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Purpose: Cognitive-communication intervention for subjective cognitive decline (SCD) is based on the profile of task performances. The purpose of this study was to identify performances in cognitive-communication and quality of life, to provide the correlation and predictive tasks of communication among subjects with SCD.Methods: SCD group (n = 19) aged 65 and over performed subtasks for the 3 domains, compared with other amnestic mild cognitive impairment (n = 22) and control (n = 24) groups.Results: The main outcomes were as follows. Firstly, the SCD and other two groups had significant differences in performances of executive function (planning/activating) and subjective communication. Secondly, semantic performances in the SCD group were significantly correlated with all cognitive tasks, and reasoning was the strongest predictor of communication. Lastly, discourse had significant correlations with all cognitive tasks in the SCD group. Reasoning (deductive/inductive) and executive function (planning) were also found to be the best predictors of communication.Conclusion: Current study provides a cognitive-communication profile to reduce the risk to develop neurological disease. These results also facilitate the preventive intervention for SCD, warranting its effect.

Las PYMES son un motor importante en la economía mexicana pero casi la mitad de ellas fracasan antes de los dos años de vida por varias razones, especialmente debido a una deficiente administración. Los autores dan a conocer que algunas PYMES mexicanas ya están implementando Balanced Score Card (BSC) con resultados positivos, de acuerdo a una investigación primaria realizada; y recomiendan la aplicación de la misma a las demás PYMES mexicanas como una herramienta innovativa con el fin de evitar posibles fracasos. Mientras tanto, el BSC puede requerir algunos cambios importantes en la cultura dentro de la empresa y requiere de la comp­rensión, el compromiso y el apoyo desde la parte superior de la empresa (Chavan, 2009: 393-406), y debe hacerse una planeación cuidadosa para asegurar los objetivos estratégicos de la empresa (Majidul, 2010).

Purpose This study investigated pathological complete response (pCR) according to androgen receptor (AR) in breast cancer patients undergoing neoadjuvant chemotherapy and estimated the relationship between AR expression and clinicopathological factors.Materials and Methods We identified 624 breast cancer patients who underwent surgery after neoadjuvant chemotherapy at the National Cancer Center in Goyang, Korea from April 2016 to October 2019. We retrospectively collected the clinicopathologic information and AR expression results and analyzed the data according to cancer stage, hormonal receptor (HR) status, human epidermal growth factor receptor 2 (HER2) status, tumor subtype, and pCR.Results Among the 624 breast cancer patients, 529 (84.8%) were AR-positive (AR+) patients and 95 (15.2%) were AR-negative (AR–) patients. AR+ patients showed more estrogen receptor (ER) positivity, progesterone receptor (PR) positivity, HER2-positivity, and HR-positive and HER2-negative (HR+/HER2–) subtype. The rate of pCR was 31.4% (196/624). AR– patients had a significantly higher rate of pCR than AR+ patients (AR– 43.2% vs. AR+ 29.3%, p=0.007). The tumor factors associated with pCR were early stage, histologic grade 3, ER-negative, PR-negative, AR-negative, HER2-positive, and high Ki-67 values. In univariable analysis, AR+ significantly decreased the state of pCR (odds ratio, 0.546; 95% confidence interval, 0.349 to 0.853; p=0.008). According to tumor subtype, AR– tumor showed higher pCR rate in HR+/HER2– subtype (AR– 28.6% vs. AR+ 7.3%, p=0.022).Conclusion AR expression is predominant in the HR+/HER2– subtype. AR– is significantly associated with the pCR rate in breast cancer patients, especially within HR+/HER2– subtype. When determining neoadjuvant chemotherapy for the HR+/HER2– subtype, AR expression can be considered as a pCR predictive marker.

Purpose NUT carcinoma (NC) is a solid tumor caused by the rearrangement of NUTM1 that usually develops in midline structures, such as the thorax. No standard treatment has been established despite high lethality. Thus, we investigated whether targeting the junction region of NUTM1 fusion breakpoints could serve as a potential treatment option for NC. Materials and Methods We designed and evaluated a series of small interfering RNAs (siRNAs) targeting the junction region of BRD4-NUTM1 fusion (B4N), the most common form of NUTM1 fusion. Droplet digital polymerase chain reaction using the blood of patients was also tested to evaluate the treatment responses by the junction sequence of the B4N fusion transcripts.Results As expected, the majority of NC fusion types were B4N (12 of 18, 67%). B4N fusion-specific siRNA treatment on NC cells showed specific inhibitory effects on the B4N fusion transcript and fusion protein without affecting the endogenous expression of the parent genes, resulting in decreased relative cell growth and attenuation of tumor size. In addition, the fusion transcript levels in platelet-rich-plasma samples of the NC patients with systemic metastasis showed a negative correlation with therapeutic effect, suggesting its potential as a measure of treatment responsiveness.Conclusion This study suggests that tumor-specific sequences could be used to treat patients with fusion genes as part of precision medicine for a rare but deadly disease.

Dong-Hoe Koo,1,* Keun Seok Lee,2,* Sung Hoon Sim,2 Heejung Chae,2 Eun-Gyeong Lee,2 Jai Hong Han,2 So-Youn Jung,2 Seeyoun Lee,2 Han-Sung Kang,2 Eun Sook Lee,2 Cheol-Young Park,1,* Sang Woo Oh3,* 1Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 2Center for Breast Cancer, Research Institute and Hospital, National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea; 3Department of Family Medicine, Center for Obesity, Metabolism, and Nutrition, Dongguk University Ilsan Hospital, Goyang-si, Gyeonggi-do, Republic of Korea*These authors contributed equally to this workCorrespondence: Cheol-Young Park, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul, 03181, Republic of Korea, Tel +82-2-2001-1869, Fax +82-2-2001-1588, Email cydoctor@chol.com Sang Woo Oh, Center for Obesity, Nutrition, and Metabolism, Department of Family Medicine, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, 27 Donggung-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 10326, Republic of Korea, Tel +82-31-961-7000, Email osw6021@gmail.comBackground: We have reported that serum progranulin (PGRN) levels are clinically significant in predicting recurrence in patients with HR-positive breast cancer. The aim of the present study was to examine whether PGRN levels might be associated with breast cancer mortality.Methods: This was a cohort study of 695 newly diagnosed breast cancer patients who underwent curative surgery between 2001 and 2004. The relationship between breast cancer mortality and pre-operative serum PGRN levels in these patients with a median follow-up of 12.7 years was evaluated until May 2020.Results: A total of 118 (17%) deaths were identified in the cohort. According to the HR status, (10, 15, and 20)-year overall survival (OS) rates were (91.4, 81.1, and 75.9) % for HR-positive patients, and (76.5, 74.2, and 69.8) % for HR-negative patients, respectively (p = 0.003). Higher levels of PGRN were significantly associated with poor OS in the HR-positive group (p for trend = 0.001). In particular, hazard ratios for PGRN quartiles suggested a dose–response relationship, with the highest quartile having the worst OS in the HR-positive group (highest vs lowest: 15-year OS, (68.3 vs 90.0) %; 20-year OS, (62.3 vs 84.8) %, even after adjusting for age, tumor stage, and metabolic confounders.Conclusion: Pre-operative serum PGRN levels had clinical significance for predicting cancer mortality in breast cancer patients independent of tumor stage and metabolic parameters, especially in HR-positive tumors.Keywords: breast cancer, progranulin, mortality, long-term follow-up

Purpose: The purpose of this study was to understand smartphone use guidance experiences of parents elementary school students.Methods: Qualitative data were collected from 10 parents of elementary school students through individual in-depth interview from January 2022 to February 2022. Collected data were analyzed using the Colaizzi’s phenomenological method.Results: The following four categories were derived from in-depth interviews: ‘Ambivalence on children's smartphone use’, ‘Limitations of guidance competence’, ‘Strategy for guidance’, and ‘New insights and challenges’.Conclusion: This study confirmed that parents of elementary school students were experiencing insight and growth in the process of constantly thinking, trying new strategies, and struggling while guiding their children’s smartphone use. Parental education on elementary school students' smartphone use guidance should include comprehensive contents that could check awareness and principles of useful smartphone use and enable effective guidance tailored to the child's developmental characteristics.

To date, various optimization algorithms have been used to design non-intuitive photonic structures with unconventional optical performance. Good training datasets facilitate the optimization process, particularly when an objective function has a non-convex shape containing multiple local optima in a continuous parametric space. Herein, we developed a discrete-to-continuous optimization algorithm and confirmed its validity by designing and fabricating deep-ultraviolet antireflective MgF2/LaF3 multilayers. For discrete optimization, a multilayer was encoded into a binary vector with multiple bits; a 10 nm thick MgF2 or LaF3 layer was assigned a binary digit of 0 or 1, respectively. Using the binary-based training datasets, a factorization machine formulated a surrogate function, which discovered the ground binary vector representing a near-optimal figure of merit. Then, the figure of merit was refined through continuous optimization (e.g., using an interior-point method) of the ground binary vector. MgF2/LaF3 multilayers with a variety of bit levels were created to attain a minimum average angular (0°–45°) reflectance at 193 nm. A MgF2/LaF3 multilayer optimized at ten bits (i.e., a total thickness of approximately 100 nm) yielded an average reflectance of 0.2%, which agreed well with the experimental results. Moreover, an integrated ray-wave optics simulation predicted that a single CaF2 plano-convex lens coated with the optimized multilayer could exhibit a transmittance of 99.7%. The developed optimization approach will be widely applicable to any photonic structures that can represent a binary vector with multiple bits, such as microwave metasurfaces, in addition to being useful for producing ideal optical multilayers.

Background: Triple-negative breast cancer (TNBC) is highly heterogeneous cancer and the most challenging subtype of breast cancer. And its prognosis is poor compared to the other subtypes. Unlike luminal type cancers, there is no valid biomarker to predict the prognosis of patients with early TNBC. To establish an elaborate therapeutic strategy for TNBC, biomarkers that accurately predict the prognosis and response to treatment are needed. Method: 184 patients with early stage TNBC (training cohort, n = 76; validation cohort, n = 108) were enrolled. Median Follow-up period was 51.5 months (range: 4.6-230.8) for training cohort and 58.3 months (range: 6.6-99.8) for validation cohort. Of the patients in training cohort, 13 patients had recurrence or metastasis. Of the patients in validation cohort, 23 patients had recurrence or metastasis. Using a HiSeq sequencer, RNA sequencing was conducted to analyze the gene expression profiles of tumor samples from TNBC patients. Gene signature was analyzed by combination of DEGs which found in gene expression profiles. Cross validation and meta-analysis were conducted as pre-validation. Meta-analysis was conducted using CBS probePINGS. To compare gene signature and other methods, PAM 50 call and TCR diversity analysis were investigated. Statistical analyses were conducted using R language (v.3.4.3). Result: To predict prognosis of recurrence or metastasis for TNBC patients, we identified the 10-gene signature (DGKH, GADD45B, KLF7, LYST, NR6A1, PYCARD, ROBO1, SLC22A20P, SLC24A3 and SLC45A4) that stratified patients with TNBC by risk score (sensitivity = 92.31%; specificity = 92.06%; accuracy = 92.11%) and validated in a cohort of separate institutions. Meta-analysis supported the biological relevance of the 10-gene signature to well-known driving pathways in TNBC. When compared with other potential biomarkers like PAM 50 call and T-cell receptor β diversity, the 10-gene signature was the only independent factor that can predict prognosis for invasive disease-free survival in multivariate analysis. Conclusion: Our novel findings can contribute to solving the diagnostic challenges in TNBC and the 10-gene signature may serve as a novel biomarker for risk-based patient care. Citation Format: Chang Min Kim, Kyong Hwa Park, Yun Suk Yu, Ju Won Kim, Jin Young Park, Jeong Eon Lee, Sung Hoon Sim, Bo Kyoung Seo, Jin Kyeoung Kim, Eun Sook Lee, Yeon Hee Park, Sun-Young Kong. A 10-gene signature to predict the prognosis of early-stage triple-negative breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-11-25.

Background: Early biologic response to endocrine therapy, such as changes in Ki67 labeling index (LI), has been suggested to predict long-term outcomes in hormone sensitive breast cancer. The addition of a CDK4/6 inhibitor to endocrine therapy has been shown to augment biological response in breast cancer. Pre-operative Endocrine Prognostic Index (PEPI) scores, generated based on post-treatment Ki67 LI, have been shown to predict patient outcomes. EndoPredict® is a multigene assay that predicts the risk of distant recurrence in patients with operable estrogen receptor (ER)-positive HER2-negative breast cancer. This study was conducted to evaluate the efficacy of the neoadjuvant endocrine therapy plus palbociclib versus neoadjuvant endocrine therapy plus placebo. Patients and Methods: This is a phase III randomized, double-blind study of neoadjuvant hormonal therapy plus palbociclib versus neoadjuvant hormonal therapy plus placebo in untreated pre/peri- and post-menopausal women with operable, hormone receptor-positive (ER and/or progesterone receptor), HER2-negative breast cancer. The other major inclusion criteria included tumor size ≥ 15mm, T1c-3N0-1, Ki67 LI ≥14% by central assessment, and no previous history of radiotherapy or systemic therapy for breast cancer. Patients were randomly assigned 1:1 to receive 16 weeks of hormonal therapy plus palbociclib or hormonal therapy plus placebo. Hormonal therapy consisted of letrozole for post-menopausal patients and tamoxifen plus LH-RH agonist for pre/peri-menopausal patients. The co-primary endpoints included PEPI score and EPclin Risk Score, a score combining EndoPredict® molecular score with clinical factors. These scores were sequentially analyzed on a modified intent-to-treat basis according to the gatekeeping procedure: if statistical significance was detected on the PEPI score, the statistical significance of EPclin Risk Score would be assessed. The sample size was 100 patients in each arm, which was calculated with < 5% type I error rate (two sided) and 80% power. Results: Between 16 July 2019 – 7 July 2021, 141 eligible patients were randomized from 25 participating institutes in Japan, Korea, Taiwan, Hong Kong and Australia. One hundred twenty-six patients completed the treatment duration and surgical samples were collected to evaluate endpoints. All randomized patients were evaluable for safety assessment. Randomization was well-balanced in terms of age, menopausal status and cancer stage. The proportion of patients who had a low, moderate, or high PEPI score was 15.2%, 50.0% and 34.8% in the hormonal therapy plus palbociclib arm and 13.3%, 55.0% and 31.7% in the hormonal therapy plus placebo arm, respectively. There was no statistically significant difference in PEPI score between two arms (one-sided p-value=0.563). The proportion of patients who had a high risk EPclin Risk Score seemed lower in the palbociclib arm than in the placebo arm (62.1% vs 68.3%) although hypothesis testing was not performed on EPclin Risk Score because statistical significance was not detected on the PEPI score. No new safety signals were found in the study. Permanent discontinuation from the study in association with adverse events was reported for 7 (9.7%) patients in the hormonal therapy plus palbociclib arm and for 0 patients in the hormonal therapy plus placebo arm. Conclusions: The addition of palbociclib to neoadjuvant hormonal therapy did not improve efficacy measured by PEPI score. In palbociclib arm, the rate of patients who had a high risk EPclin Risk Score after treatment was lower than in placebo arm. Translational researches are ongoing to analyze molecular changes by treatments. The role of chemotherapy after neoadjuvant therapy is under investigation. Clinical trial identification: NCT03969121 Funding: Pfizer Inc. Citation Format: Takayuki Ueno, Louis W.C. Chow, Wonshik Han, Chiun Sheng Huang, G Bruce Mann, Satoshi Morita, Hironori Haga, Elham Fakhrejahani, Takayuki Kobayashi, Kenichi Inoue, Mariko Tokiwa, Hirofumi Suwa, Tomoyuki Aruga, Sachiko Minamiguchi, Yosuke Yamada, Yuko Tanabe, Masahiro Takada, Toshinari Yamashita, Hiroji Iwata, Chi-Feng Chung, Sachiko Takahara, Eriko Tokunaga, Shigeru Imoto, Eun Sook Lee, Yasuaki Sagara, Jee Hyun Kim, Richard H DeBoer, Hyun-Ah Kim, Hung Wen Lai, Ming-Feng Hou, Michelle White, Yoshiko Umeyama. Neoadjuvant hormonal therapy plus palbociclib versus hormonal therapy plus placebo in women with operable, hormone sensitive and HER2-negative primary breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-09-01.

Purpose Tropomyosin receptor kinase (TRK) inhibitors are approved for the treatment of neurotrophic receptor tyrosine kinase (NTRK) fusion-positive tumors. The detection of NTRK fusion using a validated method is required before therapeutic application. An interlaboratory comparison study of next-generation sequencing (NGS)–based NTRK gene fusion detection with validated clinical samples was conducted at six major hospitals in South Korea.Materials and Methods A total of 18 samples, including a positive standard reference and eight positive and nine negative clinical samples, were validated using the VENTANA pan-TRK (EPR17341) and TruSight Oncology 500 assays. These samples were then tested using four different NGS panels currently being used at the six participating institutions.Results NTRK fusions were not detected in any of the nine negative clinical samples, demonstrating 100% specificity in all six participating institutions. All assays showed 100% analytical sensitivity to identify the NTRK fusion status in formalin-fixed paraffin-embedded (FFPE) samples, although with variable clinical sensitivity. False-negative results were due to low tumor purity, poor RNA quality, and DNA-based sequencing panel. The RNA-based targeted NGS assay showed an overall high success rate of identifying NTRK fusion status in FFPE samples.Conclusion This study is the first to test the proficiency of NGS-based NTRK detection in South Korea with the largest participating institutions. RNA-based NGS assays to detect NTRK fusions can accurately characterize fusion transcripts if sufficient RNA of adequate quality is available. The comparative performance data will support the implementation of targeted NGS-based sequencing assays for NTRK fusion detection in routine diagnostics.

We demonstrated a sensor for NO2 detection at room temperature, in which our device was fabricated via screen printing on a flexible substrate, and MoS2 and single-walled carbon nanotube (SWCNT) layer were coated on a specific area by self-assembly.