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1.
Sci Rep ; 10(1): 1745, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32019970

RESUMO

Fertilisation datasets collected from field experiments (n = 21) in tea-producing areas from 2016 to 2018 were used to build a quantitative evaluation of the fertility of tropical soils (QUEFTS) model to estimate nutrient uptake of tea plants, and to investigate relationships between tea yield and nutrient accumulation. The production of 1000 kg spring tea (based on one bud with two young expanding leaves) required 12.2 kg nitrogen (N), 1.2 kg phosphorus (P), and 3.9 kg potassium (K), and the corresponding internal efficiencies (IEs) for N, P, and K were 82.0, 833.3, and 256.4 kg kg-1. To produce 1000 kg summer tea, 9.1 kg N, 0.8 kg P, and 3.1 kg K were required, and the corresponding IEs for N, P, and K were 109.9, 1250.0, and 322.6 kg kg-1. For autumn tea, 8.8 kg N, 1.0 kg P, and 3.2 kg K were required to produce 1000 kg tea, and the corresponding IEs for N, P, and K were 113.6, 1000.0, and 312.5 kg kg-1. Field validation experiments performed in 2019 suggested that the QUEFTS model can appropriately estimate nutrient uptake of tea plants at a certain yield and contribute to developing a fertiliser recommendation strategy for tea production.

2.
Aging (Albany NY) ; 122020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32023222

RESUMO

The present study focused on the expression patterns, prognostic values and potential mechanism of the PDI family in gliomas. Most PDI family members' mRNA expressions were observed significantly different between gliomas classified by clinical features. Construction of the PDI signature, cluster and risk score models of glioma was done using GSVA, consensus clustering analysis, and LASSO Cox regression analysis respectively. High values of PDI signature/ risk score and cluster 1 in gliomas were associated with malignant clinicopathological characteristics and poor prognosis. Analysis of the distinctive genomic alterations in gliomas revealed that many cases having high PDI signature and risk score were associated with genomic aberrations of driver oncogenes. GSVA analysis showed that PDI family was involved in many signaling pathways in ERAD, apoptosis, and MHC class I among many more. Prognostic nomogram revealed that the risk score was a good prognosis indicator for gliomas. The qRT-PCR and immunohistochemistry confirmed that P4HB, PDIA4 and PDIA5 were overexpressed in gliomas. In summary, this research highlighted the clinical importance of PDI family in tumorigenesis and progression in gliomas.

3.
Environ Sci Technol ; 54(3): 1946-1954, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-31916754

RESUMO

Conventional dense thin-film composite (TFC) membranes evince a universally low water permeability, the increase of which typically relies on introducing additional transport channels based on intricate steps within a membrane preparation process. In this study, we reported a novel and simplified procedure for the fabrication of high-performance TFC membranes. Specifically, the dissolution of aqueous monomers in the casting solution was utilized for the following interfacial polymerization (IP). Since the monomers diffused to the water bath during phase inversion, the control of precipitation time enabled an effective regulation of the monomer concentration in the formed polymeric substrates, where the IP reaction was initiated by the addition of the organic phase. The entire and uniform embedment of aqueous monomers inside the substrates contributed to the formation of ultrathin and smooth selective layers. An excellent separation performance (i.e., water permeability: 34.7 L m-2 h-1 bar-1; Na2SO4 rejection: ∼96%) could be attained using two types of aqueous monomers (i.e., piperazine and ß-cyclodextrin), demonstrating the effectiveness and universality of this method. Compared to the conventional immersion-based process, this novel procedure shows distinct advantages in reducing monomer usage, shortening the production cycle, and achieving a more superior membrane performance, which is highly promising for large-scale membrane manufacture.

4.
Blood ; 135(1): 41-55, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31697823

RESUMO

To study the mechanisms of relapse in acute lymphoblastic leukemia (ALL), we performed whole-genome sequencing of 103 diagnosis-relapse-germline trios and ultra-deep sequencing of 208 serial samples in 16 patients. Relapse-specific somatic alterations were enriched in 12 genes (NR3C1, NR3C2, TP53, NT5C2, FPGS, CREBBP, MSH2, MSH6, PMS2, WHSC1, PRPS1, and PRPS2) involved in drug response. Their prevalence was 17% in very early relapse (<9 months from diagnosis), 65% in early relapse (9-36 months), and 32% in late relapse (>36 months) groups. Convergent evolution, in which multiple subclones harbor mutations in the same drug resistance gene, was observed in 6 relapses and confirmed by single-cell sequencing in 1 case. Mathematical modeling and mutational signature analysis indicated that early relapse resistance acquisition was frequently a 2-step process in which a persistent clone survived initial therapy and later acquired bona fide resistance mutations during therapy. In contrast, very early relapses arose from preexisting resistant clone(s). Two novel relapse-specific mutational signatures, one of which was caused by thiopurine treatment based on in vitro drug exposure experiments, were identified in early and late relapses but were absent from 2540 pan-cancer diagnosis samples and 129 non-ALL relapses. The novel signatures were detected in 27% of relapsed ALLs and were responsible for 46% of acquired resistance mutations in NT5C2, PRPS1, NR3C1, and TP53. These results suggest that chemotherapy-induced drug resistance mutations facilitate a subset of pediatric ALL relapses.

5.
Thorac Cancer ; 11(2): 456-460, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31865638

RESUMO

Here, we report a case of a 36-year-old female patient with metastatic non-small cell lung cancer (NSCLC) harboring EGFR-ANXA2 and EGFR-RAD51 double fusion mutations with BRCA2 (nonsense mutation of exon 11) and ATR mutations (Exon 44 variable shear mutation) identified by next generation sequencing (NGS). The efficacy was significantly improved after lobaplatin combined with pemetrexed, temozolomide and bevacizumab. This is the first report of a novel mutation type EGFR-ANXA2, as well as double EGFR fusion mutations in advanced lung adenocarcinoma. Furthermore, platinum-based chemotherapy plus bevacizumab rather than targeted therapy showed favorable effects in this patient, providing a novel therapeutic conception for patients, even with multidriver mutations.

6.
Proc Natl Acad Sci U S A ; 117(1): 271-277, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31848246

RESUMO

Brown planthopper (BPH) is one of the most destructive insects affecting rice (Oryza sativa L.) production. Phenylalanine ammonia-lyase (PAL) is a key enzyme involved in plant defense against pathogens, but the role of PAL in insect resistance is still poorly understood. Here we show that expression of the majority of PALs in rice is significantly induced by BPH feeding. Knockdown of OsPALs significantly reduces BPH resistance, whereas overexpression of OsPAL8 in a susceptible rice cultivar significantly enhances its BPH resistance. We found that OsPALs mediate resistance to BPH by regulating the biosynthesis and accumulation of salicylic acid and lignin. Furthermore, we show that expression of OsPAL6 and OsPAL8 in response to BPH attack is directly up-regulated by OsMYB30, an R2R3 MYB transcription factor. Taken together, our results demonstrate that the phenylpropanoid pathway plays an important role in BPH resistance response, and provide valuable targets for genetic improvement of BPH resistance in rice.

7.
J Cell Physiol ; 235(2): 1001-1012, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31240707

RESUMO

Emerging evidence has indicated that long noncoding RNA (lncRNAs) play crucial roles in regulating thyroid cancer (TC) development. Linc00210 is a newly identified lncRNA which plays an oncogenic role in hepatocellular carcinoma and nasopharyngeal carcinoma, but whether Linc00210 can modulate the development of TC remains elusive. Here, we found that Linc00210 expression was upregulated in TC tissues compared to the matched noncancerous tissues. Overexpression of Linc00210 augmented the proliferation, migration, and invasion of TC cells. Mechanistically, Linc00210 served as a sponge for miR-195-5p, thereby counteracting its ability in downregulating the expression of IGF1R and the activation of PI3K/Akt signaling. Moreover, inhibition of Linc00210 suppressed the growth of TC cells in nude mice. Our findings for the first time uncovered the oncogenic property of Linc00210 in TC.

8.
Virus Res ; 275: 197804, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31697988

RESUMO

Porcine circovirus 3 (PCV3) is a novel circovirus that is associated with porcine dermatitis and nephropathy syndrome, reproductive failure, and multi-systemic inflammation. The type I Interferon (IFN) signaling pathway is an important innate immune signaling pathway for defense against viral infection. Many mammalian viruses inhibit host innate immune signaling through diverse strategies. Here, we found that the PCV3 capsid protein (Cap) significantly inhibited IFN-ß-stimulated response element (ISRE) promoter activity, suggesting that Cap suppresses IFN signaling. However, Cap did not affect expression and phosphorylation levels of STAT1 and STAT2 and did not interrupt the heterodimerization of pSTAT1 and pSTAT2. Although Cap interacted with KPAN1, it did not block the interaction between KPNA1 and pSTAT1 or the nuclear translocation of pSTAT1 and pSTAT2. Interestingly, we found that Cap inhibited the activation of ISRE promoter induced by IRF9-S2C. Mechanistically, Cap interacted with the transactivation domain of STAT2, a key protein in type I IFN signaling. In addition, we found that Cap bound to ISRE and prevented ISRE binding of IRF9-S2C. This work is the first to describe the mechanism of inhibition of IFN signaling by PCV3 Cap.

9.
Brain Behav Immun ; 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31785398

RESUMO

Obesity is often accompanied by lower working memory (e.g., a lower ability to keep goal-relevant information in mind) relative to healthy weight individuals. Understanding this relative working memory impairment has important clinical implications, as working memory is thought to facilitate adherence to weight management programs. Theoretical models of obesity, self-regulation, and inflammation suggest that inflammation plays a role in obesity-related working memory impairments, but to date no study has tested this prediction. Therefore, the current study examined whether inflammation statistically mediated the relationship between obesity and working memory in a nationally representative dataset of U.S. adults from Wave IV of The National Longitudinal Study of Adolescent to Adult Health (N = 11,546, age range 25-34). Inflammation was quantified via C-reactive protein (CRP) level, and working memory was assessed using a modified digit span backward task. As expected, cross-sectional analyses showed that a body mass index (BMI) indicative of obesity-as well as greater BMI when BMI was analyzed continuously-and greater CRP were each related to lower working memory. Critically, we found that CRP levels statistically mediated the relationships between obesity/greater BMI and working memory, with CRP accounting for 44.1% of the variance explained in working memory by BMI. Moreover, these findings held both with and without controlling for relevant covariates, including demographic characteristics (e.g., age), socioeconomic status, and behavioral factors (e.g., smoking). Our results therefore point to inflammation as playing an important role in the relationship between obesity and working memory, and suggest that interventions aimed at reducing inflammation may help lessen the cognitive burden of obesity.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31829491

RESUMO

The role of endogenous serotonin (5-HT) in gastrointestinal motility is still highly controversial. Although electrochemical techniques allow for direct and real-time recording of biomolecules, the dynamic monitoring of 5-HT release from elastic and tubular intestine during motor reflexes remains a great challenge because of the specific peristalsis patterns and inevitable passivation of the sensing interface. A stretchable sensor with antifouling and decontamination properties was assembled from gold nanotubes, titanium dioxide nanoparticles, and carbon nanotubes. The sandwich-like structure endowed the sensor with satisfying mechanical stability and electrochemical performance, high resistance against physical adsorption, and superior efficiency in the photodegradation of biofouling molecules. Insertion of the sensor into the lumen of rat ileum (the last section of the small intestine) successfully mimics intestinal peristalsis, and simultaneous real-time monitoring of distension-evoked 5-HT release was possible for the first time. Our results unambiguously reveal that mechanical distension of the intestine induces endogenous 5-HT overflow, and 5-HT level is closely associated with the physiological or pathological states of the intestine.

11.
Sci Prog ; : 36850419874999, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31829856

RESUMO

This article concerns a hybrid vehicle suspension system that can regenerate energy from vibrations. To further improve the performance of the hybrid vehicle suspension system, the design of the energy-regenerative circuit is investigated. First, the force tests of the linear motor used in the hybrid vehicle suspension were carried out, and the key parameters of the linear motor were obtained. Then, the selection procedures of the protective resistance, inductance, and initial terminal voltage of the super capacitor were discussed. These aforementioned parameters' values were determined by considering the impact of the hybrid suspension on the dynamic performance indexes and the energy-regenerative efficiency. Simulations showed that, in comparison to the original hybrid suspension system, the designed hybrid suspension effectively improved the energy-regenerative efficiency, and that the dynamic performance indexes of the suspension were synchronously improved. Given the result of the simulation analysis, which were validated by bench tests, it is shown that the optimized energy-regenerative circuit presents an enhanced regeneration efficiency, with an improvement of nearly 13% compared to the original suspension system.

12.
Nat Prod Res ; : 1-8, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31680553

RESUMO

Two new norsesquiterpenoids, dioscopposin A (1) and dioscopposin B (2), as well as 21 known compounds (3-23) were isolated from the stems and leaves of Dioscorea oppositifolia L. Their structures were elucidated by detailed analysis of comprehensive spectroscopic data. The absolute configurations were deduced by the comparison of experimental and calculated electronic circular dichroism spectra. Estrogenic activity of all the isolated compounds were evaluated using MCF-7 cells proliferation assay and compounds 2, 3, 7, 13, 15, 16, 18 and 21 exhibited proliferation activity.

13.
Anal Chem ; 91(23): 15123-15129, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31697073

RESUMO

Glutamate (Glu) is a critical neurotransmitter for neuronal communication in the nervous system. In vivo studies have shown that the concentration of Glu is reduced within the brains of those afflicted with Alzheimer's disease (AD), which is also associated with the accumulation of pathogenic amyloid-beta (Aß). However, the effects of Aß peptides on the level of Glu release, as well as how Aß-mediated Glu fluctuation is initiated, remain largely unknown. Here, we fabricated a Glu electrochemical biosensor and in situ quantitatively monitored the release of Glu from a single varicosity of Aß1-42-insulted hippocampal neurons. We found that before the depletion of Glu after 300 min of treatment with Aß1-42, a short-duration (30 min) incubation with Aß1-42 caused a dramatic increase in vesicular Glu release compared to that of a control. Further investigation demonstrated that the density of vesicular glutamate transporter 1 (VGLUT1), which is responsible for transport of Glu into synaptic vesicles, also displayed a significant elevation and then dramatic depletion with the extension of the time of treatment with Aß1-42. These results indicate that at the early stage of AD, Aß1-42 induces excessive Glu release, which may overstimulate the N-methyl-d-aspartic acid (NMDA) receptor, resulting in excitotoxicity and damage to neurons. In this work, the amount of Glu released together with its fluctuations under Aß1-42 oligomers toxicity conditions was monitored for the first time, and such monitoring could provide direct and new insights for current research on Aß1-42-induced abnormalities in neurotransmitter release and neuron functions.

14.
Eat Behav ; 35: 101338, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31707244

RESUMO

A growing body of research has linked obesity to lower working memory performance. However, sex differences are often found in associations between obesity and cognition, and little work has examined potential sex differences in the association between obesity and working memory. To address this issue, the present research uses data from Wave IV of The National Longitudinal Study of Adolescent to Adult Health (N = 4,769, mean age = 29) to examine whether sex moderated the association between excess weight and working memory. As expected, we found that obesity was associated with poorer working memory, but-importantly-this association was exclusively seen in women, not men. These results held when treating BMI as a continuous or categorical variable (e.g., normal weight, obese), as well as with and without controlling for covariates. The present results therefore indicate that the association between obesity and poorer working memory performance may be sex-dependent. These results suggest that interventions targeted at reducing obesity should be tailored to an individual's sex, as adherence to these interventions often requires working memory.


Assuntos
Transtornos da Memória/epidemiologia , Memória de Curto Prazo/fisiologia , Obesidade/fisiopatologia , Obesidade/psicologia , Adulto , Conjuntos de Dados como Assunto , Feminino , Humanos , Estudos Longitudinais , Masculino , Distribuição por Sexo , Estados Unidos/epidemiologia
15.
Medicine (Baltimore) ; 98(46): e17916, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31725640

RESUMO

We aimed to evaluate the prognostic value of clinical and pathologic factors in rectal squamous cell carcinomas (SCC) and to construct a nomogram for their outcome prediction.The study cohort was selected from Surveillance, Epidemiology, and End Results (SEER) program between January 2004 and December 2013. Univariate and multivariate analyses were performed using Cox proportional hazards regression model to evaluate the prognostic value of involved variables. All prognostic factors were combined to construct a nomogram to predict the overall survival (OS), followed by discrimination as well as calibration plots and receiver operating characteristic (ROC) curves for assessing the predictive accuracy of the nomogram.We identified 806 patients with a median follow-up time of 35 months. Multivariate analyses revealed that marital status (P < .001), age (P < .001), T stage (P = .008), M stage (P < .001), surgery (P = .004), chemotherapy (P = .003) and radiotherapy (P = .016) were independent prognostic factors of OS. Finally, the 7 variables were combined to construct a 3-year and 5-year OS nomogram. The concordance indexes (C-indexes) of OS were 0.756 (95% CI, 0.726-0.786) for the internal validation and 0.729 (95% CI, 0.678-0.780) for the external validation. Additionally, there was superior discrimination power of the nomogram over the SEER stage or the 8th edition AJCC TNM staging classification (P < .001). Calibration plots further showed good consistency between the nomogram prediction and actual observation. The area under the curve (AUC) of ROC curves for 3-year OS was 0.811 (95% CI: 0.769-0.853) in the training cohort and 0.748 (95% CI: 0.681-0.815) in the validation cohort. The AUC for 5-year OS was 0.770 (95% CI: 0.721-0.819) in the training cohort and 0.797 (95% CI: 0.731-0.863) in the validation cohort. Finally, Kaplan-Meier analysis further validates the predictive potential of the nomogram.Marital status, age, T stage, M stage, surgery, chemotherapy and radiotherapy were significantly associated with OS of patients with rectal SCC. This predictive model has the potential to provide an individualized risk estimate of survival in patients with rectal SCC.


Assuntos
Carcinoma de Células Escamosas/mortalidade , Nomogramas , Neoplasias Retais/mortalidade , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Protectomia/métodos , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Radioterapia/métodos , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Programa de SEER , Fatores Sexuais , Fatores Socioeconômicos , Carga Tumoral , Estados Unidos , Adulto Jovem
16.
Org Biomol Chem ; 17(38): 8749-8755, 2019 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-31549131

RESUMO

A direct coupling of 2H-indazoles' C3 position and acyl groups has been achieved to produce 3-acyl-2H-indazoles. The Ni(ii)-catalyzed acylation might proceed through a radical pathway for the reaction of 2H-indazoles with either aryl or alkyl aldehydes in the presence of the free radical initiator TBHP and additive PivOH. This method provided a superior approach to fulfil the direct C3-acylation of 2H-indazoles with yields up to 91%. And various substituted 2H-indazoles were well tolerated with this method, enriching the diversity of 2H-indazole derivatives. In comparison with previously reported approaches for the C3-acylation of 2H-indazoles, the developed reaction represents a more convenient and economical method directly using aldehydes as the acylation agents.

17.
Small ; : e1903204, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31402582

RESUMO

As an interface between the blood flow and vessel wall, endothelial cells (ECs) are exposed to hemodynamic forces, and the biochemical molecules released from ECs-blood flow interaction are important determinants of vascular homeostasis. Versatile microfluidic chips have been designed to simulate the biological and physiological parameters of the human vascular system, but in situ and real-time monitoring of the mechanical force-triggered signals during vascular mechanotransduction still remains a significant challenge. Here, such challenge is fulfilled for the first time, by preparation of a flexible and stretchable electrochemical sensor and its incorporation into a microfluidic vascular chip. This allows simulating of in vivo physiological and biomechanical parameters of blood vessels, and simultaneously monitoring the mechanically induced biochemical signals in real time. Specifically, the cyclic circumferential stretch that is actually exerted on endothelium but is hard to reproduce in vitro is successfully recapitulated, and nitric oxide signals under normal blood pressure, as well as reactive oxygen species signals under hypertensive states, are well documented. Here, the first integration of a flexible electrochemical sensor into a microfluidic chip is reported, therefore paving a way to evaluate in vitro organs by built-in flexible sensors.

18.
Breast Cancer Res Treat ; 178(2): 379-388, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31414242

RESUMO

OBJECTIVES: The aim of this analysis was to study the impact of marital status on inflammatory breast cancer (IBC) patients, as the prognostic impact is yet to be studied in detail. METHODS: Data of IBC patients from 2004 to 2010 were sorted out from the database of surveillance, epidemiology, and end results (SEER), and overall survival (OS) rates and breast cancer-specific survival (CSS) rates were compared between a group of married and unmarried patients. The comparison was performed by Kaplan-Meier method with log-rank test, and multivariate survival analysis of CSS and OS was performed using the Cox proportional hazard model. RESULTS: Data of 1342 patients were collected from the SEER database, on an average 52% of married patients (n = 698, 52.01%) and 48% of unmarried patients (n = 644, 47.99%) for this analysis. Married patients were more likely to be more younger (aged ≤ 56) (52.44% vs. 43.94%), white ethnicity (83.24% vs. 71.58%), HoR positive (48.28% vs. 41.61%), more patients received surgery (78.51% vs. 64.60%), chemotherapy (90.69% vs. 80.12%) and radiotherapy (53.44% vs. 44.41%) compared to unmarried group, and less likely to be AJCC stage IV (26.22% vs. 35.40%) (All P ˂ 0.05). Married patients had better 5-year CSS (74.90% vs. 65.55%, P < 0.0001) and OS rates (45.43% vs. 33.11%, P < 0.0001). The multivariate analysis revealed that marital status is an independent prognostic factor, whereas the data of unmarried patients showed worse CSS (HR 1.188; 95% CI 1.033-1.367; P = 0.016) and OS rates (HR 1.245; 95% CI 1.090-1.421; P = 0.001).The subgroup analysis further revealed that the OS and CSS rates in the married group were better than the unmarried group, regardless of different AJCC stages. CONCLUSION: Marital status was an independent prognostic indicator in IBC patients. As the study reveals, the CSS and OS rates of the married patients were better than those of the unmarried patients.

19.
Cancer Med ; 8(12): 5600-5608, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31407527

RESUMO

In the present study, we examined the factors affecting survival of women with inflammatory breast cancer (IBC) and constructed and validated a nomogram to predict overall survival (OS) in these patients. The cohort was selected from the Surveillance, Epidemiology, and End Results (SEER) program between 1 January 2004 and 31 December 2013. Univariate and multivariate Cox proportional hazards regression models were constructed. A nomogram was developed based on significant prognostic indicators of OS. The discriminatory and predictive capacities of the nomogram were assessed using Harrell's concordance index (C-index) and calibration plots. A total of 1651 eligible patients were identified, with a median survival time of 31 months (range 0-131 months), and the 3- and 5-year OS rates were 52.8% and 39.5%, respectively. Multivariate analysis revealed that race (P < .001), marital status (P = .011), N stage (P = .002), M stage (P < .001), hormone receptor (P < .001), human epidermal growth factor receptor-2 (HER2) (P = .001), surgery (P < .001), chemotherapy (P < .001), and radiotherapy (P = .010) were independent prognostic indicators of IBC. These nine variables were incorporated to construct a nomogram. The C-indexes of the nomogram were 0.738 (95% confidence interval [CI]: 0.717, 0.759) and 0.741 (95% CI: 0.717, 0.765) for the internal and external validations, respectively. The nomogram had a better discriminatory capacity for predicting OS than did the SEER summary stage (P < .001) or the American Joint Committee on Cancer tumor-node metastasis staging systems (8th edition; P < .001). The calibration plot revealed satisfactory agreement between the findings and predicted outcomes in both the internal and external validations. The nomogram-based 3- and 5-year OS predictions for patients with IBC exhibited superior accuracy over the existing models.

20.
Genome Res ; 29(9): 1555-1565, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31439692

RESUMO

Variant interpretation in the era of massively parallel sequencing is challenging. Although many resources and guidelines are available to assist with this task, few integrated end-to-end tools exist. Here, we present the Pediatric Cancer Variant Pathogenicity Information Exchange (PeCanPIE), a web- and cloud-based platform for annotation, identification, and classification of variations in known or putative disease genes. Starting from a set of variants in variant call format (VCF), variants are annotated, ranked by putative pathogenicity, and presented for formal classification using a decision-support interface based on published guidelines from the American College of Medical Genetics and Genomics (ACMG). The system can accept files containing millions of variants and handle single-nucleotide variants (SNVs), simple insertions/deletions (indels), multiple-nucleotide variants (MNVs), and complex substitutions. PeCanPIE has been applied to classify variant pathogenicity in cancer predisposition genes in two large-scale investigations involving >4000 pediatric cancer patients and serves as a repository for the expert-reviewed results. PeCanPIE was originally developed for pediatric cancer but can be easily extended for use for nonpediatric cancers and noncancer genetic diseases. Although PeCanPIE's web-based interface was designed to be accessible to non-bioinformaticians, its back-end pipelines may also be run independently on the cloud, facilitating direct integration and broader adoption. PeCanPIE is publicly available and free for research use.

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