High Score Group Research Articles

Integrating bioinformatics and experimental validation to unveil disulfidptosis-related lncRNAs as prognostic biomarker and therapeutic target in hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC) stands as a prevalent malignancy globally, characterized by significant morbidity and mortality. Despite continuous advancements in the treatment of HCC, the prognosis of patients with this cancer remains unsatisfactory. This study aims at constructing a disulfidoptosis‑related long noncoding RNA (lncRNA) signature to probe the prognosis and personalized treatment of patients with HCC.MethodsThe data of patients with HCC were extracted from The Cancer Genome Atlas (TCGA) databases. Univariate, multivariate, and least absolute selection operator Cox regression analyses were performed to build a disulfidptosis-related lncRNAs (DRLs) signature. Kaplan–Meier plots were used to evaluate the prognosis of the patients with HCC. Functional enrichment analysis was used to identify key DRLs-associated signaling pathways. Spearman’s rank correlation was used to elucidate the association between the DRLs signature and immune microenvironment. The function of TMCC1-AS1 in HCC was validated in two HCC cell lines (HEP3B and HEPG2).ResultsWe identified 11 prognostic DRLs from the TCGA dataset, three of which were selected to construct the prognostic signature of DRLs. We found that the survival time of low-risk patients was considerably longer than that of high-risk patients. We further observed that the composition and the function of immune cell subpopulations were significantly different between high- and low-risk groups. Additionally, we identified that sorafenib, 5-Fluorouracil, and doxorubicin displayed better responses in the low-score group than those in the high-score group, based on IC50 values. Finally, we confirmed that inhibition of TMCC1-AS1 impeded the proliferation, migration, and invasion of hepatocellular carcinoma cells.ConclusionsThe DRL signatures have been shown to be a reliable prognostic and treatment response indicator in HCC patients. TMCC1-AS1 showed potential as a novel prognostic biomarker and therapeutic target for HCC.

Identification of cuproptosis-related diagnostic biomarkers in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease with clinical and pathological heterogeneity. Recent studies have identified cuproptosis as a novel cell death mechanism. However, the role of cuproptosis-related genes in the pathogenesis of IPF is still unclear. Two IPF datasets of the Gene Expression Omnibus database were studied. Mann-Whitney U test, correlation analysis, functional enrichment analyses, single-sample gene set enrichment analysis, CIBERSORT, unsupervised clustering, weighted gene co-expression network analysis, and receiver operating characteristic curve analysis were used to conduct our research. The dysregulated cuproptosis-related genes and immune responses were identified between IPF patients and controls. Two cuproptosis-related molecular clusters were established in IPF, the high immune score group (C1) and the low immune score group (C2). Significant heterogeneity in immunity between clusters was revealed by functional analyses results. The module genes with the strongest correlation to the 2 clusters were identified by weighted gene co-expression network analysis results. Seven hub genes were found using the Cytoscape software. Ultimately, 2 validated diagnostic biomarkers of IPF, CDKN2A and NEDD4, were obtained. Subsequently, the results were validated in GSE47460. Our investigation illustrates that CDKN2A and NEDD4 may be valid biomarkers that were useful for IPF diagnosis and copper-related clustering.

Radiation-induced xerostomia and cariogenic dietary habits

PurposeDespite the availability of various prevention methods, dental caries continue to be diagnosed in patients receiving head and neck radiotherapy (RT). Since conventional approaches do not evaluate posttreatment alterations in dietary behaviors, we aimed to assess the influence of radiation-induced xerostomia on post-RT cariogenic dietary habits in patients.MethodsFifty-seven patients completed the Xerostomia Questionnaire (XQ) and answered questions regarding daily cariogenic food and beverage (CFB) intake, daily tooth brushing, fluoride application, and subjective total taste acuity (STTA). They also underwent evaluations to determine the Simplified Oral Hygiene Index (OHI-S) score, Saxon test score, number of decayed-missing-filled teeth (DMFT), and proportion of DMFT to the test teeth (DMFT rate). Clinical records were searched for information regarding RT modalities, including the median of the mean dose to the parotid glands, days after the completion of RT, submandibular gland resection, whole-neck irradiation, and the DMFT value and rate before RT. The patients were divided into low and high XQ score groups based on the median XQ score of 47.5 for the two sample tests. Univariable and multivariable regression analyses were used to identify independent factors for frequent CFB intake.ResultsHigher XQ scores were associated with a significantly greater frequency of CFB intake (p = 0.028*). Regression analysis also identified a higher XQ score (p = 0.017*) as an independent risk factor for frequent CFB intake.ConclusionRadiation-induced xerostomia increased the frequency of CFB intake.

Is the Mayo Adhesive Probability Score Predictive in Patients Undergoing Percutaneous Nephrolithotomy?

Introduction: Mayo Adhesive Probability (MAP) score was developed as a means to predict the presence of adherent perinephric fat. Our aim was to determine the predictive value of the MAP score on surgical outcomes in patients undergoing standard adult percutaneous nephrolithotomy (PCNL). Materials and Methods: We retrospectively analyzed the data from 130 renal units that underwent PCNL between January 2022 and 2023. MAP scores 0-2 were classified as low, whereas MAP scores 3-5 were classified as high. The impact of the MAP score on perioperative and postoperative outcomes was studied. All statistical analyses were performed using SPSS 24.0 for Windows. Results: The median age of the patients at the time of surgery was 48 (21) years, with a female-to-male ratio of 1:1.82. The median MAP score was 2 (2), with 43.8% of patients falling into the high MAP score group. Advanced age, hypertension history, low estimated glomerular filtration rate (eGFR) levels, and low renal parenchymal thickness were significantly higher in the high MAP score group (P = .010, P = .004, P = .001, and P = .005, respectively). Female patients had a significantly higher MAP score of 0 (P = .021). Operation time, postoperative hematocrit decrease, blood transfusion rate, postoperative fever rate, hospitalization, and stone-free rates were comparable between the low and high MAP score groups (P = .535, P = .209, P = .313, P = .289, P = .281, and P = .264, respectively). Gender and eGFR levels were shown to be significant predictors of a MAP ≥3 (P = .004 and P = .003, respectively). Conclusion: The present study showed that the MAP score groups had similar perioperative and postoperative results. Low eGFR levels and the male gender were associated with MAP score ≥3. To determine the predictive MAP score value for PCNL outcomes, more prospective studies are needed.

RACGAP1 promotes the progression and poor prognosis of lung adenocarcinoma through its effects on the cell cycle and tumor stemness.

Investigating the key genes and mechanisms that influence stemness in lung adenocarcinoma. First, consistent clustering analysis was performed on lung adenocarcinoma patients using stemness scoring to classify them. Subsequently, WGCNA was utilized to identify key modules and hub genes. Then, machine learning methods were employed to screen and identify the key genes within these modules. Lastly, functional analysis of the key genes was conducted through cell scratch assays, colony formation assays, transwell migration assays, flow cytometry cell cycle analysis, and xenograft tumor models. First, two groups of patients with different stemness scores were obtained, where the high stemness score group exhibited poor prognosis and immunotherapy efficacy. Next, LASSO regression analysis and random forest regression were employed to identify genes (PBK, RACGAP1) associated with high stemness scores. RACGAP1 was significantly upregulated in the high stemness score group of lung adenocarcinoma and closely correlated with clinical pathological features, poor overall survival (OS), recurrence-free survival (RFS), and unfavorable prognosis in lung adenocarcinoma patients. Knockdown of RACGAP1 suppressed the migration, proliferation, and tumor growth of cancer cells. RACGAP1 not only indicates poor prognosis and limited immunotherapy benefits but also serves as a potential targeted biomarker influencing tumor stemness.

To Develop Biomarkers for Diabetic Nephropathy Based on Genes Related to Fibrosis and Propionate Metabolism and Their Functional Validation.

Propionate metabolism is important in the development of diabetes, and fibrosis plays an important role in diabetic nephropathy (DN). However, there are no studies on biomarkers related to fibrosis and propionate metabolism in DN. Hence, the current research is aimed at evaluating biomarkers associated with fibrosis and propionate metabolism and to explore their effect on DN progression. The GSE96804 (DN : control = 41 : 20) and GSE104948 (DN : control = 7 : 18) DN-related datasets and 924 propionate metabolism-related genes (PMRGs) and 656 fibrosis-related genes (FRGs) were acquired from the public database. First, DN differentially expressed genes (DN-DEGs) between the DN and control samples were sifted out via differential expression analysis. The PMRG scores of the DN samples were calculated based on PMRGs. The samples were divided into the high and low PMRG score groups according to the median scores. The PM-DEGs between the two groups were screened out. Second, the intersection of DN-DEGs, PM-DEGs, and FRGs was taken to yield intersected genes. Random forest (RF) and recursive feature elimination (RFE) analyses of the intersected genes were performed to sift out biomarkers. Then, single gene set enrichment analysis was conducted. Finally, immunoinfiltrative analysis was performed, and the transcription factor (TF)-microRNA (miRNA)-mRNA regulatory network and the drug-gene interaction network were constructed. There were 2633 DN-DEGs between the DN and control samples and 515 PM-DEGs between the high and low PMRG score groups. In total, 10 intersected genes were gained after taking the intersection of DN-DEGs, PM-DEGs, and FRGs. Seven biomarkers, namely, SLC37A4, ACOX2, GPD1, angiotensin-converting enzyme 2 (ACE2), SLC9A3, AGT, and PLG, were acquired via RF and RFE analyses, and they were found to be involved in various mechanisms such as glomerulus development, fatty acid metabolism, and peroxisome. The seven biomarkers were positively correlated with neutrophils. Moreover, 8 TFs, 60 miRNAs, and 7 mRNAs formed the TF-miRNA-mRNA regulatory network, including USF1-hsa-mir-1296-5p-AGT and HIF1A-hsa-mir-449a-5p-ACE2. The drug-gene network contained UROKINASE-PLG, ATENOLOL-AGT, and other interaction relationship pairs. Via bioinformatic analyses, the risk of fibrosis and propionate metabolism-related biomarkers in DN were explored, thereby providing novel ideas for research related to DN diagnosis and treatment.

Establishment of a tumor-associated fibroblast associated gene score based on scRNA-seq to predict prognosis in patients with triple-negative breast cancer.

The tumor microenvironment (TME) is emerging as a tool for the development of improved patient prognosis and the development of novel antitumor drugs. As the most important stromal cells in the tumor microenvironment, cancer-associated fibroblasts (CAFs) play an important role in the development of TNBC. The rise of single-cell sequencing technology has facilitated our study of the various cell types in TME. In this study, we interpreted the heterogeneity of TNBCs from the perspective of tumor-associated fibroblasts in the tumor microenvironment based on the TNBC single-cell sequencing dataset GSE118389, in the hope of providing help for individualised treatment. Combining the TCGA database and the GSE103091 dataset, four genes associated with CAFs in TNBC (CERCAM, KLF10, ECM1,HGF) were identified using the R package Seurat as well as correlation consensus clustering analysis. Meanwhile, qRT-PCR, WB and IHC experiments confirmed their expression in TNBC. Based on these genes, CAFs Score was established and validated to correlate with the prognosis of patients with TNBC, with patients in the high score group surviving significantly worse than those in the low score group (P<0.001). In addition, there were significant differences in immune cell infiltration and expression of immune checkpoints between the high and low scoring groups. Compared to Stage I & II, the CAFs Score was higher in Stage III & IV TNBC patients (P = 0.043) and higher in N1-3 TNBC patients than in N0 TNBC patients (P = 0.035). EMT scores were higher within the high CAFs Score group (P = 1.4e-11) and there was a positive correlation between Stemness Score and CAFs Score (R = 0.61, P = 3.6e-09). Drug sensitivity analysis combining the GSE128099 showed a higher sensitivity to Gemcitabine in the low CAFs Score group (P = 0.0048). We speculate that these four CAFs-related genes are likely to be involved in regulating gemcitabine resistance in TNBC patients.

High-resolution transcriptomics analysis of CXCL13+ EPSTI1+ CDK1+ cells with a specific focus on lung adenocarcinoma.

Programmed cell death ligand 1 (PD-L1) blocking therapy has transformed the treatment of lung adenocarcinoma (LUAD), which has significantly changed the landscape of immunotherapy. We aimed to explore specific cell subpopulations to understand tumor progression and identify markers of response to PD-L1 blocking therapy. Bulk, fluorescence-activated cell sorting (FACS), and single-cell RNA (scRNA) sequencing were used to profile CXCL13, EPSTI1, and CDK1. The gene set variation analysis (GSVA) R package was utilized for score calculation, and prognostic analyses included receiver operating characteristic (ROC) curves, Cox proportional hazard models, and meta-analysis. Additionally, we analyzed tumor microenvironment (TME), genomics, compound perturbations, and clinical indicators. The high-dimensional analysis captured the intrinsic characteristics of the subpopulation. Furthermore, subpopulation differential genes were used for enrichment analysis of transcription factors and compounds. Literature and website analyses supported the essential role of CXCL13, CDK1, and EPSTI1 in immunotherapy. This led us to focus specifically on LUAD by representing a pan-cancer profile of immune-sensitive genes. Logically, the high-characteristic population may consist of samples positive for CXCL13, EPSTI1, and CDK1. The three-gene signature was a favorable indicator of immunotherapy response in the Stand Up to Cancer-Mark Foundation (SU2C-MARK) LUAD cohort but showed a poor prognosis before treatment in the Lung Cancer Explorer (LCE) database. Further mechanistic exploration revealed specific mutations associated with the three-gene signature in SU2C-MARK LUAD, such as STK11. In The Cancer Genome Atlas (TCGA)-LUAD cohort, the high-scoring group exhibited a higher tumor mutational burden (TMB) and global methylation but a lower fraction genome altered (FGA) and estimated tumor purity. Moreover, dasatinib demonstrated sensitivity in the high-scoring group. The co-localization of the CXCL13, EPSTI1, and CDK1 subpopulation was validated through spatial transcriptome and immunohistochemical databases. Assessment of the subpopulation depicted high-resolution intercellular communication. Maintenance of specific pathways, such as TNF, CD74, and CD44, contributed to immunotherapy sensitivity. Finally, the subpopulation-enriched targets and drugs were confirmed through ConnectivityMap (CMAP) analysis and multi-omics, respectively. In this study, positive samples for CXCL13, EPSTI1, and CDK1 exhibited poor prognostic significance in treatment-naïve LUAD cases but demonstrated benefits from PD-L1 blockade and dasatinib therapies.

Comparison of Trifecta and Pentafecta Outcomes across 3 Surgical Modalities of Partial Nephrectomy (PN) - Open, Lap, and Robotic.

Renal cell carcinoma (RCC) is the most common solid tumor in the kidney (90%), accounting for about 3% of all cancers in adults. Partial nephrectomy (PN) is the surgical procedure primarily used for the treatment of localized kidney tumors. Two commonly used terms to describe the complexity and success of a partial nephrectomy procedure are "trifecta" and "pentafecta." Trifecta is defined as Warm ischemia time (WIT) ≤ 25min or Cold ischemia time (CIT) ≤ 60min, Negative surgical margin (NSM), and no perioperative Clavien-Dindo complications (CDC) of Gr 3 or more [8], whereas pentafecta is defined as trifecta plus >90% preservation of e-Glomerular filtration rate (GFR) and no increase in chronic kidney disease (CKD) stage at 12-months post-operative period. We retrospectively analyzed all patients who underwent partial nephrectomy at a single high-volume tertiary centre, from 2012 to 2020. We included patients who underwent partial nephrectomy by any of the three routes including open (OPN), laparoscopic (LPN), or robotic-assisted (RPN), and in which the follow-up data was available. We compared the trifecta and pentafecta outcomes across the three surgical modalities. We had a total of 183 patients in our study. Twenty-nine percent (53 patients) underwent open surgery, 12.6% (23 patients) underwent laparoscopic surgery and 58.5% (107) underwent robotic assisted surgery. The number of patients who fell under the low risk category in the RENAL scoring system were 70(38.3%), intermediate risk 79 (43.2%) and high risk 34 (18.6%). In the high risk RENAL score group, trifecta was achieved in 5 (50%) patients in OPN, 1(50%) in LPN and 7(31.8%) in RPN with no statistically significant difference (p = 0.581) whereas pentafecta was achieved in 3 (30%) patients in OPN, 1 (50%) in LPN and 7 (31.8%) in RPN with no statistically significant difference (0.855). In the overall cohort, mean WIT, mean hospital stay and mean EBL were higher in OPN as compared to LPN and RPN which was statistically significant (p < 0.001), whereas there was no statistical difference in mean operative time between the three modalities (p = 0.580). Renal tumors can be safely treated by RPN or LPN with lesser morbidity as compared to OPN. Trifecta and Pentafecta outcomes had no significant difference among OPN, LPN, and RPN. RPN and LPN may be considered feasible and safe surgical approaches ensuring good functional outcomes.

Anoikis in prostate cancer bone metastasis gene signatures and therapeutic implications.

Bone metastasis from prostate cancer severely impacts patient outcomes and quality of life. Anoikis, a form of programmed cell death triggered by the loss of cell-matrix interactions, plays a critical role in cancer progression. However, its precise relationship with prostate cancer-induced bone metastasis remains unclear. This study aims to elucidate this relationship, focusing on anoikis-related gene signatures, molecular pathways, and therapeutic implications. We used the TCGA-PRAD dataset for training, with MSKCC and GSE70769 as validation cohorts. To evaluate immunotherapy efficacy, we examined IMvigor 210 and GSE91016 datasets, and GSE137829 provided single-cell insights into prostate cancer. Specific anoikis-related genes (ARGs) were identified, and Random Survival Forest analysis and multivariate Cox regression were employed to develop anoikis-linked features. The 'clustanoikisProfilanoikis' and 'GSEA' packages were used to explore potential ARG-related pathways. Analyzing 553 samples from TCGA, 231 from MSKCC, 94 from GSE70769, and single-cell data from 6 prostate cancer patients (GSE137829), we constructed a prognostic model based on 9 ARGs. GSVA revealed upregulation of carcinogenic pathways, including epithelial-mesenchymal transition, E2F targets, and angiogenesis, with downregulation of metabolic pathways. Significant differences in somatic mutations were observed between cohorts, with a positive correlation between anoikis scores and tumor mutational burden (TMB). Immune landscape analysis suggested high-risk patients might benefit more from chemotherapy than immunotherapy based on their risk score. Single-cell analysis indicated overactivation of carcinogenic pathways in the high anoikis score group. This study elucidates the complex interplay between anoikis and bone metastasis in prostate cancer. Our findings highlight the critical role of anoikis in metastatic progression, enhancing the understanding of key biomarkers and molecular dynamics. The identified anoikis-related gene signatures and disrupted pathways offer promising avenues for predictive and therapeutic strategies in prostate cancer management.

Development and validation of matrix metalloproteinase for predicting prognosis and tumour microenvironment immune profiles in uterine corpus endometrial carcinoma.

Background: Matrix metalloproteinases (MMPs) are involved in many processes of tumour progression and invasion. However, few studies have analysed the effects of MMP expression patterns on endometrial cancer (EC) development from the perspective of the tumour microenvironment (TME). we quantified MMP expression in individual by constructing an MMP score and found MMP score effectively predict the prognosis of EC patients. Methods: MMPs expression profiles were determined based on the differential expression of 12 MMP-related regulators. Principal component analysis (PCA) was used to construct an MMP scoring system which can quantify the MMPs expression patterns individually of EC patients. Kaplan-Meier analysis, the log-rank test, and time-dependent receiver operating characteristic (ROC) curve analysis were used to evaluate the value of MMPs expression in predicting prognosis. Single-cell RNA sequencing (scRNA-seq) dataset was used to verify correlation between MMPs and progression of EC. Gene Ontology (GO) analysis was used to investigate the pathways and functions underlying MMPs expression. Tumour immune dysfunction, exclusion prediction, and pharmacotherapy response analyses were performed to assess the potential response to pharmacotherapy based on MMPs patterns. Results: We downloaded the MMPs expression data, somatic mutation data and corresponding clinical information of EC patients from the TCGA website and ICGC portal. Based on the MMP-related differentially expressed genes (DEGs), the MMP score was constructed, and EC patients were divided into high and low MMP score groups. There was a positive correlation between MMP score and prognosis of EC patients. Patients with high MMP scores had better prognosis, more abundant immune cell infiltration and stronger antitumoor immunity. Although prognosis is worse with the lower group than the high, patients with low MMP score had better response to immunotherapy, which means they could prolong the survival time through Immunological checkpoint blockade (ICB) therapy. scRNA-seq analysis identified significant heterogeneity between MMP score and classical pathways in EC. Conclusion: Our work indicates that the MMP score could be a potential tool to evaluate MMP expression patterns, immune cell infiltration, response to pharmacotherapy, clinicopathological features, and survival outcomes in EC. This will provide the more effective guide to select immunotherapeutic strategies of EC in the future.

Risk factors for the need for advanced care among prescription and over-the-counter drug overdose patients.

Prescription drug and over-the-counter (OTC) drug overdose is a major problem in emergency departments in Japan, and some need advanced care which is more than observation. We aimed to identify the prehospital risk factors for the need of advanced care among overdose patients. This was a single-center retrospective cohort study. We included overdoses patients of prescription drugs or OTC drugs, who admitted to our hospital between 2016 and 2021. We grouped them into advanced care and non-advanced care. The main outcome was the need for advanced care. We performed a multiple logistic regression analysis, calculated the PAV score (Paracetamol use, Alcohol use, abnormal Vital signs on scene) and performed a receiver operating characteristic (ROC) analysis. There were 229 subjects. The logistic regression analysis revealed that alcohol, paracetamol, and the abnormal vital signs on scene were associated with advanced care (alcohol-odds ratio [OR]: 2.95; 95% confidence interval [CI]: 1.29-6.75; paracetamol-OR: 5.47; 95% CI: 2.18-13.71; abnormal vital signs-OR: 4.61, 95% CI: 2.07-10.27). The rate of advanced care in the high PAV score (2 and 3) group was statistically higher than that in the low PAV score (0-1) group (p = 0.04). Area under the ROC curve of the PAV score was 0.72 (95% CI, 0.65-0.80). Alcohol, paracetamol use and abnormal vital signs on scene might be risk factors for advanced care among prescription drugs or OTC drugs overdose patients, and the PAV score may predict the need for advanced care.

A Predictive Model for Cancer-Associated Thrombosis in Japanese Cancer Patients: Findings from the J-Khorana Registry.

Background Although the close relationship between cancer and venous thromboembolism (VTE) has been identified, risk stratification for VTE in Japanese patients with cancer remains unclear. Objectives This study aimed to validate the Khorana VTE risk assessment score (KRS) for VTE diagnosis and establish an optimal predictive model for VTE in Japanese patients with cancer. Methods A total of 7,955 Japanese patients with cancer were subdivided into low- (0), intermediate- (1-2), and high-score (3) groups according to the KRS. Using 37 explanatory variables, a total of 2,833 patients with cancer were divided into derivation and validation cohorts (5:5). A risk model for Japanese participants was developed using the derivation cohort data. Results The prevalence of VTE in low-, intermediate-, and high-score patients was 1.2, 2.5, and 4.3%, respectively. Logistic regression analysis demonstrated that cancer stage (III-IV) and KRS ≥ 2 were independent and significant predictors of VTE onset. The risk model for VTE assigned 1 point to body mass index ≥25 kg/m 2 and 2 points each to the prevalence of osteochondral cancer and D-dimer level ≥1.47 µg/mL. The areas under the curve of the risk model were 0.763 and 0.656 in the derivation and validation cohorts, respectively. Conclusion The KRS was useful in Japanese patients, and our new predictive model may be helpful for the diagnosis of VTE in Japanese patients with cancer.

Role of Perfusion, Extent, Depth, Infection and Sensation Scores in Determining the Outcome of Patients with Diabetic Foot Ulcers: A Prospective Cohort Study

Introduction: Diabetes mellitus is a major public health problem in India. A Diabetic Foot Ulcer (DFU) is characterised by a full-thickness wound, skin necrosis, or gangrene below the ankle brought on by peripheral neuropathy or peripheral artery disease in diabetic patients. Numerous classification schemes have been put forth to classify and forecast the clinical outcomes of DFUs. The Perfusion, Extent, Depth, Infection and Sensation Score (PEDIS) classification system was developed to objectively categorise and define DFUs, facilitating communication between healthcare providers. Aim: To determine the utility of the PEDIS score in predicting the outcomes of patients with DFUs. Materials and Methods: The present single-centre prospective cohort study was conducted in the Department of General Surgery, Tezpur Medical College and Hospital, Tezpur, Assam, India, from August 1, 2022 to January 30, 2023, involving 60 patients. A PEDIS score was calculated and recorded for each patient. Patients were then classified into low-score (0-7) or high-score (8-12) groups and followed up for six months. Outcomes were categorised as healed, unhealed, amputated, or deceased. Categorical data were presented as percentages and compared using the Chi-square test. The Receiver Operating Characteristic (ROC) curve was utilised to determine the cut-off value. A p-value &lt;0.05 was considered statistically significant. Results: The mean±Standard Deviation (SD) age at presentation was 49±14 years with a male preponderance (Male:Female= 2:1). Of all patients, 40 (66.67%) were healed following debridement and dressing, 11 (18.3%) had non healing ulcers, 5 (8.3%) underwent amputation, and 4 (6.67%) expired. Thirty-four (85%) of healed patients had PEDIS scores below eight, and 7 (63.6%) of patients with non healing ulcers had high PEDIS scores. Those undergoing amputation, 4 (80%) had high PEDIS scores and all deceased patients had high PEDIS scores. Conclusion: Patients with DFUs who had higher PEDIS scores were more likely to develop complications such as non healing ulcers or require amputation. Therefore, the PEDIS score is a valuable system in clinical practice and can be uniformly applied to compare the outcomes of DFUs.

A novel basement membrane-related gene signature predicts prognosis and immunotherapy response in hepatocellular carcinoma.

Basement membranes (BMs) have recently emerged as significant players in cancer progression and metastasis, rendering them promising targets for potential anti-cancer therapies. Here, we aimed to develop a novel signature of basement membrane-related genes (BMRGs) for the prediction of clinical prognosis and tumor microenvironment in hepatocellular carcinoma (HCC). The differentially expressed BMRGs were subjected to univariate Cox regression analysis to identify BMRGs with prognostic significance. A six-BMRGs risk score model was constructed using Least Absolute Shrinkage Selection Operator (LASSO) Cox regression. Furthermore, a nomogram incorporating the BMRGs score and other clinicopathological features was developed for accurate prediction of survival rate in patients with HCC. A total of 121 differentially expressed BMRGs were screened from the TCGA HCC cohort. The functions of these BMRGs were significantly enriched in the extracellular matrix structure and signal transduction. The six-BMRGs risk score, comprising CD151, CTSA, MMP1, ROBO3, ADAMTS5 and MEP1A, was established for the prediction of clinical prognosis, tumor microenvironment characteristics, and immunotherapy response in HCC. Kaplan-Meier analysis revealed that the BMRGs score-high group showed a significantly shorter overall survival than BMRGs score-low group. A nomogram showed that the BMRGs score could be used as a new effective clinical predictor and can be combined with other clinical variables to improve the prognosis of patients with HCC. Furthermore, the high BMRGs score subgroup exhibited an immunosuppressive state characterized by infiltration of macrophages and T-regulatory cells, elevated tumor immune dysfunction and exclusion (TIDE) score, as well as enhanced expression of immune checkpoints including PD-1, PD-L1, CTLA4, PD-L2, HAVCR2, and TIGIT. Finally, a multi-step analysis was conducted to identify two pivotal hub genes, PKM and ITGA3, in the high-scoring group of BMRGs, which exhibited significant associations with an unfavorable prognosis in HCC. Our study suggests that the BMRGs score can serve as a robust biomarker for predicting clinical outcomes and evaluating the tumor microenvironment in patients with HCC, thereby facilitating more effective clinical implementation of immunotherapy.

EXPERIENCES OF TECHNOLOGY USE BY OLDER ADULTS DURING COVID-19

Abstract Computer and communications technology use expanded during the COVID-19 pandemic, but little is known about how this affected older people. Using the Unified Theory of Acceptance and Use of Technology questionnaire and qualitative interviews, we examined 18 older adults’ technology use during COVID-19 across two subgroups of nine older adults each: those scoring above (“high”) and those scoring below (“low”) the median (4.09). Overall, older adults scored fairly high (mean 4.0; SD=0.5; range 3.1-4.8 across 16 items on a scale of 1 to 5). In each group of nine older adults, four (44%) described technology as being helpful during the pandemic. Among high scoring older adults, 100% utilized technology to order either groceries or household items and six (67%) used either telehealth or online health information system (i.e., MyChart) to communicate with health services providers, compared to three (33%) and four (44%) within the low scoring group. No one in the high scoring group described a degree of cognitive difficulty whereas four 44% in the low scoring group did. All but one (94%) older adults described needing some help with technology from family members, friends, and/or paid technology services. Two themes complement these findings by reflecting strengths (“lots of ways to do everything”) and challenges (“I just get through it”) of using technology. Greater technology mastery may positively influence the ability of older adults to meet their needs, but cognitive challenges may prevent full engagement with technology.

Prognostic significance of Ishii's sarcopenia screening score for patients undergoing curative surgery for obstructive colorectal cancer after intraluminal decompression.

Sarcopenia influences the short- and long-term outcomes of various medical conditions including malignancy. Ishii's screening test estimates the probability of sarcopenia based on a score calculated by three simple variables: age, grip strength, and calf circumference. We investigated the clinical significance of Ishii's score for patients with non-metastatic obstructive colorectal cancer (OCRC) who underwent curative surgery after intraluminal decompression. Ishii's score was calculated in 79 patients with OCRC. Muscle volume loss and decreased muscle quality were evaluated by computed tomography (CT) images as skeletal muscle index (SMI) and intramuscular adipose tissue content (IMAC), respectively. There were 46 men and 33 women, with a median age of 70years old. The cutoff value for Ishii's score was 155.1 and 15 patients were in the high-score group. The high-score group was significantly associated with worse time to recurrence (TTR) and overall survival (OS), and a high Ishii's score was an independent negative prognostic factor for TTR (hazard ratio = 2.93, P = 0.015). A high Ishii's score was significantly associated with a low SMI value but not with the IMAC value. A high Ishii's score was independently associated with poorer TTR in patients with non-metastatic OCRC.

Identification of prognostic value of anoikis-related gene score model combined with tumor microenvironment score models in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) has poor survival. Effective prognostic models with high application value remain lack. Bulk RNA seq and single cell RNA-seq data were retrieved from the XENA-TCGA-ESCC cohort and GSE188900. The anoikis-related gene score (ANO score) model and tumor microenvironment score (TME score) model were constructed and merged into three subgroups. Functional annotation was analyzed by Gene Ontology terms. Univariate and multivariate Cox regression analysis, least absolute shrinkage and selection operator regression analysis and weighted gene coexpression network analysis were performed to construct prognostic prediction models and identify prognostic value. Kaplan-Meier survival curves were drawn for evaluating the overall survival (OS) of patients classified by different score subgroups. Immunotherapy response and mutation analyses were also conducted. In the ANO score model, TNFSF10 was an independent factor for the prognosis of ESCC patients. The area under the curve values of the ANO-TME score model in predicting the OS were 0.638 at 5years and 0.632 at 7years. Patients in the ANO low score-TME high score group had a much longer OS than patients in any other ANO-TME score subgroup (p < 0.001), suggesting a higher prognostic value. The differentially expressed genes of the ANO low score-TME high score group were mainly involved in cell adhesion molecules, nucleotide excision repair, the TGF-β signaling pathway and mismatch repair. TP53 (92%), TTN (38%) and NFE2L2 (31%) were the top genes with highest mutant frequency in the ANO low score-TME high score group. A novel prognostic prediction model with high application value was constructed and identified for ESCC patients, which may provide evidence for immunotherapy in the treatment of ESCC.

A prognostic model based on prognosis-related ferroptosis genes for patients with acute myeloid leukemia.

Background: Acute myeloid leukemia (AML) is a heterogeneous disorder with an unpredictable prognosis. Ferroptosis, the iron-dependent cell death program, could serve as an alternative for overcoming drug resistance. However, its effect on AML remains largely unclear. Methods: We collected RNA sequencing data and relevant clinical information of AML patients from The Cancer Genome Atlas to construct a prognosis prediction model. Risk score was calculated with eight prognosis-related ferroptosis genes (PRFGs) discovered through univariate analysis and Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression. A nomogram was constructed by incorporating LASSO risk score, age, and cytogenetic risk based on univariate/multivariate Cox regression. Results: Of the 33 AML PRFGs identified from the TCGA-derived dataset, 8 genes were used to construct a gene signature to predict AML prognosis. Principal component analysis and heatmap showed significant differences between the low and high risk score groups. Next, LASSO risk score, age, and cytogenetic risk were incorporated into the nomogram to predict the overall survival (OS) of AML patients. According to survival analysis, patients with a low risk score had markedly increased OS as compared to those with a high risk score. Based on the results of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, the differences between the two risk groups showed a close relationship with immune-related pathways and membrane transportation. The analysis of tumor-infiltrating immune cells and immune checkpoints revealed that the immunosuppressive tumor microenvironment possibly facilitated different prognostic outcomes between the two groups. Gene expression analyses showed that the mRNA expression levels of PARP1 and PARP3 (PARPs) were closely related to the different clinical subgroups and the analyzed OS in AML patients. Finally, the PARP inhibitor talazoparib and the ferroptosis inducer erastin exerted a synergistic anti-proliferative effect on AML cells. Conclusion: We constructed a nomogram by incorporating PRFGs, and the constructed nomogram showed a good performance in AML patient stratification and prognosis prediction. The combination of PARP inhibitors with ferroptosis inducers could be a novel treatment strategy for treating AML patients.

Transcriptomic correlates of cell cycle checkpoints with distinct prognosis, molecular characteristics, immunological regulation, and therapeutic response in colorectal adenocarcinoma.

Colorectal adenocarcinoma (COAD), accounting for the most common subtype of colorectal cancer (CRC), is a kind of malignant digestive tumor. Some cell cycle checkpoints (CCCs) have been found to contribute to CRC progression, whereas the functional roles of a lot of CCCs, especially the integrated role of checkpoint mechanism in the cell cycle, remain unclear. The Genomic Data Commons (GDC) The Cancer Genome Atlas (TCGA) COAD cohort was retrieved as the training dataset, and GSE24551 and GSE29623 were downloaded from Gene Expression Omnibus (GEO) as the validation datasets. A total of 209 CCC-related genes were derived from the Gene Ontology Consortium and were subsequently enrolled in the univariate, multivariate, and least absolute shrinkage and selection operator (LASSO) Cox regression analyses, finally defining a CCC signature. Cell proliferation and Transwell assay analyses were utilized to evaluate the functional roles of signature-related CCCs. The underlying CCC signature, molecular characteristics, immune-related features, and therapeutic response were finally estimated. The Genomics of Drug Sensitivity in Cancer (GDSC) database was employed for the evaluation of chemotherapeutic responses. The aberrant gene expression of CCCs greatly contributed to COAD development and progression. Univariate Cox regression analysis identified 27 CCC-related genes significantly affecting the overall survival (OS) of COAD patients; subsequently, LASSO analysis determined a novel CCC signature. Noticeably, CDK5RAP2, MAD1L1, NBN, RGCC, and ZNF207 were first identified to be correlated with the prognosis of COAD, and it was proven that all of them were significantly correlated with the proliferation and invasion of HCT116 and SW480 cells. In TCGA COAD cohort, CCC signature robustly stratified COAD patients into high and low CCC score groups (median OS: 57.24 months vs. unreached, p< 0.0001), simultaneously, with the good AUC values for OS prediction at 1, 2, and 3 years were 0.74, 0.78, and 0.77. Furthermore, the prognostic capacity of the CCC signature was verified in the GSE24551 and GSE29623 datasets, and the CCC signature was independent of clinical features. Moreover, a higher CCC score always indicated worse OS, regardless of clinical features, histological subtypes, or molecular subgroups. Intriguingly, functional enrichment analysis confirmed the CCC score was markedly associated withextracellular, matrix and immune (chemokine)-related signaling, cell cycle-related signaling, and metabolisms. Impressively, a higher CCC score was positively correlated with a majority of chemokines, receptors, immunostimulators, and anticancer immunity, indicating a relatively immune-promoting microenvironment. In addition, GSE173839, GSE25066, GSE41998, and GSE194040 dataset analyses of the underlying CCC signature suggested that durvalumab with olaparib and paclitaxel, taxane-anthracycline chemotherapy, neoadjuvant cyclophosphamide/doxorubicin with ixabepilone or paclitaxel, and immunotherapeutic strategies might be suitable for COAD patients with higher CCC score. Eventually, the GDSC database analysis showed that lower CCC scores were likely to be more sensitive to 5-fluorouracil, bosutinib, gemcitabine, gefitinib, methotrexate, mitomycin C, and temozolomide, while patients with higher CCC score seemed to have a higher level of sensitivity to bortezomib and elesclomol. The novel CCC signature exhibited a good ability for prognosis prediction for COAD patients, and the CCC score was found to be highly correlated with molecular features, immune-related characteristics, and therapeutic responses, which would greatly promote clinical management and precision medicine for COAD.