This study showed an interaction between oral bacteria, lifestyle factors and genetic polymorphisms on the risk of oral cancer. The results also provided biological support for the established ...association between poor oral hygiene and oral cancer risk.
Abstract
Poor oral hygiene may lead to overgrowth of pathogenic oral bacteria, which may induce chronic inflammation to promote the oncogenesis of oral squamous cell carcinoma (OSCC). This study investigated the association between oral bacterial profile and OSCC risk in a case-control study of 138 OSCC cases and 151 controls (88 cases and 90 controls for the discovery group and 50 cases and 61 controls for the validation group). Oral bacterial profiles were characterized by targeted sequencing of the 16S rRNA gene. Three species of periodontopathogenic bacteria, Prevotella tannerae, Fusobacterium nucleatum, and Prevotella intermedia, were associated with an increased OSCC risk. This association was modified by the genetic polymorphisms of TLR2 and TLR4. Use of alcohol, betel quids and cigarettes and poor oral hygiene were associated with a higher percentage of oral periodontopathogenic bacteria. The association between alcohol and periodontopathogenic bacteria was modified by the genetic polymorphism of ALDH2, with a stronger positive association observed among the ALDH2-deficient individuals. The percentage of periodontopathogenic bacteria was positively correlated with the level of salivary IL1β, an inflammatory cytokine. Overall, our results showed a positive association between periodontopathogenic bacteria and OSCC risk and this relationship may be influenced by lifestyle and genetic factors. Our results provided further biological support for the established association between poor oral hygiene and OSCC risk. This suggested that improving oral hygiene may reduce OSCC risk and should be part of a public health campaign to prevent the occurrence of OSCC.
Background
Lenvatinib and atezolizumab plus bevacizumab(A + B) have been used for unresectable hepatocellular carcinoma (HCC) as first‐line therapy. Real‐world studies comparison of efficacy and ...safety in these two regimens are limited, we therefore conduct this study to investigate these issues.
Methods
We retrospectively reviewed patients received lenvatinib (n = 46) and A + B (n = 46) as first‐line systemic therapy for unresectable HCC in a tertiary medical center. Objective response rate (ORR), progression free survival (PFS), and overall survival (OS) were evaluated according to modified Response Evaluation Criteria in Solid Tumors (mRECIST). Inverse probability weighting (IPW) was performed for baseline clinical features balance.
Results
A total of 92 patients with median age of 63.8 year‐old, 78.3% male, 85.9% viral hepatitis infected, 67.4% BCLC stage C were enrolled. The median treatment and follow‐up duration were 4.7 months and 9.4 months, respectively. There was no significant difference in ORR (26.1% vs. 41.3%, p = 0.1226), PFS (5.9 vs. 5.3 months, p = 0.4066), and OS (not reached vs. not reached, p = 0.7128) between the lenvatinib and A + B groups. After IPW, the results of survival and response rate were also compared. Subgroup analysis suggested that using lenvatinib was not inferior to A + B in regards of PFS, including those with elder, Child‐Pugh class B, beyond up‐to‐seven, or portal vein invasion VP4 patients. Among the lenvatinib treated patients, multivariate analysis showed patients elder than 65‐year‐old was an independent predictor associated with shorter PFS (adjust HR: 2.0850.914–4.753, p = 0.0213). The incidence rates of adverse events were similar between two groups (76 vs. 63%, p = 0.1740). Both of two regimens had similarly few impact on liver function by comparison of baseline, third month, and sixth month albumin‐bilirubin index and Child‐Pugh score.
Conclusions
The efficacy and safety of lenvatinib are similar to A + B as a first‐line systemic therapy for unresectable HCC.
This study provides real‐world experience of lenvatinib and A + B as firstline treatment for unresectable HCC. The data showed that compared survival, response rate, and adverse events between two regimens.
Non-invasive continuous blood pressure measurement is an emerging issue that potentially can be applied to cardiovascular disease monitoring and prediction. Recently, many groups have proposed the ...pulse transition time (PTT) method to estimate blood pressure for long-term monitoring. However, the PTT-based methods for blood pressure estimation are limited by non-specific estimation models and require multiple calibrations. This study aims to develop a low-cost wearable piezoelectric-based system for continuous beat-to-beat blood pressure measurement. The pressure change in the radial artery was extracted by systolic and diastolic feature points in pressure pulse wave (PPW) and the pressure sensitivity of the sensor. The proposed system showed a reliable accuracy of systolic blood pressure (SBP) (mean absolute error (MAE) ± standard deviation (SD) 1.52 ± 0.30 mmHg) and diastolic blood pressure (DBP, MAE ± SD 1.83 ± 0.50), and its performance agreed with standard criteria of MAE within 5 mmHg and SD within ±8 mmHg. In conclusion, this study successfully developed a low-cost, high-accuracy piezoelectric-based system for continuous beat-to-beat SBP and DBP measurement without multiple calibrations and complex regression analysis. The system is potentially suitable for continuous, long-term blood pressure-monitoring applications.
To identify the prevalence of mental health problems and sleep disturbances among nursing students during the COVID-19 pandemic.
As a future professional workforce, nursing students are expected to ...play a role in controlling the COVID-19 pandemic; however, physical and mental health problems may hinder their willingness to stay in the nursing profession. Evidence of the prevalence of the health problems among nursing students related to COVID-19 may allow educators to manage their students’ health problems and make them feel more positive about their future careers.
Systematic review and meta-analysis. This study was prospectively registered with PROSPERO.
Databases, including CINAHL, Embase, PubMed and Web of Science, were searched for all related journal articles, from database inception to June 29, 2021, published between 2020 and 2021.
This review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using a PICOS search strategy. A DerSimonian–Laird random-effects model was used to estimate the prevalence and potential heterogeneity among the selected studies using the Cochran Q statistic and I-square test. Publication bias was assessed using the Egger intercept test.
Seventeen studies were included in the meta-analysis, representing 13,247 nursing students. During the COVID-19 pandemic, the prevalence of four health problems and sleep disturbances were identified. The health problem with the highest prevalence in nursing students was depression (52%). Other COVID-19-related health problems were fear (41%), anxiety (32%) and stress (30%) and sleep disturbances (27%).
The findings from this study showed that strategies are necessary to manage nursing students’ teaching and learning during the COVID-19 pandemic or similar future situations. Our results suggest that preparing modified distance learning might reduce the prevalence of health problems related to the educational process. In addition, providing regular mental health assessments or online mental health services to students may improve their mental health and increase their well-being. Nursing education policies regarding clinical practice remain to be formulated to ensure the achievement of competencies to support future careers while considering the mental readiness and safety of students.
To assess the clinical efficacy and safety of neutralizing monoclonal antibodies (mABs) for outpatients with coronavirus disease 2019 (COVID‐19). PubMed, Embase, Web of Science, Cochrane Library, ...ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform (ICTRP) databases were searched from inception to July 19, 2021. Only randomized controlled trials (RCTs) that assessed the clinical efficacy and safety of neutralizing mABs in the treatment of COVID‐19 outpatients were included. The Cochrane risk‐of‐bias tool was used to assess the quality of the included RCTs. The primary outcome was the risk of COVID‐19‐related hospitalization or emergency department (ED) visits. The secondary outcomes were the risk of death and adverse events (AEs). Five articles were included, in which 3309 patients received neutralizing mAB and 2397 patients received a placebo. A significantly lower rate of hospitalization or ED visits was observed among patients who received neutralizing mABs than those who received a placebo (1.7% vs. 6.5%, odds ratios (OR): 0.26; 95% confidence interval (CI): 0.19–0.36; I2 = 0%). In addition, the rate of hospitalization was significantly lower in the patients who received neutralizing mABs than in the control group (OR: 0.24; 95% CI: 0.17−0.34; I2 = 0%). The mortality rate was also significantly lower in the patients who received neutralizing mABs than in the control group (OR: 0.16; 95% CI: 0.05−0.58; I2 = 3%). Neutralizing mABs were associated with a similar risk of any AE (OR: 0.81; 95% CI: 0.64–1.01; I2 = 52%) and a lower risk of serious AEs (OR: 0.37; 97% CI: 0.19–0.72; I2 = 45%) compared with a placebo. Neutralizing mABs can help reduce the risk of hospitalization or ED visits in COVID‐19 outpatients. For these patients, neutralizing mABs are safe and not associated with a higher risk of AEs than a placebo.
Highlights
Neutralizing monoclonal antibodies (mABs) decreased risk of hospitalization or emergence department visits in coronavirus disease 2019 (COVID‐19) outpatients.
Neutralizing mABs reduced mortality in COVID‐19 outpatients.
Neutralizing mABs had no increased risk of any adverse events (AEs) and lower risk of serious AEs.
Immunotherapy has been incorporated into the first- and second-line treatment strategies for non-small cell lung cancer (NSCLC), profoundly ushering in a new treatment landscape. However, both ...adaptive signaling and oncogenic (epidermal growth factor receptor (EGFR)-driven) signaling may induce PD-L1 upregulation in NSCLC. Nevertheless, the superiority of immune checkpoint inhibitors (ICIs) in advanced EGFR-mutant NSCLC is only moderate. ICIs appear to be well tolerated, but clinical activity for some advanced EGFR-mutant NSCLC patients has only been observed in a small proportion of trials. Hence, there are still several open questions about PD-L1 axis inhibitors in patients with NSCLC whose tumors harbor EGFR mutations, such as the effect of EGFR tyrosine kinase inhibitors (TKIs) or EGFR mutations in the tumor microenvironment (TME). Finding the answers to these questions requires ongoing trials and preclinical studies to identify the mechanisms explaining this possible increased susceptibility and to identify prognostic molecular and clinical markers that may predict benefits with PD-1 axis inhibition in this specific NSCLC subpopulation. The presence of multiple mechanisms, including dynamic immune TME profiles, changes in PD-L1 expression and low tumor mutational burdens, may explain the conflicting data regarding the correlation between PD-L1 axis inhibitors and EGFR mutation status. We conducted a review of this currently controversial topic in an attempt to aid in the decision-making process.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Display omitted
•S/A is a valuable reference for the SCC mix design.•Higher S/A means more fine aggregates to fill in the pores.•Increasing S/A undermines efforts to reduce the area affected by ...ITZ.•Higher S/A produces concrete of greater compactness and higher durability.
In this study, it evaluated the effects of sand/aggregate (S/A) ratio on the flowability, strength, durability, and microstructures of self-compacting concrete (SCC). Testing was performed on specimens using five S/A ratios: 51%, 52%, 53%, 54%, and 55%. Slump flow tests, slump tests, and box tests were used to characterize the rheological properties of the concrete as well as the mechanical properties, including compressive strength, splitting strength, slant shear strength and ultrasonic pulse velocity. Durability was evaluated using tests of absorption, resistivity and initial surface absorption. Microstructures were examined using mercury intrusion porosimetry (MIP) and scanning electron microscopy (SEM). The test results indicate that a higher S/A ratio improved flowability. A greater proportion of coarse aggregate (i.e., a decrease in S/A ratio) improved the mechanical properties by 10% compared to the control specimens (S/A ratio: 52%) at 56 days. A higher S/A ratio was shown to improve bonding capacity by enhancing the roughness of the particles and thereby increasing adhesion strength. A higher S/A ratio was also shown to improve the durability of the specimens by permitting denser packing; however, a higher S/A ratio resulted in a thinner interfacial transition zone. MIP analysis did not reveal a correlation between S/A ratio and the interfacial transition zone, whereas SEM photos indicated that a lower S/A ratio reduces the size of the interfacial transition zone.
MicroRNAs (miRNAs) are small non-coding RNAs of approximately 22 nucleotides, which negatively regulate the gene expression at the post-transcriptional level. This study describes an update of the ...miRTarBase (http://miRTarBase.mbc.nctu.edu.tw/) that provides information about experimentally validated miRNA-target interactions (MTIs). The latest update of the miRTarBase expanded it to identify systematically Argonaute-miRNA-RNA interactions from 138 crosslinking and immunoprecipitation sequencing (CLIP-seq) data sets that were generated by 21 independent studies. The database contains 4966 articles, 7439 strongly validated MTIs (using reporter assays or western blots) and 348 007 MTIs from CLIP-seq. The number of MTIs in the miRTarBase has increased around 7-fold since the 2014 miRTarBase update. The miRNA and gene expression profiles from The Cancer Genome Atlas (TCGA) are integrated to provide an effective overview of this exponential growth in the miRNA experimental data. These improvements make the miRTarBase one of the more comprehensively annotated, experimentally validated miRNA-target interactions databases and motivate additional miRNA research efforts.
Computing-in-memory (CIM) based on embedded nonvolatile memory is a promising candidate for energy-efficient multiply-and-accumulate (MAC) operations in artificial intelligence (AI) edge devices. ...However, circuit design for NVM-based CIM (nvCIM) imposes a number of challenges, including an arealatency-energy tradeoff for multibit MAC operations, patterndependent degradation in signal margin, and small read margin. To overcome these challenges, this article proposes the following: 1) a serial-input non-weighted product (SINWP) structure; 2) a down-scaling weighted current translator (DSWCT) and positive-negative current-subtractor (PN-ISUB); 3) a currentaware bitline clamper (CABLC) scheme; and 4) a triple-margin small-offset current-mode sense amplifier (TMCSA). A 55-nm 1-Mb ReRAM-CIM macro was fabricated to demonstrate the MAC operation of 2-b-input, 3-b-weight with 4-b-out. This nvCIM macro achieved T MAC = 14.6 ns at 4-b-out with peak energy efficiency of 53.17 TOPS/W.
The immunosuppressive microenvironment that is shaped by hepatic metastatic pancreatic ductal adenocarcinoma (PDAC) is essential for tumor cell evasion of immune destruction. Neutrophils are ...important components of the metastatic tumor microenvironment and exhibit heterogeneity. However, the specific phenotypes, functions and regulatory mechanisms of neutrophils in PDAC liver metastases remain unknown. Here, we show that a subset of P2RX1-negative neutrophils accumulate in clinical and murine PDAC liver metastases. RNA sequencing of murine PDAC liver metastasis-infiltrated neutrophils show that P2RX1-deficient neutrophils express increased levels of immunosuppressive molecules, including PD-L1, and have enhanced mitochondrial metabolism. Mechanistically, the transcription factor Nrf2 is upregulated in P2RX1-deficient neutrophils and associated with PD-L1 expression and metabolic reprogramming. An anti-PD-1 neutralizing antibody is sufficient to compromise the immunosuppressive effects of P2RX1-deficient neutrophils on OVA-activated OT1 CD8+ T cells. Therefore, our study uncovers a mechanism by which metastatic PDAC tumors evade antitumor immunity by accumulating a subset of immunosuppressive P2RX1-negative neutrophils.
PDF
