Automated Deep Learning Empowered Breast Cancer Diagnosis Using Biomedical Mammogram Images

Biomedical image processing is a hot research topic which helps to majorly assist the disease diagnostic process. At the same time, breast cancer becomes the deadliest disease among women and can be detected by the use of different imaging techniques. Digital mammograms can be used for the earlier identification and diagnostic of breast cancer to minimize the death rate. But the proper identification of breast cancer has mainly relied on the mammography findings and results to increased false positives. For resolving the issues of false positives of breast cancer diagnosis, this paper presents an automated deep learning based breast cancer diagnosis (ADL-BCD) model using digital mammograms. The goal of the ADL-BCD technique is to properly detect the existence of breast lesions using digital mammograms. The proposed model involves Gaussian filter based pre-processing and Tsallis entropy based image segmentation. In addition, Deep Convolutional Neural Network based Residual Network (ResNet 34) is applied for feature extraction purposes. Specifically, a hyper parameter tuning process using chimp optimization algorithm (COA) is applied to tune the parameters involved in ResNet 34 model. The wavelet neural network (WNN) is used for the classification of digital mammograms for the detection of breast cancer. The ADL-BCD method is evaluated using a benchmark dataset and the results are analyzed under several performance measures. The simulation outcome indicated that the ADL-BCD model outperforms the state of art methods in terms of different measures.     

Fractured fare

id you ever notice how half-eaten food often takes on an appearance similar to that of certain engineering alloys? Maybe not, unless you happen to be a failure analyst whose eyes have been trained to look for certain fractographic and metallographic characteristics as a result of extensive time on the job. Nonetheless, these features are encountered daily, in foods ranging from fruit to candy. The next time you are dining, take a moment for a closer look at your food, and see if you can detect a feature comparable to that of a broken metal, plastic, or glass component.     

Fourier transform infrared attenuated total reflection analysis of human hair: comparison of hair from breast cancer patients with hair from healthy subjects

A comparative study of Fourier transform infrared attenuated total reflection (FTIR-ATR) spectra of 32 scalp and pubic hair samples from individuals diagnosed with breast cancer and those who were negative for breast cancer showed increases in the beta-sheet/disorder structures (relative to alpha-helix structures) and C-H lipid content of hair from breast cancer patients. Thus, the presence of breast cancer appears to alter the hair growth process, resulting in changes in the composition and conformation of cell membrane and matrix materials of hair fiber. These appear to be consistent with the changes observed in X-ray diffraction patterns for hair from breast cancer patients. A blind study of 12 additional hair samples using these FTIR-ATR spectral differences as markers correctly identified all four hair samples from cancer patients (100%). Two of these samples were from breast cancer patients. Of the remaining two samples analyzing positive for cancer, one was from a prostate cancer patient and one from a lung cancer patient. Thus, it appears that the mechanism that alters hair fiber synthesis in the three types of cancer may be similar. The blind study incorrectly identified as positive for cancer three hair samples from two apparently healthy individuals and one patient considered cured from prostate cancer.     

How to spot a fake

Think back to the last time you visited an art gallery or museum. As you wandered through the halls and peered at the various paintings and artifacts, did you ever question the information provided on the labels or in the guidebook? Did you wonder whether that Titian really is a Titian and not a fake? Did you question whether that vase had been correctly attributed to the Ming dynasty?According to Richard Newman, head of scientific research at the Museum of Fine Arts, Boston, every museum contains artifacts that are not what they appear to be. “There are a lot of objects on display at the moment whose attributions are a little bit shaky,” he says. “There are some about which there are serious questions of authenticity and there are others we think are genuine but actually might be fakes.” Materials characterization techniques are central to identifying these fakes and to answering many other questions that the museum's curators may have about artifacts.     

Biodegradable Microalgae‐Based Carriers for Targeted Delivery and Imaging‐Guided Therapy toward Lung Metastasis of Breast Cancer

High delivery efficiency, prolonged drug release, and low systemic toxicity are effective weapons for drug delivery systems to win the battle against metastatic breast cancer. Herein, it is shown that Spirulina platensis (S. platensis) can be used as natural carriers to construct a drug‐loaded system for targeted delivery and fluorescence imaging‐guided chemotherapy on lung metastasis of breast cancer. The chemotherapeutic doxorubicin (DOX) is loaded into S. platensis (SP) via only one facile step to fabricate the DOX‐loaded SP (SP@DOX), which exhibits ultrahigh drug loading efficiency and PH‐responsive drug sustained release. The rich chlorophyll endows SP@DOX excellent fluorescence imaging capability for noninvasive tracking and real‐time monitoring in vivo. Moreover, the micrometer‐sized and spiral‐shaped SP carriers enable the as‐prepared SP@DOX to passively target the lungs and result in a significantly enhanced therapeutic efficacy on lung metastasis of 4T1 breast cancer. Finally, the undelivered carriers can be biodegraded through renal clearance without notable toxicity. The SP@DOX described here presents a novel biohybrid strategy for targeted drug delivery and effective treatment on cancer metastasis.     

乳腺癌彩色多普勒超声的诊断价值

目的:分析彩色多普勒超声诊断乳腺癌的价值。方法:选择2012年2月至2020年2月期间乳腺癌患者40例作为研究对象,采用随机数字表法将其均分为两组,各20例,分别为对照组和观察组。其中对照组采用常规乳腺癌检测方法,观察组则采用彩色多普勒超声检测方法。观察两组患者检测乳腺癌的准确率。结果:经过检测,观察组检测乳腺癌的准确率明显优于对照组,两组数据差异具有统计学意义(P<0.05)。结论:对乳腺癌患者使用彩色多普勒超声检查可提高临床诊断正确率,建议在临床上推广。     

Cuproptosis-Inducible Chemotherapeutic/Cascade Catalytic Reactor System for Combating with Breast Cancer

Cascade hydroxyl radical generating hydrogel reactor structures including a chemotherapeutic agent are invented for multiple treatment of breast cancer. Glucose oxidase (GOx) and cupric sulfate (Cu) are introduced for transforming accumulated glucose (in cancer cells) to hydroxyl radicals for starvation/chemodynamic therapy. Cu may also suppress cancer cell growth via cuproptosis-mediated cell death. Berberine hydrochloride (BER) is engaged as a chemotherapeutic agent in the hydrogel reactor for combining with starvation/chemodynamic/cuproptosis therapeutic modalities. Moreover, Cu is participated as a gel crosslinker by coordinating with catechol groups in hyaluronic acid-dopamine (HD) polymer. Controlling viscoelasticity of hydrogel reactor can extend the retention time following local injection and provide sustained drug release patterns. Low biodegradation rate of designed HD/BER/GOx/Cu hydrogel can reduce dosing frequency in local cancer therapy and avoid invasiveness-related inconveniences. Especially, it is anticipated that HD/BER/GOx/Cu hydrogel system can be applied for reducing size of breast cancer prior to surgery as well as tumor growth suppression in clinical application.     

Early Certainty in patent cases involving by opposition proceedings

To obtain certainty about the validity and enforceability of a patent one has to go to court for a ruling. It is very important for patent owners and for their competitors to make decisions on product development based upon assumptions about the validity and enforceability of patents before it reaches court. If you are in court after developing a product then something went wrong in that process. An opposition at the EPO seems to be a good idea to test the arguments of invalidity, if you are a third party worried about the scope of the patent. If an opposition is filed against a patent then the time taken until a final decision gives additional uncertainty about the scope of patent protection and may diversely affect what you may or may not do in any national proceedings. The additional time period of uncertainty caused by EPO opposition procedures is explored in this study and compared with the expected time for nullity actions at a national court, exemplified for the German patent court.     

Paclitaxel-loaded hollow-poly(4-vinylpyridine) nanoparticles enhance drug chemotherapeutic efficacy in lung and breast cancer cell lines

Paclitaxel (PTX),one of the most effective cytotoxins for the treatment of breast and lung cancer,is limited by its severe side effects and low tumor selectivity.In this work,hollow-poly(4-vinylpyridine) (hollow-p4VP) nanoparticles (NPs) have been used for the first time to generate PTX@p4VP NPs,employing a novel technique in which a gold core in the center of the NP is further oxidized to produce the hollow structure into which PTX molecules can be incorporated.The hollow-p4VP NPs exhibit good physicochemical properties and displayed excellent biocompatibility when tested on blood (no hemolysis) and cell cultures (no cytotoxicity).Interestingly,PTX@p4VP NPs significantly increased PTX cytotoxicity in human lung (A-549) and breast (MCF-7) cancer cells with a significant reduction of PTX IC50 (from 5.9 to 3.6 nM in A-549 and from 13.75 to 4.71 nM in MCF-7).In addition,PTX@p4VP caused a decrease in volume of A-549 and MCF-7 multicellular tumor spheroids (MTS),an in vitro system that mimics in vivo tumors,in comparison to free PTX.This increased antitumoral activity is accompanied by efficient cell internalization and increased apoptosis,especially in lung cancer MTS.Our results offer the first evidence that hollowp4VP NPs can improve the antitumoral activity of PTX.This system can be used as a new nanoplatform to overcome the limitations of current breast and lung cancer treatments.     

LHRH-functionalized superparamagnetic iron oxide nanoparticles for breast cancer targeting and contrast enhancement in MRI

This paper shows that superparamagnetic iron oxide nanoparticles (SPIONs) conjugated to luteinizing hormone releasing hormone (LHRH) (LHRH–SPIONs), can be used to target breast cancer cells. They also act as contrast enhancement agents during the magnetic resonance imaging of breast cancer xenografts. A combination of transmission electron microscopy (TEM) and spectrophotometric analysis was used in our experiments, to investigate the specific accumulation of the functionalized superparamagnetic iron oxide nanoparticles (SPIONs) in cancer cells. The contrast enhancement of conventional T2 images obtained from the tumor tissue and of breast cancer xenograft bearing mice is shown to be much greater than that in saline controls, when the tissues were injected with LHRH–SPIONs. Magnetic anisotropy multi-CRAZED images of tissues extracted from mice injected with SPIONs were also found to have enhanced MRI contrast in breast cancer xenografts and metastases in the lungs.     

A New Optimized Wrapper Gene Selection Method for Breast Cancer Prediction

Machine-learning algorithms have been widely used in breast cancer diagnosis to help pathologists and physicians in the decision-making process. However, the high dimensionality of genetic data makes the classification process a challenging task. In this paper, we propose a new optimized wrapper gene selection method that is based on a nature-inspired algorithm (simulated annealing (SA)), which will help select the most informative genes for breast cancer prediction. These optimal genes will then be used to train the classifier to improve its accuracy and efficiency. Three supervised machine-learning algorithms, namely, the support vector machine, the decision tree, and the random forest were used to create the classifier models that will help to predict breast cancer. Two different experiments were conducted using three datasets: Gene expression (GE), deoxyribonucleic acid (DNA) methylation, and a combination of the two. Six measures were used to evaluate the performance of the proposed algorithm, which include the following: Accuracy, precision, recall, specificity, area under the curve (AUC), and execution time. The effectiveness of the proposed classifiers was evaluated through comprehensive experiments. The results demonstrated that our approach outperformed the conventional classifiers as expected in terms of accuracy and execution time. High accuracy values of 99.77%, 99.45%, and 99.45% have been achieved by SA-SVM for GE, DNA methylation, and the combined datasets, respectively. The execution time of the proposed approach was significantly reduced, in comparison to that of the traditional classifiers and the best execution time has been reached by SA-SVM, which was 0.02, 0.03, and 0.02 on GE, DNA methylation, and the combined datasets respectively. In regard to precision and specificity, SA-RF obtained the best result of 100 on GE dataset. While SA-SVM attained the best recall result of 100 on GE dataset.     

Full surface embedding of gold clusters on silicon nanowires for efficient capture and photothermal therapy of circulating tumor cells

We report on rapid thermal chemical vapor deposition growth of silicon nanowires (Si NWs) that contain a high density of gold nanoclusters (Au NCs) with a uniform coverage over the entire length of the nanowire sidewalls. The Au NC-coated Si NWs with an antibody-coated surface obtain the unique capability to capture breast cancer cells at twice the highest efficiency currently achievable (~88% at 40 min cell incubation time) from a nanostructured substrate. We also found that irradiation of breast cancer cells captured on Au NC-coated Si NWs with a near-infrared light resulted in a high mortality rate of these cancer cells, raising a fine prospect for simultaneous capture and plasmonic photothermal therapy for circulating tumor cells.     

Gold nano-popcorn attached SWCNT hybrid nanomaterial for targeted diagnosis and photothermal therapy of human breast cancer cells

Breast cancer presents greatest challenge in health care in today's world. The key to ultimately successful treatment of breast cancer disease is an early and accurate diagnosis. Current breast cancer treatments are often associated with severe side effects. Driven by the need, we report the design of novel hybrid nanomaterial using gold nano popcorn-attached single wall carbon nanotube for targeted diagnosis and selective photothermal treatment. Targeted SK-BR-3 human breast cancer cell sensing have been performed in 10 cancer cells/mL level, using surface enhanced Raman scattering of single walls carbon nanotube's D and G bands. Our data show that S6 aptamer attached hybrid nanomaterial based SERS assay is highly sensitive to targeted human breast cancer SK-BR-3 cell line and it will be able to distinguish it from other non targeted MDA-MB breast cancer cell line and HaCaT normal skin cell line. Our results also show that 10 min of photothermal therapy treatment by 1.5 W/cm(2) power, 785 nm laser is enough to kill cancer cells very effectively using S6 aptamer attached hybrid nanomaterials. Possible mechanisms for targeted sensing and operating principle for highly efficient photothermal therapy have been discussed. Our experimental results reported here open up a new possibility for using aptamers modified hybrid nanomaterial for reliable diagnosis and targeted therapy of cancer cell lines quickly.     

Epidermal growth factor-ferritin h-chain protein nanoparticles for tumor active targeting

Human ferritin H-chain protein (FTH1)-based nanoparticles possess a precisely assembled nanometer-scale structure and high safety. However, their applications for imaging and drug delivery towards cancer cells remain limited due to a lack of target specificity. Epidermal growth factor receptor (EGFR) is overexpressed in many malignant tissues including breast cancer, and has been used as a therapeutic target for cancer treatment. Herein, a genetic method is shown to generate EGF-FTH1 chimeric proteins. EGF-FTH1 nanoparticles with EGF on the surface are then produced. The data demonstrate that EGF-FTH1 nanoparticles, with a small size (11.8 ± 1.8 nm), narrow size distribution, and high biosafety, can specifically bind to and then be taken up by breast cancer MCF-7 cells and MDA-MB-231 cells, but not normal breast epithelial MCF-10A cells. In contrast, binding and absorption of nontargeted ferritin-based nanoparticles to breast cancer cells are negligible. In vivo studies show that EGF-FTH1 nanoparticles are accumulated in breast tumors in a mouse xenograft model. Interestingly, the concentration of EGF-FTH1 nanoparticles in the tumor site is significantly reduced when mice are pretreated with an excess of free EGF. These results imply that EGF-EGFR interaction plays an important role in regulating the tumor retention of EGF-FTH1 nanoparticles.     

Surface chemistry of carbon nanoparticles functionally select their uptake in various stages of cancer cells

Relationship of the surface physicochemical characteristics of nanoparticles with their interactions with biological entities may provide critical information for nanomedicinal application.Here,we report the systematic synthesis of sub-50 nm carbon nanoparticles (CNP) presenting neutral,anionic,and cationic surface functionalities.A subset of CNPs with ～10,20,and 40 nm hydrodynamic sizes were synthesized with neutral surface headgroups.For the first time,the cellular internalization of these CNPs was systematically quantified in various stages of breast cancer cells (early,late,and metastatic),thereby providing a parametric assessment of charge and size effects.Distinct activities were observed when these systems interacted with cancer cells in various stages.Our results indicated that metastatic breast cancer could be targeted by a nanosystem presenting anionic phosphate groups.On the contrary,for patients in late stage of cancer,drugs could be delivered with sulfonate functionalized carbon nanoparticles,which have higher probability of intracellular transport.This study will facilitate the better understanding of nanoparticle-biological entity interaction,and the integration of this knowledge with pathophysiology would promote the engineering of nanomedicine with superior likelihoods of crossing the endocytic "barrier" for drug delivery inside cancerous cells.     

Use of glycan targeting antibodies to identify cancer-associated glycoproteins in plasma of breast cancer patients

Immunoaffinity chromatography (IAC) was used to isolate and identify potential cancer biomarker glycoproteins by targeting disease-associated glycans. Glycoproteins were selected from plasma of disease-free and breast cancer patients with an anti-Lewis x (Le(x)) IAC column. After extensive washing of the IAC column to remove abundant proteins, the selected proteins were eluted with an acidic mobile phase and identified in two ways. The protocol used in route A involved the steps of tryptic digestion, reversed-phase chromatographic fractionation of the digest, and identification of peptides in collected RPC fractions by MALDI-MS/MS. Route B differed in that IAC-selected proteins were further fractionated by reversed-phase chromatography before proteolysis of individual chromatographic fractions and identification by MALDI-MS/MS. Route A was the more efficacious of the two protocols in total number of proteins identified. Of the 26 proteins identified, 9 were found to be potential breast cancer marker candidates based on their elevation in breast cancer patients. The potential of these candidates as cancer markers remains to be validated in much larger, more diverse populations of breast cancer patients.     

The Fibrillar Matrix: Novel Avenues for Breast Cancer Detection and Treatment

Breast cancer is marked by large increases in the protein fibers around tumor cells. These fibers increase the mechanical stiffness of the tissue, which has long been used for tumor diagnosis by manual palpation. Recent research in bioengineering has led to the development of novel biomaterials that model the mechanical and architectural properties of the tumor microenvironment and can be used to understand how these cues regulate the growth and spread of breast cancer. Herein, we provide an overview of how the mechanical properties of breast tumor tissues differ from those of normal breast tissue and non-cancerous lesions. We also describe how biomaterial models make it possible to understand how the stiffness and viscosity of the extracellular environment regulate cell migration and breast cancer metastasis. We highlight the need for biomaterial models that allow independent analysis of the individual and different mechanical properties of the tumor microenvironment and that use cells derived from different regions within tumors. These models will guide the development of novel mechano-based therapies against breast cancer metastasis.     

Benchmarking to the Gold Standard: Hyaluronan‐Oxime Hydrogels Recapitulate Xenograft Models with In Vitro Breast Cancer Spheroid Culture

Many 3D in vitro models induce breast cancer spheroid formation; however, this alone does not recapitulate the complex in vivo phenotype. To effectively screen therapeutics, it is urgently needed to validate in vitro cancer spheroid models against the gold standard of xenografts. A new oxime‐crosslinked hyaluronan (HA) hydrogel is designed, manipulating gelation rate and mechanical properties to grow breast cancer spheroids in 3D. This HA‐oxime breast cancer model maintains the gene expression profile most similar to that of tumor xenografts based on a pan‐cancer gene expression profile (comprising 730 genes) of three different human breast cancer subtypes compared to Matrigel or conventional 2D culture. Differences in gene expression between breast cancer cultures in HA‐oxime versus Matrigel or 2D are confirmed for 12 canonical pathways by gene set variation analysis. Importantly, drug response is dependent on the culture method. Breast cancer cells respond better to the Rac inhibitor (EHT‐1864) and the PI3K inhibitor (AZD6482) when cultured in HA‐oxime versus Matrigel. This study demonstrates the superiority of an HA‐based hydrogel as a platform for in vitro breast cancer culture of both primary, patient‐derived cells and cell lines, and provides a hydrogel culture model that closely matches that in vivo.     

基于时间相关单光子计数的非接触式荧光层析成像系统

基于时间相关单光子计数(TCSPC)技术原理,研究了一套面向早期乳腺癌检测的时域荧光层析成像系统,系统采用非接触式空间光扫描测量方式,相对于传统的光纤接触式测量方法,可增大空间采样量、减小测量误差、提高空间分辨率.通过仿体实验对系统的成像质量进行了验证,结果表明:单目标仿体实验能较好地对荧光产率与寿命进行重建;在双目标仿体荧光产率的重建中,可有效对中心距为20mm、边距为15mm的目标体进行分辨,且对不同浓度荧光剂目标的重建具有较好的线性.实验结果证明系统应用于乳腺检测的可行性,进一步发展可有望应用于临床乳腺成像中.     

Nanotube-antibody biosensor arrays for the detection of circulating breast cancer cells

Recent reports have shown that nanoscale electronic devices can be used to detect a change in electrical properties when receptor proteins bind to their corresponding antibodies functionalized on the surface of the device, in extracts from as few as ten lysed tumor cells. We hypothesized that nanotube-antibody devices could sensitively and specifically detect entire live cancer cells. We report for the first time a single nanotube field effect transistor array, functionalized with IGF1R-specific and Her2-specific antibodies, which exhibits highly sensitive and selective sensing of live, intact MCF7 and BT474 human breast cancer cells in human blood. Those two cell lines both overexpress IGF1R and Her2, at different levels. Single or small bundle of nanotube devices that were functionalized with IGF1R-specific or Her2-specific antibodies showed 60% decreases in conductivity upon interaction with BT474 or MCF7 breast cancer cells in two μl drops of blood. Control experiments with non-specific antibodies or with MCF10A control breast cells produced a less than 5% decrease in electrical conductivity, illustrating the high sensitivity for whole cell binding by these single nanotube-antibody devices. We postulate that the free energy change due to multiple simultaneous cell-antibody binding events exerted stress along the nanotube surface, decreasing its electrical conductivity due to an increase in band gap. Because the free energy change upon cell-antibody binding, the stress exerted on the nanotube, and the change in conductivity are specific to a specific antigen-antibody interaction; these properties might be used as a fingerprint for the molecular sensing of circulating cancer cells. From optical microscopy observations during sensing, it appears that the binding of a single cell to a single nanotube field effect transistor produced the change in electrical conductivity. Thus we report a nanoscale oncometer with single cell sensitivity with a diameter 1000 times smaller than a cancer cell that functions in a drop of fresh blood.