Adjuvant chemotherapy and survival in males aged 70 years or older with breast cancer: a population-based retrospective study.

BACKGROUND: Male breast cancer constitutes a minority of breast cancer diagnoses, yet its incidence has been on the rise in recent decades. However, elderly male breast cancer patients have been inadequately represented in clinical trials, posing challenges in treatment decisions. This study seeks to clarify the efficacy of chemotherapy in this demographic and identify the population most likely to benefit from such intervention. METHODS: We conducted a retrospective analysis using the Surveillance, Epidemiology, and End Results (SEER) database, encompassing a total of 1900 male breast cancer patients aged 70 years or older. Among them, 1652 were categorized in the no-chemotherapy group, while 248 were in the chemotherapy group. A multifactorial logistic regression model was employed to investigate the determinants influencing the administration of chemotherapy in elderly male breast cancer patients. Additionally, the multivariate Cox proportional hazards regression model was applied to identify factors associated with outcomes, with overall survival (OS) as the primary endpoint. RESULTS: Multivariate logistic regression analysis revealed that grade, tumor size, and nodal status were robust predictors for elderly male breast cancer patients receiving chemotherapy. Furthermore, the multivariate analysis demonstrated that chemotherapy conferred benefits compared to the no-chemotherapy group (HR = 0.822, 95% CI: 0.682-0.991, p = 0.040). Stratified analyses indicated that individuals with N+, poorly/undifferentiated grade, and stage II/III disease could derive benefits from chemotherapy. Upon further investigation of progesterone receptor (PR) positive patients, it was found that only stage III patients experienced significant benefits from chemotherapy (HR = 0.571, 95% CI: 0.372-0.875, p = 0.010). Conversely, in PR negative patients, both stage II (HR = 0.201, 95% CI: 0.051-0.792, p = 0.022) and stage III patients (HR = 0.242, 95% CI: 0.060-0.972, p = 0.046) derived benefits from chemotherapy. CONCLUSION: Adjuvant chemotherapy may benefit certain elderly male breast cancer patients, specifically those with positive lymph node status, poorly/undifferentiated grade, and PR-positive in stage III, as well as PR-negative expression in stage II/III. Given favorable physical tolerance, it is advisable not to hastily dismiss chemotherapy for these elderly male breast cancer patients.

Structural and functional changes of binocular corneal innervation and ocular surface function after unilateral SMILE and tPRK.

AIMS: To evaluate the bilateral changes in the sub-basal nerve plexus of the cornea and ocular surface function after unilateral small incision lenticule extraction (SMILE) and transepithelial photorefractive keratectomy (tPRK) procedures. METHODS: 34 patients were enrolled in the study and underwent unilateral SMILE (21 of 34 patients) or unilateral tPRK (13 of 34 patients). Complete ophthalmic examinations, tear film function tests and Cochet-Bonnet esthesiometry were conducted to assess the effects of the surgeries on the corneal nerves and tear function. Morphological changes were assessed using in vivo confocal microscopy to evaluate the corneal sub-basal nerve plexus and dendritic cells. ELISA was used to measure the tear neuromediators. Clinical and morphological data at each follow-up point were compared with preoperative baseline values. RESULTS: All patients who underwent unilateral SMILE or tPRK procedures exhibited bilateral corneal nerve degenerative changes, decreased corneal sensitivity, worsening of dry eye symptoms and changes in bilateral tear neuromediators. In the SMILE group, bilateral corneal sensitivity was positively correlated with corneal nerve fibre length and negatively correlated with dendritic cell area. The dry eye severity was negatively correlated with corneal sensitivity. Tear levels of substance P and nerve growth factor were positively correlated with mean dendritic cell area and dry eye severity, but negatively correlated with corneal sensitivity. In the tPRK group, bilateral corneal sensitivity was positively correlated with corneal nerve fibre density. CONCLUSIONS: Unilateral refractive surgery may bilaterally affect the morphology and function of corneal nerves and ocular surface status postoperatively.

Therapeutic effect and mechanism of action of pterostilbene nano drugs in dry eye models.

Dry eye disease is a multifactorial dysfunction of the tear film and ocular surface, with etiology involving inflammation and oxidative stress on the ocular surface. Pterostilbene (PS) is a secondary metabolite extracted from plants, which possesses remarkable anti-inflammatory and antioxidant effects. However, its application is limited by light instability and very poor water solubility. We modified fat-soluble PS into a biparental pterostilbene-glutaric anhydride-arginine-glycine-aspartic acid (PS-GA-RGD) nanomedicine by prodrug ligation of functional peptides. The aim of this study was to explore the protective effect and potential mechanism of PS-GA-RGD on dry eye disease in vitro and in vivo. We demonstrated good long-term biocompatibility of PS-GA-RGD through rabbit eye stimulation test. Lipopolysaccharide (LPS) was used to induce murine macrophages RAW 264.7 to establish an inflammation and oxidative stress model. In this model, PS-GA-RGD effectively reduced the production of ROS and 8-OHdG, enhancing the expression of antioxidant factor Nrf2 and antioxidant enzyme heme oxygenase-1. In addition, the expression of NF-κB inflammatory pathway significantly increased in LPS-induced RAW 264.7 cells, while PS-GA-RGD could significantly reduce this pathway. Hypertonic saline was utilized to establish a hypertonic model of human corneal epithelial cells. PS-GA-RGD was found to significantly reduce the production of ROS and NLRP3 inflammasomes in this model, exhibiting superior efficacy compared to PS. Experimental dry eye animal models were co-induced with subcutaneous injection of scopolamine and an intelligently controlled environmental system. We demonstrated that PS-GA-RGD nano drugs can prevent and reduce corneal epithelial cell defects and apoptosis, protect conjunctival goblet cells, and have an excellent anti-inflammatory effect. Finally, we demonstrated that RGD sequence in PS-GA-RGD can enhance cellular uptake, corneal retention, and penetration, thereby increasing their bioavailability and efficacy by a cell uptake assay and rabbit corneal drug retention experiment. Overall, this study highlights the potential of PS-GA-RGD nanomedicines in the treatment of dry eyes.

The Numerical and Experimental Investigation of Piezoresistive Performance of Carbon Nanotube/Carbon Black/Polyvinylidene Fluoride Composite.

The composites with multiple types of nano-carbon fillers have better electrical conductivity and piezoresistive properties as compared with composites with a single type of nano-carbon fillers. As previously reported, the nano-carbon fillers with various aspect ratios, such as carbon nanotube (CNT) and carbon black (CB), have synergistic enhanced effects on the piezoresistive performance of composite sensors. However, most of the works that have been reported are experimental investigations. The efficient and usable numerical simulation investigation needs to be further developed. In this study, based on an integrated 3D statistical resistor network model, a numerical simulation model was created to calculate the piezoresistive behavior of the CNT/CB/ Polyvinylidene Fluoride (PVDF) composite. This model also takes into account the tunneling effect between nearby nano-fillers. It is found from numerical simulation results that the piezoresistive sensitivity of composite simulation cells can be influenced by the fraction of CNT and CB. In the case that the CNT content is 0.073 wt.%, the best force-electrical piezoresistive sensitivity can be achieved when the CB loading is up to 0.2 wt.%. To verify the validity of the simulation model, the previous experimental investigation results are also compared. The experimental results confirm the validity of the model. The investigation is valuable and can be utilized to design a strain sensor for this nano-composite with increased sensitivity.

Tyrosine kinase inhibitors in HER2-positive breast cancer brain metastases: A systematic review and meta-analysis.

BACKGROUND: Small tyrosine kinase inhibitors (TKIs) show activity against breast cancer brain metastases (BCBM) of the human epidermal growth factor receptor 2 (HER2)-positive subtype. This meta-analysis aimed to objectively explore the efficacy and safety of TKIs. METHODS: Electronic databases were searched for relevant clinical trials. We conducted a pairwise meta-analysis, pooled analysis, and estimated summary survival curves to compare survival outcomes following TKIs therapy for BCBM patients using Stata version 16.0 or R x64 4.0.5. RESULTS: Thirteen clinical trials involving 987 HER2-positive BCBM patients were analyzed. A trend of longer progression-free survival (PFS) was observed in the TKI-containing arm compared to the non-TKI-containing arm (hazard ratio = 0.64, 95% confidence interval [CI]: 0.35-1.15, p = 0.132), although the difference is not statistically significant. Summary survival curves reported the summary median PFS and overall survival were 7.9 months and 12.3 months. Subgroup analysis revealed that TKIs combined with capecitabine (TKI + Cap) regimens resulted in improved survival outcomes. Tucatinib may be more effective in BCBM patients. The main grade 3-5 adverse events (AEs) were diarrhea (22%, 95% CI: 14%-32%), neutropenia (11%, 95% CI: 5%-18%), hepatic toxicity (7%, 95% CI: 1%-16%), and sensory neuropathy (6%, 95% CI: 2%-12%). CONCLUSION: TKIs therapy improved the survival outcomes of HER2-positive BCBM patients, especially when combined with capecitabine and tolerable AEs. We also identified the clinical value of tucatinib, which appears to be the most favorable TKI drug for BCBM patients.

Epidemiology and a Predictive Model of Prognosis Index Based on Machine Learning in Primary Breast Lymphoma: Population-Based Study.

BACKGROUND: Primary breast lymphoma (PBL) is a rare disease whose epidemiological features, treatment principles, and factors used for the patients' prognosis remain controversial. OBJECTIVE: The aim of this study was to explore the epidemiology of PBL and to develop a better model based on machine learning to predict the prognosis for patients with primary breast lymphoma. METHODS: The annual incidence of PBL was extracted from the surveillance, epidemiology, and end results database between 1975 and 2019 to examine disease occurrence trends using Joinpoint software (version 4.9; National Cancer Institute). We enrolled data from 1251 female patients with primary breast lymphoma from the surveillance, epidemiology, and end results database for survival analysis. Univariable and multivariable analyses were performed to explore independent prognostic factors for overall survival and disease-specific survival of patients with primary breast lymphoma. Eight machine learning algorithms were developed to predict the 5-year survival of patients with primary breast lymphoma. RESULTS: The overall incidence of PBL increased drastically between 1975 and 2004, followed by a significant downward trend in incidence around 2004, with an average annual percent change (AAPC) of -0.8 (95% CI -1.1 to -0.6). Disparities in trends of PBL exist by age and race. The AAPC of the 65 years or older cohort was about 1.2 higher than that for the younger than 65 years cohort. The AAPC of White patients is 0.9 (95% CI 0.0-1.8), while that of Black patients was significantly higher at 2.1 (95% CI -2.5 to 6.9). We also identified that the risk of death from PBL is multifactorial and includes patient factors and treatment factors. Survival analysis revealed that the patients diagnosed between 2007 and 2015 had a significant risk reduction of mortality compared to those diagnosed between 1983 and 1990. The gradient booster model outperforms other models, with 0.752 for sensitivity and 0.817 for area under the curve. The important features established with the gradient booster model were the year of diagnosis, age, histologic type, and primary site, which were the 4 most relevant variables to explain 5-year survival status. CONCLUSIONS: The incidence of PBL started demonstrating a tendency to decrease after 2004, which varied by age and race. In recent years, the prognosis of patients with primary breast lymphoma has been remarkably improved. The gradient booster model had a promising performance. This model can help clinicians identify the early prognosis of patients with primary breast lymphoma and therefore improve the clinical outcome by changing management strategies and patient health care.

Anti-inflammatory and antioxidative effects of gallic acid on experimental dry eye: in vitro and in vivo studies.

BACKGROUND: To investigate the anti-inflammatory and antioxidative effects of gallic acid (GA) on human corneal epithelial cells (HCECs) and RAW264.7 macrophages as well as its therapeutic effects in an experimental dry eye (EDE) mouse model. METHODS: A cell counting kit-8 (CCK-8) assay was used to test the cytotoxicity of GA. The effect of GA on cell migration was evaluated using a scratch wound healing assay. The anti-inflammatory and antioxidative effects of GA in vitro were tested using a hypertonic model (HCECs) and an inflammatory model (RAW264.7 cells). The in vivo biocompatibility of GA was detected by irritation tests in rabbits, whereas the preventive and therapeutic effect of GA in vivo was evaluated using a mouse model of EDE. RESULTS: In the range of 0-100 µM, GA showed no cytotoxicity in RAW264.7 cells or HCECs and did not delay the HCECs monolayer wound healing within 24 h. Ocular tolerance to GA in the in vivo irritation test was good after seven days. In terms of antioxidative activity, GA significantly reduced the intracellular reactive oxygen species (ROS) in lipopolysaccharide (LPS) activated RAW264.7 macrophages and HCECs exposed to hyperosmotic stress. Furthermore, after pre-treatment with GA, the expression levels of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NADPH quinone oxidoreductase-1 (NQO-1) were significantly upregulated in RAW264.7 macrophages. GA also exhibits excellent anti-inflammatory properties. This is mainly demonstrated by the ability of GA to effectively downregulate the nuclear transcription factor-κB (NF-κB) pathway in LPS-activated RAW264.7 macrophages and to reduce inflammatory factors, such as nitric oxide (NO), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α). In vivo efficacy testing results in a mouse model of EDE showed that GA can effectively prevent and inhibit the apoptosis of corneal epithelial cells (CECs), reduce inflammatory factors in the cornea and conjunctiva as well as protect goblet cells. CONCLUSION: In vitro and in vivo results indicate that GA possesses potent anti-inflammatory and antioxidative properties with no apparent cytotoxicity within the range of 0-100 µM. It is a promising eye drop formulation for the effective prevention and treatment of dry eye disease (DED).

The impact of chemotherapy and survival prediction by machine learning in early Elderly Triple Negative Breast Cancer (eTNBC): a population based study from the SEER database.

PURPOSE: We aimed to analysis the impact of chemotherapy and establish prediction models of prognosis in early elderly triple negative breast cancer (eTNBC) by using machine learning. METHODS: We enrolled 4,696 patients in SEER Database who were 70 years or older, diagnosed with primary early TNBC(larger than 5 mm), from 2010 to 2016. The propensity-score matched method was utilized to reduce covariable imbalance. Univariable and multivariable analyses were used to compare breast cancer-specific survival(BCSS) and overall survival(OS). Nine models were developed by machine learning to predict the 5-year OS and BCSS for patients received chemotherapy. RESULTS: Compared to matched patients in no-chemotherapy group, multivariate analysis showed a better survival in chemotherapy group. Stratified analyses by stage demonstrated that patients with stage II and stage III other than stage I could benefit from chemotherapy. Further investigation in stage II found that chemotherapy was a better prognostic indicator for patients with T2N0M0 and stage IIb, but not in T1N1M0. Patients with grade III could achieve a better survival by receiving chemotherapy, but those with grade I and II couldn't. With 0.75 in 5-year BCSS and 0.81 in 5-year OS for AUC, the LightGBM outperformed other algorithms. CONCLUSION: For early eTNBC patients with stage I, T1N1M0 and grade I-II, chemotherapy couldn't improve survival. Therefore, de-escalation therapy might be appropriate for selected patients. The LightGBM is a trustful model to predict the survival and provide precious systemic treatment for patients received chemotherapy.

Graphene/Graphitized Polydopamine/Carbon Nanotube All-Carbon Ternary Composite Films with Improved Mechanical Properties and Through-Plane Thermal Conductivity.

Graphene films (GFs) are promising ultrathin thermally conductive materials for portable electronic devices because of their excellent thermally conductive property, light weight, high flexibility, and low cost. However, the application of GFs is limited due to their poor mechanical properties and through-plane thermal conductivity. Here, a graphene-(graphitized polydopamine)-(carbon nanotube) (G-gPDA-CNT) all-carbon ternary composite film was fabricated by chemical reduction, carbonization, graphitization, and mechanical compaction of the evaporation-assembled (graphene oxide)-PDA@CNT film. The G-gPDA-CNT film exhibited a uniform all-carbon composite structure in which the components of the graphene, gPDA layers, and CNTs were cross-linked by strong covalent bonds. This unique structure promoted the load transfer and energy dissipation between the components by which the mechanical properties of the G-gPDA-CNT film were substantially improved. Furthermore, electron and phonon transfers were also promoted, greatly improving the electrical and thermal conductivities, especially the through-plane thermal conductivity of the G-gPDA-CNT film. The G-gPDA-CNT film showed a tensile strength of 67.5 MPa, 15.1% ultimate tensile strain, toughness of 6.07 MJ/m3, electrical conductivity of 6.7 × 105 S·m-1, in-plane thermal conductivity of 1597 W·m-1·K-1, and through-plane thermal conductivity of 2.65 W·m-1·K-1, which were 2.24, 1.44, 3.16, 1.46, 1.15, and 3.90 times that of the pure GFs, respectively.

Different Clinicopathological Characteristics and Prognostic Factors for Occult and Non-occult Breast Cancer: Analysis of the SEER Database.

Purpose: The aim of our study was to evaluate the different clinicopathological characteristics and prognostic factors for occult and non-occult breast cancer. Methods: 572 OBC cases and 117,217 non-OBC patients between 2004 and 2015 was selected from Surveillance, Epidemiology, and End Results (SEER) database. We analyzed the clinicopathological characteristics and survival outcomes between OBC and non-OBC patients. Furthermore, the propensity score matching method was utilized to reduce the influences of baseline differences in demographic and clinical characteristics on outcome differences. Univariable and multivariable analyses were used to evaluate the prognostic factors of OBC patients. Results: Compared with non-OBC patients, OBC patients in this study presented a higher proportion of older age, American Joint Committee on Cancer (AJCC) N3 stage, estrogen receptor (ER)-negative status, progesterone receptor (PR)-negative status, and human epidermal growth factor receptor-2 (HER-2)-positive status, and underwent more chemotherapy. Multivariate analysis revealed a better survival in overall patients with OBC patients according to breast cancer-specific survival (BCSS) and overall survival (OS). Propensity score analysis also achieved a similar result for OBC patients. Stratified analyses by nodal status and molecular subtypes indicated that these survival advantage were mainly presented in patients with AJCC N2/N3 stage or hormone receptor (HR)-positive tumors. In addition, nodal status, HER-2 status, and radiation status were demonstrated to be three independent prognostic factors for OBC patients. Conclusion: Patients with OBC retained exclusive clinical characteristics and were shown to have a better outcome compared with non-OBC patients, especially for those with N2/N3 stage or HR-positive tumors.

Synergistic Delamination Toughening of Glass Fiber-Aluminum Laminates by Surface Treatment and Graphene Oxide Interleaf.

The synergistic effects of surface treatment and interleaf on the interlaminar mechanical properties of glass fiber-aluminum laminates were studied. Aluminum sheets were treated with alkaline etching. Meanwhile, a graphene oxide (GO) interleaf was introduced between the aluminum sheet and the glass fiber-reinforced epoxy composite. Double cantilever beam and end-notched flexure tests were employed to evaluate the interlaminar fracture toughness of the glass fiber-aluminum laminates. The obtained results show that the toughening efficiency of the interleaf is dependent on the aluminum surface characteristics as well as the GO loading. Further comparison reveals that the highest mode-I and mode-II fracture toughnesses are obtained in the specimens with alkali etching treatment and addition of GO interleaf with 0.5 wt% of GO loading, which are 510% and 381% higher in comparison to the plain specimen. Fracture surfaces were observed to further uncover the reinforcement mechanisms.

Impact of breast surgery on survival of patients with stage IV breast cancer: a SEER population-based propensity score matching analysis.

BACKGROUND: Breast surgery for stage IV breast cancer remains controversial. The aim of this study was to investigate the impact of breast surgery on survival of stage IV breast cancer patients based on the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. METHODS: In total, 13,034 patients were selected and divided into surgery and non-surgery groups. Univariate and multivariable analyses were conducted to determine factors related to survival. Propensity score matching method was utilized to achieve balanced covariates across different groups. One-to-one (1:1) PSM was conducted to construct a matched sample consisting of pairs of surgery and non-surgery subjects. Breast cancer-specific survival (BCSS) and overall survival (OS) of the two groups were assessed by Kaplan-Meier plots and Cox proportional hazard regression models. Stratified analysis according to different variables was also performed. RESULTS: Patients treated with breast surgery were more likely to be younger, smaller tumor size, more advanced nodal status, higher histology grade and higher proportion of bone-only metastasis. Those who received chemotherapy and radiotherapy also tended to be treated with surgery. After adjustment for potential confounders, breast surgery group exhibited a better survival both in BCSS (HR = 0.557, 95% CI [0.523-0.594], p < 0.001) and OS (HR = 0.571, 95% CI [0.537-0.607], p < 0.001). After propensity score matching, the surgery and non-surgery group consisted of 2,269 patients respectively. The median survival time was 43 months for the surgery group and 27 months for the non-surgery group. Kaplan-Meier curves indicated that breast surgery could clearly improve both the BCSS and OS for patients with stage IV breast cancer. On multivariate analysis, surgery group was associated with a better survival compared with the non-surgery group (BCSS: HR = 0.542, 95% CI [0.499-0.589], p < 0.001; OS: HR = 0.555, 95% CI [0.512-0.601], p < 0.001). Furthermore, this survival advantage persisted in all subgroups irrespective of age, race, tumor size, nodal status, histology grade, molecular subtype, chemotherapy status, radiotherapy status or status of distant metastasis. CONCLUSION: Our study provided additional evidence that patients with stage IV breast cancer could benefit from breast surgery and it might play a more important role in multimodality therapy.