Abstract
Breast cancer (BC) is characterized by high morbidity. Mitochondrial ribosomal protein (MRP) family participates in mitochondrial energy metabolism, underlying BC progression. This study ...aims to analyze the expression and prognosis effect of the MRP genes in BC patients. GEPIA2, UALCAN, cBioPortal, and MethSurv were used to demonstrate the differential expression, genomic alteration profiles, and DNA methylation of the MRP gene family in BC. Functional enrichment analysis and protein–protein interaction network construction were performed to understand the biological function. Based on 1056 TCGA samples with the transcriptional level of MRPs, Kaplan–Meier curves, Cox, and LASSO regression were applied to explore their prognostic effects. 12 MRPs were upregulated in BC, which were associated with gene amplification and DNA methylation. MRP genetic alteration occurred in 42% of BC patients, and amplification was the most frequent variation. Functioning in its entirety, the MRP family was involved in mitochondrial translational termination, elongation, translation, and poly(A) RNA binding. High expression of MRPL1, MRPL13, MRPS6, MRPS18C, and MRPS35, as well as low levels of MRPL16, and MRPL40 significantly indicated poor prognosis in BC patients. Thus, a novel MRP-based prognostic nomogram was established and verified with favorable discrimination and calibration. We not only provided a thorough expression and prognosis analysis of the MRP family in BC patients but also constructed an MRP-based prognostic nomogram. It was suggested that MRPs acted as biomarkers in individualized risk prediction and may serve as potential therapeutic targets in BC patients.
To assist improving long-term postoperative seizure-free rate, we aimed to use machine learning algorithms based on neuropsychological data to differentiate temporal lobe epilepsy (TLE) from ...extratemporal lobe epilepsy (extraTLE), as well as explore the relationship between magnetic resonance imaging (MRI) and neuropsychological tests.
Twenty-three patients with TLE and 23 patients with extraTLE underwent neuropsychological tests and MRI scans before surgery. The least absolute shrinkage and selection operator were firstly employed for feature selection, and a machine learning approach with neuropsychological tests was employed to classify TLE using leave-one-out cross-validation. A generalized linear model was used to analyze the relationship between brain alterations and neuropsychological tests.
We found that logistic regression with the selected neuropsychological tests generated classification accuracies of 87.0%, with an area under the receiver operating characteristic curve (AUC) of 0.89. Three neuropsychological tests were acquired as significant neuropsychological signatures for the diagnosis of TLE. We also found that the Right-Left Orientation Test difference was related to the superior temporal and the banks of the superior temporal sulcus (bankssts). The Conditional Association Learning Test (CALT) was associated with the cortical thickness difference in the lateral orbitofrontal area between the two groups, and the Component Verbal Fluency Test was associated with the cortical thickness difference in the lateral occipital cortex between the two groups.
These results showed that machine learning-based classification with the selected neuropsychological data can successfully classify TLE with high accuracy compared to previous studies, which could provide kind of warning sign for surgery candidate of TLE patients. In addition, understanding the mechanism of cognitive behavior by neuroimaging information could assist doctors in the presurgical evaluation of TLE.
Background
Both TP53 mutation and MYC amplification indicate poor outcomes in breast cancer (BC), but the clinical values of concurrent TP53 and MYC alterations have not been well‐characterized.
...Methods
A total of 494 BC patients diagnosed at Guangdong Provincial People's Hospital (GDPH) were retrospectively analyzed. Genomic alterations were determined using next‐generation sequencing. Survival analysis was applied to assess the effects of genetic alterations on relapse‐free survival. The prognosis was verified based on 1405 patients from METABRIC cohort. Additionally, we used logistic regression to identify the factors associated with pathological complete response (pCR) after neoadjuvant chemotherapy.
Results
In GDPH cohort, patients with TP53/MYC co‐alteration exhibited higher grade and stage, more positive HER2 status and higher Ki67 levels, but less luminal A subtypes. They also had more mutations in genes involved in ERBB and TGF‐β signaling pathways, as well as exclusive FANCG/CDKN2B/QKI copy number amplifications and SUFU/HIST3H3/ERCC4/JUN/BCR mutations. Concurrent TP53 and MYC alterations independently increased hazards of relapse (HR, 5.425; 95% CI: 2.019–14.579; p < 0.001). They maintained independent significance for relapse‐free (HR, 1.310; 95% CI: 1.012–1.697; p = 0.041) and overall survival (HR, 1.373; 95% CI: 1.093–1.725; p = 0.006) in METABRIC cohort. Among the 81 patients receiving chemotherapy, TP53 mutation (OR, 5.750; 95% CI: 1.553–25.776; p = 0.013) and earlier stage (OR, 0.275; 95% CI 0.088–0.788; p = 0.020) were associated with pCR, while the co‐alteration did not serve as an independent predictor (p = 0.199).
Conclusions
TP53/MYC co‐alteration was associated with distinct clinicopathological and genomic features. They also conferred unfavorable prognosis in BC patients, and did not improve pCR after neoadjuvant chemotherapy.
Breast cancer with concurrent TP53 mutation and MYC amplification demonstrated higher grade and stage, more positive HER2 status, higher Ki67 levels, and more mutations in genes involved in ERBB and TGF‐β signaling pathways, as well as exclusive FANCG/CDKN2B/QKI copy number amplifications. Additionally, TP53/MYC co‐alteration was associated with worse relapse‐free survival and overall survival in breast cancer patients.
Perinatal infection aggravates neonatal hypoxic–ischemic (HI) brain injury and may interfere with therapeutic hypothermia. While the NF-κB signaling pathway has been implicated in microglia ...activation in infection-sensitized HI, the current therapeutic strategies rely on systemic intervention, which could impair neonatal immunity and increase the risk of severe infection. To devise a brain-targeted anti-NF-κB strategy, we examined the effects of intranasal delivery of tat-NBD peptides in two animal models of neonatal infection-sensitized HI. Kinetic experiments showed that tat-NBD peptides entered the olfactory bulbs rapidly (10–30min) and peaked in the cerebral cortex around 60min after intranasal application in P7 rats. Further, intranasal delivery of 1.4mg/kg tat-NBD, which is only 7% of the intravenous dose in past studies, markedly attenuated NF-κB signaling, microglia activation, and brain damage triggered by HI with 4 or 72h pre-exposure to the bacterial endotoxin lipopolysaccharide (LPS). In contrast, intranasal delivery of mutant tat-NBD peptides or systemic application of minocycline failed to block LPS-sensitized HI injury. Yet, intranasal delivery of up to 5.6mg/kg tat-NBD peptides immediately after pure-HI insult showed little protection, likely due to its rapid clearance from the brain and inability to inhibit parenchymal plasminogen activators. Together, these results suggest a novel therapy of infection-sensitized HI brain injury in newborns.
► Infection drastically alters pathogenic mechanism of hypoxic–ischemic brain injury. ► Intranasal delivery of anti NFkB peptides blocks infection sensitized HI injury. ► Results suggest a safe, brain targeted anti neuroinflammatory therapy.
Purpose
This study aimed to explore the mutational characteristics and significance of cell cycle-related genes (CCGs) in hormone-receptor positive, human epidermal growth factor receptor 2 negative ...breast cancer (HR+/HER2− BC).
Methods
A total of 1668 HR+/HER2− BC patients from the Guangdong Provincial People’s Hospital (GDPH) cohort (
n
= 321) and METABRIC cohort (
n
= 1347) were included. Tumor samples from HR+/HER2− BC patients were collected for a next-generation sequencing assay in GDPH cohort, including 15 key CCGs. The association between CCGs alterations and overall survival were identified via the Cox regression analysis. The functional roles of the CCGs were explored via the Metascape database.
Results
Based on multivariate Cox regression analysis, a set of five key CCGs (
CDK4, CCND1, CDKN1A, CDKN1C
, and
CHEK2
) were identified as independent prognostic variables in HR+/HER2− BC patients. Besides, the five-CCGs-based risk score was used to effectively classify patients into the low-risk and high-risk groups (
P
< 0.0001). The potential functional pathways of the CCGs included cell cycle, cyclin D associated events in G1, and regulation of G1/S transition of mitotic cell cycle.
Conclusion
We performed the integrated analysis of the CCGs in HR+/HER2− BC patients. It has the potential to guide individualized precision oncology therapeutic schemes in HR+/HER2− BC patients.
In this letter, a localization algorithm, which combines Hough transform and Doppler processing, is proposed for Doppler radar human sensing applications. The Hough transform is first applied to ...extract the interested target components and real-time estimate their instantaneous frequencies (IFs). Then, based on the IF estimation result, the target movement trajectories are synthesized by Doppler processing. To improve the detection accuracy and robustness, a generalized linear model is proposed for Hough transform, which can achieve highly dimensional frequency fitting to compensate the nonlinear error, meanwhile maintaining a low level of computational complexity for real-time processing. Experimental results are presented to illustrate the performance of the proposed algorithm.
Programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have become integral elements within the current landscape of breast cancer treatment modalities; however, they ...are associated with interstitial lung disease (ILD), which is rare but potentially fatal. Notably, only a few studies have compared the difference in ILD incidence between PD-1 and PD-L1 inhibitors. Therefore, this study aimed to assess the discrepancies regarding ILD risk between the two immune checkpoint inhibitors. We also reported three cases of ILD after PD-1 inhibitor treatment.
We comprehensively searched PubMed, EMBASE, and the Cochrane Library to identify clinical trials that investigated PD-1/PD-L1 inhibitor treatment for patients with breast cancer. Pooled overall estimates of incidence and risk ratio (RR) were calculated with a 95% confidence interval (CI), and a mirror group analysis was performed using eligible studies.
This meta-analysis included 29 studies with 4639 patients who received PD-1/PD-L1 inhibitor treatment. A higher ILD incidence was observed among 2508 patients treated with PD-1 inhibitors than among 2131 patients treated with PD-L1 inhibitors (0.05 vs. 0.02). The mirror group analysis further revealed a higher ILD event risk in patients treated with PD-1 inhibitors than in those treated with PD-L1 inhibitors (RR = 2.34, 95% CI, 1.13–4.82, P = 0.02).
Our findings suggest a greater risk of ILD with PD-1 inhibitors than with PD-L1 inhibitors. These findings are instrumental for clinicians in treatment deliberations, and the adoption of more structured diagnostic approaches and management protocols is necessary to mitigate the risk of ILD.
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•Programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors cause interstitial lung disease (ILD).•ILD is a rare adverse event; most cases are low-grade but potentially fatal.•The present meta-analysis included 29 studies with 4639 patients with breast cancer.•Compared with PD-L1 inhibitors, PD-1 inhibitors will increase the risk of ILD in patients with breast cancer.•Suitable treatment options for ILD and its early detection and immediate management should be initiated.
This study aimed to evaluate the role of postoperative radiotherapy (RT) in dermatofibrosarcoma protuberans (DFSP) and identify the prognostic factors influencing the disease-free survival (DFS).
A ...total of 184 patients with DFSP were analyzed from 2000 to 2016. The regression model was used to examine the prognostic factors for DFS. Baseline covariates were balanced using a propensity score model. The role of RT was assessed by comparing the DFS of the surgery + RT group with that of the surgery group.
The median follow-up was 58 months (range, 6-203 months). The 5-year DFS rate was 89.8%. The univariate analysis showed that age ≥ 50 years, presence of fibrosarcoma, margins < 2 cm, and tumor size ≥5 cm were associated with worse DFS (P = 0.002, P < 0.001, P = 0.030, and P = 0.032, respectively). The multivariate Cox regression model revealed that age, margin width, lesion number, and histological subtype independently affected DFS. The Ki-67 expression was related to age and histological subtype. Patients with Ki-67 ≥ 17% showed a worse DFS than those with Ki-67 < 17% (35.8% vs 87.8%, P = 0.002). In the matched cohort, DFS was significantly higher in the S + RT group than in the S group (5-year DFS, 88.1% vs 56.2%, P = 0.044).
Age, margin width, lesion number, and histological subtype were independent risk factors for DFS in patients with DFSP. The high expression of Ki-67 could predict a poor prognosis. Postoperative RT could improve DFS for patients with DFSP.
Objective
To evaluate the application of treatment planning system (TPS)-assisted large-aperture computed tomography (CT) simulator to percutaneous biopsy.
Methods
This retrospective study enrolled ...patients that underwent TPS-assisted large-aperture CT simulator-guided percutaneous biopsy from November 2018 to December 2019. Retrospective analyses of puncture accuracy were compared using paired t-test and a Wilcoxon rank sum test. The risk factors for puncture accuracy and complications were identified.
Results
A total of 38 patients were included in this study. There were no significant differences between the planned and actual puncture depth and angle. Pulmonary puncture was significantly associated with the accuracy of the puncture angle. The diagnostic rate of malignancy was 76% (29 of 38), of which 20 of 25 patients were in the group initially diagnosed with unconfirmed lesions and nine of 13 patients were in the group of treated patients that needed additional pathological analyses. For patients that underwent a pulmonary biopsy, 12 had minor pneumothorax and three suffered needle track bleeding. No other complications were observed. Regression analyses indicated a significant correlation between puncture angle and the incidence of pneumothorax.
Conclusion
TPS-assisted large-aperture CT simulator may improve the percutaneous biopsy procedure by combining the advantages of radiotherapy specialties with computer targeting.
Plasminogen activator inhibitor-I (PAI-1), a ≈50-kDa serine protease inhibitor, markedly reduces the extravascular toxicity of tissue-type plasminogen activator in experimental hypoxic-ischemic (HI) ...brain injury of newborns. However, the current treatment with PAI-1 requires intracerebroventricle injection to cross the blood-brain barrier, which is an invasive procedure of limited clinical potential. Thus, we tested whether intranasal administration of PAI-1 can bypass blood-brain barrier and mitigate neonatal HI brain injury.
Rat pups were subjected to HI, with or without lipopolysaccharide pre-exposure, followed by intranasal delivery of a stable-mutant form of PAI-1 (CPAI).
Immunoblotting showed that CPAI sequentially entered the olfactory bulbs and cerebral cortex after intranasal delivery and reduced ≈75% of brain atrophy in HI or lipopolysaccharide-sensitized HI injury. Mechanistically, CPAI attenuated HI-induced plasminogen activators and lipopolysaccharide/HI-induced nuclear factor-κB signaling, neuroinflammation, and blood-brain barrier permeability.
Intranasal delivery of CPAI is an effective treatment of experimental HI brain injury of newborns. Clinical application of this experimental therapy merits further investigation.
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