A Novel Lactate Metabolism-Related Gene Signature for Predicting Clinical Outcome and Tumor Microenvironment in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the main subtype of primary liver cancer with high malignancy and poor prognosis. Metabolic reprogramming is a hallmark of cancer and has great importance on the tumor microenvironment (TME). As an abundant metabolite, lactate plays a crucial role in cancer progression and the immunosuppressive TME. Nonetheless, the potential roles of lactate in HCC remain unclear. In this study, we downloaded transcriptomic data of HCC patients with corresponding clinical information from the TCGA and ICGC portals. The TCGA-HCC dataset used as the training cohort, while the ICGC-LIRI-JP dataset was served as an external validation cohort. Cox regression analysis and the LASSO regression model were combined to construct the lactate metabolism-related gene signature (LMRGS). Then, we assessed the clinical significance of LMRGS in HCC. Besides, enriched molecular functions, tumor mutation burden (TMB), infiltrating immune cells, and immune checkpoint were comprehensively analyzed in different LMRGS subgroups. In total, 66 differentially expressed lactate metabolism-related genes (LMRGs) were screened. The functions of LMRGs were mainly enriched in mitochondrial activity and metabolic processes. The LMRGS comprised of six key LMRGs (FKTN, PDSS1, PET117, PUS1, RARS1, and RNASEH1) had significant clinical value for independently predicting the prognosis of HCC patients. The overall survival and median survival of patients in the LMRGS-high group were significantly shorter than in the LMRGS-low group. In addition, there were differences in TMB between the two LMRGS subgroups. The probability of genetic mutations was higher in the LMRGS-high group. Most importantly, the LMRGS reflected the TME characteristics. In the LMRGS-high group, the immune microenvironment presented a suppressed state, accompanied by more inhibitory immune cell infiltration, including follicular helper T cells and regulatory T cells. Additionally, the expression of inhibitory checkpoint molecules was much higher in the LMRGS-high group. Our study suggested that the LMRGS was a robust biomarker to predict the clinical outcomes and evaluate the TME of patients with HCC.

Comparison of Endotoxin Activity Assay and Various Biomarkers for Severity Assessment in Colorectal Perforation Patients

Colorectal perforation is a serious disease with high mortality requiring emergency surgery. This study aimed to evaluate the role of the endotoxin activity assay (EAA) to assess the severity in patients admitted to the intensive care unit after emergency surgeries for colorectal perforations. Patients were divided into high (EAA ≥.4) and low (EAA <.4) groups based on the EAA levels, and the correlation between the EAA values and clinical variables related to the severity was evaluated. The SOFA scores were significantly higher in the high group than those in the low group. The high EAA value persisted even after 48 hours and extended the ICU length of stay. These results suggest that EAA may be a potential biomarker to assess severity and useful as one of the instrumental in predicting the outcomes for colorectal perforation patients.

Combination of Radiosensitivity Gene Signature and PD-L1 Status Predicts Clinical Outcome of Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma: A Study Based on The Cancer Genome Atlas Dataset

Aim: The aim of our study was to investigate the potential predictive value of the combination of radiosensitivity gene signature and PD-L1 expression for the prognosis of locally advanced head and neck squamous cell carcinoma (HNSCC).Methods: The cohort was selected from The Cancer Genome Atlas (TCGA) and classified into the radiosensitive (RS) group and radioresistant (RR) group by a radiosensitivity-related gene signature. The cohort was also grouped as PD-L1-high or PD-L1-low based on PD-L1 mRNA expression. The least absolute shrinkage and selection operator (lasso)-based Cox model was used to select hub survival genes. An independent validation cohort was obtained from the Gene Expression Omnibus (GEO) database.Results: We selected 288 locally advanced HNSCC patients from TCGA. The Kaplan–Meier method found that the RR and PD-L1-high group had a worse survival than others (p = 0.033). The differentially expressed gene (DEG) analysis identified 553 upregulated genes and 486 downregulated genes (p &lt; 0.05, fold change &gt;2) between the RR and PD-L1-high group and others. The univariate Cox analysis of each DEG and subsequent lasso-based Cox model revealed five hub survival genes (POU4F1, IL34, HLF, CBS, and RNF165). A further hub survival gene-based risk score model was constructed, which was validated by an external cohort. We observed that a higher risk score predicted a worse prognosis (p = 0.0013). The area under the receiver operating characteristic curve (AUC) plots showed that this risk score model had good prediction value (1-year AUC = 0.684, 2-year AUC = 0.702, and 3-year AUC = 0.688). Five different deconvolution methods all showed that the B cells were lower in the RR and PD-L1-high group (p &lt; 0.05). Finally, connectivity mapping analysis showed that the histone deacetylase (HDAC) inhibitor trichostatin A might have the potential to reverse the phenotype of RR and PD-L1-high in locally advanced HNSCC (p &lt; 0.05, false discovery rate &lt;0.1).Conclusion: The combination of 31-gene signature and the PD-L1 mRNA expression had a potential predictive value for the prognosis of locally advanced HNSCC who had RT. The B cells were lower in the RR and PD-L1-high group. The identified risk gene signature of locally advanced HNSCC and the potential therapeutic drug trichostatin A for the RR and PD-L1-high group are worth being further studied in a prospective homogenous cohort.

ADS Score as a Novel Predictor of Outcomes in Patients Who Underwent Percutaneous Coronary Intervention

Objectives: A novel AFR– albumin-derived neutrophil to lymphocyte ratio (dNLR) score (ADS) were reported to associate with clinical outcome in various malignancies, However, the relation between the ADS score and outcomes in coronary artery disease (CAD) patients after percutaneous coronary intervention (PCI) has not been investigated.Methods: Three thousand five hundred and sixty-one patients were divided into two groups according to ADS score: low group (ADS score &lt;2; n = 2,682) and high group (ADS score ≥ 2; n = 879). Overall, there were 133 all-cause mortality (ACM) during the following up. The incidence of ACM in the low group is 2.7% (72/2,682) and high group is 6.9% (61/879). The ACM incidence was significantly higher in high group compared to that in the low group (P &lt; 0.001). Cardiac mortality (CM) occurred in 82 patients: 44(1.6%) in the low group and 38 (4.3%) in the high group. There was significant difference in the CM incidence between the low group and high group (P &lt; 0.001). Major adverse cardiac and cerebrovascular events (MACCE) occurred in 520 patients: 366 (13.6%) in the low group and 154 (17.5%) in the high group. There was significant difference in the MACCE incidence between the low group and high group (P = 0.005). Major adverse cardiac and events (MACE) occurred in 395 patients: 281(10.5%) in the low group and 114 (13.0%) in the high group. There was significant difference in the MACE incidence between the low group and high group (P = 0.041). The multivariate Cox proportional hazards model showed that ADS score was independently correlated with the ACM [adjusted HR = 2.031 (1.357–3.039), P = 0.001]; CM [adjusted HR = 1.883 (1.127–3.147), P = 0.016]; MACCE [adjusted HR = 1.352 (1.096–1.668), P = 0.005], and MACE [adjusted HR = 1.260 (0.987–1.608), P = 0.063].Conclusion: The present study indicated that the ADS score was associated with long-term mortality, the MACCE, and the MACE in CAD patients underwent PCI.

Penggunaan Metode K-Means Cluster Untuk Mengklasifikasikan Kemampuan 4C Mahasiswa

The K-means method is a non-hierarchical belongs to an algorithmic technique for grouping items into K clusters by minimizing the SS sum of square (SS) distance to the centroid cluster. In the K-means method, the number of clusters can be determined by the researchers themselves. The K-means method can be applied to all fields, including education. In facing the 21st century, many students must equip themselves with many abilities, including critical thinking, collaboration, communication, and creativity and innovation, referred to as 4C abilities. This study aims to apply the K-means method to classify students' 4C abilities. The population in this study were students of the English Language State Institute of Islamic Studies Ponorogo class of 2017 and class of 2018. The sampling technique was carried out using the stratified random sampling method with a sample size of 71 divided into 30 students of the 2017 class and 41 students of the 2018 class. In identifying outliers, it is known that 16 students enter outlier detection not to be analyzed. The results of the classification using the K-means method showed that there were three groups with a composition of 20 students in the high group, 20 students in the medium group, and 15 students in the low group with an R2 value of 41.7%. Based on the test results of ANOVA, it is known that the three groups, based on their ability level, have differences. These results showed that each group formed had a noticeable difference, albeit with an R2 value that was not large.

Association Between Serum Albumin and Mortality in Older People With Dysphagia: a Retrospective Cohort Study

Objective: To determine whether there is a link between serum albumin and mortality among participants in Japan older people.Methods: This is a single-center, retrospective cohort study analysis of 253 older patients with dysphagia from Japan, conducted from January 2014 and January 2017. The primary outcome was mortality. We performed Cox regression analysis to compare the mortality between the two groups (dividing by serum albumin=3g/dl).Results: A total of 253 patients were included in the analysis, of whom the number of serum albumin under 3g/dl was 93. The log-rank test showed a significantly longer mortality in the high group (serum albumin >=3g/dl) compared with the low group (median, 382 vs 176 days, P < 0.0001). Cox regression analysis showed that unadjusted HR for the high group relative to the low group was 0.40 (95% CI: 0.29–0.57; P <0.001). After adjustment 3 models in multivariable analyses, serum albumn was significantly associated with mortality. The adjusted HRs (95% CI) for total mortality rates were 0.46 (0.33~0.65) , 0.66 (0.44~0.99) and 0.64 (0.42~0.97), from model 2 to model 4.Conclusion: There is negative association between serum albumin and mortality in older people with dysphagia.

Long decay length of magnon-polarons in BiFeO3/La0.67Sr0.33MnO3 heterostructures

Magnons can transfer information in metals and insulators without Joule heating, and therefore are promising for low-power computation. The on-chip magnonics however suffers from high losses due to limited magnon decay length. In metallic thin films, it is typically on the tens of micrometre length scale. Here, we demonstrate an ultra-long magnon decay length of up to one millimetre in multiferroic/ferromagnetic BiFeO3(BFO)/La0.67Sr0.33MnO3(LSMO) heterostructures at room temperature. This decay length is attributed to a magnon-phonon hybridization and is more than two orders of magnitude longer than that of bare metallic LSMO. The long-distance modes have high group velocities of 2.5 km s−1 as detected by time-resolved Brillouin light scattering. Numerical simulations suggest that magnetoelastic coupling via the BFO/LSMO interface hybridizes phonons in BFO with magnons in LSMO to form magnon-polarons. Our results provide a solution to the long-standing issue on magnon decay lengths in metallic magnets and advance the bourgeoning field of hybrid magnonics.

Abstract 10906: Association of Serum Magnesium Level on Emergency Department Arrival and Favorable Neurologic Outcome After Out-of-Hospital Cardiac Arrest

Introduction: Electrolyte disturbances are associated with sudden cardiac arrest based on several cohort studies. However little is known about the association between serum magnesium(S-Mg) level at ED arrival and survival of out-of-hospital cardiac arrest (OHCA) patients. Hypothesis: We hypothesized S-Mg level at ED arrival is associated with favorable neurologic outcome of OHCA patients. Methods: This is an observational study using Korean Cardiac Arrest Research Consortium (KoCARC) data from October 2015 to June 2020. EMS treated OHCA patients over 18 years old who survived to ICU admission were included. Those without S-Mg level were excluded. Exposure is S-Mg level at emergency department (ED) arrival and outcome was favorable neurologic outcome (cerebral performance category 1 or 2) at hospital discharge. S-Mg was categorized into three groups; Low group; 0-1.7mg/dl, Normal group;1.7-2.3mg/dl, High group; over 2.3mg/dl). Multivariable logistic regression was performed to calculate adjusted odds ratios (AORs) with 95% confidence intervals (95% CIs) for outcome. Results: From total 10,897 OHCA patients, 2,789 patients survived to ICU admission and 1,370 patients had initial S-Mg result. Favorable neurologic outcome was 27.4% in low group, 55.7% in normal group and 23.0% in high group. After adjusting potential confounders in multivariable logistic analysis, compared to the normal group, AOR was 0.28 (95% CI 0.11-0.75) at low group and 0.43 (95% CI 0.23-0.82) at high group. Conclusion: Low (S-Mg less than 1.7 mg/dl) or high (S-Mg over 2.3mg/dl) S-Mg level measured initially at ED arrival for OHCA patients was associated with worse neurologic outcome compared to normal S-Mg level (S-Mg 1.7-2.3mg/dl). Based on this study, further study is needed to investigate the optimized S-Mg level for OHCA patient under resuscitation.

Clinicoprognostic and Histopathological Features of Guttate and Plaque Psoriasis Based on PD-1 Expression

Several studies have determined the correlation between programmed cell death protein-1 (PD-1) and chronic plaque psoriasis (CPP). However, limited studies have assessed the association between PD-1 expression and the clinicoprognostic and distinct clinicopathological characteristics of CPP and guttate psoriasis (GP). Twenty-nine patients with skin biopsy-confirmed CPP were recruited at the Asan Medical Center between January 2018 and June 2020, and 33 patients with biopsy-confirmed GP were enrolled between January 2002 and June 2020. The clinicoprognostic and histopathological characteristics were analyzed according to immunohistochemical PD-1 expression in the epidermal or dermal inflammatory infiltrates. The CPP and GP lesions were divided into PD-1-low and PD-1-high groups. The CPP epidermal PD-1-high group had typical histopathological changes and significantly higher psoriasis area and severity index scores (p = 0.014) and disease duration (p = 0.009) than the epidermal PD-1-low group. In patients with GP, compared with the dermal PD-1-high group, the dermal PD-1-low group exhibited significantly higher disease duration (p = 0.002) and relapse rate of plaque psoriasis (p = 0.005) and significantly lower relapse-free survival (p = 0.016). Upregulated epidermal PD-1 expression was correlated with the chronicity and severity of CPP, while downregulated dermal PD-1 expression was correlated with poor prognosis of GP.