Corrigendum to "Establishment and verification of the first prognostic nomograms in locally advanced thyroid cancer based on the analysis of clinical and follow-up information on 2396 patients" [Heliyon 10(3), January 2024, e24798].

[This corrects the article DOI: 10.1016/j.heliyon.2024.e24798.].

Oxidative damage to mitochondrial DNA in maternal zebrafish (Danio rerio) exposed to dibutyl phthalate at environmentally relevant level.

Dibutyl phthalate (DBP) is a widely-used plasticizer that is dispersed in various environments, causing significant pollution and health risks. The toxic mechanism of DBP has been discussed in recent years, while the susceptibility of mitochondrial DNA (mtDNA) to DBP exposure and the resulting damage remain unclear. In this study, maternal zebrafish were exposed to environmentally relevant concentration of DBP for 0, 2, 4, and 6 weeks. Results showed that DBP exposure impaired health status, leading to the reduced body length and weight, condition factor, hepatosomatic index, and gonadosomatic index. Furthermore, DBP exposure induced oxidative stress and ATP deficiency in the gill and liver in a time-dependent manner. The oxidized mtDNA (ox-mtDNA) levels in the D-loop and ND1 regions were assessed in different tissues, showing distinct response patterns. The high energy-consuming tissues such as heart, brain, gill, and liver exhibited elevated susceptibility to mitochondrial damage, with a rapid increase in ox-mtDNA levels in the short term. Conversely, in muscle, ovary, eggs, and offspring, ox-mtDNA gradually accumulated over the exposure period. Notably, the ox-mtDNA levels in the D-loop region of blood showed a prompt response to DBP exposure, making it convenient for evaluation. Additionally, decreased hatching rates, increased mortality, lipoperoxidation, and depressed swimming performance were observed in offspring following maternal DBP exposure, suggesting the inherited impairments of maternal mtDNA. These findings highlight the potential for ox-mtDNA to serve as a convenient biomarker for environmental contamination, aiding in ecological risk assessment and forewarning systems in aquatic environment.

Ultrasound-guided core needle biopsy combined with immunohistochemistry and molecular testing improve the diagnostic accuracy of bone metastases from follicular thyroid carcinoma, two case reports and analyses.

Key Clinical Message: Ultrasound-guided core needle biopsy combined with immunohistochemistry and molecular testing could improve the diagnostic accuracy of bone metastases from follicular thyroid carcinoma, help to predict distant metastasis and prognosis. Abstract: Metastatic thyroid follicular carcinoma presenting initially with bone lesion is uncommon, its prime symptom is gradual onset, localized pain. Patient with bone metastasis who were diagnosed before thyroidectomy had a higher rate of mortality, clinician should be cautious in eliciting the clinical history and this insidious symptom in middle age group, carry out further examination. We are presenting two case reports of a follicular thyroid carcinoma with bone metastasis, ultrasound-guided core needle biopsy combined with immunohistochemistry (IHC) were carried out by our clinical team to determine the source and nature of the tumor, relevant literature was reviewed, molecular testing was discussed, we believe core needle biopsy combined with IHC and molecular testing improve the diagnostic accuracy of bone metastases from follicular thyroid carcinoma.

Efficacy and Safety of Bufei Jiedu Granules in Treating Multidrug-Resistant Pulmonary Tuberculosis: A Multi-center, Double-Blinded and Randomized Controlled Trial.

OBJECTIVE: To assess the efficacy and safety of Bufei Jiedu (BFJD) ranules as adjuvant therapy for patients with multidrug-resistant pulmonary tuberculosis (MDR-PTB). METHODS: A large-scale, multi-center, double-blinded, and randomized controlled trial was conducted in 18 sentinel hospitals in China from December 2012 to December 2016. A total of 312 MDR-PTB patients were randomly assigned to BFJD Granules or placebo groups (1:1) using a stratified randomization method, which both received the long-course chemotherapy regimen for 18 months (6 Am-Lfx-P-Z-Pto, 12 Lfx-P-Z-Pto). Meanwhile, patients in both groups also received BFJD Granules or placebo twice a day for a total of 18 months, respectively. The primary outcome was cure rate. The secondary outcomes included time to sputum-culture conversion, changes in lung cavities and quality of life (QoL) of patients. Adverse reactions were monitored during and after the trial. RESULTS: A total of 216 cases completed the trial, 111 in the BFJD Granules group and 105 in the placebo group. BFJD Granules, as an adjuvant treatment, increased the cure rate by 13.6% at the end of treatment, compared with the placebo (58.4% vs. 44.8%, P=0.02), and accelerated the median time to sputum-culture conversion (5 months vs. 11 months). The cavity closure rate of the BFJD Granules group (50.6%, 43/85) was higher than that of the placebo group (32.1%, 26/81; P=0.02) in patients who completed the treatment. At the end of the intensive treatment, according to the 36-item Short Form, the BFJD Granules significantly improved physical functioning, general health, and vitality of patients relative to the placebo group (all P<0.01). Overall, the death rates in the two groups were not significantly different; 5.1% (8/156) in the BFJD Granules group and 2.6% (4/156) in the placebo group. CONCLUSIONS: Supplementing BFJD Granules with the long-course chemotherapy regimen significantly increased the cure rate and cavity closure rates, and rapidly improved QoL of patients with MDR-PTB (Registration No. ChiCTR-TRC-12002850).

TORCHLIGHT trial, brightening the life of more patients with advanced triple-negative breast cancer.

Toripalimab (JS001) is a monoclonal antibody against programmed cell death-1 (PD-1), independently developed by Shanghai Junshi Biosciences Co., LTD, which is the first domestic original PD-1 inhibitor approved in China. TORCHLIGHT is the first phase III trial of PD-1 inhibitor combined chemotherapy in advanced triple-negative breast cancer (TNBC) in China, evaluating the efficacy and safety of toripalimab plus nab-paclitaxel as first- or second-line therapy. Nab-paclitaxel has significant advantages over other chemotherapy drugs, as paclitaxel nanoparticles combine with natural albumin to increase drug delivery and bioavailability of paclitaxel. Firstly, nab-paclitaxel has a higher therapy response; Secondly, albumin carries paclitaxel out of the blood circulation faster, reducing the damage to normal tissues, ensuring the survival of more normal immune cells and exerting immune efficacy. Finally, nab-paclitaxel does not cause allergic reactions caused by organic solvents and does not require glucocorticoid pretreatment, avoiding immune suppression and ensuring the maximum efficacy of immune checkpoint inhibitors (ICIs). In TORCHLIGHT trial, 95% of subjects were on the first line treatment, with only 5% being on the second line, and 56% patients were programmed death-ligand 1 (PD-L1) positive in total population. It achieved the survival benefits of progression-free survival (PFS) and overall survival (OS) dual efficacy end points, which stood out among numerous ICIs in advanced TNBC. TORCHLIGHT trial, as the name of it, like a torch to more patients with advanced TNBC, lighting up their lives. We described the design background of TORCHLIGHT trial and reviewed primary trials of PD-1 or PD-L1 inhibitor in advanced TNBC both domestically and internationally.

A case report of low-dose apatinib in the treatment of advanced triple-negative breast cancer.

Background: The current study shows that the incidence rate of triple-negative breast cancer accounts for 10-17% of invasive ductal carcinoma of the breast. There is no specific treatment target, the age of onset is relatively small, and the recurrence rate is relatively fast. The prognosis of breast cancer in different subtypes is the most unsatisfactory, with a 5-year survival rate of less than 15%. We report a typical case of metastatic advanced triple-negative breast cancer who responded well to apatinib mesylate after chemotherapy failure and achieved significant progression-free survival, which is relatively rare in triple-negative breast cancer with limited treatment means. Case Description: A 55-year-old female was surgically diagnosed as triple-negative breast cancer on April 17, 2015. After surgery, she had lung metastasis after standard adjuvant chemotherapy and radiotherapy. After receiving the NX regimen (vinorelbine, capecitabine) for 8 cycles, she progressed. Because the patient refused later, she was adjusted to apatinib mesylate, and serious adverse reactions occurred during the treatment process. By adjusting the drug dose, and low-dose apatinib treatment, the lung lesions were close to complete response (CR), reaching a progression-free survival period of 45 months. Conclusions: Low-dose apatinib may be a promising anti-tumor drug for triple-negative breast cancer patients, which needs more samples to verify. This case may provide a reference for the treatment selection of triple-negative metastatic breast cancer in the future.

A real-world comparison of circulating tumor cells in breast cancer from China: Novel device, CTC counts and its overall survival.

Background: Both CellSearch and CellCollector have been accepted as the proper devices to capture CTC by domestic approval department. However, there is little article about the comparison between these two devices around the world. Herein, we conducted the real-world study to compare with these two devices and to re-verify the efficacy of CTC counts. Methods: Patients who meet the following points should be included in the analysis. 1. Female, aged 18 years or older; 2. Eastern Cooperative Oncology Group (ECOG) score 0-2; 3. With at least one measurable tumor lesion; 4. Clear immunohistochemistry result; 5. Accept at least one CTC test. Patients were excluded in the analysis if they had a history of malignant tumors, incomplete follow-up information. Results: 536 metastatic breast cancer patients who had been detected for CTC at least once by CellSearch or CellCollector were included in the analysis. CellCollector in vivo CTC detection technology has a higher detection rate than the CellSearch system (69.2% vs 57.4%, P = 0.009). However, the proportion of CTC≥5 detected by CellSearch was higher than CellCollector (37.4% vs 16.3%, P < 0.001). There was a statistically significant difference in overall survival of patients with CTC negative and CTC positive (mOS:49.8 months vs 26.9 months). After 4 weeks of treatment, when CTC decreased by more than 50%, there was a significant difference in survival between the two groups (40.1 months vs 25.8 months, HR = 0.588, 95% CI: 0.350-0.933). In addition, for HER2-positive patients, Patients with CTC HER2 positive had longer overall survival than patients with CTC HER2 negative (median OS: 26.7 months vs 17.3 month, HR = 0.528, 95% CI: 0.269-0.887). Conclusions: Real-world data indicate that CTC is an independent prognostic factor, and CellCollector and CellSearch have their own advantages in CTC detection.

Establishment and verification of the first prognostic nomograms in locally advanced thyroid cancer based on the analysis of clinical and follow-up information on 2396 patients.

Background and objectives: The purpose of this research was to develop and validate the first prognostic nomograms for 3-, 5-, and 10-year cancer-specific survival (CSS) and overall survival (OS) in patients diagnosed with locally advanced thyroid cancer (LATC) by evaluating independent predictors of prognosis in a population of LATC patients. Methods: Demographics, clinicopathologic characteristics, treatment, and follow-up of 2396 LATC patients in the surveillance, epidemiology, and end results database from 2004 to 2015 were retrospectively analyzed and compared with patients with LATC according to staging. We randomized all LATC patients into training and validation groups in a 7:3 ratio. Cox regression analyses helped us to derive independent prognostic factors for LATC patients. According to these results, we established and validated the first prognostic nomograms and risk stratification. Results: In our research, the clinical information of LATC patients was compared and significant differences were found in the relevant variables including CSS and OS (P < 0.05), with CSS of 82.0 % and 49.0 %, and OS of 70.6 % and 40.0 %, respectively. Cox regression analyses showed that age at diagnosis, tumor diameter, presence of DM, extrathyroidal extension sites, histological type, thyroidectomy scope, radiotherapy status, and chronological sequence of radiotherapy and surgery were observably correlated with CSS in LATC patients, and in addition to the above factors, gender, marital status, and chemotherapy status were also observably correlated with OS in LATC patients. The prognostic predictive power of the above factors is visualized by the Kaplan-Meier survival curve. The concordance index of nomograms for CSS and OS were 0.933, 0.925, and 0.926 (CSS), 0.918, 0.909, and 0.906 (OS), respectively, and the time-dependent receiver operating characteristic curve, area under curve, calibration curve and decision curve analysis curve indicate that the nomograms have good discriminatory ability, accuracy and clinical applicability in both the training and validation groups. Conclusions: In these findings, we drawed a conclusion that there were significant differences in clinical information between patients with T4a and T4b LATC, and we established and validated the first prognostic nomograms and risk stratification of CSS and OS for LATC patients at 3, 5, and 10 years, which will help clinicians to individualize their postoperative treatment and individualized follow-up.

Enhanced Contact Performance and Thermal Tolerance of Ni/Bi2Te3 Joints for Bi2Te3-Based Thermoelectric Devices.

Ni metal has been widely used as a barrier layer in Bi2Te3-based thermoelectric devices, which establishes stable joints to link Bi2Te3-based legs and electrodes. However, the Ni/Bi2Te3 joints become very fragile when the devices were exposed to high temperature, causing severe performance deterioration and even device failure. Herein, stable Ni/Bi2Te3 joints have been established by arc spraying of the Ni barrier layer on the Bi2Te3-based alloys. The interface microstructure and contact performance including the bonding strength and contact resistivity of the arc-sprayed Ni/Bi2Te3 joints are investigated. The results indicate that, as compared with traditional Ni/Bi2Te3 joints, the arc-sprayed Ni/Bi2Te3 joints have comparably low contact resistivity while possessing a 50% higher bonding strength. Aging the joints as an exposure to high-temperature circumstances, the arc-sprayed Ni/Bi2Te3 joints exhibit much better tolerance to the thermal shock with stable bonding strength and contact resistivity. The enhanced interfacial contact performance and thermal tolerance should be attributed to the thick Ni barrier layer and interface reaction layer with good Ohmic contact. This work provides an effective strategy to establish stable joints for the Bi2Te3-based thermoelectric devices with improved thermal stability.

Novel Anti-HER2 Antibody-Drug Conjugates Versus T-DM1 for HER2-Positive Metastatic Breast Cancer After Tyrosine Kinase Inhibitors Treatment.

BACKGROUND: Antibody-drug conjugates (ADCs) have been the preferred regimens for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) after trastuzumab. Unfortunately, there is little data showing which ADCs should be chosen for those patients whose treatment with tyrosine kinase inhibitors (TKIs) failed. This study aims to analyze the efficacy and safety between novel anti-HER2 ADCs and trastuzumab emtansine (T-DM1) for those with TKIs failure. MATERIALS AND METHODS: HER2-positive MBC using ADCs from January 2013 to June 2022 were included, and all of them were treated with TKIs. The primary study endpoint was progression-free survival (PFS), and the secondary study endpoints were objective response rate (ORR), clinical benefit rate (CBR), and safety. RESULTS: A total of 144 patients with 73 patients in the novel anti-HER2 ADCs group and 71 patients in the T-DM1 group. In these novel ADCs, 30 patients received trastuzumab deruxtecan (T-Dxd), 43 patients receive other novel ADCs. The median PFS in the novel ADCs group and T-DM1 group were 7.0 months versus 4.0 months, respectively, and ORR was 54.8% versus 22.5%, CBR was 65.8% versus 47.9%, respectively. In subgroups analysis, the PFS were both significantly improved in patients receiving T-Dxd and other novel ADCs compared with T-DM1. The most common grades 3-4 adverse events in the novel anti-HER-2 ADCs group were neutropenia (20.5%) and thrombocytopenia (28.1%) in the T-DM1 group. CONCLUSIONS: In patients with HER2-positive MBC previously treated with TKIs, both T-Dxd and other novel anti-HER2 ADCs yielded statistically significant better PFS than T-DM1 did, with tolerable toxicities.

The expression of agmatinase manipulates the affective state of rats subjected to chronic restraint stress.

Agmatine is an endogenous polyamine produced from l-arginine and degraded by agmatinase (AGMAT). Studies in humans and animals have shown that agmatine has neuroprotective, anxiolytic, and antidepressant-like actions. However, little is known about the role of AGMAT in the action of agmatine or in the pathophysiology of psychiatric disorders. Therefore, this study aimed to investigate the role of AGMAT in the pathophysiology of MDD. In this study, we observed that AGMAT expression increased in the ventral hippocampus rather than in the medial prefrontal cortex in the chronic restraint stress (CRS) animal model of depression. Furthermore, we found that AGMAT overexpression in the ventral hippocampus elicited depressive- and anxiety-like behaviors, whereas knockdown of AGMAT exhibited antidepressant and anxiolytic effects in CRS animals. Field and whole-cell recordings of hippocampal CA1 revealed that AGMAT blockage increased Schaffer collateral-CA1 excitatory synaptic transmission, which was expressed both pre- and post-synaptically and was probably due to the inhibition of AGMAT-expressing local interneurons. Therefore, our results suggest that dysregulation of AGMAT is involved in the pathophysiology of depression and is a potential target for designing more effective antidepressants with fewer adverse effects to offer a better therapy for depression.

Efficacy and safety of pyrotinib and radiotherapy vs. pyrotinib-based therapy in patients with HER2+ breast cancer with brain metastasis: a retrospective cohort study.

Background: At present, local therapy, such as surgery and radiotherapy, is the mainstay treatment for brain metastasis and anti-human epidermal growth factor receptor type 2 (HER2)-targeted therapy has been shown to be efficacious for HER2+ breast cancer (BC) patients with brain metastasis. However, Clinical studies comparing the combined effects of the two treatments are lacking. This study sought to investigate the efficacy and safety of pyrotinib and radiotherapy versus pyrotinib-based therapy in treating HER2+ BC patients with brain metastasis. Methods: This retrospective, observational study collected data from 79 HER2+ BC patients with brain metastasis who received pyrotinib-based therapy from May 2018 to December 2021. Among these patients, 35 received pyrotinib-based therapy concurrently with, or within 3 months before or after, brain radiotherapy (Group A), and 44 received pyrotinib-based therapy as the primary regimen (with no restriction as to whether they had received brain radiotherapy previously or not, the interval between receiving radiotherapy and receiving pyrotinib was >3 months) (Group B). Patient information was collected by the Electronic Medical Records System. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The secondary endpoints were the objective response rate (ORR), the clinical benefit rate (CBR), and safety. The assessment of adverse effects was based on CTCAE5.0. Results: The intracranial ORRs were 48.6% in Group A and 20.5% (9/44) in Group B (P=0.015). The intracranial CBRs were 80.0% in Group A and 65.9% in Group B. The median intracranial PFS times (IC-PFS) were 15.0 months and 9.0 months in Group A and Group B, respectively (P=0.385). There was no statistically significant difference in OS between the 2 groups (95.0 vs. 98.0 months, P=0.872). The subgroup analysis showed that patients with active brain metastasis who received pyrotinib and radiotherapy had a longer IC-PFS time than those who received pyrotinib-based therapy(P=0.056). No serious adverse reactions (e.g., acute brain edema, cognitive dysfunction, or treatment-related death events) were observed. Conclusions: Pyrotinib combined with radiotherapy is recommended for HER2+ breast cancer active brain metastasis patients who can tolerate radiotherapy and pyrotinib. Pyrotinib-based therapy may be considered for patients who cannot tolerate radiotherapy and pyrotinib.

[Correlation analysis of lipid level and cognitive function in middle-aged and elderly diabetic population from 2 communities in Beijing in 2017].

OBJECTIVE: To investigate the relationship between serum lipid level and cognitive function in middle-aged and elderly patients with type 2 diabetes mellitus(T2 DM). METHODS: A cross-sectional study was implemented in 2017 to explore the correlation between lipid level and cognitive function in middle-aged and elderly diabetic patients. A random sample of 1526 middle-aged and elderly people were recruited from 2 communities in Beijing. Fasting blood samples were collected for blood lipid level detection, and the cognitive function of the subjects was assessed by the Montreal Cognitive Assessment Scale(MoCA). Logistic regression model was used to analyze the correlation between serum lipid levels and mild cognitive impairment(MCI) in elderly and T2 DM patients and control group. RESULTS: Compared with the control group, there were significant differences in blood lipid levels in T2 DM group. The levels of total cholesterol(TC) and high density lipoprotein cholesterol(HDL-C) in T2 DM group were lower than those in the control group, while triglyceride(TG) and low density lipoprotein cholesterol(LDL-C) were higher than those in the control group. Logistic regression analysis showed that high level of TC was a risk factor for MCI in patients with T2 DM, while high level of LDL-C was a protective factor, but no association was observed in the control population. CONCLUSION: Phenotype of T2 DM may affect the relationship between lipid level and cognitive function in middle-aged and elderly people.

Clinical outcomes of tucidinostat-based therapy after prior CDK4/6 inhibitor progression in hormone receptor-positive heavily pretreated metastatic breast cancer.

BACKGROUND: CDK4/6 inhibitors combined with endocrine therapy are standard first- or second-line treatment for patients with HR-positive and HER2-negative advanced breast cancer, however, there is currently no optimal recommendation for therapeutic strategies after progression on CDK4/6i. The aim of this study is to analyze the efficacy and safety of HDAC inhibitor Tucidinostat combined with endocrine therapy in patients after prior CDK4/6 inhibitor progression. METHODS: The pathological and clinical data of 44 HR-positive and HER2-negative breast cancer patients treated with tucidinostat after progression on CDK4/6i at the Breast Oncology Department of the Fifth Medical Center of the PLA General Hospital from July 2019 to October 2021 were retrospectively analyzed. Observation indexes included progression-free survival (PFS), overall survival (OS), clinical benefit rate (CBR), objective response rate (ORR) and adverse events. At the same time, we attempted to identify potential genomic predictors using available next-generation sequencing (NGS). RESULTS: A total of 44 patients were enrolled in this study. Median follow-up was 10 months (1-26 months) by the data cutoff date (February 2022). The CBR was 6.8% (3/44), the median PFS was 2.0 months (95% CI 1.9-2.1), and the median OS was 14 months (95% CI 6.3-21.7). The mPFS was 4.1 months (95%CI: 0-8.2) in patients with 1 metastatic site, and the mPFS was 4.5 months (95%CI: 4.2-4.8) in patients who received sequential tucidinostat after CDK4/6i failure. Multivariate analysis showed that patients with 1 metastatic site or sequential tucidinostat treatment after failure of CDK4/6i were more likely to benefit from tucidinostat combined with endocrine therapy. Preliminary data showed PIK3CA mutation may be associated with resistance of tucidinostat therapy. No grade 4 adverse events and no treatment-related deaths were recorded in the study. Dose reductions because of adverse events occurred in 4 (9.1%) patients. CONCLUSIONS: This study preliminarily shows that tucidinostat combined with endocrine therapy may be an optional sequential strategy for patients with HR+/HER2-advanced breast cancer that has progressed on CDK4/6 inhibitor, especially for these with lower tumor burden and fewer prior palliative treatment.

An exploratory study on the checkout rate of circulating tumor cells and the prediction of efficacy of neoadjuvant therapy and prognosis in patients with HER-2-positive early breast cancer.

Background: Neoadjuvant therapy is a standard treatment for patients with large, nonmetastatic breast cancer and may allow breast-conserving surgery after tumor downsizing while decreasing the risk of subsequent relapse. Dynamic changes of circulation tumor cells (CTCs) have a role in predicting treatment efficacy of breast cancer. However, the relationship between CTC enumeration before neoadjuvant therapy and pathologic complete response rate is still uncertain. Methods: The study was exploratory. A total of 50 breast cancer patients were enrolled in a phase II clinical study of neoadjuvant therapy for HER-2-positive early breast cancer. They were enrolled for blood draws before and after neoadjuvant therapy. We used two methods (CellSearch and TUMORFISH) to detect CTCs. We compared the sensitivity of the two systems and investigated the correlation of the enumeration on baseline CTCs with the diagnosis, prognosis, and efficacy of neoadjuvant therapy of the patients with HER-2-positive early breast cancer. We also explored the dynamic change of CTCs after neoadjuvant therapy. Results: The sensitivity of TUMORFISHER (27/50) method was significantly higher than that of the CellSearch system (15/50, p=0.008). The CTC numbers detected by the two detection systems were not significantly correlated with lymph node status, clinical stage, ki-67 level and hormone receptor status. Patients with ≥1 CTC before neoadjuvant therapy measured by the TUMORFISHER system had a significant high pCR rate (74.1% vs. 39.1%, p = 0.013); whereas, there was no predictive effect on pCR by CellSearch system (73.3% vs. 51.4%, p = 0.15). Patients with a decrease in CTCs enumeration after neoadjuvant therapy were more likely to achieve pCR than those with no change or increase in CTCs enumeration (87.5% vs 50.0%, p = 0.015) by the TUMORFISHER method. Unfortunately, there was no predictive value of CTCs enumeration for EFS before and after neoadjuvant therapy by two methods. Conclusions: Our study demonstrates that the new CTCs detection method TUMORFISHER system has a higher checkout rate in early breast cancer than the CellSearch system, and shows the opportunity of CTC enumeration as a novel assistant biomarker to predict the response of neoadjuvant therapy in patients with HER-2-positive early breast cancer.

Efficacy and safety of low-dose everolimus combined with endocrine drugs for patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer.

BACKGROUND: To analyze the efficacy and safety of everolimus 5 mg/day in combination with endocrine drugs in the treatment of hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer using real-world clinical data. METHODS: Clinical data of hormone receptor (HR)-positive and HER2-negative patients with advanced breast cancer treated with everolimus combined with endocrine drugs in our center between August 2012 and May 2017 were retrospectively analyzed. Curative effect and adverse reactions were evaluated. RESULTS: A total of 110 patients were enrolled in this study, and 87.3% received salvage chemotherapy. The median number of salvage treatment lines was 5 (range: 1-19). The median follow-up duration was 12 months (range: 1-56.3 months), the overall response rate (ORR) was 6.4%, the clinical benefit rate (CBR) was 31.8%, the median progression-free survival (mPFS) was 4.0 months (95% CI: 2.9-5.1 months), and the median overall survival (OS) was 17 months (95% CI: 12.1-21.9 months). The mPFS for patients who received ≤2 treatment line was 11.8 months (95% CI: 4.3-19.3 months). Univariate and multivariate analyses suggested that absence of liver metastases, secondary endocrine resistance, and number of metastasis sites <3 were the main factors influencing the benefit of everolimus combined with endocrine therapy. The most common adverse events of grade 3 were: stomatitis (5.5%), non-infectious pneumonia (1.8%), and erythra (1.8%). No grade 4 adverse reactions were observed. CONCLUSIONS: Our results showed that everolimus (5 mg/day) combined with endocrine therapy was effective and relatively safe for patients with hormone receptor-positive, HER2-negative metastatic breast cancer.

A Multipulse Radar Signal Recognition Approach via HRF-Net Deep Learning Models.

In the field of electronic countermeasure, the recognition of radar signals is extremely important. This paper uses GNU Radio and Universal Software Radio Peripherals to generate 10 classes of close-to-real multipulse radar signals, namely, Barker, Chaotic, EQFM, Frank, FSK, LFM, LOFM, OFDM, P1, and P2. In order to obtain the time-frequency image (TFI) of the multipulse radar signal, the signal is Choi-Williams distribution (CWD) transformed. Aiming at the features of the multipulse radar signal TFI, we designed a distinguishing feature fusion extraction module (DFFE) and proposed a new HRF-Net deep learning model based on this module. The model has relatively few parameters and calculations. The experiments were carried out at the signal-to-noise ratio (SNR) of -14 ∼ 4 dB. In the case of -6 dB, the recognition result of HRF-Net reached 99.583% and the recognition result of the network still reached 97.500% under -14 dB. Compared with other methods, HRF-Nets have relatively better generalization and robustness.

A Radar Signal Recognition Approach via IIF-Net Deep Learning Models.

In the increasingly complex electromagnetic environment of modern battlefields, how to quickly and accurately identify radar signals is a hotspot in the field of electronic countermeasures. In this paper, USRP N210, USRP-LW N210, and other general software radio peripherals are used to simulate the transmitting and receiving process of radar signals, and a total of 8 radar signals, namely, Barker, Frank, chaotic, P1, P2, P3, P4, and OFDM, are produced. The signal obtains time-frequency images (TFIs) through the Choi-Williams distribution function (CWD). According to the characteristics of the radar signal TFI, a global feature balance extraction module (GFBE) is designed. Then, a new IIF-Net convolutional neural network with fewer network parameters and less computation cost has been proposed. The signal-to-noise ratio (SNR) range is -10 to 6 dB in the experiments. The experiments show that when the SNR is higher than -2 dB, the signal recognition rate of IIF-Net is as high as 99.74%, and the signal recognition accuracy is still 92.36% when the SNR is -10 dB. Compared with other methods, IIF-Net has higher recognition rate and better robustness under low SNR.

Platform-independent approach for cancer detection from gene expression profiles of peripheral blood cells.

Peripheral blood gene expression intensity-based methods for distinguishing healthy individuals from cancer patients are limited by sensitivity to batch effects and data normalization and variability between expression profiling assays. To improve the robustness and precision of blood gene expression-based tumour detection, it is necessary to perform molecular diagnostic tests using a more stable approach. Taking breast cancer as an example, we propose a machine learning-based framework that distinguishes breast cancer patients from healthy subjects by pairwise rank transformation of gene expression intensity in each sample. We showed the diagnostic potential of the method by performing RNA-seq for 37 peripheral blood samples from breast cancer patients and by collecting RNA-seq data from healthy donors in Genotype-Tissue Expression project and microarray mRNA expression datasets in Gene Expression Omnibus. The framework was insensitive to experimental batch effects and data normalization, and it can be simultaneously applied to new sample prediction.

JS001, an anti-PD-1 mAb for advanced triple negative breast cancer patients after multi-line systemic therapy in a phase I trial.

BACKGROUND: Triple negative breast cancer (TNBC), as defined by ER, PR and HER2 negative expression in tumor, has limited treatment options beyond conventional chemotherapy. JS001, a humanized IgG4 antibody for PD-1, has demonstrated acceptable safety profile and preliminary anti-tumor activity in solid tumors. METHODS: This phase I open-label study is designed to evaluate the safety, tolerability, and antitumor activity of JS001 in advanced TNBC patients who are refractory to standard systemic therapy. The study has a 3+3 dose escalation design with planned cohorts at 1, 3, and 10 mg/kg Q2W followed by a dose expansion cohort at 3 mg/kg. (Clinical Trial ID: NCT02838823). RESULTS: From August 04, 2016 to October 26, 2017, 20 heavily-pretreated advanced TNBC patients were enrolled into three dose cohorts (6 in 1 mg/kg, 8 in 3 mg/kg and 6 in 10 mg/kg). As of August 30, 2018, no DLT was observed and no MTD was reached. No AEs were grade 4 or 5. The most common treatment related AEs were all grade 1/2. Treatment related grade 3 AEs (15%) included 1 hyponatremia, 1 rash and 1 bronchospasm (infusion related reaction). Among 20 evaluable subjects, the ORR was 5%. One patient in 10 mg/kg group obtained PR, who was PD-L1 strong positive (>50%) in tumor biopsy, with treatment duration of 12.8 months as of data cutoff. As of follow-up on July 15, 2019, the patient continued PR with treatment duration of 24 months and still ongoing. Six patients achieved SD, for a DCR of 35%. The median PFS of all subjects was 1.8 months (95% CI, 1.4 to 4.6). 45% subjects are PD-L1 positive (≥1% cutoff), among whom a 11.1% ORR and a 22.2% DCR were observed. CONCLUSIONS: JS001 exhibited a favorable safety profile in advanced TNBC patients who are refractory to multi-line systemic therapy. JS001 also showed a moderate response in these TNBC patients who had limited treatment options.