Background Breast Parenchymal Signal During Menstrual Cycle on Diffusion-Weighted MRI: A Prospective Study in Healthy Premenopausal Women.

OBJECTIVE: To prospectively investigate the influence of the menstrual cycle on the background parenchymal signal (BPS) and apparent diffusion coefficient (ADC) of the breast on diffusion-weighted MRI (DW-MRI) in healthy premenopausal women. MATERIALS AND METHODS: Seven healthy premenopausal women (median age, 37 years; range, 33-49 years) with regular menstrual cycles participated in this study. DW-MRI was performed during each of the four phases of the menstrual cycle (four examinations in total). Three radiologists independently assessed the BPS visual grade on images with b-values of 800 sec/mm² (b800), 1200 sec/mm² (b1200), and a synthetic 1500 sec/mm² (sb1500). Additionally, one radiologist conducted a quantitative analysis to measure the BPS volume (%) and ADC values of the BPS (ADCBPS) and fibroglandular tissue (ADCFGT). Changes in the visual grade, BPS volume (%), ADCBPS, and ADCFGT during the menstrual cycle were descriptively analyzed. RESULTS: The visual grade of BPS in seven women varied from mild to marked on b800 and from minimal to moderate on b1200 and sb1500. As the b-value increased, the visual grade of BPS decreased. On b800 and sb1500, two of the seven volunteers showed the highest visual grade in the early follicular phase (EFP). On b1200, three of the seven volunteers showed the highest visual grades in EFP. The BPS volume (%) on b800 and b1200 showed the highest value in three of the six volunteers with dense breasts in EFP. Three of the seven volunteers showed the lowest ADCBPS in the EFP. Four of the seven volunteers showed the highest ADCBPS in the early luteal phase (ELP) and the lowest ADCFGT in the late follicular phase (LFP). CONCLUSION: Most volunteers did not exhibit specific BPS patterns during their menstrual cycles. However, the highest BPS and lowest ADCBPS were more frequently observed in EFP than in the other menstrual cycle phases, whereas the highest ADCBPS was more common in ELP. The lowest ADCFGT was more frequent in LFP.

Concordance of HER2 status between core needle biopsy and surgical resection specimens of breast cancer: an analysis focusing on the HER2-low status.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-low status has recently gained attention because of the potential therapeutic benefits of antibody-drug conjugates (ADCs) in breast cancer patients. We aimed to investigate the concordance of HER2 status between core needle biopsy (CNB) and subsequent surgical resection specimens focusing on the HER2-low status. METHODS: This retrospective study was conducted in 1,387 patients with invasive breast cancer whose HER2 status was evaluated in both CNB and surgical resection specimens. The discordance rates between CNB and surgical resection specimens and the clinicopathological features associated with HER2 status discordance were analyzed. RESULTS: The overall concordance rates of HER2 status between CNB and surgical resection specimens were 99.0% (κ = 0.925) for two-group classification (negative vs. positive) and 78.5% (κ = 0.587) for three-group classification (zero vs. low vs. positive). The largest discordance occurred in CNB-HER2-zero cases with 42.8% of them reclassified as HER2-low in surgical resection. HER2 discordance was associated with lower histologic grade, tumor multiplicity, and luminal A subtype. In multivariate analysis, tumor multiplicity and estrogen receptor (ER) positivity were independent predictive factors for HER2-zero to low conversion. CONCLUSIONS: Incorporation of HER2-low category in HER2 status interpretation reduces the concordance rate between CNB and surgical resection specimens. Tumor multiplicity and ER positivity are predictive factors for conversion from HER2-zero to HER2-low status. Therefore, HER2 status should be re-evaluated in resection specimens when considering ADCs in tumors exhibiting multiplicity and ER positivity.

Automated Versus Handheld Breast Ultrasound for Evaluating Axillary Lymph Nodes in Patients With Breast Cancer.

OBJECTIVE: Automated breast ultrasound (ABUS) is a relevant imaging technique for early breast cancer diagnosis and is increasingly being used as a supplementary tool for mammography. This study compared the performance of ABUS and handheld ultrasound (HHUS) in detecting and characterizing the axillary lymph nodes (LNs) in patients with breast cancer. MATERIALS AND METHODS: We retrospectively reviewed the medical records of women with recently diagnosed early breast cancer (≤ T2) who underwent both ABUS and HHUS examinations for axilla (September 2017-May 2018). ABUS and HHUS findings were compared using pathological outcomes as reference standards. Diagnostic performance in predicting any axillary LN metastasis and heavy nodal-burden metastases (i.e., ≥ 3 LNs) was evaluated. The ABUS-HHUS agreement for visibility and US findings was calculated. RESULTS: The study included 377 women (53.1 ± 11.1 years). Among 385 breast cancers in 377 patients, 101 had axillary LN metastases and 30 had heavy nodal burden metastases. ABUS identified benign-looking or suspicious axillary LNs (average, 1.4 ± 0.8) in 246 axillae (63.9%, 246/385). According to the per-breast analysis, the sensitivity, specificity, positive and negative predictive values, and accuracy of ABUS in predicting axillary LN metastases were 43.6% (44/101), 95.1% (270/284), 75.9% (44/58), 82.6% (270/327), and 81.6% (314/385), respectively. The corresponding results for HHUS were 41.6% (42/101), 95.1% (270/284), 75.0% (42/56), 82.1% (270/329), and 81.0% (312/385), respectively, which were not significantly different from those of ABUS (P ≥ 0.53). The performance results for heavy nodal-burden metastases were 70.0% (21/30), 89.6% (318/355), 36.2% (21/58), 97.3% (318/327), and 88.1% (339/385), respectively, for ABUS and 66.7% (20/30), 89.9% (319/355), 35.7% (20/56), 97.0% (319/329), and 88.1% (339/385), respectively, for HHUS, also not showing significant difference (P ≥ 0.57). The ABUS-HHUS agreement was 95.9% (236/246; Cohen's kappa = 0.883). CONCLUSION: Although ABUS showed limited sensitivity in diagnosing axillary LN metastasis in early breast cancer, it was still useful as the performance was comparable to that of HHUS.

Ultrafast MRI and T1 and T2 Radiomics for Predicting Invasive Components in Ductal Carcinoma in Situ Diagnosed With Percutaneous Needle Biopsy.

OBJECTIVE: This study aimed to investigate the feasibility of ultrafast magnetic resonance imaging (MRI) and radiomic features derived from breast MRI for predicting the upstaging of ductal carcinoma in situ (DCIS) diagnosed using percutaneous needle biopsy. MATERIALS AND METHODS: Between August 2018 and June 2020, 95 patients with 98 DCIS lesions who underwent preoperative breast MRI, including an ultrafast sequence, and subsequent surgery were included. Four ultrafast MRI parameters were analyzed: time-to-enhancement, maximum slope (MS), area under the curve for 60 s after enhancement, and time-to-peak enhancement. One hundred and seven radiomic features were extracted for the whole tumor on the first post-contrast T1WI and T2WI using PyRadiomics. Clinicopathological characteristics, ultrafast MRI findings, and radiomic features were compared between the pure DCIS and DCIS with invasion groups. Prediction models, incorporating clinicopathological, ultrafast MRI, and radiomic features, were developed. Receiver operating characteristic curve analysis and area under the curve (AUC) were used to evaluate model performance in distinguishing between the two groups using leave-one-out cross-validation. RESULTS: Thirty-six of the 98 lesions (36.7%) were confirmed to have invasive components after surgery. Compared to the pure DCIS group, the DCIS with invasion group had a higher nuclear grade (P < 0.001), larger mean lesion size (P = 0.038), larger mean MS (P = 0.002), and different radiomic-related characteristics, including a more extensive tumor volume; higher maximum gray-level intensity; coarser, more complex, and heterogeneous texture; and a greater concentration of high gray-level intensity. No significant differences in AUCs were found between the model incorporating nuclear grade and lesion size (0.687) and the models integrating additional ultrafast MRI and radiomic features (0.680-0.732). CONCLUSION: High nuclear grade, larger lesion size, larger MS, and multiple radiomic features were associated with DCIS upstaging. However, the addition of MS and radiomic features to the prediction model did not significantly improve the prediction performance.

Obstetric and psychiatric history as predictors for psychosomatic symptoms among Korean perimenopausal women.

OBJECTIVES: Menopause presents various physical and psychological disturbances for women and comes at a high financial cost. Therefore, this study aimed to identify factors influencing menopause symptoms. STUDY DESIGN: Data of Korean perimenopausal women aged 40-60 (n = 1060; mean age, 46.03 ± 4.08) were collected by a research company. Participants were classified into a "functional" group (n = 716) or a "dysfunctional" group (n = 344) according to the severity of their perimenopausal psychosomatic symptoms. To investigate the association of obstetric and psychiatric history with membership of the "dysfunctional" group, a hierarchical logistic regression analysis was conducted. RESULTS: The outcomes of all three hierarchical logistic regression models presented significant overall model fit. Among the independent variables, family history of menopausal symptoms, menarcheal age, number of pregnancies, history of postpartum depression, postpartum psychosis, and other psychiatric disorders were positively associated with being in the "dysfunctional" group, whereas age and number of deliveries were negatively associated with being in the "dysfunctional" group. CONCLUSION: A short reproductive period and short exposure to estrogen due to late menarche and early menopausal transition may be related to severe perimenopausal symptoms. The relationship between the history of postpartum mental illness and severe perimenopausal symptoms may be associated with heightened sensitivity to hormonal triggers when a woman is exposed to fluctuating ovarian sex steroid levels. The relationship between parity or gravidity and the severity of menopausal symptoms in Korean women differed from that in studies conducted in other countries, possibly due to the low birth rate in Korea.

Rare Case of Managing and Evaluating Viability after Replantation of a Serial Self-Amputated Bilateral Testis by a Patient with Schizophrenia: A Case Report.

Amputation of the testis is very rare in clinical situations; therefore, most surgeons have no experience with an amputated testis. In this case, a 31-year-old male with schizophrenia amputated both testes due to self-mutilation. We performed replantation surgery via microscopy. On postoperative day 1, he removed his right testis by using his hand, even though his hands were restrained. The second attack disrupted the viability of the right testis. However, after proper management, we checked the normal sex hormone level by preserving the replanted left testis. We evaluated the viability of the replanted testis by performing five examinations, namely, intraoperative indocyanine green injection, testicular scan with technetium pertechnetate, contrast-enhanced computerized tomography, Doppler ultrasonography, and serum testosterone level. In this report, we aimed to describe our rare experience about management with replantation of the amputated testes and evaluation of their viability.

NR1D1 Stimulates Antitumor Immune Responses in Breast Cancer by Activating cGAS-STING Signaling.

Potentiating antitumor immunity is a promising therapeutic approach for treating a variety of cancers, including breast cancer. One potential strategy to promote antitumor immunity is targeting DNA damage response. Given that the nuclear receptor NR1D1 (also known as REV-ERBα) inhibits DNA repair in breast cancer cells, we explored the role of NR1D1 in antitumor CD8+ T-cell responses. First, deletion of Nr1d1 in MMTV-PyMT transgenic mice resulted in increased tumor growth and lung metastasis. Orthotopic allograft experiments suggested that loss of Nr1d1 in tumor cells rather than in stromal cells played a prominent role in increasing tumor progression. Comprehensive transcriptome analyses revealed that biological processes including type I IFN signaling and T cell-mediated immune responses were associated with NR1D1. Indeed, the expression of type I IFNs and infiltration of CD8+ T cells and natural killer cells in tumors were suppressed in Nr1d1-/-;MMTV-PyMT mice. Mechanistically, NR1D1 promoted DNA damage-induced accumulation of cytosolic DNA fragments and activated cGAS-STING signaling, which increased the production of type I IFNs and downstream chemokines CCL5 and CXCL10. Pharmacologic activation of NR1D1 by its ligand, SR9009, enhanced type I IFN-mediated antitumor immunity accompanied by the suppression of tumor progression and lung metastasis. Taken together, these findings reveal the critical role of NR1D1 in enhancing antitumor CD8+ T-cell responses, suggesting that NR1D1 may be a good therapeutic target for breast cancer. SIGNIFICANCE: NR1D1 suppresses breast cancer progression and lung metastasis by enhancing antitumor immunity via cGAS-STING pathway activation, which provides potential immunotherapeutic strategies for breast cancer.

NR1D1 deficiency in the tumor microenvironment promotes lung tumor development by activating the NLRP3 inflammasome.

Nuclear receptor Rev-erbα (NR1D1) is a major negative regulator of the circadian clock. Numerous studies have investigated the role of circadian clock-related factors in the tumorigenesis of multiple cancer types, but little is known about the role of NR1D1 in cancer development. In this study, we identified the role of NR1D1 in lung tumorigenesis using genetically engineered mouse models of Nr1d1. Although NR1D1 overexpression or knockdown had little effect on the proliferation of NSCLC cells in vitro, NR1D1 deficiency in the tumor microenvironment increased lung cancer development compared with the control in the orthotopic model. NR1D1-deficient mice showed increased NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome activation, and conditioned medium (CM) from NR1D1-deficient macrophages increased the proliferation and epithelial-mesenchymal transition (EMT) of lung cancer cells. Treatment with MCC950, a specific inhibitor of NLRP3 inflammasome, blocked tumorigenesis in NR1D1-deficient mice in an orthotopic lung cancer model. In addition, MCC950 treatment blocked the increased proliferation and EMT of cancer cells induced by CM from NR1D1-deficient macrophages in vitro. Our results showed that NR1D1 in the tumor microenvironment functions as a tumor suppressor by negatively regulating the NLRP3 inflammasome, suggesting that the NLRP3 inflammasome blockade via NR1D1 activation could be a therapeutic strategy to overcome lung cancer.

Development and External Validation of a Machine Learning Model to Predict Pathological Complete Response After Neoadjuvant Chemotherapy in Breast Cancer.

PURPOSE: Several predictive models have been developed to predict the pathological complete response (pCR) after neoadjuvant chemotherapy (NAC); however, few are broadly applicable owing to radiologic complexity and institution-specific clinical variables, and none have been externally validated. This study aimed to develop and externally validate a machine learning model that predicts pCR after NAC in patients with breast cancer using routinely collected clinical and demographic variables. METHODS: The electronic medical records of patients with advanced breast cancer who underwent NAC before surgical resection between January 2017 and December 2020 were reviewed. Patient data from Seoul National University Bundang Hospital were divided into training and internal validation cohorts. Five machine learning techniques, including gradient boosting machine (GBM), support vector machine, random forest, decision tree, and neural network, were used to build predictive models, and the area under the receiver operating characteristic curve (AUC) was compared to select the best model. Finally, the model was validated using an independent cohort from Seoul National University Hospital. RESULTS: A total of 1,003 patients were included in the study: 287, 71, and 645 in the training, internal validation, and external validation cohorts, respectively. Overall, 36.3% of the patients achieved pCR. Among the five machine learning models, the GBM showed the highest AUC for pCR prediction (AUC, 0.903; 95% confidence interval [CI], 0.833-0.972). External validation confirmed an AUC of 0.833 (95% CI, 0.800-0.865). CONCLUSION: Commonly available clinical and demographic variables were used to develop a machine learning model for predicting pCR following NAC. External validation of the model demonstrated good discrimination power, indicating that routinely collected variables were sufficient to build a good prediction model.

Comprehensive Analysis of Epstein-Barr Virus LMP2A-Specific CD8+ and CD4+ T Cell Responses Restricted to Each HLA Class I and II Allotype Within an Individual.

Latent membrane protein 2A (LMP2A), a latent Ag commonly expressed in Epstein-Barr virus (EBV)-infected host cells, is a target for adoptive T cell therapy in EBV-associated malignancies. To define whether individual human leukocyte antigen (HLA) allotypes are used preferentially in EBV-specific T lymphocyte responses, LMP2A-specific CD8+ and CD4+ T cell responses in 50 healthy donors were analyzed by ELISPOT assay using artificial Ag-presenting cells expressing a single allotype. CD8+ T cell responses were significantly higher than CD4+ T cell responses. CD8+ T cell responses were ranked from highest to lowest in the order HLA-A, HLA-B, and HLA-C loci, and CD4+ T cell responses were ranked in the order HLA-DR, HLA-DP, and HLA-DQ loci. Among the 32 HLA class I and 56 HLA class II allotypes, 6 HLA-A, 7 HLA-B, 5 HLA-C, 10 HLA-DR, 2 HLA-DQ, and 2 HLA-DP allotypes showed T cell responses higher than 50 spot-forming cells (SFCs)/5×105 CD8+ or CD4+ T cells. Twenty-nine donors (58%) showed a high T cell response to at least one allotype of HLA class I or class II, and 4 donors (8%) had a high response to both HLA class I and class II allotypes. Interestingly, we observed an inverse correlation between the proportion of LMP2A-specific T cell responses and the frequency of HLA class I and II allotypes. These data demonstrate the allele dominance of LMP2A-specific T cell responses among HLA allotypes and their intra-individual dominance in response to only a few allotypes in an individual, which may provide useful information for genetic, pathogenic, and immunotherapeutic approaches to EBV-associated diseases.

[Patterns in the Use and Perception of Digital Breast Tomosynthesis: A Survey of Korean Breast Radiologists]. / 디지털 ìœ ë°© í† ëª¨ì‹ í Œì‹œìŠ¤ì— 대한 국내 사용 현황과 인식에 관한 설문조사 연구.

Purpose: To evaluate the pattern of use and the perception of digital breast tomosynthesis (DBT) among Korean breast radiologists. Materials and Methods: From March 22 to 29, 2021, an online survey comprising 27 questions was sent to members of the Korean Society of Breast Imaging. Questions related to practice characteristics, utilization and perception of DBT, and research interests. Results were analyzed based on factors using logistic regression. Results: Overall, 120 of 257 members responded to the survey (response rate, 46.7%), 67 (55.8%) of whom reported using DBT. The overall satisfaction with DBT was 3.31 (1-5 scale). The most-cited DBT advantages were decreased recall rate (55.8%), increased lesion conspicuity (48.3%), and increased cancer detection (45.8%). The most-cited DBT disadvantages were extra cost for patients (46.7%), insufficient calcification characterization (43.3%), insufficient improvement in diagnostic performance (39.2%), and radiation dose (35.8%). Radiologists reported increased storage requirements and interpretation time for barriers to implementing DBT. Conclusion: Further improvement of DBT techniques reflecting feedback from the user's perspective will help increase the acceptance of DBT in Korea.

The Value of Adding Ductography to Ultrasonography for the Evaluation of Pathologic Nipple Discharge in Women with Negative Mammography.

OBJECTIVE: The optimal imaging approach for evaluating pathological nipple discharge remains unclear. We investigated the value of adding ductography to ultrasound (US) for evaluating pathologic nipple discharge in patients with negative mammography findings. MATERIALS AND METHODS: From July 2003 to December 2018, 101 women (mean age, 46.3 ± 12.2 years; range, 23-75 years) with pathologic nipple discharge were evaluated using pre-ductography (initial) US, ductography, and post-ductography US. The imaging findings were reviewed retrospectively. The standard reference was surgery (70 patients) or > 2 years of follow-up with US (31 patients). The diagnostic performances of initial US, ductography, and post-ductography US for detecting malignancy were compared using the McNemar's test or a generalized estimating equation. RESULTS: In total, 47 papillomas, 30 other benign lesions, seven high-risk lesions, and 17 malignant lesions were identified as underlying causes of pathologic nipple discharge. Only eight of the 17 malignancies were detected on the initial US, while the remaining nine malignancies were detected by ductography. Among the nine malignancies detected by ductography, eight were detected on post-ductography US and could be localized for US-guided intervention. The sensitivities of ductography (94.1% [16/17]) and post-ductography US (94.1% [16/17]) were significantly higher than those of initial US (47.1% [8/17]; p = 0.027 and 0.013, respectively). The negative predictive value of post-ductography US (96.9% [31/32]) was significantly higher than that of the initial US (83.3% [45/54]; p = 0.006). Specificity was significantly higher for initial US than for ductography and post-ductography US (p = 0.001 for all). CONCLUSION: The combined use of ductography and US has a high sensitivity for detecting malignancy in patients with pathologic nipple discharge and negative mammography. Ductography findings enable lesion localization on second-look post-ductography US, thus facilitating the selection of optimal treatment plans.

The cost- effectiveness of early dental visit in infants and toddlers focused on regional deprivation in South Korea: A retrospective cohort study.

BACKGROUND: The aims of this study are to evaluate the cost-effectiveness of early dental visits (EDVs) and to investigate how regional deprivation impacts the economic evaluation. METHODS: This study used the South Korea National Health Insurance database, which included medical claim data and voluntary-based oral examination data. The subjects of this study included whole participants for oral examinations for infants and toddlers of the National Health Insurance Corporation. A retrospective cohort study was designed and measured all oral treatments, costs, and number of visits for 208,969 children (experimental group, 101,768; non- experimental group, 107,201) who underwent oral examination for infants and toddlers from 2007 to 2014. The cost-effectiveness was measured using the incremental cost-effectiveness ratio, and the T-health index was used as the measurement for effectiveness. In addition, the difference in the effect according to the level of regional deprivation was confirmed. RESULTS: The findings of this study showed that EDVs were cost-effective and that children who participated in EDVs had better oral health (T-health-2 index difference 0.32 point in most deprived regions) and needed 5 USD less costly dental treatments than those who did not have EDVs. The cost-effectiveness of EDVs varied according to the level of regional deprivation and was the highest in the most deprived regions. CONCLUSIONS: The study findings suggested that the provision of oral examination for infants and toddlers was a cost-effective dental policy. Additionally, EDVs were more effective in children who resided in the most deprived regions, a finding that will lead to the development of policy intervention to improve dental care despite spatial inequality for disadvantaged population groups. Regarding the distribution of dental hospitals/clinics, incentive based dental polices for either dental providers or patients are needed that will assure the delivery of dental care despite spatial inequality.

Microcalcifications and Peritumoral Edema Predict Survival Outcome in Luminal Breast Cancer Treated with Neoadjuvant Chemotherapy.

Background Little is known regarding findings at imaging associated with survival in patients with luminal breast cancer treated with neoadjuvant chemotherapy (NAC). Purpose To determine the relationship between imaging (MRI, US, and mammography) and clinical-pathologic variables in predicting distant metastasis-free survival (DMFS) and overall survival (OS) in patients with luminal breast cancer treated with NAC. Materials and Methods In this retrospective study, consecutive women with luminal breast cancer who underwent NAC followed by surgery were identified from the breast cancer registries of two hospitals. Women from one hospital between January 2003 and July 2015 were classified into the development cohort, and women from the other hospital between January 2007 and July 2015 were classified into the validation cohort. MRI scans, US scans, and mammograms before and after NAC (hereafter, referred to as pre- and post-NAC, respectively) and clinical-pathologic data were reviewed. Peritumoral edema was defined as the water-like high signal intensity surrounding the tumor on T2-weighted MRI scans. The prediction model was developed in the development cohort by using Cox regression and then tested in the validation cohort. Results The development cohort consisted of 318 women (68 distant metastases, 54 deaths) and the validation cohort consisted of 165 women (37 distant metastases, 14 deaths) (median age, 46 years in both cohorts). Post-NAC MRI peritumoral edema, age younger than 40 years, clinical N2 or N3, and lymphovascular invasion were associated with worse DMFS (all, P < .05). Pre-NAC mammographic microcalcifications, post-NAC MRI peritumoral edema, age older than 60 years, and clinical T3 or T4 were associated with worse OS (all, P < .05). The prediction model showed good discrimination ability (C index, 0.67-0.75 for DMFS and 0.70-0.77 for OS) and stratified prognosis into low-risk and high-risk groups (10-year DMFS rates, 79% vs 21%, respectively; and 10-year OS rates, 95%-96% vs 63%-67%, respectively) in the validation cohort. Conclusion MRI features and clinical-pathologic variables were identified that were associated with prolonged survival of patients with luminal breast cancer treated with neoadjuvant chemotherapy. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Kataoka in this issue.

An Artificial Tactile Neuron Enabling Spiking Representation of Stiffness and Disease Diagnosis.

Mechanical properties of biological systems provide useful information about the biochemical status of cells and tissues. Here, an artificial tactile neuron enabling spiking representation of stiffness and spiking neural network (SNN)-based learning for disease diagnosis is reported. An artificial spiking tactile neuron based on an ovonic threshold switch serving as an artificial soma and a piezoresistive sensor as an artificial mechanoreceptor is developed and shown to encode the elastic stiffness of pressed materials into spike frequency evolution patterns. SNN-based learning of ultrasound elastography images abstracted by spike frequency evolution rate enables the classification of malignancy status of breast tumors with a recognition accuracy up to 95.8%. The stiffness-encoding artificial tactile neuron and learning of spiking-represented stiffness patterns hold a great promise for the identification and classification of tumors for disease diagnosis and robot-assisted surgery with low power consumption, low latency, and yet high accuracy.

Deficits in color detection in patients with Alzheimer disease.

Deficits in color vision and related retinal changes hold promise as early screening biomarkers in patients with Alzheimer's disease. This study aimed to determine a cut-off score that can screen for Alzheimer's dementia using a novel color vision threshold test named the red, green, and blue (RGB) modified color vision plate test (RGB-vision plate). We developed the RGB-vision plate consisting of 30 plates in which the red and green hues of Ishihara Plate No.22 were sequentially adjusted. A total of 108 older people participated in the mini-mental state examination (MMSE), Ishihara plate, and RGB-vision plate. For the analyses, the participants were divided into two groups: Alzheimer's dementia (n = 42) and healthy controls (n = 38). K-means cluster analysis and ROC curve analysis were performed to identify the most appropriate cut-off score. As a result, the cut-off screening score for Alzheimer's dementia on the RGB-vision plate was set at 25, with an area under the curve of 0.773 (p<0.001). Moreover, there was a negative correlation between the RGB-vision plate thresholds and MMSE scores (r = -0.36, p = 0.02). In conclusion, patients with Alzheimer's dementia had a deficit in color vision. The RGB-vision plate is a potential early biomarker that may adequately detect Alzheimer's dementia.

Effect of Estrogen Receptor Expression Level and Hormonal Therapy on Prognosis of Early Breast Cancer.

PURPOSE: Estrogen receptor (ER) expression in breast cancer plays an essential role in carcinogenesis and disease progression. Recently, tumors with low level (1%-10%) of ER expression have been separately defined as ER low positive (ERlow). It is suggested that ERlow tumors might be morphologically and behaviorally different from tumors with high ER expression (ERhigh). MATERIALS AND METHODS: Retrospective analysis of a prospective cohort database was performed. Patients who underwent curative surgery for early breast cancer and had available medical records were included for analysis. Difference in clinicopathological characteristics, endocrine responsiveness and five-year recurrence-free survival was evaluated between different ER subgroups (ERhigh, ERlow, and ER-negative [ER-]). RESULTS: A total of 2,162 breast cancer patients were included in the analysis, Tis and T1 stage. Among them, 1,654 (76.5%) were ERhigh, 54 (2.5%) were ERlow, and 454 (21.0%) were ER- patients. ERlow cases were associated with smaller size, higher histologic grade, positive human epidermal growth factor receptor 2, negative progesterone receptor, and higher Ki-67 expression. Recurrence rate was highest in ER- tumors and was inversely proportional to ER expression. Recurrence-free survival was not affected by hormonal therapy in the ERlow group (p=0.418). CONCLUSION: ERlow breast cancer showed distinct clinicopathological features. ERlow tumors seemed to have higher recurrence rates compared to ERhigh tumors, and they showed no significant benefit from hormonal therapy. Future large scale prospective studies are necessary to validate the treatment options for ERlow breast cancer.

Highly Stable Red-Emissive Ratiometric Probe for Monitoring ß-Galactosidase Activity Using Fluorescence Microscopy and Flow Cytometry.

ß-Galactosidase (ß-gal), well known as a useful reporter enzyme, is a potent biomarker for various diseases such as colorectal and ovarian cancers. We have developed a highly stable red-emissive ratiometric fluorescent probe (CCGal1) for quantitatively monitoring the ß-gal enzyme activity in live cells and tissues. This ratiometric probe showed a fast emission color change (620-662 nm) in response to ß-gal selectively, which was accompanied by high enzyme reaction efficacy, cell-staining ability, and outstanding stability with minimized cytotoxicity. Confocal fluorescence microscopy ratiometric images, combined with fluorescence-activated cell sorting flow cytometry, demonstrated that CCGal1 could provide useful information for the diagnosis, prognosis, and treatment of ß-gal enzyme activity-related diseases such as colorectal and ovarian cancers. Further, it may yield meaningful strategies for designing and modifying multifunctional bioprobes with different biomedical applications.

Using a mobile device for margin assessment of specimen mammography in breast-conserving surgery.

ABSTRACT: To compare the performance of margin assessment of specimen mammography (SM) in patients with breast-conserving surgery (BCS) on mobile devices and 5-megapixel (5M) thin film transistor liquid crystal display (TFT-LCD) monitors based on the safety margin for pathologic results.This retrospective study was approved by the institutional review board, and the requirement for informed consent was waived. A total of 105 consecutive breast cancer SM samples from 104 women who underwent BCS were included in the study. The SM were independently reviewed by two radiologists using mobile devices and by two additional radiologists using 5M TFT-LCD monitor. Each reader was asked to measure the shortest distance between the lesion and the lesion margin. The interpretation time was recorded. The sensitivity, specificity, and interobserver agreement were analyzed.In total, 19% (20/105) breast specimens had a positive surgical margin (<1 mm). The mean absolute difference from the pathologic margin was 0.60 ±â€Š0.57 cm and 0.54 ±â€Š0.47 cm using the 5 M TFT-LCD monitor and the mobile device, respectively (without any statistical significance, P = .273). The mean interpretation time was 49.5 and 47.6 s for the 5M TFT-LCD monitor and the mobile device, respectively (P = .012). The pooled sensitivity and specificity were 60% and 74% for 5M TFT-LCD monitor, and 60% and 69% for the mobile device (P = 1.00 and P = .190, respectively). The kappa coefficient indicated moderate agreement for both the displays.The diagnostic performance for margin assessment of SM in BCS patients on mobile devices and 5M TFT-LCD monitors are showed not statistically difference. The findings of the study provide evidence of the benefit of the mobile device for SM interpretation in patients who underwent BCS. However, a large sample size study is warranted before using a mobile device for margin evaluation on SM.The mobile device showed comparable diagnostic performance with 5M TFT-LCD monitor in the evaluation of SM margin in patients with BCS and could be used as a display tool for immediate assessment when a dedicated LCD monitor is unavailable.

Ultrasonography and ultrasound-guided fine-needle aspiration biopsy can predict a heavy nodal metastatic burden in early-stage breast cancer.

PURPOSE: This study aimed to predict a heavy nodal burden (≥3 metastatic axillary lymph nodes [LNs]) using axillary ultrasonography (US) and US-guided fine-needle aspiration biopsy (FNAB) in patients with early-stage breast cancer. METHODS: We retrospectively reviewed the medical records of 403 women (404 cancers) who underwent US-guided FNAB for axillary LN staging from January 2006 to December 2015. US findings and US-guided FNAB results were reviewed and compared using pathology results as the reference. Diagnostic performance was analyzed, and clinicopathological and radiological findings were compared between patients with <3 metastatic LNs and ≥3 metastatic LNs. RESULTS: The final pathology results revealed that 20.5% of cancers had heavy nodal metastases. US-guided FNAB showed significantly higher sensitivity (79.0% vs. 63.0%, P=0.009) and specificity (84.8% vs. 79.3%, P=0.036) in predicting heavy nodal metastases than did US. The presence of a larger number of suspicious LNs (two or more) on axillary US and positive FNAB results were significantly correlated with a heavy nodal burden in the multivariate analysis. The odds ratios were 4.20 (95% confidence interval [CI], 1.90 to 9.39) for two suspicious LNs, 9.40 (95% CI, 2.99 to 29.54) for three or more suspicious LNs, and 14.22 (95% CI, 6.78 to 29.82) for positive FNAB results. CONCLUSION: The number of suspicious LNs detected on axillary US and FNAB results can help predict a heavy axillary nodal burden in patients with early-stage breast cancer.