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1.
Sensors (Basel) ; 20(15)2020 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-32727037

RESUMO

The use of digital accelerometers featuring high sensitivity and low noise levels in wireless smart sensors (WSSs) is becoming increasingly common for structural health monitoring (SHM) applications. Improvements in the design of Micro Electro-Mechanical System (MEMS) based digital accelerometers allow for high resolution sensing required for SHM with low power consumption suitable for WSSs. However, new approaches are needed to synchronize data from these sensors. Data synchronization is essential in wireless smart sensor networks (WSSNs) for accurate condition assessment of structures and reduced false-positive indications of damage. Efforts to achieve synchronized data sampling from multiple WSS nodes with digital accelerometers have been lacking, primarily because these sensors feature an internal Analog to Digital Converter (ADC) to which the host platform has no direct access. The result is increased uncertainty in the ADC startup time and thus worse synchronization among sensors. In this study, a high-sensitivity digital accelerometer is integrated with a next-generation WSS platform, the Xnode. An adaptive iterative algorithm is used to characterize these delays without the need for a dedicated evaluation setup and hardware-level access to the ADC. Extensive tests are conducted to evaluate the performance of the accelerometer experimentally. Overall time-synchronization achieved is under 15 µs, demonstrating the efficacy of this approach for synchronization of critical SHM applications.

2.
Sensors (Basel) ; 18(1)2018 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-29342102

RESUMO

Structural health monitoring (SHM) is playing an increasingly important role in ensuring the safety of structures. A shift of SHM research away from traditional wired methods toward the use of wireless smart sensors (WSS) has been motivated by the attractive features of wireless smart sensor networks (WSSN). The progress achieved in Micro Electro-Mechanical System (MEMS) technologies and wireless data transmission, has extended the effectiveness and range of applicability of WSSNs. One of the most common sensors employed in SHM strategies is the accelerometer; however, most accelerometers in WSS nodes have inadequate resolution for measurement of the typical accelerations found in many SHM applications. In this study, a high-resolution and low-noise tri-axial digital MEMS accelerometer is incorporated in a next-generation WSS platform, the Xnode. In addition to meeting the acceleration sensing demands of large-scale civil infrastructure applications, this new WSS node provides powerful hardware and a robust software framework to enable edge computing that can deliver actionable information. Hardware and software integration challenges are presented, and the associate resolutions are discussed. The performance of the wireless accelerometer is demonstrated experimentally through comparison with high-sensitivity wired accelerometers. This new high-sensitivity wireless accelerometer will extend the use of WSSN to a broader class of SHM applications.


Assuntos
Acelerometria , Aceleração , Desenho de Equipamento , Humanos , Sistemas Microeletromecânicos , Software
3.
Hepatology ; 63(5): 1544-59, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27100146

RESUMO

UNLABELLED: High-grade tumors with poor differentiation usually show phenotypic resemblance to their developmental ancestral cells. Cancer cells that gain lineage precursor cell properties usually hijack developmental signaling pathways to promote tumor malignant progression. However, the molecular mechanisms underlying this process remain unclear. In this study, the chromatin remodeler chromodomain-helicase-DNA-binding-protein 1-like (CHD1L) was found closely associated with liver development and hepatocellular carcinoma (HCC) tumor differentiation. Expression of CHD1L decreased during hepatocyte maturation and increased progressively from well-differentiated HCCs to poorly differentiated HCCs. Chromatin immunoprecipitation followed by high-throughput deep sequencing found that CHD1L could bind to the genomic sequences of genes related to development. Bioinformatics-aided network analysis indicated that CHD1L-binding targets might form networks associated with developmental transcription factor activation and histone modification. Overexpression of CHD1L conferred ancestral precursor-like properties of HCC cells both in vitro and in vivo. Inhibition of CHD1L reversed tumor differentiation and sensitized HCC cells to sorafenib treatment. Mechanism studies revealed that overexpression of CHD1L could maintain an active "open chromatin" configuration at promoter regions of estrogen-related receptor-beta and transcription factor 4, both of which are important regulators of HCC self-renewal and differentiation. In addition, we found a significant correlation of CHD1L with developmental transcriptional factors and lineage differentiation markers in clinical HCC patients. CONCLUSION: Genomic amplification of chromatin remodeler CHD1L might drive dedifferentiation of HCC toward an ancestral lineage through opening chromatin for key developmental transcriptional factors; further inhibition of CHD1L might "downgrade" poorly differentiated HCCs and provide novel therapeutic strategies.


Assuntos
Carcinoma Hepatocelular/patologia , Linhagem da Célula , Cromatina/fisiologia , DNA Helicases/fisiologia , Proteínas de Ligação a DNA/fisiologia , Neoplasias Hepáticas/patologia , Fatores de Transcrição/fisiologia , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Diferenciação Celular , Cromatina/química , Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias Hepáticas/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL , Niacinamida/análogos & derivados , Niacinamida/farmacologia , Compostos de Fenilureia/farmacologia , Receptores de Estrogênio/fisiologia , Sorafenibe
4.
Gastroenterology ; 149(4): 1068-81.e5, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26099525

RESUMO

BACKGROUND & AIMS: Levels of atonal homolog 8 (ATOH8) are reduced in 48% of hepatitis B virus-associated hepatocellular carcinoma cells (HCCs). ATOH8 downregulation is associated with loss of tumor differentiation, indicating an effect mediated by cancer stem cells. We investigated the effects of loss of ATOH8 in human hepatocellular carcinoma (HCC) cells and cell lines. METHODS: HCC and adjacent nontumor tissues were collected, from 2001 through 2012, from 242 patients undergoing hepatectomy at Sun Yat-Sen University Cancer Center in China; 83% of HCCs were associated with hepatitis B virus (HBV) infection. CD133(+) cells were isolated from tumor tissues by flow cytometry. Experiments were performed in HBV-positive and HBV-negative HCC cell lines, the immortalized liver cell line LO2, and 8 other HCC cell lines. ATOH8 was expressed from lentiviral vectors in PLC8024 and Huh7 cells; levels were knocked down with small interfering RNAs in QSG7701 cells. Cells carrying empty vectors were used as controls. Gene regulation by ATOH8 was assessed in mobility shift and luciferase reporter assays. Cells were analyzed in proliferation, foci formation, and colony formation assays. The tumorigenic and chemo-resistant potential of cells were investigated by assessing growth of xenograft tumors in immunocompromised mice. Metastatic features of cells were assessed in Matrigel invasion assays and wound healing analyses. RESULTS: Levels of ATOH8 mRNA were reduced by more than 4-fold, compared to nontumor tissues, in 118 of 242 HCC samples (48.8%). Patients with tumor reductions in ATOH8 had significantly shorter times of disease-free survival (mean, 41.4 months) than patients with normal tissue levels (mean, 52.6 months). ATOH8 expression was reduced in HepG2, Huh7, PLC8024 and CRL8064 HCC cells, as well as CD133(+) cells isolated from human HCC samples. Transgenic expression of ATOH8 in HCC cell lines significantly reduced proliferation and foci colony formation, as well as their invasive and migratory abilities. Transgenic expression of ATOH8 reduced the ability of HBV-positive PLC8024 cells to form tumors in mice, compared to control cells. Cells with ATOH8 knockdown formed xenograft tumors more rapidly, in more mice, than control cells. ATOH8 repressed transcription of stem-cell associated genes including OCT4, NANOG, and CD133. Knockdown of ATOH8 in CD133-negative QSG7701 cells caused them to express CD133; acquire self-renewal, differentiation, chemo-resistance properties; form more xenograft tumors in mice; and generate induced pluripotent stem cells (based on staining for alkaline phosphatase and their ability to form embryoid bodies and teratomas). Alternatively, expression of ATOH8 in PLC8024 and Huh7 cells significantly reduced the numbers of cells expressing CD133, and increased the chemo-sensitivity of Huh7 cells to 5-fluorouracil (5-FU) and cisplatin, in vitro and in mice. CONCLUSIONS: ATOH8 appears to be a tumor suppressor that induces stem-cell features and chemoresistance in HCC cells. Strategies to restore its levels and activities might be developed to treat patients with liver cancer.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Carcinoma Hepatocelular/metabolismo , Desdiferenciação Celular , Neoplasias Hepáticas/metabolismo , Células-Tronco Neoplásicas/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Antígeno AC133 , Animais , Antígenos CD/metabolismo , Antineoplásicos/farmacologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Movimento Celular , Proliferação de Células , Sobrevivência Celular , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Regulação para Baixo , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica , Glicoproteínas/metabolismo , Células Hep G2 , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Camundongos SCID , Invasividade Neoplásica , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Peptídeos/metabolismo , Interferência de RNA , RNA Mensageiro/metabolismo , Terapêutica com RNAi , Transdução de Sinais , Fatores de Tempo , Transcrição Gênica , Transfecção , Proteínas Supressoras de Tumor/genética , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Gut ; 63(5): 832-43, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-23766440

RESUMO

OBJECTIVE: Hepatocellular carcinoma (HCC) is a heterogeneous tumour displaying a complex variety of genetic and epigenetic changes. In human cancers, aberrant post-transcriptional modifications, such as alternative splicing and RNA editing, may lead to tumour specific transcriptome diversity. DESIGN: By utilising large scale transcriptome sequencing of three paired HCC clinical specimens and their adjacent non-tumour (NT) tissue counterparts at depth, we discovered an average of 20 007 inferred A to I (adenosine to inosine) RNA editing events in transcripts. The roles of the double stranded RNA specific ADAR (Adenosine DeAminase that act on RNA) family members (ADARs) and the altered gene specific editing patterns were investigated in clinical specimens, cell models and mice. RESULTS: HCC displays a severely disrupted A to I RNA editing balance. ADAR1 and ADAR2 manipulate the A to I imbalance of HCC via their differential expression in HCC compared with NT liver tissues. Patients with ADAR1 overexpression and ADAR2 downregulation in tumours demonstrated an increased risk of liver cirrhosis and postoperative recurrence and had poor prognoses. Due to the differentially expressed ADAR1 and ADAR2 in tumours, the altered gene specific editing activities, which was reflected by the hyper-editing of FLNB (filamin B, ß) and the hypo-editing of COPA (coatomer protein complex, subunit α), are closely associated with HCC pathogenesis. In vitro and in vivo functional assays prove that ADAR1 functions as an oncogene while ADAR2 has tumour suppressive ability in HCC. CONCLUSIONS: These findings highlight the fact that the differentially expressed ADARs in tumours, which are responsible for an A to I editing imbalance, has great prognostic value and diagnostic potential for HCC.


Assuntos
Adenosina Desaminase/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , Edição de RNA , RNA de Cadeia Dupla/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/cirurgia , Estudos de Casos e Controles , Linhagem Celular Tumoral , Intervalo Livre de Doença , Regulação para Baixo , Feminino , Seguimentos , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/cirurgia , Masculino , Camundongos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Proteínas de Ligação a RNA/metabolismo , Resultado do Tratamento , Regulação para Cima
6.
Sci Rep ; 14(1): 1732, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38242968

RESUMO

For the first time, we enable the execution of hybrid quantum machine learning (HQML) methods on real quantum computers with 100 data samples and real-device-based simulations with 5000 data samples, thereby outperforming the current state of research of Suryotrisongko and Musashi from 2022 who were dealing with 1000 data samples and quantum simulators (pure software-based emulators) only. Additionally, we beat their reported accuracy of 76.8% by an average accuracy of 91.2%, all within a total execution time of 1687 s. We achieve this significant progress through two-step strategy: Firstly, we establish a stable quantum architecture that enables us to execute HQML algorithms on real quantum devices. Secondly, we introduce new hybrid quantum binary classifiers (HQBCs) based on Hoeffding decision tree algorithms. These algorithms speed up the process via batch-wise execution, reducing the number of shots required on real quantum devices compared to conventional loop-based optimizers. Their incremental nature serves the purpose of online large-scale data streaming for domain generation algorithm (DGA) botnet detection, and allows us to apply HQML to the field of cybersecurity analytics. We conduct our experiments using the Qiskit library with the Aer quantum simulator, and on three different real quantum devices from Azure Quantum: IonQ, Rigetti, and Quantinuum. This is the first time these tools are combined in this manner.

7.
Prog Mol Subcell Biol ; 53: 299-328, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22222838

RESUMO

Phthalate esters (PAEs) are important industrial compounds mainly used as plasticizers to increase flexibility and softness of plastic products. PAEs are of major concern because of their widespread use, ubiquity in the environment, and endocrine-disrupting toxicity. In this study, two fungal strains, Fusarium sp. DMT-5-3 and Trichosporon sp. DMI-5-1 which had the capability to degrade dimethyl phthalate esters (DMPEs), were isolated from mangrove sediments in the Futian Nature Reserve of Shenzhen, China, by enrichment culture technique. These fungi were identified on the basis of spore morphology and molecular typing using 18S rDNA sequence. Comparative investigations on the biodegradation of three isomers of DMPEs, namely dimethyl phthalate (DMP), dimethyl isophthalate (DMI), and dimethyl terephthalate (DMT), were carried out with these two fungi. It was found that both fungi could not completely mineralize DMPEs but transform them to the respective monomethyl phthalate or phthalate acid. Biochemical degradation pathways for different DMPE isomers by both fungi were different. Both fungi could transform DMT to monomethyl terephthalate (MMT) and further to terephthalic acid (TA) by stepwise hydrolysis of two ester bonds. However, they could only carry out one-step ester hydrolysis to transform DMI to monomethyl isophthalate (MMI). Further metabolism of MMI did not proceed. Only Trichosporon sp. was able to transform DMP to monomethyl phthalate (MMP) but not Fusarium sp. The optimal pH for DMI and DMT degradation by Fusarium sp. was 6.0 and 4.5, respectively, whereas for Trichosporon sp., the optimal pH for the degradation of all the three DMPE isomers was at 6.0. These results suggest that the fungal esterases responsible for hydrolysis of the two ester bonds of PAEs are highly substrate specific.


Assuntos
Ésteres , Trichosporon , Biodegradação Ambiental , Ésteres/química , Fusarium/metabolismo , Plastificantes/química , Trichosporon/metabolismo
8.
J Nat Prod ; 72(3): 443-9, 2009 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-19323567

RESUMO

The overexpression of the Mcl-1 protein in cancerous cells results in the sequestering of Bak, a key component in the regulation of normal cell apoptosis. Our investigation of the ability of marine-derived small-molecule natural products to inhibit this protein-protein interaction led to the isolation of several bioactive oxy-polyhalogenated diphenyl ethers. A semipure extract, previously obtained from Dysidea (Lamellodysidea) herbacea and preserved in our repository, along with an untouched Dysidea granulosa marine sponge afforded 13 distinct oxy-polyhalogenated diphenyl ethers. Among these isolates were four new compounds, 5, 6, 10, and 12. The structure elucidation of these molecules was complicated by the plethora of structural variants that exist in the literature. During dereplication, we established a systematic method for analyzing this class of compounds. The strategy is governed by trends in the (1)H and (13)C NMR shifts of the aromatic rings, and the success of the strategy was checked by X-ray crystal structure analysis.


Assuntos
Antineoplásicos , Dysidea/química , Éteres Difenil Halogenados , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Éteres Difenil Halogenados/química , Éteres Difenil Halogenados/isolamento & purificação , Éteres Difenil Halogenados/farmacologia , Conformação Molecular , Estrutura Molecular , Proteína de Sequência 1 de Leucemia de Células Mieloides , Ressonância Magnética Nuclear Biomolecular , Proteínas Proto-Oncogênicas c-bcl-2/efeitos dos fármacos
9.
Clin Oral Implants Res ; 20(10): 1084-91, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19751357

RESUMO

OBJECTIVES: To compare the performance and safety of Inion GTR(TM) Biodegradable Membrane System and Geistlich resorbable bilayer Bio-Gide((R)) membrane in human bone regeneration. MATERIAL AND METHODS: In a multicenter, split blind, comparative, randomized, prospective, pilot study 15 patients have been randomized at surgery whether to be treated either with Inion GTR(TM) Biodegradable Membrane System on one and Geistlich resorbable bilayer Bio-Gide((R)) membrane on the other side or vice versa after surgical removal of both fully impacted wisdom teeth. During the follow-up visits at week 1, 2 and 6 and at months 3 and 6 the general state, the wound, eventual adverse events and the medication of the patients were assessed. Computed Tomography (CT) scans were performed immediately and 3 months after the surgery, before biopsy collection. Semi-quantitative histological evaluation and histomorphometric analyses were performed according to the ISO 10993-6 standard. New bone formation and membrane integration were evaluated by CT scan measurements. Tissue healing was evaluated clinically and by photographs between the time on teeth extraction and during follow ups. RESULTS: Five patients were smokers, none drank alcohol. Mild adverse events like wound infection, haematoma or late swelling of the gums occurred in three patients. The trephine bur harvest of bone biopsies under local anaesthesia was uneventful. Whereas specimens from the sites treated with the Inion membrane yielded 17.0% (SD 24%), the Bio-Gide membrane sites yielded 13.5% (SD 15%) of bone tissue density. In sites treated with the Inion membrane, 9.5% of old bone density and 7.5% of newly formed bone could be found, whereas the Bio-Gide((R)) membrane sites showed 3.8% of old bone density and 9.8% of newly formed bone. There were no statistically significant differences between the two groups with respect to the two variables. The osteoid rim was more extended with the Bio-Gide((R)) (6.6 mm) than with the Inion membrane (5.1 mm) but the difference between the two treatments did not reach statistical significance. Highly significant reductions in the area of the defect with both membranes were detected with significant increases in CT density at the immediate inferio-buccal adjacent bone and in the surgical defect area with both membranes. However, there was neither significant change in CT density in the immediate inferior-lingual adjacent bone of the two membranes, nor significant difference between the membranes on any of the four measurements (area of defect: P=0.1354; CT density immediate inferio-buccal adjacent bone: P=0.7615; CT density surgical defect area: P=0.1876; CT density immediate inferio-lingual adjacent bone: P=0.4212). CONCLUSION: The overall clinical outcome was satisfying and the majority of the patients showed an uneventful healing phase. Both membranes presented similar capacities regarding their barrier function and were associated with analogous bone regeneration. No statistically valid evidence about the superiority of one particular membrane was obtained. For the patient the only difference is that one product is animal derived and the other synthetic.


Assuntos
Processo Alveolar/fisiologia , Materiais Biocompatíveis/uso terapêutico , Regeneração Óssea/fisiologia , Regeneração Tecidual Guiada Periodontal/métodos , Membranas Artificiais , Extração Dentária , Implantes Absorvíveis , Adolescente , Adulto , Processo Alveolar/efeitos dos fármacos , Aumento do Rebordo Alveolar/métodos , Densidade Óssea/efeitos dos fármacos , Regeneração Óssea/efeitos dos fármacos , Colágeno/uso terapêutico , Feminino , Humanos , Masculino , Dente Serotino/cirurgia , Osteogênese/efeitos dos fármacos , Osteogênese/fisiologia , Projetos Piloto , Polímeros/uso terapêutico , Estudos Prospectivos , Método Simples-Cego , Dente Impactado/cirurgia , Resultado do Tratamento , Cicatrização/efeitos dos fármacos , Cicatrização/fisiologia , Adulto Jovem
10.
J Oral Maxillofac Surg ; 67(12): 2653-62, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19925987

RESUMO

PURPOSE: The aim of the present study was to describe immediate functional loading of completely edentulous maxillas and mandibles by fixed provisional prostheses and to compare cumulative survival rates between maxillas and mandibles. Contributing factors including implant diameter, system, configuration, type of abutment connections, position of implants, and insertion torque values were investigated. PATIENTS AND METHODS: From August 2001 to March 2007, 111 patients treated at the Associated Brånemark Osseointegration Center, Hong Kong, who received immediate functional loading of implants by fixed completely edentulous provisional prostheses were reviewed. Marginal bone changes were measured. RESULTS: There were 48 edentulous maxillas and 85 edentulous mandibles, in total 133 arches. Twenty-two cases received simultaneous maxillary and mandibular rehabilitation. Three hundred nineteen implants were used for the maxilla and 371 implants for the mandible, in total 690 implants. A mean of 6.65 fixtures was used to reconstruct an edentulous maxilla and a mean of 4.36 implants for an edentulous mandible. The mean follow-up period was 29.5 months, ranging from 11.5 to 71 months. Six hundred seventy-two of 690 implants (97.4%) had been followed up at least 1 year. Four implants failed in the maxilla and 5 implants failed in the mandible. Mean marginal bone loss was 0.07 mm after 1 year. Mean failure time was 2.89 months postoperatively (range, 2 to 5 mo). In those failed implants, maximal insertion torque values were significantly lower than those of successful ones. The immediate loading protocol constituted cumulative survival rates of 98.7% for the maxilla and 98.7% for the mandible, with an overall cumulative survival rate of 98.7%. There was no significant difference in survival rates between the maxillas and mandibles (chi(2) exact test, P = 1.000). The implant survival rate was found to be not related to implant diameter, system, configuration, type of abutment connections, and position of implants (P > .05). CONCLUSION: The immediate loading protocol by fixed provisional prostheses proved to be an effective method in restoring completely edentulous maxillas and mandibles, and the maximal insertion torque value may be a prognostic factor in determining success.


Assuntos
Prótese Dentária Fixada por Implante , Restauração Dentária Temporária , Arcada Edêntula/reabilitação , Adulto , Idoso , Idoso de 80 Anos ou mais , Falha de Restauração Dentária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios , Radiografia Panorâmica
11.
Oncotarget ; 8(48): 83469-83479, 2017 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-29137357

RESUMO

Hepatocellular carcinoma (HCC), which accounts for 85-90% of primary liver cancer, is now the second leading cause of cancer-related mortality worldwide. Here we reported that Aldo-Keto Reductase family 7A isoform 3 (AKR7A3) is frequently down-regulated in HCC, associating with poor overall survival rate, elevated serum α-fetoprotein (AFP) and poor differentiation of HCC. The promoter region of AKR7A3 was detected to be hypermethylated. Loss of heterozygosity (LOH) was also detected in AKR7A3. Functional assays on both AKR7A3 overexpressed and knockdown cells, including foci formation, colony formation in soft agar, migration, invasion and tumor formation in nude mice, demonstrated the strong tumor suppressive functions of AKR7A3. In addition, treatment of chemotherapy drug cisplatin showed that AKR7A3 sensitizes tumor cells to apoptosis. Mechanistically, western blot analysis showed that overexpression of AKR7A3 inhibits the activation of ERK, c-Jun and NF-κB. In summary, we found that AKR7A3 functions as a tumor suppressor gene in HCC through attenuating c-Jun, ERK and NF-κB signaling pathways.

12.
Can Urol Assoc J ; 8(1-2): 24-7, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24578738

RESUMO

INTRODUCTION: Most small renal masses (SRMs) are diagnosed incidentally and have a low malignant potential. As more elderly patients and infirm patients are diagnosed with SRMs, there is an increased interest in active surveillance (AS) with delayed intervention. Patient and tumour characteristics relating to aggressive disease have not been well-studied. The objective was to determine predictors of growth of SRMs treated with AS. METHODS: A multicentre prospective phase 2 clinical trial was conducted on 207 SRMs in 169 patients in 8 institutions in Canada from 2004 to 2009; in these patients treatment was delayed until disease progression. Patient and tumour characteristics were evaluated to determine predictors of growth of SRMs by measuring rates of change in growth (on imaging) over time. All patients underwent AS for presumed renal cell carcinoma (RCC) based on diagnostic imaging. We used the following factors to develop a predictive model of tumour growth with binary recursive partitioning analysis: patient characteristics (age, symptoms at diagnosis) and tumour characteristics (consistency [solid vs. cystic] and maximum diameter at diagnosis. RESULTS: With a median follow-up of 603 days, 169 patients (with 207 SRMs) were followed prospectively. Age, symptoms at diagnosis, tumour consistency and maximum diameter of the renal mass were not predictors of growth. This cohort was limited by lack of availability of patient and tumour characteristics, such as sex, degree of endophytic component and tumour location. CONCLUSION: Slow growth rates and the low malignant potential of SRMs have led to AS as a treatment option in the elderly and infirm population. In a large prospective cohort, we have shown that age, symptoms, tumour consistency and maximum diameter of the mass at diagnosis are not predictors of growth of T1a lesions. More knowledge on predictors of growth of SRMs is needed.

13.
Nat Med ; 19(2): 209-16, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23291631

RESUMO

A better understanding of human hepatocellular carcinoma (HCC) pathogenesis at the molecular level will facilitate the discovery of tumor-initiating events. Transcriptome sequencing revealed that adenosine-to-inosine (A→I) RNA editing of AZIN1 (encoding antizyme inhibitor 1) is increased in HCC specimens. A→I editing of AZIN1 transcripts, specifically regulated by ADAR1 (encoding adenosine deaminase acting on RNA-1), results in a serine-to-glycine substitution at residue 367 of AZIN1, located in ß-strand 15 (ß15) and predicted to cause a conformational change, induced a cytoplasmic-to-nuclear translocation and conferred gain-of-function phenotypes that were manifested by augmented tumor-initiating potential and more aggressive behavior. Compared with wild-type AZIN1 protein, the edited form has a stronger affinity to antizyme, and the resultant higher AZIN1 protein stability promotes cell proliferation through the neutralization of antizyme-mediated degradation of ornithine decarboxylase (ODC) and cyclin D1 (CCND1). Collectively, A→I RNA editing of AZIN1 may be a potential driver in the pathogenesis of human cancers, particularly HCC.


Assuntos
Carcinoma Hepatocelular/genética , Proteínas de Transporte/genética , Neoplasias Hepáticas/genética , Edição de RNA , Transporte Ativo do Núcleo Celular , Adenosina Desaminase/fisiologia , Animais , Carcinoma Hepatocelular/etiologia , Linhagem Celular Tumoral , Proliferação de Células , Ciclina D1/metabolismo , Humanos , Neoplasias Hepáticas/etiologia , Masculino , Camundongos , Ornitina Descarboxilase/metabolismo , Proteínas de Ligação a RNA
14.
Int J Med Inform ; 81(3): 182-91, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22217801

RESUMO

PURPOSE: The purpose of this study was to evaluate the functionality of eKidney as a structured reporting tool in operative note generation. To do this, we compared completeness and timeliness of eKidney template-generated nephrectomy OR notes with standard narrative dictation. METHODS: A group of academic uro-oncologists and medical informaticians at the University Health Network designed and adopted an electronic online, point-of-care clinical documentation tool, eCancerCare(Kidney) (eKidney) for kidney cancer patient care. The optimal components of clinic and operative note templates, including those for nephrectomy, were agreed upon by expert consensus of the uro-oncologists. Clinician nephrectomy OR reports were analyzed for completeness, comparing those generated in eKidney with conventionally dictated notes. Patterns of missing information from both dictated and eKidney-generated reports were analyzed. The procedure, note completion and transcription dates were recorded which generated time intervals between these events. The records of 189 procedures were included in the analysis. RESULTS: Comparison of clinicians who used both note generation modalities, revealed a mean completion rate of 92% for eKidney/structured notes and 68% for dictated notes (p<0.0001). There was no significant difference in completion rates between attending staff and trainees (residents and fellows) (p=0.131). Most notes were dictated/entered on the day of surgery. Dictated notes were transcribed to EPR a median of 2 days after dictation, however roughly 30% of dictated notes took 5 days or more to get transcribed. All notes generated using eKidney were uploaded to the EPR immediately. LIMITATIONS: Our study has three significant limitations. Firstly, our study was not randomized: physicians could elect to dictate or use eKidney. Secondly, we did not identify data from dictated notes that were not captured by eKidney. Third, we did not compare the time it took physicians to complete the fields in eKidney with the time it takes to dictate a note. CONCLUSIONS: We have demonstrated that the use of structured reporting improves the completeness and timeliness of documentation in kidney cancer surgery. eKidney is an example of the power of templates in ensuring that important details of a procedure are recorded. Future studies looking at user satisfaction, and research and educational potential of eKidney would be valuable.


Assuntos
Controle de Formulários e Registros , Neoplasias Renais/cirurgia , Sistemas Computadorizados de Registros Médicos/normas , Padrões de Prática Médica/normas , Humanos
15.
J Am Med Inform Assoc ; 18(6): 835-41, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21816957

RESUMO

OBJECTIVE: To compare the use of structured reporting software and the standard electronic medical records (EMR) in the management of patients with bladder cancer. The use of a human factors laboratory to study management of disease using simulated clinical scenarios was also assessed. DESIGN: eCancerCare(Bladder) and the EMR were used to retrieve data and produce clinical reports. Twelve participants (four attending staff, four fellows, and four residents) used either eCancerCare(Bladder) or the EMR in two clinical scenarios simulating cystoscopy surveillance visits for bladder cancer follow-up. MEASUREMENTS: Time to retrieve and quality of review of the patient history; time to produce and completeness of a cystoscopy report. Finally, participants provided a global assessment of their computer literacy, familiarity with the two systems, and system preference. RESULTS: eCancerCare(Bladder) was faster for data retrieval (scenario 1: 146 s vs 245 s, p=0.019; scenario 2: 306 vs 415 s, NS), but non-significantly slower to generate a clinical report. The quality of the report was better in the eCancerCare(Bladder) system (scenario 1: p<0.001; scenario 2: p=0.11). User satisfaction was higher with the eCancerCare(Bladder) system, and 11/12 participants preferred to use this system. LIMITATIONS: The small sample size affected the power of our study to detect differences. CONCLUSIONS: Use of a specific data management tool does not appear to significantly reduce user time, but the results suggest improvement in the level of care and documentation and preference by users. Also, the use of simulated scenarios in a laboratory setting appears to be a valid method for comparing the usability of clinical software.


Assuntos
Registros Eletrônicos de Saúde , Gestão da Informação/métodos , Sistemas Automatizados de Assistência Junto ao Leito , Software , Neoplasias da Bexiga Urinária/terapia , Atitude Frente aos Computadores , Comportamento do Consumidor , Documentação , Humanos , Armazenamento e Recuperação da Informação , Inquéritos e Questionários , Fatores de Tempo , Interface Usuário-Computador
16.
Eur Urol ; 60(1): 39-44, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21477920

RESUMO

BACKGROUND: Most early stage kidney cancers are renal cell carcinomas (RCCs), and most are diagnosed incidentally by imaging as small renal masses (SRMs). Indirect evidence suggests that most small RCCs grow slowly and rarely metastasize. OBJECTIVE: To determine the progression and growth rates for newly diagnosed SRMs stratified by needle core biopsy pathology. DESIGN, SETTING, AND PARTICIPANTS: A multicenter prospective phase 2 clinical trial of active surveillance of 209 SRMs in 178 elderly and/or infirm patients was conducted from 2004 until 2009 with treatment delayed until progression. INTERVENTION: Patients underwent serial imaging and needle core biopsies. MEASUREMENTS: We measured rates of change in tumor diameter (growth measured by imaging) and progression to ≥ 4 cm, doubling of tumor volume, or metastasis with histology on biopsy. RESULTS AND LIMITATIONS: Local progression occurred in 25 patients (12%), plus 2 progressed with metastases (1.1%). Of the 178 subjects with 209 SRMs, 127 with 151 SRMs had>12 mo of follow-up with two or more images, with a mean follow-up of 28 mo. Their tumor diameters increased by an average of 0.13 cm/yr. Needle core biopsy in 101 SRMs demonstrated that the presence of RCC did not significantly change growth rate. Limitations included no central review of imaging and pathology and a short follow-up. CONCLUSIONS: This is the first SRM active surveillance study to correlate growth with histology prospectively. In the first 2 yr, the rate of local progression to higher stage is low, and metastases are rare. SRMs appear to grow very slowly, even if biopsy proven to be RCC. Many patients with SRMs can therefore be initially managed conservatively with serial imaging, avoiding the morbidity of surgical or ablative treatment.


Assuntos
Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/terapia , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha , Progressão da Doença , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Vigilância da População , Estudos Prospectivos
17.
J Oral Maxillofac Surg ; 65(6): 1128-34, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17517296

RESUMO

PURPOSE: To describe a method for stereomodel-assisted fibula flap harvest and mandibular reconstruction utilizing multiple fibula bony segments. MATERIALS AND METHODS: Stereomodels of the mandible and the fibula were obtained from computed tomography scan data. The length of fibula to be harvested was predetermined by measurement of the stimulated of existing mandibular defect on the mandibular stereomodel. A titanium reconstruction plate was shaped to fit the original mandibular contour. The stereomodel fibula was divided into multiple segments and the segments were placed on the mandibular stereomodel in the ideal edentulous position against the upper dentition and simulate the angular contour of the mandible for best comesis. The predetermined bony segments were measured and the system was then transferred to the patient in the operation theater using acrylic locating splints. RESULTS: Experience with 8 patients (2 primary and 2 secondary reconstructions) indicated that a good clinical outcome in terms of mandibular contour and positions of the reconstructed segment was possible. The outer facial appearance and symmetry were consistently excellent and no instability or malposition of the graft segments was encountered. CONCLUSION: Stereomodel-assisted fibula flap harvest and insertion is a worthwhile attempt at improving the results of mandibular reconstruction and deserves further attention.


Assuntos
Transplante Ósseo/métodos , Desenho Assistido por Computador , Fíbula/cirurgia , Neoplasias Mandibulares/cirurgia , Modelos Anatômicos , Planejamento de Assistência ao Paciente , Procedimentos de Cirurgia Plástica/métodos , Coleta de Tecidos e Órgãos/métodos , Adolescente , Idoso , Placas Ósseas , Estética , Feminino , Fíbula/anatomia & histologia , Humanos , Arcada Edêntula/patologia , Masculino , Mandíbula/patologia , Prótese Mandibular , Pessoa de Meia-Idade , Titânio , Resultado do Tratamento
18.
Artigo em Inglês | MEDLINE | ID: mdl-16997111

RESUMO

In a patient with temporomandibular disorder who does not respond to conservative treatment, treatment with intra-articular injection of high molecular weight sodium hyaluronate can be suggested. In our study, 27 patients with nonreduced disc displacement were diagnosed clinically and confirmed by magnetic resonance imaging. The age range was from 21 to 63 years old, with a mean of 39.3 years. Two cycles of injection of high molecular weight sodium hyaluronate was performed on alternative weeks. Pain intensity was measured by the visual analog scale. Maximal mouth opening, clicking joint noise, and lateral movement were measured before and after injection for more than 6 months. Reduction of pain intensity and improvement in the maximum mouth opening parameter was statistically significant. In conclusion, this intra-articular injection using high molecular weight sodium hyaluronate looks very positive for patients affected by nonreduced disc displacement and is encouraged to be used as a primary treatment of temporomandibular joint dysfunction.


Assuntos
Ácido Hialurônico/administração & dosagem , Transtornos da Articulação Temporomandibular/tratamento farmacológico , Adulto , Dor Facial/tratamento farmacológico , Feminino , Seguimentos , Humanos , Injeções Intra-Articulares , Luxações Articulares/tratamento farmacológico , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Peso Molecular , Amplitude de Movimento Articular , Resultado do Tratamento
19.
Ann Biomed Eng ; 33(10): 1344-51, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16240083

RESUMO

We studied the mechanisms by which turbulent flow induces tracheal wall vibrations detected as tracheal breath sounds (TRBSs). The effects of flow rate at transitional Reynold's numbers (1300-10,000) and gas density on spectral patterns of TRBSs in eight normal subjects were measured. TRBSs were recorded with a contact sensor during air and heliox breathing at four flow rates (1.0, 1.5, 2.0, and 2.5 l/s). We found that normalized TRBSs were proportional to flow to the 1.89 power during inspiration and to the 1.59 power during expiration irrespective of gas density. The amplitude of TRBSs with heliox was lower than with air by a factor of 0.33 +/- 0.12 and 0.44 +/- 0.16 during inspiration and expiration, respectively. The spectral resonance frequencies were higher during heliox than air breathing by a factor of 1.75 +/- 0.2-approximately the square root of the reciprocal of the air/heliox wave propagation speed ratio. In conclusion, the flow-induced pressure fluctuations inside the trachea, which cause tracheal wall vibrations, were detected as TRBSs consist of two components: (1) a dominant local turbulent eddy component whose amplitude is proportional to the gas density and nonlinearly related to the flow; and (2) a propagating acoustic component with resonances whose frequencies correspond to the length of the upper airway and to the free-field sound speed. Therefore, TRBSs consist primarily of direct turbulent eddy pressure fluctuations that are perceived as sound during auscultation.


Assuntos
Auscultação/métodos , Diagnóstico por Computador/métodos , Modelos Biológicos , Mecânica Respiratória/fisiologia , Sons Respiratórios/fisiologia , Espectrografia do Som/métodos , Traqueia/fisiologia , Adulto , Simulação por Computador , Humanos , Masculino
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