Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibitive Effect of Artemether on Tumor Growth and Angiogenesis in the Rat C6 Orthotopic Brain Gliomas Model

To explore the inhibitive effect of artemether on glioma growth and angiogenesis in brain tumor bearing SD rat. MTT assay was used to evaluate the inhibitory effect of artemether treatment on C6 glioma cells. Forty SD rats which were subcutaneous planted with SD rat C6 glioma cell to establish SD rat orthotopic glioma model were divided resourcefully into 5 groups. each group was 8 rats. Length-path (a mm) and short-path (b mm) of tumor each rat was measured. Tumor volume was calculated using the following formula: V (mm3) = a2b_/6. Microvessel density (MVD) in different therapy groups was significantly lower than that in normal saline control group and brain glioma volume in different therapy groups was significantly smaller than that in normal saline control group. There were remarkably inhibitory effects of artmeter on brain glioma growth and angiogenesis in SD rats and the mechanism that artemether inhibited brain glioma growth might be penetrating the blood-brain barrier and inhibiting angiogenesis.
Digital Topology and Geometry in Medical Imaging: A Survey

Digital topology and geometry refers to the use of topologic and geometric properties and features for images defined in digital grids. Such methods have been widely used in many medical imaging applications, including image segmentation, visualization, manipulation, interpolation, registration, surface-tracking, object representation, correction, quantitative morphometry etc. Digital topology and geometry play important roles in medical imaging research by enriching the scope of target outcomes and by adding strong theoretical foundations with enhanced stability, fidelity, and efficiency. This paper presents a comprehensive yet compact survey on results, principles, and insights of methods related to digital topology and geometry with strong emphasis on understanding their roles in various medical imaging applications. Specifically, this paper reviews methods related to distance analysis and path propagation, connectivity, surface-tracking, image segmentation, boundary and centerline detection, topology preservation and local topological properties, skeletonization, and object representation, correction, and quantitative morphometry. A common thread among the topics reviewed in this paper is that their theory and algorithms use the principle of digital path connectivity, path propagation, and neighborhood analysis.
Characterization of a Unique ADP-Ribosyltransferase of Mycoplasma penetrans

ABSTRACT Mycoplasma penetrans is a urogenital tract pathogen implicated in the deterioration of the immune system in human immunodeficiency virus-infected AIDS patients. Here, we describe a 78-kDa protein from M. penetrans, designated MYPE9110, that exhibits sequence similarity to known ADP-ribosyltransferases (ADPRTs) such as Bordetella pertussis pertussis toxin and Mycoplasma pneumoniae community-acquired respiratory distress syndrome toxin. MYPE9110 possesses key amino acid residues found in all ADPRTs that are essential for ADPRT activity. Several mammalian cell proteins are ADP-ribosylated by MYPE9110, and the full-length recombinant protein exhibits a strong auto-ADP-ribosylating activity. In the absence of target proteins, MYPE9110 demonstrates a NAD-glycohydrolase activity by hydrolyzing NAD. Furthermore, this toxin elicits cytopathology in HeLa cells by inducing cytoplasmic vacuolization in the presence of ammonium chloride. The deletion of the C-terminal region of MYPE9110 significantly diminishes its binding to host cells while still exhibiting an ADPRT activity, suggesting that MYPE9110 is a member of the family of A-B ADPRT toxins.
Growth in a Biofilm Induces a Hyperinfectious Phenotype in Vibrio cholerae

ABSTRACT Biofilm formation plays a multifaceted role in the life cycles of a wide variety of microorganisms. In the case of pathogenic Vibrio cholerae, biofilm formation in its native aquatic habitats is thought to aid in persistence during interepidemic seasons and to enhance infectivity upon oral ingestion. The structure of V. cholerae biofilms has been hypothesized to protect the bacteria during passage through the stomach. Here, we directly test the role of biofilm architecture in the infectivity of V. cholerae by comparing the abilities of intact biofilms, dispersed biofilms, and planktonic cells to colonize the mouse small intestine. Not only were V. cholerae biofilms better able to colonize than planktonic cells, but the structure of the biofilm was also found to be dispensable: intact and dispersed biofilms colonized equally, and both vastly out-colonized planktonic cells. The infectious dose for biofilm-derived V. cholerae was orders of magnitude lower than that of planktonic cells. This biofilm-induced hyperinfectivity may be due in part to a higher growth rate of biofilm-derived cells during infection. These results suggest that the infectious dose of naturally occurring biofilms of V. cholerae may be much lower than previously estimated using cells grown planktonically in vitro. Furthermore, this work implies the existence of factors specifically induced during growth in a biofilm that augment infection by V. cholerae.
Electrophysiology Catheter Detection and Reconstruction From Two Views in Fluoroscopic Images

Electrophysiology (EP) studies and catheter ablation have become important treatment options for several types of cardiac arrhythmias. We present a novel image-based approach for automatic detection and 3-D reconstruction of EP catheters where the physician marks the catheter to be reconstructed by a single click in each image. The result can be used to provide 3-D information for enhanced navigation throughout EP procedures. Our approach involves two X-ray projections acquired from different angles, and it is based on two steps: First, we detect the catheter in each view after manual initialization using a graph-search method. Then, the detection results are used to reconstruct a full 3-D model of the catheter based on automatically determined point pairs for triangulation. An evaluation on 176 different clinical fluoroscopic images yielded a detection rate of 83.4%. For measuring the error, we used the coupling distance which is a more accurate quality measure than the average point-wise distance to a reference. For successful outcomes, the 2-D detection error was 1.7 mm ±1.2 mm. Using successfully detected catheters for reconstruction, we obtained a reconstruction error of 1.8 mm ±1.1 mm on phantom data. On clinical data, our method yielded a reconstruction error of 2.2 mm ±2.2 mm.
Direct Evaluation of Pseudomonas aeruginosa Biofilm Mediators in a Chronic Infection Model

ABSTRACT Biofilms contribute to Pseudomonas aeruginosa persistence in a variety of diseases, including cystic fibrosis, burn wounds, and chronic suppurative otitis media. However, few studies have directly addressed P. aeruginosa biofilms in vivo. We used a chinchilla model of otitis media, which has previously been used to study persistent Streptococcus pneumoniae and Haemophilus influenzae infections, to show that structures formed in vivo are biofilms of bacterial and host origin within a matrix that includes Psl, a P. aeruginosa biofilm polysaccharide. We evaluated three biofilm and/or virulence mediators of P. aeruginosa known to affect biofilm formation in vitro and pathogenesis in vivo—bis-(3′,5′)-cyclic dimeric GMP (c-di-GMP), flagella, and quorum sensing—in a chinchilla model. We show that c-di-GMP overproduction has a positive impact on bacterial persistence, while quorum sensing increases virulence. We found no difference in persistence attributed to flagella. We conclude from these studies that a chinchilla otitis media model provides a means to evaluate pathogenic mediators of P. aeruginosa and that in vitro phenotypes should be examined in multiple infection systems to fully understand their role in disease.
Protective Role for Macrophages in Respiratory Francisella tularensis Infection

ABSTRACT Francisella tularensis causes lethal pneumonia following infection of the lungs by targeting macrophages for intracellular replication; however, macrophages stimulated with interferon gamma (IFN-γ) can resist infection in vitro. We therefore hypothesized that the protective effect of IFN-γ against F. tularensisin vivo requires macrophages receptive to stimulation. We found that the lethality of pulmonary F. tularensis LVS infection was exacerbated under conditions of alveolar macrophage depletion and in mice with a macrophage-specific defect in IFN-γ signaling (termed mice with macrophages insensitive to IFN-γ [MIIG mice]). We previously found that treatment with exogenous interleukin 12 (IL-12) protects against F. tularensis infection; this protection was lost in MIIG mice. MIIG mice also exhibited reduced neutrophil recruitment to the lungs following infection. Systemic neutrophil depletion was found to render wild-type mice highly sensitive to respiratory F. tularensis infection, and depletion beginning at 3 days postinfection led to more pronounced sensitivity than depletion beginning prior to infection. Furthermore, IL-12-mediated protection required NADPH oxidase activity. These results indicate that lung macrophages serve a critical protective role in respiratory F. tularensis LVS infection. Macrophages require IFN-γ signaling to mediate protection, which ultimately results in recruitment of neutrophils to further aid in survival from infection.
AggNet : Deep Learning From Crowds for Mitosis Detection in Breast Cancer Histology Images

The lack of publicly available ground-truth data has been identified as the major challenge for transferring recent developments in deep learning to the biomedical imaging domain. Though crowdsourcing has enabled annotation of large scale databases for real world images, its application for biomedical purposes requires a deeper understanding and hence, more precise definition of the actual annotation task. The fact that expert tasks are being outsourced to non-expert users may lead to noisy annotations introducing disagreement between users. Despite being a valuable resource for learning annotation models from crowdsourcing, conventional machine-learning methods may have difficulties dealing with noisy annotations during training. In this manuscript, we present a new concept for learning from crowds that handle data aggregation directly as part of the learning process of the convolutional neural network (CNN) via additional crowdsourcing layer (AggNet). Besides, we present an experimental study on learning from crowds designed to answer the following questions. 1) Can deep CNN be trained with data collected from crowdsourcing? 2) How to adapt the CNN to train on multiple types of annotation datasets (ground truth and crowd-based)? 3) How does the choice of annotation and aggregation affect the accuracy? Our experimental setup involved Annot8, a self-implemented web-platform based on Crowdflower API realizing image annotation tasks for a publicly available biomedical image database. Our results give valuable insights into the functionality of deep CNN learning from crowd annotations and prove the necessity of data aggregation integration.
Characterization and Functional Analysis of AatB, a Novel Autotransporter Adhesin and Virulence Factor of Avian Pathogenic Escherichia coli

ABSTRACT Autotransporter (AT) proteins constitute a large family of extracellular proteins that contribute to bacterial virulence. A novel AT adhesin gene, aatB, was identified in avian pathogenic Escherichia coli (APEC) DE205B via genomic analyses. The open reading frame of aatB was 1,017 bp, encoding a putative 36.3-kDa protein which contained structural motifs characteristic for AT proteins: a signal peptide, a passenger domain, and a translocator domain. The predicted three-dimensional structure of AatB consisted of two distinct domains, the C-terminal β-barrel translocator domain and an N-terminal passenger domain. The prevalence analyses of aatB in APEC indicated that aatB was detected in 26.4% (72/273) of APEC strains and was strongly associated with phylogenetic groups D and B2. Quantitative real-time reverse transcription-PCR analyses revealed that AatB expression was increased during infection in vitro and in vivo. Moreover, AatB could elicit antibodies in infected ducks, suggesting that AatB is involved in APEC pathogenicity. Thus, APEC DE205B strains with a mutated aatB gene and mutated strains complemented with the aatB gene were constructed. Inactivation of aatB resulted in a reduced capacity to adhere to DF-1 cells, defective virulence capacity in vivo, and decreased colonization capacity in lung during systemic infection compared with the capacities of the wild-type strain. Furthermore, these capacities were restored in the complementation strains. These results indicated that AatB makes a significant contribution to APEC virulence through bacterial adherence to host tissues in vivo and in vitro. In addition, biofilm formation assays with strain AAEC189 expressing AatB indicated that AatB mediates biofilm formation.
Feasibility and Acceptability of a Tai Chi Chih Randomized Controlled Trial in Senior Female Cancer Survivors

Objective. The purpose of this randomized controlled trial (RCT) was to examine the feasibility and acceptability of a Tai Chi Chih (TCC) intervention in senior female cancer survivors with physical functioning limitations, and its effects on health-related quality of life (QOL). Design. This was a two-armed, parallel group, RCT with 12-weeks of Tai Chi Chih or Health Education Control. Methods. Sixty-three senior (M age = 67 years, SD = 7.15) female cancer survivors (83% breast cancer, stages I-III) with physical functioning limitations (SF-12 Health Survey role-physical & physical functioning subscales) were randomized to 12-weeks of TCC or Health Education control (HEC). Primary outcomes were feasibility and acceptability. Secondary outcomes included health-related QOL (SF-36 Health Survey), and participants’ qualitative feedback on the intervention. Results. Retention (TCC = 91%; HEC = 81%) and class attendance (TCC = 79%; HEC = 83%) rates, and satisfaction levels for both study arms were high, but did not significantly differ from one another. At one-week post-intervention, none of the SF-36 scores differed between the TCC and HEC groups. Within-group analyses revealed significant improvements in the mental component summary score in TCC (p = 0.01), but not in HEC. Qualitative analyses indicated that the TCC group felt they received mental and physical benefits, whereas HEC group reported on social support benefits and information received. Conclusion. The TCC intervention was found to be a feasible and acceptable modality for senior female cancer survivors. Future, larger definitive trials are needed to clarify TCC dosage effects on QOL in this vulnerable population.
Borrelia burgdorferi Needs Chemotaxis To Establish Infection in Mammals and To Accomplish Its Enzootic Cycle

ABSTRACT Borrelia burgdorferi, the causative agent of Lyme disease, can be recovered from different organs of infected animals and patients, indicating that the spirochete is very invasive. Motility and chemotaxis contribute to the invasiveness of B. burgdorferi and play important roles in the process of the disease. Recent reports have shown that motility is required for establishing infection in mammals. However, the role of chemotaxis in virulence remains elusive. Our previous studies showed that cheA 2, a gene encoding a histidine kinase, is essential for the chemotaxis of B. burgdorferi. In this report, the cheA 2 gene was inactivated in a low-passage-number virulent strain of B. burgdorferi. In vitro analyses (microscopic observations, computer-based bacterial tracking analysis, swarm plate assays, and capillary tube assays) showed that the cheA 2 mutant failed to reverse and constantly ran in one direction; the mutant was nonchemotactic to attractants. Mouse needle infection studies showed that the cheA 2 mutant failed to infect either immunocompetent or immunodeficient mice and was quickly eliminated from the initial inoculation sites. Tick-mouse infection studies revealed that although the mutant was able to survive in ticks, it failed to establish a new infection in mice via tick bites. The altered phenotypes were completely restored when the mutant was complemented. Collectively, these data demonstrate that B. burgdorferi needs chemotaxis to establish mammalian infection and to accomplish its natural enzootic cycle.
Adaptive Estimation of Active Contour Parameters Using Convolutional Neural Networks and Texture Analysis

In this paper, we propose a generalization of the level set segmentation approach by supplying a novel method for adaptive estimation of active contour parameters. The presented segmentation method is fully automatic once the lesion has been detected. First, the location of the level set contour relative to the lesion is estimated using a convolutional neural network (CNN). The CNN has two convolutional layers for feature extraction, which lead into dense layers for classification. Second, the output CNN probabilities are then used to adaptively calculate the parameters of the active contour functionalduring the segmentation process. Finally, the adaptive window size surrounding each contour point is re-estimated by an iterative process that considers lesion size and spatial texture. We demonstrate the capabilities of our method on a dataset of 164 MRI and 112 CT images of liver lesions that includes low contrast and heterogeneous lesions as well as noisy images. To illustrate the strength of our method, we evaluated it against state of the art CNN-based and active contour techniques. For all cases, our method, as assessed by Dice similarity coefficients, performed significantly better than currently available methods. An average Dice improvement of 0.27 was found across the entire dataset over all comparisons. We also analyzed two challenging subsets of lesions and obtained a significant Dice improvement of 0.24 with our method (p <0.001, Wilcoxon).
TPGS/Phospholipids Mixed Micelles for Delivery of Icariside II to Multidrug-Resistant Breast Cancer

The biggest challenge for the treatment of multidrug resistant cancer is to deliver a high concentration of anticancer drugs to cancer cells. Icariside II is a flavonoid from Epimedium koreanum Nakai with remarkable anticancer properties, but poor solubility and significant efflux from cancer cells limited its clinical use. In our previous study, a self-assembled mixture of micelles (TPGS–Icariside II–phospholipid complex) was successfully constructed, which could substantially increase the solubility of Icariside II and inhibit the efflux on Caco-2 cells. In this study, we evaluate the anticancer effect of the mixed micelles encapsulating Icariside II (Icar-MC) on MCF-7/ADR, a multidrug-resistant breast cancer cell line. The cellular uptake of the micelles was confirmed by fluorescent coumarin-6-loaded micelles. The IC50 of Icar-MC in MCF-7/ADR was 2-fold less than the free drug. The in vitro study showed Icar-MC induced more apoptosis and lactate dehydrogenase release. Intravenous injection of Icar-MC into nude mice bearing MCF-7/ADR xenograft resulted in a better antitumor efficacy compared with the administration of free drug, without causing significant body weight changes in mice. The antitumor effect was further verified by magnetic resonance imaging and immunohistochemical assays for Ki-67, a proliferative indicator. Moreover, Icar-MC treatment also elevated Bax/Bcl-2 ratio and the expressions of cleaved caspase-3, -8, -9 and AIFM1 in tumors. This study suggests that phospholipid/TPGS mixed micelles might be a suitable drug delivery system for Icariside II to treat multidrug resistant breast cancer.
Downlink Resource Allocation for OFDMA-Based Multiservice Networks with Imperfect CSI

This paper addresses practical implementation issues of resource allocation in OFDMA networks: inaccuracy of channel state information (CSI) available to the resource allocation unit (RAU) and diversity of subscribers' quality of service (QoS) requirements. The resource allocation problem in the considered point-to-multipoint (PMP) network is modeled as a network utility maximization (NUM) problem that allocates subcarriers, rate and power while satisfying orthogonal frequency division multiple access (OFDMA) constraints and QoS constraints defined in the service level agreement. Performance evaluation findings support our theoretical claims: a substantial data rate gain is achieved by considering the CSI imperfection and multiservice classes are supported with QoS guarantees by coordinating with a call admission control (CAC) scheme.
Porphyromonas gingivalis Lipids Inhibit Osteoblastic Differentiation and Function

ABSTRACT Porphyromonas gingivalis produces unusual sphingolipids that are known to promote inflammatory reactions in gingival fibroblasts and Toll-like receptor 2 (TLR2)-dependent secretion of interleukin-6 from dendritic cells. The aim of the present study was to examine whether P. gingivalis lipids inhibit osteoblastic function. Total lipids from P. gingivalis and two fractions, phosphoglycerol dihydroceramides and phosphoethanolamine dihydroceramides, were prepared free of lipid A. Primary calvarial osteoblast cultures derived from 5- to 7-day-old CD-1 mice were used to examine the effects of P. gingivalis lipids on mineralized nodule formation, cell viability, apoptosis, cell proliferation, and gene expression. P. gingivalis lipids inhibited osteoblast differentiation and fluorescence expression of pOBCol2.3GFP in a concentration-dependent manner. However, P. gingivalis lipids did not significantly alter osteoblast proliferation, viability, or apoptosis. When administered during specific intervals of osteoblast growth, P. gingivalis total lipids demonstrated inhibitory effects on osteoblast differentiation only after the proliferation stage of culture. Reverse transcription-PCR confirmed the downregulation of osteoblast marker genes, including Runx2, ALP, OC, BSP, OPG, and DMP-1, with concurrent upregulation of RANKL, tumor necrosis factor alpha, and MMP-3 genes. P. gingivalis total lipids and lipid fractions inhibited calvarial osteoblast gene expression and function in vivo, as determined by the loss of expression of another osteoblast differentiation reporter, pOBCol3.6GFPcyan, and reduced uptake of Alizarin complexone stain. Finally, lipid inhibition of mineral nodule formation in vitro was dependent on TLR2 expression. Our results indicate that inhibition of osteoblast function and gene expression by P. gingivalis lipids represents a novel mechanism for altering alveolar bone homeostasis at periodontal disease sites.
Requirement for Formin-Induced Actin Polymerization during Spread of Shigella flexneri

ABSTRACT Actin polymerization in the cytosol and at the plasma membrane is locally regulated by actin nucleators. Several microbial pathogens exploit cellular actin polymerization to spread through tissue. The movement of the enteric pathogen Shigella flexneri, both within the cell body and from cell to cell, depends on actin polymerization. During intercellular spread, actin polymerization at the bacterial surface generates protrusions of the plasma membrane, which are engulfed by adjacent cells. In the cell body, polymerization of actin by Shigella spp. is dependent on N-WASP activation of the Arp2/Arp3 complex. Here we demonstrate that, in contrast, efficient protrusion formation and intercellular spread depend on actin polymerization that involves activation of the Diaphanous formin Dia. While the Shigella virulence protein IpgB2 can bind and activate Dia1 (N. M. Alto et al., Cell 124:133-145, 2006), its absence does not result in a detectable defect in Dia-dependent protrusion formation or spread. The dependence on the activation of Dia during S. flexneri infection contrasts with the inhibition of this pathway observed during vaccinia virus infection.