The Cu migration
is controlled by using an optimized AlO
x
interfacial layer, and effects on resistive
switching performance, artificial synapse, and human saliva detection
in an ...amorphous-oxygenated-carbon (a-CO
x
)-based CBRAM platform have been investigated for the first time.
The 4 nm-thick AlO
x
layer in the Cu/AlO
x
/a-CO
x
/TiN
x
O
y
/TiN structure
shows consecutive >2000 DC switching, tight distribution of SET/RESET
voltages, a long program/erase (P/E) endurance of >10
9
cycles
at a low operation current of 300 μA, and artificial synaptic
characteristics under a small pulse width of 100 ns. After a P/E endurance
of >10
8
cycles, the Cu migration is observed by both
ex
situ high-resolution transmission electron microscopy and energy-dispersive
X-ray spectroscopy mapping images. Furthermore, the optimized Cu/AlO
x
/a-CO
x
/TiN
x
O
y
/TiN CBRAM detects
glucose with a low concentration of 1 pM, and real-time measurement
of human saliva with a small sample volume of 1 μL is also detected
repeatedly in vitro. This is owing to oxidation–reduction of
Cu electrode, and the switching mechanism is explored. Therefore,
this CBRAM device is beneficial for future artificial intelligence
application.
Background: Uterine sarcoma, frequently diagnosed postoperatively, and often misidentified as benign tumor, is commonly managed through minimally invasive surgery (MIS) and tumor morcellation. This ...study aims to investigate the survival outcomes of MIS for early-stage uterine sarcoma, and investigate the impact of tumor morcellation on oncologic outcomes. Methods: A retrospective study was conducted on 33 patients diagnosed with early-stage uterine sarcoma and were studied from January 2006 to December 2022. Patients were divided into two groups: MIS group and open group. This study assessed the 5-year progression-free survival (PFS) and overall survival (OS) in both groups. Additionally, the study investigated the impact of tumor morcellation on oncology outcomes. Results: The 5-year PFS rates in the MIS and open surgery groups were 42% and 65%, respectively (p = 0.577); the 5-year OS rates were 77% and 56%, respectively (p = 0.125). Sixteen patients had recurrence (48%). The 5-year PFS rates in the morcellated and nonmorcellated groups were 42% and 51%, respectively (p = 0.732); the 5-year overall survival rates were 75% and 68%, respectively (p = 0.584). Conclusions: Although there were not statistically significant differences in survival outcomes between the MIS group and open surgery, intraoperative tumor morcellation may increase peritoneal recurrence risk and negatively affect progression-free survival. Further, a large study is needed to investigate the outcomes of MIS.
While immunotherapy holds great promise for combating cancer, the limited efficacy due to an immunosuppressive tumor microenvironment and systemic toxicity hinder the broader application of cancer ...immunotherapy. Here, we report a combinatorial immunotherapy approach that uses a highly efficient and tumor-selective gene carrier to improve anticancer efficacy and circumvent the systemic toxicity. In this study, we engineered tumor-targeted lipid-dendrimer-calcium-phosphate (TT-LDCP) nanoparticles (NPs) with thymine-functionalized dendrimers that exhibit not only enhanced gene delivery capacity but also immune adjuvant properties by activating the stimulator of interferon genes (STING)-cGAS pathway. TT-LDCP NPs delivered siRNA against immune checkpoint ligand PD-L1 and immunostimulatory IL-2-encoding plasmid DNA to hepatocellular carcinoma (HCC), increased tumoral infiltration and activation of CD8
T cells, augmented the efficacy of cancer vaccine immunotherapy, and suppressed HCC progression. Our work presents nanotechnology-enabled dual delivery of siRNA and plasmid DNA that selectively targets and reprograms the immunosuppressive tumor microenvironment to improve cancer immunotherapy.
Cervical cancer is the fourth most common cancer in women with an estimated 570,000 new cases in 2018 which constitute about 6. 6% of all cancers in women according to WHO report 2018. Approximately ...90% of the 270,000 deaths from cervical cancer in 2015 occurred in low- and middle-income countries. In cervical cancers, which is caused by human papillomavirus (HPV) infection, the expression of HPV 16 E6 and E7 proteins are essential for tumor cell transformation and maintenance of malignancy. Prophylactic vaccines against cervical cancer caused by human papillomavirus have not proven successful. Although virus-like particle-based (VLPs) vaccines have been developed with prophylactic activities to prevent most HPV infections, the therapeutic effect of VLP vaccines has yet to be demonstrated for those who were already infected. A recent study showed that pre-conditioning mice with a potent antigen such as tetanus toxoid significantly improves lymph node homing and efficacy of dendritic cells. Tetanus toxoid has also been used in combination with DNA vaccines designed from tumor based antigens. In the present study, we pre-conditioned mice with tetanus toxoid followed by vaccination with a Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) overexpressing tumor-cell based vaccine (GVAX). We observed that pre-conditioning with tetanus toxoid followed by vaccination with GVAX regressed tumor growth and enhanced the overall survival of the mice. Pre-conditioning with tetanus toxoid enhanced the immune response which was observed by enlarged spleen size, higher proliferation rate of lymphocytes, a higher level of IFN-γ, TNF-α, and IL-4 antigen-specific secretions by the splenocytes. Pre-conditioning with tetanus toxoid increased memory T cell migration into the tumor site and spleen. The antigen-specific cytotoxic T cell lysis percentage was also found to be higher in the group of mice vaccinated with the combination of tetanus toxoid and GVAX. Hence, pre-conditioning with tetanus toxoid prior to vaccination with a tumor-cell based vaccine overexpressing GM-CSF might be an effective strategy for targeting E7-specific HPV-associated cervical malignancy.
In this letter, we demonstrate the key role of the Hf/Si interfacial layer (IL) in Al/Cu/IL/MoS2/TiN conductive bridge RAM. Owing to controlling Cu migration through Hf rather than Si, the Hf ...interface device offers consecutive >4000 DC cycles and long program/erase (P/E) endurance of >2 × 109 cycles under the low current operation of 100 μA at the fast switching speed of 100 ns. The Hf interface device shows gradual RESET, long-term potentiation/depression (LTP/LTD) pulses of 40/100 with small pulse width of 100 ns and a low power consumption of <13 pJ is needed for artificial synapse applications.
Predicting clinical patients’ vital signs is a leading critical issue in intensive care units (ICUs) related studies. Early prediction of the mortality of ICU patients can reduce the overall ...mortality and cost of complication treatment. Some studies have predicted mortality based on electronic health record (EHR) data by using machine learning models. However, the semi-structured data (i.e., patients’ diagnosis data and inspection reports) is rarely used in these models. This study utilized data from the Medical Information Mart for Intensive Care III. We used a Latent Dirichlet Allocation (LDA) model to classify text in the semi-structured data of some particular topics and established and compared the classification and regression trees (CART), logistic regression (LR), multivariate adaptive regression splines (MARS), random forest (RF), and gradient boosting (GB). A total of 46,520 ICU Patients were included, with 11.5% mortality in the Medical Information Mart for Intensive Care III group. Our results revealed that the semi-structured data (diagnosis data and inspection reports) of ICU patients contain useful information that can assist clinical doctors in making critical clinical decisions. In addition, in our comparison of five machine learning models (CART, LR, MARS, RF, and GB), the GB model showed the best performance with the highest area under the receiver operating characteristic curve (AUROC) (0.9280), specificity (93.16%), and sensitivity (83.25%). The RF, LR, and MARS models showed better performance (AUROC are 0.9096, 0.8987, and 0.8935, respectively) than the CART (0.8511). The GB model showed better performance than other machine learning models (CART, LR, MARS, and RF) in predicting the mortality of patients in the intensive care unit. The analysis results could be used to develop a clinically useful decision support system.
Bevacizumab (BEV) has been used for ovarian cancer (OC) for years in Taiwan, but the associated data related to outcome is scant. This retrospective study reviewed patients with OC treated with BEV ...and analyzed their results.
All patients with OC treated with BEV from 2009 to 2015 in the Linkou branch of Chang Gung Memorial Hospital in Northern Taiwan were included. According to the means of administration, the patients were classified into 6 groups as follows: A-BEV plus chemotherapy (C/T) for initial platinum-resistant (PR) recurrent OC, B-BEV plus C/T for initial platinum-sensitive (PS) recurrent OC, C-BEV alone for recurrent OC, D-BEV plus 1st adjuvant C/T, E-BEV plus neoadjuvant C/T, and F-intraperitoneal (IP) BEV. Progression-free survival (PFS), overall survival (OS), hazard ratios (HRs), overall response rate (ORR), and mean number of BEV cycles were analyzed for groups A to E. Clinical improvement of ascites was assessed for group F.
A comparison of early use (only one round of prior C/T) versus late use (multiple rounds of prior C/T) in patients of groups A and B showed a superior PFS (8.27 vs. 3.67, p = 0.037) in the early use group. No significant differences were found between groups A and B (PFS: 4.24 vs. 4.17 months, p = 0.690; OS: 10.06 vs. 9.93 months, p = 0.819; mean BEV cycles: 4.63 vs. 5.0 p = 0.992; ORR: 48.1% vs. 53.5%, p = 0.425). Comparing the response and non-response subgroups of patients in groups A and B, a better outcome was associated with endometrioid type cell (HR = 0.28, p = 0.008), good ECOG performance status (HR = 0.51, p = 0.005), and lack of ascites (HR = 0.67, p = 0.004). Comparing group C with groups A plus B, the BEV alone group had a poorer PFS (1.02 VS. 4.19, p = 0.04) and OS (1.42 VS. 9.99 p = 0.001) than the BEV plus C/T group. In group F, a good clinical benefit rate (85.6%) of ascites improvement was noted. Two patients had grade 5 gastrointestinal bleeding and venous/arterial thromboembolic events after administration of BEV. Grade 3 neutropenia and thrombocytopenia occurred more frequently in our study.
Early use of BEV combined with chemotherapy had a significant benefit in PFS for patients with recurrent OC. BEV plus chemotherapy was better than BEV alone for recurrent OC. In addition, IP BEV was helpful for improving clinical ascites.
Ectopic expression of codon-modified granulocyte-macrophage colony-stimulating factor (cGM-CSF) in TC-1 cells (TC-1/cGM-CSF), a model cell line for human papillomavirus (HPV)-infected cervical cancer ...cells, increased the expression level of GM-CSF and improved the efficacy of tumor cell-based vaccines in a cervical cancer mouse model. The number of vaccine doses required to induce a long-term immune response in a cervical cancer mouse model is poorly understood. Here, we investigated one, three, and five doses of the irradiated TC-1/cGM-CSF vaccine to determine which dose was effective in inducing a greater immune response and the suppression of tumors. Our findings showed that three doses of irradiated TC-1/cGM-CSF vaccine elicited slower tumor growth rates and enhanced survival rates compared with one dose or five doses of irradiated TC-1/cGM-CSF vaccine. Consistently, mice vaccinated with three doses of irradiated TC-1/cGM-CSF vaccine exhibited stronger interferon gamma (IFN-γ) production in HPV E7-specific CD8⁺ T cells and CD4⁺ T cells. A higher percentage of natural killer cells and interferon-producing killer dendritic cells (IKDCs) appeared in the splenocytes of the mice vaccinated with three doses of irradiated TC-1/cGM-CSF vaccine compared with those of the mice vaccinated with one dose or five doses of irradiated TC-1/cGM-CSF vaccine. Our findings demonstrate that single or multiple vaccinations, such as five doses, with irradiated TC-1/cGM-CSF vaccine suppressed the immune response, whereas three doses of irradiated TC-1/cGM-CSF vaccine elicited a greater immune response and subsequent tumor suppression.
Genotyping of human papillomarvirus (HPV) is crucial for patient management in a clinical setting. This study accesses the combined use of broad-range real-time PCR and high-resolution melting (HRM) ...analysis for rapid identification of HPV genotypes.
Genomic DNA sequences of 8 high-risk genotypes (HPV16/18/39/45/52/56/58/68) were subject to bioinformatic analysis to select for appropriate PCR amplicon. Asymmetric broad-range real-time PCR in the presence of HRM dye and two unlabeled probes specific to HPV16 and 18 was employed to generate HRM molecular signatures for HPV genotyping. The method was validated via assessment of 119 clinical HPV isolates.
A DNA fragment within the L1 region was selected as the PCR amplicon ranging from 215-221 bp for different HPV genotypes. Each genotype displayed a distinct HRM molecular signature with minimal inter-assay variability. According to the HRM molecular signatures, HPV genotypes can be determined with one PCR within 3 h from the time of viral DNA isolation. In the validation assay, a 91% accuracy rate was achieved when the genotypes were in the database. Concomitantly, the HRM molecular signatures for additional 6 low-risk genotypes were established.
This assay provides a novel approach for HPV genotyping in a rapid and cost-effective manner.
Sarcosine prostate cancer biomarker with the low concentration of 1 pM has been detected by controlling oxygen from 1 to 15 sccm in a NiOx membrane on chemically etched vertical Si nanowires (SiNWs) ...in an electrolyte–insulator–nanowire (EIN) structure. The vertical Si nanowires with approximately 17 μm length and polycrystalline NiOx membrane are observed by both field-emission scanning electron microscope (FE-SEM) and high-resolution transmission electron microscope (HRTEM) images, respectively. The optimized NiOx membrane with oxygen content of 4 sccm on planar SiOx/Si substrate shows good pH sensitivity of approximately 50 mV/pH, low hysteresis of 3.4 mV, and low drift rate of 2.4 mV/h as compared to other oxygen content membranes of 1, 10, and 15 sccm. Further, uric acid with the concentration of 0.1 μM is detected directly by using the optimized NiOx membrane. In addition, repeatable H2O2 sensing with the low concentration of 10 pM as well as prostate cancer biomarker is detected, which is owing to the reduction–oxidation phenomena of the NiOx membranes. The sensing mechanism is owing to the Ni2+/Ni3+ oxidation states of the NiOx membrane, which is confirmed by X-ray photoelectron spectroscopy. The optimized NiOx membrane on vertical Si nanowire in the EIN structure shows a good drift rate of 3.84 mV/h and sarcosine detection with improvement of approximately 1000 times as compared to the planar Si in an electrolyte–insulator–semiconductor (EIS) structure. This sensor paves a way to detect early-stage diagnosis of prostate cancer rapidly in the near future.
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