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1.
Sci Rep ; 10(1): 16007, 2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-32994418

RESUMO

Since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became a pandemic event in the world, it has not only caused huge economic losses, but also a serious threat to global public health. Many scientific questions about SARS-CoV-2 and Coronavirus disease (COVID-19) were raised and urgently need to be answered, including the susceptibility of animals to SARS-CoV-2 infection. Here we tested whether tree shrew, an emerging experimental animal domesticated from wild animal, is susceptible to SARS-CoV-2 infection. No clinical signs were observed in SARS-CoV-2 inoculated tree shrews during this experiment except the increasing body temperature particularly in female animals. Low levels of virus shedding and replication in tissues occurred in all three age groups. Notably, young tree shrews (6 months to 12 months) showed virus shedding at the earlier stage of infection than adult (2 years to 4 years) and old (5 years to 7 years) animals that had longer duration of virus shedding comparatively. Histopathological examine revealed that pulmonary abnormalities were the main changes but mild although slight lesions were also observed in other tissues. In summary, tree shrew is less susceptible to SARS-CoV-2 infection compared with the reported animal models and may not be a suitable animal for COVID-19 related researches. However, tree shrew may be a potential intermediate host of SARS-CoV-2 as an asymptomatic carrier.


Assuntos
Infecções por Coronavirus/veterinária , Especificidade de Hospedeiro/fisiologia , Pandemias/veterinária , Pneumonia Viral/veterinária , Tupaiidae/virologia , Animais , Betacoronavirus , Infecções por Coronavirus/patologia , Suscetibilidade a Doenças/veterinária , Suscetibilidade a Doenças/virologia , Feminino , Masculino , Pneumonia Viral/patologia , Carga Viral , Eliminação de Partículas Virais/fisiologia
2.
Nat Commun ; 11(1): 3833, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32737321

RESUMO

Polygenic risk scores (PRS) have been shown to predict breast cancer risk in European women, but their utility in Asian women is unclear. Here we evaluate the best performing PRSs for European-ancestry women using data from 17,262 breast cancer cases and 17,695 controls of Asian ancestry from 13 case-control studies, and 10,255 Chinese women from a prospective cohort (413 incident breast cancers). Compared to women in the middle quintile of the risk distribution, women in the highest 1% of PRS distribution have a ~2.7-fold risk and women in the lowest 1% of PRS distribution has ~0.4-fold risk of developing breast cancer. There is no evidence of heterogeneity in PRS performance in Chinese, Malay and Indian women. A PRS developed for European-ancestry women is also predictive of breast cancer risk in Asian women and can help in developing risk-stratified screening programmes in Asia.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Herança Multifatorial , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Ásia/epidemiologia , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etnologia , Estudos de Casos e Controles , Europa (Continente)/epidemiologia , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Pessoa de Meia-Idade , Razão de Chances , Prognóstico , Risco
3.
Signal Transduct Target Ther ; 5(1): 157, 2020 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-32814760

RESUMO

Identification of a suitable nonhuman primate (NHP) model of COVID-19 remains challenging. Here, we characterized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in three NHP species: Old World monkeys Macaca mulatta (M. mulatta) and Macaca fascicularis (M. fascicularis) and New World monkey Callithrix jacchus (C. jacchus). Infected M. mulatta and M. fascicularis showed abnormal chest radiographs, an increased body temperature and a decreased body weight. Viral genomes were detected in swab and blood samples from all animals. Viral load was detected in the pulmonary tissues of M. mulatta and M. fascicularis but not C. jacchus. Furthermore, among the three animal species, M. mulatta showed the strongest response to SARS-CoV-2, including increased inflammatory cytokine expression and pathological changes in the pulmonary tissues. Collectively, these data revealed the different susceptibilities of Old World and New World monkeys to SARS-CoV-2 and identified M. mulatta as the most suitable for modeling COVID-19.


Assuntos
Betacoronavirus/patogenicidade , Callithrix/virologia , Infecções por Coronavirus/epidemiologia , Modelos Animais de Doenças , Macaca fascicularis/virologia , Macaca mulatta/virologia , Pandemias , Pneumonia Viral/epidemiologia , Animais , Anticorpos Antivirais/biossíntese , Betacoronavirus/imunologia , Temperatura Corporal , Peso Corporal , Callithrix/imunologia , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Citocinas/biossíntese , Citocinas/classificação , Citocinas/imunologia , Suscetibilidade a Doenças , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Macaca fascicularis/imunologia , Macaca mulatta/imunologia , Masculino , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Especificidade da Espécie , Tomografia Computadorizada por Raios X , Carga Viral , Replicação Viral
4.
Int J Cancer ; 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32856720

RESUMO

The association between breast cancer risk defined by the Tyrer-Cuzick score (TC) and disease prognosis is not well established. Here, we investigated the relationship between 5-year TC and disease aggressiveness and then characterized underlying molecular processes. In a case-only study (n = 2474), we studied the association of TC with molecular subtypes and tumor characteristics. In a subset of patients (n = 672), we correlated gene expression to TC and computed a low-risk TC gene expression (TC-Gx) profile, that is, a profile expected to be negatively associated with risk, which we used to test for association with disease aggressiveness. We performed enrichment analysis to pinpoint molecular processes likely to be altered in low-risk tumors. A higher TC was found to be inversely associated with more aggressive surrogate molecular subtypes and tumor characteristics (P < .05) including Ki-67 proliferation status (P < 5 × 10-07 ). Our low-risk TC-Gx, based on the weighted sum of 37 expression values of genes strongly correlated with TC, was associated with basal-like (P < 5 × 10-13 ), HER2-enriched subtype (P < 5 × 10-07 ) and worse 10-year breast cancer-specific survival (log-rank P < 5 × 10-04 ). Associations between low-risk TC-Gx and more aggressive molecular subtypes were replicated in an independent cohort from The Cancer Genome Atlas database (n = 975). Gene expression that correlated with low TC was enriched in proliferation and oncogenic signaling pathways (FDR < 0.05). Moreover, higher proliferation was a key factor explaining the association with worse survival. Women who developed breast cancer despite having a low risk were diagnosed with more aggressive tumors and had a worse prognosis, most likely driven by increased proliferation. Our findings imply the need to establish risk factors associated with more aggressive breast cancer subtypes.

5.
Arch Oral Biol ; 114: 104692, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32305805

RESUMO

OBJECTIVE: Periodontitis is one of the most prevalent chronic inflammatory diseases causing tooth loss in patients. However, effective ways to treat periodontitis are still limited. Metformin has been suggested to have anti-inflammatory effects in the context of periodontitis, but the exact mechanisms remain largely unknown. METHODS: Human periodontal ligament cells (hPDLCs) was stimulated with P. gingivalis lipopolysaccharide (LPS) to simulate the in vivo conditions that existed in periodontitis. Inflammatory responses were monitored by measuring the protein expression and secretion of the inflammatory cytokines IL-1ß and IL-18. High-quality total RNA isolated from P. gingivalis LPS-treated cells along with or without metformin treatment were used for RNA sequencing and corresponding bioinformatics analysis. RESULTS: Metformin treatment significantly suppressed the inflammatory responses induced by P. gingivalis LPS in hPDLCs characterized by reduced production and secretion of IL-1ß and IL-18. Metformin treatment also significantly reduced expression of nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) and caspase-1 in hPDLCs. RNA-seq analysis showed that metformin treatment altered the expression of more than 300 genes, which belongs to 14 signaling pathways including the NF-κB pathway and TNF-α pathway. CONCLUSIONS: Our study provided novel insights into the anti-inflammatory effects of metformin against NLRP3 inflammasome activity, which could potentially be used for the prevention and treatment of P. gingivalis-related periodontal diseases.


Assuntos
Inflamassomos/metabolismo , Metformina/uso terapêutico , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ligamento Periodontal/citologia , Periodontite/tratamento farmacológico , Caspase 1/metabolismo , Células Cultivadas , Humanos , Interleucina-18/metabolismo , Interleucina-1beta/metabolismo , Lipopolissacarídeos , NF-kappa B/metabolismo , Porphyromonas gingivalis , RNA-Seq , Transdução de Sinais
6.
Toxins (Basel) ; 12(4)2020 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-32260237

RESUMO

We reported the conversion of deoxynivalenol-3-glucoside (D3G) to deoxynivalenol (DON) during Chinese steamed bread (CSB) processing by artificial D3G contamination. Meanwhile, the effects of enzymes in wheat flour and those produced from yeast, along with the two main components in wheat flour-wheat starch and wheat gluten-on the conversion profiles of D3G were evaluated. The results showed D3G could convert to DON during CSB processing, and the conversion began with dough making and decreased slightly after fermentation and steaming. However, there was no significant difference in three stages. When yeast was not added, or enzyme-deactivated wheat flour was used to simulate CSB process, and whether yeast was added or not, D3G conversion could be observed, and the conversion was significantly higher after dough making. Likewise, D3G converted to DON when wheat starch and wheat gluten were processed to CSB, and the conversion in wheat starch was higher.

7.
Nat Commun ; 11(1): 1217, 2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-32139696

RESUMO

Known risk variants explain only a small proportion of breast cancer heritability, particularly in Asian women. To search for additional genetic susceptibility loci for breast cancer, here we perform a meta-analysis of data from genome-wide association studies (GWAS) conducted in Asians (24,206 cases and 24,775 controls) and European descendants (122,977 cases and 105,974 controls). We identified 31 potential novel loci with the lead variant showing an association with breast cancer risk at P < 5 × 10-8. The associations for 10 of these loci were replicated in an independent sample of 16,787 cases and 16,680 controls of Asian women (P < 0.05). In addition, we replicated the associations for 78 of the 166 known risk variants at P < 0.05 in Asians. These findings improve our understanding of breast cancer genetics and etiology and extend previous findings from studies of European descendants to Asian women.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Neoplasias da Mama/genética , Grupo com Ancestrais do Continente Europeu/genética , Loci Gênicos , Predisposição Genética para Doença , Feminino , Humanos , Herança Multifatorial/genética , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas/genética , Receptores Estrogênicos/metabolismo , Fatores de Risco
8.
Cancer Med ; 9(7): 2435-2444, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32053293

RESUMO

The impact of timely treatment on breast cancer-specific survival may differ by tumor stage. We aim to study the impact of delayed first treatment on overall survival across different tumor stages. In addition, we studied the impact of delayed adjuvant treatments on survival in patients with invasive nonmetastatic breast cancer who had surgery ≤90 days postdiagnosis. This population-based study includes 11 175 breast cancer patients, of whom, 2318 (20.7%) died (median overall survival = 7.9 years). To study the impact of delayed treatment on survival, hazard ratios and corresponding 95% confidence intervals were estimated using Cox proportional-hazards models. The highest proportion of delayed first treatment (>30 days postdiagnosis) was in patients with noninvasive breast cancer (61%), followed by metastatic breast cancer (50%) and invasive nonmetastatic breast cancer (22%). Delayed first treatment (>90 vs ≤30 days postdiagnosis) was associated with worse overall survival in patients with invasive nonmetastatic (HR: 2.25, 95% CI 1.55-3.28) and metastatic (HR: 2.09, 95% CI 1.66-2.64) breast cancer. Delayed adjuvant treatment (>90 vs 31-60 days postsurgery) was associated with worse survival in patients with invasive nonmetastatic (HR: 1.50, 95% CI 1.29-1.74). Results for the Cox proportional-hazards models were similar for breast cancer-specific death. A longer time to first treatment (31-90 days postdiagnosis) may be viable for more extensive diagnostic workup and patient-doctor decision-making process, without compromising survival. However, patients' preference and anxiety status need to be considered.

9.
Sci Rep ; 10(1): 503, 2020 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-31949192

RESUMO

Incidence of breast cancer is rising rapidly in Asia. Some breast cancer risk factors are modifiable. We examined the impact of known breast cancer risk factors, including body mass index (BMI), reproductive and hormonal risk factors, and breast density on the incidence of breast cancer, in Singapore. The study population was a population-based prospective trial of screening mammography - Singapore Breast Cancer Screening Project. Population attributable risk and absolute risks of breast cancer due to various risk factors were calculated. Among 28,130 women, 474 women (1.7%) developed breast cancer. The population attributable risk was highest for ethnicity (49.4%) and lowest for family history of breast cancer (3.8%). The proportion of breast cancers that is attributable to modifiable risk factor BMI was 16.2%. The proportion of breast cancers that is attributable to reproductive risk factors were low; 9.2% for age at menarche and 4.2% for number of live births. Up to 45.9% of all breast cancers could be avoided if all women had breast density <12% and BMI <25 kg/m2. Notably, sixty percent of women with the lowest risk based on non-modifiable risk factors will never reach the risk level recommended for mammography screening. A combination of easily assessable breast cancer risk factors can help to identify women at high risk of developing breast cancer for targeted screening. A large number of high-risk women could benefit from risk-reduction and risk stratification strategies.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/epidemiologia , Medição de Risco/métodos , Índice de Massa Corporal , Densidade da Mama , Detecção Precoce de Câncer , Feminino , Humanos , Incidência , Mamografia , Pessoa de Meia-Idade , Estudos Prospectivos , Singapura/epidemiologia
10.
Sci Rep ; 10(1): 1330, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31992769

RESUMO

Breast cancer survival has improved with significant progress in treatment and disease management. However, compliance with treatment varies. Treatment guidelines for older patients are unclear. We aim to identify predictors of noncompliance with recommended therapy in a large breast cancer population and assess the impact of noncompliance on survival. Our study included 19,241 non-metastatic female breast cancer patients, of whom 3,158 (16%) died within 10 years post-diagnosis (median survival = 5.8 years). We studied the association between treatment noncompliance and factors with logistic regression, and the impact of treatment noncompliance on survival with a flexible parametric survival model framework. The highest proportion of noncompliance was observed for chemotherapy (18%). Predictors of noncompliance with chemotherapy, radiotherapy and endocrine therapy included age, tumor size, nodal involvement and subtype (except radiotherapy). Factors associated with not receiving surgery included age and subtype. Treatment noncompliance was associated with worse overall survival for surgery (HR: 2.26 [1.80-2.83]), chemotherapy (1.25 [1.11-1.41]), radiotherapy (2.28 [1.94-2.69]) and endocrine therapy (1.70 [1.41-2.04]). Worse survival was similarly observed in older patients for whom guidelines generally do not apply. Our results highlight the importance of following appropriate treatment as recommended by current guidelines. Older patients may benefit from similar recommendations.


Assuntos
Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ásia/epidemiologia , Neoplasias da Mama/epidemiologia , Terapia Combinada , Gerenciamento Clínico , Feminino , Fidelidade a Diretrizes , Humanos , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Sistema de Registros , Fatores de Risco
11.
EBioMedicine ; 48: 203-211, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31629678

RESUMO

BACKGROUND: We previously conducted a systematic field synopsis of 1059 breast cancer candidate gene studies and investigated 279 genetic variants, 51 of which showed associations. The major limitation of this work was the small sample size, even pooling data from all 1059 studies. Thereafter, genome-wide association studies (GWAS) have accumulated data for hundreds of thousands of subjects. It's necessary to re-evaluate these variants in large GWAS datasets. METHODS: Of these 279 variants, data were obtained for 228 from GWAS conducted within the Asian Breast Cancer Consortium (24,206 cases and 24,775 controls) and the Breast Cancer Association Consortium (122,977 cases and 105,974 controls of European ancestry). Meta-analyses were conducted to combine the results from these two datasets. FINDINGS: Of those 228 variants, an association was observed for 12 variants in 10 genes at a Bonferroni-corrected threshold of P < 2·19 × 10-4. The associations for four variants reached P < 5 × 10-8 and have been reported by previous GWAS, including rs6435074 and rs6723097 (CASP8), rs17879961 (CHEK2) and rs2853669 (TERT). The remaining eight variants were rs676387 (HSD17B1), rs762551 (CYP1A2), rs1045485 (CASP8), rs9340799 (ESR1), rs7931342 (CHR11), rs1050450 (GPX1), rs13010627 (CASP10) and rs9344 (CCND1). Further investigating these 10 genes identified associations for two additional variants at P < 5 × 10-8, including rs4793090 (near HSD17B1), and rs9210 (near CYP1A2), which have not been identified by previous GWAS. INTERPRETATION: Though most candidate gene variants were not associated with breast cancer risk, we found 14 variants showing an association. Our findings warrant further functional investigation of these variants. FUND: National Institutes of Health.


Assuntos
Grupo com Ancestrais do Continente Asiático , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Grupo com Ancestrais do Continente Europeu , Predisposição Genética para Doença , Variação Genética , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Caspase 8 , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Genótipo , Humanos , Razão de Chances , Polimorfismo de Nucleotídeo Único , Vigilância da População , Risco
12.
PLoS One ; 14(10): e0223679, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31581223

RESUMO

[This corrects the article DOI: 10.1371/journal.pone.0211373.].

13.
Sensors (Basel) ; 19(18)2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31527437

RESUMO

Transfer learning can enhance classification performance of a target domain with insufficient training data by utilizing knowledge relating to the target domain from source domain. Nowadays, it is common to see two or more source domains available for knowledge transfer, which can improve performance of learning tasks in the target domain. However, the classification performance of the target domain decreases due to mismatching of probability distribution. Recent studies have shown that deep learning can build deep structures by extracting more effective features to resist the mismatching. In this paper, we propose a new multi-source deep transfer neural network algorithm, MultiDTNN, based on convolutional neural network and multi-source transfer learning. In MultiDTNN, joint probability distribution adaptation (JPDA) is used for reducing the mismatching between source and target domains to enhance features transferability of the source domain in deep neural networks. Then, the convolutional neural network is trained by utilizing the datasets of each source and target domain to obtain a set of classifiers. Finally, the designed selection strategy selects classifier with the smallest classification error on the target domain from the set to assemble the MultiDTNN framework. The effectiveness of the proposed MultiDTNN is verified by comparing it with other state-of-the-art deep transfer learning on three datasets.

14.
PLoS One ; 14(8): e0211373, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31449533

RESUMO

With the exponential increase in malware, homology analysis has become a hot research topic in the malware detection field. This paper proposes MHAS, a malware homology analysis system based on ensemble learning and multifeatures. MHAS generates grayscale images from malware binary files and then uses the opcode tool IDA Pro to extract opcode sequences and system call graphs. Thus, RGB images and M-images are generated on the image matrix. Then, MHAS uses convolutional neural networks (CNNs) as base learners to perform bagging ensemble learning to learn features from the grayscale images, RGB images and M-images. Next, MHAS integrates the nine base learners using voting, learning and selective ensemble (in that order) and maps the integration results to the result matrix. Finally, the result matrix is again integrated using the learning method to obtain the final malware classification result. To verify the accuracy of MHAS, we performed a malware family classification experiment, that included samples of 10 malware families. The results showed that MHAS can reach an accuracy rate of 99.17%, meaning that it can effectively analyze and identify malware families.


Assuntos
Aprendizado de Máquina , Software , Processamento de Imagem Assistida por Computador , Redes Neurais de Computação
15.
Int J Epidemiol ; 48(3): 781-794, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31243447

RESUMO

BACKGROUND: Evidence linking breast size to breast cancer risk has been inconsistent, and its interpretation is often hampered by confounding factors such as body mass index (BMI). Here, we used linkage disequilibrium score regression and two-sample Mendelian randomization (MR) to examine the genetic associations between BMI, breast size and breast cancer risk. METHODS: Summary-level genotype data from 23andMe, Inc (breast size, n = 33 790), the Breast Cancer Association Consortium (breast cancer risk, n = 228 951) and the Genetic Investigation of ANthropometric Traits (BMI, n = 183 507) were used for our analyses. In assessing causal relationships, four complementary MR techniques [inverse variance weighted (IVW), weighted median, weighted mode and MR-Egger regression] were used to test the robustness of the results. RESULTS: The genetic correlation (rg) estimated between BMI and breast size was high (rg = 0.50, P = 3.89x10-43). All MR methods provided consistent evidence that higher genetically predicted BMI was associated with larger breast size [odds ratio (ORIVW): 2.06 (1.80-2.35), P = 1.38x10-26] and lower overall breast cancer risk [ORIVW: 0.81 (0.74-0.89), P = 9.44x10-6]. No evidence of a relationship between genetically predicted breast size and breast cancer risk was found except when using the weighted median and weighted mode methods, and only with oestrogen receptor (ER)-negative risk. There was no evidence of reverse causality in any of the analyses conducted (P > 0.050). CONCLUSION: Our findings indicate a potential positive causal association between BMI and breast size and a potential negative causal association between BMI and breast cancer risk. We found no clear evidence for a direct relationship between breast size and breast cancer risk.


Assuntos
Índice de Massa Corporal , Neoplasias da Mama/epidemiologia , Mama/anatomia & histologia , Tamanho do Órgão/genética , Neoplasias da Mama/metabolismo , Feminino , Humanos , Desequilíbrio de Ligação , Análise da Randomização Mendeliana , Receptores Estrogênicos/metabolismo
16.
Breast Cancer Res ; 21(1): 68, 2019 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-31118087

RESUMO

BACKGROUND: Mammographic breast density, adjusted for age and body mass index, and a polygenic risk score (PRS), comprised of common genetic variation, are both strong risk factors for breast cancer and increase discrimination of risk models. Understanding their joint contribution will be important to more accurately predict risk. METHODS: Using 3628 breast cancer cases and 5126 controls of European ancestry from eight case-control studies, we evaluated joint associations of a 77-single nucleotide polymorphism (SNP) PRS and quantitative mammographic density measures with breast cancer. Mammographic percent density and absolute dense area were evaluated using thresholding software and examined as residuals after adjusting for age, 1/BMI, and study. PRS and adjusted density phenotypes were modeled both continuously (per 1 standard deviation, SD) and categorically. We fit logistic regression models and tested the null hypothesis of multiplicative joint associations for PRS and adjusted density measures using likelihood ratio and global and tail-based goodness of fit tests within the subset of six cohort or population-based studies. RESULTS: Adjusted percent density (odds ratio (OR) = 1.45 per SD, 95% CI 1.38-1.52), adjusted absolute dense area (OR = 1.34 per SD, 95% CI 1.28-1.41), and the 77-SNP PRS (OR = 1.52 per SD, 95% CI 1.45-1.59) were associated with breast cancer risk. There was no evidence of interaction of the PRS with adjusted percent density or dense area on risk of breast cancer by either the likelihood ratio (P > 0.21) or goodness of fit tests (P > 0.09), whether assessed continuously or categorically. The joint association (OR) was 2.60 in the highest categories of adjusted PD and PRS and 0.34 in the lowest categories, relative to women in the second density quartile and middle PRS quintile. CONCLUSIONS: The combined associations of the 77-SNP PRS and adjusted density measures are generally well described by multiplicative models, and both risk factors provide independent information on breast cancer risk.


Assuntos
Biomarcadores Tumorais , Densidade da Mama/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Herança Multifatorial , Adulto , Idoso , Algoritmos , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Modelos Biológicos , Razão de Chances , Polimorfismo de Nucleotídeo Único , Medição de Risco , Fatores de Risco
17.
Lab Chip ; 19(11): 1953-1960, 2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31044199

RESUMO

The rope coiling observed in liquid ink with high viscosity has been exploited in additive printing to fabricate architectures with periodically curled structures and tune their mechanical properties. However, the control over the coiling path relying on mechanical motion restricts the spatiotemporal resolution. We develop an electrically assisted high-resolution technique to manipulate coiling paths of viscous ink and structures of the deposited filament. By spatially programming the voltage applied onto the viscous ink, we show that the switching between different filament structures can be accomplished at single wavelength resolution, facilitating the rapid and accurate construction of sophisticated patterns. Furthermore, translational guiding of the electrocoiling enables rapid printing of filaments with complex structures at a line speed of 102 mm s-1. With a simplified trajectory of the printing head, large-area and multiscale patterns can be printed at an unprecedented speed; for instance, centimeter-sized architectures constructed from nanofibers with micron-sized curled structures can be completed in a few minutes. By enabling the printing of complex fiber networks with tunable shape and density, our work provides a route towards custom-design of fiber architectures with unique features such as spatially varying mechanical properties.

18.
Sci Rep ; 9(1): 3527, 2019 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-30837593

RESUMO

Breast cancer patients commonly present with comorbidities which are known to influence treatment decisions and survival. We aim to examine agreement between self-reported and register-based medical records (National Patient Register [NPR]). Ascertainment of nine conditions, using individually-linked data from 64,961 women enrolled in the Swedish KARolinska MAmmography Project for Risk Prediction of Breast Cancer (KARMA) study. Agreement was assessed using observed proportion of agreement (overall agreement), expected proportion of agreement, and Cohen's Kappa statistic. Two-stage logistic regression models taking into account chance agreement were used to identify potential predictors of overall agreement. High levels of overall agreement (i.e. ≥86.6%) were observed for all conditions. Substantial agreement (Cohen's Kappa) was observed for myocardial infarction (0.74), diabetes (0.71) and stroke (0.64) between self-reported and NPR data. Moderate agreement was observed for preeclampsia (0.51) and hypertension (0.46). Fair agreement was observed for heart failure (0.40) and polycystic ovaries or ovarian cysts (0.27). For hyperlipidemia (0.14) and angina (0.10), slight agreement was observed. In most subgroups we observed negative specific agreement of >90%. There is no clear reference data source for ascertainment of conditions. Negative specific agreement between NPR and self-reported data is consistently high across all conditions.

19.
PLoS One ; 14(3): e0213615, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30856210

RESUMO

INTRODUCTION: False-positive recall is an issue in national screening programmes. The aim of this study is to investigate the recall rate at first screen and to identify potential predictors of false-positive recall in a multi-ethnic Asian population-based breast cancer screening programme. METHODS: Women aged 50-64 years attending screening mammography for the first time (n = 25,318) were included in this study. The associations between potential predictors (sociodemographic, lifestyle and reproductive) and false-positive recall were evaluated using multivariable logistic regression models. RESULTS: The recall rate was 7.6% (n = 1,923), of which with 93.8% were false-positive. Factors independently associated with higher false-positive recall included Indian ethnicity (odds ratio [95% confidence interval]: 1.52 [1.25 to 1.84]), premenopause (1.23 [1.04 to 1.44]), nulliparity (1.85 [1.57 to 2.17]), recent breast symptoms (1.72 [1.31 to 2.23]) and history of breast lump excision (1.87 [1.53 to 2.26]). Factors associated with lower risk of false-positive recall included older age at screen (0.84 [0.73 to 0.97]) and use of oral contraceptives (0.87 [0.78 to 0.97]). After further adjustment of percent mammographic density, associations with older age at screening (0.97 [0.84 to 1.11]) and menopausal status (1.12 [0.95 to 1.32]) were attenuated and no longer significant. CONCLUSION: For every breast cancer identified, 15 women without cancer were subjected to further testing. Efforts to educate Asian women on what it means to be recalled will be useful in reducing unnecessary stress and anxiety.


Assuntos
Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/psicologia , Mamografia/métodos , Mamografia/psicologia , Grupo com Ancestrais do Continente Asiático , Biópsia , Densidade da Mama , Neoplasias da Mama/diagnóstico , Reações Falso-Positivas , Feminino , Humanos , Estilo de Vida , Programas de Rastreamento/métodos , Menopausa , Pessoa de Meia-Idade , Análise Multivariada , Educação de Pacientes como Assunto , Pré-Menopausa , Reprodução , Singapura , Classe Social
20.
Breast Cancer Res ; 21(1): 34, 2019 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-30819233

RESUMO

BACKGROUND: Use of cyclin D1 (CCND1) gene amplification as a breast cancer biomarker has been hampered by conflicting assessments of the relationship between cyclin D1 protein levels and patient survival. Here, we aimed to clarify its prognostic and treatment predictive potential through comprehensive long-term survival analyses. METHODS: CCND1 amplification was assessed using SNP arrays from two cohorts of 1965 and 340 patients with matching gene expression array and clinical follow-up data of over 15 years. Kaplan-Meier and multivariable Cox regression analyses were used to determine survival differences between CCND1 amplified vs. non-amplified tumours in clinically relevant patient sets, within PAM50 subtypes and within treatment-specific subgroups. Boxplots and differential gene expression analyses were performed to assess differences between amplified vs. non-amplified tumours within PAM50 subtypes. RESULTS: When combining both cohorts, worse survival was found for patients with CCND1-amplified tumours in luminal A (HR = 1.68; 95% CI, 1.15-2.46), luminal B (1.37; 1.01-1.86) and ER+/LN-/HER2- (1.66; 1.14-2.41) subgroups. In gene expression analysis, CCND1-amplified luminal A tumours showed increased proliferation (P < 0.001) and decreased progesterone (P = 0.002) levels along with a large overlap in differentially expressed genes when comparing luminal A and B-amplified vs. non-amplified tumours. CONCLUSIONS: Our results indicate that CCND1 amplification is associated with worse 15-year survival in ER+/LN-/HER2-, luminal A and luminal B patients. Moreover, luminal A CCND1-amplified tumours display gene expression changes consistent with a more aggressive phenotype. These novel findings highlight the potential of CCND1 to identify patients that could benefit from long-term treatment strategies.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Ciclina D1/genética , Amplificação de Genes/genética , Adulto , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Feminino , Seguimentos , Testes Genéticos/métodos , Humanos , Linfonodos/patologia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Estudos Retrospectivos , Análise de Sobrevida
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