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1.
J Cell Mol Med ; 2020 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-32543783

RESUMO

This study aims to explore lipidic mechanism towards low-density lipoprotein receptor (LDLR)-mediated platinum chemotherapy resistance. By using the lipid profiling technology, LDLR knockdown was found to increase lysosomal lipids and decrease membranous lipid levels in EOC cells. LDLR knockdown also down-regulated ether-linked phosphatidylethanolamine (PE-O, lysosomes or peroxisomes) and up-regulated lysophosphatidylcholine [LPC, lipid droplet (LD)]. This implies that the manner of using Lands cycle (conversion of lysophospholipids) for LDs might affect cisplatin sensitivity. The bioinformatics analyses illustrated that LDLR-related lipid entry into LD, rather than an endogenous lipid resource (eg Kennedy pathway), controls the EOC prognosis of platinum chemotherapy patients. Moreover, LDLR knockdown increased the number of platinum-DNA adducts and reduced the LD platinum amount. By using a manufactured LPC-liposome-cisplatin (LLC) drug, the number of platinum-DNA adducts increased significantly in LLC-treated insensitive cells. Moreover, the cisplatin content in LDs increased upon LLC treatment. Furthermore, lipid profiles of 22 carcinoma cells with differential cisplatin sensitivity (9 sensitive vs 13 insensitive) were acquired. These profiles revealed low storage lipid levels in insensitive cells. This result recommends that LD lipidome might be a common pathway in multiple cancers for platinum sensitivity in EOC. Finally, LLC suppressed both cisplatin-insensitive human carcinoma cell training and testing sets. Thus, LDLR-platinum insensitivity can be due to a defective Lands cycle that hinders LPC production in LDs. Using lipidome assessment with the newly formulated LLC can be a promising cancer chemotherapy method.

2.
Trends Cancer ; 6(5): 380-391, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32348734

RESUMO

Glioblastoma is the most common primary malignant brain tumor. Although current standard therapy extends median survival to ~15 months, most patients do not have a sustained response to treatment. While O6-methylguanine (O6-MeG)-DNA methyltransferase (MGMT) promoter methylation status is accepted as a prognostic and promising predictive biomarker in glioblastoma, its value in informing treatment decisions for glioblastoma patients remains debatable. Discrepancies between MGMT promoter methylation status and treatment response in some patients may stem from inconsistencies between MGMT methylation and expression levels in glioblastoma. Here, we discuss MGMT as a biomarker and elucidate the discordance between MGMT methylation, expression, and patient outcome, which currently challenges the implementation of this biomarker in clinical practice.

3.
Anticancer Res ; 40(3): 1285-1295, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32132025

RESUMO

BACKGROUND/AIM: The role of androgen receptor (AR) in hepatocellular carcinoma (HCC) development is controversial. Therefore, the translational value of targeting AR in HCC is unknown. Sorafenib, a multiple kinase inhibitor, is the standard therapy for patients with unresectable HCC. This study investigated sorafenib effect on AR in experimental models of HCC. MATERIAL AND METHODS: AR cDNA was introduced into HCC cells and in vitro cell growth and in vivo tumor growth were measured. Sphere cells, as well as epithelial cell adhesion molecule-positive (EpCAM+) and CD133+ cells were isolated from HCC cells with/without AR expression to observe in vitro/in vivo effects. Liver specific AR knockout in mouse models of spontaneous HCC (carcinogen-induced and hepatitis B virus-related HCC) was also implemented to examine gene expression. HCC cells/tumors were treated with sorafenib in order to determine effects on tumor growth and related gene expression. RESULT: AR cDNA increased transactivation function, increased colony/sphere-forming activities, and enhanced tumorigenicity in HCC cells compared to their parental cells. Expression of the stemness marker EpCAM was also dramatically increased. In carcinogen-and HBV-induced HCC models, EpCAM+ cells were significantly reduced in AR-knockout mice compared to wild-type HCCs. In addition, AR reduced sorafenib-related signals, e.g. extracellular-regulated kinase, AKT serine/threonine kinase 1, and p38 mitogen-activated protein kinase, compared to that in parental cells. Regarding sorafenib cytotoxicity, AR-expressing cells were vulnerable to treatment. Moreover, the half maximal-inhibitory concentration (IC50) was drastically lowered in AR+/EpCAM+ compared to AR-/EpCAM- sphere cells. Strikingly, the IC50 in AR+/CD133+ vs. AR-/CD133+ cells were similar. Moreover, sorafenib robustly suppressed tumor growth in implanted AR+/EpCAM+ cells but not AR-/EpCAM- ones. Finally, bioinformatics analyses revealed EpCAM to be a prognostic biomarker in Asian and non-alcohol-consuming patients with HCC, suggesting suitability of a sorafenib regimen for such patients. CONCLUSION: AR+/EpCAM+ may be a marker of responsiveness to sorafenib for patients with HCC. Prospective surveys associating AR/EpCAM expression with therapy outcomes are essential.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Molécula de Adesão da Célula Epitelial/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Receptores Androgênicos/metabolismo , Sorafenibe/uso terapêutico , Animais , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Molécula de Adesão da Célula Epitelial/farmacologia , Humanos , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Sorafenibe/farmacologia , Transfecção
4.
Reprod Biol Endocrinol ; 18(1): 12, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32070380

RESUMO

BACKGROUND: Pregnant women have high serum concentrations of sex steroid hormones, which are major regulators of paracrine and autocrine responses for many maternal and placental functions. The main purpose of this study was to compare patients with preeclampsia and patients with uncomplicated pregnancies in terms of serum steroid hormones (estradiol [E2], progesterone [P4], dehydroepiandrosterone sulfate [DHEAS], and testosterone [T]) throughout pregnancy and the levels of cord blood and placental steroid receptors during the third trimester. METHODS: Quantitative real-time reverse transcription PCR, western blotting, and immunohistochemistry were used to determine the levels of steroid hormones in the serum and cord blood and the placental levels of estrogen receptor-α (ERα), ERß, androgen receptor (AR), and progesterone receptor (PR). RESULTS: There were 45 women in the uncomplicated pregnancy group and 30 women in the preeclampsia group. Serum levels of T were greater and serum levels of E2 were reduced in the preeclampsia group, but the two groups had similar levels of P4 and DHEAS during the third trimester. Cord blood had a decreased level of DHEAS in the preeclampsia group, but the two groups had similar levels of P4, E2, and T. The two groups had similar placental mRNA levels of ERα, ERß, AR, and PR, but the preeclampsia group had a higher level of ERß protein and a lower level of ERα protein. Immunohistochemistry indicated that the preeclampsia group had a greater level of ERß in the nucleus and cytoplasm of syncytiotrophoblasts and stromal cells. CONCLUSIONS: Women with preeclampsia had lower levels of steroid hormones, estrogen, and ERα but higher levels of T and ERß. These molecules may have roles in the pathogenesis of preeclampsia.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32102749

RESUMO

BACKGROUND: This study aims to investigate the antimicrobial ability and mechanism analysis of Lactobacillus species against carbapenemase-producing Enterobacteriaceae (CPE). METHODS: Five Lactobacillus spp. strains and 18 CPE clinical isolates were collected. Their anti-CPE effects were assessed by agar well diffusion and broth microdilution assay, as well as time-kill test. Finally, the specific anti-CPE mechanism, especially for the effect of organic acids was determined using broth microdilution method. RESULTS: All of five Lactobacilli isolates displayed the potent activity against most CPE isolates with mean zones of inhibition ranging 10.2-21.1 mm. The anti-CPE activity was not affected by heating, catalase, and proteinase treatment. Under the concentration of 50% LUC0180 cell-free supernatant (CFS), lactic acid, and mix acid could totally inhibit the growth of carbapenem-resistant Klebsiella pneumoniae (CPE0011), and acetic acid could inhibit 67.8%. In contrast, succinic acid and citric acid could not inhibit the growth of CPE0011. While we decreased the concentration to 25%, only lactic acid and mix acid displayed 100% inhibition. In contrast, succinic acid, citric acid and acetic acid did not show any inhibitory effect. CONCLUSIONS: Lactobacillus strains exhibit potent anti-CPE activity, and lactic acid produced by Lactobacillus strains is the major antimicrobial mechanism.

6.
Nanotechnology ; 31(29): 295204, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32050168

RESUMO

Organic light-emitting diodes (OLEDs) have attracted increasing attention due to their superiority as high quality displays and energy-saving lighting. However, improving the efficiency of solution-processed devices especially based on blue emitter remains a challenge. Excitation of surface plasmons on metallic nanoparticles has potential for increasing the absorption and emission from optoelectronic devices. We demonstrate here that the incorporation of gold nano particles (GNPs) in the hole injection layer of poly(3,4-ethylene dioxythiophene):polystyrene sulfonic acid with an appropriate size and doping concentration can greatly enhance the efficiency OLED device especially at higher voltage. Apparently, the spectral of the multiple plasmon resonances of the GNPs and the luminescence of the emitting materials significantly overlap with each other. At 1000 cd m-2 for example, the power efficiency of a studied green device is increased from 29.0 to 36.2 lm W-1, an increment of 24.8%, and the maximum brightness improved from 21 550 to 27 810  cd m-2, an increment of 29.1%, as 2 wt% of a 12 nm GNP is incorporated. Remarkably, designed blue OLED also exhibited an increment of 50% and 35% in power efficacy at 100 and 1000 cd m-2, respectively, for same device structure. The reason why the enhancement is marked may be attributed to a strong absorption of the short-wavelength emission from the device by the gold nano particles, which in turn initiates a strong surface plasmon resonance effect, leading to a high device efficiency.

7.
Life Sci ; 243: 117253, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31927048

RESUMO

AIMS: Weightlessness exposure conduces to substantial vascular remodeling, mechanisms behind which remain unclear. Acid sphingomyelinase (ASM) catalyzed ceramide (Cer) generation accounts for multiple vascular disorders, so the role of it in adjustment of cerebral artery (CA) and small mesenteric artery (MA) was investigated in simulated weightless rats. MAIN METHODS: Rats were hindlimb unloaded tail suspended (HU) to simulate the effect of weightlessness. Arterial morphology was examined by hematoxylin-eosin staining. Cer abundance was measured by immunohistochemistry. Western blotting was used to detect protein content. Apoptosis was detected by transferase-mediated dUTP nick end labeling. KEY FINDINGS: During 4 weeks of tail suspension, intima-media thickness (IMT) and media cross section area (CSA) were increased gradually in CA but decreased gradually in MA (P < 0.05). Correspondingly, the apoptosis and proliferation of vascular smooth muscle cells were reduced and enhanced respectively in CA (P < 0.05), while promoted and restrained in MA (P < 0.05). As compared to control, both ASM protein expression and Cer content were lowered in CA and elevated in MA of HU rats (P < 0.05). Permeable Cer incubation reversed the change of apoptosis and proliferation in CA of HU rats, while ASM inhibition recapitulated it in control rats. On the contrary, ASM inhibitors restored the alteration of apoptosis and proliferation in MA of HU. SIGNIFICANCE: The results suggest that by controlling the balance between apoptosis and proliferation, ASM/Cer exerts an important role in structural adaptation of CA and MA to simulated weightlessness.


Assuntos
Ceramidas/metabolismo , Artérias Cerebrais/metabolismo , Elevação dos Membros Posteriores , Artérias Mesentéricas/metabolismo , Esfingomielina Fosfodiesterase/metabolismo , Ausência de Peso , Animais , Apoptose , Proliferação de Células , Ratos
8.
J Exp Clin Cancer Res ; 39(1): 10, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31931847

RESUMO

In the original publication of this article [1], labelling within Fig. 7a was incorrect. The updated figure is shown below, with 'DMT1' now corrected to read 'DNMT1'.

9.
IEEE J Biomed Health Inform ; 24(5): 1367-1378, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31545751

RESUMO

The analysis of cell mitotic behavior plays important role in many biomedical research and medical diagnostic applications. To improve the accuracy of mitosis detection in automated analysis systems, this paper proposes the sequential saliency guided deep neural network (SSG-DNN) to jointly identify and localize mitotic events in time-lapse phase contrast microscopy images. It consists of three key modules. First, the module of visual context learning extracts static visual feature and dynamic visual transition within individual volumetric cell regions. Secondly, with these information, the module of sequential saliency modeling aims to discover the saliency distribution over all successive frames in each volumetric region. Finally, the module of sequence structure modeling can leverage both visual context and saliency distribution for mitosis identification and localization. SSG-DNN can jointly realize visual feature learning and sequential structure modeling in the end-to-end framework. Moreover, the proposed method is independent of complicated preconditioning methods for mitotic candidate extraction and can be applied for mitosis detection in one-shot manner. To our knowledge, it is the first weakly supervised work to realize joint mitosis identification and localization only with sequence-wise labels. In our experiments, we evaluate its performances of both tasks on the popular C3H10 dataset and a novel and large-scale dataset, C2C12-16, which contains much more mitotic events and is more challenging owing to diverse cell culture conditions. Experimental results can demonstrate the superiority of the proposed method.

10.
Reprod Biol Endocrinol ; 17(1): 87, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666062

RESUMO

BACKGROUND: Morulas with delayed growth sometimes coexist with blastocysts. There is still limited evidence regarding the optimal disposal of surplus morulas. With the advancement of vitrification, the freezing-thawing technique has been widely applied to zygotes with 2 pronuclei, as well as embryos at the cleavage and blastocyst stages. The freezing of morulas, however, has rarely been discussed. The purpose of this study was to investigate whether these poor-quality and slow-growing morulas are worthy of cryopreservation. METHODS: This is a retrospective, observational, proof-of-concept study. A total of 1033 day 5/6 surplus morulas were cryopreserved from January 2015 to December 2018. The study included 167 women undergoing 180 frozen embryo transfer cycles. After the morulas underwent freezing-thawing procedures, their development was monitored for an additional day. The primary outcome was the blastocyst formation rate. Secondary outcomes were clinical pregnancy rate, live birth rate and abortion rate. RESULTS: A total of 347 surplus morulas were thawed. All studied morulas showed delayed compaction (day 5, n = 329; day 6, n = 18) and were graded as having low (M1, n = 54), medium (M2, n = 138) or high (M3, n = 155) fragmentation. The post-thaw survival rate was 79.3%. After 1 day in extended culture, the blastocyst formation rate was 66.6%, and the top-quality blastocyst formation rate was 23.6%. The day 5 morulas graded as M1, M2, and M3 had blastocyst formation rates of 88.9, 74.0, and 52.8% (p < 0.001), respectively, and the top-quality blastocyst formation rates were 64.8, 25.2, and 9.0% (p < 0.001), respectively. The clinical pregnancy rate was 33.6%. CONCLUSIONS: The post-thaw blastocyst formation rate was satisfactory, with approximately one-half of heavily fragmented morulas (M3) developing into blastocysts. Most of the poor-quality morulas were worth to freeze, with the reasonable goal of obtaining pregnancy and live birth. This alternative strategy may be a feasible approach for coping with poor-quality surplus morulas in non-PGS (preimplantation genetic screening) cycles.


Assuntos
Blastocisto/fisiologia , Criopreservação/métodos , Mórula/fisiologia , Vitrificação , Adulto , Coeficiente de Natalidade , Blastocisto/citologia , Implantação do Embrião , Transferência Embrionária , Desenvolvimento Embrionário , Feminino , Humanos , Nascimento Vivo , Mórula/citologia , Gravidez , Taxa de Gravidez , Estudos Retrospectivos
11.
Taiwan J Obstet Gynecol ; 58(6): 880-884, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31759548

RESUMO

OBJECTIVE: Transvaginal oocyte retrieval has become the common method for infertility couples undergoing artificial reproductive technology. Although it was considered to be safe, rare complications including urinary bladder injury were reported. CASE REPORT: We described two cases of bladder injury with refractory blood clots after oocyte retrieval, for whom conservative treatment failed. Diagnostic cystoscopy was performed and an Ellik evacuator was used for clot dissolution successfully. CONCLUSION: Urinary bladder injury with clots retention is a rare complication following ovary puncture. When tenacious clots become organized, the removal with traditional bladder irrigation may be difficult. We introduce Ellik evacuator as an effective and reliable procedure for evacuating tenacious clots in the urinary bladder.


Assuntos
Cistoscopia/métodos , Hematúria/cirurgia , Recuperação de Oócitos/efeitos adversos , Trombose/cirurgia , Doenças da Bexiga Urinária/cirurgia , Bexiga Urinária/lesões , Adulto , Endossonografia/métodos , Feminino , Hematúria/diagnóstico , Hematúria/etiologia , Humanos , Trombose/diagnóstico , Trombose/etiologia , Doenças da Bexiga Urinária/diagnóstico , Doenças da Bexiga Urinária/etiologia , Vagina
12.
J Exp Clin Cancer Res ; 38(1): 474, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31771617

RESUMO

BACKGROUND: The inflammatory cytokine interleukin-6 (IL-6) is critical for the expression of octamer-binding transcription factor 4 (OCT4), which is highly associated with early tumor recurrence and poor prognosis of hepatocellular carcinomas (HCC). DNA methyltransferase (DNMT) family is closely linked with OCT4 expression and drug resistance. However, the underlying mechanism regarding the interplay between DNMTs and IL-6-induced OCT4 expression and the sorafenib resistance of HCC remains largely unclear. METHODS: HCC tissue samples were used to examine the association between DNMTs/OCT4 expression levels and clinical prognosis. Serum levels of IL-6 were detected using ELISA assays (n = 144). Gain- and loss-of-function experiments were performed in cell lines and mouse xenograft models to determine the underlying mechanism in vitro and in vivo. RESULTS: We demonstrate that levels of DNA methyltransferase 3 beta (DNMT3b) are significantly correlated with the OCT4 levels in HCC tissues (n = 144), and the OCT4 expression levels are positively associated with the serum IL-6 levels. Higher levels of IL-6, DNMT3b, or OCT4 predicted early HCC recurrence and poor prognosis. We show that IL-6/STAT3 activation increases DNMT3b/1 and OCT4 in HCC. Activated phospho-STAT3 (STAT-Y640F) significantly increased DNMT3b/OCT4, while dominant negative phospho-STAT3 (STAT-Y705F) was suppressive. Inhibiting DNMT3b with RNA interference or nanaomycin A (a selective DNMT3b inhibitor) effectively suppressed the IL-6 or STAT-Y640F-induced increase of DNMT3b-OCT4 and ALDH activity in vitro and in vivo. The fact that OCT4 regulates the DNMT1 expressions were further demonstrated either by OCT4 forced expression or DNMT1 silence. Additionally, the DNMT3b silencing reduced the OCT4 expression in sorafenib-resistant Hep3B cells with or without IL-6 treatment. Notably, targeting DNMT3b with nanaomycin A significantly increased the cell sensitivity to sorafenib, with a synergistic combination index (CI) in sorafenib-resistant Hep3B cells. CONCLUSIONS: The DNMT3b plays a critical role in the IL-6-mediated OCT4 expression and the drug sensitivity of sorafenib-resistant HCC. The p-STAT3 activation increases the DNMT3b/OCT4 which confers the tumor early recurrence and poor prognosis of HCC patients. Findings from this study highlight the significance of IL-6-DNMT3b-mediated OCT4 expressions in future therapeutic target for patients expressing cancer stemness-related properties or sorafenib resistance in HCC.

13.
Int J Mol Sci ; 20(19)2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31547176

RESUMO

Noise-induced hearing loss (NIHL) relates closely to auditory cortex (AC) injury, so countermeasures aiming at the AC recovery would be of benefit. In this work, the effect of hyperbaric oxygen treatment on NIHL was elucidated, which was imposed on mice before (HBOP), during (HBOD) or after (HBOA) noise exposure. Morphology of neurons was assayed by hematoxylin-eosin or Nissl staining. Ceramide (Cer) level was measured through immunohistochemistry analysis. Apoptotic neurons were counted using transferase-mediated dUTP nick end labeling (TUNEL) staining. We demonstrated that the intense, broad band noise raised the threshold of auditory brainstem response, evoked neuronal degeneration or apoptosis and triggered the Cer accumulation in AC, all of which were restored significantly by HBOP, but not HBOD or HBOA. Cer over-generation reversed the advantages of HBOP significantly, while its curtailment recapitulated the effect. Next, noise exposure raised the superoxide or malondialdehyde (MDA) production which was blocked by HBOP or Cer repression. Oxidative control not only attenuated the hearing loss or neurodegeneration but, in turn, reduced the Cer formation significantly. In summary, mutual regulation between Cer and oxidative stress underlies the HBOP's curative effect on hearing loss and neuronal damage in noise-exposed mice.


Assuntos
Córtex Auditivo , Ceramidas/metabolismo , Perda Auditiva , Oxigenação Hiperbárica , Ruído/efeitos adversos , Animais , Córtex Auditivo/patologia , Córtex Auditivo/fisiopatologia , Perda Auditiva/metabolismo , Perda Auditiva/patologia , Perda Auditiva/fisiopatologia , Perda Auditiva/terapia , Masculino , Camundongos
14.
Transfusion ; 59(6): 2061-2073, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30912158

RESUMO

BACKGROUND: Pooled human platelet lysate (HPL) can replace fetal bovine serum (FBS) as xeno-free supplement for ex vivo expansion of mesenchymal stromal cells (MSCs). We evaluate here whether a double-virally-inactivated HPL (DVI-HPL) prepared from expired Intercept-treated platelet concentrates (PCs) and treated by solvent/detergent (S/D) can be used for MSC expansion. STUDY DESIGN AND METHODS: Expired Intercept-treated PCs in 65% platelet (PLT) additive solution were pooled and subjected to a 1% tri-n-butyl phosphate/1% Triton X-45 treatment followed by soybean oil, hydrophobic interaction chromatography purification, and sterile filtration. Bone marrow-derived MSCs (BM-MSCs) were expanded for four passages in growth medium containing 10% DVI-HPL, I-HPL (from Intercept-PC only), untreated HPL, and FBS. MSC morphology, doubling time, immunophenotype, immunosuppressive activity, and differentiation capacity were compared. RESULTS: Expanded cells had typical spindle morphology and showed higher viability in all HPL conditions than in FBS. The DVI-HPL and FBS-expanded cells were morphologically larger than in I-HPL and HPL supplements. The cumulative population doubling was lower using DVI-HPL than with HPL and I-HPL, but significantly higher than using FBS. Immunophenotype was not affected by the supplements used. Immunosuppressive activity was maintained with all supplements. Differentiation capacity into chondrocytes and osteocytes was more effective in DVI-HPL but less toward adipocytes compared to other supplements. CONCLUSIONS: Human PLT lysate made from Intercept-PCs subjected to S/D treatment may be an alternative to untreated HPL and to I-HPL for BM-MSC expansion. This finding reinforces the potential of HPL as a virally safe alternative to FBS for clinical grade MSC expansion protocols.

15.
Artigo em Inglês | MEDLINE | ID: mdl-30281454

RESUMO

Domain-invariant (view-invariant & modalityinvariant) feature representation is essential for human action recognition. Moreover, given a discriminative visual representation, it is critical to discover the latent correlations among multiple actions in order to facilitate action modeling. To address these problems, we propose a multi-domain & multi-task learning (MDMTL) method to (1) extract domain-invariant information for multi-view and multi-modal action representation and (2) explore the relatedness among multiple action categories. Specifically, we present a sparse transfer learning-based method to co-embed multi-domain (multi-view & multi-modality) data into a single common space for discriminative feature learning. Additionally, visual feature learning is incorporated into the multitask learning framework, with the Frobenius-norm regularization term and the sparse constraint term, for joint task modeling and task relatedness-induced feature learning. To the best of our knowledge, MDMTL is the first supervised framework to jointly realize domain-invariant feature learning and task modeling for multi-domain action recognition. Experiments conducted on the INRIA Xmas Motion Acquisition Sequences (IXMAS) dataset, the MSR Daily Activity 3D (DailyActivity3D) dataset, and the Multi-modal & Multi-view & Interactive (M2I) dataset, which is the most recent and largest multi-view and multi-model action recognition dataset, demonstrate the superiority of MDMTL over the state-of-the-art approaches.

16.
Artigo em Inglês | MEDLINE | ID: mdl-30216996

RESUMO

For decades, professional divisions have been represented as the main structural divisions in Western medicine throughout the world. In Taiwan, medical policymakers are also interested in designing professional divisions of traditional Chinese medicine (TCM). Therefore, this study evaluated the current status and potentiality of professional divisions of TCM in Taiwan using data from the year 2012 obtained from the National Health Insurance Research Database; the database provides information regarding age and gender of TCM physicians (TCMPs); total visit counts; contracted medical institution codes; groupings of diseases classified under International Classification of Diseases, Ninth Revision, Clinical Modification codes; numbers of children and female patients seeking treatment; and claim disposition codes used by each TCMP. The results indicated that there were 5522 TCMPs in 2012, and 4876 (90.3%) TCMPs practiced in primary clinics. The proportions of pediatric visits to these TCMPs were mostly below 0.2, and acupuncture or traumatology-related visit proportions were below 0.5. Only a few of the studied Taiwan-based TCMPs practiced gynecology and pediatrics, but most of them performed "internal medicine", or "acupuncture" or "traumatology" treatments. Thus, the number of TCM specialists practicing gynecology or pediatrics is insufficient, indicating that a policy that forms professional divisions of TCM practitioners in Taiwan should be reconsidered.


Assuntos
Medicina Tradicional Chinesa , Médicos , Terapia por Acupuntura , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Ginecologia , Humanos , Medicina Interna , Masculino , Registros Médicos , Pessoa de Meia-Idade , Programas Nacionais de Saúde , Pediatria , Taiwan
17.
Trends Cancer ; 4(9): 605-607, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30149878

RESUMO

Isocitrate dehydrogenase (IDH) mutations are biomarkers to classify diffuse gliomas into biologically similar subgroups. Tremendous efforts have been made to understand the biology of IDH-mutant gliomas at the genetic, epigenetic, transcriptional, and protein levels. Preclinical models that recapitulate human tumor biology are crucial not only to our understanding of IDH mutations in gliomagenesis, but also in testing of novel therapeutic agents that may lead to more effective therapies for IDH-mutant glioma patients.


Assuntos
Neoplasias Encefálicas/genética , Glioma/genética , Isocitrato Desidrogenase/genética , Animais , Humanos , Mutação
18.
Ear Hear ; 39(4): 795-809, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29360687

RESUMO

OBJECTIVE: We investigate the clinical effectiveness of a novel deep learning-based noise reduction (NR) approach under noisy conditions with challenging noise types at low signal to noise ratio (SNR) levels for Mandarin-speaking cochlear implant (CI) recipients. DESIGN: The deep learning-based NR approach used in this study consists of two modules: noise classifier (NC) and deep denoising autoencoder (DDAE), thus termed (NC + DDAE). In a series of comprehensive experiments, we conduct qualitative and quantitative analyses on the NC module and the overall NC + DDAE approach. Moreover, we evaluate the speech recognition performance of the NC + DDAE NR and classical single-microphone NR approaches for Mandarin-speaking CI recipients under different noisy conditions. The testing set contains Mandarin sentences corrupted by two types of maskers, two-talker babble noise, and a construction jackhammer noise, at 0 and 5 dB SNR levels. Two conventional NR techniques and the proposed deep learning-based approach are used to process the noisy utterances. We qualitatively compare the NR approaches by the amplitude envelope and spectrogram plots of the processed utterances. Quantitative objective measures include (1) normalized covariance measure to test the intelligibility of the utterances processed by each of the NR approaches; and (2) speech recognition tests conducted by nine Mandarin-speaking CI recipients. These nine CI recipients use their own clinical speech processors during testing. RESULTS: The experimental results of objective evaluation and listening test indicate that under challenging listening conditions, the proposed NC + DDAE NR approach yields higher intelligibility scores than the two compared classical NR techniques, under both matched and mismatched training-testing conditions. CONCLUSIONS: When compared to the two well-known conventional NR techniques under challenging listening condition, the proposed NC + DDAE NR approach has superior noise suppression capabilities and gives less distortion for the key speech envelope information, thus, improving speech recognition more effectively for Mandarin CI recipients. The results suggest that the proposed deep learning-based NR approach can potentially be integrated into existing CI signal processors to overcome the degradation of speech perception caused by noise.


Assuntos
Implante Coclear , Implantes Cocleares , Surdez/reabilitação , Aprendizado Profundo , Ruído , Percepção da Fala , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão Sinal-Ruído , Adulto Jovem
19.
IEEE Trans Cybern ; 48(3): 916-928, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28212106

RESUMO

View-based 3-D model retrieval is one of the most important techniques in numerous applications of computer vision. While many methods have been proposed in recent years, to the best of our knowledge, there is no benchmark to evaluate the state-of-the-art methods. To tackle this problem, we systematically investigate and evaluate the related methods by: 1) proposing a clique graph-based method and 2) reimplementing six representative methods. Moreover, we concurrently evaluate both hand-crafted visual features and deep features on four popular datasets (NTU60, NTU216, PSB, and ETH) and one challenging real-world multiview model dataset (MV-RED) prepared by our group with various evaluation criteria to understand how these algorithms perform. By quantitatively analyzing the performances, we discover the graph matching-based method with deep features, especially the clique graph matching algorithm with convolutional neural networks features, can usually outperform the others. We further discuss the future research directions in this field.

20.
Clin Cancer Res ; 24(5): 1124-1137, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29254993

RESUMO

Purpose: Glioblastoma (GBM) is highly resistant to treatment, largely due to disease heterogeneity and resistance mechanisms. We sought to investigate a promising drug that can inhibit multiple aspects of cancer cell survival mechanisms and become an effective therapeutic for GBM patients.Experimental Design: To investigate TG02, an agent with known penetration of the blood-brain barrier, we examined the effects as single agent and in combination with temozolomide, a commonly used chemotherapy in GBM. We used human GBM cells and a syngeneic mouse orthotopic GBM model, evaluating survival and the pharmacodynamics of TG02. Mechanistic studies included TG02-induced transcriptional regulation, apoptosis, and RNA sequencing in treated GBM cells as well as the investigation of mitochondrial and glycolytic function assays.Results: We demonstrated that TG02 inhibited cell proliferation, induced cell death, and synergized with temozolomide in GBM cells with different genetic background but not in astrocytes. TG02-induced cytotoxicity was blocked by the overexpression of phosphorylated CDK9, suggesting a CDK9-dependent cell killing. TG02 suppressed transcriptional progression of antiapoptotic proteins and induced apoptosis in GBM cells. We further demonstrated that TG02 caused mitochondrial dysfunction and glycolytic suppression and ultimately ATP depletion in GBM. A prolonged survival was observed in GBM mice receiving combined treatment of TG02 and temozolomide. The TG02-induced decrease of CDK9 phosphorylation was confirmed in the brain tumor tissue.Conclusions: TG02 inhibits multiple survival mechanisms and synergistically decreases energy production with temozolomide, representing a promising therapeutic strategy in GBM, currently under investigation in an ongoing clinical trial. Clin Cancer Res; 24(5); 1124-37. ©2017 AACR.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Transcrição Genética/efeitos dos fármacos , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral/transplante , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Sinergismo Farmacológico , Metabolismo Energético/efeitos dos fármacos , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/patologia , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Temozolomida/farmacologia , Temozolomida/uso terapêutico
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