Efficacy and safety of aldosterone synthase inhibition with and without empagliflozin for chronic kidney disease: a randomised, controlled, phase 2 trial.

BACKGROUND: Excess aldosterone accelerates chronic kidney disease progression. This phase 2 clinical trial assessed BI 690517, an aldosterone synthase inhibitor, for efficacy, safety, and dose selection. METHODS: This was a multinational, randomised, controlled, phase 2 trial. People aged 18 years or older with an estimated glomerular filtration rate (eGFR) of 30 to less than 90 mL/min/1·73 m2, a urine albumin to creatinine ratio (UACR) of 200 to less than 5000 mg/g, and serum potassium of 4·8 mmol/L or less, taking an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, were enrolled. Participants were randomly assigned (1:1) to 8 weeks of empagliflozin or placebo run-in, followed by a second randomisation (1:1:1:1) to 14 weeks of treatment with once per day BI 690517 at doses of 3 mg, 10 mg, or 20 mg, or placebo. Study participants, research coordinators, investigators, and the data coordinating centre were masked to treatment assignment. The primary endpoint was the change in UACR measured in first morning void urine from baseline (second randomisation) to the end of treatment. This study is registered with ClinicalTrials.gov (NCT05182840) and is completed. FINDINGS: Between Feb 18 and Dec 30, 2022, of the 714 run-in participants, 586 were randomly assigned to receive BI 690517 or placebo. At baseline, 33% (n=196) were women, 67% (n=390) were men, 42% (n=244) had a racial identity other than White, and mean participant age was 63·8 years (SD 11·3). Mean baseline eGFR was 51·9 mL/min/1·73 m2 (17·7) and median UACR was 426 mg/g (IQR 205 to 889). Percentage change in first morning void UACR from baseline to the end of treatment at week 14 was -3% (95% CI -19 to 17) with placebo, -22% (-36 to -7) with BI 690517 3 mg, -39% (-50 to -26) with BI 690517 10 mg, and -37% (-49 to -22) with BI 690517 20 mg monotherapy. BI 690517 produced similar UACR reductions when added to empagliflozin. Investigator-reported hyperkalaemia occurred in 10% (14/146) of those in the BI 690517 3 mg group, 15% (22/144) in the BI 690517 10 mg group, and 18% (26/146) in the BI 690517 20 mg group, and in 6% (nine of 147) of those receiving placebo, with or without empagliflozin. Most participants with hyperkalaemia did not require intervention (86% [72/84]). Adrenal insufficiency was an adverse event of special interest reported in seven of 436 study participants (2%) receiving BI 690517 and one of 147 participants (1%) receiving matched placebo. No treatment-related deaths occurred during the study. INTERPRETATION: BI 690517 dose-dependently reduced albuminuria with concurrent renin-angiotensin system inhibition and empagliflozin, suggesting an additive efficacy for chronic kidney disease treatment without unexpected safety signals. FUNDING: Boehringer Ingelheim.

Peroxiredoxin 3 has a crucial role in the macrophage polarization by regulating mitochondrial homeostasis.

Acute lung injury (ALI) is one of the life-threatening complications of sepsis, and macrophage polarization plays a crucial role in the sepsis-associated ALI. However, the regulatory mechanisms of macrophage polarization in ALI and in the development of inflammation are largely unknown. In this study, we demonstrated that macrophage polarization occurs in sepsis-associated ALI and is accompanied by mitochondrial dysfunction and inflammation, and a decrease of PRDX3 promotes the initiation of macrophage polarization and mitochondrial dysfunction. Mechanistically, PRDX3 overexpression promotes M1 macrophages to differentiate into M2 macrophages, and enhances mitochondrial functional recovery after injury by reducing the level of glycolysis and increasing TCA cycle activity. In conclusion, we identified PRDX3 as a critical hub integrating oxidative stress, inflammation, and metabolic reprogramming in macrophage polarization. The findings illustrate an adaptive mechanism underlying the link between macrophage polarization and sepsis-associated ALI.

Differential expression of Semaphorin-7A /CD163-positive macrophages in large artery and cardiogenic stroke.

BACKGROUND: Identification of the causes of stroke of undetermined etiology, specifically cardioembolism (CE) and non-CE causes, can inform treatment planning and prognosis prediction. The objective of this study was to analyze the disparities in thrombus composition, particularly Semaphorin-7A (Sema7A) and CD163, between patients diagnosed with large-artery atherosclerosis (LAA) and those with CE, and to investigate their potential association with prognosis. METHODS: Thrombi were collected from patients who underwent mechanical thrombectomy at two hospitals. The patients were categorized into two groups: LAA and CE. We compared the levels of Sema7A and CD163 between these groups and analyzed their relationships with stroke severity, hemorrhagic transformation and prognosis. RESULTS: The study involved a total of 67 patients. Sema7A expression was found to be significantly higher in the CE group compared to LAA (p < 0.001). Conversely, no statistically significant differences were observed for CD163 between the groups. The presence of Sema7A/CD163 did not show any associations with stroke severity or hemorrhagic transformation (all p > 0.05). However, both Sema7A (OR, 2.017; 95% CI, 1.301-3.518; p = 0.005) and CD163 (OR, 2.283; 95% CI, 1.252-5.724; p = 0.03) were associated with the poor prognosis for stroke, after adjusting for stroke severity. CONCLUSION: This study highlights that CE thrombi exhibited higher levels of Sema7A expression compared to LAA thrombi. Moreover, we found a positive correlation between Sema7A/CD163 levels and the poor prognosis of patients with acute ischemic stroke.

A review of etching methods and applications of two-dimensional MXenes.

MXenes have been attracting much attention since their introduction due to their amazing properties such as unique structure, good hydrophilicity, metal-grade electrical conductivity, rich surface chemistry, low ionic diffusion resistance, and excellent mechanical strength. It is noteworthy that different synthesis methods have a great influence on the structure and properties of MXenes. In recent years, some modification strategies of MXenes with unique insights have been developed with the increasing research. In summary, this paper reviews and summarizes the recent research progress of MXenes from the perspective of preparation processes (including hydrofluoric acid direct etching, fluoride/concentrated acid hybrid etching, fluoride melt etching, electrochemical etching, alkali-assisted etching and Lewis acid etching strategies), which can provide valuable guidance for the preparation and application of high-performance MXenes-based materials.

Advances in the Application of AI Robots in Critical Care: Scoping Review.

BACKGROUND: In recent epochs, the field of critical medicine has experienced significant advancements due to the integration of artificial intelligence (AI). Specifically, AI robots have evolved from theoretical concepts to being actively implemented in clinical trials and applications. The intensive care unit (ICU), known for its reliance on a vast amount of medical information, presents a promising avenue for the deployment of robotic AI, anticipated to bring substantial improvements to patient care. OBJECTIVE: This review aims to comprehensively summarize the current state of AI robots in the field of critical care by searching for previous studies, developments, and applications of AI robots related to ICU wards. In addition, it seeks to address the ethical challenges arising from their use, including concerns related to safety, patient privacy, responsibility delineation, and cost-benefit analysis. METHODS: Following the scoping review framework proposed by Arksey and O'Malley and the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we conducted a scoping review to delineate the breadth of research in this field of AI robots in ICU and reported the findings. The literature search was carried out on May 1, 2023, across 3 databases: PubMed, Embase, and the IEEE Xplore Digital Library. Eligible publications were initially screened based on their titles and abstracts. Publications that passed the preliminary screening underwent a comprehensive review. Various research characteristics were extracted, summarized, and analyzed from the final publications. RESULTS: Of the 5908 publications screened, 77 (1.3%) underwent a full review. These studies collectively spanned 21 ICU robotics projects, encompassing their system development and testing, clinical trials, and approval processes. Upon an expert-reviewed classification framework, these were categorized into 5 main types: therapeutic assistance robots, nursing assistance robots, rehabilitation assistance robots, telepresence robots, and logistics and disinfection robots. Most of these are already widely deployed and commercialized in ICUs, although a select few remain under testing. All robotic systems and tools are engineered to deliver more personalized, convenient, and intelligent medical services to patients in the ICU, concurrently aiming to reduce the substantial workload on ICU medical staff and promote therapeutic and care procedures. This review further explored the prevailing challenges, particularly focusing on ethical and safety concerns, proposing viable solutions or methodologies, and illustrating the prospective capabilities and potential of AI-driven robotic technologies in the ICU environment. Ultimately, we foresee a pivotal role for robots in a future scenario of a fully automated continuum from admission to discharge within the ICU. CONCLUSIONS: This review highlights the potential of AI robots to transform ICU care by improving patient treatment, support, and rehabilitation processes. However, it also recognizes the ethical complexities and operational challenges that come with their implementation, offering possible solutions for future development and optimization.

Value of Radiomic Analysis Combined With Diffusion Tensor Imaging in Early Diagnosis of HIV-Associated Neurocognitive Disorders.

BACKGROUND: The combination of radiomics and diffusion tensor imaging (DTI) may have potential clinical value in the early stage of HIV-associated neurocognitive disorders (HAND). PURPOSE: To investigate the value of DTI-based radiomics in the early stage of HAND in people living with HIV (PLWH). STUDY TYPE: Retrospective. POPULATION: A total of 138 male PLWH were included, including 68 with intact cognition (IC) and 70 with asymptomatic neurocognitive impairment (ANI). Seventy healthy controls (HCs) were recruited for tract-based spatial statistics (TBSS) analysis. All PLWHs were randomly divided into training and validation cohorts at a 7:3 ratio. FIELD STRENGTH/SEQUENCE: A 3 T, single-shot spin-echo echo planar imaging (EPI). ASSESSMENT: The differences between the PLWH groups were compared using TBSS and region of interest (ROI) analysis. Radiomic features were extracted from the corpus callosum (CC) on DTI postprocessed images, including fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD). The performance of the radiomic signatures was evaluated by ROC curve analysis. The radiomic signature with the highest area under the curve (AUC) was combined with clinical characteristics to construct a nomogram. Decision curve analysis (DCA) was performed to evaluate the ability of different methods in discriminating ANI. STATISTICAL TESTS: Chi-square test, independent-samples t test, Kruskal-Wallis test, Mann-Whitney U test, threshold-free cluster enhancement (TFCE), ROC curve analysis, DCA, multivariate logistic regression analysis, Hosmer-Lemeshow test. P < 0.05 with TFCE corrected and P < 0.0001 without TFCE corrected were considered statistically significant. RESULTS: The ANI group showed lower FA and higher AD than the IC group. In the validation cohort, the AUCs of the FA-, AD-, MD- and RD-based radiomic signatures and the clinicoradiomic nomogram were 0.829, 0.779, 0.790, 0.864, and 0.874, respectively. DCA revealed that the nomogram was of greater clinical value than TBSS analysis, the clinical models, and the RD-based radiomic signature. DATA CONCLUSION: The combination of DTI and radiomics is correlated with early stage of HAND in PLWH. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.

Transcranial alternating current stimulation for treating depression: a randomized controlled trial.

Treatment of depression with antidepressants is partly effective. Transcranial alternating current stimulation can provide a non-pharmacological alternative for adult patients with major depressive disorder. However, no study has used the stimulation to treat first-episode and drug-naïve patients with major depressive disorder. We used a randomized, double-blind, sham-controlled design to examine the clinical efficacy and safety of the stimulation in treating first-episode drug-naïve patients in a Chinese Han population. From 4 June 2018 to 30 December 2019, 100 patients were recruited and randomly assigned to receive 20 daily 40-min, 77.5 Hz, 15 mA, one forehead and two mastoid sessions of active or sham stimulation (n = 50 for each group) in four consecutive weeks (Week 4), and were followed for additional 4-week efficacy/safety assessment without stimulation (Week 8). The primary outcome was a remission rate defined as the 17-item Hamilton Depression Rating Scale (HDRS-17) score ≤ 7 at Week 8. Secondary analyses were response rates (defined as a reduction of ≥ 50% in the HDRS-17), changes in depressive symptoms and severity from baseline to Week 4 and Week 8, and rates of adverse events. Data were analysed in an intention-to-treat sample. Forty-nine in the active and 46 in the sham completed the study. Twenty-seven of 50 (54%) in the active treatment group and 9 of 50 (18%) in the sham group achieved remission at the end of Week 8. The remission rate was significantly higher in the active group compared to that in the sham group with a risk ratio of 1.78 (95% confidence interval, 1.29, 2.47). Compared with the sham, the active group had a significantly higher remission rate at Week 4, response rates at Weeks 4 and 8, and a larger reduction in depressive symptoms from baseline to Weeks 4 and 8. Adverse events were similar between the groups. In conclusion, the stimulation on the frontal cortex and two mastoids significantly improved symptoms in first-episode drug-naïve patients with major depressive disorder and may be considered as a non-pharmacological intervention for them in an outpatient setting.

A highly active catalyst derived from CuO particles for selective hydrogenation of acetylene in large excess ethylene.

The removal of acetylene impurities is indispensable in the production of ethylene. An Ag-promoted Pd catalyst is industrially used to remove acetylene impurities by selective hydrogenation. It is highly desirable to replace Pd with non-precious metals. In the present investigation, CuO particles, which are most frequently used as the precursors for Cu-based catalysts, were prepared through the solution-based chemical precipitation method and used to prepare high-performance catalysts for selective hydrogenation of acetylene in large excess ethylene. The non-precious metal catalyst was prepared by treating CuO particles with acetylene-containing gas (0.5 vol% C2H2/Ar) at 120 °C and subsequent hydrogen reduction at 150 °C. The obtained catalyst was tested in selective hydrogenation of acetylene in a large excess of ethylene (0.72 vol% CH4 as the internal standard, 0.45 vol% C2H2, 88.83 vol% C2H4, 10.00 vol% H2). It exhibited significantly higher activity than the counterpart of Cu metals, achieving 100% conversion of acetylene without ethylene loss at 110 °C and atmospheric pressure. The characterization by means of XRD, XPS, TEM, H2-TPR, CO-FTIR, and EPR verified the formation of an interstitial copper carbide (CuxC), which was responsible for the enhanced hydrogenation activity.

High-temporal resolution DCE-MRI improves assessment of intra- and peri-breast lesions categorized as BI-RADS 4.

BACKGROUND: BI-RADS 4 breast lesions are suspicious for malignancy with a range from 2 to 95%, indicating that numerous benign lesions are unnecessarily biopsied. Thus, we aimed to investigate whether high-temporal-resolution dynamic contrast-enhanced MRI (H_DCE-MRI) would be superior to conventional low-temporal-resolution DCE-MRI (L_DCE-MRI) in the diagnosis of BI-RADS 4 breast lesions. METHODS: This single-center study was approved by the IRB. From April 2015 to June 2017, patients with breast lesions were prospectively included and randomly assigned to undergo either H_DCE-MRI, including 27 phases, or L_DCE-MRI, including 7 phases. Patients with BI-RADS 4 lesions were diagnosed by the senior radiologist in this study. Using a two-compartment extended Tofts model and a three-dimensional volume of interest, several pharmacokinetic parameters reflecting hemodynamics, including Ktrans, Kep, Ve, and Vp, were obtained from the intralesional, perilesional and background parenchymal enhancement areas, which were labeled the Lesion, Peri and BPE areas, respectively. Models were developed based on hemodynamic parameters, and the performance of these models in discriminating between benign and malignant lesions was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 140 patients were included in the study and underwent H_DCE-MRI (n = 62) or L_DCE-MRI (n = 78) scans; 56 of these 140 patients had BI-RADS 4 lesions. Some pharmacokinetic parameters from H_DCE-MRI (Lesion_Ktrans, Kep, and Vp; Peri_Ktrans, Kep, and Vp) and from L_DCE-MRI (Lesion_Kep, Peri_Vp, BPE_Ktrans and BPE_Vp) were significantly different between benign and malignant breast lesions (P < 0.01). ROC analysis showed that Lesion_Ktrans (AUC = 0.866), Lesion_Kep (AUC = 0.929), Lesion_Vp (AUC = 0.872), Peri_Ktrans (AUC = 0.733), Peri_Kep (AUC = 0.810), and Peri_Vp (AUC = 0.857) in the H_DCE-MRI group had good discrimination performance. Parameters from the BPE area showed no differentiating ability in the H_DCE-MRI group. Lesion_Kep (AUC = 0.767), Peri_Vp (AUC = 0.726), and BPE_Ktrans and BPE_Vp (AUC = 0.687 and 0.707) could differentiate between benign and malignant breast lesions in the L_DCE-MRI group. The models were compared with the senior radiologist's assessment for the identification of BI-RADS 4 breast lesions. The AUC, sensitivity and specificity of Lesion_Kep (0.963, 100.0%, and 88.9%, respectively) in the H_DCE-MRI group were significantly higher than those of the same parameter in the L_DCE-MRI group (0.663, 69.6% and 75.0%, respectively) for the assessment of BI-RADS 4 breast lesions. The DeLong test was conducted, and there was a significant difference only between Lesion_Kep in the H_DCE-MRI group and the senior radiologist (P = 0.04). CONCLUSIONS: Pharmacokinetic parameters (Ktrans, Kep and Vp) from the intralesional and perilesional regions on high-temporal-resolution DCE-MRI, especially the intralesional Kep parameter, can improve the assessment of benign and malignant BI-RADS 4 breast lesions to avoid unnecessary biopsy.

Unfolded protein response is involved in resistance to Neospora caninum infection via IRE1α-XBP1s-NOD2 Axis.

Neospora caninum, an intracellular protozoan parasite, causes neosporosis resulting in major losses in the livestock industry worldwide. However, no effective drugs or vaccines have been developed to control neosporosis. An in-depth study on the immune response against N. caninum could help to search for effective approaches to prevent and treat neosporosis. The host unfolded protein response (UPR) functions as a double-edged sword in several protozoan parasite infections, either to initiate immune responses or to help parasite survival. In this study, the roles of the UPR in N. caninum infection in vitro and in vivo were explored, and the mechanism of the UPR in resistance to N. caninum infection was analyzed. The results revealed that N. caninum triggered the UPR in mouse macrophages, such as the activation of the IRE1 and PERK branches, but not the ATF6 branch. Inhibition of the IRE1α-XBP1s branch increased the N. caninum number both in vitro and in vivo, while inhibition of the PERK branch did not affect the parasite number. Furthermore, inhibition of the IRE1α-XBP1s branch reduced the production of cytokines by inhibiting NOD2 signalling and its downstream NF-κB and MAPK pathways. Taken together, the results of this study suggest that the UPR is involved in the resistance of N. caninum infection via the IRE1α-XBP1s branch by regulating NOD2 and its downstream NF-κB and MAPK pathways to induce the production of inflammatory cytokines, which provides a new perspective for the research and development of anti-N. caninum drugs.

LATERAL BRANCHING OXIDOREDUCTASE, one novel target gene of Squamosa Promoter Binding Protein-like 2, regulates tillering in switchgrass.

Strigolactones (SLs) play a critical role in regulating plant tiller number. LATERAL BRANCHING OXIDOREDUCTASE (LBO) encodes an important late-acting enzyme for SL biosynthesis and regulates shoot branching in Arabidopsis. However, little is known about the function of LBO in monocots including switchgrass (Panicum virgatum L.), a dual-purpose fodder and biofuel crop. We studied the function of PvLBO via the genetic manipulation of its expression levels in both the wild-type and miR156 overexpressing (miR156OE ) switchgrass. Co-expression analysis, quantitative real-time polymerase chain reaction (qRT-PCR), transient dual luciferase assay, and chromatin immunoprecipitation-qPCR were all used to determine the activation of PvLBO by miR156-targeted Squamosa Promoter Binding Protein-like 2 (PvSPL2) in regulating tillering of switchgrass. PvLBOtranscripts dramatically declined in miR156OE transgenic switchgrass, and the overexpression of PvLBO in the miR156OE transgenic line produce fewer tillers than the control. Furthermore, we found that PvSPL2 can directly bind to the promoter of PvLBO and activate its transcription, suggesting that PvLBO is a novel downstream gene of PvSPL2. We propose that PvLBO functions as an SL biosynthetic gene to mediate tillering and acts as an important downstream factor in the crosstalk between the SL biosynthetic pathway and the miR156-SPL module in switchgrass.

Safety of dabigatran etexilate for the secondary prevention of venous thromboembolism in children.

This open-label, single-arm, prospective cohort trial is the first phase 3 safety study to describe outcomes in children treated with dabigatran etexilate for secondary venous thromboembolism (VTE) prevention. Eligible children aged 12 to <18 years (age stratum 1), 2 to <12 years (stratum 2), and >3 months to <2 years (stratum 3) had an objectively confirmed diagnosis of VTE treated with standard of care (SOC) for ≥3 months, or had completed dabigatran or SOC treatment in the DIVERSITY trial (NCT01895777) and had an unresolved clinical thrombosis risk factor requiring further anticoagulation. Children received dabigatran for up to 12 months, or less if the identified VTE clinical risk factor resolved. Primary end points included VTE recurrence, bleeding events, and mortality at 6 and 12 months. Overall, 203 children received dabigatran, with median exposure being 36.3 weeks (range, 0-57 weeks); 171 of 203 (84.2%) and 32 of 203 (15.8%) took capsules and pellets, respectively. Overall, 2 of 203 children (1.0%) experienced on-treatment VTE recurrence, and 3 of 203 (1.5%) experienced major bleeding events, with 2 (1.0%) reporting clinically relevant nonmajor bleeding events, and 37 (18.2%) minor bleeding events. There were no on-treatment deaths. On-treatment postthrombotic syndrome was reported for 2 of 162 children (1.2%) who had deep vein thrombosis or central-line thrombosis as their most recent VTE. Pharmacokinetic/pharmacodynamic relationships of dabigatran were similar to those in adult VTE patients. In summary, dabigatran showed a favorable safety profile for secondary VTE prevention in children aged from >3 months to <18 years with persistent VTE risk factor(s). This trial was registered at www.clinicaltrials.gov as #NCT02197416.

Grass carp (Ctenopharyngodon idella) DYRK2 modulates cell apoptosis through phosphorylating p53.

In mammals, DYRK2 increases p53 phosphorylation level by interacting with it and then promotes cell apoptosis. However, the function of fish DYRK2 has not yet been elucidated. In this paper, we cloned and identified the coding sequence (CDS) of a grass carp DYRK2 (CiDYRK2) which is 1773 bp in length and encodes 590 amino acids. SMART predictive analysis showed that CiDYRK2 possesses a serine/threonine kinase domain. Subsequently, we used the dsRNA analog polyinosinic-polycytidylic acid (poly (I:C) and Grass carp reovirus (GCRV) to stimulate grass carp and CIK cells for different times and found that CiDYRK2 mRNA was significantly up-regulated both in fish tissues and cells. To explore the function of CiDYRK2, we carried out overexpression and knockdown experiments of CiDYRK2 in CIK cells. Real-time quantitative PCR (Q-PCR), TdT-mediated dUTP nick end labeling (TUNEL) assay and flow cytometry were used to detect the ratio of BAX/BCL-2 mRNA, the number of TUNEL positive cells, the proportion of Annexin V-positive cells respectively. The results showed that CiDYRK2 significantly up-regulated BAX/Bcl-2 mRNA ratio and increased the number of TUNEL-positive cells, as well as the proportion of Annexin V-positive cells. On the contrary, knock-down of CiDYRK2 significantly down-regulated BAX/Bcl-2 mRNA ratio in the cells. Therefore, CiDYRK2 promoted cell apoptosis. To study the molecular mechanism by which CiDYRK2 promoting cell apoptosis, subcellular localization and immunoprecipitation experiments were used to study the relationship between grass carp DYRK2 and the pro-apoptotic protein p53. The results showed that CiDYRK2 and Cip53 were located and co-localized in the nucleus. Co-immunoprecipitation experiment also showed that CiDYRK2 and Cip53 can bind with each other. We further found that DYRK2 can increase the phosphorylation level of p53. In a word, our results showed that grass carp DYRK2 induces cell apoptosis by increasing the phosphorylation level of p53.

Assessing the inflammatory severity of the terminal ileum in Crohn disease using radiomics based on MRI.

BACKGROUND: Evaluating inflammatory severity using imaging is essential for Crohn's disease, but it is limited by potential interobserver variation and subjectivity. We compared the efficiency of magnetic resonance index of activity (MaRIA) collected by radiologists and a radiomics model in assessing the inflammatory severity of terminal ileum (TI). METHODS: 121 patients were collected from two centers. Patients were divided into ulcerative group and mucosal remission group based on the TI Crohn's disease Endoscopic Severity Index. The consistency of bowel wall thickness (BWT), relative contrast enhancement (RCE), edema, ulcer, MaRIA and features of the region of interest between radiologists were described by weighted Kappa test and intraclass correlation coefficient (ICC), and developed receiver operating curve of MaRIA. The radiomics model was established using reproducible features of logistic regression based on arterial staging of T1WI sequences. Delong test was used to compare radiomics with MaRIA. RESULTS: The consistency between radiologists were moderate in BWT (ICC = 0.638), fair in edema (κ = 0.541), RCE (ICC = 0.461), MaRIA (ICC = 0.579) and poor in ulcer (κ = 0.271). Radiomics model was developed by 6 reproducible features (ICC = 0.93-0.96) and equivalent to MaRIA which evaluated by the senior radiologist (0.872 vs 0.883 in training group, 0.824 vs 0.783 in validation group, P = 0.847, 0.471), both of which were significantly higher than MaRIA evaluated by junior radiologist (AUC: 0.621 in training group, 0.557 in validation group, all, P < 0.05). CONCLUSION: The evaluation of inflammatory severity could be performed by radiomics objectively and reproducibly, and was comparable to MaRIA evaluated by the senior radiologist. Radiomics may be an important method to assist junior radiologists to assess the severity of inflammation objectively and accurately.

Extracellular vesicles and the regulation of tumor immunity: Current progress and future directions.

As nano-level information carriers, extracellular vesicles (EVs) contain proteins, DNA or RNA, which maintain the transmembrane transport of biomolecules and the homeostasis of normal cells. EVs can be released by most cell types and absorbed by specific recipient cells, subsequently affecting phenotypic expression. EVs are believed to play an important role in cellular communication, especially in immune cells. During tumor development, EVs of different origins have different effects on the survival and growth of tumor cells. Some tumor cell-derived EVs can mediate tumor immunosuppressive responses by inhibiting the differentiation and maturation of dendritic cells (DCs) and by negatively regulating the expression of T cell receptors, causing tumor cells to escape immune surveillance and proliferate. EVs have therefore become a key component of tumor cell proliferation and metastasis. In contrast, EVs derived from DCs mediate antitumor immune activation by inducing the killing and inhibitory effects of the immune system. This makes it an antigen component of the antitumor response. Integrating the interaction and connection of EVs to immunosuppression and immune response is significant for the application of EVs in clinical practice. Here, we reviewed the research progress on the role of EVs in the immune regulation of tumors.

Non-contrast CT-based radiomic signature for screening thoracic aortic dissections: a multicenter study.

OBJECTIVE: To develop a non-contrast CT-based radiomic signature to effectively screen for thoracic aortic dissections (ADs). METHODS: We retrospectively enrolled 378 patients who underwent non-contrast chest CT scans along with CT angiography or MRI from 4 medical centers. The training and validation sets were from 3 centers, while the external test set was from a 4th center. Radiomic features were extracted from non-contrast CT images. The radiomic signature was created on the basis of selected features by a logistic regression algorithm. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve, accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were conducted to assess the predictive ability of radiomic signature. RESULTS: The radiomic signature demonstrated AUCs of 0.91 (95% confidence interval [CI], 0.86-0.95) in the training set, 0.92 (95% CI, 0.86-0.98) in the validation set, and 0.90 (95% CI, 0.82-0.98) in the external test set. The predicted diagnosis was in good agreement with the probability of thoracic AD. In the external test group, the diagnostic accuracy, sensitivity, specificity, PPV, and NPV were 90.5%, 85.7%, 91.7%, 70.6%, and 96.5%, respectively. CONCLUSIONS: A radiomic signature based on non-contrast CT images can effectively predict thoracic ADs. This method may serve as a potential screening tool for thoracic ADs. KEY POINTS: • The non-contrast CT-based radiomic signature can effectively predict the thoracic aortic dissections. • This radiomic signature shows better predictive performance compared to the current clinical model. • This prediction method may be a potential tool for screening thoracic aortic dissections.

Contrast-induced encephalopathy mimicking stroke after a second cerebral DSA: an unusual case report.

BACKGROUND: Contrast-induced encephalopathy (CIE) is a rare complication of the angiography process. CIE may mimic stroke symptoms clinically and subarachnoid hemorrhage radiologically. Previous CIE cases occurred after the initial digital subtraction angiography (DSA) scan. Here, we encountered an unusual case of CIE mimicking a stroke with an internal carotid artery (ICA) aneurysm and ipsilateral ICA stenosis that occurred after a second DSA procedure. CASE PRESENTATION: A 77-year-old female with a history of hypertension and coronary heart disease underwent two cerebral DSA procedures over 1 week. She was given the same nonionic and iso-osmolar Visipaque agent (smaller than 200 ml) for both procedures. However, neurological complications only occurred after the second DSA procedure. On the first diagnostic cerebral DSA, she was diagnosed with an intracranial aneurysm of the left ICA with moderate stenosis (approximately 50%) in the initial part of the ipsilateral ICA. However, after the second aneurysm embolization procedure by DSA, she developed right hemiplegia, aphasia, and epilepsy, mimicking left middle cerebral artery occlusion. An emergency CT showed a diffuse hyperdensity in the left subarachnoid space, mimicking SAH. MRI demonstrated that the lesion was hyperintense on T2WI, FLAIR imaging, and DWI but was normal on ADC mapping. On postoperative Day 6, her neurologic deficits had completely resolved after initial fluid restriction, corticosteroid treatment, and rehydration. CONCLUSION: This case indicates that clinicians should consider the occurrence of CIE following any angiography procedure, even if the initial cerebral DSA procedure is successful and without complications.

Prediction of risk factors of bronchial mucus plugs in children with Mycoplasma pneumoniae pneumonia.

BACKGROUND: Recently, many cases of pneumonia in children with Mycoplasma pneumoniae infection have been shown to have varying degrees of intrabronchial mucus plug formation. The clinical, laboratory, radiological characteristics, and treatment of patients with Mycoplasma infection are analyzed in this study. The risk factors for M. pneumoniae pneumonia (MPP) mucus plug formation in children are explored, and a risk factor scoring system is established. METHODS: MPP patients treated with bronchoscopy were retrospectively enrolled in the study from February 2015 to December 2019. The children were divided into a mucus plug group and a control group according to the presence or absence of mucus plug formation. The clinical, laboratory, radiological characteristics, and treatment of the two groups of children were compared. Univariate and multivariate logistic regression models were used to identify the risk factors for MPP mucus plug formation. The receiver operating characteristic (ROC) curve was drawn to evaluate the regression model and establish the MPP mucous plug risk factor scoring system. RESULTS: A univariate analysis showed that the children in the mucous group were older and had a longer fever duration, longer hospital stay, higher fever peak, more cases of wheezing symptoms and allergies, and azithromycin or corticosteroids were administered later. In addition, neutrophil, C-reactive protein (CRP), lactate dehydrogenase (LDH), D-dimer (DD), sputum MP-DNA copy number, and total immunoglobulin A (IgA) levels were higher, while prealbumin (PA) levels were lower. The ROC curve analysis showed that children with MPP had PA ≤144.5 mg/L, had used corticosteroids during the course of the illness of ≥4.5 days, CRP ≥12.27 mg/L, an LDH ≥ 462.65 U/L, and there was a possibility of intra-airway mucus formation. The independent risk factors were scored according to their odds ratio (OR) value. Among the 255 children with MPP, the high-risk group had 44 (83.02%) mucus plugs out of 53; the middle-risk group had 35 (34.3%) mucus plugs out of 102; and the low-risk group had 11 (11%) mucus plugs out of 100. CONCLUSIONS: PA levels, timing of corticosteroid use (use in the first few days), CRP levels, and LDH levels were independent risk factors for MPP mucus plug formation. This provides a basis for the early identification of MPP in children combined with mucus plug formation.

Rapid Photothermal Responsive Conductive MXene Nanocomposite Hydrogels for Soft Manipulators and Sensitive Strain Sensors.

Stimulus-responsive hydrogels are of great significance in soft robotics, wearable electronic devices, and sensors. Near-infrared (NIR) light is considered an ideal stimulus as it can trigger the response behavior remotely and precisely. In this work, a smart flexible stimuli-responsive hydrogel with excellent photothermal property and decent conductivity are prepared by incorporating MXene nanosheets into the physically cross-linked poly(N-isopropyl acrylamide) hydrogel matrix. Because of outstanding photothermal effect and dispersion of MXene, the composite hydrogel exhibits rapid photothermal responsiveness and excellent photothermal stability under the NIR irradiation. Furthermore, the anisotropic bilayer hydrogel actuator shows fast and controllable light-driven bending behavior, which can be used as a light-controlled soft manipulator. Meanwhile, the hydrogel sensor exhibits cycling stability and good durability in detecting various deformation and real-time human activities. Therefore, the present study involving the fabrication of MXene nanocomposite hydrogels for potential applications in remotely controlled actuator and wearable electronic device provides a new method for the development of photothermal responsive conductive hydrogels.

Thermal/Near-Infrared Light Dual-Responsive Reversible Two-Way Shape Memory cEVA/2D-MoO2 Composite for Multifunctional Applications.

Light-responsive reversible two-way shape memory polymers (2W-SMPs) are highly promising for many fields due to indirect heating, clean, and remote control. In this work, a composite with both thermal- and near-infrared (NIR) light-induced reversible two-way shape memory effect (2W-SME) is prepared by doping extremely little quantities of 2D non-layered molybdenum dioxide nanosheets (2D-MoO2 ) into semicrystalline poly(ethylene-co-vinyl acetate) (EVA) networks. This is the first report on light-induced reversible two-way shape memory composites employing 2D-MoO2 as photothermal fillers. Upon switching the NIR light on and off, due to the excellent photothermal feature and stability of 2D-MoO2 , the composite exhibits remarkable light-induced reversible 2W-SME. A light-driven actuator for sensing applications is designed based on the composite and the circuit, where the lamp acting as an alarm can raise and fade upon responding to NIR light. A completely flexible, fuel-free self-walking soft robot is designed based on the advantages of the light-responsive reversible 2W-SMPs. Additionally, the composite acting as a light-fueled crane is able to lift and lower a load that is 3846 times its own weight. The results demonstrate that the prepared composite has a promising prospect for applications as actuators, self-walking soft robot and crane.