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Abstract Detecting aberrant cell-free DNA (cfDNA) methylation is a promising strategy for lung cancer diagnosis. In this study, our aim is to identify methylation markers to distinguish patients with lung cancer from healthy individuals. Additionally, we sought to develop a deep learning model incorporating cfDNA methylation and fragment size profiles. To achieve this, we utilized methylation data collected from The Cancer Genome Atlas and Gene Expression Omnibus databases. Then we generated methylated DNA immunoprecipitation sequencing and genome-wide Enzymatic Methyl-seq (EM-seq) form lung cancer tissue and plasma. Using these data, we selected 366 methylation markers. A targeted EM-seq panel was designed using the selected markers, and 142 lung cancer and 56 healthy samples were produced with the panel. Additionally, cfDNA samples from healthy individuals and lung cancer patients were diluted to evaluate sensitivity. Its lung cancer detection performance reached an accuracy of 81.5% and an area under the receiver operating characteristic curve of 0.87. In the serial dilution experiment, we achieved tumor fraction detection of 1% at 98% specificity and 0.1% at 80% specificity. In conclusion, we successfully developed and validated a combination of methylation panel and a deep learning model that can distinguish between patients with lung cancer and healthy individuals.

Abstract Objective Problematic smartphone use has been linked to lower levels of mindfulness, impaired attentional function, and higher impulsivity. This study aimed to identify the psychological mechanisms of problematic smartphone use by exploring the relationship between addictive smartphone use, mindfulness, attentional function and impulsivity. Methods Ninety participants were evaluated with the smartphone addiction proneness scale and classified into the problematic smartphone use group (n = 42; 24 women; mean age: 27.6 ± 7.2 years) or normal use group (n = 48; 22 women; mean age: 30.1 ± 5.7 years). All participants completed self-report questionnaires evaluating their trait impulsivity and mindfulness and attention tests that assessed selective, sustained and divided attention. We compared the variables between the groups and explored the relationship between mindfulness, attentional function, impulsivity and addictive smartphone use through mediation analysis. Results The problematic smartphone use group showed higher trait impulsivity and lower mindfulness than the normal use group. There were no significant group differences in performance on attention tests. Levels of addictive smartphone use were significantly correlated with higher levels of trait impulsivity and lower levels of mindfulness, but not with performance on attention tests. Mediation analysis showed that acting with awareness, an aspect of mindfulness, reduces the degree of addictive smartphone use through attentional impulsivity, one of the trait impulsivity. Conclusion Acting without sufficient awareness could influence addictive smartphone use by mediating attentional impulsivity. This supports that executive control deficits, reflected in high attentional impulsivity, contribute to problematic smartphone use. Our findings imply that mindfulness-based interventions can enhance executive control over smartphone use by promoting awareness.

BackgroundDysarthria is a common poststroke speech disorder affecting communication and psychological well-being. Traditional speech therapy is effective but often poses challenges in terms of accessibility and patient adherence. Emerging smartphone-based therapies may offer promising alternatives for the treatment of poststroke dysarthria. ObjectiveThis study aimed to assess the efficacy and feasibility of smartphone-based speech therapy for improving speech intelligibility in patients with acute and early subacute poststroke dysarthria. This study also explored the impact of the intervention on psychological well-being, user experience, and overall feasibility in a clinical setting. MethodsParticipants were divided into 2 groups for this randomized, evaluator-blinded trial. The intervention group used a smartphone-based speech therapy app for 1 hour per day, 5 days per week, for 4 weeks, with guideline-based standard stroke care. The control group received standard guideline-based stroke care and rehabilitation. Speech intelligibility, psychological well-being, quality of life, and user acceptance were assessed using repeated measures ANOVA. ResultsIn this study, 40 patients with poststroke dysarthria were enrolled, 32 of whom completed the trial (16 in each group). The intervention group showed significant improvements in speech intelligibility compared with the control group. This was evidenced by improvements from baseline (F1,30=34.35; P

ABSTRACTMany intracellular pathogens structurally disrupt the Golgi apparatus as an evolutionarily conserved promicrobial strategy. Yet, the host factors and signaling processes involved are often poorly understood, particularly for Anaplasma phagocytophilum, the agent of human granulocytic anaplasmosis. We found that A. phagocytophilum elevated cellular levels of the bioactive sphingolipid, ceramide-1-phosphate (C1P), to promote Golgi fragmentation that enables bacterial proliferation, conversion from its non-infectious to infectious form, and productive infection. A. phagocytophilum poorly infected mice deficient in ceramide kinase, the Golgi-localized enzyme responsible for C1P biosynthesis. C1P regulated Golgi morphology via activation of a PKCα/Cdc42/JNK signaling axis that culminates in phosphorylation of Golgi structural proteins, GRASP55 and GRASP65. siRNA-mediated depletion of Cdc42 blocked A. phagocytophilum from altering Golgi morphology, which impaired anterograde trafficking of trans-Golgi vesicles into and maturation of the pathogen-occupied vacuole. Cells overexpressing phosphorylation-resistant versions of GRASP55 and GRASP65 presented with suppressed C1P- and A. phagocytophilum-induced Golgi fragmentation and poorly supported infection by the bacterium. By studying A. phagocytophilum, we identify C1P as a regulator of Golgi structure and a host factor that is relevant to disease progression associated with Golgi fragmentation.IMPORTANCECeramide-1-phosphate (C1P), a bioactive sphingolipid that regulates diverse processes vital to mammalian physiology, is linked to disease states such as cancer, inflammation, and wound healing. By studying the obligate intracellular bacterium Anaplasma phagocytophilum, we discovered that C1P is a major regulator of Golgi morphology. A. phagocytophilum elevated C1P levels to induce signaling events that promote Golgi fragmentation and increase vesicular traffic into the pathogen-occupied vacuole that the bacterium parasitizes. As several intracellular microbial pathogens destabilize the Golgi to drive their infection cycles and changes in Golgi morphology is also linked to cancer and neurodegenerative disorder progression, this study identifies C1P as a potential broad-spectrum therapeutic target for infectious and non-infectious diseases.

Abstract Seed-mediated synthesis strategies, in which small gold nanoparticle precursors are added to a growth solution to initiate heterogeneous nucleation, are among the most prevalent, simple, and productive methodologies for generating well-defined colloidal anisotropic nanostructures. However, the size, structure, and chemical properties of the seeds remain poorly understood, which partially explains the lack of mechanistic understanding of many particle growth reactions. Here, we identify the majority component in the seed solution as an atomically precise gold nanocluster, consisting of a 32-atom Au core with 8 halide ligands and 12 neutral ligands constituting a bound ion pair between a halide and the cationic surfactant: Au32X8[AQA+•X-]12 (X = Cl, Br; AQA = alkyl quaternary ammonium). Ligand exchange is dynamic and versatile, occurring on the order of minutes and allowing for the formation of 48 distinct Au32 clusters with AQAX (alkyl quaternary ammonium halide) ligands. Anisotropic nanoparticle syntheses seeded with solutions enriched in Au32X8[AQA+•X-]12 show narrower size distributions and fewer impurity particle shapes, indicating the importance of this cluster as a precursor to the growth of well-defined nanostructures.

BackgroundDysarthria is a motor speech disorder caused by various neurological diseases, particularly stroke. Individuals with post-stroke dysarthria experience impaired speech intelligibility, communication difficulties, and a reduced quality of life. However, studies on the treatment of post-stroke dysarthria are lacking. Digital speech therapy applications have the advantages of being personalized and easily accessible. However, evidence for their efficacy is not rigorous. Moreover, no studies have investigated both the acute to subacute, and chronic phases of stroke. This study aims to investigate the efficacy and feasibility of digital speech therapy applications in addressing these gaps in dysarthria treatment.Methods and designThis study is a multicenter, prospective, randomized, evaluator-blinded non-inferiority trial. We aim to recruit 76 participants with post-stroke dysarthria. Eligible participants will be stratified based on the onset period of stroke into acute to subacute, and chronic phases. Participants will be randomized in a 1:1 to receive either a personalized digital speech therapy application or conventional therapy with a workbook for 60 min daily, 5 days a week, for 4 weeks. The primary outcome is the improvement in speech intelligibility. This will be measured by how accurately independent listeners can transcribe passages read by the participants. Secondary outcomes, which include speech function, will be evaluated remotely by speech-language pathologists. This includes the maximum phonation time, oral diadochokinetic rate, and percentage of consonants correct. Participants’ psychological well-being will also be assessed using self-report questionnaires, such as depressive symptoms (Patient Health Questionnaire-9) and quality of life (Quality of Life in the Dysarthric Speaker scale). The trial will also assess the feasibility, participant adherence, and usability of the application. Rigorous data collection and monitoring will be implemented to ensure patient safety.ConclusionThis trial aims to investigate the efficacy and feasibility of digital speech therapy applications for treating post-stroke dysarthria. The results could establish foundational evidence for future clinical trials with larger sample sizes.Clinical trial registrationClinicaltrials.gov, identifier: NCT05865106.

Abstract Domestic dogs (Canis lupus familiaris) are popular companion animals. Increase in medical expenses associated with them and demand for extending their lifespan in a healthy manner has created the need to develop new diagnostic technology. Companion dogs also serve as important animal models for non-clinical research as they can provide various biological phenotypes. Proteomics have been increasingly used on dogs and humans to identify novel biomarkers of various diseases. Despite the growing applications of proteomics in liquid biopsy in veterinary medicine, no publicly available spectral assay libraries have been created for the proteome of canine serum and urine. In this study, we generated spectral assay libraries for the two-representative liquid-biopsy samples using mid-pH fractionation that allows in-depth understanding of proteome coverage. The resultant canine serum and urine spectral assay libraries include 1,132 and 4,749 protein groups and 5,483 and 25,228 peptides, respectively. We built these complimentary accessible resources for proteomic biomarker discovery studies through ProteomeXchange with the identifier PXD034770.

Abstract 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.

Video-based person re-identification (ReID) aims to exploit relevant features from spatial and temporal knowledge. Widely used methods include the part- and attention-based approaches for suppressing irrelevant spatial–temporal features. However, it is still challenging to overcome inconsistencies across video frames due to occlusion and imperfect detection. These mismatches make temporal processing ineffective and create an imbalance of crucial spatial information. To address these problems, we propose the Spatiotemporal Multi-Granularity Aggregation (ST-MGA) method, which is specifically designed to accumulate relevant features with spatiotemporally consistent cues. The proposed framework consists of three main stages: extraction, which extracts spatiotemporally consistent partial information; augmentation, which augments the partial information with different granularity levels; and aggregation, which effectively aggregates the augmented spatiotemporal information. We first introduce the consistent part-attention (CPA) module, which extracts spatiotemporally consistent and well-aligned attentive parts. Sub-parts derived from CPA provide temporally consistent semantic information, solving misalignment problems in videos due to occlusion or inaccurate detection, and maximize the efficiency of aggregation through uniform partial information. To enhance the diversity of spatial and temporal cues, we introduce the Multi-Attention Part Augmentation (MA-PA) block, which incorporates fine parts at various granular levels, and the Long-/Short-term Temporal Augmentation (LS-TA) block, designed to capture both long- and short-term temporal relations. Using densely separated part cues, ST-MGA fully exploits and aggregates the spatiotemporal multi-granular patterns by comparing relations between parts and scales. In the experiments, the proposed ST-MGA renders state-of-the-art performance on several video-based ReID benchmarks (i.e., MARS, DukeMTMC-VideoReID, and LS-VID).

The aim of this study is to analyze the performance of classifying stress and non-stress by measuring biosignal data using a wearable watch without interfering with work activities at work. An experiment is designed where participants wear a Galaxy Watch3 to measure HR and photoplethysmography data while performing stress-inducing and relaxation tasks. The classification model was constructed using k-NN, SVM, DT, LR, RF, and MLP classifiers. The performance of each classifier was evaluated using LOSO-CV as a verification method. When the top 9 features, including the average and minimum value of HR, average of NNI, SDNN, vLF, HF, LF, LF/HF ratio, and total power, were used in the classification model, it showed the best performance with an accuracy of 0.817 and an F1 score of 0.801. This study also finds that it is necessary to measure physiological data for more than 2 or 3 min to accurately distinguish stress states.

Abstract Background Differences in the composition and diversity of the gut microbial communities among individuals are influenced by environmental factors. However, there is limited research on factors affecting microbiome variation in colorectal cancer patients, who display lower inter-individual variations than that of healthy individuals. In this study, we examined the association between modifiable factors and the microbiome variation in colorectal cancer patients. Methods A total of 331 colorectal cancer patients who underwent resection surgery at the Department of Surgery, Seoul National University Hospital between October 2017 and August 2019 were included. Fecal samples from colorectal cancer patients were collected prior to the surgery. Variations in the gut microbiome among patients with different lifestyles and metabolic diseases were examined through the network analysis of inter-connected microbial abundance, the assessment of the Anna Karenina principle effect for microbial stochasticity, and the identification of the enriched bacteria using linear discrimination analysis effect size. Associations of dietary diversity with microbiome variation were investigated using the Procrustes analysis. Results We found stronger network connectivity of microbial communities in non-smokers, non-drinkers, obese individuals, hypertensive subjects, and individuals without diabetes than in their counterparts. The Anna Karenina principle effect was found for history of smoking, alcohol consumption, and diabetes (with significantly greater intra-sample similarity index), whereas obesity and hypertension showed the anti-Anna Karenina principle effect (with significantly lower intra-sample similarity index). We found certain bacterial taxa to be significantly enriched in patients of different categories of lifestyles and metabolic diseases using linear discrimination analysis. Diversity of food and nutrient intake did not shape the microbial diversity between individuals (pProcrustes>0.05). Conclusions Our findings suggested an immune dysregulation and a reduced ability of the host and its microbiome in regulating the community composition. History of smoking, alcohol consumption, and diabetes were shown to affect partial individuals in shifting new microbial communities, whereas obesity and history of hypertension appeared to affect majority of individuals and shifted to drastic reductions in microbial compositions. Understanding the contribution of modifiable factors to microbial stochasticity may provide insights into how the microbiome regulates effects of these factors on the health outcomes of colorectal cancer patients.

The endosomal Toll-like receptor 7 (TLR7) is a major driver of murine and human systemic lupus erythematosus (SLE). The role of TLR7 in lupus pathogenesis is enhanced when the regulatory role of TLR9 is absent. TLR7 signaling in plasmacytoid DCs (pDC) is generally thought to be a major driver of the IFN response and disease pathology; however, the cell types in which TLR7 acts to mediate disease have not been distinguished. To address this, we selectively deleted TLR7 in either CD11c+ cells or CD19+ cells; using a TLR7-floxed allele, we created on the lupus-prone MRL/lpr background, along with a BM chimera strategy. Unexpectedly, TLR7 deficiency in CD11c+ cells had no impact on disease, while TLR7 deficiency in CD19+ B cells yielded mild suppression of proteinuria and a trend toward reduced glomerular disease. However, in TLR9-deficient MRL/lpr mice with accelerated SLE, B cell–specific TLR7 deficiency greatly improved disease. These results support revision of the mechanism by which TLR7 drives lupus and highlight a cis regulatory interaction between the protective TLR9 and the pathogenic TLR7 within the B cell compartment. They suggest B cell–directed, dual TLR7 antagonism/TLR9 agonism or dual TLR7/9 antagonism as a potential future therapeutic strategy to treat SLE.

Previous studies have reported that low levels of physical activity result in sarcopenic obesity (SO). However, the effects of specific intensities of physical activity on SO and the optimal amount of physical activity for lowering the prevalence of SO have not been well studied. This study aimed to identify the effects of physical activity levels and intensity on SO and the optimal amount of physical activity related to a lower prevalence of SO. This cross-sectional study used data from the nationwide Korean Frailty and Aging Cohort Study (KFACS), which included 2071 older adults (1030 men, 1041 women). SO was defined according to the criteria of the European Society for Clinical Nutrition Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO). Multivariate logistic regression analysis was performed to investigate the association between the physical activity level and SO. The high activity group had a significantly lower prevalence of SO than the non-high activity (low and moderate activity) group. On the other hand, moderate-intensity physical activity was associated with a lower prevalence of SO. A total physical activity energy expenditure of > 3032 kcal/week (433 kcal/day) for men and 2730 kcal/week (390 kcal/day) for women was associated with a reduced prevalence of SO. The high physical activity and total physical energy expenditure described above may be beneficial for reducing the prevalence of SO.

Abstract We aimed to compare the short- and long-term outcomes of simultaneous laparoscopic, hybrid, and open resection for colorectal cancer and synchronous liver metastases. We retrospectively analyzed the data of 647 patients with simultaneous resection of colorectal cancer and liver metastases between January 2006 and December 2018 at three tertiary referral hospitals. Patient’s baseline characteristics, perioperative outcomes, pathological examination results, liver-specific recurrence rate and survivals were compared between the propensity score-matched groups. Forty-two and 81 patients were selected for the laparoscopic vs. hybrid groups, and 48 and 136 patients for laparoscopic vs. open groups, respectively. The laparoscopic group had fewer wound complications (2.1 vs. 13.2%; p = 0.028) than the open group, and a shorter postoperative hospital stay than the hybrid and open groups (8 vs. 11 days, p

Abstract Background Obesity is a chronic disease that causes various medical health problems, increases morbidity, and reduces the quality of life. Obesity (especially central obesity) in older adults is expected to act with the development of sarcopenia. However, the relationship between obesity, central obesity, and sarcopenia remains controversial. This study aimed to investigate the impact of obesity on sarcopenia. Methods In this cross-sectional study, we used data from the Korean Frailty and Aging Cohort Study; 1,827 community-dwelling older adults (883 men and 944 women) aged 70–84 years were recruited. The Asian Working Group for Sarcopenia (AWGS) criteria were used to evaluate sarcopenia. Subjects with a low appendicular skeletal muscle mass index (ASMI; men:

Abstract Background Social and hospital environmental factors that may be associated with hospital-acquired pneumonia (HAP) have not been evaluated. Comprehensive risk assessment for the incidence of HAP including sociodemographic, clinical, and hospital environmental factors was conducted using national health insurance claims data. Methods This is a population-based retrospective cohort study of adult patients who were hospitalized for more than 3 days from the Health Insurance Review and Assessment Service-National Inpatient Sample data between January 1, 2016 and December 31, 2018 in South Korea. Multivariable logistic regression analyses were conducted to identify the factors associated with the incidence of HAP. Results Among the 512,278 hospitalizations, we identified 25,369 (5.0%) HAP cases. In multivariable analysis, well-known risk factors associated with HAP such as older age (over 70 vs. 20–29; adjusted odds ratio [aOR], 3.66; 95% confidence interval [CI] 3.36–3.99), male sex (aOR, 1.35; 95% CI 1.32–1.39), pre-existing lung diseases (asthma [aOR, 1.73; 95% CI 1.66–1.80]; chronic obstructive pulmonary disease [aOR, 1.62; 95% CI 1.53–1.71]; chronic lower airway disease [aOR, 1.79; 95% CI 1.73–1.85]), tube feeding (aOR, 3.32; 95% CI 3.16–3.50), suctioning (aOR, 2.34; 95% CI 2.23–2.47), positioning (aOR, 1.63; 95% CI 1.55–1.72), use of mechanical ventilation (aOR, 2.31; 95% CI 2.15–2.47), and intensive care unit admission (aOR, 1.29; 95% CI 1.22–1.36) were associated with the incidence of HAP. In addition, poverty (aOR, 1.08; 95% CI 1.04–1.13), general hospitals (aOR, 1.54; 95% CI 1.39–1.70), higher bed-to-nurse ratio (Grade ≥ 5; aOR, 1.45; 95% CI 1.32–1.59), higher number of beds per hospital room (6 beds; aOR, 3.08; 95% CI 2.77–3.42), and ward with caregiver (aOR, 1.19; 95% CI 1.12–1.26) were related to the incidence of HAP. Conclusions The incidence of HAP was associated with various sociodemographic, clinical, and hospital environmental factors. Thus, taking a comprehensive approach to prevent and treat HAP is important.

Abstract In most cascading failure models in networks, overloaded nodes are assumed to fail and are removed from the network. However, this is not always the case due to network mitigation measures. Considering the effects of these mitigating measures, we propose a new cascading failure model that describes the probability that an overloaded node fails as a logistic function. By performing numerical simulations of cascading failures on Barabási and Albert (BA) scale-free networks and a real airport network, we compare the results of our model and the established model describing the probability of failure as a linear function. The simulation results show that the difference in the robustness of the two models depends on the initial load distribution and the redistribution of load. We further investigate the conditions of our new model under which the network exhibits the strongest robustness in terms of the load distribution and the network topology. We find the optimal value for the parameter of the load distribution and demonstrate that the robustness of the network improves as the average degree increases. The results regarding the optimal load distribution are verified by theoretical analysis. This work can be used to develop effective mitigation measures and design networks that are robust to cascading failure phenomena.

Abstract Photoelectrochemical (PEC) water oxidation is a highly challenging task that acts as a bottleneck for efficient solar hydrogen production. It is because each cycle of water oxidation is composed of four proton‐coupled electron transfer (PCET) processes and conventional photoanodes and cocatalysts have limited roles in enhancing the charge separation and storage rather than in enhancing catalytic activity. In this study, a simple and generally applicable strategy to improve the PEC performance of water oxidation photoanodes through their modification with polyethyleneimine (PEI) hydrogel is reported. The rich amine groups of PEI not only allow the facile and stable modification of photoanodes by crosslinking but also contribute to improving the kinetics of PEC water oxidation by boosting the PCET. Consequently, the PEC performance of various photoanodes, such as BiVO4, Fe2O3, and TiO2, is significantly enhanced in terms of photocurrent densities and onset potentials even in the presence of notable cocatalyst, cobalt phosphate. The present study provides new insights into and strategies for the design of efficient photoelectrodes and PEC devices.

Background and Objective This study aimed to investigate the changes in sleep quality with increasing age and the effect of age on the components of the Pittsburgh Sleep Quality Index (PSQI). Methods We used data from the Community Health Survey conducted by the Korea Center for Disease Control and Prevention in 2018. A total of 228340 participants in this nationwide survey. Sleep quality was assessed using the PSQI. Adults aged ≥ 19 years were divided into six age groups and one-way analysis of variance (one-way ANOVA) was used to compare the mean values of PSQI of each group. By comparing the scores for each PSQI component in those aged ≥ 65 years and < 65 years, we aimed to reveal the differences in special components according to age group. Results In total, 223334 respondents were included in the study. Based on a one-way ANOVA, the PSQI score generally increased with age. Although the average PSQI score of patients in their 40s was lower than that of patients in their 30s, there was no significant difference between the two groups (p = 0.11). When the PSQI component was compared between the population aged over and under 65 years, the population aged ≥ 65 years scored higher in most components. In contrast, daytime dysfunction scored higher in the population aged < 65 years. Conclusions Sleep quality tends to decrease with increasing age. Several factors, including physiological changes, underlying physical conditions, and psychosocial factors, may contribute to a decrease in sleep quality with age.

Abstract We investigated the clinical relevance of urinary cytokines/chemokines reflecting intrarenal immunologic micromilieu as prognostic markers and the optimal measurement timing after living donor kidney transplantation (LDKT). This prospective cohort study included 77 LDKT patients who were followed for ≥ 5 years. Patients were divided into control (n = 42) or acute rejection (AR, n = 35) group. Early AR was defined as AR occurring within 3 months. Serum and urine cytokines/chemokines were measured serially as follows: intraoperative, 8/24/72 h, 1 week, 3 months, and 1 year after LDKT. Intrarenal total leukocytes, T cells, and B cells were analyzed with immunohistochemistry followed by tissueFAXS. Urinary MCP-1 and fractalkine were also analyzed in a validation cohort. Urinary MCP-1 after one week was higher in the AR group. Urinary MCP-1, fractalkine, TNF-α, RANTES, and IL-6 after one week were significantly higher in the early AR group. Intrarenal total leukocytes and T cells were elevated in the AR group compared with the control group. Urinary fractalkine, MCP-1, and IL-10 showed positive correlation with intrarenal leukocyte infiltration. Post-KT 1 week urinary MCP-1 showed predictive value in the validation cohort. One-week post-KT urinary MCP-1 may be used as a noninvasive diagnostic marker for predicting AR after LDKT.

Background: The aim of the present study was to compare the biological and mechanical properties of a novel dual-cure, resin-modified calcium silicate material, Theracal PT® (TP), with those of Theracal LC® (TL) and BiodentineTM (BD). Methods: The cell counting kit-8 was used on human dental pulp cells to test cell the viability of the three materials. Antibacterial activity of TP, TL, and BD against Enterococcus faecalis was investigated under anaerobic conditions. The ability of the materials to support odontogenic differentiation was studied by examining the relative gene expression of osteocalcin (OCN), osteopontin (OPN), and Collagen I (ColI) using real-time polymerase chain reaction. For mechanical property tests, microhardness was evaluated using the Vickers microhardness (VHN) test, and the bond strength to the resin was evaluated using a shear bond test machine. Results: There was no significant difference in cell viability between TL and TP after 48 h, and BD showed the highest cell viability, while TP showed the highest antibacterial effect. At the 12-h time point, there was no significant difference in ColI and OCN expression between BD and TP, but TP showed a higher expression of OPN than BD. However, at the 48-h time point, ColI and OCN showed higher levels of expression for BD than for TP and TL. At the same time point, only OPN had a higher diffusion for TP than for BD. TP demonstrated a VHN of approximately 30–35. This value was higher than that of TL and lower than that of BD. In contrast to VHN, the shear bond strength to resin was significantly higher for TL and TP than for BD. Conclusion: TP showed lower biocompatibility than BD but higher OPN expression and antibacterial effects than BD and TL. TP showed higher shear bond strength than BD and higher VHN than TL and BD at the 24-h time point.

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.

Abstract Background Metastatic breast cancer (mBC) is a complex and life-threatening disease and although it is difficult to cure, patients can benefit from sequential anticancer treatment, including endocrine therapy, targeted therapy and cytotoxic chemotherapy. The patient-derived xenograft (PDX) model is suggested as a practical tool to predict the clinical outcome of this disease as well as to screen novel drugs. This study aimed to establish PDX models in Korean patients and analyze their genomic profiles and utility for translational research. Methods Percutaneous core needle biopsy or punch biopsy samples were used for xenotransplantation. Whole exome sequencing and transcriptome analysis were performed to assess the genomic and RNA expression profiles, respectively. Copy number variation and mutational burden were analyzed and compared with other metastatic breast cancer genomic results. Mutational signatures were also analyzed. The antitumor effect of an ATR inhibitor was tested in the relevant PDX model. Results Of the 151 cases studied, 40 (26%) PDX models were established. Notably, the take rate of all subtypes, including the hormone receptor-positive (HR +) subtype, exceeded 20%. The PDX model had genomic fidelity and copy number variation that represented the pattern of its donor sample. TP53, PIK3CA, ESR1, and GATA3 mutations were frequently found in our samples, with TP53 being the most frequently mutated, and the somatic mutations in these genes strengthened their frequency in the PDX model. The ESR1 mutation, CCND1 amplification, and the APOBEC signature were significant features in our HR + HER2- PDX model. Fulvestrant in combination with palbociclib showed a partial response to the relevant patient’s tumor harboring the ESR1 mutation, and CCND1 amplification was found in the PDX model. AZD6738, an ATR inhibitor, delayed tumor growth in a relevant PDX model. Conclusions Our PDX model was established using core needle biopsy samples from primary and metastatic tissues. Genomic profiles of the samples reflected their original tissue characteristics and could be used for the interpretation of clinical outcomes.

How can sport community involvement influence life satisfaction during a pandemic? Self-expansion theory posits that individuals seek to gain resources such as positive interpersonal relationships for growth and achievement. By considering psychological capital (PsyCap) as a dispositional resource intervening between sport community involvement and life satisfaction, we examined an empirical model to test the chain of effects. Based on the stress process model, distress and generational group (Generation Z vs. others) were tested as moderators. Participants (N = 233) responded to the scale item questionnaire for model assessment. Supporting the hypothesized relationships, the model was supported with a significant moderated-moderated mediation. The mediation effect of PsyCap was stronger when distress level was lower and such interaction effect was amplified for Generation Z (Gen Z). Whereas the global sport communities and Gen Z were found to be more particularly vulnerable to COVID-19, our findings suggest that there are psychological pathways for fans to maintain their resilience. It is foremost imperative to lower the stress level of sport fans for their community involvement to positively affect life satisfaction. Gen Z were more stressed during the pandemic but individuals who managed to cope with stress were able to leverage community involvement to boost positive psychological resources. Acknowledgment of these effects brings implications for better management strategies and provides avenues for new research.

The sphingolipid, ceramide-1-phosphate (C1P), has been shown to promote the inflammatory phase and inhibit the proliferation and remodeling stages of wound repair via direct interaction with group IVA cytosolic phospholipase A2, a regulator of eicosanoid biosynthesis that fine-tunes the behaviors of various cell types during wound healing. However, the anabolic enzyme responsible for the production of C1P that suppresses wound healing as well as bioactive eicosanoids and target receptors that drive enhanced wound remodeling have not been characterized. Herein, we determined that decreasing C1P activity via inhibitors or genetic ablation of the anabolic enzyme ceramide kinase (CERK) significantly enhanced wound healing phenotypes. Importantly, postwounding inhibition of CERK enhanced the closure rate of acute wounds, improved the quality of healing, and increased fibroblast migration via a “class switch” in the eicosanoid profile. This switch reduced pro-inflammatory prostaglandins (e.g., prostaglandin E2) and increased levels of 5-hydroxyeicosatetraenoic acid and the downstream metabolite 5-oxo-eicosatetraenoic acid (5-oxo-ETE). Moreover, dermal fibroblasts from mice with genetically ablated CERK showed enhanced wound healing markers, while blockage of the murine 5-oxo-ETE receptor (oxoeicosanoid receptor 1) inhibited the enhanced migration phenotype of these cell models. Together, these studies reinforce the vital roles eicosanoids play in the wound healing process and demonstrate a novel role for CERK-derived C1P as a negative regulator of 5-oxo-ETE biosynthesis and the activation of oxoeicosanoid receptor 1 in wound healing. These findings provide foundational preclinical results for the use of CERK inhibitors to shift the balance from inflammation to resolution and increase the wound healing rate.

Neuropathic pain is a chronic pain state characterized by nerve damage, inflammation, and nociceptive neuron hyperactivity. As the underlying pathophysiology is complex, a more effective therapy for neuropathic pain would be one that targets multiple elements. Here, we generated recombinant adeno-associated viruses (AAVs) encoding three therapeutic genes, namely, glutamate decarboxylase 65, glial cell-derived neurotrophic factor, and interleukin-10, with various combinations. The efficacy for pain relief was evaluated in a rat spared nerve injury model of neuropathic pain. The maximal analgesic effect was achieved when the AAVs expressing all three genes were administered to rats with neuropathic pain. The combination of two virus constructs expressing the three genes was named KLS-2031 and evaluated as a potential novel therapeutic for neuropathic pain. Single transforaminal epidural injections of KLS-2031 into the intervertebral foramen to target the appropriate dorsal root ganglion produced notable long-term analgesic effects in female and male rats. Furthermore, KLS-2031 mitigated the neuroinflammation, neuronal cell death, and dorsal root ganglion hyperexcitability induced by the spared nerve injury. These results suggest that KLS-2031 represents a promising therapeutic option for refractory neuropathic pain.

Abstract Background Cancer is a highly heterogeneous disease with varying responses to anti-cancer drugs. Although several attempts have been made to predict the anti-cancer therapeutic responses, there remains a great need to develop highly accurate prediction models of response to the anti-cancer drugs for clinical applications toward a personalized medicine. Patient derived xenografts (PDXs) are preclinical cancer models in which the tissue or cells from a patient’s tumor are implanted into an immunodeficient or humanized mouse. In the present study, we develop a bioinformatics analysis pipeline to build a predictive gene expression model (GEM) for cancer patients’ drug responses based on gene expression and drug activity data from PDX models. Results Drug sensitivity biomarkers were identified by performing an association analysis between gene expression levels and post-treatment tumor volume changes in PDX models. We built a drug response prediction model (called PDXGEM) in a random-forest algorithm by using a subset of the drug sensitvity biomarkers with concordant co-expression patterns between the PDXs and pretreatment cancer patient tumors. We applied the PDXGEM to several cytotoxic chemotherapies as well as targeted therapy agents that are used to treat breast cancer, pancreatic cancer, colorectal cancer, or non-small cell lung cancer. Significantly accurate predictions of PDXGEM for pathological response or survival outcomes were observed in extensive independent validations on multiple cancer patient datasets obtained from retrospective observational studies and prospective clinical trials. Conclusion Our results demonstrated the strong potential of using molecular profiles and drug activity data of PDX tumors in developing a clinically translatable predictive cancer biomarkers for cancer patients. The PDXGEM web application is publicly available at http://pdxgem.moffitt.org .

Abstract Intratumor heterogeneity (ITH) stands as one of the main difficulties in the treatment of colorectal cancer (CRC) as it causes the development of resistant clones and leads to heterogeneous drug responses. Here, 12 sets of patient‐derived organoids (PDOs) and cell lines (PDCs) isolated from multiple regions of single tumors from 12 patients, capturing ITH by multiregion sampling of individual tumors, are presented. Whole‐exome sequencing and RNA sequencing of the 12 sets are performed. The PDOs and PDCs of the 12 sets are also analyzed with a clinically relevant 24‐compound library to assess their drug responses. The results reveal unexpectedly widespread subregional heterogeneity among PDOs and PDCs isolated from a single tumor, which is manifested by genetic and transcriptional heterogeneity and strong variance in drug responses, while each PDO still recapitulates the major histologic, genomic, and transcriptomic characteristics of the primary tumor. The data suggest an imminent drawback of single biopsy‐originated PDO‐based clinical diagnosis in evaluating CRC patient responses. Instead, the results indicate the importance of targeting common somatic driver mutations positioned in the trunk of all tumor subregional clones in parallel with a comprehensive understanding of the molecular ITH of each tumor.

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.

Purpose The purpose of this study was to identify the effects of an educational intervention by evaluating neonatal emergency airway management knowledge, critical thinking disposition, problem- solving ability, and confidence in clinical performance after developing and operating a simulation-based neonatal emergency airway management education program for nurses in a neonatal intensive care unit. Methods The participants were 30 nurses in a neonatal intensive care unit. Data were collected from June 6 to 15, 2018 and analyzed using IBM SPSS version 22.0. Results The results of the pretest and posttest for each educational group showed statistically significant improvements in neonatal emergency airway management knowledge, critical thinking, problem- solving ability, and confidence in clinical performance. Conclusion The simulation-based neonatal emergency airway management training program was an effective educational program that enhanced neonatal emergency airway management knowledge, critical thinking disposition, problem-solving ability, and confidence in clinical performance among nurses in a neonatal intensive care unit. Therefore, it is suggested that the program described in this study can contribute to improving nursing quality by enhancing the ability of nurses to cope with emergencies in practice. It can also be used for education for new nurses and contribute to the development of nurses’ practices.

Colorectal cancer (CRC) is the third most common cancer diagnosed worldwide and represents the second most common cause of all cancer-related deaths in Korea. Although epidemiological data indicate a sharp increase in the incidence of CRC among individuals older than 50 years, more than 10% of CRCs occur before reaching 50. These are known as early-onset CRCs (EOCRCs) and are likely to be suggestive of hereditary predisposition. However, known familial CRC syndromes account for only 20% of genetic aberrations of EOCRC, and the remaining 80% are still in question. Therefore, we aimed to establish reproducible biological resources and contribute to expand the mutation database of EOCRC. Four cell lines derived from the original tumor mass of CRC patients diagnosed under age 30 years were established, and next-generation sequencing technique was used to identify the genetic features of EOCRC. We have identified one novel fusion gene, FAM174A-WWC1, and analyzed its functional role. The induction of FAM174A-WWC1 to normal fibroblast caused alternations in cellular morphology as well as intercellular expression of E-cadherin and N-cadherin. Moreover, WWC1 carrying the fused FAM174A domain not only abrogated the membrane expression of YAP1 but also significantly increased the levels of nucleic YAP1. As a result, the FAM174A-WWC1 expression increased the oncogenic capacity and invasiveness of normal fibroblasts, which suggests its role as a potential driver mutation of EOCRC.

BRAF drives MEK/ERK activation to facilitate tumorigenesis. Here, the authors show that in response to pro-inflammatory cytokines, ITCH mediates a non-proteolytic ubiquitination and activation of BRAF, which in turn sustains MEK/ERK signaling to facilitate melanoma cell growth.

A metastasis of colorectal cancer is difficult to diagnose, and has a poor prognosis. Therefore, we tried to elucidate the possibility of a diagnostic and prognostic marker. Exosomal miR-193a and let-7g were sorted by miRNA microarray. The expression of miR-193a in the PTM group was lower than that of the primary CRC group, and the expression of let-7g was higher than that of the primary CRC. MMP16 and CDKN1A expression was confirmed respectively for target genes of two miRNAs. When the mimics of these miRNAs were treated with cell lines, both MMP16 and CDKN1A decreased intracellular expression. Cell invasiveness and proliferation were decreased by miR-193a and increased by let-7g. The differences in expression of exosomal miR-193a and let-7g extracted from the plasma of patients were classified as cancer progression indicators. Furthermore, the survival rate decreased in the group with low miR-193a expression and high let-7g expression. Our study confirmed the possibility of using this as a diagnostic and prognostic marker for colorectal cancer by measuring the expression levels of exosomal miR-193a and let-7g in blood.

Sleep is one of the most essential factors required to maintain good health. However, the global prevalence of insomnia is increasing, and caffeine intake is a major trigger. The objective of this study was to investigate the inhibitory effect of black pepper, Piper nigrum extract (PE), on caffeine-induced sleep disruption and excitation in mice. Caffeine significantly decreased sleep duration in the pentobarbital-induced sleep test. It also resulted in a significant increase in sleep onset and a decrease in non-rapid eye movement sleep. Moreover, in an open-field test, caffeine-treated mice exhibited a significantly increased time in the center zone and total distance traveled. However, the co-administration of caffeine and PE did not result in similar arousal activities. Thus, our results suggest that PE can be used as a potential therapeutic agent to treat sleep problems and excitatory status associated with caffeine intake.

Uncontrolled activation of transforming growth factor (TGF)-β results in a wide range of pathologic conditions. Therapeutic interventions to regulate TGF-β signaling during fibrosis have been developed but the effectiveness is still limited. Here, we show that developmental endothelial locus-1 (Del-1) ameliorates fibrosis in mice by inhibiting αv integrin-mediated activation of TGF-β. Del-1 bound to αvβ6 integrin, an important activator of TGF-β, and inhibited the binding of αvβ6 integrin to the latency-associated peptide (LAP), thereby suppressing αv integrin-mediated activation of TGF-β. Lack of Del-1 increased colocalization of αv integrin and LAP in the lungs, which was reversed by Del-1 supplementation. The crucial role of Del-1 in regulating TGF-β activity was recapitulated in a mouse model of fibrosis using an adenovirus expressing inactive TGF-β1. Del-1 supplementation improved the pathological characteristics of the mice and reduced mortality. Thus, we propose that Del-1 is a negative regulator of TGF-β activation and a potential anti-fibrotic factor.

The choice of a group decision-making rule is one of the most important political issues. Buchanan and Tullock have provided a framework for analyzing the optimal k-majority rule from the perspective of "methodological individualism." They proposed the concept of "external costs" and "decision costs" and argued that the optimal k-majority rule takes place where the sum of these two costs-"total costs"-is minimized. Despite the fact that the approach is widely accepted as a tool for dealing with public decision-making rules, the study of formalizing these two costs in a quantitative manner has been relatively rare. We propose a systematic way of modeling these costs considering the assumptions mentioned by Buchanan and Tullock. We find that the resulting shape of the graphs is generally similar to that of the Buchanan-Tullock model, except for some minor details. Then, using this analytical model, we investigate several factors that could affect Buchanan-Tullock's two costs and the optimal k-majority rule. We show that "clustering of disadvantages" (social factor) and "loss aversion" (personal factor) could increase external costs in Buchanan-Tullock's model. These factors can result in a separation between the theoretical and actual optimal k-majority rules. Meanwhile, some recent developments in information and communication technologies can not only decrease decision costs, but also increase the same costs simultaneously through amplified "group polarization" (technological factor). If the effect of the former is not the same as that of the latter, this leads to a difference in optimal k-majority rules as well. These discrepancies bring us to the dilemma of "public choice before public choice."

High-dielectric constant (k) materials have attracted a lot of attention for use as gate insulators (GIs) that enable low-voltage operation of thin film transistors (TFTs). However, high-k GIs also induce severe degradation in TFT characteristics, such as effective mobility (μeff). Therefore, in this study, a stacked GI structure of ZrO2 and SiO2 was investigated. The mechanism by which the properties of the high-k GI influence TFT operating characteristics was revealed. Based on this mechanism, an optimized stacked GI structure that exhibited a low subthreshold swing and high μeff was found and used to achieve low-voltage operation in a TFT device.

Abstract Background Intraocular lenses (IOLs) with different diopter (D) intervals may have different tolerance, and may provide different accuracy of refractive outcome after cataract surgery. The aim of the study is to compare the accuracy of refractive outcome after implantation of IOLs with different D intervals after cataract surgery. Methods A total of 80 eyes from 40 patients who underwent phacoemulsification with implantation of a 0.50 D interval Akreos AO IOL in one eye and a 0.25 D interval Softec HD™ IOL in the other eye were enrolled. The percentages of eyes with refractive prediction error within ±0.50 D at one month after surgery were compared. To evaluate the effect of the dioptric errors of the IOL itself on refractive prediction error, the percentage of eyes with refractive prediction error within ±0.25 D of the IOL with a standard deviation (SD) of ±0.40 D was compared with that of the IOL with a SD of ±0.11 D through Monte Carlo simulations. Results In this clinical study, the percentage of eyes with refractive prediction error within ±0.50 D by the Haigis formula in the Softec HD™ group (85.0%) was significantly greater than that in the Akreos AO group (57.5%; P = 0.027). In Monte Carlo simulations, all percentages of eyes with refractive prediction error within ±0.25 D by the Haigis and SRK/T formulas in the Softec HD™ group were significantly greater than those in the Akreos AO group. Conclusions The IOL with a 0.25 D interval was more accurate than the IOL with a 0.50 D interval in predicting refractive outcome after cataract surgery. Trial registration Current Controlled Trials KCT0002192, Retrospectively registered (Date of registration: 6 January 2017).

Tuberculosis (TB) in Korea remains a serious health problem with an estimated 77 per 100,000 incidence rate for 2016. This makes Korea as the only OECD country with high incidence of TB. The government has increased budgets and strengthened patient management policies since 2011. The management of latent tuberculosis was added to the response with strengthened and extensive contact investigations in the five-year tuberculosis control plan (2013–2017) and implementation was established in 2013. Due to these efforts Korea has achieved an average 5.2% reduction annually in tuberculosis incidence rate between 2011 and 2016. To further expedite the reduction of the TB burden the government has introduced additional measures including mandatory screening of latent tuberculosis infection for community workers in congregate settings including daycare centers for children, kindergarten, and teachers in schools and health care workers in clinics and hospitals to solve the problems identified through contact investigations in 2017.Providing high quality free diagnosis and treatment of active TB including for multidrug resistant TB combined with active contact investigations is the mainstay of the current programmatic response in Korea. However, the limitation of existing tools for LTBI pose challenge including absence of best mechanism for effective communication with professionals and the public, the need for at least 3 months of treatment and the risk of side effects. Developing effective tools will help to overcome these challenges. Keywords: Tuberculosis, Latent tuberculosis infection, End TB, Contact investigations, Epidemiology

This study examined patterns of father involvement and their relations with social, behavioral, and cognitive development among low-income children < 5 years. Latent class analysis on data from 2650 fathers (Mage = 29.35 years) in the Supporting Healthy Marriages program revealed four father involvement patterns: (1) High positive involvement (48%); (2) engaged but harsh discipline (42%); (3) low cognitive stimulation (8%); and (4) lower involvement (2%). The low cognitive stimulation pattern was associated with greater father- and mother-reported child behavior problems and lower child socioemotional and cognitive functioning. The engaged but harsh discipline pattern was associated with more father-reported child behavior problems. These findings highlight the need for active engagement of fathers in parenting interventions to promote child development.

In this study, we fabricated three-dimensional (3D) hierarchical plasmo-photonic nanoarchitectures by epitaxially integrating semiconducting zinc oxide (ZnO) nanowires with vertically oriented plasmonic gold (Au) and silver (Ag) nanoplatforms and investigated their growth mechanisms in detail. We synthesized 3D hierarchical Au–ZnO nanostructures via a vapor–solid mechanism leading to the epitaxial growth of ZnO nanowires on vertically oriented single-crystalline Au nanowires on a strontium titanate (SrTiO3) substrate. The elongated half-octahedral Au nanowires with a rhombus cross-section were transformed into thermodynamically stable elongated cuboctahedral Au nanowires with a hexagonal cross-section during the reaction. After the transformation, ZnO thin films with six twinned domains were formed on the side planes of the elongated cuboctahedral Au nanowire trunks, and six ZnO nanowire branches were grown on the ZnO thin films. Further, 3D hierarchical Ag–ZnO nanostructures were obtained via the same vapor–solid mechanism leading to the epitaxial growth of ZnO nanowires on vertically oriented Ag nanoplates on an aluminum oxide (Al2O3) substrate. Therefore, the growth mechanism developed herein can be generally employed to fabricate 3D hierarchical plasmo-photonic nanoarchitectures.

Lactobacillus plantarum is a popular probiotic species due to its safe and beneficial effects on humans; therefore, novel L. plantarum strains have been isolated and identified from various dietary products. Given that bacteria-derived extracellular vesicles (EVs) have been considered as efficient carriers of bioactive materials and shown to evoke cellular responses effectively, L. plantarum-derived EVs are expected to efficiently elicit health benefits. Herein, we identified L. plantarum APsulloc 331261 living in green tea leaves and isolated EVs from the culture medium. We performed quantitative lipidomic analysis of L. plantarum APsulloc 331261 derived EVs (LEVs) using liquid chromatography-mass spectrometry. In comparison to L. plantarum APsulloc 331261, in LEVs, 67 of 320 identified lipid species were significantly increased and 19 species were decreased. In particular, lysophosphatidylserine(18:4) and phosphatidylcholine(32:2) were critically increased, showing over 21-fold enrichment in LEVs. In addition, there was a notable difference between LEVs and the parent cells in the composition of phospholipids. Our results suggest that the lipidomic profile of bacteria-derived EVs is different from that of the parent cells in phospholipid content and composition. Given that lipids are important components of EVs, quantitative and comparative analyses of EV lipids may improve our understanding of vesicle biogenesis and lipid-mediated intercellular communication within or between living organisms.

Energy harvesting technologies have found significant importance over the past decades due to the increasing demand of energy and self-powered design of electronic and implantable devices. Herein, we demonstrate the design and application of in situ poled highly flexible piezoelectric poly vinylidene fluoride (PVDF) graphene oxide (GO) hybrid nanofibers in aligned mode for multifaceted applications from locomotion sensors to self-powered motion monitoring. Here we exploited the simplest and most versatile method, called electrospinning, to fabricate the in situ poled nanofibers by transforming non-polar α-phase of PVDF to polar β- phase structures for enhanced piezoelectricity under high bias voltage. The flexible piezoelectric device fabricated using the aligned mode generates an improved output voltage of 2.1 V at a uniform force of 12 N. The effective piezoelectric transduction exhibited by the proposed system was tested for its multiple efficacies as a locomotion detector, bio-e-skin, smart chairs and so on.

We constructed a physiologically plausible computationally efficient model of a motor unit and developed simulation software that allows for integrative investigations of the input–output processing in the motor unit system. The model motor unit was first built by coupling the motoneuron model and muscle unit model to a simplified axon model. To build the motoneuron model, we used a recently reported two-compartment modeling approach that accurately captures the key cell-type-related electrical properties under both passive conditions (somatic input resistance, membrane time constant, and signal attenuation properties between the soma and the dendrites) and active conditions (rheobase current and afterhyperpolarization duration at the soma and plateau behavior at the dendrites). To construct the muscle unit, we used a recently developed muscle modeling approach that reflects the experimentally identified dependencies of muscle activation dynamics on isometric, isokinetic and dynamic variation in muscle length over a full range of stimulation frequencies. Then, we designed the simulation software based on the object-oriented programing paradigm and developed the software using open-source Python language to be fully operational using graphical user interfaces. Using the developed software, separate simulations could be performed for a single motoneuron, muscle unit and motor unit under a wide range of experimental input protocols, and a hierarchical analysis could be performed from a single channel to the entire system behavior. Our model motor unit and simulation software may represent efficient tools not only for researchers studying the neural control of force production from a cellular perspective but also for instructors and students in motor physiology classroom settings.

This simulation study aims to propose an optimal starting model to search for the accurate growth trajectory in Latent Growth Models (LGM). We examine the performance of four different starting models in terms of the complexity of the mean and within-subject variance-covariance (V-CV) structures when there are time-invariant covariates embedded in the population models. Results showed that the model search starting with the fully saturated model (i.e., the most complex mean and within-subject V-CV model) recovers best for the true growth trajectory in simulations. Specifically, the fully saturated starting model with using ΔBIC and ΔAIC performed best (over 95%) and recommended for researchers. An illustration of the proposed method is given using the empirical secondary dataset. Implications of the findings and limitations are discussed.