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Neoadjuvant therapy (NAT) treats early‐stage breast cancers, especially triple‐negative breast cancers (TNBCs). NAT improves pathological complete response (pCR) rates for different breast cancer patients. Recently, immune checkpoint inhibitors that target programmed death 1 (PD‐1) or programmed death ligand 1 (PD‐L1) in combination with NAT have shown antitumor activity in patients with early breast cancer. However, the tumor immune microenvironment (TME) in different subtypes of breast cancers, like TNBC, hormone receptor‐positive (HR+), and human epidermal growth factor receptor 2 amplified (HER2+) and its changes by NAT remain to be fully characterized. We analyzed pre‐NAT tumor biopsies from TNBC (n = 27), HR+ (n = 24), and HER2+ (n = 30) breast cancer patients who received NAT, followed by surgery. The different immune makers (PD‐1, PD‐L1, CD3, and CD8) of tumor‐infiltrating lymphocytes (TILs) were identified with immunofluorescence‐based microenvironment analysis. TILs within cancer parenchyma (iTILs) and in cancer stroma (sTILs) were counted separately. We found that PD‐L1+ cells in tumor and stroma were significantly higher in TNBC patients than in others. PD‐L1+ sTILs were significantly higher in pCR than in non‐pCR patients of all the subtypes. The infiltration scores of B‐cell memory, T‐cell CD4+ memory activated, T‐cell follicular helper, and Macrophage M0 and M1 were relatively higher in TNBC patients, indicating immunoreactive TME in TNBC. Analysis of TCGA‐BRCA RNA‐seq indicated that PD‐L1 was highly expressed in TNBC patients compared with HR+ and HER2+ patients. Higher PD‐L1 expression in TNBC patients was associated with significantly longer overall survival (OS). Our results demonstrated that PD‐L1 expression level of iTILs and sTILs is highest in TNBC among breast cancers. TNBC patients had significantly different immunoreactive TME compared with HR+ and HER2+ patients, suggesting potentially favorable outcomes for immunotherapy in these patients. Also, PD‐L1+ could be a powerful predictor of pCR in TNBC patients after NAT. [ABSTRACT FROM AUTHOR]

Background: Several studies have explored the relationship between intratumoral microvessel density (MVD) and the risk of postoperative biochemical recurrence (BCR) in prostate cancer (PCa), although the results are contradictory. Therefore, we conducted a meta‐analysis to investigate the effect of MVD on BCR in PCa. Method: We searched PubMed, MEDLINE, Science Direct/Elsevier, the Cochrane Library, CNKI, and EMBase databases from inception through January 2022, with no year or language restrictions, and used NOS guidelines to evaluate the quality of the 19 eligible studies. The derived hazard ratio (HR) and 95% confidence interval (95%CI) were used to assess each endpoint. Data synthesis was performed with RevMan to assess the prognostic value of MVD in PCa and its heterogeneity, while the publication bias was examined using STATA 16.0. Results: Our meta‐analysis included 19 articles (4 for T1‐2, 6 for T1‐3, and 9 for T1‐4) on postoperative biochemical recurrence of PCa, among which, 3933 patients were pooled. The predictive ability of intratumoral MVD for different stages of PCa on BCR was T1‐2 (HR, 2.46; 95% CI, 1.08–5.58; p = 0.03; I2 = 83%), T1‐3 (HR, 2.38, 95% CI, 1.41–4.01; p = 0.001; I2 = 82%), T1‐4 (HR, 1.61; 95% CI, 1.19–2.19; p = 0.002; I2 = 61%).The subgroup analyses based on European and immunohistochemical antibody none‐factor VII were consistent with primary one. Sensitivity analysis excluding those studies judged to be at high risk of bias in T1‐2 showed a HR of 2.99[1.70,5.27] (I2 = 38%, p = 0.0001), demonstrating the robustness of risk estimates of MVD for the assessment of biochemical recurrence. Conclusion: Microvessel density is a predictor of BCR among patients with PCa, and earlier T stage PCa with a stronger MVD is associated with BCR. Further studies are needed to investigate neoangiogenesis in different T stages of PCa and whether MVD will be of benefit to the EAU‐recommended tool for biochemical recurrence risk assessment. [ABSTRACT FROM AUTHOR]

Clustered regularly interspaced short palindromic repeats‐CRISPR‐associated 9 (CRISPR‐Cas9) and base editors (BEs) are revolutionary gene‐editing technology that has been widely utilized in biology, biotechnology and medicine. However, recent reports show that CRISPR‐Cas9‐mediated genome editing can induce a p53‐mediated stress response and cell cycle arrest in human cells, while not illustrated in gene‐editing animals. In the study, to verify whether there is a phenomenon of p53 activation, by analysing nine gene‐edited rabbits using CRISPR‐Cas9 and BEs, we provide the first evidence that no apparent p53 expression changes in those rabbits generated by Cas9 or BE‐edited, suggesting that p53 may not need to consider for application in gene‐edited animals. [ABSTRACT FROM AUTHOR]

In recent years, large‐scale satellite networks have been studied emphatically due to its advantages in high throughput and low latency. Many companies and institutions are keen to build large‐scale low earth orbit satellite constellations to provide space‐based Internet services, which poses a great demand for the design of efficient and reliable routing schemes. Three attribute indexes to evaluate the performance of the satellites are proposed. With the Dempster–Shafer theory, the attributes can be fused for the routing decision‐making process. Based on the Message Identification divergence (M‐I divergence) measure method, a Belief Message Importance divergence based Routing algorithm is proposed. By adjusting the characteristic parameter, it can amplify the divergence between distance‐based evidence and others properly. In this way, Belief Message Importance divergence‐based Routing attempts to find the optimal shortest path according to the status of intermediate nodes. Compared with existing satellite routing schemes, the algorithm that is proposed can approach the optimal routing performance, increasing the throughput by 47.2% on average, and decreasing the total delay and packet drop rate by 59.5% and 42.1% on average, respectively. [ABSTRACT FROM AUTHOR]