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The extracellular matrix in solid tumor immunotherapy
No full textThe extracellular matrix (ECM) of solid tumors impacts the antitumor activities of CD8+ T and natural killer (NK) cells in a variety of ways. Cell motility is restricted by the tumor ECM which creates physical barriers. The tumor ECM directly alter the phenotypes and functions of cytotoxic lymphocytes, and indirectly influences immunological synapse-mediated interactions between cytotoxic lymphocytes and cancer cells. Therefore, strategies to improve solid tumor immunotherapy should be established by considering complex ternary interactions between cytotoxic lymphocytes, cancer cells, and the tumor ECM. Novel bioengineering tools approximating key characteristics of the tumor ECM, such as in vitro reconstituted 3D ECMs and microfluidics are valuable from a fundamental study viewpoint and from a translational perspective, aiming to enable systematic screening approaches.N
Contemporary Statistics of Acute Ischemic Stroke and Transient Ischemic Attack in 2021: Insights From the CRCS-K-NIH Registry
No full textThis report presents the latest statistics on the stroke population in South Korea, sourced from the Clinical Research Collaborations for Stroke in Korea-National Institute for Health (CRCS-K-NIH), a comprehensive, nationwide, multicenter stroke registry. The Korean cohort, unlike western populations, shows a male-to-female ratio of 1.5, attributed to lower risk factors in Korean women. The average ages for men and women are 67 and 73 years, respectively. Hypertension is the most common risk factor (67%), consistent with global trends, but there is a higher prevalence of diabetes (35%) and smoking (21%). The prevalence of atrial fibrillation (19%) is lower than in western populations, suggesting effective prevention strategies in the general population. A high incidence of large artery atherosclerosis (38%) is observed, likely due to prevalent intracranial arterial disease in East Asians and advanced imaging techniques. There has been a decrease in intravenous thrombolysis rates, from 12% in 2017-2019 to 10% in 2021, with no improvements in door-to-needle and door-to-puncture times, worsened by the coronavirus disease 2019 pandemic. While the use of aspirin plus clopidogrel for non-cardioembolic stroke and direct oral anticoagulants for atrial fibrillation is well-established, the application of direct oral anticoagulants for non-atrial fibrillation cardioembolic strokes in the acute phase requires further research. The incidence of early neurological deterioration (13%) and the cumulative incidence of recurrent stroke at 3 months (3%) align with global figures. Favorable outcomes at 3 months (63%) are comparable internationally, yet the lack of improvement in dependency at 3 months highlights the need for advancements in acute stroke care.Y
Medical Costs of Nontuberculous Mycobacterial Pulmonary Disease, South Korea, 2015–2019
No full textNontuberculous mycobacterial pulmonary disease (NTM-PD) prevalence is a rising public health concern. We assessed the long-term healthcare systems perspective of costs incurred by 147 NTM-PD patients at a tertiary hospital in South Korea. Median cumulative total medical cost in managing NTM-PD patients was US 3,586–$9,680) over 49.7 months (interquartile range 33.0–68.2 months) of follow-up. The major cost drivers were diagnostic testing and medication, accounting for 59.6% of total costs. Higher costs were associated with hospitalization for Mycobacterium abscessus infection and pulmonary comorbidities. Of the total medical care costs, 50.2% were patient co-payments resulting from limited national health insurance coverage. As South Korea faces significant problems of poverty during old age and increasing NTM-PD prevalence, the financial and socio-economic burden of NTM-PD may become a major public health concern that should be considered with regard to adequate strategies for NTM-PD patients.N
물리 전공이 아닌 중학교 과학교사가 물리 영역을 가르칠 때의 어려움
No full textScience teachers are expected to have high teaching expertise. However, middle school science teachers experience difficulties when teaching all subject areas of science beyond their in-field major. This study investigated the difficulties of middle school science teachers in teaching physics units which are considered to be most difficult to teach. For this purpose, difficulties related to Subject Matter Knowledge(SMK) and Pedagogical Content Knowledge(PCK) were analyzed through open-ended surveys conducted on 36 middle school science teachers with non-physics major, and difficulty factors were analyzed through in-depth interviews conducted on 7 of them. As a result, there were 13 difficulties related to SMK and PCK. In addition, abstract concepts, laws expressed in formulas, and ideal conditions appeared to be factors that caused 13 difficulties when teachers with non-physics major teach physics units. Educational implications for increasing the expertise of science teachers are proposed based on the findings.N
Architecture and anatomy of executive processes: evidence from verbal fluency and Trail Making Test in 2009 stroke patients
No full textObjectivesThe few voxel-wise lesion-symptom mapping (VLSM) studies aimed at identifying the anatomy of executive function are limited by the absence of a model and by small populations. Using Trail Making Test (TMT) and verbal fluency and a model of their architectures, our objective was to identify the key structures underlying two major executive processes, set-shifting and strategic word search.MethodsWe applied a validated VLSM analysis to harmonized cognitive and imaging data from 2009 ischemic stroke patients as a part of the Meta VCI Map consortium. All contrast analyses used an adjusted threshold with 2000 Freedman-Lane permutations (p <= 0.05).ResultsThe TMT parts A and B were associated with structures involved in visual-spatial processing, the motor system, the frontal lobes, and their subcortical connections. Set-shifting depended on the left dorsomedial frontal region. Both semantic and phonemic fluency tests depended on verbal output abilities and processing speed with similar slopes in different languages. The strategic search process depended on Broca's area, F2 and related tracts, temporal and deep regions. Lastly, the lesion map of set-shifting did not overlap with those of strategic word search processes.InterpretationOur results identify the anatomical substrates of two main executive processes, revealing that they represent only a specific subpart of previously reported structures. Finally, our results indicate that executive functions depend on several specific, anatomically separable executive processes mainly operating in various parts of the frontal lobes.N
Transcriptomic Heterogeneity of EGFR-Mutant Non–Small Cell Lung Cancer Evolution Toward Small-Cell Lung Cancer
No full textPurpose: Histologic transformation from EGFR-mutant non-small cell lung cancer (NSCLC) to small-cell lung cancer (SCLC) is a key mechanism of resistance to EGFR tyrosine kinase inhibitors (TKI). However, transcriptomic changes between NSCLC and transformed SCLC (t-SCLC) remain unexplored. Experimental Design: We conducted whole-transcriptome analysis of 59 regions of interest through the spatial profiling of formalin-fixed, paraffin-embedded tissues obtained from 10 patients (lung adenocarcinoma, 22; combined SCLC/NSCLC, 7; and t-SCLC, 30 regions of interests). Transcriptomic profiles and differentially expressed genes were compared between pre- and post-transformed tumors. Results: Following EGFR-TKI treatment, 93.7% (15/16) of t-SCLC components evolved into neuroendocrine-high subtypes (SCLC-A or SCLC-N). The transition to t-SCLC occurred regardless of EGFR-TKI treatment and EGFR mutational status, with a notable decrease in EGFR expression (P < 0.001) at both mRNA and protein levels. Pathway analysis revealed that gene overexpression was related to epigenetic alterations in t-SCLC. Interestingly, histone deacetylase inhibitors restored EGFR expression in SNU-2962A cells and their organoid model. The synergistic effects of third-generation EGFR-TKI osimertinib and the histone deacetylase inhibitor fimepinostat were validated in both in vitro and in vivo models. Conclusions: Our study demonstrated that most t-SCLC cases showed neuronal subtypes with low EGFR expression. Differentially expressed gene analysis and t-SCLC preclinical models identified an epigenetic modifier as a promising treatment strategy for t-SCLC.N
Synthesis of Monodisperse and Discrete Ultra-High Nickel LiNi<sub>0.97</sub>Co<sub>0.02</sub>Mn<sub>0.01</sub>O<sub>2</sub> Octahedral Single Crystals via Single Crystal Intermediates for Li-Ion Batteries
No full textMicrometer-sized single crystal cathodes have garnered significant interest as promising cathode materials for lithium-ion batteries due to their ability to reduce surface area exposure to electrolytes and suppress side reactions, thereby enhancing electrochemical performance. One of the challenging issues with single crystal cathode materials is synthesizing monodisperse and discrete single crystals rather than agglomerated quasi-single crystals. However, conventional solid-state synthesis of most single crystals results in severe agglomeration and cation mixing, as it requires high temperatures to promote particle growth to several micrometers. In this study, a novel morphology-conserving reaction strategy that employs octahedron single crystal intermediates is introduced to synthesize discrete, monodisperse LiNi0.97Co0.02Mn0.01O2 octahedron single crystals. This scalable and cost-effective approach involves using rock-salt Ni0.97Co0.02Mn0.01O1+x octahedrons as single crystal intermediates, which are transformed in unreactive unary lithium salt melts (LiCl and Li2SO4) from spherical Ni0.97Co0.02Mn0.01(OH)2 obtained via coprecipitation. These intermediates are then subjected to a stoichiometric amount of Li precursor in a conventional solid-state synthesis to produce layered LiNi0.97Co0.02Mn0.01O2. This process is a morphology-conserving lithiation reaction, leading to the formation of discrete and monodisperse LiNi0.97Co0.02Mn0.01O2 octahedron single crystals. The resultant LiNi0.97Co0.02Mn0.01O2 single crystals demonstrate superior electrochemical performance, including stable capacity retention over 150 cycles, which surpasses that of typical quasi-single crystals produced through conventional methods. This is attributed to negligible crack formation during cycling, in contrast to significant cracking observed in conventional quasi-single crystals. This implies that single-crystal forms are preferred over agglomerated quasi-single crystal forms for enhancing cycle performance. These findings provide valuable insights into the industrial synthesis of discrete and monodisperse ultrahigh-nickel oxide cathode materials.N
규장각한국학연구원 소장 영변부(寧邊府) 책판의 현황과 특징
No full text본 논문의 목적은 규장각한국학연구원에 소장된 영변부 책판의 목록을 검토하고, 목판조사 결과에 근거하여 그 특징을 살펴보는 것이다. 2장에서는 규장각한국학연구원에 소장된 영변부 책판의 목록을 검토하고, 칠서구해 세트 외에도 『사략』, 『명고집』 2종의 책판이 영변판이라는 것을 고증하였고, 1840년 『각도책판목록』 영변부 항목에 기재된 내용과 거의 일치함을 확인하였다. 이들은 모두 이르면 18세기 중반부터 19세기 중반에 판각된 책판으로 추정되며 판심 등에서 일관된 특징이 관찰된다. 3장에서는 영변부 책판의 판심에 나타나는 특징을 고찰하였다. 대표적인 특징은 판심 부분에 새겨진 각수명과 각종 문양이다. 각수명을 새긴 까닭은 각수들의 작업량을 확인하기 위한 것으로 추정되며, 책판마다 적게는 5~6명 많게는 60명 이상의 각수들이 판각에 참여하였다. 판심에 새겨진 다양한 문양은 각수의 개성을 반영하고 있다. 특히 불상 등 불교 관련 문양을 포함하여 다양한 동물과 사물 묘사가 나타난다. 이것은 내각(內閣), 영영(嶺營) 등 다른 관찬 책판에서는 보이지 않는 영변부 책판만의 특징이다. 마지막으로 일부 각수의 정체를 밝혔다. 어미의 각수명은 대부분 한 글자로 새겨져 있어 그 정체를 밝히기 쉽지 않다. 그러나 승별훈(僧別訓) 서명(瑞明) 등의 사례를 통해 관찬 유교 책판의 판각에 보현사 소속 승려들이 참여하였음을 확인하였다. 이처럼 영변부 책판은 타지역의 책판과 다른 특징을 지니고 있으며, 특히 조선 후기 유교 책판의 판각에 승려들이 참여한 사례를 직접 보여준다는 점에서 중요한 의의가 있다
A syntactic analysis of why definite articles cannot be used in the relative superlatives of Spanish adverbs, verbs, and nouns
No full text본고의 목표는 스페인어의 상대적 최상급과 관련한 몇 가지 질문을 던지고 이에 대해 통사
적 관점에서 답변을 제시하는 것이다. 첫째, 학습자들이 부사, 동사, 명사의 최상급을 표현할 때 종
종 범하는 오류는 정관사를 사용하는 것이다. 이들 세 범주의 최상급을 표현할 때 정관사가 사용될
수 없는 이유는 불어와 달리 스페인어는 최상급 의미 표시를 담당하는 S-DegP의 핵에 한정성 자
질이 없어서 정관사로 문자화될 수 없기 때문이다. 둘째, S-DegP가 최상급 의미를 표시할 수 있
으려면 한정 명사구에 내포되어야 한다. 그 이유는 한정성 자질 결여로 인해 독자적으로는 최상급
의미를 나타낼 수 없는 S-DegP가 한정 명사구에 내포되게 되면 최상급 의미 표시에 필수적인 한
정성 자질을 D로부터 넘겨받을 수 있는 구조적 환경이 만들어지기 때문이다. 셋째, 부사, 동사, 명
사의 최상급을 표현하기 위해서는 관계절을 사용해야 한다. 그 이유는 S-DegP가 관계절 내부에
출현하게 되면 한정 명사구에 내포되는 구조가 형성되어 D로부터 한정성 자질을 넘겨받을 수 있
기 때문이다. 끝으로, 최상급을 내포하는 한정 명사구는 겉모습과 달리 비한정적인 것으로 간주되
는데, 그 이유는 D가 S-DegP의 핵에게 자신의 한정성 자질을 넘겨줌으로써 한정적 특성을 상실
하게 되기 때문이다.
The goal of the present paper is to provide answers from a syntactic
point of view to some questions raised about Spanish relative superlatives. First,
we point out that one of the errors that learners make when expressing the
superlatives of adverbs, verbs, and nouns is the use of definite articles. We
explain why definite articles cannot be used. The reason is that, unlike French, in
Spanish the head of S-DegP (superlative degree phrase), which is responsible
for indicating the superlative meaning, does not have the definiteness feature
and therefore cannot be spelled-out as a definite article. Second, we explain why
S-DegP, which cannot express the superlative meaning on its own, must be
embedded within a definite NP in order to express the superlative meaning. The
reason is that when S-DegP is embedded in a definite NP, it can take over from
D the definiteness feature, which is essential for expressing the superlative
meaning. Third, we explain why relative clauses must be used to express the
superlative meaning of adverbs, verbs, and nouns. The reason is that when
S-DegP appears inside a relative clause, a structure in which S-DegP is embedded
within a definite NP is formed and as a result, S-Deg can take over the definiteness
feature from D. Finally, we explain why definite NPs containing superlatives are
considered indefinite despite their appearance. This is because D loses its
definiteness by transferring the definiteness feature to S-Deg