RESUMEN
BACKGROUND: Melanoma is a highly aggressive tumor, predominantly found in the skin, recognized as skin cutaneous melanoma (SKCM). Lymph node metastasis is commonly used as the route of metastasis in SKCM, necessitating the discovery of prognostic genes associated with this process for improved prognosis. METHODS: The prognostic significance of lymph node metastasis in SKCM was assessed through Kaplan-Meier analysis in SEER and TCGA-SKCM datasets. Prognostic genes were identified and a prognostic risk model was constructed Enrichment analysis and immune cell infiltration analysis were also carried out.Moreover, a validation in vitro and in vivo were conducted by CCK8,flow cytometry, transwell and animal study. RESULTS: The Kaplan-Meier survival curve revealed that patients with lymph node metastasis had a worse prognosis compared to those without. FCGR3B and PRF1 were screened by TCGA analysis.Additionally, significant differences in nine immune cell types were observed between the two risk groups. Notably, a strong positive association with CD8 T cells and a negative relationship with M2 macrophages were exhibited by PRF1. The validation of our nomogram were conducted in vitro and in vivo, and the results showed the correlations between CD8+ T cell and PRF1. CONCLUSION: In summary, two prognostic genes (FCGR3B and PRF1) were identified, and a prognostic risk model was developed for SKCM. These findings provide a novel approach for the diagnosis and treatment of SKCM.
RESUMEN
Hafnium-based ferroelectric memories are a promising approach to enhancing integrated circuit performance, offering advantages such as miniaturization, compatibility with CMOS technology, fast read and write speeds, non-volatility, and low power consumption. However, FeRAM (Ferroelectric Random Access Memory) still faces challenges related to endurance and retention susceptibility to process variations. Hence, testing and obtaining the core parameters of ferroelectric capacitors continuously is essential to investigate these phenomena and explore the potential solution. The traditional method for measuring ferroelectric capacitors has limitations in timing generation capability, introduces parasitic capacitance, and lacks accuracy for small-area capacitors. In this study, we analyzed the working principle of ferroelectric capacitors and designed a method to detect the remnant polarization, saturation polarization, and imprint offset of ferroelectric capacitors. Further, we further proposed a circuit implementation method. The proposed test circuit conquers these limitations and enables high-precision testing of ferroelectric capacitors, contributing to developing hafnium-based ferroelectric memories. The circuit includes a flip-readout circuit, a capacitance calibration circuit, and a voltage-to-time converter and time-to-digital converter (VTC&TDC) readout circuit. According to simulation results, the capacitance calibration circuit reduces the deviation of the capacitance by 84%, and the accuracy of the readout circuit is 5.91 bits, with a readout time of 150 ns and a power consumption of 1 mW. This circuit enables low-cost acquisition of array-level small-area ferroelectric capacitance data, which can guide subsequent device optimization and circuit design.
RESUMEN
Resistance random access memory (RRAM) based true random number generator (TRNG) has great potential to be applied to hardware security owing to its intrinsic switching variability. Especially the high resistance state (HRS) variation is usually taken as the entropy source of RRAM-based TRNG. However, the small HRS variation of RRAM may be introduced owing to fabrication process fluctuations, which may lead to error bits and be vulnerable to noise interference. In this work, we propose an RRAM-based TRNG with a 2T1R architecture scheme, which can effectively distinguish the resistance values of HRS with an accuracy of 1.5 kΩ. As a result, the error bits can be corrected to a certain extent while the noise is suppressed. Finally, a 2T1R RRAM-based TRNG macro is simulated and verified using the 28 nm CMOS process, which suggests its potential for hardware security applications.
RESUMEN
BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers worldwide. As the molecular mechanism for liver metastasis of CRC has not yet been completely discovered, identification of hub genes and pathways of this disease is of importance for revealing potential molecular mechanism of colorectal cancer progression. This study aimed to identify potential biomarkers and survival analysis of hub genes for CRC treatment. METHODS: The differentially expressed genes (DEGs) between colorectal cancer liver metastasis and primary tumor were screened using microarray data from two datasets GSE179979, GSE144259 obtained from the Gene Expression Omnibus (GEO) database. Gene ontology (GO) and KEGG pathway enrichment analyses were performed for DEGs using DAVID database, the protein-protein interaction (PPI) network was constructed using the Cytoscape software, and module analysis was performed using MCODE. Then, overall survival (OS), progression free interval (PFI) and disease specific survival (DSS) analysis of hub genes was performed by using TCGA database. The correlations between hub genes and clinical values were validated through CRN and immunohistochemistry (IHC) stain. RESULTS: A total of 64 DEGs were obtained, KEGG pathway analysis showed that the significant pathways included PPAR signaling pathway, Complement and coagulation cascades. Four hub genes (ITIH2, ALB, CPB2, HGFAC) and two biomarkers (CPB2, HGFAC) with significantly prognostic values were verified by Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) cohort. CONCLUSIONS: CPB2 and HGFAC may serve as new biomarkers in diagnosing liver metastasis of CRC or potential drug target.
Asunto(s)
Neoplasias Colorrectales , Neoplasias Hepáticas , Humanos , Transcriptoma , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Colorrectales/genética , Biología ComputacionalRESUMEN
Background and Purpose: To evaluate the different response patterns after Stereotactic Body Radiation Therapy (SBRT) and their predictive value in local control and progression of hepatocellular carcinoma (HCC). Materials and methods: Seventy-two HCC patients who were treated with SBRT during 2015-2020 were included in this retrospective study. The assessment was made using MRI, CT, and PET-CT. Local and systemic responses were determined according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria during follow up. Patients were categorized as early responders (complete response during 6 months after radiotherapy) or non-early responders (the rest of the patients). Prognostic factors were determined using multivariate logistic models. Results: The median follow-up was 24.0 months (range, 7.7-74.5 months). We found that 84.7%ï¼61/72) of patients achieved a complete response. Early responses occurred in 45 patients (45/72, 62.5%), and they had 1-, 2-, and 5- year intrahepatic outfield-free survival (OutFFS) rates of 86.2%, 80.3%, and 76.3% vs. 55.3%, 44.7%, and 33.5% in non-early responses patients, whereas the 1-, 2-, and 5- year distant metastasis-free survival (DMFS) were 95.5%, 84.5% and 79.5% and 74.1%, 56.2% and 56.2%, respectively. The 1-, 2-, and 5-year overall survival (OS) were 97.7%, 92.1%, 79.1%, and 85.2%, 53.8%, and 40.3%, respectively. Multivariate analysis revealed that early tumor response was an independent predictor of OutFFS, DMFS, and OS. Conclusions: Early complete tumor response within 6 months after radiotherapy predicted better intrahepatic outfield-free survival, distant metastasis-free survival, and overall survival outcomes. Confirmation is warranted for early response on SBRT to guide decision making.
RESUMEN
BACKGROUND AND PURPOSE: This study aims to evaluate whether dosimetric parameters affect the intrahepatic out-field recurrence or distant metastasis-free survival following the stereotactic body radiation therapy (SBRT) in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A total of 76 patients with HCC who were treated with SBRT from January 2015 to May 2020 were included in this retrospective study. The main clinical endpoints considered were intrahepatic out-field free survival (OutFFS) and distant metastasis-free survival (DMFS). The target parameters and the liver were documented including tumor diameters, gross tumor volume (GTV), Liver minus GTV volume (LGV), and Liver minus GTV mean dose (LGD). Multivariable Cox regression with forward stepwise selection was performed to identify independent risk factors for OutFFS and DMFS. Maximally selected rank statistics were used to determine the most informative cut-off value for age and LGD. RESULTS: The median follow-up was 28.2 months (range, 7.7-74.5 months). LGD higher than 12.54 Gy [HR, 0.861(0.747-0.993); p = 0.040] and age greater than 67-year-old [HR, 0.966(0.937-0.997); p = 0.030] are two independent predictors of OutFFS, previous TACE treatment [HR, 0.117(0.015-0.891); p = 0.038] was an independent predictor of DMFS. CONCLUSIONS: The results of this study suggested that the higher the dose received by the normal liver (greater than 12.54 Gy) the better the intrahepatic out-field recurrence-free survival (RFS) rate. Further study is warranted to confirm and to better understand this phenomenon.
RESUMEN
Probabilistic computing is an emerging computational paradigm that uses probabilistic circuits to efficiently solve optimization problems such as invertible logic, where traditional digital computations are difficult to solve. This paper proposes a true random number generator (TRNG) based on resistive random-access memory (RRAM), which is combined with an activation function implemented by a piecewise linear function to form a standard p-bit cell, one of the most important parts of a p-circuit. A p-bit multiplexing strategy is also applied to reduce the number of p-bits and improve resource utilization. To verify the superiority of the proposed probabilistic circuit, we implement the invertible p-circuit on a field-programmable gate array (FPGA), including AND gates, full adders, multi-bit adders, and multipliers. The results of the FPGA implementation show that our approach can significantly save the consumption of hardware resources.
RESUMEN
PURPOSE: To assess the efficacy and safety of different peri-operative regimens using the network meta-analysis for hepatocellular carcinoma (HCC) with portal/hepatic vein tumor thrombosis. The interested modalities included neoadjuvant three-dimensional radiotherapy (3D-CRT), post-operative intensity modulated radiation therapy (IMRT), post-operative transarterial chemoembolization (TACE), 3DCRT plus TACE and surgery alone. METHODS: PubMed and Cochrane Library electronic databases were systematically searched for eligible studies published up to March 2021. Data related to treatment efficacy including overall survival (OS) and disease-free survival (DFS) were extracted and compared using a Bayesian approach. Adverse events (AEs) were assessed and compared. RESULTS: Five studies published between 2009 and 2021 were enrolled in this network meta-analysis. The comparison showed that surgery with IMRT ranks relatively higher in prolonging OS in advanced HCC patients, followed by neoadjuvant 3DCRT and surgery plus TACE. Neoadjuvant 3DCRT and postoperative IMRT appear to be better choices than 3DCRT plus TACE in terms of OS. IMRT, TACE and neoadjuvant 3DCRT group were all superior to surgery alone in terms of DFS. The rate of AEs did not differ significantly. CONCLUSIONS: Adjuvant IMRT showed more favorable treatment responses compared to other regimens in HCC patients as a peri-operative regimen.
Asunto(s)
Carcinoma Hepatocelular/secundario , Carcinoma Hepatocelular/terapia , Venas Hepáticas , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Células Neoplásicas Circulantes , Vena Porta , China , Humanos , Metaanálisis en Red , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
PURPOSE: To assess the efficacy and safety of different perioperative regimens using network meta-analysis for hepatocellular carcinoma (HCC) with hepatic/portal vein thrombosis. The interested modalities included neoadjuvant three-dimensional conformal radiotherapy (3D-CRT), post-operative intensity modulated radiation therapy (IMRT). post-operative transarterial chemoembolization (TACE) and surgery alone. METHODS: PubMed and Cochrane Library electronic databases were systematically searched for eligible studies published up to November 2020. Data related to treatment efficacy including overall survival (OS), and disease-free survival (DFS) were extracted and compared using a Bayesian approach. Adverse events (AEs) were assessed and compared. RESULTS: Four studies published between 2005 and 2020 involving a total of 422 patients were enrolled in this network meta-analysis. The comparison showed that surgery with IMRT ranked relatively higher in prolonging OS in advanced HCC patients, followed by neoadjuvant 3DCRT and surgery plus TACE. Postoperative IMRT appeared better choice in terms of DFS. The rate of AEs did not significantly differ. CONCLUSION: Adjuvant IMRT showed more favorable treatment responses compared with other regimens in HCC patients with hepatic/portal vein thrombosis.
Asunto(s)
Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/terapia , Venas Hepáticas , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/terapia , Vena Porta , Trombosis de la Vena/complicaciones , Trombosis de la Vena/terapia , Carcinoma Hepatocelular/cirugía , China , Terapia Combinada , Humanos , Neoplasias Hepáticas/cirugía , Metaanálisis en Red , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
Osteoarticular tuberculosis (OAT) may cause severe complications and disability. Due to its indolent nature, OAT is difficult to diagnose in the early stages. Diagnosis by conventional culture is time-consuming and insensitive, and polymerase chain reaction-based molecular diagnostic methods are incapable of excluding co-infections. Metagenomic next-generation sequencing (mNGS) may identify a broad spectrum of microorganisms, including Mycobacterium, bacteria and fungi, in clinical specimens. Therefore, the diagnosis of OAT may be rapidly performed using mNGS. The present study reports on a case of OAT. The patient presented with right knee swelling and pain for 1 year; his C-reactive protein levels and erythrocyte sedimentation rate were markedly elevated. Although multiple pre-operative cultures were negative, mNGS was finally used to successfully detect the underlying pathogen. The result was confirmed by other molecular biology methods and Mycobacterium culture. Anti-tuberculosis therapy was administered accordingly and the patient finally recovered. In conclusion mNGS, with the ability to detect Mycobacterium and other microorganisms in a single assay, is an emerging approach for rapidly and accurately diagnosing OAT. This method may provide significant support to guide physicians in selecting the appropriate pharmacotherapy and surgical treatments.
RESUMEN
PURPOSE: This study compared the diagnostic capabilities of culture and broad-range polymerase chain reaction (PCR) using joint fluid (JF), periprosthetic tissue (PT), and sonicated fluid (SF) for the diagnosis of periprosthetic joint infection (PJI). METHODS: Sixty-seven subjects underwent knee or hip revision surgery, with 53 PJI and 14 aseptic failure (AF) cases included retrospectively. JF, PT, and SF samples were collected after a suspension of antibiotics more than two weeks, and culture and broad-range PCR were performed for all samples. RESULTS: The sensitivities of SF culture (83.0%), JF-PCR (83.0%), and SF-PCR (84.9%) were similar (P > 0.05), but each was significantly more sensitive than JF culture (69.8%), PT culture (71.7%), and PT-PCR (34.0%) (P < 0.05). The specificities of JF culture, PT culture, SF culture, JF-PCR, PT-PCR, and SF-PCR were similar (100, 100, 85.7, 85.7, 100, and 78.6%, respectively) (P > 0.05). PCR was unable to accurately detect six polymicrobial infections and two fungal infections. CONCLUSIONS: SF culture, JF-PCR, and SF-PCR were more sensitive than JF culture, PT culture, and PT-PCR for diagnosing PJI among patients who have stopped taking antibiotics for two weeks or more. Compared with PCR methods, SF culture has the advantage of detecting polymicrobial or fungal infections. PT-PCR proved to be insufficiently sensitive for providing correct diagnoses.