the upregulation of ROS and 1O2 levels in the CRS group was not counteracted by chronic Oxo treatment. The results revealed a hippocampal anti-inflammatory and antioxidant effect of Oxo treatment in both basal conditions and anti-inflammatory in the CRS rat model.
Development of experimental silicosis in inbred and outbred mice depends on instillation volume
Authors: Mayeux Jessica M. , Kono Dwight H. , Pollard Kenneth Michael 
Published: October 2019

AbstractThere is considerable variation in methods to induce experimental silicosis with the effects of dose and route of exposure being well documented. However, to what extent the volume of silica suspension alters the dispersion and severity of silicosis has not been adequately investigated. In this study, the optimal volume of a crystalline silica suspension required to obtain uniform distribution and greatest incidence and severity of silicosis was determined in inbred and outbred mice. Silica dispersal, detected by co-inspiration with India ink and polarized light microscopy, was highly dependent upon volume. Furthermore, although peribronchitis, perivasculitis, and increases in bronchoalveolar lavage fluid cell numbers were detected a lower doses and volumes, significant alveolitis required exposure to 5 mg of silica in 50 μl. This dose and volume of transoral instillation led to a greater penetrance of silicosis in the genetically heterogeneous Diversity Outbred strain as well as greater alveolar inflammation typical of the silicosis in human disease. These findings underscore the critical importance of instillation volume on the induction, severity, and type of inflammatory pathology in experimental silicosis.