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2.
  • Klionsky, Daniel J., et al. (author)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Research review (peer-reviewed)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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  • Zhuang, Xiahai, et al. (author)
  • Evaluation of algorithms for Multi-Modality Whole Heart Segmentation : An open-access grand challenge.
  • 2019
  • In: Medical Image Analysis. - : Elsevier BV. - 1361-8415 .- 1361-8423. ; 58
  • Journal article (peer-reviewed)abstract
    • Knowledge of whole heart anatomy is a prerequisite for many clinical applications. Whole heart segmentation (WHS), which delineates substructures of the heart, can be very valuable for modeling and analysis of the anatomy and functions of the heart. However, automating this segmentation can be challenging due to the large variation of the heart shape, and different image qualities of the clinical data. To achieve this goal, an initial set of training data is generally needed for constructing priors or for training. Furthermore, it is difficult to perform comparisons between different methods, largely due to differences in the datasets and evaluation metrics used. This manuscript presents the methodologies and evaluation results for the WHS algorithms selected from the submissions to the Multi-Modality Whole Heart Segmentation (MM-WHS) challenge, in conjunction with MICCAI 2017. The challenge provided 120 three-dimensional cardiac images covering the whole heart, including 60 CT and 60 MRI volumes, all acquired in clinical environments with manual delineation. Ten algorithms for CT data and eleven algorithms for MRI data, submitted from twelve groups, have been evaluated. The results showed that the performance of CT WHS was generally better than that of MRI WHS. The segmentation of the substructures for different categories of patients could present different levels of challenge due to the difference in imaging and variations of heart shapes. The deep learning (DL)-based methods demonstrated great potential, though several of them reported poor results in the blinded evaluation. Their performance could vary greatly across different network structures and training strategies. The conventional algorithms, mainly based on multi-atlas segmentation, demonstrated good performance, though the accuracy and computational efficiency could be limited. The challenge, including provision of the annotated training data and the blinded evaluation for submitted algorithms on the test data, continues as an ongoing benchmarking resource via its homepage (www.sdspeople.fudan.edu.cn/zhuangxiahai/0/mmwhs/).
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5.
  • Abdoullaye, Doukary, et al. (author)
  • Permanent genetic resources added to molecular ecology resources database 1 August 2009 - 30 September 2009
  • 2010
  • In: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 10:1, s. 232-236
  • Journal article (peer-reviewed)abstract
    • This article documents the addition of 238 microsatellite marker loci and 72 pairs of Single Nucleotide Polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Adelges tsugae, Artemisia tridentata, Astroides calycularis, Azorella selago, Botryllus schlosseri, Botrylloides violaceus, Cardiocrinum cordatum var. glehnii, Campylopterus curvipennis, Colocasia esculenta, Cynomys ludovicianus, Cynomys leucurus, Cynomys gunnisoni, Epinephelus coioides, Eunicella singularis, Gammarus pulex, Homoeosoma nebulella, Hyla squirella, Lateolabrax japonicus, Mastomys erythroleucus, Pararge aegeria, Pardosa sierra, Phoenicopterus ruber ruber and Silene latifolia. These loci were cross-tested on the following species: Adelges abietis, Adelges cooleyi, Adelges piceae, Pineus pini, Pineus strobi, Tubastrea micrantha, three other Tubastrea species, Botrylloides fuscus, Botrylloides simodensis, Campylopterus hemileucurus, Campylopterus rufus, Campylopterus largipennis, Campylopterus villaviscensio, Phaethornis longuemareus, Florisuga mellivora, Lampornis amethystinus, Amazilia cyanocephala, Archilochus colubris, Epinephelus lanceolatus, Epinephelus fuscoguttatus, Symbiodinium temperate-A clade, Gammarus fossarum, Gammarus roeselii, Dikerogammarus villosus and Limnomysis benedeni. This article also documents the addition of 72 sequencing primer pairs and 52 allele specific primers for Neophocaena phocaenoides.
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  • Chen, Guang, et al. (author)
  • A Novel Visible Light Positioning System With Event-Based Neuromorphic Vision Sensor
  • 2020
  • In: IEEE Sensors Journal. - : Institute of Electrical and Electronics Engineers (IEEE). - 1530-437X .- 1558-1748. ; 20:17, s. 10211-10219
  • Journal article (peer-reviewed)abstract
    • With the advanced development of image processing technology, visible light positioning (VLP) system based on image sensors has attracted more and more attention. However, as a commonly used light receiver, traditional CMOS camera has limited dynamic range and high latency, which is susceptible to various lighting and environmental factors. Moreover, high computational cost from image processing is unavoidable for most of visible light positioning systems. In our work, a novel VLP system using an event-based neuromorphic vision sensor (event camera) as the light receiver is proposed. Due to the low latency and microsecond-level temporal resolution of the event camera, our VLP system is able to identify multiple high-frequency flickering LEDs in asynchronous events simultaneously leaving out the need for data association and traditional image processing methods. A multi-LED fusion method is applied and a high positioning accuracy of 3cm is achieved when the height between LEDs and the event camera is within 1m.
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  • Han, Yang, et al. (author)
  • X-radiation inhibits histone deacetylase 1 and 2, upregulates Axin expression and induces apoptosis in non-small cell lung cancer
  • 2012
  • In: Radiation Oncology. - : BioMed Central. - 1748-717X. ; 7:183
  • Journal article (peer-reviewed)abstract
    • BackgroundHistone deacetylase (HDAC) plays an important role in the deacetylation of histone, which can alter gene expression patterns and affect cell behavior associated with malignant transformation. The aims of this study were to investigate the relationships between HDAC1, HDAC2, clinicopathologic characteristics, patient prognosis and apoptosis, to clarify the mechanism of upregulation of the Axis inhibitor Axin (an important regulator of the Wnt pathway) by X-radiation and to elucidate the effect of siRNA on radiation therapy of non-small cell lung cancer (NSCLC).MethodsHDAC1 and HDAC2 expression levels were measured by immunohistochemistry and reverse transcription PCR. Apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling and fluorescence activated cell sorting. BE1 cells expressing Axin were exposed to 2 Gy of X-radiation.ResultsExpression of HDAC1 and that of HDAC2 were correlated, and significantly higher in NSCLC tissues than in normal lung tissues (P < 0.05). HDAC1 and HDAC2 expression was correlated with pTNM stage and negatively correlated with differentiation of NSCLC and apoptotic index (P < 0.05). The prognosis of patients with low expression of HDAC1 and HDAC2 was better than that of those with high expression. X-radiation and siRNA inhibited HDAC1 and HDAC2 expression in NSCLC cells and Axin levels were significantly higher in BE1 cells.ConclusionsX-radiation and siRNA inhibit expression of HDAC1 and HDAC2, weaken the inhibitory effect of HDAC on Axin, upregulate Axin expression and induce apoptosis of lung cancer cells. Inhibition of HDAC1 and HDAC2 is a means of enhancing the radiosensitivity of NSCLC.
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  • Ho, Tiffany C, et al. (author)
  • Functional connectivity of negative emotional processing in adolescent depression.
  • 2014
  • In: Journal of Affective Disorders. - : Elsevier BV. - 0165-0327 .- 1573-2517. ; 155, s. 65-74
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The subgenual anterior cingulate cortex (sgACC) and its connected circuitry have been heavily implicated in emotional functioning in adolescent-onset major depressive disorder (MDD). While several recent studies have examined sgACC functional connectivity (FC) in depressed youth at rest, no studies to date have investigated sgACC FC in adolescent depression during negative emotional processing.METHODS: Nineteen medication-naïve adolescents with MDD and 19 matched healthy controls (HCL) performed an implicit fear facial affect recognition task during functional magnetic resonance imaging (fMRI). We defined seeds in bilateral sgACC and assessed FC using the psychophysiological interaction method. We also applied cognitive behavioral modeling to estimate group differences in perceptual sensitivity in this task. Finally, we correlated connectivity strength with clinical data and perceptual sensitivity.RESULTS: Depressed adolescents showed increased sgACC-amygdala FC and decreased sgACC-fusiform gyrus, sgACC-precuneus, sgACC-insula, and sgACC-middle frontal gyrus FC compared to HCL (p<0.05, corrected). Among the MDD, sgACC-precuneus FC negatively correlated with depression severity (p<0.05, corrected). Lastly, MDD adolescents exhibited poorer perceptual sensitivity in the task than HCL, and individual differences in perceptual sensitivity significantly correlated with sgACC FC and depression scores (p<0.05, corrected).LIMITATIONS: Subjects were clinically homogenous, possibly limiting generalizability of the findings.CONCLUSIONS: Adolescent depression is associated with biased processing of negative stimuli that may be driven by sgACC dysregulation and may possibly lead to an imbalance among intrinsic functional brain networks. This work also establishes the use of combining neuroimaging and cognitive behavioral modeling methods to investigate cognitive and neural differences between psychiatric and healthy populations.
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9.
  • Hong, Yuanyuan, et al. (author)
  • A Multi-Floor Arrayed Waveguide Grating Based Architecture with Grid Topology for Datacenter Networks
  • 2020
  • In: IEEE Access. - 2169-3536 .- 2169-3536. ; 8, s. 107134-107145
  • Journal article (peer-reviewed)abstract
    • This paper proposes a grid topology based passive optical interconnect (POI) architecture that is composed of multiple floors of arrayed waveguide grating routers (AWGRs) to offer high connectivity and scalability for datacenter networks. In the proposed POI signal only needs to pass one AWGR, and thus can avoid the crosstalk accumulation and cascaded filtering effects, which exist in many existing POI architectures based on cascaded AWGRs. Meanwhile, due to high connectivity, the proposed grid topology based POI also has the potential advantage of high reliability. Simulation results validate the network performance. With a proper node degree, the proposed grid topology can achieve acceptable blocking probability. Besides, steady performance is kept when the number of floors increases, indicating good scalability of the proposed POI.
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10.
  • Liu, Wei, et al. (author)
  • Coherent dynamics of multi-spin V-B(-) center in hexagonal boron nitride
  • 2022
  • In: Nature Communications. - : Nature Portfolio. - 2041-1723. ; 13:1
  • Journal article (peer-reviewed)abstract
    • Hexagonal boron nitride (hBN) has recently been demonstrated to contain optically polarized and detected electron spins that can be utilized for implementing qubits and quantum sensors in nanolayered-devices. Understanding the coherent dynamics ofmicrowave driven spins in hBN is of crucial importance for advancing these emerging new technologies. Here, we demonstrate and study the Rabi oscillation and related phenomena of a negatively charged boron vacancy (V-B(-)) spin ensemble in hBN. We report on different dynamics of the V-B(-) spins at weak and strong magnetic fields. In the former case the defect behaves like a single electron spin system, while in the latter case it behaves like a multi-spin system exhibiting multiple-frequency dynamical oscillation as beat in the Ramsey fringes. We also carry out theoretical simulations for the spin dynamics of V-B(-) and reveal that the nuclear spins can be driven via the strong electron nuclear coupling existing in V-B(-) center, which can be modulated by the magnetic field and microwave field.
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  • Sun, Hui-Min, et al. (author)
  • SERPINA4 is a novel independent prognostic indicator and a potential therapeutic target for colorectal cancer
  • 2016
  • In: American Journal of Cancer Research. - Madison : E-CENTURY PUBLISHING CORP. - 2156-6976. ; 6:8, s. 1636-1649
  • Journal article (peer-reviewed)abstract
    • Serpina family A member 4 (SERPINA4), also known as kallistatin, exerts important effects in inhibiting tumor growth and angiogenesis in many malignancies. However, the precise role of SERPINA4 in CRC has not been fully elucidated. The present study aimed to investigate the expression of SERPINA4 and its clinical significance in CRC. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analyses showed that the mRNA and protein expression of SERPINA4 in colorectal cancer (CRC) specimens was significantly decreased than that in adjacent normal mucosa. Immunohistochemistry (IHC) was conducted to characterize the expression pattern of SERPINA4 by using a tissue microarray (TMA) containing 327 archived paraffin-embedded CRC specimens. Statistical analyses revealed that decreased SERPINA4 expression was significantly associated with invasion depth, nodal involvement, distant metastasis, American Joint Committee on Cancer (AJCC) stage, and tumor differentiation. SERPINA4 was also an independent prognostic indicator of disease-free survival and overall survival in patients with CRC. Furthermore, the impact of altered SERPINA4 expression on CRC cells was analyzed with a series of in vitro and in vivo assays. The results demonstrated that SERPINA4 significantly inhibits malignant tumor progression and serves as a novel prognostic indicator and a potential therapeutic target for CRC.
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13.
  • Tian, Chao, et al. (author)
  • Overexpression of connective tissue growth factor WISP-1 in Chinese primary rectal cancer patients
  • 2007
  • In: World Journal of Gastroenterology. - 1007-9327 .- 2219-2840. ; 13:28, s. 3878-3882
  • Journal article (peer-reviewed)abstract
    • Aim: To clarify the expression change of Wnt-induced secreted protein-1 (WISP-1) in human rectal cancer and to determine whether it is correlated with invasion and metastasis of human rectal cancer. Methods: Eighty-six paired samples of rectal cancer and surgically resected distant normal rectal tissue were collected and allocated into cancer group and control group respectively. WISP-1 mRNA was detected by relative quantitative real-time RT-PCR and WISP-1 protein was examined by immunohistochemical staining. Results: WISP-1 gene overexpression was found in 65% (56/86) primary rectal cancers, 2-30 times that of the level in normal matched rectal tissues (P = 0.001). The mRNA expression level was correlated with Duke's staging, histological differentiation grade and lymph node status. The WISP-1 protein expression was in accordance with mRNA expression level. The positive degree of immunohistochemical staining in the cancer group (1.40 ± 0.35) was different from that in control group (1.04 ± 0.08, P < 0.001). Moreover, in cancer group the positive staining degree in high-level mRNA cancers (1.46 ± 0.37, n = 56) was higher than that in low-level mRNA (1.28 ± 0.28, n = 30, P = 0.018). Conclusion: Aberrant levels of WISP-1 expression may play a role in rectal tumorigenesis. WISP-1 may be used as a specific clinical diagnosis and prognosis marker in rectal cancer. © 2007 WJG. All rights reserved.
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  • Wang, Mo-Jin, et al. (author)
  • Downregulation of microRNA-124 is an independent prognostic factor in patients with colorectal cancer
  • 2013
  • In: International Journal of Colorectal Disease. - : Springer Verlag (Germany). - 0179-1958 .- 1432-1262. ; 28:2, s. 183-189
  • Journal article (peer-reviewed)abstract
    • PurposeRecently, microRNA-124 (miR-124) has been demonstrated as a potential tumor suppressor in several types of cancers. However, the role of miR-124 in colorectal cancer remains unclear. This study was aimed at investigating the clinicopathological significance of miR-124 expression in colorectal cancer.MethodsQuantitative real-time PCR was used to analyze miR-124 expression in 96 colorectal cancers and individual-matched normal mucosa samples. The expression of miR-124 was assessed for associations with clinicopathological characteristics using chi-square test. The survival curves were calculated by the Kaplan–Meier method. The influence of each variable on survival was examined by the Cox multivariate regression analysis.ResultsThe miR-124 expression was significantly downregulated in colorectal cancer compared to normal mucosa (P = 0.001). In colorectal cancer, miR-124 decreased expression correlated significantly with the grade of differentiation (P  = 0.021). Univariate survival analysis showed that the downregulated miR-124 was significantly correlated with worse prognosis, both in terms of overall survival (P = 0.017) and disease-free survival (DFS) (P  = 0.014). Further, the downregulated miR-124 was demonstrated as a prognostic factor for overall survival (hazard ratio, HR = 4.634; 95 % confidence interval, CI, 1.731–12.404; P = 0.002) and DFS (HR = 4.533, 95 % CI 1.733–11.856, P = 0.002), independently of gender, age, location, maximum tumor size, depth of invasion, differentiation, and TNM stage.ConclusionsMiR-124 may play a certain role in the development of colorectal cancer. The downregulation expression of miR-124 is an independent prognostic factor in patients with colorectal cancer.
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  • Wang, Mo-Jin, et al. (author)
  • The Ile646Val (2073A > G) Polymorphism in the Kinase-Binding Domain of A-Kinase Anchoring Protein 10 and the Risk of Colorectal Cancer
  • 2009
  • In: ONCOLOGY. - : S. Karger AG. - 0030-2414 .- 1423-0232. ; 76:3, s. 199-204
  • Journal article (peer-reviewed)abstract
    • Objective: The purpose of this study is to investigate whether the Ile646Val (2073A>G) polymorphism in the kinase-binding domain of A-kinase anchoring protein 10 (AKAP10) is related to the risk of colorectal cancer (CRC), clinicopathological variables and the environmental factors for the development of CRC. Methods: Applying TaqMan allelic discrimination, we investigated AKAP10 Ile646Val (2073A>G) polymorphism in 288 Chinese CRC patients and 281 healthy controls. Results: Logistic regression analysis revealed a significant association of AKAP10 Ile646Val (2073A>G) polymorphism with increased CRC risk (adjusted OR = 1.44, 95% CI 1.01-2.07, p = 0.02). Stratification analysis showed that the increased risk associated with the variant genotypes (GG+AG) was more evident in male subjects (adjusted OR = 1.48, 95% CI 0.94-2.34, p = 0.03). Compared with the AA genotype, the adjusted OR for the variant genotypes was 1.81 (95% CI 1.08 - 3.05, p = 0.01) among young subjects (age ! 57 years). Among individuals who did not smoke or who smoked lightly, there was a significantly increased risk with the variant genotypes (adjusted OR = 1.66, 95% CI 1.08 - 2.56, p = 0.02). We did not observe a relationship between the AKAP10 polymorphism and other clinicopathological and environmental factors. Conclusions: Our data suggested that the AKAP10 2073A>G variation is associated with an increased risk of CRC in the Chinese population.
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  • Wang, Mo-Jin, et al. (author)
  • The prognostic factors and multiple biomarkers in young patients with colorectal cancer
  • 2015
  • In: Scientific Reports. - : Nature Publishing Group: Open Access Journals - Option C / Nature Publishing Group. - 2045-2322. ; 5:10645
  • Journal article (peer-reviewed)abstract
    • The incidence of colorectal cancer (CRC) in young patients (less than= 50 years of age) appears to be increasing. However, their clinicopathological characteristics and survival are controversial. Likewise, the biomarkers are unclear. We used the West China (2008-2013, China), Surveillance, Epidemiology, and End Results program (1973-2011, United States) and Linkoping Cancer (1972-2009, Sweden) databases to analyse clinicopathological characteristics, survival and multiple biomarkers of young CRC patients. A total of 509,934 CRC patients were included from the three databases. The young CRC patients tended to have more distal location tumours, fewer tumour numbers, later stage, more mucinous carcinoma and poorer differentiation. The cancer-specific survival (CSS) of young patients was significantly better. The PRL (HR = 12.341, 95% CI = 1.615-94.276, P = 0.010), RBM3 (HR = 0.093, 95% CI = 0.012-0.712, P = 0.018), Wrap53 (HR = 1.952, 95% CI = 0.452-6.342, P = 0.031), p53 (HR = 5.549, 95% CI = 1.176-26.178, P = 0.045) and DNA status (HR = 17.602, 95% CI = 2.551-121.448, P = 0.001) were associated with CSS of the young patients. In conclusion, this study suggests that young CRC patients present advanced tumours and more malignant pathological features, while they have a better prognosis. The PRL, RBM3, Wrap53, p53 and DNA status are potential prognostic biomarkers for the young CRC patients.
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17.
  • Wang, Yong, et al. (author)
  • mRNA expression of minichromosome maintenance 2 in colonic adenoma and adenocarcinoma
  • 2009
  • In: EUROPEAN JOURNAL OF CANCER PREVENTION. - 0959-8278. ; 18:1, s. 40-45
  • Journal article (peer-reviewed)abstract
    • As proliferation is essential for Progression from normal cells to tumor, certain markers specific to proliferating cells may permit detection of premalignant lesions. Here, we aimed to evaluate the possible value of a proliferation marker, minichromosome maintenance 2 (MCM2), in the early diagnosis of colorectal cancer, by analyzing the difference in MCM2 expression among normal mucosa, adenoma, and adenocarcinoma, and investigating the relationship of MCM2 expression in adenomas with clinicopathologic variables. Using immunohistochemistry and real-time reverse transcription-PCR, we observed that the expression of MCM2 protein was present on basal third to half of colonic crypts in normal mucosa, whereas throughout the epithelium in adenomas and adenocarcinomas, the expression of MCM2 mRNA in adenocarcinomas was significantly higher than in adenomas (P=0.001), whereas the difference between adenoma and normal mucosa was not significant (P=0.184); we also found that the expression of MCM2 mRNA tended to be increased in the adenomas with high-grade dysplasia, or in older patients, respectively, compared with those with low-grade dysplasia, and younger patients. These results suggested the potential value of MCM2 in early diagnosis of colorectal cancer.
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18.
  • Yang, Lie, et al. (author)
  • Efficacy of Surgery and Adjuvant Therapy in Older Patients With Colorectal Cancer A STROBE-compliant article
  • 2014
  • In: Medicine. - : Lippincott, Williams andamp; Wilkins. - 0025-7974 .- 1536-5964. ; 93:28
  • Journal article (peer-reviewed)abstract
    • The present study aimed to assess the efficacy of surgery and adjuvant therapy in older patients (age greater than= 70 years) with colorectal cancer (CRC). Older CRC patients are under-represented in available clinical trials, and therefore their outcomes after receiving surgery and adjuvant therapy are unclear. From two prospective Swedish databases, we assessed a cohort of 1021 patients who underwent curative surgery for stage I, II, or III primary CRC, with or without adjuvant chemotherapy/ radiotherapy. Of the patients with colon cancer (n = 467), 182 (39%) were aged less than70 years, 162 (35%) aged 70 to 80 years, and 123 (26%) were aged greater than= 80 years. Of rectal cancer patients (n = 554), 264 (48%) were aged less than70 years, 234 (42%) aged 70 to 80 years, and 56 (10%) aged greater than= 80 years. Older patients with either colon or rectal cancer had higher comorbidity than did younger patients. Older patients with colon cancer had equivalent postoperative morbidity and 30-day mortality to younger patients. Rectal cancer patients aged greater than= 80 years had a higher 30-day mortality than younger patients (odds ratio OR], 2.37; 95% confidence interval CI], 1.6-4.55; P = 0.03). For either colon or rectal cancer, adjuvant chemotherapy compromised the 5-year overall survival (OS) of older patients with stage II disease and had no effect on those with stage III disease. Receiving adjuvant chemotherapy was a poor factor of OS for older patients with either colon (HR 1.88, 95% CI: 1.20-4.35, P = 0.03) or rectal cancer (HR 1.72, 95% CI: 1.052.26, P = 0.004). Preoperative short-course radiotherapy improved both OS and local control for older patients with stage III rectal cancer and had no effect on those with stage II disease. Radiotherapy was a favorable factor for the OS of the older patients with rectal cancer (HR 0.42, 95% CI: 0.21-3.57, P = 0.01). In conclusion, Older CRC patients had equal safety of surgery as younger patients, except rectal cancer patients aged greater than= 80 years that had a higher mortality. Adjuvant 5FU-based chemotherapy did not benefit older CRC patient, while neoadjuvant radiotherapy improved the prognosis of older patients with stage III rectal cancer.
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19.
  • Yang, Wen-Yi, et al. (author)
  • Association of Office and Ambulatory Blood Pressure With Mortality and Cardiovascular Outcomes
  • 2019
  • In: Journal of the American Medical Association (JAMA). - : AMER MEDICAL ASSOC. - 0098-7484 .- 1538-3598. ; 322:5, s. 409-420
  • Journal article (peer-reviewed)abstract
    • ImportanceBlood pressure (BP) is a known risk factor for overall mortality and cardiovascular (CV)-specific fatal and nonfatal outcomes. It is uncertain which BP index is most strongly associated with these outcomes. ObjectiveTo evaluate the association of BP indexes with death and a composite CV event. Design, Setting, and ParticipantsLongitudinal population-based cohort study of 11135 adults from Europe, Asia, and South America with baseline observations collected from May 1988 to May 2010 (last follow-ups, August 2006-October 2016). ExposuresBlood pressure measured by an observer or an automated office machine; measured for 24 hours, during the day or the night; and the dipping ratio (nighttime divided by daytime readings). Main Outcomes and MeasuresMultivariable-adjusted hazard ratios (HRs) expressed the risk of death or a CV event associated with BP increments of 20/10 mm Hg. Cardiovascular events included CV mortality combined with nonfatal coronary events, heart failure, and stroke. Improvement in model performance was assessed by the change in the area under the curve (AUC). ResultsAmong 11135 participants (median age, 54.7 years, 49.3% women), 2836 participants died (18.5 per 1000 person-years) and 2049 (13.4 per 1000 person-years) experienced a CV event over a median of 13.8 years of follow-up. Both end points were significantly associated with all single systolic BP indexes (P<.001). For nighttime systolic BP level, the HR for total mortality was 1.23 (95% CI, 1.17-1.28) and for CV events, 1.36 (95% CI, 1.30-1.43). For the 24-hour systolic BP level, the HR for total mortality was 1.22 (95% CI, 1.16-1.28) and for CV events, 1.45 (95% CI, 1.37-1.54). With adjustment for any of the other systolic BP indexes, the associations of nighttime and 24-hour systolic BP with the primary outcomes remained statistically significant (HRs ranging from 1.17 [95% CI, 1.10-1.25] to 1.87 [95% CI, 1.62-2.16]). Base models that included single systolic BP indexes yielded an AUC of 0.83 for mortality and 0.84 for the CV outcomes. Adding 24-hour or nighttime systolic BP to base models that included other BP indexes resulted in incremental improvements in the AUC of 0.0013 to 0.0027 for mortality and 0.0031 to 0.0075 for the composite CV outcome. Adding any systolic BP index to models already including nighttime or 24-hour systolic BP did not significantly improve model performance. These findings were consistent for diastolic BP. Conclusions and RelevanceIn this population-based cohort study, higher 24-hour and nighttime blood pressure measurements were significantly associated with greater risks of death and a composite CV outcome, even after adjusting for other office-based or ambulatory blood pressure measurements. Thus, 24-hour and nighttime blood pressure may be considered optimal measurements for estimating CV risk, although statistically, model improvement compared with other blood pressure indexes was small.
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20.
  • Zhang, Ming-Ran, et al. (author)
  • Prognostic role of the lymph node ratio in node positive colorectal cancer: a meta-analysis
  • 2016
  • In: Oncotarget. - : IMPACT JOURNALS LLC. - 1949-2553. ; 7:45, s. 72898-72907
  • Journal article (peer-reviewed)abstract
    • The lymph node ratio (LNR) (i. e. the number of metastatic lymph nodes divided by the number of totally resected lymph nodes) has recently emerged as an important prognostic factor in colorectal cancer (CRC). However, the tumor node metastasis (TNM) staging system for colorectal cancer does not consider it as a prognostic parameter. Therefore, we conducted a meta-analysis to evaluate the prognostic role of the LNR in node positive CRC. A systematic search was performed in PubMed, Embase and the Cochrane Library for relevant studies up to November 2015. As a result, a total of 75,838 node positive patients in 33 studies were included in this meta-analysis. Higher LNR was significantly associated with shorter overall survival (OS) (HR = 1.91; 95% CI 1.71-2.14; P = 0.0000) and disease free survival (DFS) (HR = 2.75; 95% CI: 2.14-3.53; P = 0.0000). Subgroup analysis showed similar results. Based on these results, LNR was an independent predictor of survival in colorectal cancer patients and should be considered as a parameter in future oncologic staging systems.
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21.
  • Zhao, Guang-Jiu, et al. (author)
  • Photoinduced intramolecular charge transfer and S-2 fluorescence in thiophene-pi-conjugated donor-acceptor systems : Experimental and TDDFT studies
  • 2008
  • In: Chemistry - A European Journal. - : Wiley. - 0947-6539 .- 1521-3765. ; 14:23, s. 6935-6947
  • Journal article (peer-reviewed)abstract
    • Experimental and theoretical methods were used to study newly synthesized thiophene-pi-cojugated donor-acceptor compounds, which were found to exhibit efficient intramolecular charge-transfer emission in polar solvents with relatively large Stokes shifts and strong solvatochromism. To gain insight into the solvatochromic behavior of these compounds, the dependence of the spectra on solvent polarity was studied on the basis of Lippert-Mataga models. We found that intramolecular charge transfer in these donor-acceptor systems is significantly dependent on the electron-with-drawing substituents at the thienyl 2-position. The dependence of the absorption and emission spectra of these compounds in methanol on the concentration of trifluoroacetic acid was used to confirm intramolecular charge-tranfer emission. Moreover, the calculated absorption and emission energies, which are in accordance with the experimental values, suggested that fluorescence can be emitted from different geometric confirmations. In addition, a novel S-2 fluorescence phenomenon for some of these compounds was also be observed. The fluorescence excitation spectra were used to confirm the S-2 fluorescence. We demonstrate that S-2 fluorescence can be explained by the calculated energy gap between the S-2 and S-1 states of these molecules. Furthermore, nonlinear optical behavior of the thiophene-pi-conjugated compound with diethylcyanomethylphosphonate substituents was predicted in theory.
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22.
  • Zhou, Bin, et al. (author)
  • Worldwide trends in diabetes since 1980: A pooled analysis of 751 population-based studies with 4.4 million participants
  • 2016
  • In: The Lancet. - : Elsevier B.V.. - 0140-6736 .- 1474-547X. ; 387:10027, s. 1513-1530
  • Journal article (peer-reviewed)abstract
    • Background: One of the global targets for non-communicable diseases is to halt, by 2025, the rise in the age standardised adult prevalence of diabetes at its 2010 levels. We aimed to estimate worldwide trends in diabetes, how likely it is for countries to achieve the global target, and how changes in prevalence, together with population growth and ageing, are aff ecting the number of adults with diabetes.Methods: We pooled data from population-based studies that had collected data on diabetes through measurement of its biomarkers. We used a Bayesian hierarchical model to estimate trends in diabetes prevalence-defined as fasting plasma glucose of 7.0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs-in 200 countries and territories in 21 regions, by sex and from 1980 to 2014. We also calculated the posterior probability of meeting the global diabetes target if post-2000 trends continue.Findings: We used data from 751 studies including 4372000 adults from 146 of the 200 countries we make estimates for. Global age-standardised diabetes prevalence increased from 4.3% (95% credible interval 2.4-17.0) in 1980 to 9.0% (7.2-11.1) in 2014 in men, and from 5.0% (2.9-7.9) to 7.9% (6.4-9.7) in women. The number of adults with diabetes in the world increased from 108 million in 1980 to 422 million in 2014 (28.5% due to the rise in prevalence, 39.7% due to population growth and ageing, and 31.8% due to interaction of these two factors). Age-standardised adult diabetes prevalence in 2014 was lowest in northwestern Europe, and highest in Polynesia and Micronesia, at nearly 25%, followed by Melanesia and the Middle East and north Africa. Between 1980 and 2014 there was little change in age-standardised diabetes prevalence in adult women in continental western Europe, although crude prevalence rose because of ageing of the population. By contrast, age-standardised adult prevalence rose by 15 percentage points in men and women in Polynesia and Micronesia. In 2014, American Samoa had the highest national prevalence of diabetes (>30% in both sexes), with age-standardised adult prevalence also higher than 25% in some other islands in Polynesia and Micronesia. If post-2000 trends continue, the probability of meeting the global target of halting the rise in the prevalence of diabetes by 2025 at the 2010 level worldwide is lower than 1% for men and is 1% for women. Only nine countries for men and 29 countries for women, mostly in western Europe, have a 50% or higher probability of meeting the global target.Interpretation: Since 1980, age-standardised diabetes prevalence in adults has increased, or at best remained unchanged, in every country. Together with population growth and ageing, this rise has led to a near quadrupling of the number of adults with diabetes worldwide. The burden of diabetes, both in terms of prevalence and number of adults aff ected, has increased faster in low-income and middle-income countries than in high-income countries.
  •  
23.
  • Zhou, Jin, et al. (author)
  • The prognostic significance of peroxisome proliferator-activated receptor beta expression in the vascular endothelial cells of colorectal cancer
  • 2014
  • In: Journal of gastroenterology. - : Springer Verlag (Germany). - 0944-1174 .- 1435-5922. ; 49:3, s. 436-445
  • Journal article (peer-reviewed)abstract
    • Currently, little is known regarding the role of peroxisome proliferator-activated receptor-beta (PPAR beta) in the vascular endothelial cells (VECs) of colorectal cancers (CRCs). The aim of this study was to investigate the relationship of PPAR beta expression in the VECs of CRCs in terms of the prognosis and clinicopathological features of CRC patients. The expression and localization of PPAR beta in the primary cancers and the matched normal mucosal samples of 141 Swedish CRC patients were analyzed in terms of its correlation with clinicopathological features and the expression of angiogenesis-related genes. This study also included 92 Chinese CRC patients. PPAR beta was predominantly localized in the cytoplasm and was significantly downregulated in the VECs of CRC compared to that of the normal mucosa. The low expression levels of PPAR beta in the VECs of CRC were statistically correlated with enhanced differentiation, early staging and favorable overall survival and were associated with the increased expression of VEGF and D2-40. The patients exhibiting elevated expression of PPAR beta in CRC cells but reduced expression in VECs exhibited more favorable survival compared with the other patients, whereas the patients with reduced expression of PPAR beta in CRC cells but increased expression in VECs exhibited less favorable prognosis. PPAR beta might play a tumor suppressor role in CRC cells in contrast to a tumor promoter role in the VECs of CRCs.
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24.
  • Astaraki, Mehdi, PhD Student, 1984-, et al. (author)
  • A Comparative Study of Radiomics and Deep-Learning Based Methods for Pulmonary Nodule Malignancy Prediction in Low Dose CT Images
  • 2021
  • In: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 11
  • Journal article (peer-reviewed)abstract
    • Objectives: Both radiomics and deep learning methods have shown great promise in predicting lesion malignancy in various image-based oncology studies. However, it is still unclear which method to choose for a specific clinical problem given the access to the same amount of training data. In this study, we try to compare the performance of a series of carefully selected conventional radiomics methods, end-to-end deep learning models, and deep-feature based radiomics pipelines for pulmonary nodule malignancy prediction on an open database that consists of 1297 manually delineated lung nodules.Methods: Conventional radiomics analysis was conducted by extracting standard handcrafted features from target nodule images. Several end-to-end deep classifier networks, including VGG, ResNet, DenseNet, and EfficientNet were employed to identify lung nodule malignancy as well. In addition to the baseline implementations, we also investigated the importance of feature selection and class balancing, as well as separating the features learned in the nodule target region and the background/context region. By pooling the radiomics and deep features together in a hybrid feature set, we investigated the compatibility of these two sets with respect to malignancy prediction.Results: The best baseline conventional radiomics model, deep learning model, and deep-feature based radiomics model achieved AUROC values (mean ± standard deviations) of 0.792 ± 0.025, 0.801 ± 0.018, and 0.817 ± 0.032, respectively through 5-fold cross-validation analyses. However, after trying out several optimization techniques, such as feature selection and data balancing, as well as adding context features, the corresponding best radiomics, end-to-end deep learning, and deep-feature based models achieved AUROC values of 0.921 ± 0.010, 0.824 ± 0.021, and 0.936 ± 0.011, respectively. We achieved the best prediction accuracy from the hybrid feature set (AUROC: 0.938 ± 0.010).Conclusion: The end-to-end deep-learning model outperforms conventional radiomics out of the box without much fine-tuning. On the other hand, fine-tuning the models lead to significant improvements in the prediction performance where the conventional and deep-feature based radiomics models achieved comparable results. The hybrid radiomics method seems to be the most promising model for lung nodule malignancy prediction in this comparative study.
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25.
  • Bauer, Franz E., et al. (author)
  • A new, faint population of X-ray transients
  • 2017
  • In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 467:4, s. 4841-4857
  • Journal article (peer-reviewed)abstract
    • We report on the detection of a remarkable new fast high-energy transient found in the Chandra Deep Field-South, robustly associated with a faint (mR = 27.5mag, zph ~2.2) host in the CANDELS survey. The X-ray event is comprised of 115+12 -11 net 0.3-7.0 keV counts, with a light curve characterized by an ~100 s rise time, a peak 0.3-10 keV flux of ~5 × 10-12 erg s-1 cm-2 and a power-law decay time slope of -1.53 ± 0.27. The average spectral slope is Γ = 1.43+0.23 -0.13, with no clear spectral variations. The X-ray and multiwavelength properties effectively rule out the vast majority of previously observed highenergy transients. A few theoretical possibilities remain: an 'orphan' X-ray afterglow from an off-axis short-duration gamma-ray burst (GRB) with weak optical emission, a low-luminosity GRB at high redshift with no prompt emission below ~20 keV rest frame, or a highly beamed tidal disruption event (TDE) involving an intermediate-mass black hole and a white dwarf with little variability. However, none of the above scenarios can completely explain all observed properties. Although large uncertainties exist, the implied rate of such events is comparable to those of orphan and low-luminosity GRBs as well as rare TDEs, implying the discovery of an untapped regime for a known transient class, or a new type of variable phenomena whose nature remains to be determined.
  •  
26.
  • Bentham, James, et al. (author)
  • A century of trends in adult human height
  • 2016
  • In: eLIFE. - 2050-084X. ; 5
  • Journal article (peer-reviewed)abstract
    • Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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27.
  • Bentham, James, et al. (author)
  • A century of trends in adult human height
  • 2016
  • In: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
  • Journal article (peer-reviewed)abstract
    • Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
  •  
28.
  • Chen, Geng, et al. (author)
  • Experimental Test of the State Estimation-Reversal Tradeoff Relation in General Quantum Measurements
  • 2014
  • In: Physical Review X. - 2160-3308. ; 4:5, s. 021043-
  • Journal article (peer-reviewed)abstract
    • When a measurement has limited strength, only partial information, regarding the initial state, is extracted, and, correspondingly, there is a probability to reverse its effect on the system and retrieve the original state. Recently, a clear and direct quantitative description of this complementary relationship, in terms of a tradeoff relation, was developed by Y. K. Cheong and S. W. Lee. [Phys. Rev. Lett. 109, 150402 (2012)]. Here, this tradeoff relation is experimentally verified using polarization-encoded single photons from a quantum dot. Measurement operators representing a complete range, from not affecting the system to a projection to a single polarization state, are realized. In addition, for each measurement operator, an optimal reversal operator is also implemented. The upper bound of the tradeoff relation is mapped to experimental parameters representing the measurement strength. Our results complement the theoretical work and provide a hands-on characterization of general quantum measurements.
  •  
29.
  • Chen, Haiyang, et al. (author)
  • A guest-assisted molecular-organization approach for >17% efficiency organic solar cells using environmentally friendly solvents
  • 2021
  • In: Nature Energy. - : NATURE PORTFOLIO. - 2058-7546. ; 6:11, s. 1045-1053
  • Journal article (peer-reviewed)abstract
    • The power conversion efficiencies (PCEs) of laboratory-sized organic solar cells (OSCs), usually processed from low-boiling-point and toxic solvents, have reached high values of over 18%. However, there is usually a notable drop of the PCEs when green solvents are used, limiting practical development of OSCs. Herein, we obtain certificated PCEs over 17% in OSCs processed from a green solvent paraxylene (PX) by a guest-assisted assembly strategy, where a third component (guest) is employed to manipulate the molecular interaction of the binary blend. In addition, the high-boiling-point green solvent PX also enables us to deposit a uniform large-area module (36 cm(2)) with a high efficiency of over 14%. The strong molecular interaction between the host and guest molecules also enhances the operational stability of the devices. Our guest-assisted assembly strategy provides a unique approach to develop large-area and high-efficiency OSCs processed from green solvents, paving the way for industrial development of OSCs. Organic solar cells processed from green solvents are easier to implement in manufacturing yet their efficiency is low. Chen et al. devise a guest molecule to improve the molecular packing, enabling devices with over 17% efficiency.
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30.
  • Chen, Ke-Ling, et al. (author)
  • Effects of Tocilizumab on Experimental Severe Acute Pancreatitis and Associated Acute Lung Injury
  • 2016
  • In: Critical Care Medicine. - : LIPPINCOTT WILLIAMS & WILKINS. - 0090-3493 .- 1530-0293. ; 44:8, s. E664-E677
  • Journal article (peer-reviewed)abstract
    • Objective: To examine the therapeutic effects of tocilizumab, an antibody against interleukin-6 receptor, on experimental severe acute pancreatitis and associated acute lung injury. The optimal dose of tocilizumab and the activation of interleukin-6 inflammatory signaling were also investigated. Design: Randomized experiment. Setting: Research laboratory at a university hospital. Subject: Experimental severe acute pancreatitis in rats. Interventions: Severe acute pancreatitis was induced by retrograde injection of sodium taurocholate (50 mg/kg) into the biliopancreatic duct. In dose-study, rats were administered with different doses of tocilizumab (1, 2, 4, 8, and 16 mg/kg) through the tail vein after severe acute pancreatitis induction. In safety-study, rats without severe acute pancreatitis induction were treated with high doses of tocilizumab (8, 16, 32, and 64 mg/kg). Serum and tissue samples of rats in time-study were collected for biomolecular and histologic evaluations at different time points (2, 6, 12, 18, and 24 hr). Measurements and Main Results: 1) Under the administration of tocilizumab, histopathological scores of pancreas and lung were decreased, and severity parameters related to severe acute pancreatitis and associated lung injury, including serum amylase, C-reactive protein, lung surfactant protein level, and myeloperoxidase activity, were all significant alleviated in rat models. 2) Dose-study demonstrated that 2 mg/kg tocilizumab was the optimal treatment dose. 3) Basing on multi-organ pathologic evaluation, physiological and biochemical data, no adverse effect and toxicity of tocilizumab were observed in safety-study. 4) Pancreatic nuclear factor-kappa B and signal transducer and activator of transcription 3 were deactivated, and the serum chemokine (C-X-C motif) ligand 1 was down-regulated after tocilizumab administration. Conclusions: Our study demonstrated tocilizumab, as a marketed drug commonly used for immune-mediated diseases, was safe and effective for the treatment of experimental severe acute pancreatitis and associated acute lung injury. Our findings provide experimental evidences for potential clinical application of tocilizumab in severe acute pancreatitis and associated complications.
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31.
  • Cheng, Yi-Bang, et al. (author)
  • Outcome-Driven Thresholds for Ambulatory Blood Pressure Based on the New American College of Cardiology/American Heart Association Classification of Hypertension
  • 2019
  • In: Hypertension. - 0194-911X .- 1524-4563. ; 74:4, s. 776-783
  • Journal article (peer-reviewed)abstract
    • The new American College of Cardiology/American Heart Association guideline reclassified office blood pressure and proposed thresholds for ambulatory blood pressure (ABP). We derived outcome-driven ABP thresholds corresponding with the new office blood pressure categories. We performed 24-hour ABP monitoring in 11 152 participants (48.9% women; mean age, 53.0 years) representative of 13 populations. We determined ABP thresholds resulting in multivariable-adjusted 10-year risks similar to those associated with elevated office blood pressure (120/80 mm Hg) and stages 1 and 2 of office hypertension (130/80 and 140/90 mm Hg). Over 13.9 years (median), 2728 (rate per 1000 person-years, 17.9) people died, 1033 (6.8) from cardiovascular disease; furthermore, 1988 (13.8), 893 (6.0), and 795 (5.4) cardiovascular and coronary events and strokes occurred. Using a composite cardiovascular end point, systolic/diastolic outcome-driven thresholds indicating elevated 24-hour, daytime, and nighttime ABP were 117.9/75.2, 121.4/79.6, and 105.3/66.2 mm Hg. For stages 1 and 2 ambulatory hypertension, thresholds were 123.3/75.2 and 128.7/80.7 mm Hg for 24-hour ABP, 128.5/79.6 and 135.6/87.1 mm Hg for daytime ABP, and 111.7/66.2 and 118.1/72.5 mm Hg for nighttime ABP. ABP thresholds derived from other end points were similar. After rounding, approximate thresholds for elevated 24-hour, daytime, and nighttime ABP were 120/75, 120/80, and 105/65 mm Hg, and for stages 1 and 2, ambulatory hypertension 125/75 and 130/80 mm Hg, 130/80 and 135/85 mm Hg, and 110/65 and 120/70 mm Hg. Outcome-driven ABP thresholds corresponding to elevated blood pressure and stages 1 and 2 of hypertension are similar to those proposed by the current American College of Cardiology/American Heart Association guideline.
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32.
  • Danaei, Goodarz, et al. (author)
  • Effects of diabetes definition on global surveillance of diabetes prevalence and diagnosis: a pooled analysis of 96 population-based studies with 331288 participants
  • 2015
  • In: The Lancet Diabetes & Endocrinology. - 2213-8595 .- 2213-8587. ; 3:8, s. 624-637
  • Journal article (peer-reviewed)abstract
    • Background Diabetes has been defined on the basis of different biomarkers, including fasting plasma glucose (FPG), 2-h plasma glucose in an oral glucose tolerance test (2hOGTT), and HbA(1c). We assessed the effect of different diagnostic definitions on both the population prevalence of diabetes and the classification of previously undiagnosed individuals as having diabetes versus not having diabetes in a pooled analysis of data from population-based health examination surveys in different regions. Methods We used data from 96 population-based health examination surveys that had measured at least two of the biomarkers used for defining diabetes. Diabetes was defined using HbA(1c) (HbA(1c) >= 6 . 5% or history of diabetes diagnosis or using insulin or oral hypoglycaemic drugs) compared with either FPG only or FPG-or-2hOGTT definitions (FPG >= 7 . 0 mmol/L or 2hOGTT >= 11 . 1 mmol/L or history of diabetes or using insulin or oral hypoglycaemic drugs). We calculated diabetes prevalence, taking into account complex survey design and survey sample weights. We compared the prevalences of diabetes using different definitions graphically and by regression analyses. We calculated sensitivity and specificity of diabetes diagnosis based on HbA1c compared with diagnosis based on glucose among previously undiagnosed individuals (ie, excluding those with history of diabetes or using insulin or oral hypoglycaemic drugs). We calculated sensitivity and specificity in each survey, and then pooled results using a random-effects model. We assessed the sources of heterogeneity of sensitivity by meta-regressions for study characteristics selected a priori. Findings Population prevalence of diabetes based on FPG- or-2hOGTT was correlated with prevalence based on FPG alone (r= 0 . 98), but was higher by 2-6 percentage points at different prevalence levels. Prevalence based on HbA(1c) was lower than prevalence based on FPG in 42 . 8% of age-sex-survey groups and higher in another 41 . 6%; in the other 15 . 6%, the two definitions provided similar prevalence estimates. The variation across studies in the relation between glucose-based and HbA(1c)-based prevalences was partly related to participants' age, followed by natural logarithm of per person gross domestic product, the year of survey, mean BMI, and whether the survey population was national, subnational, or from specific communities. Diabetes defined as HbA(1c) 6 . 5% or more had a pooled sensitivity of 52 . 8% (95% CI 51 . 3-54 . 3%) and a pooled specificity of 99 . 74% (99 . 71-99 . 78%) compared with FPG 7 . 0 mmol/L or more for diagnosing previously undiagnosed participants; sensitivity compared with diabetes defined based on FPG-or-2hOGTT was 30 . 5% (28 . 7-32 . 3%). None of the preselected study-level characteristics explained the heterogeneity in the sensitivity of HbA(1c) versus FPG. Interpretation Different biomarkers and definitions for diabetes can provide different estimates of population prevalence of diabetes, and differentially identify people without previous diagnosis as having diabetes. Using an HbA(1c)-based definition alone in health surveys will not identify a substantial proportion of previously undiagnosed people who would be considered as having diabetes using a glucose-based test.
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33.
  •  
34.
  • Fang, Evandro F., et al. (author)
  • A research agenda for ageing in China in the 21st century (2nd edition): Focusing on basic and translational research, long-term care, policy and social networks.
  • 2020
  • In: Ageing Research Reviews. - : Elsevier BV. - 1568-1637. ; 64
  • Journal article (peer-reviewed)abstract
    • One of the key issues facing public healthcare is the global trend of an increasingly ageing society which continues to present policy makers and caregivers with formidable healthcare and socio-economic challenges. Ageing is the primary contributor to a broad spectrum of chronic disorders all associated with a lower quality of life in the elderly. In 2019, the Chinese population constituted 18 % of the world population, with 164.5 million Chinese citizens aged 65 and above (65+), and 26 million aged 80 or above (80+). China has become an ageing society, and as it continues to age it will continue to exacerbate the burden borne by current family and public healthcare systems. Major healthcare challenges involved with caring for the elderly in China include the management of chronic non-communicable diseases (CNCDs), physical frailty, neurodegenerative diseases, cardiovascular diseases, with emerging challenges such as providing sufficient dental care, combating the rising prevalence of sexually transmitted diseases among nursing home communities, providing support for increased incidences of immune diseases, and the growing necessity to provide palliative care for the elderly. At the governmental level, it is necessary to make long-term strategic plans to respond to the pressures of an ageing society, especially to establish a nationwide, affordable, annual health check system to facilitate early diagnosis and provide access to affordable treatments. China has begun work on several activities to address these issues including the recent completion of the of the Ten-year Health-Care Reform project, the implementation of the Healthy China 2030 Action Plan, and the opening of the National Clinical Research Center for Geriatric Disorders. There are also societal challenges, namely the shift from an extended family system in which the younger provide home care for their elderly family members, to the current trend in which young people are increasingly migrating towards major cities for work, increasing reliance on nursing homes to compensate, especially following the outcomes of the ‘one child policy’ and the ‘empty-nest elderly’ phenomenon. At the individual level, it is important to provide avenues for people to seek and improve their own knowledge of health and disease, to encourage them to seek medical check-ups to prevent/manage illness, and to find ways to promote modifiable health-related behaviors (social activity, exercise, healthy diets, reasonable diet supplements) to enable healthier, happier, longer, and more productive lives in the elderly. Finally, at the technological or treatment level, there is a focus on modern technologies to counteract the negative effects of ageing. Researchers are striving to produce drugs that can mimic the effects of ‘exercising more, eating less’, while other anti-ageing molecules from molecular gerontologists could help to improve ‘healthspan’ in the elderly. Machine learning, ‘Big Data’, and other novel technologies can also be used to monitor disease patterns at the population level and may be used to inform policy design in the future. Collectively, synergies across disciplines on policies, geriatric care, drug development, personal awareness, the use of big data, machine learning and personalized medicine will transform China into a country that enables the most for its elderly, maximizing and celebrating their longevity in the coming decades. This is the 2nd edition of the review paper (Fang EF et al., Ageing Re. Rev. 2015).
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35.
  • Franklin, Stanley S., et al. (author)
  • The Cardiovascular Risk of White-Coat Hypertension
  • 2016
  • In: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 68:19, s. 2033-2043
  • Journal article (peer-reviewed)abstract
    • BACKGROUND The role of white-coat hypertension (WCH) and the white-coat-effect (WCE) in development of cardiovascular disease (CVD) risk remains poorly understood. OBJECTIVES Using data from the population-based, 11-cohort IDACO (International Database on Ambulatory Blood Pressure Monitoring in Relation to Cardiovascular Outcomes), this study compared daytime ambulatory blood pressure monitoring with conventional blood pressure measurements in 653 untreated subjects with WCH and 653 normotensive control subjects. METHODS European Society Hypertension guidelines were used as a 5-stage risk score. Low risk was defined as 0 to 2 risk factors, and high risk was defined as >= 3 to 5 risk factors, diabetes, and/or history of prior CVD events. Age-and cohort-matching was done between 653 untreated subjects with WCH and 653 normotensive control subjects. RESULTS In a stepwise linear regression model, systolic WCE increased by 3.8 mm Hg (95% confidence interval [CI]: 3.1 to 4.6 mm Hg) per 10-year increase in age, and was similar in low-and high-risk subjects with or without prior CVD events. Over a median 10.6-year follow-up, incidence of new CVD events was higher in 159 high-risk subjects with WCH compared with 159 cohort-and age-matched high-risk normotensive subjects (adjusted hazard ratio [HR]: 2.06; 95% CI: 1.10 to 3.84; p = 0.023). The HR was not significant for 494 participants with low-risk WCH and age-matched low-risk normotensive subjects. Subgroup analysis by age showed that an association between WCH and incident CVD events is limited to older (age >= 60 years) high-risk WCH subjects; the adjusted HR was 2.19 (95% CI: 1.09 to 4.37; p = 0.027) in the older high-risk group and 0.88 (95% CI: 0.51 to 1.53; p = 0.66) in the older low-risk group (p for interaction = 0.044). CONCLUSIONS WCE size is related to aging, not to CVD risk. CVD risk in most persons with WCH is comparable to age-and risk-adjusted normotensive control subjects.
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36.
  • Gavish, Benjamin, et al. (author)
  • Predictive power of 24-h ambulatory pulse pressure and its components for mortality and cardiovascular outcomes in 11 848 participants recruited from 13 populations
  • 2022
  • In: Journal of Hypertension. - : Ovid Technologies (Wolters Kluwer Health). - 0263-6352 .- 1473-5598. ; 40:11, s. 2245-2255
  • Journal article (peer-reviewed)abstract
    • Background: The role of pulse pressure (PP) 'widening' at older and younger age as a cardiovascular risk factor is still controversial. Mean PP, as determined from repeated blood pressure (BP) readings, can be expressed as a sum of two components: 'elastic PP' (elPP) and 'stiffening PP' (stPP) associated, respectively, with stiffness at the diastole and its relative change during the systole. We investigated the association of 24-h ambulatory PP, elPP, and stPP ('PP variables') with mortality and composite cardiovascular events in different age classes. Method: Longitudinal population-based cohort study of adults with baseline observations that included 24-h ambulatory BP. Age classes were age 40 or less, 40-50, 50-60, 60-70, and over 70 years. Co-primary endpoints were total mortality and composite cardiovascular events. The relative risk expressed by hazard ratio per 1SD increase for each of the PP variables was calculated from multivariable-adjusted Cox regression models. Results: The 11 848 participants from 13 cohorts (age 53 +/- 16 years, 50% men) were followed for up for 13.7 +/- 6.7 years. A total of 2946 participants died (18.1 per 1000 person-years) and 2093 experienced a fatal or nonfatal cardiovascular event (12.9 per 1000 person-years). Mean PP, elPP, and stPP were, respectively, 49.7, 43.5, and 6.2 mmHg, and elPP and stPP were uncorrelated (r = -0.07). At age 50-60 years, all PP variables displayed association with risk for almost all outcomes. From age over 60 years to age over 70 years, hazard ratios of of PP and elPP were similar and decreased gradually but differently for pulse rate lower than or higher than 70 bpm, whereas stPP lacked predictive power in most cases. For age 40 years or less, elPP showed protective power for coronary events, whereas stPP and PP predicted stroke events. Adjusted and unadjusted hazard ratio variations were similar over the entire age range. Conclusion: This study provides a new basis for associating PP components with outcome and arterial properties in different age groups and at different pulse rates for both old and young age. The similarity between adjusted and unadjusted hazard ratios supports the clinical usefulness of PP components but further studies are needed to assess the prognostic significance of the PP components, especially at the young age.
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37.
  • Guang, Liang, et al. (author)
  • Embedding Fault-Tolerance with Dual-Level Agents in Many-Core Systems
  • 2012
  • In: First MEDIAN Workshop (MEDIAN'12).
  • Conference paper (other academic/artistic)abstract
    • Dual-level fault-tolerance is presented on many-core systems, provided by the software-based system agent and hardware-based local agents. The system agent performs fault-triggered energy-aware remapping with bandwidth constraints, addressing coarse-grained processor failures. The local agents achieve fine-grained link-level fault tolerance against transient and permanent errors. The paper concisely presents the architecture, dual-level fault-tolerant techniques and experiment results.
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38.
  • Guang, Liang, et al. (author)
  • Hierarchical Agent Monitoring Design Platform - towards Self-aware and Adaptive Embedded Systems
  • 2011
  • In: PECCS 2011 - Proceedings of the 1st International Conference on Pervasive and Embedded Computing and Communication Systems. ; , s. 573-581
  • Conference paper (peer-reviewed)abstract
    • Hierarchical agent monitoring design platform(HAM) is presented as a generic design approach for the emerging self-aware and adaptive embedded systems. Such systems, with various existing proposals for different advanced features, call for a concrete, practical and portable design approach. HAM addresses this necessity by providing a scalable and generically applicable design platform. This paper elaborately describes the hierarchical agent monitoring architecture, with extensive reference to the state-of-the-art technology in embedded systems. Two case studies are exemplified to demonstrate the design process and benefits of HAM design platform. One is about hierarchical agent monitored Network-on-Chip with quantitative experiments of hierarchical energy management. The other one is a projectional study of applying HAM on smart house systems, focusing on the design for enhanced dependability.
  •  
39.
  • Guang, Liang, et al. (author)
  • Hierarchical power monitoring on NoC - a case study for hierarchical agent monitoring design approach
  • 2010
  • In: 28th Norchip Conference, NORCHIP 2010. - 9781424489732 ; , s. 5669428-
  • Conference paper (peer-reviewed)abstract
    • A case study is presented for hierarchical agent monitoring design approach, which provides a high level abstraction for designing monitoring functions on massively parallel and distributed systems. The case study features hierarchical power monitoring on NoC platforms, where each level of agents perform specific monitoring operations based on their granularity. The monitoring hierarchy and operations are specified by a formal language for consistent and non-ambiguous system design. Various benchmarks are mapped onto NoCs, running with hierarchical power monitoring agents. Quantitative evaluations are performed in terms of energy efficiency, communication latency, and silicon overhead.
  •  
40.
  • Guang, Liang, et al. (author)
  • Hierarchical supporting structure for dynamic organization in many-core computing systems
  • 2013
  • In: PECCS 2013. ; , s. 252-261
  • Conference paper (peer-reviewed)abstract
    • Hierarchical supporting structures for dynamic organization in many-core computing systems are presented.With profound hardware variations and unpredictable errors, dependability becomes a challenging issue in theemerging many-core systems. To provide fault-tolerance against processor failures or performance degradation,dynamic organization is proposed which allows clusters to be created and updated at the run-time. Hierarchicalsupporting structures are designed for each level of monitoring agents, to enable the tracing, storingand updating of component and system status. These supporting structures need to follow software/hardwareco-design to provide small and scalable overhead, while accommodating the functions of agents on the correspondinglevel. This paper presents the architectural design, functional simulation and implementationanalysis. The study demonstrates that the proposed structures facilitate the dynamic organization in caseof processor failures and incur small area overhead on many-core systems.
  •  
41.
  • Han, Xin-Bao, et al. (author)
  • Fe-substituted cobalt-phosphate polyoxometalates as enhanced oxygen evolution catalysts in acidic media
  • 2020
  • In: Cuihuà xuébào. - : Science Press. - 0253-9837 .- 1872-2067. ; 41:5, s. 853-857
  • Journal article (peer-reviewed)abstract
    • All-inorganic and earth-abundant bi-/trimetallic hydr(oxy)oxides are widely used as oxygen evolution electrocatalysts owing to their remarkable performance. However, their atomically precise structures remain undefined, complicating their optimization and limiting the understanding of their enhanced performance. Here, the underlying structure-property correlation is explored by using a well-defined cobalt-phosphate polyoxometalate cluster [{Co-4(OH)(3)(PO4)}(4)(SiW9O34)(4)](32-) (1), which may serve as a molecular model of multimetal hydr(oxy)oxides. The catalytic activity is enhanced upon replacing Co by Fe in 1, resulting in a reduced overpotential (385 mV) for oxygen evolution (by 66 mV) compared to that of the parent 1 at 10 mA cm(-2) in an acidic medium; this overpotential is comparable to that for the IrO2 catalyst. These abundant-metal-based polyoxometalates exhibit high stability, with no evidence of degradation even after 24 h of operation.
  •  
42.
  •  
43.
  • Hong, Feng, et al. (author)
  • Bacterial cellulose production from cotton-based waste textiles : enzymatic saccharification enhanced by ionic liquid pretreatment
  • 2012
  • In: Bioresource Technology. - Oxford : Elsevier. - 0960-8524 .- 1873-2976. ; 104, s. 503-508
  • Journal article (peer-reviewed)abstract
    • Cotton-based waste textiles were explored as alternative feedstock for production of bacterial cellulose (BC) by Gluconacetobacter xylinus. The cellulosic fabrics were treated with the ionic liquid (IL) 1-allyl-3-methylimidazolium chloride ([AMIM]Cl). [AMIM]Cl caused 25% inactivation of cellulase activity at a concentration as low as of 0.02 g/mL and decreased BC production during fermentation when present in concentrations higher than 0.0005 g/mL. Therefore, removal of residual IL by washing with hot water was highly beneficial to enzymatic saccharification as well as BC production. IL-treated fabrics exhibited a 5-7-fold higher enzymatic hydrolysis rate and gave a seven times larger yield of fermentable sugars than untreated fabrics. BC from cotton cloth hydrolysate was obtained at an yield of 10.8 g/L which was 83% higher than that from the culture grown on glucose-based medium. The BC from G. xylinus grown on IL-treated fabric hydrolysate had a 79% higher tensile strength than BC from glucose-based culture medium which suggests that waste cotton pretreated with [AMIM]Cl has potential to serve as a high-quality carbon source for BC production.
  •  
44.
  • Hu, Guangzhi, et al. (author)
  • Atomistic understanding of the origin of high oxygen reduction electrocatalytic activity of cuboctahedral Pt3Co-Pt core-shell nanoparticles
  • 2016
  • In: Catalysis Science & Technology. - : Royal Society of Chemistry (RSC). - 2044-4753 .- 2044-4761. ; 6:5, s. 1393-1401
  • Journal article (peer-reviewed)abstract
    • PtM-based core-shell nanoparticles are a new class of active and stable nanocatalysts for promoting oxygen reduction reaction (ORR); however, the understanding of their high electrocatalytic performance for ORR at the atomistic level is still a great challenge. Herein, we report the synthesis of highly ordered and homogeneous truncated cuboctahedral Pt3Co-Pt core-shell nanoparticles (cs-Pt3Co). By combining atomic resolution electron microscopy, X-ray photoelectron spectroscopy, extensive first-principles calculations, and many other characterization techniques, we conclude that the cs-Pt3Co nanoparticles are composed of a complete or nearly complete Pt monolayer skin, followed by a secondary shell containing 5-6 layers with similar to 78 at% of Pt, in a Pt3Co configuration, and finally a Co-rich core with 64 at% of Pt. Only this particular structure is consistent with the very high electrocatalytic activity of cs-Pt3Co nanoparticles for ORR, which is about 6 times higher than commercial 30%-Pt/Vulcan and 5 times more active than non-faceted (spherical) alloy Pt3Co nanoparticles. Our study gives an important insight into the atomistic design and understanding of advanced bimetallic nanoparticles for ORR catalysis and other important industrial catalytic applications.
  •  
45.
  • Hu, Guangzhi, et al. (author)
  • Small palladium islands embedded in palladium-tungsten bimetallic nanoparticles form catalytic hotspots for oxygen reduction
  • 2014
  • In: Nature Communications. - : Macmillan Publishers Ltd.. - 2041-1723. ; 5, s. Article number: 5253-
  • Journal article (peer-reviewed)abstract
    • The sluggish kinetics of the oxygen reduction reaction at the cathode side of proton exchange membrane fuel cells is one major technical challenge for realizing sustainable solutions for the transportation sector. Finding efficient yet cheap electrocatalysts to speed up this reaction therefore motivates researchers all over the world. Here we demonstrate an efficient synthesis of palladium-tungsten bimetallic nanoparticles supported on ordered mesoporous carbon. Despite a very low percentage of noble metal (palladium: tungsten = 1:8), the hybrid catalyst material exhibits a performance equal to commercial 60% platinum/Vulcan for the oxygen reduction process. The high catalytic efficiency is explained by the formation of small palladium islands embedded at the surface of the palladium-tungsten bimetallic nanoparticles, generating catalytic hotspots. The palladium islands are similar to 1 nm in diameter, and contain 10-20 palladium atoms that are segregated at the surface. Our results may provide insight into the formation, stabilization and performance of bimetallic nanoparticles for catalytic reactions.
  •  
46.
  • Hu, Li-Xin, et al. (author)
  • What is in Nigerian waters? Target and non-target screening analysis for organic chemicals
  • 2021
  • In: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 284
  • Journal article (peer-reviewed)abstract
    • Emerging organic contaminants (e.g., active pharmaceutical ingredients and personal care products ingredients) are ubiquitous in the environment and potentially harmful to ecosystems, have gained increasing public attention worldwide. Nevertheless, there is a scarcity of data on these contaminants in Africa. In this study, various types of water samples (wastewater, surface water and tap water) collected from Lagos, Nigeria were analyzed for these chemicals by both target and non-target analysis on an UHPLC-Orbitrap-MS/MS. In total, 109 compounds were identified by non-target screening using the online database mzCloud. Level 1 identification confidence was achieved for 13 compounds for which reference standards were available and level 2 was achieved for the rest. In the quantitative analysis, 18 of 38 target compounds were detected, including the parent compounds and their metabolites. Acetaminophen, sulfamethoxazole, acesulfame, and caffeine were detected in all samples with their highest concentrations at 8000, 5300, 16, and 7700 μg/L in wastewater, 140000, 3300, 7.7, and 12000 μg/L in surface water, and 66, 62, 0.17 and 1000 μg/L in tap water, respectively. The occurrence of psychoactive substances, anticancer treatments, antiretrovirals, antihypertensives, antidiabetics and their metabolites were reported in Nigeria for the first time. These results indicate poor wastewater treatment and management in Nigeria, and provide a preliminary profile of organic contaminants occurring in Nigerian waters. The findings from this study urge more future research on chemical pollution in the aquatic environments in Nigeria.
  •  
47.
  • Li, Bing, et al. (author)
  • An Efficient Method for Solving Frequency Responses of Power-Line Networks
  • 2015
  • In: Progress in Electromagnetics Research B. - : EMW Publishing. - 1937-6472. ; 62:1, s. 303-317
  • Journal article (peer-reviewed)abstract
    • This paper presents a novel approach for solving the frequency responses of a powerline network, which is a two-parallel-conductor system with multiple junctions and branches. By correcting the reflection coefficient and transmission coefficient of each junction, a complex network can be decomposed into several, single-junction, units. Based on the Baum-Liu-Tesche (BLT) equation, we preliminarily propose the calculation method of frequency responses for single-junction network. In accordance with the direction of power transfer, we calculate the frequency responses of loads connected to each junction sequentially, from the perspective of the network structure. This approach greatly simplifies the computational complexity of the network frequency responses. To verify the proposed algorithm, networks with various numbers of junctions and branches are investigated, and the results are compared with a commercial electromagnetic simulator based on the topology. The analytical results agree well with the simulated ones.
  •  
48.
  •  
49.
  • Li, Yan, et al. (author)
  • Opposing Age-Related Trends in Absolute and Relative Risk of Adverse Health Outcomes Associated With Out-of-Office Blood Pressure
  • 2019
  • In: Hypertension. - : Lippincott Williams & Wilkins. - 0194-911X .- 1524-4563. ; 74:6, s. 1333-1342
  • Journal article (peer-reviewed)abstract
    • Participant-level meta-analyses assessed the age-specific relevance of office blood pressure to cardiovascular complications, but this information is lacking for out-of-office blood pressure. At baseline, daytime ambulatory (n=12 624) or home (n=5297) blood pressure were measured in 17 921 participants (51.3% women; mean age, 54.2 years) from 17 population cohorts. Subsequently, mortality and cardiovascular events were recorded. Using multivariable Cox regression, floating absolute risk was computed across 4 age bands (<= 60, 61-70, 71-80, and >80 years). Over 236 491 person-years, 3855 people died and 2942 cardiovascular events occurred. From levels as low as 110/65 mm Hg, risk log-linearly increased with higher out-of-office systolic/diastolic blood pressure. From the youngest to the oldest age group, rates expressed per 1000 person-years increased (P<0.001) from 4.4 (95% CI, 4.0-4.7) to 86.3 (76.1-96.5) for all-cause mortality and from 4.1 (3.9-4.6) to 59.8 (51.0-68.7) for cardiovascular events, whereas hazard ratios per 20-mm Hg increment in systolic out-of-office blood pressure decreased (P <= 0.0033) from 1.42 (1.19-1.69) to 1.09 (1.05-1.12) and from 1.70 (1.51-1.92) to 1.12 (1.07-1.17), respectively. These age-related trends were similar for out-of-office diastolic pressure and were generally consistent in both sexes and across ethnicities. In conclusion, adverse outcomes were directly associated with out-of-office blood pressure in adults. At young age, the absolute risk associated with out-of-office blood pressure was low, but relative risk high, whereas with advancing age relative risk decreased and absolute risk increased. These observations highlight the need of a lifecourse approach for the management of hypertension.
  •  
50.
  • Liu, Yong, et al. (author)
  • Deletion Of XIAP reduces the severity of acute pancreatitis via regulation of cell death and nuclear factor-kappa B activity
  • 2017
  • In: Cell Death and Disease. - : NATURE PUBLISHING GROUP. - 2041-4889. ; 8
  • Journal article (peer-reviewed)abstract
    • Severe acute pancreatitis (SAP) still remains a clinical challenge, not only for its high mortality but the uncontrolled inflammatory progression from acute pancreatitis (AP) to SAP. Cell death, including apoptosis and necrosis are critical pathology of AP, since the severity of pancreatitis correlates directly with necrosis and inversely with apoptosis Therefore, regulation of cell death from necrosis to apoptosis may have practicably therapeutic value. X-linked inhibitor of apoptosis protein (XIAP) is the best characterized member of the inhibitor of apoptosis proteins (IAP) family, but its function in AP remains unclear. In the present study, we investigated the potential role of XIAP in regulation of cell death and inflammation during acute pancreatitis. The in vivo pancreatitis model was induced by the administration of cerulein with or without lipopolysaccharide (LPS) or by the administration of L-arginine in wild-type or XIAP-deficient mice, and ex vivo model was induced by the administration of cerulein+LPS in AR42J cell line following XIAP inhibition. The severity of acute pancreatitis was determined by serum amylase activity and histological grading. XIAP deletion on cell apoptosis, necrosis and inflammatory response were examined. Caspases activities, nuclear factor kappa B (NF-kappa B) activation and receptor-interacting protein kinase1 (RIP1) degradation were assessed by western blot. Deletion of XIAP resulted in the reduction of amylase activity, decrease of NF-kappa B activation and less release of TNF-alpha and IL-6, together with increased caspases activities and RIP1 degradation, leading to enhanced apoptosis and reduced necrosis in pancreatic acinar cells and ameliorated the severity of acute pancreatitis. Our results indicate that deletion of XIAP switches cell death away from necrosis to apoptosis and decreases the inflammatory response, effectively attenuating the severity of AP/SAP. The critical role of XIAP in cell death and inflammation suggests that inhibition of XIAP represents a potential therapeutic strategy for the treatment of acute pancreatitis.
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