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Hui Ma,1,2 Ping Kuen Lam,3 Wing Sum Siu,1,2 Cindy See Wai Tong,3 Kin Ki Yan Lo,3 Chi Man Koon,1,2 Xiao Xiao Wu,1,2 Xiang Li,1,2 Wen Cheng,1,2 Wai Ting Shum,1,2 Ping Chung Leung1,2 1Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, Special Administrative Region of China; 2State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants, The Chinese University of Hong Kong, Shatin, Hong Kong, Special Administrative Region of China; 3Chow Tai Fook-Cheng Yu Tung Surgical Stem Cell Research Center, Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong, Special Administrative Region of ChinaCorrespondence: Ping Chung LeungInstitute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, Special Administrative Region of ChinaTel +85222528868Email pingcleung@cuhk.edu.hkIntroduction: The biological role of mesenchymal stem cells (MSCs) in wound healing has been demonstrated. However, there were limited studies on the healing effect of secretome which consists of many biological factors secreted by MSCs. In this study, we aimed to compare the therapeutic effects of secretome with MSCs on facilitating wound healing.Methods: Green fluorescent protein labelled adipose-derived MSCs (GFP-ADMSCs) or secretome was injected in the full-thickness skin excision model on SD rats. The wound healing process was evaluated by calculating the healing rate and the histological examinations on skin biopsy. The cell viability, proliferation and mobility of the rat dermal fibroblasts were compared after different treatments. The inflammatory response in macrophages was indicated by the level of nitric oxide (NO) and inflammatory cytokines through NO assay and ELISA.Results: On day 5 and day 14, both MSCs and secretome accelerated the wound healing, secretome further enhanced the process. GFP-MSCs were detected 10 days after transplantation. The level of IL-6 and TNF-α in blood was reduced after MSCs and secretome treatments. The expressions of VEGF and PCNA were increased after treatment, higher intensity of VEGF was observed in secretome-injected tissue. The concentrations of total protein and VEGF in secretome were 2.2 ± 0.5 mg/mL and 882.0 ± 72.7 pg/mL, respectively. The cell viability and proliferation of FR were promoted significantly after the treatment. The scratch test showed that secretome accelerated the wound healing speed. Secretome reduced the metabolism of macrophages remarkably, but it did not decrease the level of macrophage-secreted NO. The expression of the pro-inflammatory cytokines (IL-6, MCP-1 and TNF-α) was downregulated significantly.Conclusion: Our study indicated both MSCs and MSCs-derived secretome enhanced the wound healing process in early phase. Secretome further promoted the healing effects through promoting the fibroblast proliferation and migration and suppressing the inflammatory response.Keywords: MSCs, secretome, wound healing, local injection, skin

Objective: To evaluate real-time shear wave ultrasound elastography (SWE) for characterizing focal thyroid lesions in routine clinical practice.Methods: Seventy-four patients with 81 focal thyroid lesions undergoing conventional US with needle cytology also underwent SWE. Absolute and relative SWE stiffness measurements on colour-coded elastograms were correlated with cytology and their discriminatory performances assessed.Results: Seventeen nodules were malignant (13 papillary, 4 other cancers), 45 benign (43 hyperplastic nodules, 2 focal thyroiditis), 5 indeterminate ("follicular lesions"), and 5 had inadequate cytology. SWE results were higher in malignant than benign nodules (P values 0.02-0.05) although their discriminatory performances were mediocre (AUCs 0.58-0.74). The most accurate SWE cut-off, 34.5 kPa for a 2-mm region of interest, achieved 76.9 % sensitivity and 71.1 % specificity for discriminating papillary cancer from benign nodules. No thresholds produced high sensitivity without lowering specificity appreciably, and vice versa. Nodule size correlated with SWE for benign nodules (P < 0.01). Intranodular cystic change or calcification did not influence SWE. Qualitatively, elastographic artefacts and foci lacking colour elasticity signal occurred in some solid nodules.Conclusion: Although malignant nodules are generally stiffer than benign nodules, the precision results do not suggest a definitive role for SWE, at present, in identifying or excluding thyroid malignancy.Key Points: • Shear wave ultrasound elastography (SWE) offers new insight into thyroid disease. • Papillary cancers have higher SWE indices (equating to higher stiffness) than benign nodules. • SWE appears limited in terms of identifying or excluding thyroid malignancy accurately. • Vertically aligned elastographic artefacts can occur in thyroid SWE. • Areas lacking SWE colour signal can occur in some solid thyroid nodules. [ABSTRACT FROM AUTHOR]

Actin assembly and dynamics are crucial for maintaining cell structure and changing physiological states. The broad impact of actin on various cellular processes makes it challenging to dissect the specific role of actin regulatory proteins. Using actin waves that propagate on the cortex of mast cells as a model, we discovered that formins (FMNL1 and mDia3) are recruited before the Arp2/3 complex in actin waves. GTPase Cdc42 interactions drive FMNL1 oscillations, with active Cdc42 and the constitutively active mutant of FMNL1 capable of forming waves on the plasma membrane independently of actin waves. Additionally, the delayed recruitment of Arp2/3 antagonizes FMNL1 and active Cdc42. This antagonism is not due to competition for monomeric actin but rather for their common upstream regulator, active Cdc42, whose levels are negatively regulated by Arp2/3 via SHIP1 recruitment. Collectively, our study highlights the complex feedback loops in the dynamic control of the actin cytoskeletal network., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The coordination between actin and microtubule network is crucial, yet this remains a challenging problem to dissect and our understanding of the underlying mechanisms remains limited. In this study, we used travelling waves in the cell cortex to characterize the collective dynamics of cytoskeletal networks. Our findings show that Cdc42 and F-BAR-dependent actin waves in mast cells are mainly driven by formin-mediated actin polymerization, with the microtubule-binding formin FH2 domain-containing protein 1 (FHDC1) as an early regulator. Knocking down FHDC1 inhibits actin wave formation, and this inhibition require FHDC1's interaction with both microtubule and actin. The phase of microtubule depolymerization coincides with the nucleation of actin waves and microtubule stabilization inhibit actin waves, leading us to propose that microtubule shrinking and the concurrent release of FHDC1 locally regulate actin nucleation. Lastly, we show that FHDC1 is crucial for multiple cellular processes such as cell division and migration. Our data provided molecular insights into the nucleation mechanisms of actin waves and uncover an antagonistic interplay between microtubule and actin polymerization in their collective dynamics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Tong, Su, Sun, Chua, Xiong, Guo, Raj, Ong, Lee, Miao and Wu.)

While rhythmic contractile behavior is commonly observed at the cellular cortex, the primary focus has been on excitable or periodic events described by simple activator-delayed inhibitor mechanisms. We show that Rho GTPase activation in nocodazole-treated mitotic cells exhibits both simple oscillations and complex mixed-mode oscillations. Rho oscillations with a 20- to 30-s period are regulated by phosphatidylinositol (3,4,5)-trisphosphate (PIP 3 ) via an activator-delayed inhibitor mechanism, while a slow reaction with period of minutes is regulated by phosphatidylinositol 4-kinase via an activator-substrate depletion mechanism. Conversion from simple to complex oscillations can be induced by modulating PIP 3 metabolism or altering membrane contact site protein E-Syt1. PTEN depletion results in a period-doubling intermediate, which, like mixed-mode oscillations, is an intermediate state toward chaos. In sum, this system operates at the edge of chaos. Small changes in phosphoinositide metabolism can confer cells with the flexibility to rapidly enter ordered states with different periodicities., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Clinicians need reliable outcome predictors to improve the prognosis of septic patients. Mouse models are widely used in sepsis research. We aimed to review how mouse models were used to search for novel prognostic biomarkers of sepsis in order to optimize their use for future biomarker discovery., Methods: We searched PubMed from 2012 to July 2022 using "((sepsis) AND (mice)) AND ((prognosis) OR (prognostic biomarker))"., Results: A total of 412 publications were retrieved. We selected those studies in which mouse sepsis was used to demonstrate prognostic potential of biomarker candidates and/or assist the subsequent evaluation in human sepsis for further appraisal. The most frequent models were lipopolysaccharide (LPS) injection and caecal ligation and puncture (CLP) using young male mice. Discovery technologies applied on mice include setting survival and nonsurvivable groups, detecting changes of biomarker levels and measuring physiological parameters during sepsis. None of the biomarkers achieved sufficient clinical performance for clinical use., Conclusions: The number of studies and strategies using mouse models to discover prognostic biomarkers of sepsis are limited. Current mouse models need to be further optimized to better conform to human sepsis. Current biomarker platforms do not achieve predictive performance for clinical use., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

C-reactive protein (CRP) is an acute phase reactant secreted by hepatocytes as a pentamer. The structure formation of pentameric CRP has been demonstrated to proceed in a stepwise manner in live cells. Here, we further dissect the sequence determinants that underlie the key steps in cellular folding and assembly of CRP. The initial folding of CRP subunits depends on a leading sequence with a conserved dipeptide that licenses the formation of the hydrophobic core. This drives the bonding of the intra-subunit disulfide requiring a favorable niche largely conferred by a single residue within the C-terminal helix. A conserved salt bridge then mediates the assembly of folded subunits into pentamer. The pentameric assembly harbors a pronounced plasticity in inter-subunit interactions, which may form the basis for a reversible activation of CRP in inflammation. These results provide insights into how sequence constraints are evolved to dictate structure and function of CRP., (Copyright © 2020 Lv, Chen, Liu, Yao, Wu, Tong and Cheng.)

Background: The neuroprotective effects of mesenchymal stem cells (MSCs) have been reported in rodent and in preliminary clinical studies. MSCs are usually transplanted to patients by systemic infusion. However, only a few of the infused MSCs are delivered to the brain because of pulmonary trapping and the blood-brain barrier. In this study, MSCs were topically applied to the site of traumatic brain injury (TBI) and the neuroprotective effects were assessed., Materials and Methods: TBI was induced in Sprague-Dawley (SD) rats with an electromagnetically controlled cortical impact device after craniotomy was performed between the bregma and lambda, 1 mm lateral to the midline. We applied 1.5 million MSCs, derived from the adipose tissue of transgenic green fluorescent protein (GFP)-SD rats, to the exposed cerebral cortex at the injured site. The MSCs were held in position by a thin layer of fibrin. Neurological function in the test (n = 10) and control (n = 10) animals was evaluated using the rotarod test, the water maze test, and gait analysis at different time points., Results: Within 5 days following topical application, GFP-positive cells were found in the brain parenchyma. These cells co-expressed with markers of Glial fibrillary acidic protein (GFAP), nestin, and NeuN. There was less neuronal death in CA1 and CA3 of the hippocampus in the test animals. Neurological functional recovery was significantly improved., Conclusion: Topically applied MSCs can migrate to the injured brain parenchyma and offer neuroprotective effects.

Objective: To evaluate the morphologic changes of aldosterone-producing adenoma (APA) on computed tomography (CT) before and after radiofrequency ablation (RFA) and to assess the factors that are important in determining successful complete ablation of these tumours., Method: Between August 2004 and August 2011, 24 consecutive patients with APA undergoing CT-guided percutaneous RFA were identified from our prospective database. The pre-RFA and post-RFA CT appearances of these APAs that showed positive biochemical response were reviewed retrospectively for their 3-dimensional size, tumour volume, and CT attenuation in terms of Hounsfield units (HU). A comparison of these parameters before and after RFA was performed., Results: In this study, there were 23 APAs in these 24 patients that showed biochemical cure of primary aldosteronism after RFA. When comparing post-RFA to pre-RFA CTs, there was no significant change in tumour size (14.5 mm vs 14.6 mm: P = .83) and tumour volume (1.55 cm(3) vs 1.59 cm(3); P = .41) after RFA. In nonenhanced CT images, there was no significant reduction in HU from pre-RFA to post-RFA measurements (4.4 HU vs 7.9 HU; P = .52). In contrast-enhanced CTs, there was a significant drop in HU after RFA (from 48.3 HU to 14.7 HU; P = .03). None of the included cases showed a focal region of contrast enhancement to suggest residual tumour., Conclusion: A change in tumour size, tumour volume, and HU in nonenhanced CT were unreliable in defining radiologic treatment success. Only changes in HU in contrast-enhanced CT was useful in confirming a positive treatment response after RFA for APA., (Copyright © 2014 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.)

Purpose: This study compares the diagnostic performance of multidetector CT arthrography (CTA), conventional 3-T MR and MR arthrography (MRA) in detecting intrinsic ligament and triangular fibrocartilage complex (TFCC) tears of the wrist., Materials and Methods: Ten cadaveric wrists of five male subjects with an average age 49.6years (range 26-59years) were evaluated using CTA, conventional 3-T MR and MRA. We assessed the presence of scapholunate ligament (SLL), lunotriquetral ligament (LTL), and TFCC tears using a combination of conventional arthrography and arthroscopy as a gold standard. All images were evaluated in consensus by two musculoskeletal radiologists with sensitivity, specificity, and accuracy being calculated., Results: Sensitivities/specificity/accuracy of CTA, conventional MRI, and MRA were 100%/100%/100%, 66%/86%/80%, 100%/86%/90% for the detection of SLL tear, 100%/80%/90%, 60%/80%/70%, 100%/80%/90% for the detection of LTL tear, and 100%/100%/100%, 100%/86%/90%, 100%/100%/100% for the detection of TFCC tear. Overall CTA had the highest sensitivity, specificity, and accuracy among the three investigations while MRA performed better than conventional MR. CTA also had the highest sensitivity, specificity, and accuracy for identifying which component of the SLL and LTL was torn. Membranous tears of both SLL and LTL were better visualized than dorsal or volar tears on all three imaging modalities., Conclusion: Both CT and MR arthrography have a very high degree of accuracy for diagnosing tears of the SLL, LTL, and TFCC with both being more accurate than conventional MR imaging.

Our purpose is to compare ultrasound and fluoroscopic-guided approaches to the glenohumeral joint at the rotator cuff interval for magnetic resonance (MR) arthrography of the shoulder. Forty consecutive patients were prospectively studied. 20 patients underwent ultrasound-guided and 20 patients underwent fluoroscopic guided injection. Successful rate of ultrasound guidance is 95%. No significant difference in pain score and duration of injection between two methods (P>.05). Ultrasound-guided rotator cuff interval injection of the glenohumeral joint for MR arthrography is comparable with fluoroscopic-guided injection. Ultrasound is the preferred method as there is no ionizing radiation., (Copyright © 2013 Elsevier Inc. All rights reserved.)

This paper investigates the organic pollution status of shallow aquifer sediments and groundwater around Zhoukou landfill. Chlorinated aliphatic hydrocarbons, monocylic aromatic hydrocarbons, halogenated aromatic hydrocarbons, organochlorine pesticides and other pesticides, and polycyclic aromatic hydrocarbons (PAHs) have been detected in some water samples. Among the detected eleven PAHs, phenanthrene, fluorine, and fluoranthene are the three dominant in most of the groundwater samples. Analysis of groundwater samples around the landfill revealed concentrations of PAHs ranging from not detected to 2.19 μg/L. The results show that sediments below the waste dump were low in pollution, and the shallow aquifer, at a depth of 18-30 m, was heavily contaminated, particularly during the wet season. An oval-shaped pollution halo has formed, spanning 3 km from west to east and 2 km from south to north, and mainly occurs in groundwater depths of 2-4 m. For PAH source identification, both diagnostic ratios of selected PAHs and principal component analysis were studied, suggesting mixed sources of pyro- and petrogenic derived PAHs in the Zhoukou landfill. Groundwater table fluctuations play an important role in the distribution of organic pollutants within the shallow aquifer. A conceptual model of leachate migration in the Quaternary aquifers surrounding the Zhoukou landfill has been developed to describe the contamination processes based on the major contaminant (PAHs). The groundwater zone contaminated by leachate has been identified surrounding the landfill.

Wavefront sensing systems measure the slope or curvature of a surface by calculating the centroid displacement of two focal spot images. Accurately finding the centroid of each focal spot determines the measurement results. This paper studied several widely used centroid-finding techniques and observed that thresholding is the most critical factor affecting the centroid-finding accuracy. Since the focal spot image of a freeform surface usually suffers from various types of image degradation, it is difficult and sometimes impossible to set a best threshold value for the whole image. We propose an adaptive centroid-finding algorithm to tackle this problem and have experimentally proven its effectiveness in measuring freeform surfaces.

Purpose: To evaluate the reliability of shear wave ultrasound elastography (SWE) in the neck., Materials and Methods: 176 neck lesions (40 thyroid, 56 lymph nodes, 46 salivary, 34 miscellaneous) identified in a routine US clinic underwent SWE by one or two blinded radiologists. For this study, SWE required the operator to acquire three 10 second dynamic colour-coded SWE cineloops per lesion, select one static image per cineloop, and place circular regions-of-interest within the entire lesion and stiffest part to generate 3 SWE measurements per static image. For logistical reasons, one radiologist evaluated all 176 lesions and the other evaluated 58 lesions. Both radiologists also reviewed 27 archived cineloops independently to assess SWE excluding practical technique. Reliability was assessed using intraclass correlation coefficients (ICCs) concordance correlation coefficients (CCCs) and coefficients of repeatability (CORs)., Results: Test-retest ICCs for the radiologist evaluating 176 lesions were 0.78 - 0.85 (fair-excellent agreement), CCCs were 0.85 - 0.88 (substantial agreement), and CORs were 14.9 - 36.1 kPa. For both radiologists evaluating 58 lesions, intra-rater and inter-rater ICCs were 0.65 - 0.78 and 0.72 - 0.77 respectively. For SWE excluding practical technique, inter-rater ICCs were 0.97 - 0.98 (excellent agreement). ICCs differed according to tissue, being higher in thyroid lesions than lymph nodes (p < 0.001), and higher in benign than malignant lesions (p values < 0.001)., Conclusion: Intra- and inter-rater reliability of SWE is fair to excellent according to ICCs. SWE reliability is influenced appreciably by acquisition technique. Nevertheless, CORs for SWE are not negligible. To determine whether these results are acceptable clinically, further research is required to establish SWE stiffness values of normal and pathological tissues in the neck., (© Georg Thieme Verlag KG Stuttgart · New York.)

A pilot study was performed to evaluate shear wave ultrasound elastography (SWE) for miscellaneous non-nodal/salivary/thyroid neck lesions. Forty-six lesions undergoing conventional sonography also underwent SWE. Elastic moduli from the stiffest areas in lesions were correlated with diagnosis. Forty lesions were benign (9 lipomas, 8 lymphatic/venous vascular malformations, 7 thyroglossal duct cysts, 4 branchial cleft cysts, 4 abscesses/phlegmons, 3 neurogenic tumors and 1 each of paraganglioma, sebaceous cyst, pseudotumor, hypertrophic scar, ranula) and 6 were malignant (1 malignant fibrous histiocytoma, 2 primary squamous cell carcinomas and 3 intramuscular metastases [2 squamous cell carcinomas, 1 malignant melanoma]).Median stiffness of malignant lesions (226.4 kPa, range 55.6 to 300.0) was higher than benign lesions (28.3 kPa, range 4.0 to 300.0) (p < 0.001). SWE cut-off with highest accuracy (174.4 kPa) achieved 83.3% sensitivity and 97.5% specificity, and the cut-off with 100% sensitivity (55.6 kPa) achieved 75% specificity. All malignant lesions were suspected on conventional sonography. The preliminary data indicate that SWE is feasible for miscellaneous neck lesions. SWE would not have altered management in terms of detecting undisclosed malignancies, although as a quantitative technique, it may increase the diagnostic confidence of less experienced operators performing head and neck ultrasound., (Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate shear wave elastography (SWE) for focal lesions in major salivary glands., Methods: Sixty lesions (49 parotid, 11 submandibular) undergoing routine ultrasound (grey scale and Doppler) also underwent SWE before US-guided needle aspiration for cytology. Quantitative indices of the shear elastic modulus (stiffness) were compared with cytological results., Results: Fifty-five lesions were benign (21 pleomorphic adenomas, 18 Warthin's tumours; 16 others) and 5 malignant (2 mucoepidermoid carcinomas, 1 myoepithelial carcinoma, 1 B-cell lymphoma, 1 nodal metastasis). Shear modulus of benign lesions, median 18.3 kPa, overlapped appreciably with malignant lesions, median 13.5 kPa. However, 2 mucoepidermoid carcinomas had the highest stiffness values (81.9 kPa, 132.0 kPa). Stiffness of pleomorphic adenomas (median 22.5 kPa) was higher than Warthin's tumours (16.9 kPa) (P = 0.05 Mann-Whitney U-test). The standard deviation of stiffness values within a lesion, used as an indicator of spatial heterogeneity, was highest in mucoepidermoid cancers (median 44.2 kPa), followed by pleomorphic adenomas (median 12.4 kPa) and remaining lesions (medians 1.4-10.3 kPa)., Conclusion: This study shows a degree of clustering of SWE indices according to pathology although it appears that SWE has suboptimal performance for ruling out malignancy, thus limiting its use in routine practice., Key Points: • Shear wave elastography is a feasible technique for focal salivary gland lesions. • Elastographic artefacts aggravated by the regional anatomy may hinder this technique. • Elastographic indices vary according to pathology but there is appreciable overlap. • Overlapping indices for malignant and benign lesions limit its utility. • Pleomorphic adenomas have higher elasticity indices, i.e. are stiffer, than Warthin's tumours.

A pilot study of real-time shear wave ultrasound elastography (SWE) for cervical lymphadenopathy in routine clinical practice was conducted on 55 nodes undergoing conventional ultrasound (US) with US-guided needle aspiration for cytology. Elastic moduli of stiffest regions in nodes were measured on colour-coded elastograms, which were correlated with cytology. Malignant nodes (n = 31, 56.4%) were stiffer (median 25.0 kPa, range 6.9-278.9 kPa) than benign nodes (median 21.4 kPa, range 8.9-30.2 kPa) (p = 0.008, Mann Whitney U test). A cut-off of 30.2 kPa attained highest accuracy of 61.8%, corresponding to 41.9% sensitivity, 100% specificity and 0.77 area under the receiver operating characteristic curve. Qualitatively, elastograms of benign nodes were homogeneously soft; malignant nodes were homogeneously soft or markedly heterogeneous with some including regions lacking elasticity signal. SWE is feasible for neck nodes. It appears unsuitable for cancer screening but may detect a subset of malignant nodes. The cause of spatial heterogeneity of malignant nodes on SWE is yet to be established., (Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

We describe the uncommon development of leptomeningeal lipomatosis in a girl with encephalocraniocutaneous lipomatosis (ECCL). Leptomeningeal involvement had not been present at 2 years of age, but was demonstrated on CT and MRI at 10 years of age. Our case demonstrates follow-up neuroimaging features of ECCL that may be helpful to radiologists in suggesting the correct diagnosis, as ocular and cutaneous lesions may be non-specific clinically. The developmental nature of leptomeningeal involvement in our case suggests that close clinical and radiological follow-up is important in children with suspected or established ECCL.

This paper presents a multiphase fuzzy region competition model that takes into account spatial and frequency information for image segmentation. In the proposed energy functional, each region is represented by a fuzzy membership function and a data fidelity term that measures the conformity of spatial and frequency data within each region to (generalized) gaussian densities whose parameters are determined jointly with the segmentation process. Compared with the classical region competition model, our approach gives soft segmentation results via the fuzzy membership functions, and moreover, the use of frequency data provides additional region information that can improve the overall segmentation result. To efficiently solve the minimization of the energy functional, we adopt an alternate minimization procedure and make use of Chambolle's fast duality projection algorithm. We apply the proposed method to synthetic and natural textures as well as real-world natural images. Experimental results show that our proposed method has very promising segmentation performance compared with the current state-of-the-art approaches.

The modeling of image data by a general parametric family of statistical distributions plays an important role in many applications. In this paper, we propose to adopt the three-parameter generalized Gamma density (GGammaD) for modeling wavelet detail subband histograms and for texture image retrieval. The advantage of GGammaD over the existing generalized Gaussian density (GGD) is that it provides more flexibility to control the shape of model which is critical for practical histogram-based applications. To measure the discrepancy between GGammaDs, we use the symmetrized Kullback-Leibler distance (SKLD) and derive a closed form for the SKLD between GGammaDs. Such a distance can be computed directly and effectively via the model parameters, making our proposed scheme particularly suitable for image retrieval systems with large image database. Experimental results on the well-known databases reveal the superior performance of our proposed method compared with the current existing approaches.

This article presents a novel and effective multistage system for classifying Chinese Materia Medica microscopic starch grain images. The proposed classification system is constructed based on the Gaussian mixture model-based clustering, the feature assignment algorithm, and the similarity measurement. Several features for each starch grain image are extracted and every class of drug is represented by a set of characteristic features. For each stage of the system, only one feature is chosen and assigned to that stage via the feature assignment algorithm, and the corresponding characteristic features are subdivided into smaller subsets based on clustering techniques. At the final stage, each subset contains a certain class of drugs (with corresponding characteristic features) and similarity measurement is carried out for starch grain classification. Three sets of the current state-of-the-art starch grain features including the granulometric size distribution, the chord length distribution, and the wavelet signature are used to construct the system. Experimental results on a database of 240 images of 24 classes of drugs reveal the superior performance of the multistage system. Comparison with the traditional starch grain classification approaches indicates that our proposed multistage method produces a marked improvement in classification performance., ((c) 2009 Wiley-Liss, Inc.)

Dendritic spines play an essential role in the central nervous system. Recent experiments have revealed that neuron functional properties are highly correlated with the statistical and morphological changes of the dendritic spines. In this paper, we propose a new multi scale approach for detecting dendritic spines in a 2D Maximum Intensity Projection (MIP) image of the 3D neuron data stacks collected from a 2-photon laser scanning confocal microscope. The proposed method utilizes the curvilinear structure detector in conjunction with the multi scale spine detection algorithm which automatically and accurately extracts and segments the spines with variational sizes along the dendrite. In addition, a slice-based spine detection algorithm is also proposed to detect spines which are hidden from the MIP image within the dendrite area. Experimental results show that our proposed method is effective for automatic spine detection and is able to accurately segment dendrite.

Acetaminophen is a commonly used drug for the treatment of patients with common cold and influenza. However, an overdose of acetaminophen may be fatal. In this study we investigated whether mice, administered intraperitoneally with a lethal dose of acetaminophen, when followed by oral administration of Phyllanthus urinaria extract, may be prevented from death. Histopathological analysis of mouse liver sections showed that Phyllanthus urinaria extract may protect the hepatocytes from acetaminophen-induced necrosis. Therapeutic dose of Phyllanthus urinaria extract did not show any toxicological phenomenon on mice. Immunohistochemical staining with the cytochrome P450 CYP2E1 antibody revealed that Phyllanthus urinaria extract reduced the cytochrome P450 CYP2E1 protein level in mice pre-treated with a lethal dose of acetaminophen. Phyllanthus urinaria extract also inhibited the cytochrome P450 CYP2E1 enzymatic activity in vitro. Heavy metals, including arsenic, cadmium, mercury and lead, as well as herbicide residues were not found above their detection limits. High performance liquid chromatography identified corilagin and gallic acid as the major components of the Phyllanthus urinaria extract. We conclude that Phyllanthus urinaria extract is effective in attenuating the acetaminophen induced hepatotoxicity, and inhibition of cytochrome P450 CYP2E1 enzyme may be an important factor for its therapeutic mechanism.

A series of 2,6-dimethoxylpyridinyl phosphine oxides have been synthesized and examined for their antitumor activity. 2,6-Dimethoxy-3-phenyl-4-diphenylphosphinoylpyridine 2 has been employed as the lead compound for this study. We found out that the presence of phosphine oxide on the 2,6-dimethoxylpyridine ring is important for the antitumor activity; the presence of bromine on this core leads to a further enhancement of its antitumor activity. This is the first reported work on the antitumor activity of the 2,6-dimethoxy-3,5-dibromopyridinyl phosphine oxide 5b towards MDAMB-231 breast cancer and SKHep-1 hepatoma cell lines.

As tradition Chinese herbal medicine becomes increasingly popular, there is an urgent need for efficient and accurate methods for the authentication of the Chinese Materia Medica (CMM) used in the herbal medicine. In this work, we present a denoising filter and introduce the use of chord length distribution (CLD) for the classification of starch grains in microscopic images of Chinese Materia Medica. Our simple denoising filter is adaptive to the background and is shown to be effective to remove noise, which appears in CMM microscopic starch grains images. The CLD is extracted by considering the frequency of the chord length in the binarized starch grains image, and we shall show that the CLD is an efficient and effective characterization of the starch grains. Experimental results on 240 starch grains images of 24 classes show that our method outperforms benchmark result using the current state-of-the-art method based on circular size distribution extracted by morphological operators at much higher computational cost.

The modeling of wavelet subband histograms via the product Bernoulli distributions (PBD) has received a lot of interest and the PBD model has been applied successfully in texture image retrieval. In order to fully understand the usefulness and effectiveness of the PBD model and its associated signature, namely, the bit-plane probability (BP) signature on image processing applications, we discuss and investigate some of their statistical properties. These properties would help to clarify the sufficiency of the BP signature to characterize wavelet subbands, which, in turn, justifies its use in real time applications. We apply the BP signature on supervised texture classification problem and experimental results suggest that the weighted L(1)-norm (rather than the standard L (1)-norm) should be used for the BP signature. Comparative classification experiments show that our method outperforms the current state-of-the-art Generalized Gaussian Density approaches.

This study demonstrates the feasibility of feature extraction and similarity measurement for the identification of starch grains, which are often found in microscopic images of Chinese Materia Medica (CMM) and as such is an important feature for use in the authentication of CMM with abundance of starch grains and otherwise without other special microscopic characteristics. Our proposed image signature, namely, the size distribution, indicates that it is effective to characterize starch grains in microscopic images of those CMM. Experimental results in a small scale study show that the recognition rate for the proposed signature using different measures of discrepancy is around 90%, which is considered very good while the benchmark wavelet-based energy signature has only about 60% recognition. Moreover, the extraction of the size distribution only requires moderate level of computational complexity. In this study, our proposed image signature provides greater accuracy and flexibility in capturing starch grains information for the authentication of CMM, compared with other existing preliminary identification approach in which manual image segmentation is necessary., (Copyright (c) 2007 Wiley-Liss, Inc.)

This paper presents a novel, effective, and efficient characterization of wavelet subbands by bit-plane extractions. Each bit plane is associated with a probability that represents the frequency of 1-bit occurrence, and the concatenation of all the bit-plane probabilities forms our new image signature. Such a signature can be extracted directly from the code-block code-stream, rather than from the de-quantized wavelet coefficients, making our method particularly adaptable for image retrieval in the compression domain such as JPEG2000 format images. Our signatures have smaller storage requirement and lower computational complexity, and yet, experimental results on texture image retrieval show that our proposed signatures are much more cost effective to current state-of-the-art methods including the generalized Gaussian density signatures and histogram signatures.

Objectives: Paraoxonase (PON1), an enzyme associated with high-density lipoprotein (HDL) particles, inhibits oxidation and atherogenesis. We sought to investigate the association of the PON1 Q192R polymorphism with stroke and heart disease., Design and Methods: In a case control study, we genotyped 242 ischemic stroke, 231 myocardial infarction (MI), and 310 healthy control subjects, all Chinese., Results: R-containing genotypes (R+) were associated with vascular disease, OR = 1.5, P = 0.03. RR was increased in MI patients who were either smokers (OR = 3.1, P = 0.01), male, or younger than 60. R+ but not RR genotypes were increased in stroke patients, particularly large artery type (OR = 2.6 and P = 0.02 for R+, OR = 1.0 for RR) or among smokers. The relative dearth of RR in stroke might be due to earlier MI or death in at-risk people, such as smokers. R+ genotypes were increased with stroke in hypertensive (OR = 2.1, P = 0.02) but not normotensive (OR = 1.0) subjects., Conclusions: PON1 192R+ genotypes were associated with stroke and MI, particularly in subsets of patients, in patterns suggesting a possible survivor effect.

Background: Because apolipoprotein E (apoE) and lipopoprotein lipase (LPL) polymorphisms interact with each other and with other factors to affect lipid metabolism, we sought to determine their separate and combined effects in association with ischemic vascular disease., Methods: We performed a case-control study of 816 subjects: 246 acute ischemic stroke patients, 234 acute myocardial infarction patients, and 336 controls. APOE exon 4 and LPL S447X genotypes were determined., Results: APOE epsilon2 and epsilon4 homozygotes were increased in stroke (4.5% vs. 1.0%, p = 0.008), while in myocardial infarction the epsilon4 allele was increased (12.6% vs. 9.5%, p = 0.006) but epsilon2 was decreased (3.7% vs. 12.1%, p = 0.000006). For subjects with either APOE epsilon2 or epsilon4 alleles, LPL X alleles were increased in vascular disease (OR = 2.2, p = 0.01). LPL X alleles displayed opposite tendencies toward association with disease when subjects were divided by sex, smoking, or APOE genotype. Meta-analysis and regression analysis of previous studies supported the sex and smoking dichotomies., Conclusion: This is the first report of an association of vascular disease with an interaction of APOE exon 4 and LPL S447X genotypes. Therefore, APOE genotypes and LPL S447X interactions with apoE, sex, and smoking may affect the risk of myocardial infarction and ischemic stroke.

Background: Vascular endothelial growth factor (VEGF) and endostatin stimulate and inhibit tumour angiogenesis respectively. Recent studies have demonstrated the prognostic value of serum levels of both VEGF and endostatin in patients with various types of cancer. Their significance in patients with hepatocellular carcinoma (HCC) remains unclear., Methods: Serum VEGF and endostatin levels were measured by enzyme immunoassay in 108 patients with HCC before surgical resection and in 20 healthy controls. Preoperative serum VEGF and endostatin levels were correlated with clinicopathological features and long-term survival., Results: Serum VEGF levels in patients with HCC were significantly higher than those in controls, but serum levels of endostatin were similar in the two groups. High serum levels of VEGF, but not endostatin, were significantly associated with venous invasion and advanced tumour stage. Patients with a serum VEGF level higher than median (over 245.0 pg/ml) had significantly worse overall and disease-free survival than those with a lower level (P = 0.012 and P = 0.022 respectively). On multivariate analysis, serum VEGF level was an independent prognostic factor (hazard ratio 1.86 (95 per cent confidence interval 1.10 to 3.92); P = 0.032). Serum endostatin levels did not have significant prognostic influence on overall or disease-free survival., Conclusion: A high serum level of VEGF is a predictor of poor outcome after resection of HCC. Serum VEGF, but not endostatin, may be a useful prognostic marker in patients with HCC., (Copyright (c) 2004 British Journal of Surgery Society Ltd)

Aim: To evaluate the correlation between serum vascular cellular adhesion molecule-1 (VCAM-1) levels and clinicopathological features in patients with hepatocellular carcinoma (HCC)., Methods: Ninety-six patients who underwent HCC resection were recruited in the study. Preoperative serum levels of soluble VCAM-1 were measured by enzyme-linked immunosorbent assay., Results: Serum VCAM-1 level in HCC patients was inversely correlated with platelet count (r=-0.431, P<0.001) and serum albumin level (r=-0.279, P<0.001), and positively correlated with serum bilirubin level (r=0.379, P<0.001). Serum VCAM-1 level was not associated with tumor characteristics such as tumor size, venous invasion, presence of microsatellite nodules, tumor grade and tumor stage. Serum VCAM-1 level was significantly higher in HCC patients with cirrhosis compared with those without cirrhosis (median 704 vs 546 ng/mL, P<0.001). Furthermore, a significantly better disease-free survival was observed in HCC patients with low VCAM-1 level (P=0.019)., Conclusion: Serum VCAM-1 level appears to reflect the severity of underlying chronic liver disease rather than the tumor status in HCC patients, and low preoperative serum VCAM-1 level is predictive of better disease-free survival after surgery.

Fractal image encoding is a computationally intensive method of compression due to its need to find the best match between image subblocks by repeatedly searching a large virtual codebook constructed from the image under compression. One of the most innovative and promising approaches to speed up the encoding is to convert the range-domain block matching problem to a nearest neighbor search problem. This paper presents an improved formulation of approximate nearest neighbor search based on orthogonal projection and pre-quantization of the fractal transform parameters. Furthermore, an optimal adaptive scheme is derived for the approximate search parameter to further enhance the performance of the new algorithm. Experimental results showed that our new technique is able to improve both the fidelity and compression ratio, while significantly reduce memory requirement and encoding time.

FoxM1 (previously named WIN, HFH-11 or Trident) is a Forkhead box (Fox) transcription factor widely expressed in proliferating cells. Various findings, including a recent analysis of FoxM1 knockout mice, suggest that FoxM1 is required for normal S-M coupling during cell cycle progression. To study the regulatory role of FoxM1 and its downstream regulatory targets, three stably transfected HeLa lines that display doxycycline (dox)-inducible FoxM1 expression were established. Over-expression of FoxM1 by dox induction facilitates growth recovery from serum starvation. Quantitation of cyclin B1 and D1 levels using flow cytometric, Western and Northern analyses reveals that elevated FoxM1 levels lead to stimulation of cyclin B1 but not cyclin D1 expression. Transient reporter assays in the dox-inducible lines and upon co-transfection with a constitutive FoxM1 expression plasmid suggest that FoxM1 can activate the cyclin B1 promoter.

This paper presents a new adaptive search approach to reduce the computational complexity of fractal encoding. A simple but very efficient adaptive necessary condition is introduced to exclude a large number of unqualified domain blocks so as to speed-up fractal image compression. Furthermore, we analyzed an unconventional affine parameter that has better properties than the conventional luminance offset. Specifically, we formulated an optimal bit allocation scheme for the simultaneous quantizations of the usual scaling and the aforementioned unconventional affine parameter. Experiments on standard images showed that our adaptive search method yields superior performance over conventional fractal encoding.