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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.

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.

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.

Purpose The objective is to develop a real-time Mitochondrial ATP contents and Response Against Inhibiting and Stimulating Substrates (MitoRAISE) assay and assess its potential to evaluate the mitochondrial oxidative phosphorylation function. Methods MitoRAISE measures the total ATP contents, ATP synthesis capacity, and the response to inhibitory substrates. The measurements were all quantified with an ATP standard curve and validated with in vitro testing. MitoRAISE was then applied using peripheral blood mononuclear cells (PBMCs) from 35 healthy volunteers and 20 breast cancer patients. Result Results from isolated mitochondria, cells with different permeabilization percentages, and cells with damaged mitochondria demonstrated the ability of capturing ATP signals specifically from the mitochondria. Breast cancer PBMCs exhibited a significant increase in glutamic acid- and malic acid-induced mitochondrial ATP synthesis capacity yet a significant decrease in mitochondrial DNA copy number (mtDNA CN) compared to healthy PBMCs. Furthermore, breast cancer PBMCs mostly showed negative correlation between mtDNA CN and parameters from MitoRAISE but healthy individuals showed positive correlation. Conclusion We developed a quick and easy method to detect real-time mitochondrial activity in live cells. Monitoring mitochondrial ATP synthesis capacity and sensitivity to inhibitory substrates could aid in assessing the functional status of mitochondrial oxidative phosphorylation.

Purpose: This study intends to analyze the current status and characteristics of the hearing impaired by analyzing ‘actual survey data for the disabled’ from 2005 to recent, and to use them as basic data for establishing rehabilitation and welfare service policies for the hearing impaired.Methods: Among the items related to hearing impairment in the survey data, longitudinal, and meaningful areas such as general characteristics, hearing aid and communication, education and welfare services of the hearing impaired were mainly analyzed.Results: The prevalence of hearing impairment was 0.65% to 0.66% and the age distribution of the hearing impaired increased rapidly after the age of 50, and the proportion of over 65 years old increased by about 17.9% from 55.3% in 2008 to 73.2% in 2017. The rate of acquired factors (5.2% as of 2017) was higher than that of congenital factors as the cause of hearing impairment. The rate of people with hearing impairment who did not attend school increased as they went up from elementary school to high school, and the rate was the highest among the major areas of disability. Among the welfare needs of the hearing impaired, income security (40.4% as of 2017) was the highest.Conclusion: If research that reflects the various characteristics of hearing impairment is expanded in addition to periodic actual surveys for the disabled in the future, the current results is expected that it can be used as basic data for mid- to long-term welfare policies for the hearing impaired.

Supplementary Information

Combination therapy of ALK and β3 inhibitors shows promising results in vivo and in ALK-rearranged NSCLC

Treatment information of patients who received crizotinib

Purpose: Anaplastic lymphoma kinase (ALK)-positive cancers are sensitive to small-molecule ALK kinase inhibitors, but most cases experience failure following treatment. Hence, additional drug targets and combination therapeutic treatments are needed. We investigated gene expression that is regulated by the expression of ALK and explored its roles in cancer progression and therapeutic implication.Experimental Design: We screened ALK-rearranged non–small cell lung cancer (NSCLC) cases using immunohistochemistry and fluorescence in situ hybridization and then conducted multiplex gene expression analysis. We also performed a clinicopathologic analysis to validate the findings. Additional cellular experiments, including inhibition and migration assays, and in vivo lung cancer model studies were performed.Results: Among patients with ALK-rearranged NSCLC, integrin β3 (ITGB3) was one of the overexpressed genes in comparison with that in ALK-negative NSCLC (P = 0.0003). ALK and integrin β3 expression were positively correlated, and we discovered that high integrin β3 mRNA expression was associated with metastasis and more advanced tumor stages (P < 0.005; P < 0.05). Furthermore, we found that inhibition of both ALK and integrin β3 led to increased drug sensitivity in vitro and in vivo (both P < 0.05).Conclusions: We discovered a positive correlation between ALK and integrin β3 expression levels in ALK-rearranged NSCLC. Our findings suggest that high integrin β3 expression in ALK-rearranged NSCLC is associated with tumor progression and a worse prognosis. This finding demonstrates the prognostic value of integrin β3 and provides a rationale for combination treatment with ALK and integrin β3 inhibitors in patients with ALK-rearranged NSCLC. Clin Cancer Res; 24(17); 4162–74. ©2018 AACR.

Purpose: The “oldest-old” is the heterogeneous population compared with the younger-old in several cognitive-communication aspects. Accordingly, it is necessary to intervene in them discriminately. This study aimed to suggest the performance profiles by cognitive-communication tasks for intervention in oldest-old.Methods: Sixty-four oldest-old subjects aged 80 or older years performed 16 subtasks for the five cognitive-communication domains. And the performance profiles of group I (84.00 ± 2.62 years) and II (93.38 ± 1.61 years) were analyzed.Results: The main findings were as follows. Firstly, two groups had significant differences in performances of most tasks including working memory, reasoning, word fluency, and subjective communication. Secondly, five communication tasks were significantly correlated with all cognitive tasks and were predicted by the reasoning tasks like similarity in group I. Thirdly, word fluency and pragmatic expression tasks were significantly correlated with all cognitive tasks. Tasks including verbal problem solving were found to be the best predictors of confrontation naming in group II.Conclusion: Current study provides evidence-based information to support cognitive-communication intervention for the oldest-old. These results also can contribute to increase the efficacy of the cognitive-communicative intervention.

Mild cognitive impairment (MCI) is the sign of dementia, and is critical for prediction and preventing its progressions. This study aimed to review literature on cognitive communication intervention of MCI patients systematically, and propose the evidence-based data, including their effect sizes using a meta-analysis method. Thirty-eight researches published since 2012, meeting the inclusion and exclusion criteria, were entered into this analysis. They were analyzed in qualitative aspects, and their effect sizes were calculated in a level of mean and each domain. Outcome measures included the domains of 10 cognitions and 4 communications. The main findings were as follows. Firstly, the general target population for studies was MCI over the age of 50, and intervention programs were designed diversely in a session or mode. Secondly, several domains, including attention, memory, and executive function held a large portion of the intervention programs. Thirdly, the average effect size of interventions was large. Lastly, processing speed and word fluency were very effective and significant among domains in the results of treatment. Current study provides evidence-based information to support cognitive-communication intervention for individuals with MCI. These results also can contribute to diversify intervention approaches and verify their efficacies. Given this, it is possible to facilitate the cognitive-communication intervention for MCI in clinical settings.

Mild cognitive impairment (MCI) is the preclinical stage and sign of dementia. It is also important for guidance in the prevention and intervention of neurological disease. The purpose of this study was to review literatures on cognitive/communicative and other predictors of MCI patients systematically, and to propose the evidence-based data including effect sizes of them using a meta-analysis method. Fifty-seven researches published since 2010, meeting the inclusion and exclusion criteria, were entered into the analysis. They were analyzed in a methodological and content level, and the effect sizes were calculated by 3 predictors. Predictive values were pooled from cognitive (10 domains), communicative (9 domains), and other (3 domains). The main findings were as follows. Firstly, the general target population for studies was older adults over the age of 55, and most studies included at least 2 types of predictors. Secondly, average effect sizes of 3 predictors in MCI were all significant. Thirdly, cognitive predictors like memory and general cognition had significant and high-level effect sizes. Fourthly, communicative predictors including comprehension and word fluency had moderate-level effect sizes significantly. Lastly, all demographic and neuropsychological (age, education, depression) predictors had significant and moderate-level effect sizes. Our results provide the evidence-based information to predict MCI. Especially, specific cognitive and communicative predictors may contribute to increase the diagnostic and prognostic accuracy in MCI. This study is also expected to present clinically available data and increase the effect in intervention for MCI.

Purpose: Higher order cognition (HOC) is commonly impaired in neurological disease including mild cognitive impairment (MCI) and dementia of Alzheimer’s type (DAT). The impact of this deficit is particularly prominent in communication. The purpose of this preliminary study was to investigate the correlation between HOC and communication in MCI and DAT using Brief test of Cognitive-Communication Disorders (BCCD), and to demonstrate subdomains of communication as predictors of HOC.Methods: Healthy controls (n = 40), persons with MCI (n = 31) and DAT (n = 40) completed the subtests of HOC and communication in BCCD. HOC and communication tests consisted of 9 (organization/reasoning/problem solving/executive function) and 12 (comprehension/expression/reading & writing/pragmatic language) items respectively.Results: The main findings were as follows. Firstly, there was a significant difference among three groups in most subdomains and total scores of HOC and communication. Secondly, HOC was significantly associated with comprehension and total score in MCI. A significant relationship between HOC and all domains of communication was also observed in DAT. Thirdly, expression, pragmatic language, and total score were predictors of HOC in MCI, while only total score of communication predicted HOC for individuals with DAT.Conclusion: This study is expected to present clinically available data in assessment and intervention for cognitive-communication disorders. Specific communication measures as powerful indicators of HOC may contribute to increase the diagnostic and prognostic accuracy in MCI and DAT.

The purpose of this study was to investigate the effects of working memory intervention on language production by people with mild or moderate Alzheimer's disease (AD). A total of 39 AD patients, 21 with mild AD and 18 with moderate AD and 18 normal controls were given 18 sessions of working memory intervention. After these sessions, the transfer effects and maintenance effects at the 3-month follow-up were assessed. A word-span task and a digit-span task were used to evaluate working memory. Language-production abilities were compared through four tasks: a verbal fluency, a confrontation naming, a word definition, and a picture-description task. Task performances of working memory and language production were the lowest in the baseline stage and the highest in the transfer-effect stage. The three groups had transfer effects in all tasks, while the maintenance effects were limited by groups and tasks. This study proves that working memory intervention for AD patients is effective for language production. In addition, we have paved the way for working memory intervention to improve language production by AD patients in clinical settings by presenting the transfer and maintenance effect for each task of language production.

대한민국 국민의 해외여행 비율은 매년 증가 추세인데 반해, 국내여행 비율은 수년간 답보 상태에 있다. 이에, 정부에서는 다양한 국내 관광 활성화 정책을 시행하고 있으나, 이를 통한 국내관광 증진 효과는 제한적이다. 국내관광을 활성화시키기 위해서는, 여행자들별로 선호하는 여행 방식에 차이가 있음을 이해하고, 이에 맞춤화된 여행 서비스를 제공할 필요가 있다. 본 연구는 대한민국 국민들의 세대별 여행 방식의 특징을 분석한 후, 각 세대별로 맞춤화된 여행 서비스를 구성하기 위한 시사점을 도출하였다. ‘세대’란 같은 시대에 살면서, 비슷한 생애주기에 유사한 내/외부의 경험을 하기 때문에 (김기연 등, 2003), 다른 세대와는 구별되는, 그 세대만의 관광 방식이 있을 수 있다. 본 연구는 여행상품 구성의 관점에서 세대 간 차이를 살펴보았다. 즉, 여행 상품 구성 및 마케팅에 필요한 요소인, 여행 정보 수집 방식 및 출처, 사전 예약 상품의 종류, 패키지 이용 여부, 여행 시기/기간 및 장소, 여행시 주요활동 그리고, 여행만족도에 영향을 미치는 요인 등에 대한 세대 간 차이를 파악하고 시사점을 도출하였다. 본 연구에는 한국 문화체육관광연구원에서 수집한 2017년 국민 여행 실태조사 데이터 16,713건이 활용되었으며, 데이터는 패널들의 세대에 따라서, 밀레니얼(19세~34세), X세대(35세~54세), 베이비부머(55세~64세), 시니어(65세 이상) 등으로 구분하여 사용하였다. 본 연구결과, 전 세대 모두 자연경관이 수려하고, 문화유산이 풍부하며, 숙박 시설이 쾌적할 때, 여행만족도가 유의미하게 향상되었다. 또한, 전체 패키지보다는 숙박, 차량 대여 등 개별 상품을 쉽게 구매할 수 있도록 하고, 맛집 탐방 상품을 제공하는 것도 유효할 수 있을 것이다. 각 세대별로는, 밀레니얼은 여름철 성수기에 인기 방문지를 중심으로 체험 상품을 구성하는 것이 좋으며, 이들을 위한 관광 안내 시설을 잘 마련할 필요가 있겠다. 또한, 포털사이트와 소셜네트워크 서비스를 통한 마케팅도 밀레니얼 세대에게 효과적일 것으로 보인다. X세대는 자가용으로 여행하기 좋은 지역에, 자녀와 함께 할 수 있는 체험형 여행상품이 유효할 것으로 보인다. 이들에게는 교통만족도가 중요하며, 여름철 성수기에 인기 관광지로 여행을 많이 간다는 특징은 밀레니얼 세대와 유사하다. 베이비부머와 시니어 세대의 경우, 자연 감상 및 휴식, 쇼핑 등을 포함한 여행 상품을 구성하는 것이 좋을 것으로 보이며, 인터넷을 통한 마케팅보다는 구전 효과를 이용하는 것이 유효하겠다. 특히 시니어 세대의 경우, 봄가을을 중심으로, 당일 여행 패키지 상품을 구성하는 것도 효과적일 것으로 보인다. 이러한 세대별 여행 특성을 고려하여 맞춤화된 관광 상품을 구성한다면, 궁극적으로 국내관광산업을 활성화에 기여할 수 있을 것으로 기대된다.