Multiparametric MRI radiomics fusion for predicting the response and shrinkage pattern to neoadjuvant chemotherapy in breast cancer

PurposeDuring neoadjuvant chemotherapy (NACT), breast tumor morphological and vascular characteristics are usually changed. This study aimed to evaluate the tumor shrinkage pattern and response to NACT by preoperative multiparametric magnetic resonance imaging (MRI), including dynamic contrast-enhanced MRI (DCE-MRI), diffuse weighted imaging (DWI) and T2 weighted imaging (T2WI).MethodIn this retrospective analysis, female patients with unilateral unifocal primary breast cancer were included for predicting tumor pathologic/clinical response to NACT (n=216, development set, n=151 and validation set, n=65) and for discriminating the tumor concentric shrinkage (CS) pattern from the others (n=193; development set, n=135 and validation set, n=58). Radiomic features (n=102) of first-order statistical, morphological and textural features were calculated on tumors from the multiparametric MRI. Single- and multiparametric image-based features were assessed separately and were further combined to feed into a random forest-based predictive model. The predictive model was trained in the testing set and assessed on the testing dataset with an area under the curve (AUC). Molecular subtype information and radiomic features were fused to enhance the predictive performance.ResultsThe DCE-MRI-based model showed higher performance (AUCs of 0.919, 0.830 and 0.825 for tumor pathologic response, clinical response and tumor shrinkage patterns, respectively) than either the T2WI or the ADC image-based model. An increased prediction performance was achieved by a model with multiparametric MRI radiomic feature fusion.ConclusionsAll these results demonstrated that multiparametric MRI features and their information fusion could be of important clinical value for the preoperative prediction of treatment response and shrinkage pattern

The prospective outcome of the monkeypox outbreak in 2022 and characterization of monkeypox disease immunobiology

A new threat to global health re-emerged with monkeypox’s advent in early 2022. As of November 10, 2022, nearly 80,000 confirmed cases had been reported worldwide, with most of them coming from places where the disease is not common. There were 53 fatalities, with 40 occurring in areas that had never before recorded monkeypox and the remaining 13 appearing in the regions that had previously reported the disease. Preliminary genetic data suggest that the 2022 monkeypox virus is part of the West African clade; the virus can be transmitted from person to person through direct interaction with lesions during sexual activity. It is still unknown if monkeypox can be transmitted via sexual contact or, more particularly, through infected body fluids. This most recent epidemic’s reservoir host, or principal carrier, is still a mystery. Rodents found in Africa can be the possible intermediate host. Instead, the CDC has confirmed that there are currently no particular treatments for monkeypox virus infection in 2022; however, antivirals already in the market that are successful against smallpox may mitigate the spread of monkeypox. To protect against the disease, the JYNNEOS (Imvamune or Imvanex) smallpox vaccine can be given. The spread of monkeypox can be slowed through measures such as post-exposure immunization, contact tracing, and improved case diagnosis and isolation. Final Thoughts: The latest monkeypox epidemic is a new hazard during the COVID-19 epidemic. The prevailing condition of the monkeypox epidemic along with coinfection with COVID-19 could pose a serious condition for clinicians that could lead to the global epidemic community in the form of coinfection

Association between systemic immune-inflammation index and chronic obstructive pulmonary disease: a population-based study

Abstract Background The Systemic Immune-Inflammation Index (SII) is a quantitative measurement of the systemic immune-inflammatory response in the human body. The SII has been shown to have prognostic value in various clinical settings, including critical illness, sepsis, and cancer. Its role in chronic obstructive pulmonary disease (COPD) remains unclear and requires further investigation. Methods We analyzed demographic data from 16,636 participants in the National Health and Nutrition Examination Survey. Logistic regression analysis was performed to assess the correlation between COPD, lung function, chronic respiratory symptoms and SII. We used Cox proportional hazards (PH) model to analyze the relationship between SII and mortality in COPD patients and healthy individuals. We used propensity score matching (PSM) method to match the COPD population with similar baseline levels with the normal population to further analyze the correlation between SII and COPD. Results We recruited 16,636 participants, ages 40 and above, for the study. A multivariable logistic regression analysis revealed that a higher SII level was independently associated with an elevated likelihood of COPD (Odds Ratio (OR) = 1.449; 95% Confidence Interval (CI): 1.252–1.676, P < 0.0001) after controlling for all other factors. Results of subgroup analysis showed a significant positive correlation between SII and COPD in different age groups, gender, Body Mass Index, smoking status, and those with a history of hypertension. The SII index had positive correlation with COPD after PSM (OR = 1.673; 95%CI: 1.443–1.938). After full adjustment, an increase in the SII is associated with a higher all-cause mortality rate. The hazard ratio (HR) with a 95% CI in the general population, COPD patients, and healthy individuals are 1.161 (1.088, 1.239), 1.282 (1.060, 1.550), and 1.129 (1.055, 1.207), respectively. Conclusions Higher SII levels are linked to higher prevalence of COPD. COPD patients with a higher SII levels have a higher risk of all-cause mortality. Additional large-scale, long-term studies are necessary to confirm these results

Inhibition of ovarian cancer by RGD-P125A-endostatin-Fc fusion proteins

Previous studies have shown that a single point mutation in endostatin at position 125 (P125A) can improve the biological activity of endostatin. Addition of an integrin-targeting moiety, R-G-D, resulted in better localization to tumor vasculature and improved the antiangiogenic activity of endostatin. Because endostatin has relatively shorter serum half-life, frequent dosing was required for inhibiting tumor growth. In our study, we have genetically fused RGD-P125A-endostatin to Fc of IgG4 isotype and evaluated its antiangiogenic and antitumor effects in athymic mice. Two genetic constructs were made, RGD-P125A-endostatin-Fc (RE-Fc) and P125A-endostatin-RGD-Fc (ER-Fc). Both constructs were cloned and expressed in mammalian cells. Purified fusion proteins inhibited endothelial cell migration and proliferation better than yeast-derived P125A-endostatin. Both RE-Fc and ER-Fc inhibited ovarian cancer growth and were found to be as effective as Bevacizumab treatment. Fusion protein showed marked increased half-life. Combination treatment with Bevacizumab and ER-Fc showed additive inhibition of ovarian cancer growth. These studies demonstrate that genetic fusion with human IgG4-Fc increases the half-life of P125A-endostatin and can be used along with Bevacizumab to improve antiangiogenic and antitumor activities

USP38 Inhibits Zika Virus Infection by Removing Envelope Protein Ubiquitination

Zika virus (ZIKV) is a mosquito-borne flavivirus, and its infection may cause severe neurodegenerative diseases. The outbreak of ZIKV in 2015 in South America has caused severe human congenital and neurologic disorders. Thus, it is vitally important to determine the inner mechanism of ZIKV infection. Here, our data suggested that the ubiquitin-specific peptidase 38 (USP38) played an important role in host resistance to ZIKV infection, during which ZIKV infection did not affect USP38 expression. Mechanistically, USP38 bound to the ZIKV envelope (E) protein through its C-terminal domain and attenuated its K48-linked and K63-linked polyubiquitination, thereby repressed the infection of ZIKV. In addition, we found that the deubiquitinase activity of USP38 was essential to inhibit ZIKV infection, and the mutant that lacked the deubiquitinase activity of USP38 lost the ability to inhibit infection. In conclusion, we found a novel host protein USP38 against ZIKV infection, and this may represent a potential therapeutic target for the treatment and prevention of ZIKV infection

Zika virus dysregulates the expression of astrocytic genes involved in neurodevelopment.

Zika virus (ZIKV) is a kind of flavivirus emerged in French Polynesia and Brazil, and has led to a worldwide public health concern since 2016. ZIKV infection causes various neurological conditions, which are associated with fetus brain development or peripheral and central nervous systems (PNS/CNS) functional problems. To date, no vaccine or any specific antiviral therapy against ZIKV infection are available. It urgently needs efforts to explore the underlying molecular mechanisms of ZIKV-induced neural pathogenesis. ZIKV favorably infects neural and glial cells specifically astrocytes, consequently dysregulating gene expression and pathways with impairment of process neural cells. In this study, we applied a model for ZIKV replication in mouse primary astrocytes (MPAs) and profiled temporal alterations in the host transcriptomes upon ZIKV infection. Among the RNA-sequencing data of 27,812 genes, we examined 710 genes were significantly differentially expressed by ZIKV, which lead to dysregulation of numerous functions including neurons development and migration, glial cells differentiation, myelinations, astrocytes projection, neurogenesis, and brain development, along with multiple pathways including Hippo signaling pathway, tight junction, PI3K-Akt signaling pathway, and focal adhesion. Furthermore, we confirmed the dysregulation of the selected genes in MPAs and human astroglioma U251 cells. We found that PTBP1, LIF, GHR, and PTBP3 were upregulated while EDNRB and MBP were downregulated upon ZIKV infection. The current study highlights the ZIKV-mediated potential genes associated with neurodevelopment or related diseases

Association between Gut Microbiota and Biological Aging: A Two-Sample Mendelian Randomization Study

Recent observational studies revealed an association between gut microbiota and aging, but whether gut microbiota are causally associated with the aging process remains unknown. We used a two-sample Mendelian randomization approach to investigate the causal association between gut microbiota and biological age acceleration using the largest available gut microbiota GWAS summary data from the MiBioGen consortium and GWAS data on biological age acceleration. We further conducted sensitivity analysis using MR-PRESSO, MR-Egger regression, Cochran Q test, and reverse MR analysis. Streptococcus (IVW, β = 0.16, p = 0.0001) was causally associated with Bioage acceleration. Eubacterium (rectale group) (IVW, β = 0.20, p = 0.0190), Sellimonas (IVW, β = 0.06, p = 0.019), and Lachnospira (IVW, β = −0.18, p = 0.01) were suggestive of causal associations with Bioage acceleration, with the latter being protective. Actinomyces (IVW, β = 0.26, p = 0.0083), Butyricimonas (IVW, β = 0.21, p = 0.0184), and Lachnospiraceae (FCS020 group) (IVW, β = 0.24, p = 0.0194) were suggestive of causal associations with Phenoage acceleration. This Mendelian randomization study found that Streptococcus was causally associated with Bioage acceleration. Further randomized controlled trials are needed to investigate its role in the aging process