Circulating tumor DNA: from discovery to clinical application in breast cancer.

Breast cancer (BC) stands out as the cancer with the highest incidence of morbidity and mortality among women worldwide, and its incidence rate is currently trending upwards. Improving the efficiency of breast cancer diagnosis and treatment is crucial, as it can effectively reduce the disease burden. Circulating tumor DNA (ctDNA) originates from the release of tumor cells and plays a pivotal role in the occurrence, development, and metastasis of breast cancer. In recent years, the widespread application of high-throughput analytical technology has made ctDNA a promising biomarker for early cancer detection, monitoring minimal residual disease, early recurrence monitoring, and predicting treatment outcomes. ctDNA-based approaches can effectively compensate for the shortcomings of traditional screening and monitoring methods, which fail to provide real-time information and prospective guidance for breast cancer diagnosis and treatment. This review summarizes the applications of ctDNA in various aspects of breast cancer, including screening, diagnosis, prognosis, treatment, and follow-up. It highlights the current research status in this field and emphasizes the potential for future large-scale clinical applications of ctDNA-based approaches.

Comparison of neoadjuvant chemotherapy response and prognosis between HR-low/HER2-negative BC and TNBC: an exploratory real-world multicentre cohort study.

Objective: Hormone receptor (HR)-low/HER2-negative breast cancers (BCs) are more likely to be basal-like BCs, with similar molecular features and gene expression profiles to HR-negative (estrogen receptor <1% or negative and progesterone receptor <1% or negative) BCs. Recently, with the clinical application of adjuvant intensive therapy for triple-negative breast cancer (TNBC), the prognosis of TNBC patients without pathological complete response (pCR) has significantly improved. Therefore, it is necessary to reanalyse the prognostic characteristics of clinically high-risk HR-low/HER2-negative BC. Methods: According to the inclusion and exclusion standards, 288 patients with HR-low/HER2-negative BC and TNBC who received NAC and were followed up between 2015 and 2022 at three breast centres in Hunan Province, China, were enrolled. Inverse probability of treatment weighting (IPTW) was utilized to mitigate imbalances in baseline characteristics between the HR-low/HER2-negative BC group and TNBC group regarding event-free survival (EFS) and overall survival (OS). The primary clinical endpoints were pCR and EFS, while the secondary endpoints included OS, objective response rate (ORR), and clinical benefit rate (CBR). Results: The pCR rate (27.1% vs. 28.0%, P = 1.000), ORR rate (76.9% vs. 78.3%, P = 0.827) and CBR rate (89.7% vs. 96.5%, P = 0.113) after NAC were similar between the HR-low/HER2-negative BC and the TNBC group. EFS in patients with non-pCR from the 2 groups was significantly inferior in comparison to patients with pCR (P = 0.001), and the 3-year EFS was 94.74% (95% CI = 85.21% to 100.00%) and 57.39% (95% CI =43.81% to 75.19%) in patients with pCR and non-pCR from the HR-low/HER2-negative BC group, respectively, and 89.70% (95% CI = 82.20% to 97.90%) and 69.73% (95% CI = 62.51% to 77.77%) in the TNBC patients with pCR and non-pCR, respectively. Conclusions: In the real world, the therapeutic effects of NAC for HR-low/HER2-negative BCs and TNBCs were similar. EFS of patients with non-pCR in the HR-low/HER2-negative BC group was inferior to that of the TNBC group with non-pCR, suggesting that it is necessary to explore new adjuvant intensive therapy strategies for these patients.

Measurement and Data Correction of Channel Sampling Timing Walk-Off of Photonic Analog-to-Digital Converter in Signal Recovery.

A two-channel, time-wavelength interleaved photonic analog-to-digital converter (PADC) system with a sampling rate of 10.4 GSa/s was established, and a concise method for measuring and data correcting the channel sampling timing walk-off of PADCs for signal recovery was proposed. The measurements show that for the two RF signals of f1 = 100 MHz and f2 = 200 MHz, the channel sampling timing walk-off was 12 sampling periods, which results in an ENOB = -0.1051 bits for the 100 MHz directly synthesized signal, while the ENOB improved up to 4.0136 bits using shift synthesis. In addition, the peak limit method (PLM) and normalization processing were introduced to reduce the impacts of signal peak jitter and power inconsistency between two channels, which further improve the ENOB of the 100 MHz signal up to 4.5668 bits. All signals were analyzed and discussed in both time and frequency domains. The 21.1 GHz signal was also collected and converted using the established two-channel PADC system with the data correction method, combining the PLM, normalization, and shift synthesis, showing that the ENOB increased from the initial -0.9181 to 4.1913 bits, which demonstrates that our method can be effectively used for signal recovery in channel-interleaved PADCs.

Immune characteristics and clinical significance of peripheral blood lymphocytes in breast cancer.

BACKGROUND: In the context of breast cancer (BC), the correlation between lymphocytes and clinical outcomes, along with treatment response, has garnered attention. Despite this, few investigations have delved into the interplay among distinct peripheral blood lymphocyte (PBL) types, immune attributes, and their clinical implications within the BC landscape. METHODS: The primary objective of this study was to scrutinize the baseline status of PBL subsets in patients with primary BC, track their dynamic changes throughout treatment, and ascertain their interrelation with prognosis. Flow cytometry was employed to analyse PBLs from a cohort of 74 BC patients. RESULTS: Our analysis revealed that baseline levels of Treg and PD-L1 + T cells were lower in BC patients compared to the reference values. Notably, a disparity in baseline PD-L1 + T cell levels surfaced between patients who underwent adjuvant therapy and those subjected to neoadjuvant therapy (NAT). Furthermore, a meticulous evaluation of PBL subsets before and after treatment underscored discernible alterations in 324 + T cells and CD19 + CD32 + B cells over the course of therapy. Strikingly, heightened CD4 + T cell levels at baseline were linked to enhanced event-free survival (EFS) (p = 0.02) and a robust response to chemotherapy. CONCLUSIONS: These results indicate that PBLs may serve as a significant marker to assess the immune status of BC patients, and therapy has the potential to modify patient immune profiles. In addition, peripheral blood CD4 + T cell levels may serve as promising biomarkers for diagnosis and prognosis in future studies of BC.

Comparative effectiveness of nipple-sparing mastectomy and breast-conserving surgery on long-term prognosis in breast cancer.

Background: The frequency of nipple-sparing mastectomy (NSM) surgery is presently increasing. Nonetheless, there is a paucity of long-term prognosis data on NSM. This study compared the long-standing prognosis of NSM in relation to breast-conserving surgery (BCS). Methods: Population-level data for 438,588 female breast cancer patients treated with NSM or BCS and postoperative radiation from 2000 to 2018 were identified in the Surveillance, Epidemiology, and End Results (SEER) database; 321 patients from the Second Xiangya Hospital of Central South University were also included. Propensity score matching (PSM) was performed to reduce the influence of selection bias and confounding variables to make valid comparisons. The Kaplan-Meier analysis, log-rank test, and Cox regression were applied to analyze the data. Results: There were no significant differences in long-term survival rates between patients who underwent NSM and those who underwent BCS+radiotherapy (BCS+RT), as indicated by the lack of significant differences in overall survival (OS) (p = 0.566) and breast cancer-specific survival (BCSS) (p = 0.431). Cox regression indicated that NSM and BCS+RT had comparable prognostic values (p = 0.286) after adjusting for other clinicopathological characteristics. For OS and BCSS, subgroup analysis showed that the majority of patients achieved an analogous prognosis whether they underwent NSM or BCS. The groups had comparable recurrence-free survival (RFS), with no significant difference found (p = 0.873). Conclusions: This study offers valuable insights into the long-term safety and comparative effectiveness of NSM and BCS in the treatment of breast cancer. These findings can assist clinicians in making informed decisions on a case-by-case basis.

Effects of Optical Sampling Pulse Power, RF Power, and Electronic Back-End Bandwidth on the Performance of Photonic Analog-to-Digital Converter.

The effects of optical sampling pulse power, RF power, and electronic back-end bandwidth on the performance of time- and wavelength-interleaved photonic analog-to-digital converter (PADC) with eight-channel 41.6 GHz pulses have been experimentally investigated in detail. The effective number of bits (ENOB) and peak-to-peak voltage (Vpp) of converted 10.6 GHz electrical signals were used to characterize the effects. For the 1550.116 nm channel with 5.2 G samples per second, an average pulse power of 0 to -10 dBm input to the photoelectric detector (PD) has been tested. The Vpp increased with increasing pulse power. And the ENOB for pulse power -9~-3 dBm was almost the same and all were greater than four. Meanwhile, the ENOB decreased either when the pulse power was more than -2 dBm due to the saturation of PD or when the pulse power was less than -10 dBm due to the non-ignorable noise relative to the converted weak signal. In addition, RF powers of -10~15 dBm were loaded into the Mach-Zehnder modulator (MZM). The Vpp increased with the increase in RF power, and the ENOB also showed an increasing trend. However, higher RF power can saturate the PD and induce greater nonlinearity in MZM, leading to a decrease in ENOB, while lower RF power will convert weak electrical signals with more noise, also resulting in lower ENOB. In addition, the back-end bandwidths of 0.2~8 GHz were studied in the experiments. The Vpp decreased as the back-end bandwidth decreased from 8 to 3 GHz, and remained nearly constant for the bandwidth between the Nyquist bandwidth and the subsampled RF signal frequency. The ENOB was almost the same and all greater than four for a bandwidth from 3 to 8 GHz, and gradually increased up to 6.5 as the back-end bandwidth decreased from the Nyquist bandwidth to 0.25 GHz. A bandwidth slightly larger than the Nyquist bandwidth was recommended for low costs and without compromising performance. In our experiment, the -3 to -5 dBm average pulse power, about 10 dBm RF power, and 3 GHz back-end bandwidth were recommended to accomplish both a high ENOB more than four and large Vpp. Our research provides a solution for selecting optical sampling pulse power, RF power, and electronic back-end bandwidth to achieve low-cost and high-performance PADC.

Multi-omics analysis reveals the involvement of origin recognition complex subunit 6 in tumor immune regulation and malignant progression.

Background: Origin recognition complex 6 (ORC6) is one of the six highly conserved subunit proteins required for DNA replication and is essential for maintaining genome stability during cell division. Recent research shows that ORC6 regulates the advancement of multiple cancers; however, it remains unclear what regulatory impact it has on the tumor immune microenvironment. Methods: Unpaired Wilcoxon rank sum and signed rank tests were used to analyze the differences in the expression of ORC6 in normal tissues and corresponding tumor tissues. Multiple online databases have evaluated the genetic alterations, protein expression and localization, and clinical relevance of ORC6. To evaluate the potential prognostic impact and diagnostic significance of ORC6 expression, we carried out log-rank, univariate Cox regression, and receiver operating characteristic curve analysis. The ICGC-LIRI-JP cohort, CGGA-301 cohort, CGGA-325 cohort, CGGA-693 cohort, and GSE13041 cohort were used for external validation of the study findings. The associations between ORC6 expression and immune cell infiltration, immune checkpoint expression, and immunotherapy cohorts was further analyzed. To explore the functional and signaling pathways related to ORC6 expression, gene set enrichment analysis was performed. To clarify the expression and function of ORC6 in hepatocellular carcinoma (LIHC) and glioma, we conducted in vitro experiments. Results: Expression of ORC6 is upregulated in the majority of cancer types and is associated with poor patient prognosis, notably in cases of LIHC and gliomas. In addition, ORC6 may be involved in multiple signaling pathways related to cancer progression and immune regulation. High expression of ORC6 correlates with an immunosuppressive state in the tumor microenvironment. The results of further immunotherapy cohort analysis suggested that patients in the ORC6 high-expression group benefited from immunotherapy. Inhibiting ORC6 expression suppressed the proliferative and migratory abilities of LIHC and glioma cells. Conclusion: High expression of ORC6 may be used as a biomarker to predict the poor prognosis of most tumor patients. The high expression of ORC6 may be involved in the regulation of the tumor immunosuppressive environment, and it is expected to become a molecular target for inhibiting tumor progression.

A comprehensive analysis of the role of QPRT in breast cancer.

To explore the clinical role of QPRT in breast cancer. The gene expression, methylation levels and prognostic value of QPRT in breast cancer was analyzed using TCGA data. Validation was performed using the data from GEO dataset and TNMPLOT database. Meta analysis method was used to pool the survival data for QPRT. The predictive values of QPRT for different drugs were retrieved from the ROC plot. The expression differences of QPRT in acquired drug-resistant and sensitive cell lines were analyzed using GEO datasets. GO and KEGG enrichment analysis were conducted for those genes which were highly co-expressed with QPRT in tissue based on TCGA data and which changed after QPRT knockdown. Timer2.0 was utilized to explore the correlation between QPRT and immune cells infiltration, and the Human Protein Atlas was used to analyse QPRT's single-cell sequencing data across different human tissues. The expression of QPRT in different types of macrophages, and the expression of QPRT were analysed after coculturing HER2+ breast cancer cells with macrophages. Additionally, TargetScan, Comparative Toxicogenomics and the connectivity map were used to research miRNAs and drugs that could regulate QPRT expression. Cytoscape was used to map the interaction networks between QPRT and other proteins. QPRT was highly expressed in breast cancer tissue and highly expressed in HER2+ breast cancer patients (P < 0.01). High QPRT expression levels were associated with worse OS, DMFS, and RFS (P < 0.01). Two sites (cg02640602 and cg06453916) were found to be potential regulators of breast cancer (P < 0.01). QPRT might predict survival benefits in breast cancer patients who received taxane or anthracycline. QPRT was associated with tumour immunity, especially in macrophages. QPRT may influence the occurrence and progression of breast cancer through the PI3K-AKT signalling pathway, Wnt signalling pathway, and cell cycle-related molecules.

Regulation and clinical potential of telomerase reverse transcriptase (TERT/hTERT) in breast cancer.

Telomerase reverse transcriptase (TERT/hTERT) serves as the pivotal catalytic subunit of telomerase, a crucial enzyme responsible for telomere maintenance and human genome stability. The high activation of hTERT, observed in over 90% of tumors, plays a significant role in tumor initiation and progression. An in-depth exploration of hTERT activation mechanisms in cancer holds promise for advancing our understanding of the disease and developing more effective treatment strategies. In breast cancer, the expression of hTERT is regulated by epigenetic, transcriptional, post-translational modification mechanisms and DNA variation. Besides its canonical function in telomere maintenance, hTERT exerts non-canonical roles that contribute to disease progression through telomerase-independent mechanisms. This comprehensive review summarizes the regulatory mechanisms governing hTERT in breast cancer and elucidates the functional implications of its activation. Given the overexpression of hTERT in most breast cancer cells, the detection of hTERT and its associated molecules are potential for enhancing early screening and prognostic evaluation of breast cancer. Although still in its early stages, therapeutic approaches targeting hTERT and its regulatory molecules show promise as viable strategies for breast cancer treatment. These methods are also discussed in this paper. Video Abstract.

1,3-Pentadiene-Assistant Living Anionic Terpolymerization: Composition Impact on Kinetics and Microstructure Sequence Primary Analysis.

The combination of a living anionic technology and a unique alternating strategy provided an exciting opportunity to prepare novel and well-defined poly(1,3-pentadiene-co-syrene-co-1,1-diphenylethylene) resins consisting of three alternating sequences of modules (A/B/C zwitterions). "A" being Styrene (St)/1,3-pentadiene (PD), "B" being diphenylethylene (DPE)/PD, "A" being DPE/St, respectively, A wide composition range of new polyolefin resins, i.e., poly (A-co-B), poly (A-co-C), and poly (B-co-C), with controlled molecular weight and very narrow molecular weight and composition distributions have been prepared by a one-pot living characteristic method. In the section of kinetic analysis, the terpolymer yields and kinetic parameters were strongly dependent on the feed/comonomer ratio as well as the content of the alternating structure. The competition copolymerization behaviors of A/B, B/C, and A/C were studied in detail in this work. By contrast, the microstructure and the thermal property of the resulting terpolymer were investigated via Nuclear magnetic resonance (NMR) and Differential scanning calorimetry (DSC) analysis. The results of 1H NMR tracking the change of [Aromatic ring]/[C=C] value indicated the distinctive copolymer-ization behavior of the selective "alternating-modules". The glass transition temperature (Tg) was very sensitive to the terpolymer composition. By contrast to poly(A-ran-B) with only one obvious Tg, there were two Tgs in the A/C and B/C copolymerization cases. Moreover, the desirable high Tg ~ 140 °C resin was limited to the terpolymers with up to 50 mol % DPE. Finally, the "ABC-X" mechanism was proposed to interpret the unique terpolymerization behavior, which belongs to the classical "bond-forming initiation" theory.

Targeting lncRNA DDIT4-AS1 Sensitizes Triple Negative Breast Cancer to Chemotherapy via Suppressing of Autophagy.

In this study, it is found that the lncRNA, DNA damage inducible transcript 4 antisense RNA1 (DDIT4-AS1), is highly expressed in triple-negative breast cancer (TNBC) cell lines and tissues due to H3K27 acetylation in the promoter region, and promotes the proliferation, migration, and invasion of TNBC cells via activating autophagy. Mechanistically, it is shown that DDIT4-AS1 induces autophagy by stabilizing DDIT4 mRNA via recruiting the RNA binding protein AUF1 and promoting the interaction between DDIT4 mRNA and AUF1, thereby inhibiting mTOR signaling pathway. Furthermore, silencing of DDIT4-AS1 enhances the sensitivity of TNBC cells to chemotherapeutic agents such as paclitaxel both in vitro and in vivo. Using a self-activatable siRNA/drug core-shell nanoparticle system, which effectively deliver both DDIT4-AS1 siRNA and paclitaxel to the tumor-bearing mice, a significantly enhanced antitumor activity is achieved. Importantly, the codelivery nanoparticles exert a stronger antitumor effect on breast cancer patient-derived organoids. These findings indicate that lncRNA DDIT4-AS1-mediated activation of autophagy promotes progression and chemoresistance of TNBC, and targeting of DDIT4-AS1 may be exploited as a new therapeutic approach to enhancing the efficacy of chemotherapy against TNBC.

Deep learning-based multifeature integration robustly predicts central lymph node metastasis in papillary thyroid cancer.

BACKGROUND: Few highly accurate tests can diagnose central lymph node metastasis (CLNM) of papillary thyroid cancer (PTC). Genetic sequencing of tumor tissue has allowed the targeting of certain genetic variants for personalized cancer therapy development. METHODS: This study included 488 patients diagnosed with PTC by ultrasound-guided fine-needle aspiration biopsy, collected clinicopathological data, analyzed the correlation between CLNM and clinicopathological features using univariate analysis and binary logistic regression, and constructed prediction models. RESULTS: Binary logistic regression analysis showed that age, maximum diameter of thyroid nodules, capsular invasion, and BRAF V600E gene mutation were independent risk factors for CLNM, and statistically significant indicators were included to construct a nomogram prediction model, which had an area under the curve (AUC) of 0.778. A convolutional neural network (CNN) prediction model built with an artificial intelligence (AI) deep learning algorithm achieved AUCs of 0.89 in the training set and 0.78 in the test set, which indicated a high prediction efficacy for CLNM. In addition, the prediction models were validated in the subclinical metastasis and clinical metastasis groups with high sensitivity and specificity, suggesting the broad applicability of the models. Furthermore, CNN prediction models were constructed for patients with nodule diameters less than 1 cm. The AUCs in the training set and test set were 0.87 and 0.76, respectively, indicating high prediction efficacy. CONCLUSIONS: The deep learning-based multifeature integration prediction model provides a reference for the clinical diagnosis and treatment of PTC.

METTL3 depletion contributes to tumour progression and drug resistance via N6 methyladenosine-dependent mechanism in HR+HER2-breast cancer.

BACKGROUND: Chemotherapy is an important strategy for the treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+HER2-) breast cancer (BC), but this subtype has a low response rate to chemotherapy. Growing evidence indicates that N6-methyladenosine (m6A) is the most common RNA modification in eukaryotic cells and that methyltransferase-like 3 (METTL3) participates in tumour progression in several cancer types. Therefore, exploring the function of METTL3 in HR+HER2- BC initiation and development is still important. METHODS: mRNA and protein expression levels were analysed by quantitative real-time polymerase chain reaction and western blotting, respectively. Cell proliferation was detected by CCK-8 and colony formation assays. Cell cycle progression was assessed by flow cytometry. Cell migration and invasion were analysed by wound healing assays and transwell assays, respectively, and apoptosis was analysed by TUNEL assays. Finally, m6A modification was analysed by methylated RNA immunoprecipitation. RESULTS: Chemotherapy-induced downregulation of the m6A modification is regulated by METTL3 depletion in HR+HER2- BC. METTL3 knockdown in MCF-7/T47D cells decreased the drug sensitivity of HR+HER2- BC cells by promoting tumour proliferation and migration and inhibiting apoptosis. Mechanistically, CDKN1A is a downstream target of METTL3 that activates the AKT pathway and promotes epithelial-mesenchymal transformation (EMT). Moreover, a decrease in BAX expression was observed when m6A modification was inhibited with METTL3 knockdown, and apoptosis was inhibited by the reduction of caspase-3/-9/-8. CONCLUSION: METTL3 depletion promotes the proliferation and migration and decreases the drug sensitivity of HR+HER2- BC via regulation of the CDKN1A/EMT and m6A-BAX/caspase-9/-3/-8 signalling pathways, which suggests METTL3 played a tumour-suppressor role and it could be a potential biomarker for predicting the prognosis of patients with HR+HER2- BC.

RNA-Seq-based transcriptomics analysis during the photodynamic therapy of primary cells in secondary hyperparathyroidism.

BACKGROUND: The aim of this study was to identify changes in gene expression before and after 5-aminolevulinic acid-mediated photodynamic therapy (5-ALA-PDT) and to investigate the potential mechanism of 5-ALA-PDT based on ribonucleic acid sequencing (RNA-Seq) analysis. METHODS: Secondary hyperparathyroidism (SHPT) primary cells were isolated from surgically excised specimens and exposed to laser light. The transcription profiles of SHPT primary cells were identified through RNA-Seq. Differentially expressed genes (DEGs) were identified. Enrichment of functions and signaling pathway analysis were performed based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Quantitative real-time polymerase chain reaction (RT-qPCR) and western blot analysis were used to validate genes based on RNA-Seq results. RESULTS: In total, 1320 DEGs were identified, of which 1019 genes were upregulated and 301 genes were downregulated. GO and KEGG pathway analyses identified significantly enriched pathways in DEGs, including TGF beta in extracellular matrix (ECM), negative regulation of triglyceride biosynthetic process, protein heterodimerization activity, systemic lupus erythematosus, ECM-receptor interaction, focal adhesion and protein digestion and absorption. Protein-protein interaction (PPI) network analyses identified potential heat shock protein (HSP) interactions among the DEGs. Eight HSP genes were also identified that were most likely involved in 5-ALA-PDT, which were further validated by RT-qPCR and western blotting. CONCLUSIONS: The findings of this descriptive study reveal changes in the transcriptome profile during 5-ALA-PDT, suggesting that gene expression and mutation, signaling pathways, and the molecular network are altered in SHPT primary cells. The above findings provide new insight for further studies on the mechanisms underlying 5-ALA-PDT in SHPT.

Highly precise timing alignment of multi-wavelength interleaved cavity-less pulse sources with FROG.

Strictly uniform time interval between adjacent channels is a crucial requirement for the multi-wavelength interleaved (MWI) pulse sources, which difficult alignment can be easily solved by what we believe to be our novel method based on frequency-resolved optical gating (FROG). By utilizing highly precise measurements from FROG, which provide fully two-dimensional information of the pulses in time and frequency domain, we can intuitively identify the time mismatches between different channels in the MWI pulse sources. This enables us to directly align the timing of each channel with sub-picosecond resolution at the first time. MWI pulse sources with total repetition rate of 20.8 GHz (four wavelengths) and 41.6 GHz (eight wavelengths) are precisely aligned by the proposed method, this achievement will pave the way for advancements in photonic analog-digital converters (PADC), high-speed optical communications and so on.

Refinement method for compressive hyperspectral data cubes based on self-fusion.

Compressive hyperspectral images often suffer from various noises and artifacts, which severely degrade the imaging quality and limit subsequent applications. In this paper, we present a refinement method for compressive hyperspectral data cubes based on self-fusion of the raw data cubes, which can effectively reduce various noises and improve the spatial and spectral details of the data cubes. To verify the universality, flexibility, and extensibility of the self-fusion refinement (SFR) method, a series of specific simulations and practical experiments were conducted, and SFR processing was performed through different fusion algorithms. The visual and quantitative assessments of the results demonstrate that, in terms of noise reduction and spatial-spectral detail restoration, the SFR method generally is much better than other typical denoising methods for hyperspectral data cubes. The results also indicate that the denoising effects of SFR greatly depend on the fusion algorithm used, and SFR implemented by joint bilateral filtering (JBF) performs better than SRF by guided filtering (GF) or a Markov random field (MRF). The proposed SFR method can significantly improve the quality of a compressive hyperspectral data cube in terms of noise reduction, artifact removal, and spatial and spectral detail improvement, which will further benefit subsequent hyperspectral applications.

Autoantibodies as biomarkers for breast cancer diagnosis and prognosis.

Breast cancer is the most common cancer in women worldwide and is a substantial public health problem. Screening for breast cancer mainly relies on mammography, which leads to false positives and missed diagnoses and is especially non-sensitive for patients with small tumors and dense breasts. The prognosis of breast cancer is mainly classified by tumor, node, and metastasis (TNM) staging, but this method does not consider the molecular characteristics of the tumor. As the product of the immune response to tumor-associated antigens, autoantibodies can be detected in peripheral blood and can be used as noninvasive, presymptomatic, and low-cost biomarkers. Therefore, autoantibodies can provide a possible supplementary method for breast cancer screening and prognosis classification. This article introduces the methods used to detect peripheral blood autoantibodies and the research progress in the screening and prognosis of breast cancer made in recent years to provide a potential direction for the examination and treatment of breast cancer.

Prognosis comparison between intraoperative radiotherapy and whole-breast external beam radiotherapy for T1-2 stage breast cancer without lymph node metastasis treated with breast-conserving surgery: A case-control study after propensity score matching.

Background: External beam radiotherapy (EBRT), an adjuvant to breast-conserving surgery (BCS), requires a long treatment period, is costly, and is associated with numerous complications. Large sample studies with long follow-up periods are lacking regarding whether intraoperative radiotherapy (IORT), an emerging radiotherapy modality, can replace EBRT for patients with T1-2 early stage breast cancer without lymph node metastasis treated with BCS. Methods: We identified 270,842 patients with T1-2N0M0 breast cancer from 2000 to 2018 in the Surveillance, Epidemiology, and End Results (SEER) database. A total of 10,992 patients were matched by propensity score matching (PSM). According to the radiotherapy method, the patients were divided into the IORT and EBRT groups. Overall survival (OS) and breast cancer-specific survival (BCSS) rates were analyzed and compared between the IORT and EBRT groups by Kaplan-Meier analysis. Bilateral P < 0.05 was considered to indicate significance. Results: After PSM, the survival analysis showed no significant differences in OS or BCSS rates between the IORT and EBRT groups. In the subgroup analysis, the IORT population diagnosed from 2010 to 2013 (HRs = 0.675, 95% CI 0.467-0.976, P = 0.037) or with T2 stage (HRs = 0.449, 95% CI 0.261-0.772, P = 0.004) had better OS rates, but in the overall population, the OS and BCSS rates were better in patients with T1 stage than in patients with T2 stage (P < 0.0001), and the proportion of chemotherapy was significantly higher in T2 stage than in T1 stage. Patients who had EBRT with unknown estrogen receptor had better OS rates (HRs = 3.392, 95% CI 1.368-8.407, P = 0.008). In addition, the IORT group had better BCSS rates for married (HRs = 0.403, 95% CI 0.184-0.881, P = 0.023), grade III (HRs = 0.405, 95% CI 0.173-0.952, P = 0.038), and chemotherapy-receiving (HRs = 0.327, 95% CI 0.116-0.917, P = 0.034) patients with breast cancer compared to the EBRT group. Conclusion: Intraoperative radiotherapy results of non-inferior OS and BCSS rates, compared to those of EBRT, in patients with early stage breast cancer without lymph node metastasis treated with BCS, and IORT may provide substantial benefits to patients as an effective alternative to standard treatment. This finding provides new insights into radiotherapy strategies for early stage breast cancer.

3D reconstruction based novel methods are more effective than traditional clinical assessment in breast cancer axillary lymph node metastasis prediction.

The status of axillary lymph node metastases determines the treatment and overall survival of breast cancer (BC) patients. Three-dimensional (3D) assessment methods have advantages for spatial localization and are more responsive to morphological changes in lymph nodes than two-dimensional (2D) assessment methods, and we speculate that methods developed using 3D reconstruction systems have high diagnostic efficacy. This exploratory study included 43 patients with histologically confirmed BC diagnosed at Second Xiangya Hospital of Central South University between July 2017 and August 2020, all of whom underwent preoperative CT scans. Patients were divided into a training cohort to train the model and a validation cohort to validate the model. A 3D axillary lymph node atlas was constructed on a 3D reconstruction system to create various methods of assessing lymph node metastases for a comparison of diagnostic efficacy. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic values of these methods. A total of 43 patients (mean [SD] age, 47 [10] years) met the eligibility criteria and completed 3D reconstruction. An axillary lymph node atlas was established, and a correlation between lymph node sphericity and lymph node metastasis was revealed. By continuously fitting the size and characteristics of axillary lymph nodes on the 3D reconstruction system, formulas and models were established to determine the presence or absence of lymph node metastasis, and the 3D method had better sensitivity for axillary lymph node assessment than the 2D method, with a statistically significant difference in the correct classification rate. The combined diagnostic method was superior to a single diagnostic method, with a 92.3% correct classification rate for the 3D method combined with ultrasound. In addition, in patients who received neoadjuvant chemotherapy (NAC), the correct classification rate of the 3D method (72.7%) was significantly higher than that of ultrasound (45.5%) and CT (54.5%). By establishing an axillary lymph node atlas, the sphericity formula and model developed with the 3D reconstruction system achieve a high correct classification rate when combined with ultrasound or CT and can also be applied to patients receiving NAC.