[Automated cephalometric landmark identification and location based on convolutional neural network].

Objective: To develop an automated landmark location system applicable to the case of landmark missing. Methods: Four and eighty-one lateral cephalograms, which contained 240 males and 241 females, with an average age of (24.5±5.6) years, taken from January 2015 to January 2021 in the Department of Orthodontics, Capital Medical University School of Stomatology, and met the inclusion criteria were collected. Five postgraduate orthodontic students were the annotators to manually locate 61 possible landmarks in 481 lateral cephalograms. Two assistant professors in the department as reviewers performed calibration. Two professors as arbitrators, made final decision. Data sets were established (341 were used as training set, 40 as validation set, and 100 as test set). In this paper, an automatic landmarks identification and location model based on convolutional neural networks (CNN), CephaNET, was developed. The model was trained by feeding the original image into the feature extraction module and convolutional pose machine (CPM) module to locate landmarks with high accuracy using deep supervision. Training set was enhanced to 1 684 images by histogram equalization, cropping, and adjustment of brightness. The model was trained to compare the Gaussian heat maps output from the network with the set threshold to identify landmark missing cases. Test set of 100 lateral cephalograms was used to test the accuracy of the model. The evaluation criteria used were success detection rate of missing landmark, mean radial error (MRE) and success detection rate (SDR) in the range of 2.0, 2.5, 3.0, 3.5 and 4.0 mm. Results: The model identified and located 61 commonly used landmarks in 0.13 seconds on average. It had an average accuracy of 93.5% in identifying missing landmarks. The MRE of our testing set was (1.19±0.91) mm. SDR of 2.0, 2.5, 3.0, 3.5 and 4.0 mm were 85.4%, 90.2%, 93.5%, 95.4%, 97.0% respectively. Conclusions: The model proposed in this paper could adapt to the absence of landmark in lateral cephalograms and locate 61 commonly used landmarks with high accuracy to meet the requirements of different cephalometric analysis methods.

[Automated diagnostic classification with lateral cephalograms based on deep learning network model].

Objective: To establish a comprehensive diagnostic classification model of lateral cephalograms based on artificial intelligence (AI) to provide reference for orthodontic diagnosis. Methods: A total of 2 894 lateral cephalograms were collected in Department of Orthodontics, Capital Medical University School of Stomatology from January 2015 to December 2021 to construct a data set, including 1 351 males and 1 543 females with a mean age of (26.4± 7.4) years. Firstly, 2 orthodontists (with 5 and 8 years of orthodontic experience, respectively) performed manual annotation and calculated measurement for primary classification, and then 2 senior orthodontists (with more than 20 years of orthodontic experience) verified the 8 diagnostic classifications including skeletal and dental indices. The data were randomly divided into training, validation, and test sets in the ratio of 7∶2∶1. The open source DenseNet121 was used to construct the model. The performance of the model was evaluated by classification accuracy, precision rate, sensitivity, specificity and area under the curve (AUC). Visualization of model regions of interest through class activation heatmaps. Results: The automatic classification model of lateral cephalograms was successfully established. It took 0.012 s on average to make 8 diagnoses on a lateral cephalogram. The accuracy of 5 classifications was 80%-90%, including sagittal and vertical skeletal facial pattern, mandibular growth, inclination of upper incisors, and protrusion of lower incisors. The acuracy rate of 3 classifications was 70%-80%, including maxillary growth, inclination of lower incisors and protrusion of upper incisors. The average AUC of each classification was ≥0.90. The class activation heat map of successfully classified lateral cephalograms showed that the AI model activation regions were distributed in the relevant structural regions. Conclusions: In this study, an automatic classification model for lateral cephalograms was established based on the DenseNet121 to achieve rapid classification of eight commonly used clinical diagnostic items.

[Research on multi-class orthodontic image recognition system based on deep learning network model].

Objective: To develop a multi-classification orthodontic image recognition system using the SqueezeNet deep learning model for automatic classification of orthodontic image data. Methods: A total of 35 000 clinical orthodontic images were collected in the Department of Orthodontics, Capital Medical University School of Stomatology, from October to November 2020 and June to July 2021. The images were from 490 orthodontic patients with a male-to-female ratio of 49∶51 and the age range of 4 to 45 years. After data cleaning based on inclusion and exclusion criteria, the final image dataset included 17 453 face images (frontal, smiling, 90° right, 90° left, 45° right, and 45° left), 8 026 intraoral images [frontal occlusion, right occlusion, left occlusion, upper occlusal view (original and flipped), lower occlusal view (original and flipped) and coverage of occlusal relationship], 4 115 X-ray images [lateral skull X-ray from the left side, lateral skull X-ray from the right side, frontal skull X-ray, cone-beam CT (CBCT), and wrist bone X-ray] and 684 other non-orthodontic images. A labeling team composed of orthodontic doctoral students, associate professors, and professors used image labeling tools to classify the orthodontic images into 20 categories, including 6 face image categories, 8 intraoral image categories, 5 X-ray image categories, and other images. The data for each label were randomly divided into training, validation, and testing sets in an 8∶1∶1 ratio using the random function in the Python programming language. The improved SqueezeNet deep learning model was used for training, and 13 000 natural images from the ImageNet open-source dataset were used as additional non-orthodontic images for algorithm optimization of anomaly data processing. A multi-classification orthodontic image recognition system based on deep learning models was constructed. The accuracy of the orthodontic image classification was evaluated using precision, recall, F1 score, and confusion matrix based on the prediction results of the test set. The reliability of the model's image classification judgment logic was verified using the gradient-weighted class activation mapping (Grad-CAM) method to generate heat maps. Results: After data cleaning and labeling, a total of 30 278 orthodontic images were included in the dataset. The test set classification results showed that the precision, recall, and F1 scores of most classification labels were 100%, with only 5 misclassified images out of 3 047, resulting in a system accuracy of 99.84%(3 042/3 047). The precision of anomaly data processing was 100% (10 500/10 500). The heat map showed that the judgment basis of the SqueezeNet deep learning model in the image classification process was basically consistent with that of humans. Conclusions: This study developed a multi-classification orthodontic image recognition system for automatic classification of 20 types of orthodontic images based on the improved SqueezeNet deep learning model. The system exhibitted good accuracy in orthodontic image classification.

Factors associated with treatment escalation among MS specialists and general neurologists: Results from an International cojoint study.

BACKGROUND: Previous studies in multiple sclerosis (MS) showed that therapeutic inertia (TI) affects 60-90% of neurologists and up to 25% of daily treatment decisions. The objective of this study was to determine the most common factors and attribute levels associated with decisions to treatment escalation in an international study in MS care. METHODS: 300 neurologists with MS expertise from 20 countries were invited to participate. Participants were presented with 12 pairs of simulated MS patient profiles described by 13 clinically relevant factors. We used disaggregated discrete choice experiments to estimate the weight of factors and attributes affecting physicians' decisions when considering treatment selection. Participants were asked to select the ideal candidate for treatment escalation from modest to higher-efficacy therapies. RESULTS: Overall, 229 neurologists completed the study (completion rate: 76.3%). The top 3 weighted factors associated with treatment escalation were: previous relapses (20%), baseline expanded disability status scale [EDSS] (18%), and MRI activity (13%). Patient demographics and desire for pregnancy had a modest influence (≤ 3%). We observed differences in the weight of factors associated with treatment escalation between MS specialists and non-MS specialists. CONCLUSIONS: Our results provide critical information on factors influencing neurologists' treatment decisions and should be applied to continuing medical education strategies.

Building on existing tools to improve chronic disease prevention and screening in public health: a cluster randomized trial.

BACKGROUND: The BETTER (Building on Existing Tools to Improve Chronic Disease Prevention and Screening in Primary Care) intervention was designed to integrate the approach to chronic disease prevention and screening in primary care and demonstrated effective in a previous randomized trial. METHODS: We tested the effectiveness of the BETTER HEALTH intervention, a public health adaptation of BETTER, at improving participation in chronic disease prevention and screening actions for residents of low-income neighbourhoods in a cluster randomized trial, with ten low-income neighbourhoods in Durham Region Ontario randomized to immediate intervention vs. wait-list. The unit of analysis was the individual, and eligible participants were adults age 40-64 years residing in the neighbourhoods. Public health nurses trained as "prevention practitioners" held one prevention-focused visit with each participant. They provided participants with a tailored prevention prescription and supported them to set health-related goals. The primary outcome was a composite index: the number of evidence-based actions achieved at six months as a proportion of those for which participants were eligible at baseline. RESULTS: Of 126 participants (60 in immediate arm; 66 in wait-list arm), 125 were included in analyses (1 participant withdrew consent). In both arms, participants were eligible for a mean of 8.6 actions at baseline. At follow-up, participants in the immediate intervention arm met 64.5% of actions for which they were eligible versus 42.1% in the wait-list arm (rate ratio 1.53 [95% confidence interval 1.22-1.84]). CONCLUSION: Public health nurses using the BETTER HEALTH intervention led to a higher proportion of identified evidence-based prevention and screening actions achieved at six months for people living with socioeconomic disadvantage. TRIAL REGISTRATION: NCT03052959 , registered February 10, 2017.

Comparison of mRNA expression from Y-chromosome X-degenerate region genes in taurine cattle, yaks and interspecific hybrid bulls.

The yattle (dzo) is an interspecific hybrid of the taurine cattle (Bos taurus) and the domestic yak (Bos grunniens). F1 hybrid yattle bulls are sterile due to spermatogenic arrest and have misregulation of spermatogenesis genes in the testes. However, the expression pattern of Y chromosome-linked genes in cattle, yaks and yattle testes is still unknown. In this study, we analyzed the mRNA expression pattern of 10 genes known to be present as single copies in the X-degenerate region of the bovine male-specific region of the Y chromosome. Using male-specific primers and reverse transcription quantitative PCR, the ubiquitously transcribed tetratricopeptide repeat gene, Y-linked (UTY), oral-facial-digital syndrome 1, Y-linked (OFD1Y) and ubiquitin specific peptidase 9, Y-linked (USP9Y) genes were ubiquitously expressed and significantly more highly expressed in yattle than in cattle and yaks testes (P < 0.001). RNA binding motif protein, Y-linked (RBMY) had testes-specific expression, and eukaryotic translation initiation factor 1A, Y-linked (EIF1AY) was expressed mainly in testis, whereas yattle and cattle did not show significant differences with respect to the expression of RBMY and EIF1AY. Thus, based on the model of yattle bull sterility, the high expression of UTY, OFD1Y and USP9Y may be associated with yattle infertility.

[Effectiveness of bupropion and counseling for smoking cessation].

OBJECTIVE: To evaluate the effectiveness of bupropion for smoking cessation among Chinese smokers at a smoking cessation clinic. METHODS: A prospective observational study was conducted in a hospital located in Beijing during 2008 and from 28 to 31 October 2014. A total of 287 smokers (265 men and 22 women) were assessed using data from structured questionnaires at baseline and were followed up at 1 and 6 months. Trained physician counselors provided free brief education and individual counseling sessions for all participants at the first visit. A total 131 participants were prescribed bupropion in addition to counseling. The counseling plus bupropion group was compared with the group who underwent counseling without bupropion. Outcomes were self-reported 7-day point prevalence abstinence rates at 1- and 6-month follow-up and continuous abstinence rates at 6-month follow-up. Smoking reduction rates at 1 and 6 months were also measured. RESULTS: By intention-to-treat analysis, the 7-day point prevalence abstinence rate of the bupropion group at 1 and 6 months was higher than for the counseling-only group: at 1-month follow-up, 26.0% (34/131) vs. 15.4% (24/156), with OR (95% CI) 1.93(1.07-3.46); these rates at 6-month follow-up were 27.8% (35/131) vs. 15.4% (24/156), with OR (95% CI) 2.01(1.12-3.59). The 1-month continuous abstinence rate at 6 months was higher in the bupropion group: 26.0% (34/131) vs. 14.7% (23/156), with OR (95%CI) 2.03(1.12-3.66). Participants in the bupropion group also had a higher smoking reduction rate at 1 month than those in the counseling-only group: 55.0% (72/131) vs. 38.5% (60/156), with OR (95%CI) 1.95 (1.22-3.13). CONCLUSION: Prescription of bupropion at this smoking cessation clinic was effective in doubling the quitting rates and smoking reduction rates among Chinese smokers.

A tremendous expansion of copy number in crossbred bulls ( × ).

Crossbreeding between cattle () and yak () exhibits significant hybrid advantages in milk yield and meat production. By contrast, cattle-yak F hybrid bulls are sterile. Copy number variations (CNV) of multicopy gene families in male-specific regions of the mammalian Y chromosome (MSY) affect human and animal fertility. The present study investigated CNV of (), (), (), and () in 5 yak breed bulls ( = 63), cattle-yak F ( = 22) and F ( = 2) hybrid bulls, and Chinese Yellow (CY) cattle bulls ( = 10) by quantitative real-time PCR. showed restricted amplification in yak bulls in that the average geometric mean copy number (CN) was estimated to be 4 copies. The most compelling finding is that there is a tremendous expansion of CN in F hybrids (385 copies; 95% confidence interval [CI] = 351-421) and F hybrids (356 copies) compared with the male parent breed CY cattle (142 copies; 95% CI = 95-211). Copy numbers of and were also extensively expanded on the Y chromosome in yak and CY cattle bulls. The geometric mean CN of and were estimated to be 123 (95% CI = 114-132) and 250 copies (95% CI = 233-268) in yak bulls and 71 (95% CI = 61-82) and 133 (95% CI = 107-164) copies in CY cattle, respectively. Yak and CY cattle have 2 copies of the gene on the Y chromosome. Similarly to gene, the F and F hybrid bulls have higher CN of , , and than CY cattle ( < 0.01). These results indicated that the MSY of yak and cattle-yak crossbred hybrids was fundamentally different from cattle MSY in the context of genomic organization. Based on the model of cattle-yak F and F hybrid bull sterility, the CNV of may serve as a potential risk factor for crossbred bull ( × ) infertility. To our knowledge, this is the first study to examine differences in multicopy genes in MSY between yak and cattle-yak bulls.

Bifidobacteria possess inhibitory activity against dipeptidyl peptidase-IV.

UNLABELLED: The incretin hormones are extremely rapidly metabolized by the ubiquitous enzyme dipeptidyl peptidase IV (DPP-IV). Therefore, DPP-IV inhibitors which can prolong the incretin effect are the newest and promising drugs for management of type 2 diabetes. In this study, we investigated whether Bifidobacteria colonizing the human gut possess DPP-IV inhibitory activity. Cell-free intracellular extracts of 13 Bifidobacterium strains isolated from breast-fed infant faecal samples were prepared and screened for DPP-IV inhibitory activity, and two Bifidobacterium strains-Bif. longum BBMN68 and Bif. lactis Bb12-were used as reference strains. Most of the strains showed varying levels of DPP-IV inhibitory property (7-27%). Strains of Bifidobacterium adolescentis IF1-11 and Bifidobacterium bifidum IF3-211 showed the greatest DPP-IV inhibitory activity (27 and 25%) as well as good in vitro probiotic properties. This initial finding suggested that new beneficial function of Bifidobacteria is strain-dependent and the strains or their components may have the potential application for management of type 2 diabetes via inhibiting gastrointestinal DPP-IV activity. Further investigations into the isolation and identification of the bioactive components of Bifidobacteria are warranted. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results show that Bifidobacteria isolated from breast-fed infants' faecal samples possess DPP-IV inhibitory activity. Strains of Bifidobacterium bifidum IF3-211 and Bifidobacterium adolescentis IF1-11, which showed excellent DPP-IV inhibitory properties as well as good in vitro probiotic properties, are expected to be beneficial for application as anti-diabetic probiotics.

A randomized trial testing the efficacy of modifications to the nutrition facts table on comprehension and use of nutrition information by adolescents and young adults in Canada.

INTRODUCTION: Given the proposed changes to nutrition labelling in Canada and the dearth of research examining comprehension and use of nutrition facts tables (NFts) by adolescents and young adults, our objective was to experimentally test the efficacy of modifications to NFts on young Canadians' ability to interpret, compare and mathematically manipulate nutrition information in NFts on prepackaged food. METHODS: An online survey was conducted among 2010 Canadians aged 16 to 24 years drawn from a consumer sample. Participants were randomized to view two NFts according to one of six experimental conditions, using a between-groups 2 x 3 factorial design: serving size (current NFt vs. standardized serving-sizes across similar products) x percent daily value (% DV) (current NFt vs. "low/med/high" descriptors vs. colour coding). The survey included seven performance tasks requiring participants to interpret, compare and mathematically manipulate nutrition information on NFts. Separate modified Poisson regression models were conducted for each of the three outcomes. RESULTS: The ability to compare two similar products was significantly enhanced in NFt conditions that included standardized serving-sizes (p ≤ .001 for all). Adding descriptors or colour coding of % DV next to calories and nutrients on NFts significantly improved participants' ability to correctly interpret % DV information (p ≤ .001 for all). Providing both standardized serving-sizes and descriptors of % DV had a modest effect on participants' ability to mathematically manipulate nutrition information to calculate the nutrient content of multiple servings of a product (relative ratio = 1.19; 95% confidence limit: 1.04-1.37). CONCLUSION: Standardizing serving-sizes and adding interpretive % DV information on NFts improved young Canadians' comprehension and use of nutrition information. Some caution should be exercised in generalizing these findings to all Canadian youth due to the sampling issues associated with the study population. Further research is needed to replicate this study in a more heterogeneous sample in Canada and across a range of food products and categories.

TITRE: Essai randomisé mesurant l'efficacité des modifications apportées au tableau de la valeur nutritive sur la compréhension et l'utilisation de l'information nutritionnelle par les adolescents et les jeunes adultes au Canada. INTRODUCTION: Compte tenu des changements proposés à l'étiquetage nutritionnel au Canada et de la rareté des travaux de recherche portant sur la compréhension et l'utilisation des tableaux de la valeur nutritive (tVN) chez les adolescents et les jeunes adultes, notre objectif consistait à réaliser un essai expérimental pour déterminer si les modifications apportées au tVN permettaient d'améliorer efficacement la façon dont les jeunes Canadiens interprètent, comparent et manipulent, sur le plan mathématique, l'information nutritionnelle figurant dans le tVN de denrées préemballées. MÉTHODOLOGIE: Une enquête en ligne a été menée auprès d'un échantillon de consommateurs composé de 2 010 Canadiens âgés de 16 à 24 ans. Nous avons réparti les participants de façon aléatoire en six groupes d'étude, et nous avons présenté à chacun des groupes deux des six tVN définis comme conditions expérimentales, selon un plan factoriel 2 x 3 : portion de référence (tVN actuel et portions de référence normalisées pour tous les produits similaires) x pourcentage de la valeur quotidienne (% VQ) (tVN actuel, ajout des descripteurs « faible/moyen/élevé ¼ et ajout d'un code de couleurs). L'enquête comprenait sept tâches consistant à interpréter, comparer et manipuler, sur le plan mathématique, l'information nutritionnelle figurant dans les tVN. Des modèles de régression de Poisson modifiés ont été élaborés pour chacun des trois résultats. RÉSULTATS: La capacité à comparer deux produits similaires s'est révélée significativement meilleure quand le tVN incluait une portion de référence normalisée (p ≤ 0,001 dans tous les cas). L'ajout de descripteurs ou d'un code de couleurs indiquant, sur le tVN, le % VQ pour les calories et les nutriments a amélioré de façon significative la capacité des participants à interpréter correctement l'information à propos de ce % VQ (p ≤ 0,001 dans tous les cas). Le fait de présenter aux participants des portions de référence normalisées et des descripteurs du % VQ a eu un effet modeste sur leur capacité à manipuler, sur le plan mathématique, l'information nutritionnelle pour calculer la valeur nutritive de plusieurs portions d'un produit (ratio relatif = 1,19; intervalle de confiance à 95 % : 1,04 à 1,37). CONCLUSION: La normalisation des portions de référence et l'ajout d'information sur l'interprétation du % VQ dans le tVN ont permis aux jeunes Canadiens de mieux comprendre et utiliser l'information nutritionnelle. Il faut néanmoins faire preuve de prudence avant de généraliser les résultats de l'enquête à l'ensemble des jeunes Canadiens en raison de l'échantillonnage de la population à l'étude. D'autres travaux de recherche sont nécessaires afin de reproduire cette étude au Canada avec un échantillon plus hétérogène, et en utilisant un éventail de produits alimentaires et de catégories d'aliments.

Identification and partial characterization of lactic acid bacteria isolated from traditional dairy products produced by herders in the western Tianshan Mountains of China.

UNLABELLED: Thirty strains of lactic acid bacteria (LAB) were isolated from herders' traditional dairy products collected from Xinjiang, China. The species Lactobacillus, Lactococcus, Enterococcus, Pediococcus and Leuconostoc were identified by 16S ribosomal RNA gene sequencing analysis and conventional observation. The strains' fermentation characteristics, including milk acidification, proteolysis, autolysis, antimicrobial activity and diacetyl production, were assayed and compared. Strains NL24 and NL31 showed the highest proteolytic activity-2·75 and 2·08 mmol Phe l(-1) milk, respectively. Strains C, NL41, SW2, Z3-11, NL42 and Z2-91 had high autolytic activity. In addition, most of the wild strains produced diacetyl, half of them to high levels. This study provides a clue to LAB biodiversity in traditional dairy foods produced by herders in the western Tianshan Mountains. High-performing strains should be further evaluated for practical application in value-added fermented dairy products. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results reveal a certain variety of lactic acid bacteria (LAB) in traditional dairy products from Xinjiang. Some of the LAB strains, such as Lactobacillus rhamnosus NL24 and Lactobacillus paracasei SW2, possess excellent functional properties and have the potential for application in indigenous fermented dairy products. Performance of the newly isolated strains in cheese or yogurt manufacturing was further evaluated. Application of the high-performing strains to enrich the flavour of fermented dairy products is highly desirable and holds great commercial potential.

Mechanism of the reversal effect of mifepristone on drug resistance of the human cervical cancer cell line HeLa/MMC.

We examined the ability of mifepristone to reverse the in vitro drug resistance of human cervical cancer cells resistant to mitomycin-C (HeLa/MMC) cells and investigated the mechanism of this effect. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to detect the drug resistance of HeLa/MMC cells and the reversed drug resistance in vitro. Expression levels of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and glucosylceramide synthase (GCS) were measured in HeLa and HeLa/MMC cells. The resistance index of HeLa/MMC cells on MMC was reduced from 5.02 to 1.46 after 10 mg/mL mifepristone exposure. A combination of mifepristone upregulated the Bax/Bcl-2 protein expression ratio and apoptosis in HeLa/MMC cells. GCS expression was significantly higher in HeLa/MMC cells than in HeLa cells (P < 0.01), but distinctly declined in both cell lines after mifepristone application (P < 0.01). Mifepristone reversed the resistance of HeLa/MMC cells to MMC in vitro; the overexpression of the GCS gene and the increased expression of apoptosis-related protein Bcl-2 may play important roles in the formation of multidrug resistance in cervical cancer.

Enhanced expression and significance of glycosylphosphatidylinositol anchor attachment protein 1 in colorectal cancer.

The aim of this study was to investigate the expression of glycosylphosphatidylinositol anchor attachment protein 1 (GPAA1) and its significance in patients with colorectal cancer. Fifty-two patients with primary colorectal cancer were included in this study. GPAA1 expression was detected by immunohistochemistry, reverse transcription-polymerase chain reaction, and Western blot analysis. A cell invasion assay was performed by the transwell method. The interacting proteins of GPAA1 were detected by co-immunoprecipitation and matrix assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF/TOF-MS). The expression of GPAA1 mRNA and protein in primary colorectal tumor tissues and liver metastasis tissues was significantly higher than that in normal mucosa tissues (P < 0.01). The number of highly expressing GPAA1 cells penetrating the Matrigel membrane was significantly higher than that of mildly expressing GPAA1 cells (P < 0.05). The results of co-immunoprecipitation and MALDI-TOF/TOF-MS confirmed the identity of the protein. GPAA1 is highly expressed in patients with colorectal cancer, which indicates that it might play an important role in the proliferation, invasion, and metastasis of colorectal cancer.

Developing human capital for successful implementation of international marine scientific research projects.

The oceans play a crucial role in the global environment and the sustainability of human populations, because of their involvement in climate regulation and provision of living and non-living resources to humans. Maintenance of healthy oceans in an era of increasing human pressure requires a high-level understanding of the processes occurring in the marine environment and the impacts of anthropogenic activities. Effective protection and sustainable resource management must be based, in part, on knowledge derived from successful research. Current marine research activities are being limited by a need for high-quality researchers capable of addressing critical issues in broad multidisciplinary research activities. This is particularly true for developing countries which will require the building of capacity for marine scientific research. This paper reviews the current activities aimed at increasing marine research capacity in developing and emerging countries and analyses the challenges faced, including: appropriate alignment of the research goals and societal and policy-relevant needs; training in multidisciplinary research; increasing capacity for overall synthesis of scientific data; building the capacity of technical staff; keeping highly qualified personnel in marine scientific research roles; cross-cultural issues in training; minimising duplication in training activities; improving linkages among human capital, project resources and infrastructure. Potential solutions to these challenges are provided, along with some priorities for action aimed at improving the overall research effort.

Apoptosis of peripheral T cells in rodent cardiac allograft recipients induced by donor-specific transfusion with impaired inducible costimulator/B7 homologous protein allorecognition.

OBJECTIVE: To investigate apoptosis of the CD8(+) T cells (Tc) subpopulation in rodent cardiac allograft recipients, which were treated by donor specific transfusion combined with blockade of Inducible costimulator (ICOS)/B7 homologous protein (B7h) costimulation. METHODS: Donor hearts were heterotopically transplanted into the necks of recipient mice using Chen's technique. Postoperative graft survival was recorded. Both the percentage of CD3(+)CD8(+)ICOS(+) Tc in recipients' peripheral blood and the apoptosis of CD8(+) Tc in recipient draining lymph nodes were detected by flow cytometry analysis. RESULTS: In comparison with the allogeneic group, the survival of cardiac grafts was prolonged by combined treatment with 5 × 10(6) ICOS-Fc-targeted B cells on day 0 of transplantation and 10 mg/kg/d ICOS-Fc on days 0 to 6 (84.38 ± 29.14 days versus 7.00 ± 0.76 days, P < .01). The treatment group showed a stable CD8(+)Tc clone size in recipient peripheral blood (49.4% ± 3.11% versus 50.0% ± 2.46%, P > .05); however, the percentage of CD3(+)CD8(+)ICOS(+) Tc decreased significantly compared with the allogeneic group (7.5% ± 2.02% versus 14.0% ± 3.03%, P < .05). Compared with allogeneic group, apoptosis of the CD8(+) Tc subpopulation in recipient draining lymph nodes was up-regulated significantly at postoperative 7 days in the treatment group (19.53% ± 5.10% versus 8.70 ± 3.14%, P < .05). CONCLUSION: Apoptosis of CD8(+) Tc in recipient draining lymph nodes was enhanced by pretreatment with donor specific transfusion and impaired ICOS/B7h allorecognition, which may have been associated with the variation in the CD3(+)CD8(+)ICOS(+) Tc subpopulation in peripheral blood and at least partially contributed to unresponsiveness toward cardiac allograft.

Inhibition of T-cell expansion caused by inducible costimulator/B7h costimulation blockade in direct allorecognition pathway.

OBJECTIVE: Inducible costimulator (ICOS)/B7h costimulation plays a crucial role in acute and chronic allograft rejection. To test the role of the ICOS signal in T-cell activation and expansion, we used ICOS-Fc-targeted B cells as donor antigen presenting cells to challenge the allogeneic response in vitro. METHODS: In vitro, the binding of ICOS-Fc with B7h on splenic B cells was confirmed by flow cytometry analysis. To evaluate the capacity of ICOS-Fc-targeted B cells to elicit an allogeneic response in vitro, we performed mixed lymphocyte reactions. RESULTS: The binding of B7h on splenic B cells by ICOS-Fc was confirmed at a saturating concentration of 100 µg/mL. Blockade of ICOS/B7h in direct allorecognition depressed proliferation of alloreactive T cells in vitro. CONCLUSIONS: ICOS/B7h signal plays an important role in direct allorecognition, eliciting allogeneic responses in vitro.

Liver cancer: increased microwave delivery to ablation zone with cooled-shaft antenna--experimental and clinical studies.

PURPOSE: To prospectively investigate whether the ablation zone induced with microwaves could be increased by delivering greater energy with a cooled-shaft antenna. MATERIALS AND METHODS: All studies were animal care and ethics committee approved. Written informed consent was obtained from all patients. Microwave ablation was performed by using a cooled-shaft antenna in 48 ex vivo and 12 in vivo experiments with porcine livers. The coagulation diameters achieved in different microwave ablation parameter groups (60-90 W for 5-25 minutes) were compared. Ninety patients (78 men, 12 women; mean age, 53 years; age range, 20-82 years) with 133 0.8-8.0-cm (mean, 2.7 cm +/- 1.5 [standard deviation]) primary or metastatic liver cancers were treated with the same microwave ablation technique. Complete ablation (CA) and local tumor progression (LTP) rates were determined. Generalized estimating equations were used to compare differences in tumor size, ablation zone diameter, and CA and LTP rates between different patient subgroups. RESULTS: In the ex vivo livers, in vivo livers, and liver cancers, one application of microwave energy with 80 W for 25 minutes produced mean coagulation diameters of 5.6 x 7.4 cm, 3.5 x 5.9 cm, and 3.6 x 5.0 cm, respectively. Skin burn was not observed. CA rates in small (

Determination of 14 chemical constituents in the traditional Chinese medicinal preparation Huangqin-Tang by high performance liquid chromatography.

The high performance liquid chromatographic (HPLC) method for the identification and determination of baicalin (BG), wogonoside (WG), oroxylin-A-glucoside (OG), baicalein (B), wogonin (W), orxylin-A (O), paeoniflorin (PF), glycyrrhizic acid (GL), glycyrrhetinic acid (GA), liquiritin (LG), isoliquirition (ILG), liquiritigenin (L), isoliquiritigenin (IL) and ononin (ON) in Huangqin-Tang [Chinese characters: see text] was established. The samples were separated with a Wakosil C18 column (4.6 x 150 mm) by linear gradient elution using A (MeOH-HAC 100:1, v/v)-B (Water-HAC 100:1, v/v) (0 min, 30:70; 15 min, 40:60; 30 min, 60:40; 45 min, 80:20; 60 min, 100:0) as the mobile phase at a flow-rate of 1.0 ml/min. The detection was by diode-array UV/Vis detector (DAD), and the wavelength was set at the range of 200-400 nm. Satisfactory results were obtained within 60 min for the simultaneous determination of the 14 constituents. The repeatability (RSD) of the method was generally less than 2% (n=5, interday and intraday). The recovery of BG was 96.9+/-1.71, WG was 98.9+/-2.99, PF was 99.7+/-0.52, LG was 95.3+/-2.67, GL was 96.7+/-3.44, and GA was 94.8+/-4.16, respectively.

[Study of deletion and mutation of p16 gene in primary hepatocellular carcinoma].

OBJECTIVE: To investigate the role the deletion and mutation of p16 gene plays in the pathogenesis of human primary hepatocarcinoma. METHODS: Thirty-one cases of human hepatocarcinoma, 31 cases of adjacent noncancerous liver cirrhosis and the leukocytes of 8 normal human subjects were analyzed for deletion and mutation in p16 gene exons 1, 2 and introns 1, 2 with comparative multiple PCR and PCR-SSCP. RESULTS: Deletion of p16 gene exon 1 and partial intron 1 was found in 4 of 31 cases (13/%). No deletion of exon 2 or intron 2 was found. Three patterns of p16 gene intron 1 and 18 bp-flanking sequence in exon 2 at SSCP analysis were observed in hepatocellular carcinoma and corresponding adjacent noncancerous cirrhosis, and two patterns were found in human normal leukocyte DNA. No aberrant single strand at SSCP in p16 gene exon 1 or most part of exon 2 or intron 2 was detected. CONCLUSION: Low frequency of deletion and rare mutation of p16 suppressor gene occurred in hepatocellular carcinoma.