Autophagy is a highly conserved self-digestion process, which is essential for maintaining homeostasis and viability in response to nutrient starvation. Although the components of autophagy in the ...cytoplasm have been well studied, the molecular basis for the transcriptional and epigenetic regulation of autophagy is poorly understood. Here we identify co-activator-associated arginine methyltransferase 1 (CARM1) as a crucial component of autophagy in mammals. Notably, CARM1 stability is regulated by the SKP2-containing SCF (SKP1-cullin1-F-box protein) E3 ubiquitin ligase in the nucleus, but not in the cytoplasm, under nutrient-rich conditions. Furthermore, we show that nutrient starvation results in AMP-activated protein kinase (AMPK)-dependent phosphorylation of FOXO3a in the nucleus, which in turn transcriptionally represses SKP2. This repression leads to increased levels of CARM1 protein and subsequent increases in histone H3 Arg17 dimethylation. Genome-wide analyses reveal that CARM1 exerts transcriptional co-activator function on autophagy-related and lysosomal genes through transcription factor EB (TFEB). Our findings demonstrate that CARM1-dependent histone arginine methylation is a crucial nuclear event in autophagy, and identify a new signalling axis of AMPK-SKP2-CARM1 in the regulation of autophagy induction after nutrient starvation.
Nature-based therapy (NBT), which centers around engaging in activities within natural surroundings, has consistently demonstrated therapeutic benefits for mental health. While NBT highlights the ...potential of nature as a therapeutic resource for promoting mental health, there is limited knowledge regarding its underlying mechanisms.
Two hundred seventy-six Korean participants (204 women, mean age = 54.99 ± 23.25 years) participated in a 30-session gardening program held twice weekly for 15 weeks. Structural equation modeling with a two-wave autoregressive cross-lagged model was used to investigate the mediating effects of mindfulness.
NBT significantly improved the mean scores of all psychological variables. The mediation model was partially confirmed, with mindfulness at post-intervention (T2) mediating the relationship between baseline (T1) depression and anxiety and post-intervention (T2) life satisfaction. However, no significant indirect effect was observed between the path from stress (T1) to life satisfaction (T2).
Mindfulness is a crucial component for improving mental health outcomes. This study underscores the need to prioritize and emphasize mindfulness practices in NBT.
Self-report multiple choice questionnaires have been widely utilized to quantitatively measure one's personality and psychological constructs. Despite several strengths (e.g., brevity and utility), ...self-report multiple choice questionnaires have considerable limitations in nature. With the rise of machine learning (ML) and Natural language processing (NLP), researchers in the field of psychology are widely adopting NLP to assess psychological construct to predict human behaviors. However, there is a lack of connections between the work being performed in computer science and that of psychology due to small data sets and unvalidated modeling practices.
The current article introduces the study method and procedure of phase II which includes the interview questions for the five-factor model (FFM) of personality developed in phase I. This study aims to develop the interview (semi-structured) and open-ended questions for the FFM-based personality assessments, specifically designed with experts in the field of clinical and personality psychology (phase 1), and to collect the personality-related text data using the interview questions and self-report measures on personality and psychological distress (phase 2). The purpose of the study includes examining the relationship between natural language data obtained from the interview questions, measuring the FFM personality constructs, and psychological distress to demonstrate the validity of the natural language-based personality prediction.
Phase I (pilot) study was conducted to fifty-nine native Korean adults to acquire the personality-related text data from the interview (semi-structured) and open-ended questions based on the FFM of personality. The interview questions were revised and finalized with the feedback from the external expert committee, consisting of personality and clinical psychologists. Based on the established interview questions, a total of 300 Korean adults will be recruited using a convenience sampling method
online survey. The text data collected from interviews will be analyzed using the natural language processing. The results of the online survey including demographic data, depression, anxiety, and personality inventories will be analyzed together in the model to predict individuals' FFM of personality and the level of psychological distress (phase 2).
With the International Maritime Organization (IMO) reinforcing environmental regulations on the shipbuilding industry, the demand for fuels, such as liquefied natural gas (LNG) and liquefied ...petroleum gas (LPG), has soared. Therefore, the demand for a Liquefied Gas Carrier for such LNG and LPG also increases. Recently, CCS carrier volume has been increasing, and damage to the lower CCS panel has occurred. To withstand liquefied gas loads, the CCSs should be fabricated using a material with improved mechanical strength and thermal performance compared with the conventional material. This study proposes a polyvinyl chloride (PVC)-type foam as an alternative to commercial polyurethane foam (PUF). The former material functions as both insulation and a support structure primarily for the LNG-carrier CCS. To investigate the effectiveness of the PVC-type foam for a low-temperature liquefied gas storage system, various cryogenic tests, namely tensile, compressive, impact, and thermal conductivity, are conducted. The results illustrate that the PVC-type foam proves stronger than PUF in mechanical performance (compressive, impact) across all temperatures. In the tensile test, there are reductions in strength with PVC-type foam but it meets CCS requirements. Therefore, it can serve as insulation and improve the overall CCS mechanical strength against increased loads under cryogenic temperatures. Additionally, PVC-type foam can serve as an alternative to other materials in various cryogenic applications.
During the COVID-19 pandemic, the world population faced various mental health challenges, highlighting a need for new community-based psychosocial interventions. This study aimed to investigate the ...effectiveness and feasibility of Nature-Based Therapy (NBT) for the community experiencing psychological distress during the pandemic. A multi-site trial comparing NBT and control groups was conducted in Korea with 291 participants exhibiting mild to severe depression or anxiety. A total of 192 participated in 30 sessions of therapeutic gardening, while 99 remained in the control group. Psychological distress and well-being were assessed using seven measures of depression, anxiety, daily activity, life satisfaction, mindfulness, stress, and loneliness. The effect sizes (Cohen's d) of NBT compared to the control group were medium to large: depression (0.583), anxiety (0.728), daily activity (1.002), life satisfaction (0.786), mindfulness (0.645), stress (0.903), and loneliness (0.695). Multilevel analysis revealed significant Time × Group interaction effects for all measures. Pearson correlation (r = - 0.28 to 0.71) showed that changes in all variables correlated significantly with each other, with small to large effect sizes. Therapeutic alliance at post-test positively moderated the intervention effects on the outcomes. We concluded that NBT is a promising psychosocial intervention for treating psychological distress for community dwellers.
Endocrine therapy resistance in hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer (BC) is a significant clinical challenge that poses several unmet needs in the management of the ...disease. This study aimed to investigate the prognostic value of c-MET-positive circulating tumor cells (cMET+ CTCs), ESR1/PIK3CA mutations, and cell-free DNA (cfDNA) concentrations in patients with hormone receptor-positive (HR+) metastatic breast cancer (mBC).
Ninety-seven patients with HR+ mBC were prospectively enrolled during standard treatment at Samsung Medical Center. CTCs were isolated from blood using GenoCTC
and EpCAM or c-MET CTC isolation kits. PIK3CA and ESR1 hotspot mutations were analyzed using droplet digital PCR. CfDNA concentrations were calculated using internal control copies from the ESR1 mutation test. Immunocytochemistry was performed to compare c-MET overexpression between primary and metastatic sites.
The proportion of c-MET overexpression was significantly higher in metastatic sites than in primary sites (p = 0.00002). Survival analysis showed that c-MET+ CTC, cfDNA concentration, and ESR1 mutations were significantly associated with poor prognosis (p = 0.0026, 0.0021, and 0.0064, respectively) in HR+/HER2- mBC. By contrast, EpCAM-positive CTC (EpCAM+ CTC) and PIK3CA mutations were not associated with progression-free survival (PFS) in HR+/HER2- mBC. Multivariate analyses revealed that c-MET+ CTCs and cfDNA concentration were independent predictors of PFS in HR+/HER2- mBC.
Monitoring c-MET+ CTC, rather than assessing c-MET expression in the primary BC site, could provide valuable information for predicting disease progression, as c-MET expression can change during treatment. The c-MET+ CTC count and cfDNA concentration could provide complementary information on disease progression in HR+ /HER2- mBC, highlighting the importance of integrated liquid biopsy.
Surgical outcomes of degenerative cervical spinal disease are dependent on the selection of surgical techniques. Although a standardized decision cannot be made in an actual clinical setting, ...continued education is provided to standardize the medical practice among surgeons. Therefore, it is necessary to supervise and regularly update overall surgical outcomes. This study aimed to compare the rate of additional surgery between anterior and posterior surgeries for degenerative cervical spinal disease using the National Health Insurance Service-National Sample Cohort (NHIS-NSC) nationwide patient database. The NHIS-NSC is a population-based cohort with about a million participants. This retrospective cohort study included 741 adult patients (> 18 years) who underwent their first cervical spinal surgery for degenerative cervical spinal disease. The median follow-up period was 7.3 years. An event was defined as the registration of any type of cervical spinal surgery during the follow-up period. Event-free survival analysis was used for outcome analysis, and the following factors were used as covariates for adjustment: location of disease, sex, age, type of insurance, disability, type of hospital, Charles comorbidity Index, and osteoporosis. Anterior cervical surgery was selected for 75.0% of the patients, and posterior cervical surgery for the remaining 25.0%. Cervical radiculopathy due to foraminal stenosis, hard disc, or soft disc was the primary diagnosis in 78.0% of the patients, and central spinal stenosis was the primary diagnosis in 22.0% of them. Additional surgery was performed for 5.0% of the patients after anterior cervical surgery and 6.5% of the patients after posterior cervical surgery (adjusted subhazard ratio, 0.83; 95% confidence interval, 0.40-1.74). The rates of additional surgery were not different between anterior and posterior cervical surgeries. The results would be helpful in evaluating current practice as a whole and adjusting the health insurance policy.
A critical issue that needs to be addressed for wider utilization of hydrogen as fuel is protection against hydrogen embrittlement during cryogenic storage as it weakens the microstructure bonding ...force of metals through hydrogen penetration. Austenitic stainless steel, which is usually used in cryogenic vessels and is well known for its high hydrogen resistance at room temperature, has also been reported to be vulnerable to hydrogen embrittlement under cryogenic temperatures. In addition, because large storage vessels are operated over a wide range of temperatures, material behavior at various temperature conditions should also be considered. Therefore, in the present study, hydrogen charging of austenitic stainless steel was performed under various temperature conditions for carrying out prestrain and tensile tests. A decrease in the tensile strength and elongation and an increase in the yield strength were observed in all cases. In particular, the case of 20% prestrain at cryogenic temperature followed by tensile test at room temperature after hydrogen charging showed fracture in the elastic region. The hydrogen index was evaluated from the perspective of elongation and reduction in area, which are factors that indicate the degree of ductility. The aforementioned case showed the most severe results, while non-prestraining followed by tensile tests at room temperature was the least effected by hydrogen. In addition, the effect of strain-induced martensite on hydrogen embrittlement was analyzed using electron backscattered diffraction (EBSD). It was observed that the higher is the prestrain at cryogenic temperatures, the greater is the volume fraction of α’ martensite, which leads to hydrogen embrittlement. The edges and center of the fracture surface were analyzed using scanning electron microscopy (SEM). The hydrogen-charged specimens exhibited brittle fractures at the edges and ductile fractures at the center. The more severe the embrittlement, the more were the number of intergranular fractures and microdimples observed at the edges.
Epidermal growth factor receptor (EGFR) exon 20 insertion mutations (E20ins) are the third most frequent mutations observed in non-small cell lung cancer, accounting for approximately 1–10% of all ...EGFR mutations. In the era of precision medicine and targeted therapies, consistent naming of genetic alterations is crucial to avoid confusion and errors. However, the annotation of EGFR E20ins mutations has been inconsistent, leading to confusion in the scientific literature and product documentation. In this study, our primary objective was to investigate the usage of different annotation related to EGFR E20ins in independent studies. Additionally, we assessed the distribution of EGFR E20ins mutations and estimated the detection coverage expected from each available EGFR E20ins detection assay. A total of 1,418 EGFR E20ins mutations were collected from six studies (FoundationInsights, Geneseeq Technology Inc, mobocertinib phase I/II trial, poziotinib phase II trial, sunvozertinib phase I trial, and Samsung Medical Center) and reorganised according to Human Genome Variation Society (HGVS) nomenclature. Our analysis revealed that the majority of EGFR E20ins mutations requiring correction were ‘insertion’ or ‘deletion-insertion’, which should be appropriately designated as ‘duplication’. Additionally, duplicated variants were reported using different annotations in each study, and furthermore, even identical variant sequences were annotated differently within the same study. In all six studies, p.A767_V769dup and p.S768_D770dup were the most frequently observed EGFR E20ins. The Oncomine Dx Target Test showed the highest patient coverage at 77.2%, followed by the Droplex EGFR Mutation Test v2 with a patient coverage of 70.5% for EGFR E20ins patients. To ensure comprehensive coverage in real-world settings, it is essential to standardise the annotations for each variant, for example using the HGVS nomenclature. The accurate classification and analysis of drug responsiveness in EGFR E20ins necessitate consideration of the nomenclature, particularly with respect to the locations where the actual mutations occur.
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