Breast cancer is one of the most commonly diagnosed cancers and one of the most significant sources of cancer mortality. Triple negative breast cancer (TNBC) is a particularly aggressive subtype that has proven diffic...Breast cancer is one of the most commonly diagnosed cancers and one of the most significant sources of cancer mortality. Triple negative breast cancer (TNBC) is a particularly aggressive subtype that has proven difficult to treat with standard chemotherapies. Obesity has also been shown to exacerbate breast cancer, and diagnoses of these two diseases frequently overlap. Both conditions are regulated in part by the fat mass and obesity-associated (FTO) demethylase, an RNA demethylase which may drive breast cancers through epigenetic alterations to gene expression. Methods of inhibiting FTO have been researched in vitro and in vivo as an alternative or adjunct to chemotherapies in multiple cancers, including breast cancer. Translating knowledge of the role of FTO in breast cancer and the development of novel agents may allow for improvements in the treatment of this refractory cancer. This review therefore aims to provide an overview of existing and developing chemical inhibitors of FTO that could be innovatively studied for the treatment of TNBC and associated comorbidity.展开更多
Diffusion weighted imaging(DWI) evolved as a complementary tool to morphologic imaging by offering additional functional information about lesions. Although the technique utilizes movement of water molecules to charac...Diffusion weighted imaging(DWI) evolved as a complementary tool to morphologic imaging by offering additional functional information about lesions. Although the technique utilizes movement of water molecules to characterize biological tissues in terms of their cellularity, there are other factors related to the histological constitution of lesions which can have a significant bearing on DWI. Benign lesions with atypical histology including presence of lymphoid stroma, inherently increased cellularity or abundant extracellular collagen can impede movement of water molecules similar to malignant tissues and thereby, show restricted diffusion. Knowledge of these atypical entities while interpreting DWI in clinical practice can avoid potential misdiagnosis. This review aims to present an imaging spectrum of such benign neck masses which, owing to their distinct histology, can show discordant behavior on DWI.展开更多
Background: The purpose of this study was to evaluate the association between the body mass index (BMI) of breast cancer patients and non-cancer females of the Eastern Province of Saudi Arabia. Methods: The weight, he...Background: The purpose of this study was to evaluate the association between the body mass index (BMI) of breast cancer patients and non-cancer females of the Eastern Province of Saudi Arabia. Methods: The weight, height and age was obtained from the patient records of 706 newly diagnosed breast cancer patients and of 20,872 non-cancer female patients who consulted the two largest hospitals in the Eastern Province of Saudi Arabia between 2006 and 2012. Factorial analysis of variance (ANOVA) was used to assess the association between the BMI, age and breast cancer status. Results: The mean BMI of the non-cancer females was 29.4 and the percentage of obese patients of the different age groups ranged from 23.9% to 66.5%. The BMI increased significantly with age. The ANOVA revealed that breast cancer patients older than 50 years had a significantly lower BMI compared to their non-cancer counterparts (p = 0.01). Conclusion: Our data confirm the high BMI of the Saudi Arabian female population. The reason for our finding of a lower BMI of postmenopausal breast cancer patients compared to their non-cancer counterparts is unclear. Future studies are warranted to assess the impact of possible confounding factors on the association between obesity and breast cancer risk. An interesting factor to investigate in future studies would particularly be the use of the anti-diabetic and cancer-protective drug metformin considering that diabetes mellitus is endemic in Saudi Arabia with a prevalence of 30%.展开更多
It is important to segment mass region accurately in a computer-aided diagnosis (CADx) scheme for evaluating the likelihood of malignancy of the mass on ultrasonographic breast image. The purpose of this study was to ...It is important to segment mass region accurately in a computer-aided diagnosis (CADx) scheme for evaluating the likelihood of malignancy of the mass on ultrasonographic breast image. The purpose of this study was to develop a novel level set method for segmentation of breast mass on ultrasonographic image. Our database consisted of 151 ultrasonographic images with 70 malignant and 81 benign breast masses. In a novel level set method, an energy function was defined with region-based, edge-based, and regularizing terms. The region-based term analyzed global information, whereas the edge-based term analyzed local information. The regularizing term also controlled the length of the boundary curve. The region of breast mass was segmented so that the energy based on those terms was minimized. With our proposed method, true positive (TP) ratio, false positive (FP) ratio, jaccard similarity (JS), and Dice similarity coefficient (DSC) were 92.2%, 9.1%, 84.2%, and 91.3%, respectively. These results tended to be substantially higher than those with two conventional segmentation methods. Our proposed method based on the novel level set method was shown to segment mass region accurately on ultrasonographic breast image.展开更多
Objective To explore the influence factors in hematoma formation after removing benign breast lesions with an ultrasound-guided vacuum-assisted system.Methods A total of 232 females with 312 benign breast masses recei...Objective To explore the influence factors in hematoma formation after removing benign breast lesions with an ultrasound-guided vacuum-assisted system.Methods A total of 232 females with 312 benign breast masses received excisional biopsy with ultrasoundguided vacuum-assisted system.The pathology of patients,results of hematoma development and outcome,influence factors for hematoma occurrence(nodule size,nodule location,number of nodule,breast shape,menstrual period,efficacy time of bandage,and application of hemostatic agents during the procedure) were recorded.Results Pathologic examination revealed fibroadenomas in 138 lesions,fibroadenosis in 127 lesions,intraductal papillomas in 39 lesions,inflammatory change in 4 lesions,retention cyst of the breast in 3 lesions,and benign phyllodes tumor in 1 lesion.Thirty hematomas were observed in patients(9.6%).Finally,97.0%hematomas were absorbed completely within 6 months follow-up.The incidence rates of hematoma were increased by 24.7%,10.0%,63.2%,13.9%in the nodule diameter larger or equal to 25 mm group,removal of larger or equal to two nodules once time from one patient group,menstrual period group,and larger and loose breast group,respectively(all P<0.05).However,the incidences were decreased by 60.6%in the bandage performed for 12-24 hours or beyond 24 hours group(P<0.05).The multiple logistic regression models revealed that nodule size(x^2=15.227,P<0.001),number of nodule(x^2=7.767,P=0.005),menstrual period(x^2=24.530,P<0.001),and breast shape(x^2=9.559,P=0.002) were independent risk factors associated with hematoma occurrence,but efficacy time of bandage was a protective factor associated with hematoma occurrence.Conclusion The occurrence of hematoma after the minimally invasive operation was associated with nodule size,number of nodule,menstrual period,breast shape,and efficacy time of bandage.展开更多
Objective: To explore the selection of the best incision for operative treatment of benign breast tumor. Methods: The clinical data of 1000 cases of benign breast tumor operated by cosmetology incision were retrospect...Objective: To explore the selection of the best incision for operative treatment of benign breast tumor. Methods: The clinical data of 1000 cases of benign breast tumor operated by cosmetology incision were retrospectively analyzed. Results: All patients underwent tumor resection and were satisfied with the incision. Conclusions: Benign breast tumor can be excised through cosmetology incision, and no obvious scar leaves behind, so it can satisfy the cosmetic requirement of many patients.展开更多
BACKGROUND Giant ovarian cysts(≥15 cm in diameter)are rare.The size limit of cysts and the methodology for a safe and successful minimally invasive surgery has not been established.Here we report a case of a large 10...BACKGROUND Giant ovarian cysts(≥15 cm in diameter)are rare.The size limit of cysts and the methodology for a safe and successful minimally invasive surgery has not been established.Here we report a case of a large 10-kg multi-locular ovarian mass,which was successfully laparoscopically removed:Our aim was to innovate the surgical practice in this field by providing a safe,effective,and minimally invasive management method for such complex and rare cases.CASE SUMMARY A 49-year-old nulliparous woman presented with abdominal distension,lasting from six Mo prior to admission;she reported worsening abdominal pain,abdominal swelling,and mild dyspnea.Imaging showed a presumed benign multi-locular(>10 locules)left ovarian cyst that measured about 30 cm in diameter.Based on the IOTA-ADNEX model the mass had a 27.5%risk of being a borderline or malignant tumor.The patient was successfully treated via a direct laparoscopic approach with salpingo-oophorectomy,followed by the external drainage of the cyst.Tumor spillage was successfully avoided during this procedure.The final volume of the drained mucinous content was 8950 L;the cyst wall,extracted through the minilaparotomy,weighed about 1200 g.The pathologic gross examination revealed a 24 cm×15 cm×10 cm mass;the histologic examination diagnosed a mucinous cystoadenoma.To our knowledge,this is the first case of a giant multi-locular ovarian cyst treated with a direct laparoscopy with salpingo-oophorectomy followed by external decompression.CONCLUSION Choosing the appropriate technique and surgeon skill are necessary for a safe and effective minimally-invasive approach of unique cases involving giant ovarian cysts.展开更多
Purpose: To study the specificity of mammography and ultrasonography separately and in combination for detection of breast masses (ultrasonography-mammography correlation);To study the investigations to evaluate vario...Purpose: To study the specificity of mammography and ultrasonography separately and in combination for detection of breast masses (ultrasonography-mammography correlation);To study the investigations to evaluate various breast masses;To describe suitable indications, advantages and limitations of each technique compared with other available modalities;To study the mimics of breast masses;To have histopathology follow-up and retrospective evaluation with imaging findings to improve diagnostic skills in series of 166 patients complaining of breast mass. Material: The prospective clinical study was carried out in the department of Radiodiagnosis for a period of 2 year extending from December 2010 to December 2012 infemale patients complaining of breast mass. Well informed written consent was obtained from them. Histopathology follow up was obtained from either biopsy or post operative tissue. USG machine: Philips HD 11 XE USG of the breasts and axillary region done in supine position in presence of female attendant;Mammography machine: Allengers machine with Agfa special mammography cassettes. Cranio caudal and Medio-Lateral Oblique views are taken in the presence of female attendant. MRI: PHILIPS 1.5 T machine;CT: SIEMENS duel slice CT machine. Results: Ultrasonography and mammography was done in most of the cases were sufficient to diagnose the lesion in most of the cases especially in benign breast masses. MRI and CT scan was used in special cases to know the extent of the lesions, in mimics of breast masses, bony extensions, primary muscular and bony lesions. Total 166 patients complaining of breast mass in one or both breasts were examined and evaluated with USG and mammography. The lesions were confirmed on histopathology (FNAC/biopsy). Out of 30 diagnosed malignancies two lesions were missed on mammography and four lesions were missed on ultrasonography. One of them was missed on both. For malignancies specificity of mammography is 93.3% and that of ultrasonography is 86.67%. Combining both the modalities specificity is near 97%. Out of total 92 abnormal breasts 12 were missed on USG and 20 were missed on mammography. Combining both the modalities only 2 lesions were missed and were diagnosed on histopathology alone. Overall specificity for USG in breast masses is 86.9% and for mammography it is 78.6%. Combining both the modalities the specificity is 97.6%. The “p” value is obtained which is highly significant for combination of ultrasonography and mammography in comparison with any individual modality (p = 0.0059 & p = 0.0001 respectively). Conclusion: Our study confirms the higher combined sensitivity rate for ultrasonography and mammography for detection of breast masses including malignancies. USG is useful in cystic lesions, ectasias, infections, pregnancy-lactation, and dense breast evaluation and for image guidance, whereas mammography is useful in detecting microcalcifications, spiculated masses for early detection of malignancies and for stereotactic biopsies. To suggest single modality, ultrasonography is better in younger population and BIRAD 1, 2 & 3 lesions. Whereas, mammography is better in older population and BIRAD 4 & 5 lesions. However, sono-mammographic correlation is best in both.展开更多
BACKGROUND Breast non-mass-like lesions(NMLs)account for 9.2%of all breast lesions.The specificity of the ultrasound diagnosis of NMLs is low,and it cannot be objectively classified according to the 5th Edition of the...BACKGROUND Breast non-mass-like lesions(NMLs)account for 9.2%of all breast lesions.The specificity of the ultrasound diagnosis of NMLs is low,and it cannot be objectively classified according to the 5th Edition of the Breast Imaging Reporting and Data System(BI-RADS).Contrast-enhanced ultrasound(CEUS)can help to differentiate and classify breast lesions but there are few studies on NMLs alone.AIM To analyze the features of benign and malignant breast NMLs in grayscale ultrasonography(US),color Doppler flow imaging(CDFI)and CEUS,and to explore the efficacy of the combined diagnosis of NMLs and the effect of CEUS on the BI-RADS classification of NMLs.METHODS A total of 51 breast NMLs verified by pathology were analyzed in our hospital from January 2017 to April 2019.All lesions were examined by US,CDFI and CEUS,and their features from those examinations were analyzed.With pathology as the gold standard,binary logic regression was used to analyze the independent risk factors for malignant breast NMLs,and a regression equation was established to calculate the efficiency of combined diagnosis.Based on the regression equation,the combined diagnostic efficiency of US combined with CEUS(US+CEUS)was determined.The initial BI-RADS-US classification of NMLs was adjusted according to the independent risk factors identified by CEUS,and the diagnostic efficiency of CEUS combined with BI-RADS(CEUS+BI-RADS)was calculated based on the results.ROC curves were drawn to compare the diagnostic values of the three methods,including US,US+CEUS,and CEUS+BI-RADS,for benign and malignant NMLs.RESULTS Microcalcification,enhancement time,enhancement intensity,lesion scope,and peripheral blood vessels were significantly different between benign and malignant NMLs.Among these features,microcalcification,higher enhancement,and lesion scope were identified as independent risk factors for malignant breast NMLs.When US,US+CEUS,and CEUS+BI-RADS were used to identify the benign and malignant breast NMLs,their sensitivity rates were 82.6%,91.3%,and 87.0%,respectively;their specificity rates were 71.4%,89.2%,and 92.9%,respectively;their positive predictive values were 70.4%,87.5%,and 90.9%,respectively;their negative predictive values were 83.3%,92.6%,and 89.7%,respectively;their accuracy rates were 76.5%,90.2%,and 90.2%,respectively;and their corresponding areas under ROC curves were 0.752,0.877 and 0.903,respectively.Z tests showed that the area under the ROC curve of US was statistically smaller than that of US+CEUS and CEUS+BI-RADS,and there was no statistical difference between US+CEUS and CEUS+BI-RADS.CONCLUSION US combined with CEUS can improve diagnostic efficiency for NMLs.The adjustment of the BI-RADS classification according to the features of contrastenhanced US of NMLs enables the diagnostic results to be simple and intuitive,facilitates the management of NMLs,and effectively reduces the incidence of unnecessary biopsy.展开更多
<strong>Objective:</strong> To explore the clinical effects of conventional surgery, ultrasound-guided microwave ablation and rotational adenomammectomy on the prognosis of benign breast nodules. <stron...<strong>Objective:</strong> To explore the clinical effects of conventional surgery, ultrasound-guided microwave ablation and rotational adenomammectomy on the prognosis of benign breast nodules. <strong>Methods:</strong> 232 cases of patients with benign breast nodules confirmed by pathological examination who received surgical treatment in the breast surgery department of our hospital from December 2016 to December 2020 were included. According to the surgical methods, they were divided into microwave ablation group (n = 48), conventional surgery group (n = 105) and rotational adenomammectomy group (n = 79). The clinical parameters were compared and analyzed between the three groups, and the postoperative pain, residual tumor, breast beauty and complication rate of the patients were evaluated. <strong>Results:</strong> Operative time, intraoperative blood loss, healing time and postoperative pain in microwave ablation group were lower than those of rotational adenomammectomy group (P < 0.05) and those of conventional surgery group (P < 0.05). Besides, those in the rotational adenomammectomy group were lower than those in the conventional surgery group (P < 0.05). The residual tumor rates in microwave ablation group and rotational adenomammectomy group were 4.17% and 3.80%, respectively. And the difference was not statistically significant (P > 0.05). Both of them were lower than 6.66% in conventional surgery group, with statistically significant differences (P < 0.05). The effective rates of breast beauty were 91.67%, 82.28% and 68.58% in the microwave ablation group, the rotational adenomammectomy group and the conventional surgery group, respectively. And the difference between groups was statistically significant (P < 0.05). The rate of postoperative complications in microwave ablation group and rotational adenomammectomy group were 4.17% and 3.80% respectively, both of which were significantly lower than 6.66% in conventional surgery group (P < 0.05). <strong>Conclusion:</strong> Microwave ablation, rotational adenomammectomy and conventional surgery are effective for the treatment of benign breast tumors. Among them, microwave ablation is the best option with many advantages of shorter operative time, less intraoperative blood loss, more beautiful breast shape, less postoperative pain, a lower residual rate after surgery, and a lower complication rate.展开更多
The role of human papillomavirus in breast cancer pathogenesis is an area of considerable debate following differing results from all over the world. This study analyzed paraffin embedded tissue from 19 patients with ...The role of human papillomavirus in breast cancer pathogenesis is an area of considerable debate following differing results from all over the world. This study analyzed paraffin embedded tissue from 19 patients with benign or malignant breast disease. Standard PCR with GP5+/6+ and FAP primers, proved negative in all cases. However, qRT-PCR using the SF10 primer set detected HPV DNA in 2 out of these samples. Whilst our data does not support a major role for HPV in the pathogenesis of breast disease in Malta, it definitely does not exclude it totally. This study also clearly shows that the method of analysis is one of the variables resulting in the range of differing results witnessed worldwide in this area of study.展开更多
One of the most commonly used non-invasive methods for assessing human exposure to pollution is the analysis of human milk.Human milk analyses help estimate the exposure of infants[1].This is why breast milk is receiv...One of the most commonly used non-invasive methods for assessing human exposure to pollution is the analysis of human milk.Human milk analyses help estimate the exposure of infants[1].This is why breast milk is receives scientific interest,and various methods for determining different pollutants from the environment are being developed[2,3].展开更多
Background: Obesity is a well-known risk factor for breast cancer recurrence and poor prognosis. The objective of this study was to evaluate the effect of body mass index (BMI) on survival in breast cancer patients. M...Background: Obesity is a well-known risk factor for breast cancer recurrence and poor prognosis. The objective of this study was to evaluate the effect of body mass index (BMI) on survival in breast cancer patients. Methods: We performed a retrospective analysis of 50 breast cancer patients treated in our hospital from January 2012 to December 2013. Patients were divided according to body mass index when diagnosed into: normal weight BMI 25 Kg/m2, over weight BMI ≥ 25 Kg/m2 to 2, obesity BMI ≥ 30 Kg/m2. In this study the effect of body mass index on progression free survival (PFS) and overall survival (OS) was evaluated. Results: The disease free survival (DFS) and overall survival (OS) decreased in overweight and obese patients. Both overweight and obesity were predictors for increased risks of breast cancer relapse and mortality with a median disease free survival for overweight 29 mons and obese patients 11 mons and a median overall survival for overweight patients 49 mons and obese patients 39 mons. Conclusion: Obesity and overweight are associated with poorer disease free survival and overall survival in patients with breast cancer.展开更多
Cystic lesions are very commonly encountered entities in the breast. </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><spa...Cystic lesions are very commonly encountered entities in the breast. </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">Among</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> these, Complex Cystic Breast Masses (CCBM</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">s</span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">), which contain both anechoic </span><span style="font-family:Verdana;">and echogenic components, can result in a variety of imaging appearances.</span><span style="font-family:Verdana;"> These include cystic lesions with thick walls and/or internal septa, intracystic nodular lesions, and solid-cystic masses of varying com</span><span style="font-family:Verdana;">positions. Ultrasound is the mainstay for evaluating cystic lesions, and thus recognizing the imaging features appropriately and suggesting suitable interventional procedures are </span><span style="font-family:Verdana;">included in their management. In this pictorial essay, we describe the</span><span style="font-family:Verdana;"> wide</span><span style="font-family:Verdana;"> range of ultrasound appearances of CCBMs with a number of clinically encountered examples from our institution. This article would enhance the understanding of readers in possible differentials to be included in their clinical </span><span style="font-family:Verdana;">practice and to suggest appropriate further intervention, when deemed ne</span><span style="font-family:Verdana;">cessary.展开更多
Identification and quantification of low abundance growth factors and regulators in complex biological samples still present a challenging task in analytical biochemistry. Immunoassays are often used for such purpose ...Identification and quantification of low abundance growth factors and regulators in complex biological samples still present a challenging task in analytical biochemistry. Immunoassays are often used for such purpose but immunoassays face limitation of both availability and qualities of antibody reagents that are necessary for development of immune assays. With genomics data base available, mass spectrometry (MS) can analyze protein tryptic peptides directly for quantitative determination of proteins. In this study, we report a method for detection of matrix metalloproteinase 1 (MMP1), an important extracellular matrix modulator, in human breast cancer cells by quadrupole time-of-flight (Q-TOF) MS. Absolute quantification of MMP1 was conducted using the selected reaction monitoring (SRM) on a triple quadrupole (Triple-Quad) MS via transitions selected from MMP1 tryptic peptides using non isotope labeled MMP1 protein as a titration standard. In comparison with immune based assay, this MS method showed picogram level sensitivity for quantitative determination of MMP1 intotal cell lysates. Our results demonstrated the feasibility of absolute quantification of low abundance proteins using label-free protein standard by mass spectrometry. Therefore, this method provides not only advantages of high sensitivity but also cost saving in comparison with the commonly used mass spectrometry that currently employs isotype labeled proteins for quantitative analysis.展开更多
Objectives:To investigate diagnostic value of ultrasound and magnetic resonance imaging(MRI)for malignant and benign breast lesions.Methods:Retrospective analysis of treatment data of 48 patients diagnosed with malign...Objectives:To investigate diagnostic value of ultrasound and magnetic resonance imaging(MRI)for malignant and benign breast lesions.Methods:Retrospective analysis of treatment data of 48 patients diagnosed with malignant and benign breast lesions in our hospital,collected from December 2017 to November 2018.A total number of 56 breast masses were examined by both ultrasound and MRI,and were compared with postoperative pathological biopsy results.Results:Postoperative pathological biopsy results showed that there were 26 and 30 malignant and benign lesions respectively.Comparison of MRI curve type of malignant and benign lesions showed statistical significance(P<0.05).By comparison with pathological biopsy results,specificity and sensitivity of ultrasound diagnosis were 83.33%(25/30)and 84.61%(22/26)respectively;specificity and sensitivity of MRI diagnosis were 96.66%(29/30)and 92.30%(24/26)respectively.Conclusions:Ultrasonographic examination of malignant and benign breast lesions is straight-forward,simple and inexpensive.Accuracy,specificity and sensitivity of MRI are significantly higher than ultrasound in examining malignant and benign breast lesions,this can reduce misdiagnosis.展开更多
<strong>Introduction:</strong> Unilateral nasal mass can be benign or malignant. Very rarely we will find benign salivary gland tumor in nasal cavity. Pleomorphic adenoma is still the most common pathologi...<strong>Introduction:</strong> Unilateral nasal mass can be benign or malignant. Very rarely we will find benign salivary gland tumor in nasal cavity. Pleomorphic adenoma is still the most common pathological variety either in major or minor salivary gland tumors. In the nasal cavity, even though most of the accessory salivary glands are present in the lateral wall of nose, nasal septum remains the most common site of origin. <strong>Case Report:</strong> A 40-year-old female presented with right-sided nasal obstruction and epistaxis. CT scan of Nose and Paranasal sinuses found a lesion involving the anterior third of the right nasal cavity. The patient underwent complete surgical resection of the tumor via an endonasal approach. Histological examination found a mixed cellular component (epithelial and myoepithelial) and mesenchymatous tissue with chondromyxoid stroma, enabling diagnosis of a typical pleomorphic adenoma. <strong>Conclusion:</strong> Pleomorphic adenoma is the most common salivary gland tumor but rare to find in the nasal cavity with only few cases reported in the literature. Although benign, the risk of local recurrence, malignant transformation and metastasis requires close long-term follow-up.展开更多
Breast cancer is the most ordinary malignant tumor in women worldwide. Early breast cancer screening is the key to reduce mortality. Clinical trials have shown that Computer Aided Design improves the accuracy of breas...Breast cancer is the most ordinary malignant tumor in women worldwide. Early breast cancer screening is the key to reduce mortality. Clinical trials have shown that Computer Aided Design improves the accuracy of breast cancer detection. Segmentation of mammography is a critical step in Computer Aided Design. In recent years, FCN has been applied in the field of image segmentation. Generative Adversarial Networks is also popularized for its ability on generate images which is difficult to distinguish from real images, and have been applied in the image semantic segmentation domain. We apply the Dilated Convolutions to the partial convolutional layer of the Multi-FCN and use the ideas of Generative Adversarial Networks to train and correct our segmentation network. Experiments show that the Dice index of the model DMulti- FCN-CRF-Adversarial Training on the datasets InBreast and DDSMBCRP can be increased to 91.15% and 91.8%.展开更多
Breast cancer is a global health concern with a significant impact on the well-being of women. Worldwide, the past several decades have witnessed changes in the incidence and mortality of breast cancer. Additionally,e...Breast cancer is a global health concern with a significant impact on the well-being of women. Worldwide, the past several decades have witnessed changes in the incidence and mortality of breast cancer. Additionally,epidemiological data reveal distinct geographic and demographic disparities globally. A range of modifiable and non-modifiable risk factors are established as being associated with an increased risk of developing breast cancer.This review discusses genetic, hormonal, behavioral, environmental, and breast-related risk factors. Screening plays a critical role in the effective management of breast cancer. Various screening modalities, including mammography,ultrasound, magnetic resonance imaging(MRI), and physical examination, have different applications, and a combination of these modalities is applied in practice. Current screening recommendations are based on factors including age and risk, with a significant emphasis on minimizing potential harms to achieve an optimal benefits-to-harms ratio. This review provides a comprehensive insight into the epidemiology, risk factors, and screening of breast cancer. Understanding these elements is crucial for improving breast cancer management and reducing its burden on affected individuals and healthcare systems.展开更多
文摘Breast cancer is one of the most commonly diagnosed cancers and one of the most significant sources of cancer mortality. Triple negative breast cancer (TNBC) is a particularly aggressive subtype that has proven difficult to treat with standard chemotherapies. Obesity has also been shown to exacerbate breast cancer, and diagnoses of these two diseases frequently overlap. Both conditions are regulated in part by the fat mass and obesity-associated (FTO) demethylase, an RNA demethylase which may drive breast cancers through epigenetic alterations to gene expression. Methods of inhibiting FTO have been researched in vitro and in vivo as an alternative or adjunct to chemotherapies in multiple cancers, including breast cancer. Translating knowledge of the role of FTO in breast cancer and the development of novel agents may allow for improvements in the treatment of this refractory cancer. This review therefore aims to provide an overview of existing and developing chemical inhibitors of FTO that could be innovatively studied for the treatment of TNBC and associated comorbidity.
文摘Diffusion weighted imaging(DWI) evolved as a complementary tool to morphologic imaging by offering additional functional information about lesions. Although the technique utilizes movement of water molecules to characterize biological tissues in terms of their cellularity, there are other factors related to the histological constitution of lesions which can have a significant bearing on DWI. Benign lesions with atypical histology including presence of lymphoid stroma, inherently increased cellularity or abundant extracellular collagen can impede movement of water molecules similar to malignant tissues and thereby, show restricted diffusion. Knowledge of these atypical entities while interpreting DWI in clinical practice can avoid potential misdiagnosis. This review aims to present an imaging spectrum of such benign neck masses which, owing to their distinct histology, can show discordant behavior on DWI.
文摘Background: The purpose of this study was to evaluate the association between the body mass index (BMI) of breast cancer patients and non-cancer females of the Eastern Province of Saudi Arabia. Methods: The weight, height and age was obtained from the patient records of 706 newly diagnosed breast cancer patients and of 20,872 non-cancer female patients who consulted the two largest hospitals in the Eastern Province of Saudi Arabia between 2006 and 2012. Factorial analysis of variance (ANOVA) was used to assess the association between the BMI, age and breast cancer status. Results: The mean BMI of the non-cancer females was 29.4 and the percentage of obese patients of the different age groups ranged from 23.9% to 66.5%. The BMI increased significantly with age. The ANOVA revealed that breast cancer patients older than 50 years had a significantly lower BMI compared to their non-cancer counterparts (p = 0.01). Conclusion: Our data confirm the high BMI of the Saudi Arabian female population. The reason for our finding of a lower BMI of postmenopausal breast cancer patients compared to their non-cancer counterparts is unclear. Future studies are warranted to assess the impact of possible confounding factors on the association between obesity and breast cancer risk. An interesting factor to investigate in future studies would particularly be the use of the anti-diabetic and cancer-protective drug metformin considering that diabetes mellitus is endemic in Saudi Arabia with a prevalence of 30%.
文摘It is important to segment mass region accurately in a computer-aided diagnosis (CADx) scheme for evaluating the likelihood of malignancy of the mass on ultrasonographic breast image. The purpose of this study was to develop a novel level set method for segmentation of breast mass on ultrasonographic image. Our database consisted of 151 ultrasonographic images with 70 malignant and 81 benign breast masses. In a novel level set method, an energy function was defined with region-based, edge-based, and regularizing terms. The region-based term analyzed global information, whereas the edge-based term analyzed local information. The regularizing term also controlled the length of the boundary curve. The region of breast mass was segmented so that the energy based on those terms was minimized. With our proposed method, true positive (TP) ratio, false positive (FP) ratio, jaccard similarity (JS), and Dice similarity coefficient (DSC) were 92.2%, 9.1%, 84.2%, and 91.3%, respectively. These results tended to be substantially higher than those with two conventional segmentation methods. Our proposed method based on the novel level set method was shown to segment mass region accurately on ultrasonographic breast image.
基金Supported by the National Major Scientific Equipment Special Project(2012YQ16020304)
文摘Objective To explore the influence factors in hematoma formation after removing benign breast lesions with an ultrasound-guided vacuum-assisted system.Methods A total of 232 females with 312 benign breast masses received excisional biopsy with ultrasoundguided vacuum-assisted system.The pathology of patients,results of hematoma development and outcome,influence factors for hematoma occurrence(nodule size,nodule location,number of nodule,breast shape,menstrual period,efficacy time of bandage,and application of hemostatic agents during the procedure) were recorded.Results Pathologic examination revealed fibroadenomas in 138 lesions,fibroadenosis in 127 lesions,intraductal papillomas in 39 lesions,inflammatory change in 4 lesions,retention cyst of the breast in 3 lesions,and benign phyllodes tumor in 1 lesion.Thirty hematomas were observed in patients(9.6%).Finally,97.0%hematomas were absorbed completely within 6 months follow-up.The incidence rates of hematoma were increased by 24.7%,10.0%,63.2%,13.9%in the nodule diameter larger or equal to 25 mm group,removal of larger or equal to two nodules once time from one patient group,menstrual period group,and larger and loose breast group,respectively(all P<0.05).However,the incidences were decreased by 60.6%in the bandage performed for 12-24 hours or beyond 24 hours group(P<0.05).The multiple logistic regression models revealed that nodule size(x^2=15.227,P<0.001),number of nodule(x^2=7.767,P=0.005),menstrual period(x^2=24.530,P<0.001),and breast shape(x^2=9.559,P=0.002) were independent risk factors associated with hematoma occurrence,but efficacy time of bandage was a protective factor associated with hematoma occurrence.Conclusion The occurrence of hematoma after the minimally invasive operation was associated with nodule size,number of nodule,menstrual period,breast shape,and efficacy time of bandage.
文摘Objective: To explore the selection of the best incision for operative treatment of benign breast tumor. Methods: The clinical data of 1000 cases of benign breast tumor operated by cosmetology incision were retrospectively analyzed. Results: All patients underwent tumor resection and were satisfied with the incision. Conclusions: Benign breast tumor can be excised through cosmetology incision, and no obvious scar leaves behind, so it can satisfy the cosmetic requirement of many patients.
文摘BACKGROUND Giant ovarian cysts(≥15 cm in diameter)are rare.The size limit of cysts and the methodology for a safe and successful minimally invasive surgery has not been established.Here we report a case of a large 10-kg multi-locular ovarian mass,which was successfully laparoscopically removed:Our aim was to innovate the surgical practice in this field by providing a safe,effective,and minimally invasive management method for such complex and rare cases.CASE SUMMARY A 49-year-old nulliparous woman presented with abdominal distension,lasting from six Mo prior to admission;she reported worsening abdominal pain,abdominal swelling,and mild dyspnea.Imaging showed a presumed benign multi-locular(>10 locules)left ovarian cyst that measured about 30 cm in diameter.Based on the IOTA-ADNEX model the mass had a 27.5%risk of being a borderline or malignant tumor.The patient was successfully treated via a direct laparoscopic approach with salpingo-oophorectomy,followed by the external drainage of the cyst.Tumor spillage was successfully avoided during this procedure.The final volume of the drained mucinous content was 8950 L;the cyst wall,extracted through the minilaparotomy,weighed about 1200 g.The pathologic gross examination revealed a 24 cm×15 cm×10 cm mass;the histologic examination diagnosed a mucinous cystoadenoma.To our knowledge,this is the first case of a giant multi-locular ovarian cyst treated with a direct laparoscopy with salpingo-oophorectomy followed by external decompression.CONCLUSION Choosing the appropriate technique and surgeon skill are necessary for a safe and effective minimally-invasive approach of unique cases involving giant ovarian cysts.
文摘Purpose: To study the specificity of mammography and ultrasonography separately and in combination for detection of breast masses (ultrasonography-mammography correlation);To study the investigations to evaluate various breast masses;To describe suitable indications, advantages and limitations of each technique compared with other available modalities;To study the mimics of breast masses;To have histopathology follow-up and retrospective evaluation with imaging findings to improve diagnostic skills in series of 166 patients complaining of breast mass. Material: The prospective clinical study was carried out in the department of Radiodiagnosis for a period of 2 year extending from December 2010 to December 2012 infemale patients complaining of breast mass. Well informed written consent was obtained from them. Histopathology follow up was obtained from either biopsy or post operative tissue. USG machine: Philips HD 11 XE USG of the breasts and axillary region done in supine position in presence of female attendant;Mammography machine: Allengers machine with Agfa special mammography cassettes. Cranio caudal and Medio-Lateral Oblique views are taken in the presence of female attendant. MRI: PHILIPS 1.5 T machine;CT: SIEMENS duel slice CT machine. Results: Ultrasonography and mammography was done in most of the cases were sufficient to diagnose the lesion in most of the cases especially in benign breast masses. MRI and CT scan was used in special cases to know the extent of the lesions, in mimics of breast masses, bony extensions, primary muscular and bony lesions. Total 166 patients complaining of breast mass in one or both breasts were examined and evaluated with USG and mammography. The lesions were confirmed on histopathology (FNAC/biopsy). Out of 30 diagnosed malignancies two lesions were missed on mammography and four lesions were missed on ultrasonography. One of them was missed on both. For malignancies specificity of mammography is 93.3% and that of ultrasonography is 86.67%. Combining both the modalities specificity is near 97%. Out of total 92 abnormal breasts 12 were missed on USG and 20 were missed on mammography. Combining both the modalities only 2 lesions were missed and were diagnosed on histopathology alone. Overall specificity for USG in breast masses is 86.9% and for mammography it is 78.6%. Combining both the modalities the specificity is 97.6%. The “p” value is obtained which is highly significant for combination of ultrasonography and mammography in comparison with any individual modality (p = 0.0059 & p = 0.0001 respectively). Conclusion: Our study confirms the higher combined sensitivity rate for ultrasonography and mammography for detection of breast masses including malignancies. USG is useful in cystic lesions, ectasias, infections, pregnancy-lactation, and dense breast evaluation and for image guidance, whereas mammography is useful in detecting microcalcifications, spiculated masses for early detection of malignancies and for stereotactic biopsies. To suggest single modality, ultrasonography is better in younger population and BIRAD 1, 2 & 3 lesions. Whereas, mammography is better in older population and BIRAD 4 & 5 lesions. However, sono-mammographic correlation is best in both.
文摘BACKGROUND Breast non-mass-like lesions(NMLs)account for 9.2%of all breast lesions.The specificity of the ultrasound diagnosis of NMLs is low,and it cannot be objectively classified according to the 5th Edition of the Breast Imaging Reporting and Data System(BI-RADS).Contrast-enhanced ultrasound(CEUS)can help to differentiate and classify breast lesions but there are few studies on NMLs alone.AIM To analyze the features of benign and malignant breast NMLs in grayscale ultrasonography(US),color Doppler flow imaging(CDFI)and CEUS,and to explore the efficacy of the combined diagnosis of NMLs and the effect of CEUS on the BI-RADS classification of NMLs.METHODS A total of 51 breast NMLs verified by pathology were analyzed in our hospital from January 2017 to April 2019.All lesions were examined by US,CDFI and CEUS,and their features from those examinations were analyzed.With pathology as the gold standard,binary logic regression was used to analyze the independent risk factors for malignant breast NMLs,and a regression equation was established to calculate the efficiency of combined diagnosis.Based on the regression equation,the combined diagnostic efficiency of US combined with CEUS(US+CEUS)was determined.The initial BI-RADS-US classification of NMLs was adjusted according to the independent risk factors identified by CEUS,and the diagnostic efficiency of CEUS combined with BI-RADS(CEUS+BI-RADS)was calculated based on the results.ROC curves were drawn to compare the diagnostic values of the three methods,including US,US+CEUS,and CEUS+BI-RADS,for benign and malignant NMLs.RESULTS Microcalcification,enhancement time,enhancement intensity,lesion scope,and peripheral blood vessels were significantly different between benign and malignant NMLs.Among these features,microcalcification,higher enhancement,and lesion scope were identified as independent risk factors for malignant breast NMLs.When US,US+CEUS,and CEUS+BI-RADS were used to identify the benign and malignant breast NMLs,their sensitivity rates were 82.6%,91.3%,and 87.0%,respectively;their specificity rates were 71.4%,89.2%,and 92.9%,respectively;their positive predictive values were 70.4%,87.5%,and 90.9%,respectively;their negative predictive values were 83.3%,92.6%,and 89.7%,respectively;their accuracy rates were 76.5%,90.2%,and 90.2%,respectively;and their corresponding areas under ROC curves were 0.752,0.877 and 0.903,respectively.Z tests showed that the area under the ROC curve of US was statistically smaller than that of US+CEUS and CEUS+BI-RADS,and there was no statistical difference between US+CEUS and CEUS+BI-RADS.CONCLUSION US combined with CEUS can improve diagnostic efficiency for NMLs.The adjustment of the BI-RADS classification according to the features of contrastenhanced US of NMLs enables the diagnostic results to be simple and intuitive,facilitates the management of NMLs,and effectively reduces the incidence of unnecessary biopsy.
文摘<strong>Objective:</strong> To explore the clinical effects of conventional surgery, ultrasound-guided microwave ablation and rotational adenomammectomy on the prognosis of benign breast nodules. <strong>Methods:</strong> 232 cases of patients with benign breast nodules confirmed by pathological examination who received surgical treatment in the breast surgery department of our hospital from December 2016 to December 2020 were included. According to the surgical methods, they were divided into microwave ablation group (n = 48), conventional surgery group (n = 105) and rotational adenomammectomy group (n = 79). The clinical parameters were compared and analyzed between the three groups, and the postoperative pain, residual tumor, breast beauty and complication rate of the patients were evaluated. <strong>Results:</strong> Operative time, intraoperative blood loss, healing time and postoperative pain in microwave ablation group were lower than those of rotational adenomammectomy group (P < 0.05) and those of conventional surgery group (P < 0.05). Besides, those in the rotational adenomammectomy group were lower than those in the conventional surgery group (P < 0.05). The residual tumor rates in microwave ablation group and rotational adenomammectomy group were 4.17% and 3.80%, respectively. And the difference was not statistically significant (P > 0.05). Both of them were lower than 6.66% in conventional surgery group, with statistically significant differences (P < 0.05). The effective rates of breast beauty were 91.67%, 82.28% and 68.58% in the microwave ablation group, the rotational adenomammectomy group and the conventional surgery group, respectively. And the difference between groups was statistically significant (P < 0.05). The rate of postoperative complications in microwave ablation group and rotational adenomammectomy group were 4.17% and 3.80% respectively, both of which were significantly lower than 6.66% in conventional surgery group (P < 0.05). <strong>Conclusion:</strong> Microwave ablation, rotational adenomammectomy and conventional surgery are effective for the treatment of benign breast tumors. Among them, microwave ablation is the best option with many advantages of shorter operative time, less intraoperative blood loss, more beautiful breast shape, less postoperative pain, a lower residual rate after surgery, and a lower complication rate.
文摘The role of human papillomavirus in breast cancer pathogenesis is an area of considerable debate following differing results from all over the world. This study analyzed paraffin embedded tissue from 19 patients with benign or malignant breast disease. Standard PCR with GP5+/6+ and FAP primers, proved negative in all cases. However, qRT-PCR using the SF10 primer set detected HPV DNA in 2 out of these samples. Whilst our data does not support a major role for HPV in the pathogenesis of breast disease in Malta, it definitely does not exclude it totally. This study also clearly shows that the method of analysis is one of the variables resulting in the range of differing results witnessed worldwide in this area of study.
基金supported by the Bilateral Scientific-research Project between the Republic of Croatia and Serbia 2019-2020[337-00-205/2019-09/22]Croatian Science Foundation[Project OPENTOX,No.8366]the Ministry of Education,Science and Technological Development of the Republic of Serbia[Project No.III43007].
文摘One of the most commonly used non-invasive methods for assessing human exposure to pollution is the analysis of human milk.Human milk analyses help estimate the exposure of infants[1].This is why breast milk is receives scientific interest,and various methods for determining different pollutants from the environment are being developed[2,3].
文摘Background: Obesity is a well-known risk factor for breast cancer recurrence and poor prognosis. The objective of this study was to evaluate the effect of body mass index (BMI) on survival in breast cancer patients. Methods: We performed a retrospective analysis of 50 breast cancer patients treated in our hospital from January 2012 to December 2013. Patients were divided according to body mass index when diagnosed into: normal weight BMI 25 Kg/m2, over weight BMI ≥ 25 Kg/m2 to 2, obesity BMI ≥ 30 Kg/m2. In this study the effect of body mass index on progression free survival (PFS) and overall survival (OS) was evaluated. Results: The disease free survival (DFS) and overall survival (OS) decreased in overweight and obese patients. Both overweight and obesity were predictors for increased risks of breast cancer relapse and mortality with a median disease free survival for overweight 29 mons and obese patients 11 mons and a median overall survival for overweight patients 49 mons and obese patients 39 mons. Conclusion: Obesity and overweight are associated with poorer disease free survival and overall survival in patients with breast cancer.
文摘Cystic lesions are very commonly encountered entities in the breast. </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">Among</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> these, Complex Cystic Breast Masses (CCBM</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">s</span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">), which contain both anechoic </span><span style="font-family:Verdana;">and echogenic components, can result in a variety of imaging appearances.</span><span style="font-family:Verdana;"> These include cystic lesions with thick walls and/or internal septa, intracystic nodular lesions, and solid-cystic masses of varying com</span><span style="font-family:Verdana;">positions. Ultrasound is the mainstay for evaluating cystic lesions, and thus recognizing the imaging features appropriately and suggesting suitable interventional procedures are </span><span style="font-family:Verdana;">included in their management. In this pictorial essay, we describe the</span><span style="font-family:Verdana;"> wide</span><span style="font-family:Verdana;"> range of ultrasound appearances of CCBMs with a number of clinically encountered examples from our institution. This article would enhance the understanding of readers in possible differentials to be included in their clinical </span><span style="font-family:Verdana;">practice and to suggest appropriate further intervention, when deemed ne</span><span style="font-family:Verdana;">cessary.
文摘Identification and quantification of low abundance growth factors and regulators in complex biological samples still present a challenging task in analytical biochemistry. Immunoassays are often used for such purpose but immunoassays face limitation of both availability and qualities of antibody reagents that are necessary for development of immune assays. With genomics data base available, mass spectrometry (MS) can analyze protein tryptic peptides directly for quantitative determination of proteins. In this study, we report a method for detection of matrix metalloproteinase 1 (MMP1), an important extracellular matrix modulator, in human breast cancer cells by quadrupole time-of-flight (Q-TOF) MS. Absolute quantification of MMP1 was conducted using the selected reaction monitoring (SRM) on a triple quadrupole (Triple-Quad) MS via transitions selected from MMP1 tryptic peptides using non isotope labeled MMP1 protein as a titration standard. In comparison with immune based assay, this MS method showed picogram level sensitivity for quantitative determination of MMP1 intotal cell lysates. Our results demonstrated the feasibility of absolute quantification of low abundance proteins using label-free protein standard by mass spectrometry. Therefore, this method provides not only advantages of high sensitivity but also cost saving in comparison with the commonly used mass spectrometry that currently employs isotype labeled proteins for quantitative analysis.
文摘Objectives:To investigate diagnostic value of ultrasound and magnetic resonance imaging(MRI)for malignant and benign breast lesions.Methods:Retrospective analysis of treatment data of 48 patients diagnosed with malignant and benign breast lesions in our hospital,collected from December 2017 to November 2018.A total number of 56 breast masses were examined by both ultrasound and MRI,and were compared with postoperative pathological biopsy results.Results:Postoperative pathological biopsy results showed that there were 26 and 30 malignant and benign lesions respectively.Comparison of MRI curve type of malignant and benign lesions showed statistical significance(P<0.05).By comparison with pathological biopsy results,specificity and sensitivity of ultrasound diagnosis were 83.33%(25/30)and 84.61%(22/26)respectively;specificity and sensitivity of MRI diagnosis were 96.66%(29/30)and 92.30%(24/26)respectively.Conclusions:Ultrasonographic examination of malignant and benign breast lesions is straight-forward,simple and inexpensive.Accuracy,specificity and sensitivity of MRI are significantly higher than ultrasound in examining malignant and benign breast lesions,this can reduce misdiagnosis.
文摘<strong>Introduction:</strong> Unilateral nasal mass can be benign or malignant. Very rarely we will find benign salivary gland tumor in nasal cavity. Pleomorphic adenoma is still the most common pathological variety either in major or minor salivary gland tumors. In the nasal cavity, even though most of the accessory salivary glands are present in the lateral wall of nose, nasal septum remains the most common site of origin. <strong>Case Report:</strong> A 40-year-old female presented with right-sided nasal obstruction and epistaxis. CT scan of Nose and Paranasal sinuses found a lesion involving the anterior third of the right nasal cavity. The patient underwent complete surgical resection of the tumor via an endonasal approach. Histological examination found a mixed cellular component (epithelial and myoepithelial) and mesenchymatous tissue with chondromyxoid stroma, enabling diagnosis of a typical pleomorphic adenoma. <strong>Conclusion:</strong> Pleomorphic adenoma is the most common salivary gland tumor but rare to find in the nasal cavity with only few cases reported in the literature. Although benign, the risk of local recurrence, malignant transformation and metastasis requires close long-term follow-up.
基金the National Natural Science Foundation of China under Grant No. 61672181, No. 51679058Natural Science Foundation of Heilongjiang Province under Grant No. F2016005.
文摘Breast cancer is the most ordinary malignant tumor in women worldwide. Early breast cancer screening is the key to reduce mortality. Clinical trials have shown that Computer Aided Design improves the accuracy of breast cancer detection. Segmentation of mammography is a critical step in Computer Aided Design. In recent years, FCN has been applied in the field of image segmentation. Generative Adversarial Networks is also popularized for its ability on generate images which is difficult to distinguish from real images, and have been applied in the image semantic segmentation domain. We apply the Dilated Convolutions to the partial convolutional layer of the Multi-FCN and use the ideas of Generative Adversarial Networks to train and correct our segmentation network. Experiments show that the Dice index of the model DMulti- FCN-CRF-Adversarial Training on the datasets InBreast and DDSMBCRP can be increased to 91.15% and 91.8%.
基金supported by the CAMS Innovation Fund for Medical Sciences (No. 2021-I2M-1-014 and No. 2022-I2M-2-002)。
文摘Breast cancer is a global health concern with a significant impact on the well-being of women. Worldwide, the past several decades have witnessed changes in the incidence and mortality of breast cancer. Additionally,epidemiological data reveal distinct geographic and demographic disparities globally. A range of modifiable and non-modifiable risk factors are established as being associated with an increased risk of developing breast cancer.This review discusses genetic, hormonal, behavioral, environmental, and breast-related risk factors. Screening plays a critical role in the effective management of breast cancer. Various screening modalities, including mammography,ultrasound, magnetic resonance imaging(MRI), and physical examination, have different applications, and a combination of these modalities is applied in practice. Current screening recommendations are based on factors including age and risk, with a significant emphasis on minimizing potential harms to achieve an optimal benefits-to-harms ratio. This review provides a comprehensive insight into the epidemiology, risk factors, and screening of breast cancer. Understanding these elements is crucial for improving breast cancer management and reducing its burden on affected individuals and healthcare systems.