Objective To discuss the value of MSCT 3D and MPR in diagnosis of angioma of head and cervix in children. Materials and Methods 22 cases with angiomas in head and cervical examined by 16MSCT enhanced CT scan were analyzed respectively, and to observe the shape, in and out vessels of angioma, relation between the angioma and encephalic structure.Results 22 cases were manifested as homogeneous or inhomogeneous enhancement, the angioma's location, shape, size, range, relation with surrounding structure, supplying and drainage vessels were displayed in 16 cases, not displayed in 2 cases, supplying vessel not be displayed and draining vein displayed in 4 cases by 3D MPR. 20 cases had no relationship with encephalic structure, 2 cases had vessels between the angioma and encephalic blood sinus or vessel.Conclusion MSCT 3D and MPR have advantage in showing the shape, location, in and out vessels of angioma, relation between the angioma and encephalic structure, it is a first choice to diagnose angioma of head and cervix.
Abstract Protection from boosting with updated SARS-CoV-2 vaccines containing emerging Omicron sub-variants like BA.1 or BA.5 was not satisfying, especially the neutralizing ability against the newly emerged BQ and XBB related variants. Similar with influenza virus, antigenic drift is highly relevant to SARS-CoV-2 evolution, and immune imprinting may limit the performance of updated vaccines. In this study, we investigated whether repeated infection with Omicron variant could reduce the immune imprinting. A total of 194 participants with different status of vaccination (unvaccinated, regular vaccination and booster vaccination) confirmed for first infection and re-infection with BA.5, BF.7 and XBB variants were enrolled, and the neutralizing profiles against wild type (WT) SARS-CoV-2 and Omicron sub-variants were analyzed. The results showed that neutralizing potency against the corresponding infected variant is significantly hampered along with the doses of vaccination during first infection. However, for the participants with first infection of BA.5/BF.7 variants and re-infection of XBB variant, immune imprinting was obviously alleviated, indicated as significantly increased ratio of the corresponding infected variant/WT ID 50 titers and higher percentage of samples with high neutralizing activities (ID 50 > 500) against BA.5, BF.7 and XBB variants. Moreover, repeated Omicron infection could induce strong neutralizing potency with broad neutralizing profiles against a series of other Omicron sub-variants including the newly emerged EG.5.1 variant, both in the vaccine naïve and vaccine experienced individuals. In conclusion, our results provide useful information for the antigen selection and vaccination strategies, and indicated that repeated boosting vaccination with Omicron based vaccines especially the XBB sub-variant without the WT spike protein might achieve broad and efficient antibody responses against Omicron variant.
Immunosuppression in the solid tumor microenvironment (TME) is a critical obstacle that has limited the efficacy of T cell engager (TCE) immunotherapies. Though TCEs can direct T cell cytotoxicity towards tumors, T cell activation and inflammation can induce tumor cell and T cell expression of immune checkpoint proteins, such as PD-L1. This treatment-related increase in immune suppression in the TME further limits clinical responses. We have previously presented screening data on a panel of trispecific T cell engagers (TriTCEs). Preliminary mechanistic data showed enhanced antitumor activity where TriTCEs can concurrently direct T cell activity towards tumor cells while eliciting PD-1/PD-L1 checkpoint inhibition (CPI) by the addition of an affinity-engineered PD-1 domain to the TCE. Here, we present data that further characterizes and differentiates the lead TriTCE CPI formats.
Methods
Lead TriTCE CPI formats were screened for potency in vitro. Co-engagement of CD3, tumor-associated antigen (TAA), and PD-L1 by TriTCE CPIs was determined using on-cell binding measurements to exhausted T cells and tumor cells stimulated with IFNγ to upregulate PD-L1 and recapitulate cellular phenotypes expected to be found in an immunosuppressed TME. TriTCE CPI mediated T cell activation in the presence of PD-L1 expressing dendritic cells was assayed in co-culture. In vivo activity was determined using humanized PBMC and syngeneic mouse models.
Results
Lead TriTCE CPI formats were compared by assaying TAA-dependent cytotoxicity where addition of affinity-engineered PD-1 increased potency in vitro. Format-dependent differences in PD-1 location on the TriTCE and the presence of one or two α-TAA binding arms was found to enhance avidity-driven binding, which translated into increased T cell-dependent cytotoxicity compared to clinical benchmark controls. Lead TriTCE CPIs had broad anti-tumor activity across tumor cell lines with varying TAA and PD-L1 expression levels. In vivo testing of lead TriTCE CPI formats demonstrated tumor growth inhibition and enabled preliminary assessment of toxicity. A threshold for tolerability of affinity-engineered PD-1 was identified in humanized syngeneic mouse model.
Conclusions
Our next-generation TriTCE CPIs aim to leverage PD-L1-mediated immunosuppression for enhanced avidity-driven tumor cell targeting and CPI in the TME to improve T cell responses in solid tumors. Addition of an affinity-engineered PD-1 to the TCE enhanced activity across multiple tumor cell lines compared to a bispecific TCE, supporting that TriTCE CPIs can be active against primary and acquired PD-L1 resistance mechanisms. Humanized immunocompetent syngeneic mouse models suggest a widened therapeutic window based on measures of tumor regression with a favorable safety profile.
Ethics Approval
The protocol and procedures involving the care and use of animals in these studies was conducted in accordance with the regulations of the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) and were reviewed and approved by the Institutional Animal Care and Use Committee (IACUC; CrownBio, Jackson ImmunoResearch).
In this study, the diffusion process of water molecules in poly(ε-caprolactone) (PCL) has been investigated using in-situ attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy. In our system, the original broad water OH bands in 1D IR spectra can be effectively differentiated into four bands, located at 3641, 3593, 3410, and 3203 cm−1, respectively, using 2D correlation analysis. The bands at 3641 cm−1 (antisymmetric) and 3593 cm−1 (symmetric) are assigned to the OH stretching vibration of water partially hydrogen bonded with hydrophilic carbonyl group (C=O) of PCL, while the other band pair at 3410 cm−1 (antisymmetric) and 3203 cm−1 (symmetric) could be attributed to the stretching vibration of water fully hydrogen bonded with another water molecule. According to the result of the asynchronous correlation, it was concluded that the water molecules at first diffuse into free volume (microvoids) or are molecularly dispersed into the PCL matrix and then form hydrogen bond with the C=O group of the polymer during the process of water diffusion. In addition, the diffusion coefficient was estimated using nonlinear curve fitting of OH band areas in the range of 3800–3000 cm−1.
Conduct a bibliometric analysis to review the knowledge structure and research trends regarding the association between periodontal disease and cardiovascular disease (CVD).
Liver iron and fat are often co-deposited, synergistically aggravating the progression of chronic liver disease. Accurate determination of liver iron and fat content is helpful for patient management. To assess the accuracy of hepatic iron/fat decomposition using dual-energy computed tomography (DECT) for simultaneously quantifying hepatic iron and fat when both are present.Sixty-eight New Zealand rabbits on a high-fat/cholesterol diet plus iron injections were used to establish a model of coexisting hepatic iron/fat. Abdominal imaging was performed using dual-source DECT. The iron and fat fractions (Iron-CT and Fat-CT, respectively) were calculated using a 3-material decomposition algorithm. The spectroscopic liver iron concentration (LIC) grading (normal, mild, moderate, severe, and massive iron overload) and the histopathological fat fraction (Fat-ref) grading (normal, mild, moderate, severe steatosis) were used as references. Correlations between the DECT parameters and the references were analyzed. Hepatic iron/fat quantification equations were established and validated. Analysis of covariance was used to assess the influence of fat on iron measurements and vice versa.Iron-CT highly correlated with LIC (r=0.94, P<0.001), and Fat-CT highly correlated with Fat-ref (r=0.88, P<0.001). Both the Iron-CT- and Fat-CT-derived LIC and fat fraction showed good agreement with spectroscopy/histology. The linear relationship between Iron-CT and spectroscopic LIC was not affected by the grade of hepatic fat (F=1.93, P=0.16). The linear relationship between Fat-CT and Fat-ref was unaffected by hepatic iron grades from normal to severe (F=0.18, P=0.91). However, with massive iron overload [>15.0 mg Fe/g (270 µmol/g)] the regression began to deviate, causing fat underestimation (F=5.50, P=0.04).Our DECT-based iron/fat decomposition algorithm accurately measured hepatic iron and fat when both were present in a rabbit model. Hepatic fat may be underestimated when there is massive iron overload.
SARS-CoV-2 infection is a global public health threat. Vaccines are considered amongst the most important tools to control the SARS-CoV-2 pandemic. As expected, deaths from SARS-CoV-2 infection have dropped dramatically with widespread vaccination. However, there are concerns over the duration of vaccine-induced protection, as well as their effectiveness against emerging variants of concern. Here, we constructed a recombinant chimpanzee adenovirus vectored vaccine expressing the full-length spike of SARS-CoV-2 (AdC68-S). Rapid and high levels of humoral and cellular immune responses were observed after immunization of C57BL/6J mice with one or two doses of AdC68-S. Notably, neutralizing antibodies were observed up to at least six months after vaccination, without substantial decline. Single or double doses AdC68-S immunization resulted in lower viral loads in lungs of mice against SARS-CoV-2 challenge both in the short term (21 days) and long-term (6 months). Histopathological examination of AdC68-S immunized mice lungs showed mild histological abnormalities after SARS-CoV-2 infection. Taken together, this study demonstrates the efficacy and durability of the AdC68-S vaccine and constitutes a promising candidate for clinical evaluation.
BACKGROUND Radiogenomics is an emerging technology that integrates genomics and medical image–based radiomics, which is considered a promising approach toward achieving precision medicine. OBJECTIVE The aim of this study was to quantitatively analyze the research status, dynamic trends, and evolutionary trajectory in the radiogenomics field using bibliometric methods. METHODS The relevant literature published up to 2023 was retrieved from the Web of Science Core Collection. Excel was used to analyze the annual publication trend. VOSviewer was used for constructing the keywords co-occurrence network and the collaboration networks among countries and institutions. CiteSpace was used for citation keywords burst analysis and visualizing the references timeline. RESULTS A total of 3237 papers were included and exported in plain-text format. The annual number of publications showed an increasing annual trend. China and the United States have published the most papers in this field, with the highest number of citations in the United States and the highest average number per item in the Netherlands. Keywords burst analysis revealed that several keywords, including “big data,” “magnetic resonance spectroscopy,” “renal cell carcinoma,” “stage,” and “temozolomide,” experienced a citation burst in recent years. The timeline views demonstrated that the references can be categorized into 8 clusters: lower-grade glioma, lung cancer histology, lung adenocarcinoma, breast cancer, radiation-induced lung injury, epidermal growth factor receptor mutation, late radiotherapy toxicity, and artificial intelligence. CONCLUSIONS The field of radiogenomics is attracting increasing attention from researchers worldwide, with the United States and the Netherlands being the most influential countries. Exploration of artificial intelligence methods based on big data to predict the response of tumors to various treatment methods represents a hot spot research topic in this field at present.