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MOTIVATION: The acquisition of somatic mutations in hematopoietic stem and progenitor stem cells with resultant clonal expansion, termed clonal hematopoiesis (CH), is associated with increased risk of hematologic malignancies and other adverse outcomes. CH is generally present at low allelic fractions, but clonal expansion and acquisition of additional mutations leads to hematologic cancers in a small proportion of individuals. With high depth and high sensitivity sequencing, CH can be detected in most adults and its clonal trajectory mapped over time. However, accurate CH variant calling is challenging due to the difficulty in distinguishing low frequency CH mutations from sequencing artifacts. The lack of well-validated bioinformatic pipelines for CH calling may contribute to lack of reproducibility in studies of CH. RESULTS: Here, we developed ArCH, an Artifact filtering Clonal Hematopoiesis variant calling pipeline for detecting single nucleotide variants and short insertions/deletions by combining the output of four variant calling tools and filtering based on variant characteristics and sequencing error rate estimation. ArCH is an end-to-end cloud-based pipeline optimized to accept a variety of inputs with customizable parameters adaptable to multiple sequencing technologies, research questions, and datasets. Using deep targeted sequencing data generated from six acute myeloid leukemia patient tumor: normal dilutions, 31 blood samples with orthogonal validation, and 26 blood samples with technical replicates, we show that ArCH improves the sensitivity and positive predictive value of CH variant detection at low allele frequencies compared to standard application of commonly used variant calling approaches. AVAILABILITY AND IMPLEMENTATION: The code for this workflow is available at: https://github.com/kbolton-lab/ArCH.
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Hematopoiese Clonal , Neoplasias Hematológicas , Adulto , Humanos , Sequenciamento de Nucleotídeos em Larga Escala , Software , Reprodutibilidade dos Testes , Mutação , Hematopoese/genéticaRESUMO
BACKGROUND: DNA sequencing is a critical tool in modern biology. Over the last two decades, it has been revolutionized by the advent of massively parallel sequencing, leading to significant advances in the genome and transcriptome sequencing of various organisms. Nevertheless, challenges with accuracy, lack of competitive options and prohibitive costs associated with high throughput parallel short-read sequencing persist. RESULTS: Here, we conduct a comparative analysis using matched DNA and RNA short-reads assays between Element Biosciences' AVITI and Illumina's NextSeq 550 chemistries. Similar comparisons were evaluated for synthetic long-read sequencing for RNA and targeted single-cell transcripts between the AVITI and Illumina's NovaSeq 6000. For both DNA and RNA short-read applications, the study found that the AVITI produced significantly higher per sequence quality scores. For PCR-free DNA libraries, we observed an average 89.7% lower experimentally determined error rate when using the AVITI chemistry, compared to the NextSeq 550. For short-read RNA quantification, AVITI platform had an average of 32.5% lower error rate than that for NextSeq 550. With regards to synthetic long-read mRNA and targeted synthetic long read single cell mRNA sequencing, both platforms' respective chemistries performed comparably in quantification of genes and isoforms. The AVITI displayed a marginally lower error rate for long reads, with fewer chemistry-specific errors and a higher mutation detection rate. CONCLUSION: These results point to the potential of the AVITI platform as a competitive candidate in high-throughput short read sequencing analyses when juxtaposed with the Illumina NextSeq 550.
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Sequenciamento de Nucleotídeos em Larga Escala , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Análise de Sequência de DNA/métodos , Análise de Sequência de RNA/métodos , Humanos , Análise de Célula Única/métodos , Biblioteca GênicaRESUMO
The recent groundbreaking achievement in the synthesis of large-sized single crystal C60 monolayer, which is covalently bonded in a plane using C60 as building blocks. The asymmetric lattice structure endows it with anisotropic phonon modes and conductivity. If these C60 are arranged in form of 1D fiber, the improved manipulation of phonon conduction along the fiber axis could be anticipated. Here, thermal properties of C60-fiber, including thermal transfer along the C60-fiber axis and across the interlayer interface are investigated using molecular dynamic simulations. Taking advantage of the distinctively hollow spherical structure of C60 building blocks, the spherical structure deformation and encapsulation induced thermal reduction can be up to 56% and 80%, respectively. By applying external electronic fields in H2O@C60 model, its thermal conductivity decreases up to 60%, which realizes the contactless thermal regulation. ln particular, the thermal rectification phenomenon is discovered by inserting atoms/molecules in C60 with a rational designed mass-gradient, and its maximum thermal rectification factor is predicted to ≈45%. These investigations aim to achieve effective regulation of the thermal conductivity of C60-fibers. This work showcases the potential of C60-fiber in the realms of thermal management and thermal sensing, paving the way to C60-based functional materials.
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Liquid biopsy technology provides invaluable support for the early diagnosis of tumors and surveillance of disease course by detecting tumor-related biomarkers in bodily fluids. Currently, liquid biopsy techniques are mainly divided into two categories: biomarker and label-free. Biomarker liquid biopsy techniques utilize specific antibodies or probes to identify and isolate target cells, exosomes, or molecules, and these techniques are widely used in clinical practice. However, they have certain limitations including dependence on tumor markers, alterations in cell biological properties, and high cost. In contrast, label-free liquid biopsy techniques directly utilize physical or chemical properties of cells, exosomes, or molecules for detection and isolation. These techniques have the advantage of not needing labeling, not impacting downstream analysis, and low detection cost. However, most are still in the research stage and not yet mature. This review first discusses recent advances in liquid biopsy techniques for early tumor diagnosis and disease surveillance. Several current techniques are described in detail. These techniques exploit differences in biomarkers, size, density, deformability, electrical properties, and chemical composition in tumor components to achieve highly sensitive tumor component identification and separation. Finally, the current research progress is summarized and the future research directions of the field are discussed.
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The construction of high-performance n-type semiconductors is crucial for the advancement of organic electronics. As an attractive n-type semiconductor, molecular systems based on perylene diimide derivatives (PDIs) have been extensively investigated over recent years. Owing to the fascinating aggregated structure and high performance, S-heterocyclic annulated PDIs (SPDIs) are receiving increasing attention. However, the relationship between the structure and the electrical properties of SPDIs has not been deeply revealed, restricting the progress of PDI-based organic electronics. Here, we developed two novel SPDIs with linear and dendronized substituents in the imide position, named linear SPDI and dendronized SPDI, respectively. A series of structural and property characterizations indicated that linear SPDI formed a long-range-ordered crystalline structure based on helical supramolecular columns, while dendronized SPDI, with longer alkyl side chains, formed a 3D-ordered crystalline structure at a low temperature, which transformed into a hexagonal columnar liquid crystal structure at a high temperature. Moreover, no significant charge carrier transport signal was examined for linear SPDI, while dendronized SPDI had a charge carrier mobility of 3.5 × 10-3 cm2 V-1 s-1 and 2.1 × 10-3 cm2 V-1 s-1 in the crystalline and liquid crystalline state, respectively. These findings highlight the importance of the structure-function relationship in PDIs, and also offer useful roadmaps for the design of high-performance organic electronics for down-to-earth applications.
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BACKGROUND AND AIMS: In stomach, metaplasia can arise from differentiated chief cells that become mitotic via paligenosis, a stepwise program. In paligenosis, mitosis initiation requires reactivation of the cellular energy hub mTORC1 after initial mTORC1 suppression by DNA damage induced transcript 4 (DDIT4 aka REDD1). Here, we use DDIT4-deficient mice and human cells to study how metaplasia increases tumorigenesis risk. METHODS: A tissue microarray of human gastric tissue specimens was analyzed by immunohistochemistry for DDIT4. C57BL/6 mice were administered combinations of intraperitoneal injections of high-dose tamoxifen (TAM) to induce spasmolytic polypeptide-expressing metaplasia (SPEM) and rapamycin to block mTORC1 activity, and N-methyl-N-nitrosourea (MNU) in drinking water to induce spontaneous gastric tumors. Stomachs were analyzed for proliferation, DNA damage, and tumor formation. CRISPR/Cas9-generated DDIT4-/- and control human gastric cells were analyzed for growth in vitro and in xenografts with and without 5-fluorouracil (5-FU) treatment. RESULTS: DDIT4 was expressed in normal gastric chief cells in mice and humans and decreased as chief cells became metaplastic. Paligenotic Ddit4-/- chief cells maintained constitutively high mTORC1, causing increased mitosis of metaplastic cells despite DNA damage. Lower DDIT4 expression correlated with longer survival of patients with gastric cancer. 5-FU-treated DDIT4-/- human gastric epithelial cells had significantly increased cells entering mitosis despite DNA damage and increased proliferation in vitro and in xenografts. MNU-treated Ddit4-/- mice had increased spontaneous tumorigenesis after multiple rounds of paligenosis induced by TAM. CONCLUSIONS: During injury-induced metaplastic proliferation, failure of licensing mTORC1 reactivation correlates with increased proliferation of cells harboring DNA damage, as well as increased tumor formation and growth in mice and humans.
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Celulas Principais Gástricas/patologia , Metaplasia/etiologia , Metaplasia/patologia , Fatores de Transcrição/fisiologia , Animais , Carcinogênese , Técnicas de Cultura de Células , Proliferação de Células , Humanos , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Acute ischemic stroke is one of the leading causes of death in developed countries and the most common cause of disability in adults worldwide. Despite advances in the understanding of stroke pathophysiology, therapeutic options remain limited. In this study, we explored the interaction of Shrm4 and the metabotropic gamma-aminobutyric acid (GABA) receptors (GABAB ) in ischemic stroke. A transient middle cerebral artery occlusion (MCAO) model was induced by filament insertion in Shrm4+/+ and wild-type C57BL/6J mice, followed by reperfusion for up to 7 days. Baclofen was administered was used to activate GABAB in vivo during reperfusion. Neurological deficits, motor and memory functions, and infarct volume were determined in the various mouse groups. Furthermore, we also developed an oxygen-glucose deprivation (OGD) cell model in primary neurons to test Shrm4/GABAB interactions in vitro. Shrm4 was observed to decrease infarct volume and neuronal cell loss in penumbra, and rescue neurological deficits in MCAO mice. Notably, Shrm4 also increased pole climbing speed, reduced foot faults, and increased escape latency in the Morris water maze test, while reducing neuron autophagy through an interaction with GABAB receptors. GABAB activation using baclofen further reduced OGD-induced neuron damage in culture and stroke outcomes of MCAO, relative to Shrm4 alone. Taken together, Shrm4-mediated GABAB activation confers neuroprotection by reducing neuronal autophagy in acute ischemic stroke.
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Autofagia/fisiologia , Isquemia Encefálica/metabolismo , Proteínas do Citoesqueleto/metabolismo , AVC Isquêmico/metabolismo , Proteínas dos Microfilamentos/metabolismo , Neuroproteção/fisiologia , Ácido gama-Aminobutírico/metabolismo , Animais , Células Cultivadas , Glucose/metabolismo , Células HEK293 , Humanos , Infarto da Artéria Cerebral Média/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Oxigênio/metabolismoRESUMO
Truncated carbon nanocones (CNCs) can be taken as energy suppliers because of their special structures. In this paper, we demonstrate the stability of truncated CNCs under compression and the escape behavior of a fullerene catapulted from a compressed CNC by molecular dynamics simulations and theoretical models. The strain energy of a CNC and cohesive energy between a fullerene and the CNC (due to their van der Waals interactions) dominate the stability and catapulting capability of the cone, which strongly depend on geometrical parameters (apex angle, top radius and height) of each CNC and axial distances between them. In particular, the additional transverse vibration of buckled CNCs after released plays a significant role in their catapulting abilities and efficiencies. Finally, finite element method and experiments are further performed to validate the escape mechanism. This study should be of great importance to providing a theoretical support for designing novel nanodevices in mico/nanoelectromechanical systems.
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BACKGROUND: Salmonella and Shigella are often associated with fecal-oral transmission and cause large-scale outbreaks in centralized catering units and, therefore, should be frequently and strictly monitored, especially among food handlers. However, no specific and sensitive on-site detection method is available until now. METHODS: In this study, an insulated isothermal PCR assay for the detection of Salmonella and Shigella on a field-deployable PCR system was developed. Specificity, sensitivity, reproducibility, and clinical accuracy of the assay were characterized and evaluated. RESULTS: The insulated isothermal PCR assay could be completed within 58 minutes with minimal pretreatment needed. The assay was specific and with good reproducibility. The limit of detection was 103 CFU/mL and 101 CFU/mL for Salmonella and Shigella, respectively, which was comparable to multiplex real-time PCR. Mock on-site clinical evaluation results showed that the analytical sensitivity and specificity of the insulated isothermal PCR assay were 100% and 96.6%, while the positive predictive value and negative predictive value were 94.1% and 100%, respectively. CONCLUSION: Based on our results, we believe that the assay developed herein could serve as an alternative method for preliminary screening and provide a valuable platform for the on-site detection of Salmonella and Shigella, especially in resource-limited and developing countries.
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The failure modes of ZnO nanowires (NWs) with hexagonal cross section subjected to a uniaxial load are systematically investigated by using molecular dynamics (MD) simulations and two theoretical models considering the surface effect. Our results show that two different failure modes of the phase transition and buckling are triggered when the NWs are under uniaxial compression along the [0001] direction, in which the transformation between the two modes is related to the slenderness ratios of the NWs. Such slenderness-ratio-dependent mode transformation is mainly attributed to the competition between the critical stresses of phase transition and buckling. The Euler and Timoshenko models considering surface effect are further proposed to derive the critical slenderness for such mode transformation. The obtained analytical threshold values agree well with those of present MD simulations. Our results should be of great help for shedding some light on the design and application of functional devices based on ZnO NWs.
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Long non-coding RNAs (lncRNAs) have been demonstrated to be involved in the progression of various cancers. In this study, we aim to investigate the role of lncRNA RUNX1-IT1 in the development of colorectal cancer (CRC). The expression levels of lncRNA RUNX1-IT1 were measured using quantitative real-time Polymerase Chain Reaction(qRT-PCR). CCK8 proliferation assay, transwell assay, and flow cytometry were performed to evaluate the effect of lncRNA RUNX1-IT1 on CRC cell proliferation, migration, and apoptosis. The proliferation markers (PCNA, Ki67), apoptosis markers (cleaved-PARP, cleaved-caspase3), and MMP9 are detected by western blotting. Significant down regulation of lncRNA RUNX1-IT1 was measured in CRC tissues and three CRC cell lines (HCT116, HT29, and RKO) compared with paired nontumorous adjacent tissues (P < 0.01) or the normal colonic epithelial cell line FHC (P < 0.05), respectively. Moreover, the proliferative and migration potential of CRC cells were inhibited by overexpressing lncRNA RUNX1-IT1, which could be obviously improved by knocking down lncRNA RUNX1-IT1. The protein levels of PCNA, Ki67, and MMP9 were upregulated by overexpressing lncRNA RUNX1-IT1 and down regulated in si-RUNX1-IT1 cells. Besides, lncRNA RUNX1-IT1 could also promote the apoptosis of CRC cells. In conclusion, lncRNA RUNX1-IT1 is downregulated in CRC and plays a tumour-suppressive role due to the regulatory of cell proliferation, migration, and apoptosis. SIGNIFICANCE OF THE STUDY: We demonstrated that lncRNA RUNX1-IT1 was down regulated both in CRC tissues and cell lines. Besides, lncRNA RUNX1-IT1 could serve as a potential diagnostic biomarker and play a tumour-suppressive role owing to its good diagnostic efficacy and inhibition of CRC cell proliferation and migration.
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Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Genes Supressores de Tumor , RNA Longo não Codificante/genética , Proteína 1 Parceira de Translocação de RUNX1/genética , Idoso , Apoptose/genética , Células Cultivadas , Neoplasias Colorretais/diagnóstico , Regulação para Baixo/genética , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Early detection is vital for prolonging 5-year survival for patients with gastric cancer (GC). Numerous studies indicate that circulating long non-coding RNAs (lncRNAs) can be used to diagnose malignant tumours. This study aimed to investigate the capacity of novel lncRNAs for diagnosing GC. A lncRNA microarray assay was used to screen differentially expressed lncRNAs between plasma of patients with GC and healthy controls. Plasma samples from 100 patients with healthy controls were used to construct a multiple-gene panel. An additional 50 pairs of GC patients with healthy controls were used to evaluate the diagnostic accuracy of the panel. Expression levels of lncRNAs were quantified through real-time polymerase chain reaction. The receiver operating characteristic curve and area under curve (AUC) were used to estimate the diagnostic capacity. We identified three lncRNAs, CTC-501O10.1, AC100830.4 and RP11-210K20.5 that were up-regulated in the plasma of GC patients with AUCs 0.724, 0.730 and 0.737, respectively (P < .01). Based on the logistic regression model, the combined AUC of the three lncRNAs was 0.764. The AUC of the panel was 0.700 in the validation cohort. These findings indicate that plasma lncRNAs can serve as potential biomarkers for detection of GC.
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Ácidos Nucleicos Livres/sangue , RNA Longo não Codificante/sangue , Neoplasias Gástricas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Linhagem Celular Tumoral , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Buckling behaviors of single-walled carbon nanotubes (SWCNTs) inserted with a linear carbon-atom chain (CAC) (the composite structures are also called carbon nanowires (CNWs)) under torsion and bending as well as compression are studied using molecular dynamics (MD) simulations, respectively. Our MD results show that the critical buckling angles (or strains) of CNWs under the three presented kinds of loading patterns can be two times those of corresponding independent SWCNTs for long CNWs, while the buckling improvement is not obvious for short ones. The main reason is that the radial van der Waals force between the CAC and the SWCNT is very small for a short CNW, while it increases with increasing length and then tends to a constant for a long CNW. The obtained MD results agree well with those from available theoretical models. These findings will be a great help towards understanding the stability and reliability of the special CNT structures, and designing flexible CNT-based devices.
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BACKGROUND Ovarian cancer is the most lethal malignant tumor of the female reproductive system, and the metastasis is one of the major factors that contribute to the poor outcome of patients with OC. Accumulating evidence indicates that lncRNAs are expressed and play important regulatory roles in ovarian cancer. MATERIAL AND METHODS Aberrant lncRNAs in primary ovarian cancer tissues (POCTs) and paired omental metastasis tissues (OMTs) of patients with HGSOC were studied via lncRNA microarray. Real-time PCR was performed to examine CTD-2020K17.1 expression in HGSOC tissues from 38 patients, a normal ovarian surface epithelium cell line, and 4 ovarian cancer cell lines. Additionally, Transwell assays, wound healing assays, CCK-8 proliferation assays, and flow cytometry were used to explore the biological function of CTD-2020K17.1 in ovarian cancer cells. Finally, Western blot analysis was used to verify the potential target gene of CTD-2020K17.1. RESULTS A novel lncRNA named CTD-2020K17.1 was identified via microarray analysis. Expression of CTD-2020K17.1 was significantly increased in OMTs and in 4 ovarian cancer cell lines compared with POCTs (P<0.05) or normal ovarian surface epithelial cell line (P<0.05). Moreover, CTD-2020K17.1 overexpression promoted migration, invasion, and proliferation of ovarian cancer cells, and CTD-2020K17.1 regulated the expression of CARD11. CONCLUSIONS CTD-2020K17.1 is significantly upregulated in OMTs and ovarian cancer cell lines. It can promote the migration, invasion, and proliferation of ovarian cancer cells, and CARD11 is regulated by CTD-2020K17.1.
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Cistadenocarcinoma Seroso/genética , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Ovarianas/genética , RNA Longo não Codificante/biossíntese , Carcinoma Epitelial do Ovário , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Cistadenocarcinoma Seroso/patologia , Feminino , Humanos , Invasividade Neoplásica , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , RNA Longo não Codificante/genética , Regulação para CimaRESUMO
We asked what preoperative radiotherapy/chemoradiotherapy (PRT/PCRT) has brought to patients in terms of perioperative and long-term outcomes over the past decades. A systematic review and meta-analysis was conducted using PubMed, Embase and Web of Science databases. All original comparative studies published in English that were related to PRT/PCRT and surgical resection and which analyzed survival, postoperative and quality of life outcomes were included. Data synthesis and statistical analysis were carried out using Stata software. Data from 106 comparative studies based on 80 different trials enrolling 41,121 patients were included in our study. Based on our overall analyses, PRT/PCRT significantly improved patients' local recurrence-free survival (LRFS), but neither overall survival (OS) nor metastasis-free survival (MFS) showed improvement. In addition, PRT significantly increased the postoperative morbidity and mortality but PCRT did not have a significant effect. Furthermore, PRT/PCRT significantly increased the risk of postoperative wound complications but not anastomotic leakage and bowel obstruction. Our comprehensive subgroup analyses further supported the aforementioned results. Meanwhile, long-term anorectal symptoms (impaired squeeze pressures, use of pads, incontinence and urgency) and erectile dysfunction were also significantly increased in patients after PRT/PCRT. The benefits of PRT/PCRT as applied over the last several decades have not been sufficient to improve OS. Metastases of primary tumor and postoperative adverse effects were the two primary obstacles for an improved OS. In fact, the greatest advantage of PRT/PCRT is still local tumor control and a significantly improved LRFS.
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Quimiorradioterapia Adjuvante/métodos , Terapia Neoadjuvante/métodos , Neoplasias Retais/terapia , Humanos , Neoplasias Retais/mortalidade , Resultado do TratamentoRESUMO
BACKGROUND: F-18- fluorodeoxyglucose Positron emission tomography (18FDG-PET) has been widely used in clinical practice. However, the prognostic value of the pretreatment standardized uptake value (SUV) for patients with gastric cancer remains controversial. METHODS: Major databases were systematically searched. The quality of the included studies was assessed using the Newcastle-Ottawa scale; the PET protocols were also evaluated. The pooled hazard ratio (HR) for overall survival (OS) and recurrence-free survival (RFS) were used to estimate the effect size. Data from the included studies were analyzed using Review Manager Software version 5.2. RESULTS: Eight studies with 1080 patients were included. The pooled HR for OS of six studies including 672 patients was 1.72 (95% CI [1.28-2.3], p = 0.0004, I2 = 0%), indicating that patients with high SUVs may have poor prognosis. The pooled HR for RFS was 1.70 (95% CI [1.20-2.39], p = 0.003, I2 = 0%). Subgroup analysis based on the cutoff values determining method indicated that the receiver operating characteristic (ROC) method could better define the cutoff value. Subgroup analysis based on the therapeutic strategies used subsequently indicated the significant prognostic value of SUV. CONCLUSION: In conclusion, our meta-analysis indicated that pretreatment SUV in primary lesions can be an important prognostic factor for overall survival and recurrence-free survival in patients with gastric cancer. High SUVs may indicate poor prognosis.
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Fluordesoxiglucose F18/farmacocinética , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/farmacocinética , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/metabolismo , Intervalo Livre de Doença , Humanos , PrognósticoRESUMO
BACKGROUND: Growing evidence has indicated that some inflammatory markers, including lymphocyte to monocyte ratio (LMR), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and prognostic nutritional index (PNI), can be used as indicators in the prognosis of colorectal cancer (CRC). However, there is controversy concerning what is the best predictor of prognosis in CRC. METHODS: A cohort of 1744 CRC patients in our institution was analyzed retrospectively. Harrell's concordance index (c-index) and Bayesian information criterion (BIC) were used to determine the optimal cut-off values of inflammatory markers and compare their predictive capacity. The association of inflammatory markers with overall survival (OS) and cancer-specific survival (CSS) was analyzed using Kaplan-Meier methods with log-rank test, followed by multivariate Cox proportional hazards model. RESULTS: The multivariate analysis indicated that among these inflammatory markers, NLR (< 2.0 vs. ≥ 2.0) was the only independent prognostic factor for poor OS [hazard ratio (HR) = 0.758, 95% confidence intervals (CI) = 0.598-0.960, P = 0.021)] and CSS (HR = 0.738, 95% CI = 0.573-0.950, P = 0.018). Among these inflammatory markers, the c-index and BIC value for NLR were maximum and minimum for OS, respectively. In addition, the c-index was higher and the BIC value was smaller in TNM staging combined with NLR compared with the values obtained in TNM staging alone. CONCLUSION: NLR is a superior indicator of prognosis compared with LMR, PLR, and PNI in CRC patients, and NLR may serve as an additional indicator based on the current tumor staging system.
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Biomarcadores Tumorais/sangue , Neoplasias Colorretais/sangue , Inflamação/sangue , Prognóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Inflamação/patologia , Inflamação/cirurgia , Estimativa de Kaplan-Meier , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neutrófilos/patologia , Contagem de Plaquetas , Adulto JovemRESUMO
From the macro- to the nanoscale, kirigami structures show novel and tunable properties by tailoring the original two-dimensional sheets. In this study, the large stretchability and failure behavior in graphene nanoribbon kirigami (GNR-k) are obtained using the finite element (FE) method and molecular dynamics (MD) simulations. The carbon-carbon bond in the FE method is equivalent to a nonlinear Timoshenko beam based on the Tersoff-Brenner potential. All the results from the present FE method are in reasonable agreement with those from our MD simulations using the REBO potential. These results from the two methods show that the maximum ultimate strain of GNR-k (around 100%) is around 4 times higher than that of a pristine graphene nanoribbon (GNR), whereas the minimum ultimate stress of GNR-k is around one order of magnitude lower than that of the GNR. In particular, the large stretchability of GNR-k is indirectly proven to be mainly derived from the out-of-plane bending deformation by measuring the nonlinear mechanical properties of paper kirigami. Our results provide physical insights into the origins of the large stretchability of GNR-k and make GNR-k applicable to flexible nanodevices.
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BACKGROUND: The preferred chemotherapy method for gastric cancer continues to be matter of debate. We performed a meta-analysis to comparing prognosis and safety between perioperative chemotherapy and adjuvant chemotherapy to identify the better chemotherapy option for gastric cancer. METHODS: We searched the PubMed, EMBASE, Cochrane Library, and Ovid databases for eligible studies until February 2016. The main endpoints were prognostic value (hazard ratio [HR] for overall survival [OS] and 1-, 2-, 3-, and 5-year survival rate), response rate of chemotherapy, radical resection rate, post-operative complication rate, and adverse effects of chemotherapy. RESULTS: Five randomized controlled trials and six clinical controlled trials involving 1,240 patients were eligible for analysis. Compared with the adjuvant chemotherapy group, the perioperative chemotherapy group had significantly better prognosis (HR, 0.74; 95 % CI, 0.61 to 0.89; P < 0.01). The difference between the two groups remained significant in the studies that used combination chemotherapy as the neoadjuvant chemotherapy regimen (HR, 0.59; 95 % CI, 0.46 to 0.76; P < 0.01) but were not significant in the studies that used fluoropyrimidine monotherapy (HR, 0.93; 95 % CI, 0.56 to 1.55; P = 0.84). Furthermore, the two groups showed no significant differences in the post-operative complication rates (relative risk, 0.98; 95 % CI, 0.63 to 1.51; P = 0.91) or adverse effects of chemotherapy (P > 0.05 for all adverse effects). CONCLUSION: Perioperative chemotherapy showed improved survival compared to adjuvant chemotherapy for gastric cancer. In addition, combination chemotherapy resulted in better survival compared to monotherapy in the neoadjuvant chemotherapy regimens.
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Antineoplásicos/uso terapêutico , Terapia Neoadjuvante/métodos , Assistência Perioperatória/métodos , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Laparoscopic methods and fast-track surgery (FTS) can enhance recovery and reduce postoperative hospital stay. However, whether laparoscopic surgery can provide short-term benefits within FTS is controversial. Thus, we conducted a meta-analysis of published studies to evaluate the effect of laparoscopic colorectal surgery within FTS. METHODS: We searched PubMed, EMBASE, Cochrane Library, and Ovid databases for eligible studies. Endpoints were duration of postoperative hospital stay, time to first bowel movement, total postoperative complication rate, readmission rate, mortality within 30 days after surgery, and conversation rate of laparoscopic surgery. RESULTS: Four randomized controlled trials and six clinical controlled trials (1510 patients) were eligible for analyses. Duration of postoperative hospital stay (weighted mean difference, -1.65 days; p < 0.001), time to first bowel movement (-1.13 days; p < 0.001), total postoperative complication rate (risk ratio [RR], 0.65; p < 0.001), readmission rate (0.46; p < 0.001), and mortality (0.45; p < 0.001) were significantly reduced in the laparoscopic surgery group. Overall conversion rate of laparoscopic surgery was 11.1%. Subgroup analyses based on each FT element demonstrated that studies without the element "prevention of hypothermia," "no bowel preparation," or "no routine use of drains" did not show significant differences between two groups with regard to duration of postoperative hospital stay or total prevalence of postoperative complications. CONCLUSION: Within FTS, laparoscopic methods can significantly shorten postoperative hospital stay, accelerate postoperative recovery, and enhance safety in colorectal surgery. The FT elements "prevention of hypothermia," "no bowel preparation," and "no routine use of drains" may play important parts in the combined effect of these two methods.