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Background: Current protein biomarkers are only moderately predictive at identifying individuals with mild traumatic brain injury or concussion. Therefore, more accurate diagnostic markers are needed for sport-related concussion. Methods: This was a multicenter, prospective, case-control study of athletes who provided blood samples and were diagnosed with a concussion or were a matched non-concussed control within the National Collegiate Athletic Association–Department of Defense Concussion Assessment, Research, and Education Consortium conducted between 2015 and 2019. The blood was collected within 48 h of injury to identify protein abnormalities at the acute and subacute timepoints. Athletes with concussion were divided into 6 h post-injury (0–6 h post-injury) and after 6 h post-injury (7–48 h post-injury) groups. We applied a highly multiplexed proteomic technique that used a DNA aptamers assay to target 1305 proteins in plasma samples from athletes with and without sport-related concussion. Results: A total of 140 athletes with concussion (79.3% males; aged 18.71 ± 1.10 years, mean ± SD) and 21 non-concussed athletes (76.2% males; 19.14 ± 1.10 years) were included in this study. We identified 338 plasma proteins that significantly differed in abundance (319 upregulated and 19 downregulated) in concussed athletes compared to non-concussed athletes. The top 20 most differentially abundant proteins discriminated concussed athletes from non-concussed athletes with an area under the curve (AUC) of 0.954 (95% confidence interval: 0.922‒0.986). Specifically, after 6 h of injury, the individual AUC of plasma erythrocyte membrane protein band 4.1 (EPB41) and alpha-synuclein (SNCA) were 0.956 and 0.875, respectively. The combination of EPB41 and SNCA provided the best AUC (1.000), which suggests this combination of candidate plasma biomarkers is the best for diagnosing concussion in athletes after 6 h of injury. Conclusion: Our data suggest that proteomic profiling may provide novel diagnostic protein markers and that a combination of EPB41 and SNCA is the most predictive biomarker of concussion after 6 h of injury.

ObjectiveTo investigate the plasma proteomic profiling in identifying biomarkers related to return to sport (RTS) following a sport-related concussion (SRC).MethodsThis multicenter, prospective, case-control study was part of a larger cohort study conducted by the NCAA-DoD Concussion Assessment, Research, and Education (CARE) Consortium, athletes (n = 140) with blood collected within 48 h of injury and reported day to asymptomatic were included in this study, divided into two groups: (1) recovery

A regional wave forecasting system in East Asia, including the Korean Peninsula, was built based on WAVEWATCH III using offshore wind forecast data from the Global Data Assimilation Prediction System. The numerical simulations were performed on the sensitivity of the interaction between input wind and wave development. The forecasts for each condition were compared and verified with the observational data of marine meteorological buoys from 1 August to 30 September 2020. The sensitivity conditions were configured to have a specific range of variables related to the directional distribution of input winds (SINA0) and variables indicating the development of input wind–wave (CDFAC) in the ST6. The results were presented by calculating the mean error and root mean square error for all observation points. Overall, as the CDFAC increased, the mean error tended to decrease according to the forecast time and the root mean square error increased. Although the effect of SINA0 at the same CDFAC was insignificant, when SINA0 increased in sections where the significant wave height decreased rapidly, the significant wave height tended to decrease. In addition, the main variables that affect the physical process of wind–wave interaction should be considered to improve wave model forecasting performance and accuracy.

To date, 19 species of spiny lobsters from the genus Panulirus have been discovered, of which only P. japonicus, P. penicilatus, P. stimpsoni, and P. versicolor have been documented in South Korean waters. In this study, we aimed to identify and update the current list of spiny lobster species that inhabit South Korean waters based on the morphological features and the phylogenetic profile of cytochrome oxidase I (COI) of mitochondrial DNA (mtDNA). Spiny lobsters were collected from the southern and eastern coasts of Jeju Island, South Korea. Phylogenetic analyses were performed using neighbor-joining (NJ), maximum likelihood (ML), and Bayesian inference (BI) methods. The ML tree was used to determine the spiny lobster lineages, thereby clustering the 17 specimens collected in this study into clades A, B, C, and D, which were reciprocally monophyletic with P. japonicus, P. homarus homarus, P. longipes, and P. stimpsoni, respectively. These clades were also supported by morphological examinations. Interestingly, morphological variations, including the connected pleural and transverse groove at the third abdominal somite, were observed in four specimens that were genetically confirmed as P. japonicus. This finding is novel within the P. japonicus taxonomical reports. Additionally, this study updates the documentation of spiny lobsters inhabiting South Korean waters as P. longipes and P. homarus homarus were recorded for the first time in this region.

Post-traumatic stress disorder (PTSD) and major depressive disorder (MDD) are commonly experienced after exposure to highly stressful events, including physical trauma, yet, biological predictors remain elusive. Methylation of DNA may provide key insights, as it likely is reflective of factors that may increase the risk in trauma patients, as DNA methylation is altered by previous stressors. Here, we compared DNA methylation patterns using bisulfite sequencing in patients with a physical trauma that required more than a 24-h hospitalization (n = 33). We then compared DNA methylation in patients who developed and compared the following groups (1) PTSD and MDD; n = 12), (2) MDD (patients with MDD only; n = 12), and (3) control (patients who did not have PTSD or MDD; n = 9), determined by the PTSD Checklist (PCL-5) and Quick Inventory of Depressive Symptomatology (QIDS) at 6-months follow-up. We identified 17 genes with hypermethylated cytosine sites and 2 genes with hypomethylated sites in comparison between PTSD and control group. In comparison between MDD and control group, we identified 12 genes with hypermethylated cytosine sites and 6 genes with hypomethylated sites. Demethylation of these genes altered the CREB signaling pathway in neurons and may represent a promising therapeutic development target for PTSD and MDD. Our findings suggest that epigenetic changes in these gene regions potentially relate to the onset and symptomology of PTSD and MDD and could be used as potential biomarkers in predicting the onset of PTSD or MDD following traumatic events.

Blast exposure is common in military personnel during training and combat operations, yet biological mechanisms related to cell survival and function that coordinate recovery remain poorly understood. This study explored how moderate blast exposure influences gene expression; specifically, gene-network changes following moderate blast exposure. On day 1 (baseline) of a 10-day military training program, blood samples were drawn, and health and demographic information collected. Helmets equipped with bilateral sensors worn throughout training measured overpressure in pounds per square inch (psi). On day 7, some participants experienced moderate blast exposure (peak pressure ≥5 psi). On day 10, 3 days post-exposure, blood was collected and compared to baseline with RNA-sequencing to establish gene expression changes. Based on dysregulation data from RNA-sequencing, followed by top gene networks identified with Ingenuity Pathway Analysis, a subset of genes was validated (NanoString). Five gene networks were dysregulated; specifically, two highly significant networks: (1) Cell Death and Survival (score: 42), including 70 genes, with 50 downregulated and (2) Cell Structure, Function, and Metabolism (score: 41), including 69 genes, with 41 downregulated. Genes related to ubiquitination, including neuronal development and repair: UPF1, RNA Helicase and ATPase (UPF1) was upregulated while UPF3 Regulator of Nonsense Transcripts Homolog B (UPF3B) was downregulated. Genes related to inflammation were upregulated, including AKT serine/threonine kinase 1 (AKT1), a gene coordinating cellular recovery following TBIs. Moderate blast exposure induced significant gene expression changes including gene networks involved in (1) cell death and survival and (2) cellular development and function. The present findings may have implications for understanding blast exposure pathology and subsequent recovery efforts.

Repetitive low-level blast exposure is one of the major occupational health concerns among US military service members and law enforcement. This study seeks to identify gene expression using microRNA and RNA sequencing in whole-blood samples from experienced breachers and unexposed controls. We performed experimental RNA sequencing using Illumina’s HiSeq 2500 Sequencing System, and microRNA analysis using NanoString Technology nCounter miRNA expression panel in whole-blood total RNA samples from 15 experienced breachers and 14 age-, sex-, and race-matched unexposed controls. We identified 10 significantly dysregulated genes between experienced breachers and unexposed controls, with FDR corrected LINC00996 (long intergenic non-protein coding RNA 996); and nine downregulated genes, IGLV3-16 (immunoglobulin lambda variable 3-16), CD200 (CD200 molecule), LILRB5 (leukocyte immunoglobulin-like receptor B5), ZNF667-AS1 (ZNF667 antisense RNA 1), LMOD1 (leiomodin 1), CNTNAP2 (contactin-associated protein 2), EVPL (envoplakin), DPF3 (double PHD fingers 3), and IGHV4-34 (immunoglobulin heavy variable 4-34). The dysregulated gene expressions reported here have been associated with chronic inflammation and immune response, suggesting that these pathways may relate to the risk of lasting neurological symptoms following high exposures to blast over a career.

Chronic mild traumatic brain injury (mTBI) has long-term consequences, such as neurological disability, but its pathophysiological mechanism is unknown. Exosomal microRNAs (exomiRNAs) may be important mediators of molecular and cellular changes involved in persistent symptoms after mTBI. We profiled exosomal microRNAs (exomiRNAs) in plasma from young adults with or without a chronic mTBI to decipher the underlying mechanisms of its long-lasting symptoms after mTBI. We identified 25 significantly dysregulated exomiRNAs in the chronic mTBI group (n = 29, with 4.48 mean years since the last injury) compared to controls (n = 11). These miRNAs are associated with pathways of neurological disease, organismal injury and abnormalities, and psychological disease. Dysregulation of these plasma exomiRNAs in chronic mTBI may indicate that neuronal inflammation can last long after the injury and result in enduring and persistent post-injury symptoms. These findings are useful for diagnosing and treating chronic mTBIs.

In this study, we constructed a rapid refresh wave forecast model using sea winds from the Korea Local Analysis and Prediction System as input forcing data. The model evaluated the changes in forecast performance considering the influence of input wind–wave interaction, which is an important factor that determines forecast performance. The forecast performance was evaluated by comparing the forecast results of the wave model with the significant wave height, wave period, and wave direction provided by moored buoy observations. During the typhoon season, the model tended to underestimate the conditions, and the root mean square error (RMSE) was reduced by increasing the wind and wave interaction parameter. The best value of the interaction parameter that minimizes the RMSE was determined based on the results of the numerical experiments performed during the typhoon season. The forecast error in the typhoon season was higher than that observed in the analysis results of the non-typhoon season. This can be attributed to the variations of the wave energy caused by the relatively strong typhoon wind field considered in the wave model.

This study examines the sustainable landscapes displayed in traditional Korean houses of the Joseon Dynasty (1392–1910) by investigating urban agricultural practices implemented in the palace, private houses, and an imaginary garden (Uiwon). Currently popular productive gardening applications, such as urban agriculture, productive landscapes, and edible landscapes, also formed the backbone of the traditional Korean housing environment in the Joseon Dynasty, which has had substantial implications for today’s landscaping practices. Landscapes that are productive rather than decorative are important for environmentally sound and sustainable development not only for South Korea but also for modern housing design worldwide. This research provides concrete discussions of the definition and range of urban agriculture, agricultural methods, and principal agents of gardening-related businesses. This information advances the cultural conversation as well as the understanding and application of gardening in the modern context. Through a comparison of traditional and modern South Korean housing environments, this study contributes to developing the research on the role of gardens in sustainable landscapes.

A wave forecast numerical simulation was performed for Typhoon Lingling around the Korean Peninsula and in the East Asia region using sea winds from 24 members produced by the Ensemble Prediction System for Global (EPSG) of Korea Meteorological Administration (KMA). Significant wave height was observed by the ocean data buoys used to verify data of the ensemble wave model, and the results of the ensemble members were analyzed through probability verification. The forecast performance for the significant wave height improved by approximately 18% in the root mean square error in the three-day lead time compared to that of the deterministic model, and the difference in performance was particularly distinct towards mid-to-late lead times. The ensemble spread was relatively appropriate, even in the longer lead time, and each ensemble model runs were all stable. As a result of the probability verification, information on the uncertainty that could not be provided in the deterministic model could be obtained. It was found that all the Relative Operating Characteristic (ROC) curves were 0.9 or above, demonstrating good predictive performance, and the ensemble wave model is expected to be useful in identifying and determining hazardous weather conditions.

Background In 2004, Sharon Keene introduced a video microscope to the hair transplant field and discussed about the benefits such as ergonomics, quality assurance, and easy teaching. In 2009, our clinic set up digital video microscope systems. CCD-chip-loaded hand-held digital video microscope was connected to a 19-inch high definition (HD) LCD monitor. We compared the transection rates and graft-cutting time of two graft-dissecting methods to decide which one is more efficient. Methods Two technicians performed follicular unit graft dissection via two different methods of video microscopic and a combination of video microscope for slivering and loupe magnification for graft-cutting. All the procedures were recorded on high-definition digital video camera and cross-checked on the video clips. Results The transection rate of digital video microscope use was 2.2% while the combination method with 1.6%. For comparison of graft-producing time, the combination method could produce about equal amount of grafts in 186% faster the time. Conclusions The work efficiency was greater with the combination method. The total graft productivity was nearly 2 times larger while the transection rates of two methods showed very close results.

Diabetes is a major risk factor for cardiovascular disease. To examine how diabetes interacts with a mildly compromised lipid metabolism, we introduced the diabetogenic Ins2C96Y/+ (Akita) mutation into mice expressing human apoE4 (E4) combined with either an overexpressing human LDL receptor gene (hLDLR) or the wild-type mouse gene. The hLDLR allele caused 2-fold reductions in plasma HDL-cholesterol, plasma apoA1, and hepatic triglyceride secretion. Diabetes increased plasma total cholesterol 1.3-fold and increased apoB48 secretion 3-fold, while reducing triglyceride secretion 2-fold. Consequently, diabetic E4 mice with hLDLR secrete increased numbers of small, cholesterol-enriched, apoB48-containing VLDL, although they have near normal plasma cholesterol (

OBJECTIVES:There is much speculation on which hypervariable region provides the highest bacterial specificity in 16S rRNA sequencing. The optimum solution to prevent bias and to obtain a comprehensive view of complex bacterial communities would be to sequence the entire 16S rRNA gene; however, this is not possible with second generation standard library design and short-read next-generation sequencing technology. METHODS:This paper examines a new process using seven hypervariable or V regions of the 16S rRNA (six amplicons: V2, V3, V4, V6-7, V8, and V9) processed simultaneously on the Ion Torrent Personal Genome Machine (Life Technologies, Grand Island, NY). Four mock samples were amplified using the 16S Ion Metagenomics Kit™ (Life Technologies) and their sequencing data is subjected to a novel analytical pipeline. RESULTS:Results are presented at family and genus level. The Kullback-Leibler divergence (DKL), a measure of the departure of the computed from the nominal bacterial distribution in the mock samples, was used to infer which region performed best at the family and genus levels. Three different hypervariable regions, V2, V4, and V6-7, produced the lowest divergence compared to the known mock sample. The V9 region gave the highest (worst) average DKL while the V4 gave the lowest (best) average DKL. In addition to having a high DKL, the V9 region in both the forward and reverse directions performed the worst finding only 17% and 53% of the known family level and 12% and 47% of the genus level bacteria, while results from the forward and reverse V4 region identified all 17 family level bacteria. CONCLUSIONS:The results of our analysis have shown that our sequencing methods using 6 hypervariable regions of the 16S rRNA and subsequent analysis is valid. This method also allowed for the assessment of how well each of the variable regions might perform simultaneously. Our findings will provide the basis for future work intended to assess microbial abundance at different time points throughout a clinical protocol.

The recognition of object categories is effortlessly accomplished in everyday life, yet its neural underpinnings remain not fully understood. In this electroencephalography (EEG) study, we used single-trial classification to perform a Representational Similarity Analysis (RSA) of categorical representation of objects in human visual cortex. Brain responses were recorded while participants viewed a set of 72 photographs of objects with a planned category structure. The Representational Dissimilarity Matrix (RDM) used for RSA was derived from confusions of a linear classifier operating on single EEG trials. In contrast to past studies, which used pairwise correlation or classification to derive the RDM, we used confusion matrices from multi-class classifications, which provided novel self-similarity measures that were used to derive the overall size of the representational space. We additionally performed classifications on subsets of the brain response in order to identify spatial and temporal EEG components that best discriminated object categories and exemplars. Results from category-level classifications revealed that brain responses to images of human faces formed the most distinct category, while responses to images from the two inanimate categories formed a single category cluster. Exemplar-level classifications produced a broadly similar category structure, as well as sub-clusters corresponding to natural language categories. Spatiotemporal components of the brain response that differentiated exemplars within a category were found to differ from those implicated in differentiating between categories. Our results show that a classification approach can be successfully applied to single-trial scalp-recorded EEG to recover fine-grained object category structure, as well as to identify interpretable spatiotemporal components underlying object processing. Finally, object category can be decoded from purely temporal information recorded at single electrodes.

Apolipoprotein E-null mice on a DBA/2J genetic background (DBA-apoE) are highly susceptible to atherosclerosis in the aortic root area compared with those on a 129S6 background (129-apoE). To explore atherosclerosis-responsible genetic regions, we performed a quantitative trait locus (QTL) analysis using 172 male and 137 female F2 derived from an intercross between DBA-apoE and 129-apoE mice. A genome-wide scan identified two significant QTL for the size of lesions at the root: one is Ath44 on Chromosome (Chr) 1 at 158 Mb, and the other Ath45 on Chr 2 at 162 Mb. Ath44 co-localizes with but appears to be independent of a previously reported QTL, Ath1, while Ath45 is a novel QTL. DBA alleles of both Ath44 and Ath45 confer atherosclerosis-susceptibility. In addition, a QTL on Chr 14 at 73 Mb was found significant only in males, and 129 allele conferring susceptibility. Further analysis detected female-specific interactions between a second QTL on Chr 1 at 73 Mb and a QTL on Chr 3 at 21 Mb, and between Chr 7 at 84 Mb and Chr 12 at 77 Mb. These loci for the root atherosclerosis were independent of QTLs for plasma total cholesterol and QTLs for triglycerides, but a QTL for HDL (Chr 1 at 126 Mb) overlapped with the Ath44. Notably, haplotype analysis among 129S6, DBA/2J and C57BL/6 genomes and their gene expression data narrowed the candidate regions for Ath44 and Ath45 to less than 5 Mb intervals where multiple genome wide associations with cardiovascular phenotypes have also been reported in humans. SNPs in or near Fmo3, Sele and Selp for Ath44, and Lbp and Pkig for Ath45 were suggested for further investigation as potential candidates underlying the atherosclerosis susceptibility.

Neuropathic pain (NP) is a debilitating condition associated with traumatic, metabolic, autoimmune and neurological etiologies. Although the triggers for NP are diverse, there are common underlying pathways, including activation of immune cells in the spinal cord and up-regulation of the N-methyl-D-aspartate receptor (NMDAR). Ketamine, a well-known NDMAR antagonist, reduces neuropathic pain in a sustained manner. Recent study has shown that the novel 11-amino acid peptide erythropoietin derivative ARA290 produces a similar, long-lasting relief of NP. Here, we show that both drugs also have similar effects on the expression of mRNA of the NMDAR, as well as that of microglia, astrocytes and chemokine (C-C motif) ligand 2, all-important contributors to the development of NP. Although the effects of ketamine and ARA 290 on NP and its molecular mediators suggest a common mechanism of action, ARA 290 has no affinity for the NMDAR and acts specifically via the innate repair receptor (IRR) involved in tissue protection. We speculated therefore, that the IRR might be critically involved in the action of ketamine on neuropathic pain. To evaluate this, we studied the effects of ketamine and ARA 290 on acute pain, side effects, and allodynia following a spared nerve injury model in mice lacking the β-common receptor (βcR), a structural component of the IRR. Ketamine (50 mg/kg) and ARA 290 (30 µg/kg) produced divergent effects on acute pain: ketamine produced profound antinociception accompanied with psychomotor side effects, but ARA290 did not, in both normal and knock out mice. In contrast, while both drugs were antiallodynic in WT mice, they had no effect on NP in mice lacking the βcR. Together, these results show that an intact IRR is required for the effective treatment of NP with either ketamine or ARA 290, but is not involved in ketamine's analgesic and side effects.

Connective tissue growth factor (CTGF) is an important mediator of fibrosis; emerging evidence link changes in plasma and urinary CTGF levels to diabetic kidney disease. To further ascertain the role of CTGF in responses to high glucose, we assessed the consequence of 4 months of streptozotocin-induced diabetes in wild type (+/+) and CTGF heterozygous (+/-) mice. Subsequently, we studied the influence of glucose on gene expression and protein in mice embryonic fibroblasts (MEF) cells derived from wildtype and heterozygous mice. At study initiation, plasma glucose, creatinine, triglyceride and cholesterol levels were similar between non-diabetic CTGF+/+ and CTGF+/- mice. In the diabetic state, plasma glucose levels were increased in CTGF+/+ and CTGF+/- mice (28.2 3.3 mmol/L vs 27.0 3.1 mmol/L), plasma triglyceride levels were lower in CTGF+/- mice than in CTGF+/+ (0.7 0.2 mmol/L vs 0.5 0.1 mmol/L, p

Connective tissue growth factor (CTGF) is a signaling molecule that primarily functions in extracellular matrix maintenance and repair. Increased Ctgf expression is associated with fibrosis in chronic organ injury. Studying the role of CTGF in fibrotic disease in vivo, however, has been hampered by perinatal lethality of the Ctgf null mice as well as the limited scope of previous mouse models of Ctgf overproduction. Here, we devised a new approach and engineered a single mutant mouse strain where the endogenous Ctgf-3' untranslated region (3'UTR) was replaced with a cassette containing two 3'UTR sequences arranged in tandem. The modified Ctgf allele uses a 3'UTR from the mouse FBJ osteosarcoma oncogene (c-Fos) and produces an unstable mRNA, resulting in 60% of normal Ctgf expression (Lo allele). Upon Cre-expression, excision of the c-Fos-3'UTR creates a transcript utilizing the more stable bovine growth hormone (bGH) 3'UTR, resulting in increased Ctgf expression (Hi allele). Using the Ctgf Lo and Hi mutants, and crosses to a Ctgf knockout or Cre-expressing mice, we have generated a series of strains with a 30-fold range of Ctgf expression. Mice with the lowest Ctgf expression, 30% of normal, appear healthy, while a global nine-fold overexpression of Ctgf causes abnormalities, including developmental delay and craniofacial defects, and embryonic death at E10-12. Overexpression of Ctgf by tamoxifen-inducible Cre in the postnatal life, on the other hand, is compatible with life. The Ctgf Lo-Hi mutant mice should prove useful in further understanding the function of CTGF in fibrotic diseases. Additionally, this method can be used for the production of mouse lines with quantitative variations in other genes, particularly with genes that are broadly expressed, have distinct functions in different tissues, or where altered gene expression is not compatible with normal development.

Purpose: This study investigated the efficacy of intravesical gemcitabine as an alternative to bacillus Calmette-Guérin (BCG) therapy. Materials and Methods: Data were retrospectively collected across seven institutions from February 1999 to May 2023. Inclusion criteria included patients with intermediate- or high-risk non-muscle invasive bladder cancer (NMIBC) who underwent transurethral resection of bladder tumors (TURBT) and received at least four sessions of intravesical gemcitabine or BCG induction therapy. Patient characteristics, complete remission (CR), occurrence, and progression rates were compared. Results: In total, 149 patients were included in this study (gemcitabine, 63; BCG, 86). No differences were apparent between the two groups in baseline characteristics, except for the follow-up period (gemcitabine, 9.2±5.9 months vs. BCG, 43.9±41.4 months, p<0.001). There were no consistent significant differences observed between the two groups in the 3-month (gemcitabine, 98.4% vs. BCG, 95.3%; p=0.848), 6-month (94.9% vs. 90.0%, respectively; p=0.793) and 1-year CR rates (84.2% vs. 83.3%, respectively; p=0.950). Also, there was no significant statistical difference in progression-free survival between the two groups (p=0.953). The occurrence rates of adverse events were similar between the groups (22.2% vs. 22.1%; p=0.989); however, the rate of Clavien-Dindo grade 2 or higher was significantly higher in the BCG group (1.6% vs. 16.3%, respectively; p<0.001). Conclusions: Intravesical gemcitabine demonstrated efficacy comparable to BCG therapy for the first year in patients with intermediate- and high-risk NMIBC. However, long-term follow-up studies are warranted. [ABSTRACT FROM AUTHOR]