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Human skin incurs damage in various ways; a few of the recognizable factors are electric burns, chemical burns, scalding burns, surgery, and physical injuries, such as automobile accidents. If skin damage is extensive and severe enough [second degree and total body surface area (TBSA) involvement of >20%], the skin will lose the ability to regenerate itself. Burn wounds are treated in various ways. For full-thickness skin defects, the mainstay of treatment is an autologous split-thickness skin graft. However, there are some limitations due to scars, poor elasticity, and limitations in the joint movements due to contractures. Recently, artificial dermis has been widely used to minimize contractures. The use of dermal replacements for the treatment of burns brings new hope in maintaining the characteristics of the normal dermis. Herein, Insuregraf® was used for skin regeneration in patients who had burn injury from flames, electricity, heat, or steam. The mean take-rate values at 7 and 14 days after operation were 94.55 ± 3.02% and 97.40 ± 2.57%, respectively. Furthermore, areas covered by Insuregraf® showed higher mean values of trans-epidermal water loss (24.6 ± 3.9 g h-1 m-2), gross elasticity (Ua/Uf = 0.76 ± 0.24), and biological elasticity (Ur/Uf = 0.55 ± 0.1). These values were much better than those of the control where Insuregraf® was not used (p = 0.030, p = 0.040, and p = 0.013, respectively). Furthermore, the biomechanical scar properties of Insuregraf® and Matriderm were very similar. Hence, we suggest that Insuregraf® can be used in the medical field.

Anthocyanins are generally accumulated within a few layers, including the epidermal cells of leaves and stems in plants. Solanum tuberosum cv. ‘Jayoung’ (hereafter, JY) is known to accumulate anthocyanin both in inner tissues and skins. We discovered that anthocyanin accumulation in the inner tissues of JY was almost diminished (more than 95% was decreased) in tuber induction condition. To investigate the transcriptomic mechanism of anthocyanin accumulation in JY flesh, which can be modulated by growth condition, we performed mRNA sequencing with white-colored flesh tissue of Solanum tuberosum cv. ‘Atlantic’ (hereafter, ‘Daeseo’, DS) grown under canonical growth conditions, a JY flesh sample grown under canonical growth conditions, and a JY flesh sample grown under tuber induction conditions. We could identify 36 common DEGs (differentially expressed genes) in JY flesh from canonical growth conditions that showed JY-specifically increased or decreased expression level. These genes were enriched with flavonoid biosynthetic process terms in GO analysis, as well as gene set enrichment analysis (GSEA) analysis. Further in silico analysis on expression levels of anthocyanin biosynthetic genes including rate-limiting genes such as StCHS and StCHI followed by RT-PCR and qRT-PCR analysis showed a strong positive correlation with the observed phenotypes. Finally, we identified StWRKY44 from 36 common DEGs as a possible regulator of anthocyanin accumulation, which was further supported by network analysis. In conclusion, we identified StWRKY44 as a putative regulator of tuber-induction-dependent anthocyanin accumulation.

It is a well-known fact that it is important to accurately measure blood pressure. In particular, it is an even more important vital sign for the elderly and patients in hospitals. Non-invasive techniques for blood pressure measurement only afford discrete results. Although invasive measurement techniques overcome this issue and provide continuous results, they involve the risk of bleeding or infection and also cause discomfort to the patient. To address this issue, in this study, we developed a deep learning model that can estimate the arterial blood pressure (ABP) in real time using the waveform signals from electrocardiograms (ECGs) and photoplethysmograms (PPGs), without handcraft setting. Data pertaining to patients with various disorders admitted in the intensive care unit (necg, ppg= 1,126,870) were used. The performance of the model was evaluated (RSBP= 0.96, RMAP=0.92, and RDBP = 0.90) and verified to meet international standards. Even if the actual value changes dramatically, the estimated value shows a graph that follows the trend. Additionally, the ABP of patients with atrial fibrillation could be measured continuously and in real time.

Background: In the treatment of type 2 diabetes mellitus (T2DM) in atrial fibrillation (AF) patients, evidence of the comparative effectiveness of sodium-glucose cotransporter 2 (SGLT2) inhibitors vs the other hypoglycemic drugs on cardiovascular morbidity and mortality is lacking. This study aimed to evaluate the comparative effectiveness of SGLT2 inhibitors vs the other hypoglycemic drugs on major adverse cardiovascular events and heart failure for hospitalization in patients with T2DM and AF.Methods: A cohort study used data from the Korean National Health Insurance Service database compared the use of SGLT2 inhibitors vs the other hypoglycemic drugs for treatment of T2DM in AF patients. We identified 40,268 patients with T2DM and AF who were newly prescribed oral hypoglycemic drugs (2,977 individualst with SGLT2 inhibitors and 37,291 individuals without SGLT2 inhibitors) between 2014 and 2018. After 1:4 propensity score matching, patients who received SGLT2 inhibitors (n=2,958) and those who did not receive SGLT2 inhibitors (n=10,691) were enrolled, and followed up until December 31, 2018. The primary study outcome was major adverse cardiovascular events (MACE), a composite of cardiovascular mortality, myocardial infarction, or ischemic stroke. Secondary outcoms were hospitalization for heart failure and all-cause mortality. The risks of study outcomes were assessed using a Cox proportional hazard model.Results: Mean age of all participants was 59.7 ± 11.9 years and 8.023 [58%] were male. During a mean follow-up duration of 2.1 ± 1.4 years, SGLT2 inhibitors were not significantly associated with reduced risk of MACE(hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.76-1.21) compared with the other hypoglycemic drugs. However, patients who received SGLT2 inhibitors had significantly lower risks of hospitalization for heart failure (HR, 0.70; 95% CI, 0.53-0.93) and all-cause mortality (HR, 0.74; 95% CI, 0.56-0.98) than those who did not receive SGLT2 inhibitors. Conclusions: In this real-world cohort of Asian patients with T2DM and AF, new use of SGLT2 inhibitors was associated with a lower risk of hospitalization for heart failure compared with use of the other hypoglycemic drugs.

A paucity of studies evaluating failed cases of ABO grouping using autoanalyzers exists. We investigated autoanalyzer rejected cases, including serologically suspicious ABO subgroups and discrepant ABO blood grouping results from Erytra Eflexis (Grifols, Spain), to demonstrate efficient use of autoanalyzers for ABO grouping.Samples requested for ABO grouping throughout 2020 were tested using two Eflexis instruments and standard ABO RhD and reverse grouping cards. Neonatal cards were not used. When necessary, a conventional tube technique (TUBE) was used to resolve rejected/discrepant Eflexis ABO grouping results.The overall sample rejection rate (RR) was 3.2% (628/19,466), 1.3% of which were due to various error flags and 1.9% for discrepant results. Cases from neonates ≤1 year old accounted for 35.3% of the rejected cases based on Eflexis results. The ABO groups with the highest and lowest RR (excluding neonates) were A and O, respectively. The 628 samples resulted in 682 rejections, which were frequently associated with reverse grouping, including 28.4% against AThe ABO group and a proportion of neonatal samples influenced the RR due to weak reverse grouping reactivity, especially toward B red cells. Confirmatory ABO grouping by TUBE in a new patient and/or extra rejection criteria for forward grouping are needed to detect cis-AB, which is relatively common in Korea.

Coronavirus disease 2019, caused by SARS-CoV-2, remains an on-going pandemic, partly due to the emergence of variant viruses that can “break-through” the protection of the current vaccines and neutralizing antibodies (nAbs), highlighting the needs for broadly nAbs and next-generation vaccines. We report an antibody that exhibits breadth and potency in binding the receptor-binding domain (RBD) of the virus spike glycoprotein across SARS coronaviruses. Initially, a lead antibody was computationally discovered and crystallographically validated that binds to a highly conserved surface of the RBD of wild-type SARS-CoV-2. Subsequently, through experimental affinity enhancement and computational affinity maturation, it was further developed to bind the RBD of all concerning SARS-CoV-2 variants, SARS-CoV-1 and pangolin coronavirus with pico-molar binding affinities, consistently exhibited strong neutralization activity against wild-type SARS-CoV-2 and the Alpha and Delta variants. These results identify a vulnerable target site on coronaviruses for development of pan-sarbecovirus nAbs and vaccines.

The timely diagnosis of different stages in NAFLD is crucial for disease treatment and reversal. We used hepatocellular ballooning to determine different NAFLD stages.We analyzed differentially expressed genes (DEGs) in 78 patients with NAFLD and in healthy controls from previously published RNA-seq data. We identified two expression types in NAFLD progression, calculated the predictive power of candidate genes, and validated them in an independent cohort. We also performed cancer studies with these candidates retrieved from the Cancer Genome Atlas.We identified 103 DEGs in NAFLD patients compared to healthy controls: 75 genes gradually increased or decreased in the NAFLD stage, whereas 28 genes showed differences only in NASH. The former were enriched in negative regulation and binding-related genes; the latter were involved in positive regulation and cell proliferation. Feature selection showed the gradual up- or down-regulation of 21 genes in NASH compared to controls; 18 were highly expressed only in NASH. Using deep-learning method with subset of features from lasso regression, we obtained reliable determination performance in NAFL and NASH (accuracy: 0.857) and validated these genes using an independent cohort (accuracy: 0.805). From cancer studies, we identified significant differential expression of several candidate genes in LIHC; 5 genes were gradually up-regulated and 6 showing high expression only in NASH were influential to patient survival.The identified biomolecular signatures may determine the spectrum of NAFLD and its relationship with HCC, improving clinical diagnosis and prognosis and enabling a therapeutic intervention for NAFLD.

Purpose Upfront systemic chemotherapy with target agents has been recommended for patients with stage IV colon cancer. Some with partial response are considered for curative resection. There is high risk of developing postoperative complications following upfront systemic chemotherapy. We aimed to evaluate short-term perioperative outcomes of curative surgery after upfront chemotherapy in comparison with upfront surgery in patients with metastatic colon cancer. Methods Between January 2010 and October 2015, 146 patients (80 in the surgery first group, 66 in the upfront chemotherapy group) who underwent surgical resection before or after systemic chemotherapy for metastatic colon cancer were included in the present study. All decisions for treatment were made through a multidisciplinary team. Postoperative clinical outcomes and complications were analyzed to compare the groups. Results There was no difference between the 2 groups in terms of postoperative clinical outcomes. Overall complication rates were not different between the groups (surgery first group: 46.3% vs. upfront chemotherapy group: 60.6%; P = 0.084). When classified according to the Clavien-Dindo method, there was no difference between the 2 groups in terms of major complications (grade 3 or more) (surgery first group: 18.9% vs. upfront chemotherapy group: 27.5%; P = 0.374). Conclusion There was no significant increase in major postoperative complications in metastatic colon cancer patients who received upfront chemotherapy followed by curative surgery. Careful patient selection and treatment planning are important.

Our objective was to determine how much PaO2 levels increase after normobaric oxygen (NBO) therapy and whether NBO therapy exerts therapeutic effects regardless of the PaO2 level. We suggest the optimal PaO2 level to use during NBO therapy for the acute treatment of carbon monoxide (CO) poisoning. This retrospective study included 311 patients who received oxygen administration after CO poisoning and had a measurable PaO2 level upon arrival. Baseline characteristics, clinical courses and long-term neurological outcome were collected and compared. The PaO2 level upon arrival was 192 (161-225) mm Hg, and 272 (87.5%) of the patients presented with hyperoxia. The incidence of poor long-term neurological outcome was 11.3% at a median follow-up period of 35 months. PaO2 levels upon arrival were higher in patients with good long-term neurological outcome than in those with poor outcome. The incidence of poor long-term neurological outcome was significantly dependent on the PaO2 level when patients were stratified at 100-mm Hg increments. A multivariate regression analysis showed that PaO2 levels, when considered a continuous, interval or ordinal variable, were associated with long-term neurological outcome in separate models. According to the three models, a PaO2 level of 200-300 mm Hg has the lowest risk of poor long-term neurological outcome. The results of the analysis of the predicted probability of poor long-term outcome according to the PaO2 level exhibited a U-shaped curve. Further large-scale studies are needed to confirm the association between 200-300 mm Hg of PaO2 and long-term neurological outcome and evaluate the impact of PaO2 levels above 300 mm Hg on acute CO poisoning outcome.

Document representation is central to modern natural language processing systems including document clustering. Empirical experiments in recent studies provide strong evidence that unsupervised language models can learn context-aware representations in the given documents and advance several NLP benchmark results. However, existing clustering approaches focus on the dimensionality reduction and do not exploit these informative representations. In this paper, we propose a conceptually simple but experimentally effective clustering framework called Advanced Document Clustering (ADC). In contrast to previous clustering methods, ADC is designed to leverage syntactically and semantically meaningful features through feature-extraction and clustering modules in the framework. We first extract features from pre-trained language models and initialize cluster centroids to spread out uniformly. In the clustering module of ADC, the semantic similarity can be measured using the cosine similarity and centroids update while assigning centroids to a mini-batch input. Also, we utilize cross entropy loss partially, as the self-training scheme can be biased when parameters in the model are inaccurate. As a result, ADC can take advantages of contextualized representations while mitigating the limitations introduced by high-dimensional vectors. In numerous experiments with four datasets, the proposed ADC outperforms other existing approaches. In particular, experiments on categorizing news corpus with fake news demonstrated the effectiveness of our method for contextualized representations.

This study aimed to evaluate the association between acute kidney injury (AKI) and 6 months neurological outcome after out-of-hospital cardiac arrest (OHCA).Prospective multi-center observational cohort included adult OHCA patients treated with targeted temperature management (TTM) across 20 hospitals in the South Korea between October 2015 and October 2017. The diagnosis of AKI was made using the Kidney Disease: Improving Global Outcomes criteria. The outcome was neurological outcome at 6 months evaluated using the modified Rankin scale (MRS).Among 5676 patients with OHCA, 583 patients were enrolled. AKI developed in 348 (60%) patients. Significantly more non-AKI patients had good neurological outcome at 6 months (MRS 0-3) than AKI patients (134/235 [57%] vs. 69/348 [20%], P .001). AKI was associated with poor neurological outcome at six months in multivariate logistic regression analysis (adjusted odds ratio: 0.206 [95% confidence interval: 0.099-0.426], P .001]). Cox regression analysis with time-varying covariate of AKI showed that patients with AKI had a higher risk of death than those without AKI (hazard ratio: 2.223; 95% confidence interval: 1.630-3.030, P .001).AKI is associated with poor neurological outcome (MRS 4-6) at 6 months in OHCA patients treated with TTM.NCT02827422.

Background Robot-assisted gait training (RAGT) is more effective in the range of motion (ROM) and isometric strength in patients with burns than conventional training. However, concerns have been raised about whether RAGT might negatively affect the scars of patients with burns. Therefore, we investigated the effects of RAGT-induced mechanical load on the biomechanical properties of burn scars. Methods This was a single-blind, randomized clinical trial conducted on inpatients admitted to the Department of Rehabilitation Medicine between September 2020 and August 2021. RAGT was conducted for 30 min per day, five days a week for 12 weeks and the control group received conventional gait training for 12 weeks. The pre-training ROM of lower extremity joints was evaluated and the levels of melanin, erythema, trans-epidermal water loss, scar distensibility and elasticity were assessed before training and at 4 and 12 weeks after training. Finally, 19 patients in the gait assistance robot (GAR) group and 20 patients in the control group completed the 12-week trial and all evaluations. Results There were no significant differences in the epidemiologic characteristics, pre-training ROM of joints and pre-training biomechanical properties of the burn scar between the groups (p > 0.05 for all). None of the patients experienced skin abrasion around the burn scar where the fastening belts were applied or musculoskeletal or cardiovascular adverse events during the training. Scar thickness significantly increased in both groups (p = 0.037 and p = 0.019) and scar distensibility significantly decreased in the control group (p = 0.011) during the training. Hysteresis was significantly decreased in the GAR group during the training (p = 0.038). The GAR and control groups showed significant difference in the change in the values of hysteresis between pre-training and 12 weeks after training (p = 0.441 and p = 0.049). Conclusions RAGT significantly decreased hysteresis in hypertrophic burn scars and did not cause a significant decrease in skin distensibility. Moreover, no skin complications around the burn scars were detected during RAGT. Trial registration This study registered on the Clinical Research Information Service (KCT0005204).

Cryogenic electron microscopy (cryo-EM) has become a widely used tool for determining protein structure. Despite recent technology advances, sample preparation remains a major bottleneck for several reasons, including protein denaturation at the air/water interface, the presence of preferred orientations, nonuniform ice layers, etc. Graphene, a two-dimensional allotrope of carbon consisting of a single atomic layer, has recently gained attention as a near-ideal support film for cryo-EM that can overcome these challenges because of its superior properties, including mechanical strength and electrical conductivity. Here, we introduce a reliable, easily implemented, and reproducible method to produce 36 graphene-coated grids within 1.5 days. To demonstrate their practical application, we determined the cryo-EM structure of Methylococcus capsulatus soluble methane monooxygenase hydroxylase (sMMOH) at resolutions of 2.9 and 2.4 Å using Quantifoil and graphene-coated grids, respectively. We found that the graphene-coated grid has several advantages, including less amount of protein required and avoiding protein denaturation at the air/water interface. By comparing the cryo-EM structure of sMMOH with its crystal structure, we identified subtle yet significant geometrical changes at the non-heme di-iron center, which may better indicate the active site configuration of sMMOH in the resting/oxidized state.

Cryo-EM structures of the KMT2A/MLL1 core complex bound on nucleosome core particles (NCPs) suggest unusual rotational dynamics of the MLL1 complex approaching its physiological substrate. However, the functional implication of such dynamics remains unclear. Here, we show that the MLL1 core complex also shows high rotational dynamics bound on the NCP carrying the catalytically inert histone H3 lysine 4 to methionine (K4M) mutation. There are two major binding modes of the MLL1 complex on the NCP

Purpose To assess the performance of the post-cardiac arrest (CA) prognostication strategy algorithm recommended by the European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM) in 2020. Methods This was a retrospective analysis of the Korean Hypothermia Network Prospective Registry 1.0. Unconscious patients without confounders at day 4 (72–96 h) after return of spontaneous circulation (ROSC) were included. The association between the prognostic factors included in the prognostication strategy algorithm, except status myoclonus and the neurological outcome, was investigated, and finally, the prognostic performance of the prognostication strategy algorithm was evaluated. Poor outcome was defined as cerebral performance categories 3–5 at 6 months after ROSC. Results A total of 660 patients were included in the final analysis. Of those, 108 (16.4%) patients had a good neurological outcome at 6 months after CA. The 2020 ERC/ESICM prognostication strategy algorithm identified patients with poor neurological outcome with 60.2% sensitivity (95% CI 55.9–64.4) and 100% specificity (95% CI 93.9–100) among patients who were unconscious or had a GCS_M score ≤ 3 and with 58.2% sensitivity (95% CI 53.9–62.3) and 100% specificity (95% CI 96.6–100) among unconscious patients. When two prognostic factors were combined, any combination of prognostic factors had a false positive rate (FPR) of 0 (95% CI 0–5.6 for combination of no PR/CR and poor CT, 0–30.8 for combination of No SSEP N20 and NSE 60). Conclusion The 2020 ERC/ESICM prognostication strategy algorithm predicted poor outcome without an FPR and with sensitivities of 58.2–60.2%. Any combinations of two predictors recommended by ERC/ESICM showed 0% of FPR.

Parkinson’s disease (PD) is a movement disorder caused by progressive degeneration of the midbrain dopaminergic (mDA) neurons in the substantia nigra pars compacta (SNc). Despite intense research efforts over the past decades, the etiology of PD remains largely unknown. Here, we discovered the involvement of trophoblast glycoprotein (Tpbg) in the development of PD-like phenotypes in mice. Tpbg expression was detected in the ventral midbrain during embryonic development and in mDA neurons in adulthood. Genetic ablation of Tpbg resulted in mild degeneration of mDA neurons in aged mice (12–14 months) with behavioral deficits reminiscent of PD symptoms. Through in silico analysis, we predicted potential TPBG-interacting partners whose functions were relevant to PD pathogenesis; this result was substantiated by transcriptomic analysis of the SNc of aged Tpbg knockout mice. These findings suggest that Tpbg is a new candidate gene associated with PD and provide a new insight into PD pathogenesis.

Characterizing the genetic diversity and population structure of breeding materials is essential for breeding to improve crop plants. The potato is an important non-cereal food crop worldwide, but breeding potatoes remains challenging owing to their auto-tetraploidy and highly heterozygous genome. We evaluated the genetic structure of a 110-line Korean potato germplasm using the SolCAP 8303 single nucleotide polymorphism (SNP) Infinium array and compared it with potato clones from other countries to understand the genetic landscape of cultivated potatoes. Following the tetraploid model, we conducted population structure analysis, revealing three subpopulations represented by two Korean potato groups and one separate foreign potato group within 110 lines. When analyzing 393 global potato clones, country/region-specific genetic patterns were revealed. The Korean potato clones exhibited higher heterozygosity than those from Japan, the United States, and other potato landraces. We also employed integrated extended haplotype homozygosity (iHS) and cross-population extended haplotype homozygosity (XP-EHH) to identify selection signatures spanning candidate genes associated with biotic and abiotic stress tolerance. Based on the informativeness of SNPs for dosage genotyping calls, 10 highly informative SNPs discriminating all 393 potatoes were identified. Our results could help understanding a potato breeding history that reflects regional adaptations and distinct market demands.

Smad4 and p53 mutations are the most common mutations in human colorectal cancers (CRCs). We evaluated whether and how they are synergistic in intestinal carcinogenesis using novel autochthonous mouse models.To recapitulate human CRCs, we generated Villin-Cre;Smad4Twenty-week-old Villin-Cre;Smad4Smad4 loss and p53 loss are synergistic in autochthonous intestinal carcinogenesis, by downregulating p21 and activating Wnt/β-catenin pathway.

Interspecific somatic hybridization has been performed in potato breeding experiments to increase plant resistance against biotic and abiotic stress conditions. We analyzed the mitochondrial and plastid genomes and 45S nuclear ribosomal DNA (45S rDNA) for the cultivated potato (S. tuberosum, St), wild potato (S. commersonii, Sc), and their somatic hybrid (StSc). Complex genome components and structure, such as the hybrid form of 45S rDNA in StSc, unique plastome in Sc, and recombinant mitogenome were identified. However, the mitogenome exhibited dynamic multipartite structures in both species as well as in the somatic hybrid. In St, the mitogenome is 756,058 bp and is composed of five subgenomes ranging from 297,014 to 49,171 bp in St. In Sc, it is 552,103 bp long and is composed of two sub-genomes of 338,427 and 213,676 bp length. StSc has 447,645 bp long mitogenome with two subgenomes of length 398,439 and 49,206 bp. The mitogenome structure exhibited dynamic recombination mediated by tandem repeats; however, it contained highly conserved genes in the three species. Among the 35 protein-coding genes of the StSc mitogenome, 21 were identical for all the three species, and 12 and 2 were unique in Sc and St, respectively. The recombinant mitogenome might be derived from homologous recombination between both species during somatic hybrid development.

Background We assessed the prognostic accuracy of the standardized electroencephalography (EEG) patterns (“highly malignant,” “malignant,” and “benign”) according to the EEG timing (early vs. late) and investigated the EEG features to enhance the predictive power for poor neurologic outcome at 1 month after cardiac arrest. Methods This prospective, multicenter, observational, cohort study using data from Korean Hypothermia Network prospective registry included adult patients with out-of-hospital cardiac arrest (OHCA) treated with targeted temperature management (TTM) and underwent standard EEG within 7 days after cardiac arrest from 14 university-affiliated teaching hospitals in South Korea between October 2015 and December 2018. Early EEG was defined as EEG performed within 72 h after cardiac arrest. The primary outcome was poor neurological outcome (Cerebral Performance Category score 3–5) at 1 month. Results Among 489 comatose OHCA survivors with a median EEG time of 46.6 h, the “highly malignant” pattern (40.7%) was most prevalent, followed by the “benign” (33.9%) and “malignant” (25.4%) patterns. All patients with the highly malignant EEG pattern had poor neurologic outcomes, with 100% specificity in both groups but 59.3% and 56.1% sensitivity in the early and late EEG groups, respectively. However, for patients with “malignant” patterns, 84.8% sensitivity, 77.0% specificity, and 89.5% positive predictive value for poor neurologic outcome were observed. Only 3.5% (9/256) of patients with background EEG frequency of predominant delta waves or undetermined had good neurologic survival. The combination of “highly malignant” or “malignant” EEG pattern with background frequency of delta waves or undetermined increased specificity and positive predictive value, respectively, to up to 98.0% and 98.7%. Conclusions The “highly malignant” patterns predicted poor neurologic outcome with a high specificity regardless of EEG measurement time. The assessment of predominant background frequency in addition to EEG patterns can increase the prognostic value of OHCA survivors. Trial registration KORHN-PRO, NCT02827422. Registered 11 September 2016—Retrospectively registered.

Background: Acute appendicitis is the most common surgical abdominal emergency. Single-port laparoscopic appendectomy (SPLA) has been suggested potential advantages including less postoperative pain and better cosmesis. The aim of this study was to compare the postoperative pain and cosmetic outcomes between SPLA and multi-port laparoscopic appendectomy (MPLA) for acute appendicitis.Materials and methods: The study included 47 patients who underwent SPLA and 51 patients who underwent MPLA for acute appendicitis between August 2014 and November 2017. The patient scar assessment questionnaire (PSAQ) was used to assess cosmetic outcomes. Results: MPLA involved a longer median operative time than MPLA (60 vs. 47.5 minutes, p=0.02). There were no apparent differences in the time before diet tolerance, length of hospital stay, inflammatory laboratory findings including C-reactive protein and white blood cell count, and postoperative complication rate. SPLA patients had a smaller total incision length (2.0 vs. 2.5 cm, pConclusion: SPLA is safe and feasible and provides better cosmetic outcomes and less analgesic requirements on the day of surgery compared to MPLA.

An understanding of the anatomy of the Denonvilliers’ fascia is essential for successful surgical outcomes for patients with rectal cancer in the mid- to lower regions, especially near the seminal vesicles and prostate in males. Whether the correct surgical plane during a total mesorectal excision should be anterior or posterior to the Denonvilliers’ fascia is currently under debate. This study aimed to investigate the Denonvilliers’ fascia using micro-computed tomography (micro-CT) to acquire three-dimensional images nondestructively for assessments of the relationship between the Denonvilliers’ fascia, the mesorectal fascia, and neurovascular bundles to elucidate the correct anterior total mesorectal excision plane. Eight specimens were obtained bilaterally from four fresh human cadavers. Four specimens were stained with phosphotungstic acid to visualize the soft tissue, and micro-CT images were obtained; the other four specimens were stained with Masson’s trichrome to visualize connective tissue. Micro-CT images corroborate that the Denonvilliers’ fascia consists of a multilayered structure that separates the rectum from the seminal vesicles and the prostate. Specimens stained with Masson’s trichrome showed that the urogenital neurovascular bundle located at the posterolateral corner of the prostate is separated from the mesorectum by the Denonvilliers’ fascia. For the preservation of autonomic nerves necessary for urogenital function and optimal oncologic outcomes in patients with rectal cancer, a successful mesorectal excision requires a dissection plane posterior to the Denonvilliers’ fascia.

Aims The nuclear factor-κB (NF-κB) signalling pathway plays a critical role in the pathogenesis of multiple vascular diseases. However, in endothelial cells (ECs), the molecular mechanisms responsible for the negative regulation of the NF-κB pathway are poorly understood. In this study, we investigated a novel role for protein tyrosine phosphatase type IVA1 (PTP4A1) in NF-κB signalling in ECs. Methods and results In human tissues, human umbilical artery ECs, and mouse models for loss of function and gain of function of PTP4A1, we conducted histological analysis, immunostaining, laser-captured microdissection assay, lentiviral infection, small interfering RNA transfection, quantitative real-time PCR and reverse transcription-PCR, as well as luciferase reporter gene and chromatin immunoprecipitation assays. Short hairpin RNA-mediated knockdown of PTP4A1 and overexpression of PTP4A1 in ECs indicated that PTP4A1 is critical for inhibiting the expression of cell adhesion molecules (CAMs). PTP4A1 increased the transcriptional activity of upstream stimulatory factor 1 (USF1) by dephosphorylating its S309 residue and subsequently inducing the transcription of tumour necrosis factor-alpha-induced protein 3 (TNFAIP3/A20) and the inhibition of NF-κB activity. Studies on Ptp4a1 knockout or transgenic mice demonstrated that PTP4A1 potently regulates the interleukin 1β-induced expression of CAMs in vivo. In addition, we verified that PTP4A1 deficiency in apolipoprotein E knockout mice exacerbated high-fat high-cholesterol diet-induced atherogenesis with upregulated expression of CAMs. Conclusion Our data indicate that PTP4A1 is a novel negative regulator of vascular inflammation by inducing USF1/A20 axis-mediated NF-κB inactivation. Therefore, the expression and/or activation of PTP4A1 in ECs might be useful for the treatment of vascular inflammatory diseases.

The effectiveness of extracorporeal membrane oxygenation (ECMO) for patients with refractory cardiogenic shock or cardiac arrest is being established, and serum lactate is well known as a biomarker of end-organ perfusion. We evaluated the efficacy of pre-ECMO lactate for predicting 6-month survival in patients with acute coronary syndrome (ACS) undergoing ECMO.We reviewed the medical records of 148 patients who underwent veno-arterial (VA) ECMO for ACS between January 2015 and June 2020. These patients were divided into survivors and non-survivors based on 6-month survival. All clinical data before and during ECMO were compared between the 2 groups.Patients' mean age was 66.0±10.5 years, and 116 (78.4%) were men. The total survival rate was 45.9% (n=68). Cox regression analysis showed that the pre-ECMO lactate level was an independent predictor of 6-month mortality (hazard ratio, 1.210; 95% confidence interval [CI], 1.064-1.376; p=0.004). The area under the receiver operating characteristic curve of pre-ECMO lactate was 0.64 (95% CI, 0.56-0.72; p=0.002; cut-off value=9.8 mmol/L). Kaplan-Meier survival analysis showed that the cumulative survival rate at 6 months was significantly higher among patients with a pre-ECMO lactate level of 9.8 mmol/L or less than among those with a level exceeding 9.8 mmol/L (57.3% vs. 31.8%, p=0.0008).A pre-ECMO lactate of 9.8 mmol/L or less may predict a favorable outcome at 6 months in ACS patients undergoing VA-ECMO. Further research aiming to improve the accuracy of predictions of reversibility in patients with high pre-ECMO lactate levels is essential.

Transcranial brain stimulation (TMS) was introduced in 1985 by Barker and his colleagues. Since then, further improvements in technology have allowed additional applications and new stimulation protocols. In the last decade, while the use of TMS has expanded enormously in basic science as well as in the clinical scenario, the underlying neurophysiological or neurochemical mechanisms are still not fully understood. Positron emission tomography (PET) and single-photon emission computerized tomography (SPECT) are neuroimaging modalities utilized to investigate brain functions. In spite of their lower spatial and time resolution compared with functional magnetic resonance imaging (fMRI) and electroencephalography (EEG), PET/SPECT have helped to elucidate some of the neurochemical mechanisms and neural plastic changes associated with TMS. In this chapter, we will provide an overview of these techniques, describing methodological details and application of TMS-PET/SPECT imaging in basic and clinical studies.

In underwater acoustic cellular (UWAC) systems, underwater equipment or sensor nodes (UE/SN) should perform downlink synchronisation and a cell search during the initial access stage using the preambles received from adjacent underwater base stations (UWBSs). The UE/SN needs to estimate accurate timing and cell ID (CID) using the received preambles, and synchronise with a serving UWBS, even in high-Doppler environments. In this paper, a sequence design technique for joint estimation of accurate timing and CID in UWAC systems with a high Doppler is proposed to decrease the receiver complexity and processing time. A generalised Zadoff–Chu sequence is proposed for the preamble design. This sequence is decomposed into multiple short sub-sequences to reduce the effect of Doppler shift on the timing and CID estimation. The performance loss caused by the short sequence length is compensated by combining the sub-sequences using the repetition property of the ZC sequence. The properties (autocorrelation and cross-correlation) of the proposed sequence are derived analytically in the presence of Doppler shift and compared with the simulation results. The simulation results reveal that the proposed technique performs better than existing techniques in both additive white Gaussian noise and multipath channels with a high-Doppler. It is concluded that the proposed technique is suitable for accurate timing estimation and CID detection in UWAC systems with a high Doppler.