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1.
Transl Oncol ; 14(7): 101109, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33946034

RESUMO

Lower-grade gliomas (LGGs) have a good prognosis with a wide range of overall survival (OS) outcomes. An accurate prognostic system can better predict survival time. An RNA-Sequencing (RNA-seq) prognostic signature showed a better predictive power than clinical predictor models. A signature constructed using gene pairs can transcend changes from biological heterogeneity, technical biases, and different measurement platforms. RNA-seq coupled with corresponding clinical information were extracted from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). Immune-related gene pairs (IRGPs) were used to establish a prognostic signature through univariate and multivariate Cox proportional hazards regression. Weighted gene co-expression network analysis (WGCNA) was used to evaluate module eigengenes correlating with immune cell infiltration and to construct gene co-expression networks. Samples in the training and testing cohorts were dichotomized into high- and low-risk groups. Risk score was identified as an independent predictor, and exhibited a closed relationship with prognosis. WGCNA presented a gene set that was positively correlated with age, WHO grade, isocitrate dehydrogenase (IDH) mutation status, 1p/19 codeletion, risk score, and immune cell infiltrations (CD4 T cells, B cells, dendritic cells, and macrophages). A nomogram comprising of age, WHO grade, 1p/19q codeletion, and three gene pairs (BIRC5|SSTR2, BMP2|TNFRSF12A, and NRG3|TGFB2) was established as a tool for predicting OS. The IPGPs signature, which is associated with immune cell infiltration, is a novel tailored tool for individual-level prediction.

2.
Nano Lett ; 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33881887

RESUMO

Organolead trihalide perovskite single crystals (SCs) offer unprecedented opportunity for X-ray and visible light detection. Nevertheless, it remains a challenge to keep simultaneous high-performance and stability at a high-temperature working mode. Herein, formamidinium lead bromide (FAPbBr3) SCs are developed to successfully address these issues. Low-temperature crystallized induced FAPbBr3 SCs possess an excellent mobility-lifetime product and an ultralow surface charge recombination velocity, thus exhibiting an X-ray dose rate as low as 0.3 µGyair s-1 as a sensitive radiation detector. Furthermore, it also contributes a specific detectivity as high as 3.5 × 1012 cm Hz1/2 W-1, keeping stable at high-temperature of 460 K as a photodetector. A prototype of an imaging system with diffuse reflection mode is constructed using detectors as receivers, enabling defined scanning images in a high temperature environment. The bifunctional FAPbBr3 SC detectors will motivate new strategies for stable detection in an extreme space environment.

3.
J Phys Chem Lett ; 12(11): 2937-2943, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33725450

RESUMO

Ultra-narrow-band NIR photomultiplication organic photodetectors (PM-OPDs) were realized in ITO/PEDOT:PSS/active layers/Al based on an interfacial-trap-induced charge injection narrowing (CIN) concept. The rather less Bod Ethex-Hex (BEH) is imbedded in a polymer donor matrix to form large amounts of isolated electron traps. Trapped electrons in BEH close to an Al electrode will enforce hole-tunneling injection induced by interfacial band bending, resulting in a photomultiplication phenomenon. PM-OPDs with P3HT:BEH as the active layer exhibit a narrow response peak at 850 nm with a full-width at half-maximum (fwhm) of 27 nm as well as a rather weak response from 650 to 800 nm. The EQE of 29 700% at 850 nm was achieved in PM-OPDs by incorporating 0.02 wt % of F6TCNNQ under -13 V of applied voltage. The rejection ratio (RR) of the optimized PM-OPDs with F6TCNNQ is 11 for EQE850 nm/EQE700 nm and 10 for EQE850 nm/EQE750 nm, respectively. An EQE of 15 300% at 850 nm was achieved in the ternary PM-OPDs under -13 V of applied voltage, with markedly enhanced RRs of 44 for EQE850 nm/EQE700 nm and 30 for EQE850 nm/EQE750 nm.

4.
Ann Med ; 53(1): 448-455, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33733974

RESUMO

BACKGROUND: To compare the recurrence rate and outcomes of double-headed pterygia using fibrin glue versus suture closure of conjunctival autograft. METHODS: All patients with double-headed pterygia who underwent pterygia excision with conjunctival autograft from January 2012 to January 2019 in the National University Hospital of Singapore were included. Patients were divided into 2 groups depending on whether fibrin glue or sutures were used to secure the conjunctival autograft in place. All patients had a minimum of 6 months follow-up. RESULTS: A total (26 patients) of 22 eyes had fibrin glue, while eight eyes underwent suture closure of their conjunctival autograft. Fibrin glue group had 4.5% recurrence rate, while suture group had 37.5% recurrence rate (p = .021). There is statistically significant improvement for overall visual acuity (p = .009) and cylinder (p = .002). There is also statistically significant improvement for visual acuity in the glue group (p = .026), but not in the suture group. Fibrin glue group had a shorter operation duration time compared to suture group (p < .001).There were no cases of graft dislocation, contraction or limbal stem cell deficiency. CONCLUSIONS: Low recurrence rates and good postoperative visual outcomes can be achieved with the split conjunctival autograft technique. Our study suggests that fibrin glue has an additional benefit over the use of sutures in the management of these complex cases.

5.
Diabetes Metab J ; 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33752319

RESUMO

Background: Type 2 diabetes mellitus (T2DM) is characterized by elevated fasting glucagon and impaired suppression of postprandial glucagon secretion, which may participate in diabetic complications. Therefore, we investigated the associations of plasma glucagon with estimated glomerular filtration rate (eGFR), albuminuria and diabetic kidney disease (DKD) in T2DM patients. Methods: Fasting glucagon and postchallenge glucagon (assessed by area under the glucagon curve [AUCgla]) levels were determined during oral glucose tolerance tests. Patients with an eGFR <60 mL/min/1.73 m2 and/or a urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g who presented with diabetic retinopathy were identified as having DKD. Results: Of the 2,436 recruited patients, fasting glucagon was correlated with eGFR and UACR (r=-0.112 and r=0.157, respectively; P<0.001), and AUCgla was also correlated with eGFR and UACR (r=-0.267 and r=0.234, respectively; P<0.001). Moreover, 31.7% (n=771) presented with DKD; the prevalence of DKD was 27.3%, 27.6%, 32.5%, and 39.2% in the first (Q1), second (Q2), third (Q3), and fourth quartile (Q4) of fasting glucagon, respectively; and the corresponding prevalence for AUCgla was 25.9%, 22.7%, 33.7%, and 44.4%, respectively. Furthermore, after adjusting for other clinical covariates, the adjusted odds ratios (ORs; 95% confidence intervals) for DKD in Q2, Q3, and Q4 versus Q1 of fasting glucagon were 0.946 (0.697 to 1.284), 1.209 (0.895 to 1.634), and 1.521 (1.129 to 2.049), respectively; the corresponding ORs of AUCgla were 0.825 (0.611 to 1.114), 1.323 (0.989 to 1.769), and 2.066 (1.546 to 2.760), respectively. Additionally, when we restricted our analysis in patients with glycosylated hemoglobin <7.0% (n=471), we found fasting glucagon and AUCgla were still independently associated with DKD. Conclusion: Both increased fasting and postchallenge glucagon levels were independently associated with DKD in T2DM patients.

6.
ACS Appl Mater Interfaces ; 13(5): 6421-6429, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33523641

RESUMO

A new non-interpenetrated three-dimensional (3D) pillared-layered TPP-based LMOF [Zn3(TPyTPP)0.5(BDC)3]·8DMF (denoted as Zn-MOF 1) was successfully prepared (TPyTPP = tetrakis(4-(pyridin-4-yl)phenyl)pyrazine and H2BDC = 1,4-benzenedicarboxylic acid). Zn-MOF 1 was characterized by single-crystal X-ray diffraction, PXRD, IR, N2 adsorption, thermogravimetric analysis, and luminescent spectrum. Impressively, luminescent sensing studies reveal that activated Zn-MOF 1 not only displays excellent luminescence-quenching efficiency with the values of high Ksv and low LODs toward 5-hydroxytryptamine (5-HT) and 5-hydroxyindole-3-acetic acid (5-HIAA), respectively, but also possesses outstanding sensing characteristics in terms of fast response, high sensitivity, and specific selectivity. Zn-MOF 1 performs as efficient sensing of carcinoid biomarkers to provide a fresh detection platform for the diagnosis of carcinoids. In addition, the sensing mechanism was also explored on the basis of ultraviolet-visible (UV-vis) absorption, DFT calculations, and structural analysis.


Assuntos
Biomarcadores Tumorais/análise , Tumor Carcinoide/diagnóstico por imagem , Substâncias Luminescentes/química , Estruturas Metalorgânicas/química , Pirazinas/química , Zinco/química , Humanos , Ácido Hidroxi-Indolacético/análise , Luminescência , Substâncias Luminescentes/síntese química , Medições Luminescentes , Estruturas Metalorgânicas/síntese química , Estrutura Molecular , Tamanho da Partícula , Serotonina/análise , Propriedades de Superfície
7.
J Alzheimers Dis ; 80(1): 271-281, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33523009

RESUMO

BACKGROUND: Identifying modifiable risk factors, such as obesity, to lower the prevalence of Alzheimer's disease (AD) has gained much interest. However, whether the association is causal remains to be evaluated. OBJECTIVE: The present study was designed: 1) to make a quantitative assessment of the association between obesity and AD; 2) to validate whether there was a causal association between them; and 3) to provide genetic clues for the association through a network-based analysis. METHODS: Two-sample Mendelian randomization (2SMR) analysis, meta-analysis, and protein-protein interaction (PPI) network analysis, were employed. RESULTS: Firstly, the meta-analysis based on 9 studies comprising 6,986,436 subjects indicated that midlife obesity had 33%higher AD odds than controls (OR = 1.33, 95%CI = [1.03, 1.62]), while late-life obesity were inversely associated with AD risk (OR = 0.57, 95%CI = [0.47, 0.68]). Secondly, 2SMR analysis indicated that there was no causal association between them. Thirdly, CARTPT was identified to be shared by the anti-obesity drug targets and AD susceptibility genes. Further PPI network analysis found that CARTPT interacted with CD33, a strong genetic locus linked to AD. Finally, 2SMR analysis showed that CNR1 could be a protective factor for AD. CONCLUSION: Multiple bioinformatic analyses indicated that midlife obesity might increase the risk of AD, while current evidence indicated that there was no causal association between them. Further, CARTPT might be an important factor linking the two disease conditions. It could help to better understand the mechanisms underlying the associations between obesity and AD.

8.
FEMS Microbiol Lett ; 368(5)2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33606020

RESUMO

In recent years, the relationship between type 2 diabetes (T2D) and gut microbiota has attracted much interest. Dendrobium officinale is a valuable traditional Chinese medicine (TCM) with anti-T2D potential, while its action mechanism remains to be further studied. This study was designed to investigate the modulation effects of D. officinale on gut microbiota of T2D model mice to provide clues to its pharmacology by high-throughput sequencing techniques. It was found that D. officinale supplement could significantly reduce the fasting blood glucose levels of T2D mice. Dendrobium officinale supplement could modulate the composition of gut microbiota and increase the relative abundances of key bacterial taxa associated with T2D development, including Akkermansia and Parabacteroides. Compared with placebo group mice, several Kyoto Encyclopedia of Gene and Genomes pathways associated with T2D altered in the D. officinale treated group. These findings indicated the modulation of D. officinale on gut microbiota of T2D mice, which provide potential pharmacological implications.

9.
Aging (Albany NY) ; 13(5): 7300-7313, 2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33640883

RESUMO

mTOR is well known to promote tumor growth but its roles in enhancing chemotherapy and radiotherapy have not been well studied. mTOR inhibition by rapamycin can sensitize cancer cells to radiotherapy. Here we show that Maf1 is required for rapamycin to increase radio-sensitivity in A549 lung cancer cells. In response to ionizing radiation (IR), Maf1 is inhibited by Akt-dependent re-phosphorylation, which activates mitochondrial unfolded protein response (UPRmt) through ATF5. Rapamycin suppresses IR-induced Maf1 re-phosphorylation and UPRmt activation in A549 cells, resulting in increased sensitivity to IR-mediated cytotoxicity. Consistently, Maf1 knockdown activates ATF5-transcription of mtHSP70 and HSP60, enhances mitochondrial membrane potential, reduces intracellular ROS levels and dampens rapamycin's effect on increasing IR-mediated cytotoxicity. In addition, Maf1 overexpression suppresses ethidium bromide-induced UPRmt and enhances IR-mediated cytotoxicity. Supporting our cell-based studies, elevated expression of UPRmt makers (mtHSP70 and HSP60) are associated with poor prognosis in patients with lung adenocarcinoma (LAUD). Together, our study reveals a novel role of Maf1-UPRmt axis in mediating rapamycin's enhancing effect on IR sensitivity in A549 lung cancer cells.

10.
Biochem J ; 478(4): 911-926, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33527978

RESUMO

M-cadherin is a skeletal muscle-specific transmembrane protein mediating the cell-cell adhesion of myoblasts during myogenesis. It is expressed in the proliferating satellite cells and highly induced by myogenic regulatory factors (MRFs) during terminal myogenic differentiation. Several conserved cis-elements, including 5 E-boxes, 2 GC boxes, and 1 conserved downstream element (CDE) were identified in the M-cadherin proximal promoter. We found that E-box-3 and -4 close to the transcription initiation site (TIS) mediated most of its transactivation by MyoD, the strongest myogenic MRF. Including of any one of the other E-boxes restored the full activation by MyoD, suggesting an essential collaboration between E-boxes. Stronger activation of M-cadherin promoter than that of muscle creatine kinase (MCK) by MyoD was observed regardless of culture conditions and the presence of E47. Furthermore, MyoD/E47 heterodimer and MyoD ∼ E47 fusion protein achieved similar levels of activation in differentiation medium (DM), suggesting high affinity of MyoD/E47 to E-boxes 3/4 under DM. We also found that GC boxes and CDE positively affected MyoD mediated activation. The CDE element was predicted to be the target of the chromatin-modifying factor Meis1/Pbx1 heterodimer. Knockdown of Pbx1 significantly reduced the expression level of M-cadherin, but increased that of N-cadherin. Using ChIP assay, we further found significant reduction in MyoD recruitment to M-cadherin promoter when CDE was deleted. Taken together, these observations suggest that the chromatin-modifying function of Pbx1/Meis1 is critical to M-cadherin promoter activation before MyoD is recruited to E-boxes to trigger transcription.

11.
PLoS One ; 16(2): e0247248, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33600459

RESUMO

The conversion of cellular prion protein (PrPC) to disease-provoking conformer (PrPSc) is crucial in the pathogenesis of prion diseases. Heparin has been shown to enhance mammalian prion protein misfolding. As spontaneous prion disease has not been reported in non-mammalian species, such as chicken, it is interesting to explore the influence of heparin on the conversion of chicken prion protein (ChPrP). Herein, we investigated the influences of heparin on biochemical properties of full-length recombinant ChPrP, with murine prion protein (MoPrP) as control. The results showed that at low heparin concentration (10 µg/mL), a great loss of solubility was observed for both MoPrP and ChPrP using solubility assays. In contrast, when the concentration of heparin was high (30 µg/mL), the solubility of MoPrP and ChPrP both decreased slightly. Using circular dichroism, PK digestion and transmission electron microscopy, significantly increased ß-sheet content, PK resistance and size of aggregates were observed for MoPrP interacted with 30 µg/mL heparin, whereas 30 µg/mL heparin-treated ChPrP showed less PK resistance and slight increase of ß-sheet structure. Therefore, heparin can induce conformational changes in both MoPrP and ChPrP and the biochemical properties of the aggregates induced by heparin could be modified by heparin concentration. These results highlight the importance of concentration of cofactors affecting PrP misfolding.

12.
J Alzheimers Dis ; 80(2): 787-797, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33579846

RESUMO

BACKGROUND: In recent years, the efficacy of type 2 diabetes mellitus (T2DM) drugs in the treatment of Alzheimer's disease (AD) has attracted extensive interest owing to the close associations between the two diseases. OBJECTIVE: Here, we screened traditional Chinese medicine (TCM) and multi-target ingredients that may have potential therapeutic effects on both T2DM and AD from T2DM prescriptions. METHODS: Network pharmacology and molecular docking were used. RESULTS: Firstly, the top 10 frequently used herbs and corresponding 275 active ingredients were identified from 263 T2DM-related TCM prescriptions. Secondly, through the comparative analysis of 208 potential targets of ingredients, 1,740 T2DM-related targets, and 2,060 AD-related targets, 61 common targets were identified to be shared. Thirdly, by constructing pharmacological network, 26 key targets and 154 representative ingredients were identified. Further enrichment analysis showed that common targets were involved in regulating multiple pathways related to T2DM and AD, while network analysis also found that the combination of Danshen (Radix Salviae)-Gancao (Licorice)-Shanyao (Rhizoma Dioscoreae) contained the vast majority of the representative ingredients and might be potential for the cotreatment of the two diseases. Fourthly, MAPK1, PPARG, GSK3B, BACE1, and NR3C1 were selected as potential targets for virtual screening of multi-target ingredients. Further docking studies showed that multiple natural compounds, including salvianolic acid J, gancaonin H, gadelaidic acid, icos-5-enoic acid, and sigmoidin-B, exhibited high binding affinities with the five targets. CONCLUSION: To summarize, the present study provides a potential TCM combination that might possess the potential advantage of cotreatment of AD and T2DM.

13.
Appl Microbiol Biotechnol ; 105(3): 1007-1015, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33449129

RESUMO

Transition metal ions are essential micronutrients for all living organisms and exert a wide range of effects on human health. The uptake of transition metal ions occurs primarily in the gastrointestinal tract, which is colonized by trillions of bacterial cells. In recent years, increasing studies have indicated that transition metals have regulatory effects on the gut microbiota. In view of the significant effect of the gut microbiota on human health and involvement in the pathogenesis of a wide range of diseases, in this paper, we provide a comprehensive discussion on the regulatory effects of four kinds of transition metal ions on the gut microbiota. A total of 20 animal model and human studies concerning the regulatory effects of four types of transition metal ions (i.e., iron, copper, zinc, and manganese) on gut microbiota were summarized. Both the deficiency and supplementation of these transition metal ions on the gut microbiota were considered. Furthermore, the potential mechanisms governing the regulatory effects of transition metal ions on the gut microbiota were also discussed. KEY POINTS : • Regulatory effects of iron, copper, zinc, and manganese on gut microbiota were reviewed. • Both deficiency and supplementation of metal ions on gut microbiota were considered. • Mechanisms governing effects of metal ions on gut microbiota were discussed.

14.
J Agric Food Chem ; 69(5): 1714-1726, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33512142

RESUMO

Ginseng contains a variety of flavonol glycosides that possess diverse biological activities; however, scant information of flavonoid glycosylation was reported in ginseng. We found that panasenoside and kaempferol 3-O-glucoside were commonly accumulated along with cultivation years in leaves. In order to explore the procedure of flavonol glycosylation in ginseng, 50 UDP-glycosyltransferases (UGTs) were screened out using differentiated data-independent acquisition (DIA) proteomics and phylogenetic analysis. UGT92A10 and UGT94Q4 were found contributing to the formation of kaempferol 3-O-glucoside. UGT73A18, UGT74T4, and UGT75W1 could catalyze galactosylation of kaempferol 3-O-glucoside. Ser278, Trp335, Gln338, and Val339 were found forming hydrogen bonds with UDP-galactose in UGT75W1 by docking. MeJA induced transcripts of UGT73A18 and UGT74T4 by over fourfold, consistent with the decrease of kaempferol 3-O-glucoside, which indicated that these genes may be related to resisting adversity stress in ginseng. These results highlight the significance of integrative metabolite profiles, proteomics, and phylogenetic analysis for exploring flavonol glycosylation in ginseng.


Assuntos
Flavonoides/biossíntese , Glucosídeos/biossíntese , Glicosiltransferases/metabolismo , Panax/genética , Proteínas de Plantas/metabolismo , Flavonoides/química , Regulação da Expressão Gênica de Plantas , Glucosídeos/química , Glicosilação , Glicosiltransferases/genética , Panax/classificação , Panax/enzimologia , Panax/metabolismo , Filogenia , Proteínas de Plantas/genética , Proteômica
15.
Ann Surg Oncol ; 28(5): 2474-2482, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33393052

RESUMO

BACKGROUND: Outcomes commonly used to ascertain success of metastatic spine tumour surgery (MSTS) are 30-day complications/mortality and overall/disease-free survival. We believe a new, effective outcome indicator after MSTS would be the absence of unplanned hospital readmission (UHR) after index discharge. We introduce the concept of readmission-free survival (ReAFS), defined as 'the time duration between hospital discharge after index operation and first UHR or death'. The aim of this study is to identify factors influencing ReAFS in MSTS patients. PATIENTS AND METHODS: We retrospectively analysed 266 consecutive patients who underwent MSTS between 2005 and 2016. Demographics, oncological characteristics, procedural, preoperative and postoperative details were collected. ReAFS of patients within 2 years or until death was reviewed. Perioperative factors predictive of reduced ReAFS were evaluated using multivariate regression analysis. RESULTS: Of 266 patients, 230 met criteria for analysis. A total of 201 had UHR, whilst 1 in 8 (29/230) had no UHR. Multivariate analysis revealed that haemoglobin ≥ 12 g/dL, ECOG score of ≤ 2, primary prostate, breast and haematological cancers, comorbidities ≤ 3, absence of preoperative radiotherapy and shorter postoperative length of stay significantly prolonged the time to first UHR. CONCLUSIONS: Readmission-free survival is a novel concept in MSTS, which relies on patients' general condition, appropriateness of interventional procedures and underlying disease burden. Additionally, it may indicate the successful combination of a multi-disciplinary treatment approach. This information will allow oncologists and surgeons to identify patients who may benefit from increased surveillance following discharge to increase ReAFS. We envisage that ReAFS is a concept that can be extended to other surgical oncological fields.

16.
Eur Spine J ; 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33459874

RESUMO

PURPOSE: The aim of this study was to investigate rates, causes, and risk factors of unplanned hospital readmissions (UHR) within 30 days, 90 days, 1 year and 2 years after metastatic spine tumour surgery (MSTS) to augment multi-disciplinary treatment planning and improve patient education. METHODS: We retrospectively reviewed 272-patients who underwent MSTS between 2005 and 2016. Hospital records were utilised to obtain demographics, oncological, procedural details, and postoperative outcomes. All UHR within 2 years were reviewed. Primary outcomes were rates, causes, and risk factors of UHR. Risk factors for UHR were evaluated utilising multivariate logistic regression analysis. RESULTS: Thirty-day, 90 day, 1 year, and 2 year UHR-rates after MSTS were 17.2%, 31.1%, 46.2%, and 52.7%, respectively. Lung cancer primaries had the highest UHR-events (24.7%) whilst renal/thyroid displayed the least (6.6%). Disease-related causes (16.2%) were the most common reason for readmissions across all timeframes, followed by respiratory (13.7%) and progression of metastatic spine disease (12.7%). Urological conditions accounted for majority of readmissions within 30-days; disease-related causes, symptomatic spinal metastases, and respiratory conditions represented the most common causes at 30-90 days, 90 days-1 year, and 1-2 years, respectively. An ECOG >1 (p = 0.057), CCI >7 (p = 0.01), and primary lung tumour (p = 0.02) significantly increased UHR-risk on multivariate analysis. CONCLUSION: Seventy-four percent of patients had at least one UHR within 2 years of MSTS and majority were secondary to disease-related causes. Majority of first UHR occurred between 30 and 90 days post-surgery. Local disease progression and overall disease progression account for the highest UHR-events at 90 days-1 year and 1-2 year timeframes, respectively. We define UHR in specific timeframes, thus enabling better surveillance and reducing unnecessary morbidity.

17.
Genes (Basel) ; 11(12)2020 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-33260650

RESUMO

Hypersialylation caused by the overexpression of sialyltransferases (STs) is a common feature in cancer that is associated with several characteristics of tumorigenesis. Thus, identifying cancer-associated STs is critical for cancer therapy. However, ST screening has been frequently conducted in cell line models. In this study, we conducted a comprehensive analysis of STs in the clinical database and identified the STs related with the survival of breast cancer patients. RNA sequencing (RNA-Seq) data of 496 patients were obtained from The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA). Of the eight mapped STs, ST3GAL5, and ST8SIA1 met the acceptable area under the curve (AUC) criteria for overall survival (OS). Using Kaplan-Meier methods, we determined that high expression of ST8SIA1 was associated with poor 10-year OS in all patients, triple-negative breast cancer (TNBC), and non-TNBC patients, and poor disease-free survival (DFS) rates particularly in TNBC. ST8SIA1 also had superior AUC values in terms of OS/DFS. High ST8SIA1 levels showed a higher risk for poor OS in different groups of patients and a higher risk for poor DFS particularly in TNBC. In summary, we conducted a comprehensive analysis of STs from the clinical database and identified ST8SIA1 as a crucial survival-related ST, which might be a potential therapeutic target for breast cancer and TNBC patients.

18.
PLoS One ; 15(12): e0241783, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33382683

RESUMO

BACKGROUND: Biomedical research is overseen by numerous Institutional Review Boards (IRBs) in Singapore but there has been no research that examines how the research review process is perceived by the local research community nor is there any systematic data on perceptions regarding the review process or other research ethics processes and IRB characteristics. The aim of this study was to ascertain general views regarding the overall perceived value of ethics review processes; to measure perceptions about local IRB functions and characteristics; to identify IRB functions and characteristics viewed as important; and to compare these views with those of other international studies. METHODS: An online survey was used with the main component being the IRB-Researcher Assessment Tool (IRB-RAT), a validated tool, to evaluate perceptions of ideal and actual IRB functions and characteristics held by Singaporean researchers and research support staff. Data were analysed descriptively first, with mean and SD of each item of IRB-RAT questionnaire reported, excluding the respondents whose answers were unknown or not applicable. The Wilcoxon Sign Rank test was used to compare the ideal and actual ratings of each IRB-RAT item, while the Mann-Whitney U test was used to compare the ratings of each IRB-RAT item between respondents with different characteristics. The Z-test was used to compare the mean ratings of our cohort with the mean ratings reported in the literature. The correlation between our mean ideal scores and those of two international studies also employing the IRB-RAT was examined. RESULTS: Seventy-one respondents completed the survey. This cohort generally held positive views of the impact of the ethics review process on: the quality of research; establishing and maintaining public trust in research; the protection of research participants; and on the scientific validity of research. The most important ideal IRB characteristics were timeliness, upholding participants' rights while also facilitating research, working with investigators to find solutions when there are disagreements, and not allowing biases to affect reviews. For almost all 45 IRB-RAT statements, the rating of the importance of the characteristic was higher than the rating of how much that characteristic was descriptive of IRBs the respondents were familiar with. There was a significant strong correlation between our study's scores on the ideal IRB characteristics and those of the first and largest published study that employed the IRB-RAT, the US National Validation (USNV) sample in Keith-Spiegel et al. [19]. CONCLUSIONS: An understanding of the perceptions held by Singaporean researchers and research support staff on the value that the ethics review process adds, their perceptions of actual IRB functions and characteristics as well as what they view as central to high functioning IRBs is the first step to considering the aspects of the review process that might benefit from improvements. This study provides insight into how our cohort compares to others internationally and highlights strengths and areas for improvement of Singapore IRBs as perceived by a small sample of the local research community. Such insights provide a springboard for additional research and may assist in further enhancing good relations so that both are working towards the same end.


Assuntos
Pesquisa Biomédica/ética , Comitês de Ética em Pesquisa/ética , Pesquisadores/psicologia , Percepção Social/psicologia , Adulto , Ética em Pesquisa , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Singapura , Inquéritos e Questionários
19.
Front Immunol ; 11: 603341, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33363544

RESUMO

Background: Lower-grade gliomas (LGGs) have more favorable outcomes than glioblastomas; however, LGGs often progress to process glioblastomas within a few years. Numerous studies have proven that the tumor microenvironment (TME) is correlated with the prognosis of glioma. Methods: LGG RNA-Sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) were extracted and then divided into training and testing cohorts, respectively. Immune-related differentially expressed genes (DEGs) were screened to establish a prognostic signature by a multivariate Cox proportional hazards regression model. The immune-related risk score and clinical information, such as age, sex, World Health Organization (WHO) grade, and isocitrate dehydrogenase 1 (IDH1) mutation, were used to independently validate and develop a prognostic nomogram. GO and KEGG pathway analyses to DEGs between immune-related high-risk and low-risk groups were performed. Results: Sixteen immune-related genes were screened for establishing a prognostic signature. The risk score had a negative correlation with prognosis, with an area under the receiver operating characteristic (ROC) curve of 0.941. The risk score, age, grade, and IDH1 mutation were identified as independent prognostic factors in patients with LGGs. The hazard ratios (HRs) of the high-risk score were 5.247 [95% confidence interval (CI) = 3.060-8.996] in the multivariate analysis. A prognostic nomogram of 1-, 3-, and 5-year survival was established and validated internally and externally. Go and KEGG pathway analyses implied that immune-related biological function and pathways were involved in the TME. Conclusion: The immune-related prognostic signature and the prognostic nomogram could accurately predict survival.

20.
ACS Appl Mater Interfaces ; 12(49): 55064-55071, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33231418

RESUMO

Planar heterojunction (PHJ) organic photodetectors are potentially more stable than traditional bulk heterojunction counterparts because of the absence of uncontrolled phase separation in the donor and acceptor binary blend system. This work reports a new class of PHJ organic photodetectors based on the medium-band gap fullerene C60 and low-band gap fused-ring non-fullerene acceptor ID-MeIC bilayer structure, which allows a wide range of spectral response tuning across the UV-visible-near-infrared (UV-vis-NIR) region by tailoring individual layer thickness. The C60 layer not only increases the external quantum efficiency at 745 nm by 57% but also reduces dark currents by two orders of magnitude. More importantly, the p-type poly[N,N'-bis(4-butylphenyl)-N,N'-bis(phenyl)-benzi] is found to be the key compound to conduct the layer-by-layer fabrication as combined with n-type ID-MeIC for higher charge extraction efficiency. In light of the above information, PHJ organic photodetectors exhibited a specific detectivity of 6.5 × 1010 Jones to detect NIR light at 745 nm under -0.1 V. The linear dynamic range was estimated to be 80 dB. This work has demonstrated a feasible approach to develop a PHJ architecture with tunable spectral response in the UV-vis-NIR range toward long-term stable organic photodetectors for potential applications in flexible and wearable biomedical sensors.

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