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Purse seine fishing gear is one of the fishing gear used by the fisherman at the Tegal Fish Landing to catch pelagic fish. This study aims to analyze the composition of purse seine catches and catch rates based on the number of catches and trips to sea, determine the selectivity of purse seine fishing gear base on the number and species. The research method used survey methods and data in quantitative analysis, the analysis of the composition of the catch is secondary to the volume of purse seine catches at Tegal Fish Landing throughout September to November 2019. The capture rate was calculated using secondary data on the number of trips and the total production of purse seine at the Tegal Fish Landing from 2014 to 2018. Selectivity of puse seine fishing gear using primary data includes the number and weight of catches, identification of fishing gear, work equpment, safety equipment, supplies, navigation tools, accident history. The dominant variety of catch species was small pelagic fish, namely Decapterus macrosoma, Sardinella lemuru, and Rastrelliger kanagurta. The largest percentage of catches in September was 52% Decapterus macrosoma, 13% Sardinella lemuru, and Rastrelliger kanagurta. The location of the fishing grounds is in the WPP area 712 and 713 the average CPUE purse seine per year at Tegal Fish Landing was 26.710 kg or 26,7 tons per trip for each vessel. This shows that purse seine capture productivity was still quite low when compared to the size of Gross Tonnage. Purse seine gear for five fishing vessels that landed at Tegal Fish Landing selectively. During the study the proportion of the amount and weight of the five vessels was more thant 60%.

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Purpose:We evaluated the role of everolimus in the prevention of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) progression.Experimental Design:The effects of everolimus on breast cancer cell invasion, DCIS formation, and DCIS progression to IDC were investigated in a 3D cell culturing model, intraductal DCIS xenograft model, and spontaneous MMTV-Her2/neu mouse model. The effect of everolimus on matrix metalloproteinase 9 (MMP9) expression was determined with Western blotting and IHC in these models and in patients with DCIS before and after a window trial with rapamycin. Whether MMP9 mediates the inhibition of DCIS progression to IDC by everolimus was investigated with knockdown or overexpression of MMP9 in breast cancer cells.Results:Everolimus significantly inhibited the invasion of human breast cancer cells in vitro. Daily intragastric treatment with everolimus for 7 days significantly reduced the number of invasive lesions from intraductal DCIS foci and inhibited DCIS progression to IDC in the MMTV-Her2/neu mouse mammary tumor model. Mechanistically, everolimus treatment decreased the expression of MMP9 in the in vitro and in vivo models, and in breast tissues from patients with DCIS treated with rapamycin for 1 week. Moreover, overexpression of MMP9 stimulated the invasion, whereas knockdown of MMP9 inhibited the invasion of breast cancer cell–formed spheroids in vitro and DCIS in vivo. Knockdown of MMP9 also nullified the invasion inhibition by everolimus in vitro and in vivo.Conclusions:Targeting mTORC1 can inhibit DCIS progression to IDC via MMP9 and may be a potential strategy for DCIS or early-stage IDC therapy.

mTOR inhibition decreases MMP9 expression. A, Everolimus treatment for 24 hours did not reduced MMP2 protein levels in SUM225 cells. B, C and D figures were the MMP-9 IHC quantification data measuring average optical density using ImageJ d 1.47 software. B, one-week Everolimus treatments at 2 mg/kg/day significantly decreased MMP9 protein levels in the mammary gland of MMTV/neu mice (n=3). C, one-week-Everolimus treatments at 2 mg/kg decreased MMP9 protein levels in the mammary gland of SUM225-MIND mouse mammary tissues detected by IHC (n=4). D, one-week-rapamycin treatments at 2 mg/day reduced MMP9 protein levels in mammary glands of DCIS patients detected by IHC. **p

Ductal carcinoma in situ (DCIS) is the most common form of breast cancer and is a predecessor to invasive carcinoma development. The origins for early breast cancer have been attributed to aberrant single cells, which may include adult stem and progenitor cells. We performed a window trial with mTOR inhibitor sirolimus in patients with atypical ductal hyperplasia (ADH) or DCIS and investigated the epithelial populations in adjacent normal and ADH/DCIS breast tissues along with their residing stem and progenitor cell activity. Differences associated with age, menopausal status, and treatment by sirolimus have also been explored. While the mammary epithelial populations were seen to be unchanged in aging, we found that age correlates with a decline in stem cell activity. mTOR inhibition was also able to abrogate mammary stem cell activity and decrease luminal progenitor passaging lifespan, particularly in postmenopausal patients. While mTOR inhibition had no effect on myoepithelial populations, it did decrease premenopausal luminal cell populations and reduced prognostic markers associated with breast cancer progression from DCIS to invasive breast cancer. These markers include p16INK4A, COX-2, and Ki67, which were reduced in DCIS breast tissue from patients administered with sirolimus as shown through quantitative analysis of immunohistochemistry. Overall, these findings indicate a link from mTOR signaling to mammary stem cell activity and cancer progression. mTOR inhibitors may have potential for breast cancer prevention. Citation Format: Larry E Broome, Hakim Bouamar, Kate Lathrop, Ismail Jatoi, Andrew Brenner, Michael Garcia, Alia Nazarullah, Karla Moncada, Virginia Kaklamani, Lu-Zhe Sun. Effect of aging and mTOR inhibition on human mammary stem cells and early breast cancer progression markers [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-10-06.

Individual responses to the COVID-19 pandemic are influenced by their knowledge and perception of the pandemic. This study aims to determine the relationship between knowledge and risk perception of MAN 1 Pidie students against Covid-19. This research is a descriptive study using quantitative methods with a survey model, namely a cross-sectional survey. The research population was all MAN 1 Pidie who were selected using a total sampling technique. Data was collected using a questionnaire with the help of the Google Forms application. The data obtained were analyzed descriptively using the Pearson correlation test and simple linear regression test. This study indicates that students' knowledge about covid-19 is in the high category, while students' risk perceptions are in the medium category. Statistical test results show the value of sig. 0.0000.05. Thus, this study concludes a significant relationship between students' knowledge about COVID-19 and their perception of risk for COVID-19.AbstrakRespons individu terhadap pandemi covid-19 dipengaruhi oleh pengetahuan dan persepsinya terhadap pandemi tersebut. Penelitian ini bertujuan untuk mengetahui hubungan antara pengetahuan dan persepsi risiko siswa MAN 1 Pidie terhadap Covid-19. Penelitian ini adalah penelitian deskriptif menggunakan metode kuantitatif dengan model survei yaitu cross sectional survei. Populasi penelitian adalah seluruh siswa MAN 1 Pidie yang dipilih menggunakan teknik total sampling. Data dikumpulkan menggunakan kuesioner dengan bantuan aplikasi google formulir. Data yang diperoleh dianalisis secara deskriptif dan menggunakan uji korelasi Pearson dan uji regresi linier sederhana. Hasil penelitian ini menunjukkan bahwa pengetahuan siswa tentang covid-19 berada pada kategori tinggi, sedangkan persepsi risiko siswa berada pada kategori sedang. Hasil uji statistik menunjukkan nilai sig. 0,0000,05. Dengan demikian penelitian ini menyimpulkan bahwa terdapat hubungan yang signifikan antara pengetahuan siswa tentang covid-19 dengan persepsi resiko mereka terhadap covid-19.

This study attempts to describe the communication strategies used and various kinds of activities carried out by UIN Ar-Raniry public relations in establishing relationships with the press media. The research method used in this study is the qualitative method with a descriptive approach. The data sources of this study were obtained from respondents as the primary data source through several stages in the form of observations records, in-depth interviews, and documentation. The data analysis was performed by using descriptive qualitative analysis techniques through three flows of activities that were carried out simultaneously, namely data reduction, data presentation, and conclusion drawing. The result of the study revealed that the role of public relations of UIN Ar-Raniry in establishing relations with the press media has been going well. It can be seen from the communication strategies used and the various forms of activities that is organized by UIN Ar-Raniry public relation in developing relations with the press media. The communication strategy used is a two-way symmetrical and Reciprocity communication strategy that conforms to the principles of media relations. Several kinds of activities carried out by UIN Ar-Raniry public relations in developing relationships with the press media are Press Coverage, Press Conference, Press Release, Press Statement, Press Interview, and Electronics Communications. Meanwhile, the informal activities are Press Reception and Morning Coffee.

Context.— Associations between granulomatous lobular mastitis (GLM) and Corynebacterium kroppenstedtii have been reported since 2002, but large-scale studies to assess the actual prevalence of this bacterium in GLM have not been performed. Objective.— To assess the prevalence of C kroppenstedtii in GLM using real-time polymerase chain reaction and Sanger sequencing. Design.— We analyzed formalin-fixed, paraffin-embedded tissues from 67 cases of GLM by sequential DNA amplification and sequencing to assess the rate of C kroppenstedtii detection in GLM. A retrospective analysis including patient demographics, history of pregnancy and lactation, clinical signs and symptoms, radiographic findings, histologic pattern, Gram stain results, and microbial cultures was performed on 67 cases of GLM. In addition, 10 cases of nongranulomatous breast abscess were included as controls. Results.— C kroppenstedtii 16S rRNA SYBR real-time polymerase chain reaction was positive on formalin-fixed, paraffin-embedded tissues from 46 of 67 (68.7%) GLM cases, while all control cases were negative. Among the positive cases, the majority showed features of cystic neutrophilic granulomatous mastitis. Conclusions.— C kroppenstedtii was highly prevalent in GLM cases and was not found to be associated with nongranulomatous breast abscess in our study (P < .001).

Dermatofibrosarcoma protuberans (DFSP) is a rare, CD34+ mesenchymal neoplasm that classically involves the dermis. A COL1A1::PDGFB t(17;22) translocation is present in 91.4% to 96% of cases, resulting in aberrant proliferation due to tyrosine kinase hyperactivity. Here, we present a postmenopausal woman with a CD34-positive spindle cell neoplasm of the breast without cutaneous involvement, lacking muscle marker expression, STAT6 expression, and 13q14 deletion by fluorescence in situ hybridization (FISH). Although the classic PDGFB translocation was not detected by FISH, the overall features were highly suspicious for DFSP. Subsequent RNA-based next-generation sequencing revealed an EMILIN2::PDGFD fusion. A literature review showed that PDGFD fusions can be detected in up to 55% PDGFB FISH negative cases, with EMILIN2::PDGFD fusion highly associated with fibrosarcomatous transformation. This holds important diagnostic and prognostic information as fibrosarcomatous-DFSP is associated with higher recurrence and metastatic potential. The tumor was completely resected with clear margins, showed no fibrosarcomatous areas, and no evidence of recurrence is documented 2 years since resection. This review and case report adds to the literature regarding PDGFD-translocation positive DFSP as a differential diagnosis of CD34-positive spindle cell tumors of the breast, while emphasizing the prognostic importance of EMILIN2::PDGFD fusions.

Gene expression profiles of some subtypes of breast cancer were shown to correspond to the profiles of the basal or luminal mammary stem/progenitor cell-enriched epithelial cells implicating the mammary stem cells (MaSCs) as tumor-initiating cells for certain types of breast cancer. Moreover, there is growing evidence that MaSCs may initiate neoplastic transformation when dysregulated in mouse models. We have previously reported an increased frequency of the MaSC-enriched Lin-/CD49fhigh/CD24+ basal cells in old mice (>27 month) compared to young ones (2-4 month) along with an increase of hyperplasic lesions. Gene expression profile revealed an increase of immune and inflammatory responses in old basal cells and stroma cells indicating that aging-induced immune and inflammatory responses might initiate basal cell expansion and transformation. Our preliminary data on mice using rapamycin, an immune and inflammation inhibitor, were very encouraging so we decided to start a clinical window trial (NCT02642094) to test whether rapamycin could reduce biomarkers associated with progression to invasive breast cancer and MaSC numbers in postmenopausal patients with atypical ductal hyperplasia (ADH) or ductal carcinoma in situ (DCIS). The patients enrolled in the trial took rapamycin (sirolimus, 2mg/day) for 5-7 days with 3-7 days of washout before surgery. The adjacent non-tumor surgical tissues were used for the measurements of sphere formation efficiency (SFE) of the basal and luminal cells. The control group were patients with ADH/DCIS who did not take the drug. Rapamycin treatment significantly diminished the SFE of the basal MaSC. Immunohistochemical staining of the biopsies and surgical tissues showed that rapamycin treatment significantly decreased the levels of COX2 (an inflammation marker) and p16 (a senescence marker), and moderately increased p62 (an autophagy marker). Furthermore, rapamycin significantly reduced the proliferation marker Ki67 staining. In conclusion, rapamycin inhibits MaSCs function and senescence and inflammation features in human mammary glands. Whether the suppression of the senescence-associated inflammatory responses is the mechanism by which rapamycin suppresses MaSC function is under investigation. Citation Format: Hakim Bouamar, Larry Broome, Xiang Gu, Alia Nazarullah, Andrew Brenner, Virginia Kaklamani, Ismail Jatoi, Lu-Zhe Sun. Rapamycin inhibits stem cell function and diminishes inflammation and senescence markers in human mammary gland [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-17.

Introduction: Patients with TNBC breast cancer have inferior treatment outcomes compared to other breast cancer subtypes and targeted therapies are lacking. S-equol is a novel oral Estrogen Receptor (ER) Beta agonist with preclinical data showing suppression of TNBC cellular proliferation, and recently presented data showed a decrease in Ki-67 in patients treated with S-equol. This abstract will present the molecular markers that correlate with Ki-67 change in patients with TNBC treated with neoadjuvant S-equol. Methods: We conducted a neoadjuvant window trial that enrolled 39 patients with confirmed TNBC on diagnostic core needle biopsy. Cohort A (20 patients) received a daily dose of 50 mg PO twice daily and Cohort B (19 patients) received a higher dose of 150 mg twice daily. Paired biopsies were evaluable for 36 patients. Both cohorts were treated for a duration of 10-21 days. Primary outcome was change from pre- to post-treatment Ki-67 evaluated by paired t-test and that data was previously published. Secondary endpoints include: Tumor infiltrating lymphocytes in intratumoral and peritumoral (stromal) locations using CD3 (pan T cell) and CD8 (cytotoxic T cell) immunohistochemistry, density of lymphocytes per high power field (40x) for both locations in pre-treatment and post-treatment specimens, Cyclin-D1 protein expression in pre-treatment and post-treatment biopsies as percentage of total tumor cells in pre-treatment and post-treatment specimens, and total estrogen receptor-beta protein expression using immunohistochemistry qualitatively and quantitatively using All-red score in pre-treatment and post-treatment specimens.Results: The primary outcome of Ki-67 decrease of at least 20% from baseline was observed in 28% of the patients. This is a placeholder abstract and an updated abstract with the correlative molecular markers as outlined above will be provided. Conclusion: S-equol is a novel well tolerated oral ER-Beta agonist with inhibition of proliferation in patients with TNBC as measured by a decrease in Ki-67. RNA-seq data, also previously presented, supports potential immune activation during this short period of drug exposure. Future studies aim to evaluate S-equol as an immune activating agent for combination with immunotherapies such as checkpoint inhibitors in TNBC. The pending molecular predictors of response will inform future therapeutic clinical trials for this novel therapy. Citation Format: Kate Lathrop, Virginia Kaklamani, Andrew Brenner, Rong Li, Alia Nazarullah, Sarah Hackman, Courtney Thomas, Jonathan Gelfond, Marisa Rodriguez, Richard Elledge. Molecular markers of response to s-equol, a novel oral estrogen receptor (ER) beta agonist for triple negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS5-31.

Kemiskinan adalah masalah utama di Indonesia, untuk mengatasinya dibutuhkan solusi yang melibatkan masyarakat secara partisipatoris agar mencapai pemberdayaan. Untuk itu pemberdayaan dilakukan oleh Koperasi ini dapat berperan dalam peningkatan kesejahteraan ekonomi. program yang bisa dijalankan yaitu; pembiayaan, pendampingan usaha. Skripsi ini bertujuan untuk (1) menjelaskan bagaimana Program Pemberdayaan Koperasi Lembaga Keuangan Mikro Syariah Amanah Makmur Sejahtera; (2) Bagaimana Program Pemberdayaan Koperasi Lembaga Keuangan Mikro Syariah Amanah Makmur Sejahtera dalam Meningkatkan Kesejahteraan Keluarga.Penelitian ini menggunakan pendekatan kualitatif deskriptif, dengan menggunakan tiga metode pengumpulan data, yaitu metode observasi, wawancara, dan dokumentasi. Untuk menganalisis data, peneliti menggunakan tiga jalur analisis yaitu reduksi data, penyajian data, dan penarikan kesimpulan data. Untuk pengecekan keabsahan data, Pengecekan keabsahan data adalah perpanjangan waktu peneliti di Koperasi Lembaga Keuangan Mikro Syariah Amanah Makmur Sejahtera , ketekunan pengamatan serta triangulasi.Hasil penelitian mengungkapkan bahwa Program Pemberdayaan Koperasi Lembaga Keuangan Mikro Syariah Amanah Makmur sejahtera mampu meningkatkan kesejahteraan nasabahnya Mayoritas nasabah menyatakan bahwa setelah adanya Program Pemberdayaan Koperasi sampai saat ini memang berperan besar dalam membantu meningkatkan perekonomian nasabah. Pada saat ini nasabah telah mengalami sejahtera selaras dengan teori menurut Sugiharto bahwa indikator kesejahteraan antara lain pendapatan, konsumsi atau pengeluaran keluarga, keadaan tempattinggal, kesehatan anggota keluarga, kemudahan mendapatkan pelayanan kesehatan, kemudahan memasuki anak ke jenjang pendidikan dan kemudahan mendapatkan fasilitas transportasi.

Penelitian ini bertujuan untuk mengetahui pengaruh mol rebung bambu dan tingkat kematangan bokashi terhadap pertumbuhan dan hasil tanaman kacang tanah (Arachis hypogaea) ” serta ada tidaknya interaksi antara kedua faktor yang dicobakan.Penelitian ini dilaksanakan dikebun percobaan Fakultas Pertanian Universitas Jabal Ghafur. Penelitian ini menggunakan Rancangan Acak Kelompok (RAK) pola faktorial 3 x 3 dengan 3 ulangan. Faktor perlakuan mol rebung bambu (M) yaitu:M 1 = 75 cc/liter air, M 2 = 150 cc/literair, M 3 = 225 cc/liter air. Faktor pemberian bokasi pemberian yaitu : B 1 = 15 kg/plot, B 2 = 30 kg/plot, B 3 = 45 kg/plot. Parameter yang diamati pada komponen tanaman jagung meliputi : tinggi tanaman (umur 15, 30 dan 45 HST), jumlah polong dalam satu tanaman dan berat polong/plot (kg). Hasil penelitian menunjukan bahwa, pemberian mol rebung bambu tidak berpengaruh nyata terhadap semua pengamatan yang sudah dicobakan. Pemberian bokashi berpengaruh sangat nyata terhadap parameter tinggi tanaman kacang tanah pada umur 15 HST, dan tidak berpengaruh nyata terhadap parameter lainnya pada umur 30 HST dan 45 HST. Perlakuan terbaik di jumpai B 1 (15 kg/plot). Tidak terdapat interaksi yang nyata antara pemberian mol rebung bambu dan tingkat kematangan bokashi terhadap semua pengamatan diamati. Kata kunci : Mol Rebung Bambu, Kematangan Bokhasi, Tanaman Kacang Tanah

Nuclear NADPH oxidase-4 (Nox4) is a key component of metabolic reprogramming and is often overexpressed in renal cell carcinoma (RCC). However, its prognostic role in RCC remains unclear. Here we examined the significance of nuclear Nox4 on disease progression and development of drug resistance in advanced RCC. We analyzed human RCC tissue from multiple regions in the primary index tumor, cancer-associated normal adjacent parenchyma, intravascular tumor in locally advanced cancer patients. We found that the higher nuclear Nox4 expression was significantly associated with progression and death. These findings were consistent after controlling for other competing clinical variables. In contrast, patients with lower nuclear Nox4, even in higher stage RCC had better prognosis. We identified a subset of patients with high nuclear Nox4 who had rapid disease progression or died within 6 months of surgery. In addition, higher nuclear Nox4 level correlated with resistance to targeted therapy and immunotherapy. Western blotting performed on fresh human RCC tissue as well as cell-lines revealed increased nuclear Nox4 expression. Our data support an important prognostic role of Nox4 mediated regulation of RCC independent of other competing variables. Nox4 localizes to the nucleus in high-grade, high-stage RCC. Higher nuclear Nox4 has prognostic significance for disease progression, poor survival, and development of drug resistance in RCC.

Objectives Peripheral blood abnormalities in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been fully elucidated. We report qualitative and quantitative peripheral blood findings in coronavirus disease 2019 (COVID-19) patients and compare them with a control group. Methods We reviewed electronic medical records, complete blood counts, peripheral blood smears, and flow cytometry data in 12 patients with SARS-CoV-2. These were compared with 10 control patients with symptoms suspicious for SARS-CoV-2 but who tested negative. Results No significant differences were noted in blood counts, except that absolute lymphopenia was present frequently in the control group (P < .05). Acquired Pelger-Huët anomaly (APHA) was noted in all COVID-19 cases, in most cases affecting over 5% of granulocytes. This contrasted with APHA in only 50% of control cases, affecting fewer than 5% of granulocytes in all cases (P < .05). Monolobate neutrophils were exclusive to COVID-19 cases. COVID-19 patients had greater frequency of plasmacytoid lymphocytes (P < .05). Flow cytometry data revealed absolute CD3+ T-cell count reduction in 6 of 7 patients; all of them required mechanical ventilation. Conclusions Lymphopenia was infrequent in our COVID-19 cohort; however, flow cytometric analysis revealed absolute T-cell count reduction in most cases. COVID-19 cases had significant APHA with monolobate neutrophils and plasmacytoid lymphocytes as compared to controls.

EBV-related lymphoproliferations in post-transplant settings range from non-destructive hyperplasia to polymorphic post-transplant lymphoproliferative disorder (PTLD) to overt lymphoma. Here we present two unusual cases of pediatric non-mass-forming gastrointestinal (GI) PTLDs with mixed pathologic features of non-destructive and polymorphic categories. Both patients were EBV naive and presented within 1 year of transplant with non-specific gastrointestinal symptoms (diarrhea, abdominal pain, and food intolerance) with hypoalbuminemia, cytopenia, and EBV viremia. No mass lesions were found on imaging and endoscopy. Random GI biopsies showed a non-mass-forming, but polymorphic-appearing lymphoid infiltrate with EBV positivity, monotypic plasma cells, and clonal B cells. Cyclophosphamide, steroids, and rituximab treatment had good clinical response in all cases, including one case which had poor response initially with rituximab alone. Based on these cases, we conclude that GI PTLD in children can present with vague abdominal symptoms, cytopenia, and hypoalbuminemia, and can be non-mass-forming and non-destructive. A high level of suspicion with random GI biopsies and clinicopathologic and laboratory correlation are required. Since these patients have no mass lesions, evaluating symptomatic relief, EBV viral load, improvement in cytopenia(s), serum albumin levels, and/or resolution of other systemic symptoms may be needed to monitor response to therapy.

Purpose: We evaluated the role of everolimus in the prevention of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) progression. Experimental Design: The effects of everolimus on breast cancer cell invasion, DCIS formation, and DCIS progression to IDC were investigated in a 3D cell culturing model, intraductal DCIS xenograft model, and spontaneous MMTV-Her2/neu mouse model. The effect of everolimus on matrix metalloproteinase 9 (MMP9) expression was determined with Western blotting and IHC in these models and in patients with DCIS before and after a window trial with rapamycin. Whether MMP9 mediates the inhibition of DCIS progression to IDC by everolimus was investigated with knockdown or overexpression of MMP9 in breast cancer cells. Results: Everolimus significantly inhibited the invasion of human breast cancer cells in vitro. Daily intragastric treatment with everolimus for 7 days significantly reduced the number of invasive lesions from intraductal DCIS foci and inhibited DCIS progression to IDC in the MMTV-Her2/neu mouse mammary tumor model. Mechanistically, everolimus treatment decreased the expression of MMP9 in the in vitro and in vivo models, and in breast tissues from patients with DCIS treated with rapamycin for 1 week. Moreover, overexpression of MMP9 stimulated the invasion, whereas knockdown of MMP9 inhibited the invasion of breast cancer cell–formed spheroids in vitro and DCIS in vivo. Knockdown of MMP9 also nullified the invasion inhibition by everolimus in vitro and in vivo. Conclusions: Targeting mTORC1 can inhibit DCIS progression to IDC via MMP9 and may be a potential strategy for DCIS or early-stage IDC therapy.

Microscopic granulosa cell proliferations are rare incidental findings in ovarian and extraovarian tissue, and can simulate granulosa cell tumors. We report a case of a 22-yr-old nulliparous woman with incidental microscopic granulosa cell proliferation in the wall of an endometriotic cyst. Excision of the cyst revealed extensive endometriosis and incidental microscopic nests and cords of granulosa cells measuring 1.5 mm and positive for inhibin A and calretinin. A rare Call-Exner body was noted. An extensive literature review of both ovarian and extraovarian granulosa cell proliferations were performed to determine their possible origin, variable morphologic features and differential diagnosis. Forty-seven cases were identified occurring in pregnant (26%) and nonpregnant (74%) settings. The nonpregnant cases reveal an association with endometriosis and endometrioid adenocarcinomas. Follow-up data is very limited, but no reports of subsequent granulosa cell tumors are reported. We hypothesize that possible anovulation may play a role in the development of these proliferations. Because of unknown pathogenesis and limited follow-up data being available, their clinical significance and risk of neoplasia remain unclear.

Purpose: To develop and validate a convolutional neural network (CNN) to identify regions of interest (ROIs) suspicious for ductal carcinoma in situ (DCIS) and residual malignancy in lumpectomy margins using wide-field optical coherence tomography (WF-OCT). Background: WF-OCT is the optical analog of high-frequency ultrasound and produces high-resolution intraoperative imaging in real time, with a tissue penetration depth up to 2 mm. Multi-reader studies of WF-OCT have demonstrated the ability to differentiate normal breast parenchyma from neoplasms with greater than 85% sensitivity and specificity. Intraoperative evaluation of lumpectomy specimens using WF-OCT may aid in achieving negative margins at the time of primary surgery and avoid re-excisions. CNNs, a form of artificial intelligence (AI), can be trained to spot ROIs in WF-OCT images of margins suspicious for DCIS and, more generally, residual malignancy. Methods: Lumpectomy margins from 126 patients with ductal malignancy were imaged using WF-OCT, compared to permanent histology (PH), and annotated by board-certified breast pathologists to create a training set of 25,000 control ROIs. A CNN algorithm was developed with 3 convolutional layers, a 3x3 kernel, and 3 fully connected layers to perform binary classification of images as either “suspicious” or “non-suspicious” for malignancy. A weighted loss function was implemented to balance the training data available for non-suspicious vs. suspicious images and to tune sensitivity and specificity. Once trained and properly weighted, the CNN was tested in a prospective study using WF-OCT images of margins from 29 lumpectomy specimens from 29 patients with biopsy-proven DCIS, invasive ductal carcinoma (IDC), or both. The CNN results were compared to PH. Results: Patients were 61.5 ± 7.3 years old, 100% female, with Stage 0-1 disease. Disease types included DCIS (n=27), atypical ductal hyperplasia (n=24), IDC (n=20), invasive lobular carcinoma (n=2), mixed (n=74), and benign findings including usual ductal hyperplasia (n=35), atypical lobular hyperplasia (n=19), duct ectasia (n=17), lymphatic invasion (n=13), and lobular carcinoma in situ (n=12). Following primary surgery, fresh margins were scanned using WF-OCT and approximately 1.9M ROIs were analyzed by the CNN, yielding 15,136 as suspicious for malignancy. Overall, four hundred and ten (410) ROIs were correctly identified, yielding a 74% true positive and 0.8% false positive detection rate; sensitivity and specificity were 74.4% and 99.2%, respectively. Specific to DCIS, the CNN demonstrated a 73% true and 0.5% false positive rate; sensitivity and specificity were 73.0% and 99.5%, respectively. Conclusions: Automated analysis of WF-OCT images of lumpectomy specimens, using a trained CNN to identify ROIs suspicious for malignancy is feasible, demonstrating high concordance with PH. Specific to DCIS, the CNN demonstrated equivalent utility with a lower false positive rate. A prospective trial is needed to evaluate specimens in real time to determine improvement in re-excision rates. Citation Format: David Rempel, Andrew Berkeley, Alastair Thompson, Savitri Krishnamurthy, Beryl Augustine, Kelly Hunt, Ismail Jatoi, Alia Nazarullah, Chandandeep Nagi, Yanir Levy. Development and validation of a convolutional neural network to identify ductal carcinoma in situ in lumpectomy margins using wide field optical coherence tomography [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr A004.