bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microarray Embedding/Sectioning for Parallel Analysis of 3D Cell Spheroids
Authors: Gabriel Jonathan , Brennan David , Elisseeff Jennifer H. , Beachley Vince 
Published: November 2019

AbstractThree-dimensional cell spheroid models can be used to predict the effect of drugs and therapeutics and to model tissue development and regeneration. The utility of these models is enhanced by high throughput 3D spheroid culture technologies allowing researchers to efficiently culture numerous spheroids under varied experimental conditions. Detailed analysis of high throughput spheroid culture is much less efficient and generally limited to narrow outputs, such as metabolic viability. We describe a microarray approach that makes traditional histological embedding/sectioning/staining feasible for large 3D cell spheroid sample sets. Detailed methodology to apply this technology is provided. Analysis of the technique validates the potential for efficient histological analysis of up to 96 spheroids in parallel. By integrating high throughput 3D spheroid culture technologies with advanced immunohistochemical techniques, this approach will allow researchers to efficiently probe expression of multiple biomarkers with spatial localization within 3D structures. Quantitative comparison of staining will have improved inter- and intra-experimental reproducibility as multiple samples are collectively processed, stained, and imaged on a single slide.
Stochastic and Heterogeneous Cancer Cell Migration: Experiment and Theory
Authors: Kwon Taejin , Kwon Ok-Seon , Cha Hyuk-Jin , Sung Bong June 
Published: November 2019

AbstractCell migration, an essential process for normal cell development and cancer metastasis, differs from a simple random walk: the mean-square displacement (〈(Δr)2(t)〉) of cells sometimes shows non-Fickian behavior, and the spatiotemporal correlation function (G(r, t)) of cells is often non-Gaussian. We find that this intriguing cell migration should be attributed to heterogeneity in a cell population, even one with a homogeneous genetic background. There are two limiting types of heterogeneity in a cell population: cellular heterogeneity and temporal heterogeneity. Cellular heterogeneity accounts for the cell-to-cell variation in migration capacity, while temporal heterogeneity arises from the temporal noise in the migration capacity of single cells. We illustrate that both cellular and temporal heterogeneity need to be taken into account simultaneously to elucidate cell migration. We investigate the two-dimensional migration of A549 lung cancer cells using time-lapse microscopy and find that the migration of A549 cells is Fickian but has a non-Gaussian spatiotemporal correlation. We find that when a theoretical model considers both cellular and temporal heterogeneity, the model reproduces all of the anomalous behaviors of cancer cell migration.
RNF34 overexpression exacerbates neurological deficits and brain injury in a mouse model of intracerebral hemorrhage by potentiating mitochondrial dysfunction-mediated oxidative stress
Authors: Qu Xin , Wang Ning , Chen Wenjin , Qi Meng , Xue Yueqiao , Cheng Weitao 
Published: November 2019

AbstractIntracerebral hemorrhage (ICH) is a common neurological condition associated with high disability and mortality. Alterations in protein ubiquitination have emerged as a key mechanism in the pathogenesis of neurological diseases. Here, we investigated the effects of the E3 ubiquitin ligase ring finger protein 34 (RNF34) on neurological deficits and brain injury in ICH mice. An ICH model was established via intracerebral injection of autologous blood into wild-type and RNF34 transgenic mice. Brain injury, neurological function, neuronal activity, and oxidative stress levels were measured, respectively. The underlying mechanisms were explored by molecular and cellular approaches. Our results showed that RNF34 overexpression in mice significantly aggravated the ICH-induced memory impairment, brain edema, infarction, hematoma volume, and loss of neuronal activity. RNF34 and oxidative stress levels gradually increased from 6 to 48 h after the ICH challenge and were positively correlated. The ICH-induced increase in intracellular ROS, superoxide anion, and mROS generation and the decrease in adenosine triphosphate production were exacerbated in RNF34 transgenic mice, but NADPH oxidase activity was unaffected. Moreover, RNF34 upregulation potentiated the ICH-induced decrease in PGC-1α, UCP2, and MnSOD expressions. RNF34 interacted with PGC-1α and targeted it for ubiquitin-dependent degradation. This study reveals that RNF34 exacerbates neurological deficits and brain injury by facilitating PGC-1α protein degradation and promoting mitochondrial dysfunction-mediated oxidative stress.
Identifying inaccuracies in gene expression estimates from unstranded RNA-seq data
Authors: Pomaznoy Mikhail , Sethi Ashu , Greenbaum Jason , Peters Bjoern 
Published: November 2019

AbstractRNA-seq methods are widely utilized for transcriptomic profiling of biological samples. However, there are known caveats of this technology which can skew the gene expression estimates. Specifically, if the library preparation protocol does not retain RNA strand information then some genes can be erroneously quantitated. Although strand-specific protocols have been established, a significant portion of RNA-seq data is generated in non-strand-specific manner. We used a comprehensive stranded RNA-seq dataset of 15 blood cell types to identify genes for which expression would be erroneously estimated if strand information was not available. We found that about 10% of all genes and 2.5% of protein coding genes have a two-fold or higher difference in estimated expression when strand information of the reads was ignored. We used parameters of read alignments of these genes to construct a machine learning model that can identify which genes in an unstranded dataset might have incorrect expression estimates and which ones do not. We also show that differential expression analysis of genes with biased expression estimates in unstranded read data can be recovered by limiting the reads considered to those which span exonic boundaries. The resulting approach is implemented as a package available at https://github.com/mikpom/uslcount.
Novel Gd3+-doped silica-based optical fiber material for dosimetry in proton therapy
Authors: Hoehr C. , Morana A. , Duhamel O. , Capoen B. , Trinczek M. , Paillet P. , Duzenli C. , Bouazaoui M. , Bouwmans G. , Cassez A. , Ouerdane Y. , Boukenter A. , El Hamzaoui H. , Girard S. 
Published: November 2019

AbstractOptical fibers hold promise for accurate dosimetry in small field proton therapy due to their superior spatial resolution and the lack of significant Cerenkov contamination in proton beams. One known drawback for most scintillation detectors is signal quenching in areas of high linear energy transfer, as is the case in the Bragg peak region of a proton beam. In this study, we investigated the potential of innovative optical fiber bulk materials using the sol-gel technique for dosimetry in proton therapy. This type of glass is made of amorphous silica (SiO$${}_{2}$$

2

) and is doped with Gd$${}^{3+}$$

3
+

ions and possesses very interesting light emission properties with a luminescence band around 314 nm when exposed to protons. The fibers were manufactured at the University of Lille and tested at the TRIUMF Proton Therapy facility with 8.2–62.9 MeV protons and 2–6 nA of extracted beam current. Dose-rate dependence and quenching were measured and compared to other silica-based fibers also made by sol-gel techniques and doped with Ce$${}^{3+}$$

3
+

and Cu$${}^{+}$$

+

. The three fibers present strong luminescence in the UV (Gd) or visible (Cu,Ce) under irradiation, with the emission intensities related directly to the proton flux. In addition, the 0.5 mm diameter Gd$${}^{3+}$$

3
+

-doped fiber shows superior resolution of the Bragg peak, indicating significantly reduced quenching in comparison to the Ce$${}^{3+}$$

3
+

and Cu$${}^{+}$$

+

fibers with a Birks’ constant, k$${}_{B}$$

B

, of (0.0162 $$\pm $$
±
0.0003) cm/MeV in comparison to (0.0333 $$\pm $$
±
0.0006) cm/MeV and (0.0352 $$\pm $$
±
0.0003) cm/MeV, respectively. To our knowledge, this is the first report of such an interesting k$${}_{B}$$

B

for a silica-based optical fiber material, showing clearly that this fiber presents lower quenching than common plastic scintillators. This result demonstrates the high potential of this inorganic fiber material for proton therapy dosimetry.
Blood Pressure Estimation Using On-body Continuous Wave Radar and Photoplethysmogram in Various Posture and Exercise Conditions
Authors: Pour Ebrahim Malikeh , Heydari Fatemeh , Wu Taiyang , Walker Katherine , Joe Keith , Redoute Jean-Michel , Yuce Mehmet Rasit 
Published: November 2019

AbstractThe pulse arrival time (PAT), pre-ejection period (PEP) and pulse transit time (PTT) are calculated using on-body continuous wave radar (CWR), Photoplethysmogram (PPG) and Electrocardiogram (ECG) sensors for wearable continuous systolic blood pressure (SBP) measurements. The CWR and PPG sensors are placed on the sternum and left earlobe respectively. This paper presents a signal processing method based on wavelet transform and adaptive filtering to remove noise from CWR signals. Experimental data are collected from 43 subjects in various static postures and 26 subjects doing 6 different exercise tasks. Two mathematical models are used to calculate SBPs from PTTs/PATs. For 38 subjects participating in posture tasks, the best cumulative error percentage (CEP) is 92.28% and for 21 subjects participating in exercise tasks, the best CEP is 82.61%. The results show the proposed method is promising in estimating SBP using PTT. Additionally, removing PEP from PAT leads to improving results by around 9%. The CWR sensors present a low-power, continuous and potentially wearable system with minimal body contact to monitor aortic valve mechanical activities directly. Results of this study, of wearable radar sensors, demonstrate the potential superiority of CWR-based PEP extraction for various medical monitoring applications, including BP measurement.
Reduced RhoA expression enhances breast cancer metastasis with a concomitant increase in CCR5 and CXCR4 chemokines signaling
Authors: Kalpana Gardiyawasam , Figy Christopher , Yeung Miranda , Yeung Kam C. 
Published: November 2019

AbstractThe role of RhoA GTPases in breast cancer tumorigenesis and metastasis is unclear. Early studies within which mutations in RhoA were designed based on cancer-associated mutations in Ras supported an oncogene role for RhoA. However, recent whole-genome sequencing studies of cancers raised the possibility that RhoA may have a tumor suppression function. Here, using a syngeneic triple negative breast cancer murine model we investigated the physiological effects of reduced RhoA expression on breast cancer tumorigenesis and metastasis. RhoA knockdown had no effect on primary tumor formation and tumor proliferation, concurring with our in vitro findings where reduced RhoA had no effect on breast cancer cell proliferation and clonogenic growth. In contrast, primary tumors with RhoA knockdown efficiently invaded sentinel lymph nodes and significantly metastasized to lungs compared to control tumors. Mechanistically, the current study demonstrated that this is achieved by promoting a pro-tumor microenvironment, with increased cancer-associated fibroblasts and macrophage infiltration, and by modulating the CCL5-CCR5 and CXCL12-CXCR4 chemokine axes in the primary tumor. To our knowledge, this is the first such mechanistic study in breast cancer showing the ability of RhoA to suppress chemokine receptor expression in breast tumor cells. Our work suggests a physiological lung and lymph node metastasis suppressor role for RhoA GTPase in breast cancer.
Temperature elevation and Vibrio cyclitrophicus infection reduce the diversity of haemolymph microbiome of the mussel Mytilus coruscus
Authors: Li Yi-Feng , Chen Yan-Wen , Xu Jia-Kang , Ding Wen-Yang , Shao An-Qi , Zhu You-Ting , Wang Chong , Liang Xiao , Yang Jin-Long 
Published: November 2019

AbstractHaemolymph microbiome was considered to be unique to healthy invertebrates and beneficial to the host against external pathogens, including disease resistance and maintenance of homeostasis. Here, we investigated the effects of elevated water temperature on infection of haemolymph microbiome of the hard-shelled mussel (Mytilus coruscus). Exposure toVibrio.cyclitrophicusresulted in high mortality of mussels on day nine at 27 °C. The haemolymph was collected to determine the microbiota by 16 S rRNA gene sequencing. Exposure to waterborneV.cyclitrophicusincreased the mortality of mussels that was associated with a reduction in the diversity of their microbial community. Principal coordinate analysis (PCoA) revealed that temperature was an essential factor in shaping microbial communities in mussel haemolymph.Vibrioexposure promoted the proliferation of opportunistic pathogens (e.g.,ArcobacterandFrancisella) at a lower temperature. A high abundance ofVibriopresent in live and dead mussels, at 27 °C might contribute greatly to mortality, as indicated by linear discriminant analysis effect size (LEfSe). These data suggested that the dynamics of microbial community have unique biomarker species in mussel haemolymph that could be used as health indicators. An elevated temperature may reduce the ability of bacterial elimination function against infection in mussel haemolymph.
Risk of harm from alcohol use and heavy alcohol consumption: Its association with other NCD risk factors in Thailand
Authors: Jakkaew Nalinee , Pinyopornpanish Kanokporn , Jiraporncharoen Wichuda , Wisetborisut Anawat , Jiraniramai Surin , Hashmi Ahmar , Angkurawaranon Chaisiri 
Published: November 2019

AbstractWhile there is an abundance of literature examining the relation between quantity of alcohol consumption and risk factors for non-communicable diseases (NCD), there is less evidence on whether the risk of harm from alcohol use would have a similar relationship with NCD risk factors. The study aims to determine the association between level of harm from alcohol use and NCD risk factors. A cross-sectional survey was conducted among health care workers in Thailand in 2013. The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) was used to assessed risk of harm from alcohol use. The results suggest that higher risk of harm from alcohol use was associated with two of the eight NCD risk factors among women (higher blood pressure and higher triglyceride level) and five of the eight NCD risk factors among men (smoking, physical inactivity, higher blood pressure, higher blood glucose and higher triglyceride level). For men, assessing risk of harm could be incorporated as part of NCD programs as practitioners do not have to worry about the accuracy of the alcohol quantification and conversion to standard drinks. However, among women, quantifying volume may still be needed.
Simvastatin mediates inhibition of exosome synthesis, localization and secretion via multicomponent interventions
Authors: Kulshreshtha Ankur , Singh Swati , Ahmad Mohd , Khanna Kritika , Ahmad Tanveer , Agrawal Anurag , Ghosh Balaram 
Published: November 2019

AbstractDiscovery of exosomes as modulator of cellular communication has added a new dimension to our understanding of biological processes. Exosomes influence the biological systems by mediating trans-communication across tissues and cells, which has important implication for health and disease. In absence of well-characterized modulators of exosome biogenesis, an alternative option is to target pathways generating important exosomal components. Cholesterol represents one such essential component required for exosomal biogenesis. We initiated this study to test the hypothesis that owing to its cholesterol lowering effect, simvastatin, a HMG CoA inhibitor, might be able to alter exosome formation and secretion. Simvastatin was tested for its effect on exosome secretion under various in-vitro and in-vivo settings and was found to reduce the secretion of exosome from various cell-types. It was also found to alter the levels of various proteins important for exosome production. Murine model of Acute Airway Inflammation was used for further validation of our findings. We believe that the knowledge acquired in this study holds potential for extension to other exosome dominated pathologies and model systems.
Factors Affecting Repeatability of Assessment of the Retinal Microvasculature Using Optical Coherence Tomography Angiography in Healthy Subjects
Authors: Lee Taek Hoon , Lim Hyung Bin , Nam Ki Yup , Kim Kyeungmin , Kim Jung Yeul 
Published: November 2019

AbstractVarious factors can affect repeatability of optical coherence tomography angiography (OCTA) measurements, and they have not been studied sufficiently. We aimed to investigate the factors associated with the repeatability of automated superficial retinal vessel density (VD) and foveal avascular zone (FAZ) metrics acquired from OCTA. A total of 141 normal eyes from 141 healthy subjects were included, and two consecutive macular 6 × 6-mm angiography scans were performed. VD, perfusion density (PD), and FAZ of the superficial capillary plexus were calculated automatically. Reproducibility was assessed based on intraclass correlations (ICCs) and coefficients of variation (CVs). VD (ICC: 0.824, CV: 3.898) and PD (ICC: 0.845, CV: 4.042) over the entire 6-mm scan area showed better repeatability than VD (ICC: 0.752, CV: 17.470) and PD (ICC: 0.752, CV: 18.552) in the 1-mm scan, and with respect to the obtained FAZ metrics (ICC < 0.75, CV > 10.0%). Regression analyses showed that two factors, signal strength (p = 0.004) and average VD over the total 6-mm scan area (p < 0.001), were significantly correlated with the CV of the VD. Signal strength was associated with the repeatability of OCTA measurements and should be considered in the analysis of retinal VD and FAZ.
Upregulation of Yy1 Suppresses Dilated Cardiomyopathy caused by Ttn insufficiency
Authors: Liao Dan , Chen Weiming , Tan Chia Yee , Wong Jing Xuan , Chan Pui Shi , Tan Lek Wen , Foo Roger , Jiang Jianming 
Published: November 2019

AbstractTruncating variants in TTN (TTNtv), coding for the largest structural protein in the sarcomere, contribute to the largest portion of familial and ambulatory dilated cardiomyopathy (DCM). TTN haploinsufficiency caused by TTNtv is suggested as the disease mechanism. However, it is unclear whether TTN insufficiency causes DCM. Moreover, it is unknown whether modulation of downstream pathways serves as a therapeutic strategy for DCM caused by TTN insufficiency. Here, we show that reduction of cardiac Ttn expression by adeno-associated virus mediated shRNA (Ttn shRNA) generated DCM in mouse, demonstrating impaired cardiac performance, enlarged left ventricle (LV) and reduced LV wall thickness. A screen of 10 dysregulated and selected genes identified that Yin Yang 1 (Yy1) significantly suppressed DCM caused by Ttn shRNA. Gene profiling by RNAseq showed Yy1 modulated cell growth related genes. Ttn insufficiency activated cardiomyocyte cell cycle reentry by upregulating of Ccnd1 and Ccnd2. Cardiomyocytes activated by Ttn insufficiency did not advance to S phase by EdU incorporation assay. Yy1 promoted cardiomyocyte cell cycle by further enhancing Ccnd1 and Ccnd2 and increasing DNA replication without undergoing cell division. Importantly, upregulation of Ccnd1 and Ccnd2 suppressed DCM caused by Ttn insufficiency. Our findings demonstrate that DCM caused by Ttn insufficiency can be treated by therapeutically promoting cardiac cell cycle.
Cell proliferation and invasion are regulated differently by EGFR and MRP1 in T-DM1-resistant breast cancer cells
Authors: Endo Yukinori , Lyon Sarah , Shen Yi , Mohan Nishant , Wu Wen Jin 
Published: November 2019

AbstractWe recently reported that T-DM1-resistant JIMT1 (T-DM1R-JIMT1) cells exhibited high invasive activity via EGFR and integrin cooperated pathways and gained cross-resistance to doxorubicin. Here, we show that EGFR positively coordinates with MRP1 in T-DM1R-JIMT1 cells to contribute to cross-resistance to doxorubicin. Downregulating EGFR and MRP1 inhibits T-DM1R-JIMT1 cell growth and re-sensitizes T-DM1R cells to doxorubicin, suggesting that dual targeting EGFR and MRP1 could serve as a therapeutic approach to overcome T-DM1 resistance. However, it increases cell invasion activity of T-DM1R-JIMT1 cells with molecular and cellular phenotypes similar to the breast cancer cells that express low levels of HER2 (MDA-MB-231 and BT-549 cells). Importantly, the invasion activity of MDA-MB-231 and BT-549 cells is also significantly increased after chronically exposed to T-DM1 although cell growth of MDA-MB-231 and BT-549 cells is not inhibited by T-DM1. These results highlight the importance of HER2 heterogenicity in HER-positive breast cancers treated with T-DM1. Our study also provides evidence demonstrating that proliferation and invasion activities of T-DM1R-JIMT1, and MDA-MB-231 and BT-549 cells are regulated by different mechanisms and that different aspects of cancer cell behaviors affected by targeted-therapeutics should be fully characterized in order to overcome T-DM1-resistant disease and to prevent cancer metastasis.
Signal Strength as an Important Factor in the Analysis of Peripapillary Microvascular Density Using Optical Coherence Tomography Angiography
Authors: Lim Hyung Bin , Kim Yong Woo , Nam Ki Yup , Ryu Cheon Kuk , Jo Young Joon , Kim Jung Yeul 
Published: November 2019

AbstractThe quality of the scan image is important in peripapillary circulation analysis using optical coherence tomography angiography (OCTA). We aimed to investigate the effects of signal strength (SS) on the peripapillary microvascular density acquired from OCTA. A total of 259 eyes from 259 young healthy subjects were included. Peripapillary OCTA images using 3 × 3 mm angiography scan were acquired from all participants. Subjects were divided into four groups according to the SS: SS 7, SS 8, SS 9, and SS 10. Vessel density (VD) and perfusion density (PD) of the superficial capillary plexus were calculated. VD and PD were compared among the four groups, and linear regression analyses were performed to identify and evaluate the clinical factors associated with average VD. As the SS increased from 7 to 10, the average VD and PD increased; these increases were statistically significant (all, p < 0.001). Regression analyses showed that four factors were significantly correlated with average VD: age (partial r = 0.133), average retinal nerve fiber layer thickness (partial r = 0.169), cup/disc ratio (partial r =−0.481), and SS (partial r = 0.413). SS is a significant factor affecting peripapillary microvascular density, and its influence is similar to well-known structural parameters associated with glaucoma.