Peroxiredoxin I deficiency increases keratinocyte apoptosis in a skin tumor model via the ROS-p38 MAPK pathway.

Keratinocyte hyperproliferation is an essential link in skin cancer pathogenesis. Peroxiredoxin I (Prx I) is known to regulate cancer cell proliferation, differentiation, and apoptosis, but its role in skin cancer remains unclear. This study aimed to elucidate the role and mechanism of Prx I in skin cancer pathogenesis. Dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) were used to create a skin tumor model of the initiation/promotion stage of cancer. The role of Prx I in H2O2-induced keratinocyte apoptosis was also investigated. After DMBA/TPA treatment, Prx I deficiency was significantly associated with less skin tumors, lower Bcl-2 expression, and higher p-p38 and cleaved caspase-3 expressions in Prx I knockout tumors than in wild-type controls. H2O2 stimulation caused more cellular apoptosis in Prx I knockdown HaCaT cells than in normal HaCaT cells. The signaling study revealed that Bcl-2, p-p38, and cleaved caspase-3 expressions were consistent with the results in the tumors. In conclusion, the deletion of Prx I triggered the DMBA/TPA-induced skin tumor formation in vivo and in vitro by regulating the reactive oxygen species (ROS)-p38 mitogen-activated protein kinase (MAPK) pathway. These findings provide a theoretical basis for treating skin cancer.

Breast Density in a Contemporary Cohort of Women With Ductal Carcinoma In Situ (DCIS).

BACKGROUND: Mammographic breast density (MBD) is an independent risk factor for breast cancer. Information regarding the relationship of MBD and breast cancer biology in women with ductal carcinoma in situ (DCIS) is currently lacking. This study aimed to examine the clinicopathologic characteristics of DCIS in women stratified by MBD. METHODS: A retrospective review was performed to identify women with pure DCIS who underwent preoperative mammography between 2010 and 2018. Clinicopathologic and demographic data were collected. For the purpose of analysis, MBD was categorized as "non-dense" (Breast Imaging-Reporting and Data System [BI-RADS] density categories A and B) or "dense" (BI-RADS C and D) according to its identification in radiology reports. RESULTS: Of 3227 patients with a breast cancer diagnosis enrolled in the institutional Breast Cancer Database during the study period, 658 (20%) had pure DCIS. Of these 658 patients, 42% had non-dense breasts, and 58% had dense breasts. Most lesions were non-palpable (92%) and detected by mammography (84%). Patients with dense breasts were more likely to be younger at the time of diagnosis (p < 0.001), premenopausal (p < 0.001), and Asian (p = 0.018), and to have higher-grade disease (p = 0.006; Table 2). Family history, BRCA status, parity, mammogram frequency, palpability, method of presentation, lesion size, hormone receptor status, comedo histology, and recurrence did not differ significantly between the two groups (Table 1). The median follow-up period was 7.1 years. CONCLUSION: Women with pure DCIS and higher MBD are more likely to be younger at the time of diagnosis, premenopausal, and Asian, and to present with higher-grade disease. Further research on the relationship of age, MBD, and tumor biology in DCIS is warranted.

Calotropis gigantea extract induces apoptosis through extrinsic/intrinsic pathways and reactive oxygen species generation in A549 and NCI-H1299 non-small cell lung cancer cells.

BACKGROUND: Calotropis gigantea (CG) is a tall and waxy flower that is used as a traditional remedy for fever, indigestion, rheumatism, leprosy, and leukoderma. However, the precise mechanisms of its anticancer effects have not yet been examined in human non-small cell lung cancer (NSCLC) cells. In this study, we investigated whether CG extract exerted an apoptotic effect in A549 and NCI-H1299 NSCLC cells. METHODS: The ethanol extract of CG was prepared, and its apoptotic effects on A549 and NCI-H1299 NSCLC cells were assessed by using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxy methoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, annexin V-fluorescein isothiocyanate/propidium iodide (PI) staining, cell cycle analysis, real-time polymerase chain reaction (RT-PCR), western blotting, JC-1 staining, and ROS detection assay. RESULTS: The CG extract induced apoptosis through the stimulation of intrinsic and extrinsic signaling pathways in A549 and NCI-H1299 lung cancer cells. Cell cycle arrest was induced by the CG extract in both cell lines. Reactive oxygen species (ROS), which can induce cell death, were also generated in the CG-treated A549 and NCI-H1299 cells. CONCLUSIONS: These data confirmed that CG caused apoptosis through the activation of extrinsic and intrinsic pathways, cell cycle arrest, and ROS generation in A549 and NCI-H1299 lung cancer cells. Thus, CG can be suggested as a potential agent for lung cancer therapy.

Preoperative Breast MRI: Surgeons' Patient Selection Patterns and Potential Bias in Outcomes Analyses.

OBJECTIVE: The purpose of this study is to determine which patient- and tumor-related and clinical variables influence dedicated breast surgeons' and general surgeons' referrals for preoperative breast MRI for patients with newly diagnosed breast cancer. MATERIALS AND METHODS: Surgeons who perform breast surgery responded to a survey from June 16, 2014, through August 11, 2014. Participants self-identified as breast or general surgeons and provided professional practice details. They used Likert scores (range, 1-7 with increasing likelihood to order MRI) to weigh numerous patient- and tumor-related and clinical variables. Mean likelihood scores were calculated and compared using a linear mixed model. A p ≤ 0.05 was considered statistically significant. RESULTS: Two hundred eighty-nine surveys from 154 (53%) breast surgeons and 135 (47%) general surgeons showed an overall likelihood to refer for patients with a BRCA mutation (mean Likert score, 6.17), familial (mean Likert score, 5.33) or personal (mean Likert score, 5.10) breast cancer history, extremely dense breasts (mean Likert score, 5.30), age younger than 40 years (mean Likert score, 5.24), axillary nodal involvement (mean Likert score, 6.22), tumor that is mammographically occult (mean Likert score, 5.62) or fixed to the pectoralis (mean Likert score, 5.49), tumor that is a candidate for neoadjuvant treatment (mean Likert score, 5.38), multifocal or multicentric disease (mean Likert score, 5.22), invasive lobular carcinoma (mean Likert score, 5.20), T3 (mean Likert score, 4.48) or T2 (mean Likert score, 4.41) tumor, triple-negative breast cancer (mean Likert score, 4.66), a patient who is a candidate for mastectomy requesting breast conservation therapy (mean Likert score, 5.27), and radiologists' recommendations (mean Likert score, 5.19). Across all patient ages, breast surgeons referred more often than did general surgeons (mean Likert score, 4.32 vs 3.92; p = 0.03), especially for patients with BRCA mutation (mean Likert score, 6.39 vs 5.93; p = 0.01) and tumors smaller than 1 cm (mean Likert score, 3.84 vs 3.40; p = 0.002). Breast surgeons referred less often than did general surgeons for multifocal or multicentric disease (mean Likert score, 5.02 vs 5.44; p = 0.001). Breast surgeons and general surgeons similarly weighed other variables. CONCLUSION: Preoperative breast MRI referral trended with certain higher risk patient- and tumor-related and clinical variables and were nonuniform between the breast surgeons and general surgeon cohorts. Selection bias could affect outcomes analyses for preoperative breast MRI.

Canadian Radiologists Do Not Support Screening Mammography Guidelines of the Canadian Task Force on Preventive Health Care.

PURPOSE: The study sought to determine screening mammography recommendations that radiologists in Canada promote to average-risk patients and family or friends, and do or would do for themselves. METHODS: An online survey was delivered from February 19, 2014, to July 11, 2014. Data included radiologists' recommendations for mammography and their personal screening habits based on gender. The 3 radiologists' cohorts were women ≥40 years of age, women <40 years of age, and men. The distribution of responses for each question was summarized, and proportions for the entire group and individual cohorts were computed. RESULTS: Of 402 surveys collected, 97% (299 of 309) radiologists recommended screening every 1-2 years, 62% (192 of 309) starting ≥40 years of age and 2% (5 of 309) recommended screening every 2-3 years for women 50-74 years of age. Recommendations were similar for family and friends: 96% (294 of 305) recommended screening every 1-2 years, 66% (202 of 305) recommended screening every 1-2 years for women ≥40 years of age, and 2% (5 of 305) recommended screening every 2-3 years. For women radiologists ≥40 years of age, 76% (48 of 63) underwent screening every 1-2 years and started at 40 years of age, 76% (16 of 21) female radiologists <40 years of age would undergo screening ≥40 years of age, 100% every 1-2 years, and 90% (151 of 167) male radiologists would undergo screening every 1-2 years, with 71% (120 of 169) beginning at 40 years of age. CONCLUSION: The majority of Canadian radiologists recommend screening mammography every 1-2 years for average-risk women ≥40 years of age, whether they are patients or family and friends.

A Prospective, Single Arm, Multi-site, Clinical Evaluation of a Nonradioactive Surgical Guidance Technology for the Location of Nonpalpable Breast Lesions during Excision.

OBJECTIVES: This study was a multicenter evaluation of the SAVI SCOUT(®) breast localization and surgical guidance system using micro-impulse radar technology for the removal of nonpalpable breast lesions. The study was designed to validate the results of a recent 50-patient pilot study in a larger multi-institution trial. The primary endpoints were the rates of successful reflector placement, localization, and removal. METHODS: This multicenter, prospective trial enrolled patients scheduled to have excisional biopsy or breast-conserving surgery of a nonpalpable breast lesion. From March to November 2015, 154 patients were consented and evaluated by 20 radiologists and 16 surgeons at 11 participating centers. Patients had SCOUT(®) reflectors placed up to 7 days before surgery, and placement was confirmed by mammography or ultrasonography. Implanted reflectors were detected by the SCOUT(®) handpiece and console. Presence of the reflector in the excised surgical specimen was confirmed radiographically, and specimens were sent for routine pathology. RESULTS: SCOUT(®) reflectors were successfully placed in 153 of 154 patients. In one case, the reflector was placed at a distance from the target that required a wire to be placed. All 154 lesions and reflectors were successfully removed during surgery. For 101 patients with a preoperative diagnosis of cancer, 86 (85.1 %) had clear margins, and 17 (16.8 %) patients required margin reexcision. CONCLUSIONS: SCOUT(®) provides a reliable and effective alternative method for the localization and surgical excision of nonpalpable breast lesions using no wires or radioactive materials, with excellent patient, radiologist, and surgeon acceptance.

"Do unto others as you would have them do unto you": breast imagers' perspectives regarding screening mammography for others and for themselves--do they practice what they preach?

OBJECTIVE: Our aim was to determine the screening recommendations that breast radiologists promote to average-risk patients and family or friends and do or would follow for themselves. MATERIALS AND METHODS: A survey of breast radiologists in the United States collected data regarding their personal and practice backgrounds, their recommendations to others for mammography and clinical and self-breast examination, and their personal screening habits based on respondent sex. The radiologists were divided into three cohorts: women 40 years old or older (group 1), women younger than 40 years (group 2), and men (group 3). The distribution of responses for each question was summarized, and proportions of total radiologists and cohorts were computed. RESULTS: Four hundred eighty-seven surveys were collected. None of the radiologists recommended biennial mammography for patients ages 50-74 years, 98% (477/487) recommended yearly mammography for patients 40 years old and older, and 99% (470/476) recommended yearly mammography for family and friends 40 years old and older. The most common reasons for variance were institutional policy or provider preferences. In group 1, 96% (191/198) have yearly mammography. In group 2, 100% (83/83) have or will have yearly mammography at age 40 years and beyond. In group 3, 97% (171/176) would have yearly mammography at age 40 years and beyond if they were women. Overall, 97% (445/457) of radiologists have or would have yearly mammography at age 40 years and beyond. CONCLUSION: Nearly all (98%) of the radiologists recommend yearly mammography for average-risk women 40 years old and older and were consistent in that they "practice what they preach." Because radiologists diagnose all stages of breast cancer, their personal convictions should influence providers, patients, and the public when considering the U.S. Preventive Services Task Force screening guidelines.

Blended knowledge sharing model in design professional.

Grounded in Nonaka and Takeuchi (Long Range Plan 54(4):102070, 2021) Socialization, Externalization, Combination, and Internalization (SECI) model, the present research develops a Blended Knowledge Sharing Activity (BKSA) model tailored for design practitioners, targeting the enhancement of learning outcomes and creativity. The investigation centers around the influence of BKSA on higher education students' learning achievements and creative potential, further delving into their application and performance relative to social media within design-related coursework. Employing a comprehensive methodological approach including sampling, t-tests, and structural equation modeling, questionnaires were disseminated to a cohort of 105 undergraduate students from two sophomore-level design classes. It is worth underscoring that despite the SECI model finding extensive applicability across numerous domains, its implementation within the context of design education remains comparatively underrepresented. This research lacuna served as a catalyst in our endeavor to apply the SECI model within knowledge-sharing activities specific to design majors, in anticipation of uncovering more potent strategies for learning and innovation. Our findings disclose a tangible positive correlation between BKSA and both the learning outcomes and creativity of undergraduate students. Moreover, the instrument we devised and utilized, acting as a robust measurement tool for the SECI model, provided additional validation for the beneficial influence of BKSA on university students' learning achievements and creative capacities. This novel insight not only redresses the underexplored application of the SECI model in design education but also furnishes a fresh theoretical vantage point for the amalgamation of blended learning and knowledge sharing paradigms.

The relationship of mammographic density and age: implications for breast cancer screening.

OBJECTIVE: Breast density is increasingly recognized as an independent risk factor for the development of breast cancer, because it has been shown to be associated with a four- to sixfold increase in a woman's risk of malignant breast disease. Increased breast density as identified on mammography is also known to decrease the diagnostic sensitivity of the examination, which is of great concern to women at increased risk for breast cancer. Dense tissue has generally been associated with younger age and premenopausal status, with the assumption that breast density gradually decreases after menopause. However, the actual proportion of older women with dense breasts is unknown. The purpose of this study was to examine the relationship between age and breast density, particularly focusing on postmenopausal women. MATERIALS AND METHODS: All screening mammograms completed at the New York University Langone Medical Center in 2008 were retrospectively reviewed. Analysis of variance and descriptive analyses were used to evaluate the relationship between patient age and breast density. RESULTS: A total of 7007 screening mammograms were performed. The median age of our cohort was 57 years. Within each subgroup categorized by decade of age, there was a normal distribution among the categories of breast density. There was a significant inverse relationship between age and breast density (p < 0.001). Seventy-four percent of patients between 40 and 49 years old had dense breasts. This percentage decreased to 57% of women in their 50s. However, 44% of women in their 60s and 36% of women in their 70s had dense breasts as characterized on their screening mammograms. CONCLUSION: In general, we found an inverse relationship between patient age and mammographic breast density. However, there were outliers at the extremes of age. A meaningful proportion of young women had predominantly fatty breasts and a subset of older women had extremely dense breasts. Increased density renders mammography a less sensitive tool for early detection. Breast density should be considered when evaluating the potential benefit of extended imaging for breast cancer screening, especially for women at increased risk for the disease.

Transitioning From Training to Breast Imaging Practice: Building an Academic Career.

Launching an academic career in breast imaging presents both challenges and opportunities for the newly graduated trainee. A strategic plan aligned with one's personal strengths and interests facilitates career success and professional satisfaction. Academic departments offer multiple tracks to accommodate diverse faculty goals. The specific requirements of various tracks vary across institutions. The clinician-educator track typically encourages a focus on medical education and educational scholarship. The clinician-investigator or clinician-scholar track supports original research and grant-funded clinical trials. Finally, the clinical and clinician-administrator tracks allow for emphasis on clinical program development and leadership. As definitions of scholarship broaden, many opportunities are accessible to demonstrate excellence in the traditional areas of clinical practice, education, and research, as well as the broader fields of leadership and administration. Departmental and national society resources that advance knowledge in one's chosen area of interest are available and should be explored. Mentorship and sponsorship can provide valuable insight into identifying such resources and devising a plan for sustainable career success and work-life integration.

Differences between human and machine perception in medical diagnosis.

Deep neural networks (DNNs) show promise in image-based medical diagnosis, but cannot be fully trusted since they can fail for reasons unrelated to underlying pathology. Humans are less likely to make such superficial mistakes, since they use features that are grounded on medical science. It is therefore important to know whether DNNs use different features than humans. Towards this end, we propose a framework for comparing human and machine perception in medical diagnosis. We frame the comparison in terms of perturbation robustness, and mitigate Simpson's paradox by performing a subgroup analysis. The framework is demonstrated with a case study in breast cancer screening, where we separately analyze microcalcifications and soft tissue lesions. While it is inconclusive whether humans and DNNs use different features to detect microcalcifications, we find that for soft tissue lesions, DNNs rely on high frequency components ignored by radiologists. Moreover, these features are located outside of the region of the images found most suspicious by radiologists. This difference between humans and machines was only visible through subgroup analysis, which highlights the importance of incorporating medical domain knowledge into the comparison.

Upgrade rate of intraductal papilloma diagnosed on core needle biopsy in a single institution.

The management of intraductal papilloma (IDP) diagnosed on core needle biopsy (CNB) is controversial due to the variable upgrade rates to breast carcinoma (BC) on subsequent surgical excision reported in the literature. The purpose of our study was to investigate the upgrade rate of IDP diagnosed on CNB to BC in subsequent surgical excision and the impact of clinical, pathologic, and radiologic variables. This is a retrospective cohort of all women who had a diagnosis of IDP on a CNB between 2005 and 2018 in a tertiary academic center with subsequent surgical excision. Upgrade was defined as ductal carcinoma in situ (DCIS) and invasive carcinoma on surgical excision. Statistical analyses included Pearson's chi-square, Wilcoxon rank-sum, and logistic regression. A total of 216 women with IDP in a CNB were included. Nineteen patients (8.8%) upgraded to BC in the overall cohort, including 14 DCIS and 5 invasive carcinomas. An upgrade rate of 27% was found in atypical IDP (14 of 51 cases), while only 3% of pure IDP upgraded to BC (5 of 165 cases). Older age (>53 years) at the time of biopsy (odds ratio [OR] = 1.05, 95% confidence interval [CI] = 1.01-1.09, p = 0.027) and concomitant atypical ductal hyperplasia (ADH) (OR = 9.69, 95% CI = 3.37-27.81, p < 0.0001) were significantly associated with upgrade. Our results support surgical excision of IDP on CNB when associated with ADH or diagnosed in women aged older than 53 years. The low surgical upgrade rate of 3% for pure IDP on CNB in younger women should be part of the management discussion.

Paramedic interactions with the packaging of medications and medical supplies: Poor package design has the potential to impact patient outcomes.

BACKGROUND: Settings where Emergency Medical Services (EMS) are provided to stabilize patients and transport them to locations better equipped to provide comprehensive care, "prehospital settings," are not frequently considered when designing packaged products. Packaging design is an understudied area, potentially impacting both healthcare provider behavior and patient outcomes. Our objectives were to: 1) describe difficulties associated with packaging in prehospital settings 2) investigate the coping strategies used by paramedics when difficulties occurred, and 3) assess the potential impacts these difficulties had on patient care. METHODS: An online, cross-sectional survey was distributed via email using the National EMS Certification database maintained by the National Registry of Emergency Medical Technicians (NREMT) to a random sample of nationally-certified paramedics. Eligible respondents were aged 18 and older, employed as paramedics and had administered care in a prehospital setting within the previous 12 months. Survey items explored difficulties experienced and coping strategies used when difficulty was encountered identifying or opening medications and/or medical supplies. Descriptive statistics and logistic regression were calculated to analyse responses for trends. RESULTS: Of the 12,000 emails sent, 1,912 participants responded (response rate = 16%). After removing respondents who had not administered care within the past 12 months and partial surveys, data from 1,702 respondents were analysed. Nearly 20% of all respondents reported that they had experienced difficulties identifying (21.1%) or opening (20.5%) medications and identifying (17.0%) or opening (23.4%) medical supplies within the past year. Between 1.2% (identifying a medication) and 3.0% (opening supplies) of those included in the analysis indicated that reported difficulties had negatively impacted patient care. Common coping strategies reported to deal with difficulty opening included partner assistance, tool use (scissors, pens, and knives), and the use of teeth, all potential pathways for the transmission of microbes, conceivably further impacting outcomes. CONCLUSION: More thoughtfully designed packaging for prehospital settings has the potential to benefit both EMS providers and the patients that they care for.

Development and Optimization of a Rapid Colorimetric Membrane Immunoassay for Porphyromonas gingivalis.

Porphyromonas gingivalis (P. gingivalis) is a major bacterial pathogen that causes periodontitis, a chronic inflammatory disease of tissues around the teeth. Periodontitis is known to be related to other diseases, such as oral cancer, Alzheimer's disease, and rheumatism. Thus, a precise and sensitive test to detect P. gingivalis is necessary for the early diagnosis of periodontitis. The objective of this study was to optimize a rapid visual detection system for P. gingivalis. First, we performed a visual membrane immunoassay using 3,3',5,5'-tetramethylbenzidine (TMB; blue) and coating and detection antibodies that could bind to the host laboratory strain, ATCC 33277. Antibodies against the P. gingivalis surface adhesion molecules RgpB (arginine proteinase) and Kgp (lysine proteinase) were determined to be the most specific coating and detection antibodies, respectively. Using these two selected antibodies, the streptavidin-horseradish peroxidase (HRP) reaction was performed using a nitrocellulose membrane and visualized with a detection range of 103-105 bacterial cells/ml following incubation for 15 min. These selected conditions were applied to test other oral bacteria, and the results showed that P. gingivalis could be detected without crossreactivity to other bacteria, including Streptococcus mutans and Escherichia fergusonii. Furthermore, three clinical strains of P. gingivalis, KCOM 2880, KCOM 2803, and KCOM 3190, were also recognized using this optimized enzyme immunoassay (EIA) system. To conclude, we established optimized conditions for P. gingivalis detection with specificity, accuracy, and sensitivity. These results could be utilized to manufacture economical and rapid detection kits for P. gingivalis.

Methyl Linderone Suppresses TPA-Stimulated IL-8 and MMP-9 Expression Via the ERK/STAT3 Pathway in MCF-7 Breast Cancer Cells.

Methyl linderone (ML), a cyclo-pentenedione, was isolated from the fruit of Lindera erythrocarpa Makino (family Lauraceae). This plant has well-known anti-inflammatory effects; however, the anti-cancer effects of ML have not yet been reported. Thus, in the present study we investigated the effects of ML on the metastasis of human breast cancer cells. We used 12-O-tetradecanoyl phorbol-13-acetate (TPA)-stimulated MCF-7 cells as the cell model to study the effects of ML on invasion and migration. ML was found to reduce the invasion and migration rate of TPA-stimulated MCF-7 cells. Moreover, it inhibited two metastasis-related factors, matrix metalloproteinase-9 (MMP-9) and interleukin-8 (IL-8), at the mRNA and protein expression levels, in TPA-treated MCF-7 cells. The mechanism by which ML exerted these effects was through the inhibition of translocation of activator protein-1 (AP-1) and signal transducer and activator of transcription-3 (STAT3), mediated via phosphorylation of extracellular signal-regulated kinase (ERK). Taken together, our findings indicated that ML attenuated the TPA-stimulated invasion and migration of MCF-7 cells by suppressing the phosphorylation of ERK and its downstream factors, AP-1 and STAT3. Therefore, ML is a potential agent for the treatment of breast cancer metastasis.

Resolvin D5, a Lipid Mediator, Inhibits Production of Interleukin-6 and CCL5 Via the ERK-NF-κB Signaling Pathway in Lipopolysaccharide-Stimulated THP-1 Cells.

One of the omega-3 essential fatty acids, docosahexaenoic acid (DHA), is a significant constituent of the cell membrane and the precursor of several potent lipid mediators. These mediators are considered to be important in preventing or treating several diseases. Resolvin D5, an oxidized lipid mediator derived from DHA, has been known to exert anti-inflammatory effects. However, the detailed mechanism underlying these effects has not yet been elucidated in human monocytic THP-1 cells. In the present study, we investigated the effects of resolvin D5 on inflammation-related signaling pathways, including the extracellular signal-regulated kinase (ERK)-nuclear factor (NF)-κB signaling pathway. Resolvin D5 downregulated the production of interleukin (IL)-6 and chemokine (C-C motif) ligand 5 (CCL5). Additionally, these inhibitory effects were found to be modulated by mitogen-activated protein kinase (MAPK) and NF-κB in lipopolysaccharide (LPS)-treated THP-1 cells. Resolvin D5 inhibited the LPS-stimulated phosphorylation of ERK and translocation of p65 and p50 into the nucleus, resulting in the inhibition of IL-6 and CCL5 production. These results revealed that resolvin D5 exerts anti-inflammatory effects in LPS-treated THP-1 cells by regulating the phosphorylation of ERK and nuclear translocation of NF-kappaB.

Kanakugiol, a Compound Isolated from Lindera erythrocarpa, Promotes Cell Death by Inducing Mitotic Catastrophe after Cell Cycle Arrest.

A novel compound named 'kanakugiol' was recently isolated from Lindera erythrocarpa and showed free radical-scavenging and antifungal activities. However, the details of the anticancer effect of kanakugiol on breast cancer cells remain unclear. We investigated the effect of kanakugiol on the growth of MCF-7 human breast cancer cells. Kanakugiol affected cell cycle progression, and decreased cell viability in MCF-7 cells in a dose-dependent manner. It also enhanced PARP cleavage (50 kDa), whereas DNA laddering was not induced. FACS analysis with annexin V-FITC/PI staining showed necrosis induction in kanakugiol-treated cells. Caspase-9 cleavage was also induced. Expression of death receptors was not altered. However, Bcl-2 expression was suppressed, and mitochondrial membrane potential collapsed, indicating limited apoptosis induction by kanakugiol. Immunofluorescence analysis using α-tubulin staining revealed mitotic exit without cytokinesis (4N cells with two nuclei) due to kanakugiol treatment, suggesting that mitotic catastrophe may have been induced via microtubule destabilization. Furthermore, cell cycle analysis results also indicated mitotic catastrophe after cell cycle arrest in MCF-7 cells due to kanakugiol treatment. These findings suggest that kanakugiol inhibits cell proliferation and promotes cell death by inducing mitotic catastrophe after cell cycle arrest. Thus, kanakugiol shows potential for use as a drug in the treatment of human breast cancer.

Deep Neural Networks Improve Radiologists' Performance in Breast Cancer Screening.

We present a deep convolutional neural network for breast cancer screening exam classification, trained, and evaluated on over 200000 exams (over 1000000 images). Our network achieves an AUC of 0.895 in predicting the presence of cancer in the breast, when tested on the screening population. We attribute the high accuracy to a few technical advances. 1) Our network's novel two-stage architecture and training procedure, which allows us to use a high-capacity patch-level network to learn from pixel-level labels alongside a network learning from macroscopic breast-level labels. 2) A custom ResNet-based network used as a building block of our model, whose balance of depth and width is optimized for high-resolution medical images. 3) Pretraining the network on screening BI-RADS classification, a related task with more noisy labels. 4) Combining multiple input views in an optimal way among a number of possible choices. To validate our model, we conducted a reader study with 14 readers, each reading 720 screening mammogram exams, and show that our model is as accurate as experienced radiologists when presented with the same data. We also show that a hybrid model, averaging the probability of malignancy predicted by a radiologist with a prediction of our neural network, is more accurate than either of the two separately. To further understand our results, we conduct a thorough analysis of our network's performance on different subpopulations of the screening population, the model's design, training procedure, errors, and properties of its internal representations. Our best models are publicly available at https://github.com/nyukat/breast_cancer_classifier.

Is breast MRI helpful in the evaluation of inconclusive mammographic findings?

OBJECTIVE: The purpose of this study was to evaluate the usefulness of MRI of the breast in cases in which mammographic or sonographic findings are inconclusive. MATERIALS AND METHODS: We retrospectively reviewed images from 115 MRI examinations of the breast performed from 1999 to 2005 for the indication of problem-solving for inconclusive findings on a mammogram. Forty-eight of the 115 women (41.8%) were at high risk. We discerned whether sonography or MRI was used as an adjunctive tool and correlated the findings with those in the pathology database. RESULTS: The equivocal findings most frequently leading to MRI were asymmetry and architectural distortion. No suspicious MRI correlate was found in 100 of 115 cases (87%). These cases were found stable at follow-up mammography or MRI after a mean of 34 months. Fifteen enhancing masses (13%) that corresponded to the mammographic abnormality were seen on MR images. All masses identified at MRI were accurately localized for biopsy, and six malignant lesions were identified. Four of six malignant tumors were seen in one mammographic view only; two were seen on second-look ultrasound images. MRI had a sensitivity of 100% and compared with mammography had significantly higher specificity (91.7% vs 80.7%, p = 0.029), positive predictive value (40% vs 8.7%, p = 0.032), and overall accuracy (92.2% vs 78.3%, p = 0.0052). Eighteen incidental lesions (15.7%) were detected at MRI, and all were subsequently found benign. CONCLUSION: We found breast MRI to be a useful adjunctive tool when findings at conventional imaging were equivocal. Strict patient selection criteria should be used because of the high frequency of incidental lesions seen on MR images.

Investigating the efficacy of an interactive warning for use in labeling strategies used by us pharmacies.

BACKGROUND: United States pharmacies repackage medications into multi-dose vials, enabling customized dosing for prescription drugs. Investment in infrastructure has made this the predominant approach to packaging for US prescriptions. Although recent changes to labeling now discourage the use of auxiliary labels (small stickers highlighting information germane to the safe and effective use), they are still allowed by USP<17>, provided their use comes from an evidence-based perspective. OBJECTIVES: Evaluate how 'interactive,' placements of auxiliary labels (placement requiring physical manipulation of the warning to accomplish a task (e.g. opening)) garner attention as compared to those placed vertically or horizontally. METHODS: Ninety-six participants were eye tracked while opening three prescription vials (each with an auxiliary warning label with a different placement: vertical, horizontal and interactive). Recall and recognition were tested subsequently. Linear mixed models were used to analyze the continuous variables while the binary response variables were analyzed using generalized linear mixed models. The effect of auxiliary labels was fitted as a fixed effect and the subject-to-subject variation was considered as a random effect in the model. Participants' age, health literacy and sex were added to the models if their effect was statistically significant at alpha=0.05. RESULTS: The placement of the warnings significantly impacted the time spent viewing the information they contained at alpha=0.05; people spent significantly longer on interactive placements (0.96; SD 0.13 seconds) than either, horizontal placements (0.27; SD 0.037 seconds) or those placed vertically (0.18 seconds; SD 0.035). Participants were equally as likely to see information presented in an interactive placement (90%; SD 3.8) or horizontal placement (78%; SD 05.5) but less likely to view warnings placed vertically (60%; SD 6.9). Free recall responses also supported the use of interactive placement (62%; SD 6.8 recall) as compared to horizontal placements which were 29%; SD 3.0 and 20%; SD 6.0 for vertical placements. CONCLUSIONS: Data provides evidence which suggests that interactive and horizontal placements out-perform auxiliary labels placed vertically on prescription vials with regard to garnering patient attention.