The lipopolysaccharide-triggered mesangial transcriptome: Evaluating the role of interferon regulatory factor-1

The lipopolysaccharide-triggered mesangial transcriptome: Evaluating the role of interferon regulatory factor-1.BackgroundPresently, we do not have a clear picture of how the mesangial transcriptome evolves following stimulation. The present study was designed to address this, using an innate trigger to stimulate murine mesangial cells.MethodsThree independent mesangial cell lines derived from C57BL/6 mice were stimulated with lipopolysaccharide (LPS). The mesangial cell transcriptomes were defined 1, 6, 24, and 60 hours poststimulation with LPS, using a 17,000 gene oligonucleotide array.ResultsInterferon regulatory factor-1 (IRF-1), ScyA2/MCP1, ScyA20/MIP3α (ScyB1/Gro1, and ScyB2/MIP2α/Gro2 were the earliest genes to be hyperexpressed after LPS stimulation. Later-appearing genes included ScyA7/MCP3, ScyD1/fractalkine, GM-CSF/CSF-2, PDGF, epiregulin, NfKb, C/EBP, TIMP-1, MMP11, MMP13, PTGS2/COX2, SpI2-1, Spp1, PAI-1, VCAM-1, C3, and defensin-β1, among others. Several of these changes were validated by real-time polymerase chain reaction (PCR) or enzyme-linked immunosorbent assay (ELISA). Rapid IRF-1 hyperexpression was also noted following stimulation of mesangial cells with peptidoglycan, poly I:poly C, interferon-γ?(IFN-γ), and heat-aggregated IgG. However, the blocking of IRF-1 using RNA interference and the use of mesangial cells isolated from IRF-1–deficient mice could not substantiate an obligatory role for IRF-1 in LPS-induced mesangial cell activation. Likewise, IRF-1 deficiency did not impact the development of anti-glomerular basement membrane (GBM)-induced immune nephritis.ConclusionInnate stimuli such as LPS appear to trigger successive waves of mesangial cell gene expression. Although IRF-1 surfaces as an “early-on, early-off” transcription factor following several different triggers, it does not appear to be an essential molecule for mesangial cell activation by innate triggers or for anti-GBM disease

Development of a mobile application for identification of grapevine (Vitis vinifera L.) cultivars via deep learning

Acknowledgements: The authors would like to express their gratitude to the Teaching Experiment Farm of Ningxia University, for their kind help. This study was supported by the Key R & D projects of Ningxia Hui Autonomous Region (Grant No. 2019BBF02013)Peer reviewedPublisher PD

The Relative Risk and Incidence of Immune Checkpoint Inhibitors Related Pneumonitis in Patients With Advanced Cancer: A Meta-Analysis

Background: Recently, immune checkpoint inhibitors (ICIs) have been proved one of the most promising anti-cancer therapy, series clinical trials have confirmed their efficacy. But they are also associated with distinctive set of toxic effects, which are recognized as immune-related adverse events. Among those immune-related adverse events, pneumonitis is rare, but it is often clinically serious and potentially life-threatening. Although many clinical trial results of PD-1/PD-L1 inhibitors had been reported incidence of pneumonitis, the knowledge based on the individual cohort data from each clinical trial is limited. So we conducted a meta-analysis of trials of PD-1/PD-L1 inhibitors in patients with advanced cancer and compared relative risk and incidence among different tumor types and therapeutic regimens. Such an analysis may provide important knowledge of this rare but clinically significant and potentially serious immune-related adverse event.Methods: Electronic databases were used to search eligible literatures, include randomized controlled trials (RCTs) comparing immune checkpoint inhibitors vs. standard therapies. All-grade (1–4) or high-grade (3–4) pneumonitis events were extracted. The summary relative risk, summary incidence, and 95% confidence intervals were calculated.Results: The incidence of all-grade and high-grade pneumonitis in non-small cell lung cancer (NSCLC) was significantly higher compared with other tumor types, such as Melanoma, urothelial carcinoma (UC), head and neck squamous cell carcinoma (HNSCC) (3.1% vs. 2.0%; p = 0.02, 1.4% vs. 0.6%; p = 0.03). The risk of all-grade pneumonitis was obtained from all patients in both experimental arm and control arm. Treatment with immune checkpoint inhibitors targeting PD-1/PD-L1 did significantly increase the risk of all-grade and high-grade pneumonitis compared with controls (fixed effects, RR: 4.70; 95% CI: 2.81–7.85; p < 0.00001, RR: 3.33; 95% CI: 1.68–6.59; p = 0.0006).Conclusion: The incidence of immune checkpoint inhibitors related pneumonitis was higher in NSCLC than other tumor types. Patients treated with immune checkpoint inhibitor in experiment arms are more likely to experience any grade pneumonitis than control arms. These findings suggest that clinician need to draw more attention on this rare but serious adverse event

Can Language Model Moderators Improve the Health of Online Discourse?

Human moderation of online conversation is essential to maintaining civility and focus in a dialogue, but is challenging to scale and harmful to moderators. The inclusion of sophisticated natural language generation modules as a force multiplier aid moderators is a tantalizing prospect, but adequate evaluation approaches have so far been elusive. In this paper, we establish a systematic definition of conversational moderation effectiveness through a multidisciplinary lens that incorporates insights from social science. We then propose a comprehensive evaluation framework that uses this definition to asses models' moderation capabilities independently of human intervention. With our framework, we conduct the first known study of conversational dialogue models as moderators, finding that appropriately prompted models can provide specific and fair feedback on toxic behavior but struggle to influence users to increase their levels of respect and cooperation.Comment: 9 page

COVID-19 vaccination coverage and its cognitive determinants among older adults in Shanghai, China, during the COVID-19 epidemic

ObjectivesThis study aimed to examine the coverage of coronavirus disease 2019 (COVID-19) vaccination and its cognitive determinants among older adults.MethodsA cross-sectional study was conducted using a questionnaire to conduct a survey among 725 Chinese older adults aged 60 years and above in June 2022, 2 months after the mass COVID-19 outbreak in Shanghai, China. The questionnaire covered demographic characteristics, COVID-19 vaccination status, internal risk perception, knowledge, and attitude toward the efficacy and safety of COVID-19 vaccines.ResultsThe vaccination rate was 78.3% among the surveyed individuals. Self-reported reasons for unwillingness to get vaccinated (multiple selections) were “concerns about acute exacerbation of chronic diseases after vaccination (57.3%)” and “concerns regarding vaccine side effects (41.4%).” Compared to the unvaccinated group, the vaccinated group tended to have a higher score in internal risk perception (t = 2.64, P < 0.05), better knowledge of COVID-19 vaccines (t = 5.84, P < 0.05), and a more positive attitude toward the efficacy and safety of COVID-19 vaccines (t = 7.92, P < 0.05). The path analysis showed that the cognitive effect on vaccination behavior is relatively large, followed by the internal risk perception, and then the attitude toward COVID-19 vaccines. The more knowledgeable the participants were about COVID-19 vaccines, the more likely they were to receive the COVID-19 vaccines. In the multivariate logistic regression, the increased coverage of COVID-19 vaccination was associated with reduced age (OR = 0.53 95% CI 0.43–0.66, P < 0.001), being a resident in other places than Shanghai (OR = 0.40, 95% CI 0.17–0.92, P < 0.05), a shorter time of lockdown (OR = 0.33, 95% CI 0.13–0.83, P < 0.05), a history of other vaccines (OR = 2.58, 95% CI 1.45–4.60, P < 0.01), a fewer number of chronic diseases (OR = 0.49, 95% CI 0.38–0.62, P < 0.001), better knowledge about COVID-19 vaccines (OR = 1.60, 95% CI 1.17–2.19, P < 0.01), and a positive attitude toward COVID-19 vaccines (OR = 9.22, 95% CI 4.69–18.09, P < 0.001).ConclusionAcquiring accurate knowledge and developing a positive attitude toward COVID-19 vaccines are important factors associated with COVID-19 vaccination. Disseminating informed information on COVID-19 vaccines and ensuring efficacious communication regarding their efficacy and safety would enhance awareness about COVID-19 vaccination among older adults and consequently boost their vaccination coverage

Does the pain sensitivity questionnaire correlate with tourniquet pain in patients undergoing ankle surgery?

BackgroundTourniquet pain is the most prominent problem in ankle surgery, and there is no proper method to predict it. It was reported that pain sensitivity questionnaires could evaluate the pain sensitivity of subjects. Its potential to predict tourniquet pain in ankle surgery is constructive and meaningful.MethodsOne hundred and twenty patients undergoing ankle surgery were included in this study. The pain sensitivity questionnaire (PSQ) and self-rating anxiety scale (SAS) were completed before the operation. The methods included an ultrasound-guided popliteal sciatic, a femoral nerve block, and a proximal thigh tourniquet. The pressure of the tourniquet was set according to the systolic blood pressure (SBP + 100 mmHg). A visual analogue scale (VAS) was used to assess the tourniquet pain. Also, the onset time of tourniquet pain ≥4 VAS units was recorded.ResultsThe PSQ-total and PSQ-minor scores were significantly correlated with the onset time when the tourniquet pain ≥4 VAS units (r = −0.763, r = −0.731, P < 0.001). The PSQ-total score <6.5 group gave significantly lower ratings for items 3, 4, 14, and 16 in the PSQ survey compared to the PSQ-total score ≥6.5 group (P < 0.05). Patients with high pain sensitivity have a higher need for analgesic drugs (P < 0.001). PSQ-total score ≥6.5 (OR = 185.8, 95% CI = 39.8–1,437.6, P < 0.001), sex (male, OR = 0.11, 95% CI = 0.018–0.488, P < 0.05), and age (OR = 0.92, 95% CI = 0.842–0.995, P < 0.05) were risk factors for reporting a tourniquet pain ≥4 VAS units within 30 min.ConclusionThe PSQ score is found to be correlated with intraoperative tourniquet pain. In addition, sex and age also affect the time of having intraoperative tourniquet pain

Interplay between moment-dependent and field-driven unidirectional magnetoresistance in CoFeB/InSb/CdTe heterostructures

Magnetoresistance effects are crucial for understanding the charge/spin transport as well as propelling the advancement of spintronic applications. Here we report the coexistence of magnetic moment-dependent (MD) and magnetic field-driven (FD) unidirectional magnetoresistance (UMR) effects in CoFeB/InSb/CdTe heterostructures. The strong spin-orbital coupling of InSb and the matched impedance at the CoFeB/InSb interface warrant a distinct MD-UMR effect at room temperature, while the interaction between the in-plane magnetic field and the Rashba effect at the InSb/CdTe interface induces the marked FD-UMR signal that dominates the high-field region. Moreover, owning to the different spin transport mechanisms, these two types of nonreciprocal charge transport show opposite polarities with respect to the magnetic field direction, which further enable an effective phase modulation of the angular-dependent magnetoresistance. Besides, the demonstrations of both the tunable UMR response and two-terminal spin-orbit torque-driven magnetization switching validate our CoFeB/InSb/CdTe system as a suitable integrated building block for multifunctional spintronic device design