A multiview deep learning-based prediction pipeline augmented with confident learning can improve performance in determining knee arthroplasty candidates.

PURPOSE: Preoperative prudent patient selection plays a crucial role in knee osteoarthritis management but faces challenges in appropriate referrals such as total knee arthroplasty (TKA), unicompartmental knee arthroplasty (UKA) and nonoperative intervention. Deep learning (DL) techniques can build prediction models for treatment decision-making. The aim is to develop and evaluate a knee arthroplasty prediction pipeline using three-view X-rays to determine the suitable candidates for TKA, UKA or are not arthroplasty candidates. METHODS: A study was conducted using three-view (anterior-posterior, lateral and patellar) X-rays and surgical data of patients undergoing TKA, UKA or nonarthroplasty interventions from sites A and B. Data from site A were used to derive and validate models. Data from site B were used as external test set. A DL pipeline combining YOLOv3 and ResNet-18 with confident learning (CL) was developed. Multiview Convolutional Neural Network, EfficientNet-b4, ResNet-101 and the proposed model without CL were also trained and tested. The models were evaluated using metrics such as area under the receiver operating characteristic curve (AUC), accuracy, precision, specificity, sensitivity and F1 score. RESULTS: The data set comprised a total of 1779 knees. Of which 1645 knees were from site A as a derivation set and an internal validation cohort. The external validation cohort consisted of 134 knees. The internal validation cohort demonstrated superior performance for the proposed model augmented with CL, achieving an AUC of 0.94 and an accuracy of 85.9%. External validation further confirmed the model's generalisation, with an AUC of 0.93 and an accuracy of 82.1%. Comparative analysis with other neural network models showed the proposed model's superiority. CONCLUSIONS: The proposed DL pipeline, integrating YOLOv3, ResNet-18 and CL, provides accurate predictions for knee arthroplasty candidates based on three-view X-rays. This prediction model could be useful in performing decision making for the type of arthroplasty procedure in an automated fashion. LEVEL OF EVIDENCE: Level III, diagnostic study.

Pan-cancer analysis of ARFs family and ARF5 promoted the progression of hepatocellular carcinoma.

Background: ARF family proteins are a kind of small GTPases, which are involved in regulating a variety of basic functions of cells. In recent years, the role and molecular regulatory mechanisms of ARFs in tumor progression have received increasing attention, and research reports on most of their family members are increasing. However, research on the clinical and pathological relevance of ARF5 in cancer, especially in hepatocellular carcinoma, still needs to be improved. Methods: RNA-seq data in the Cancer Genome Atlas (TCGA) and genome tissue expression (GTEx) databases were used to analyze the expression and pathological data of ARFs family in Pan-cancer. Kaplan-Meier and Cox regression were used for prognostic analysis of ARF5 and Pan-cancer. Combined with ImmuCellAI database and TIMER2 database, the relationship between ARF5 expression and immune cell tumor infiltration in hepatocellular carcinoma (HCC) was analyzed. WGCNA is used to construct the co-expression gene network related to ARF5 expression in HCC and screen important modules and central genes. GO and KEGG path enrichment analysis were carried out for the genes in the modules with clinical significance. GSEA analysis was performed to take into account the role of genes with small differences. Finally, ceRNA network analysis was used to explore the molecular mechanism of miRNAs and lncRNAs regulating ARF5 expression. Results: ARFs family (ARF1, ARF3, ARF4, ARF5, ARF6) are generally highly expressed in Pan-cancer. ARF5 is significantly highly expressed in 29 cancers, and the high expression of ARF5 in HCC patients is significantly negatively correlated with OS, DFI, PFI and DSS, which may lead to cancer deterioration by participating in tumor immune infiltration of HCC. Through WGCNA analysis, the expression of ARF5 in HCC may be involved in many cellular processes that consume a lot of energy, such as ribosome formation, RNA and protein synthesis and lipids, as well as COVID-19, nonalcoholic fatty liver, neurodegenerative diseases and other disease pathways. Conclusion: ARFs, especially ARF5, are overexpressed in many human tumors. This study shows for the first time that ARF5 is significantly correlated with the poor prognosis of HCC patients, which may play a role as an oncogene, suggesting that ARF5 has the potential as a biomarker for the diagnosis and treatment of HCC.

Sugar-coated bullets: Unveiling the enigmatic mystery 'sweet arsenal' in osteoarthritis.

Glycosylation is a crucial post-translational modification process where sugar molecules (glycans) are covalently linked to proteins, lipids, or other biomolecules. In this highly regulated and complex process, a series of enzymes are involved in adding, modifying, or removing sugar residues. This process plays a pivotal role in various biological functions, influencing the structure, stability, and functionality of the modified molecules. Glycosylation is essential in numerous biological processes, including cell adhesion, signal transduction, immune response, and biomolecular recognition. Dysregulation of glycosylation is associated with various diseases. Glycation, a post-translational modification characterized by the non-enzymatic attachment of sugar molecules to proteins, has also emerged as a crucial factor in various diseases. This review comprehensively explores the multifaceted role of glycation in disease pathogenesis, with a specific focus on its implications in osteoarthritis (OA). Glycosylation and glycation alterations wield a profound influence on OA pathogenesis, intertwining with disease onset and progression. Diverse studies underscore the multifaceted role of aberrant glycosylation in OA, particularly emphasizing its intricate relationship with joint tissue degradation and inflammatory cascades. Distinct glycosylation patterns, including N-glycans and O-glycans, showcase correlations with inflammatory cytokines, matrix metalloproteinases, and cellular senescence pathways, amplifying the degenerative processes within cartilage. Furthermore, the impact of advanced glycation end-products (AGEs) formation in OA pathophysiology unveils critical insights into glycosylation-driven chondrocyte behavior and extracellular matrix remodeling. These findings illuminate potential therapeutic targets and diagnostic markers, signaling a promising avenue for targeted interventions in OA management. In this comprehensive review, we aim to thoroughly examine the significant impact of glycosylation or AGEs in OA and explore its varied effects on other related conditions, such as liver-related diseases, immune system disorders, and cancers, among others. By emphasizing glycosylation's role beyond OA and its implications in other diseases, we uncover insights that extend beyond the immediate focus on OA, potentially revealing novel perspectives for diagnosing and treating OA.

The causal relationship between psoriasis and artificial joint re-operation after arthroplasty: A two-sample Mendelian randomization study.

BACKGROUND: Psoriasis is observationally associated with a higher risk of complications of arthroplasty; however, the causal effects of psoriasis on complications of arthroplasty are yet to be established. This study was to explore the causal effect of psoriasis on artificial joint re-operation after arthroplasty through two-sample Mendelian randomization (MR). METHODS: In the MR analysis, psoriasis was selected as the exposure in this study while single-nucleotide polymorphisms (SNPs) from a genome-wide association study (GWAS) were selected as the instrumental variables (IVs). Summary statistics data on artificial joint re-operation was extracted from publicly available GWAS data, including 218 792 European descent individuals. MR analysis was performed using the standard inverse variance weighted method (IVW). Furthermore, MR Egger, weighted median, simple mode, weighted mode, and the MR-PRESSO (Mendelian Randomization Pleiotropy Residual Sum and Outlier) test were also done to verify the results. Finally, the sensitivity analysis was executed. RESULTS: The IVW showed that psoriasis increases the risk of artificial joint re-operation (OR = 1.12; 95% CI = (1.01, 1.25); p = 0.036). This outcome was also verified by other methods including weighted median (OR = 1.16; 95% CI = (1.03, 1.31); p = 0.015), MR Egger (OR = 1.22; 95% CI = (1.03, 1.44); p = 0.038), and weighted mode (OR = 1.16; 95% CI = (1.03, 1.30); p = 0.025). No heterogeneity and directional pleiotropy were observed upon sensitivity analysis. CONCLUSION: The present study showed that psoriasis has a potential causal effect on artificial joint re-operation after arthroplasty. Further studies are warranted to elucidate the underlying mechanisms of causal associations between psoriasis on re-operation.

A double-edged sword: DLG5 in diseases.

Discs large homolog 5 (DLG5), a key member of the membrane-associated guanylate kinase (MAGUKs) family, is a scaffold molecule for signal transduction complexes and is responsible for assembling receptors and adapters. This scaffold protein stabilizes adhesion and tight bonding complexes in many organs and tissues, and is involved of maintaining epithelial polarity. Although DLG5 plays a role in normal development in mice, it has also been linked to the onset and development of several diseases, particularly Crohn's disease and various malignancies. DLG5 has been shown to impact the progression of cancer through direct or indirect interactions with H-catenin, E-cadherin, Vimentin, p53, P21, Cyclin D1, TGF-ß1, AKT, Hippo, and classic G protein signaling pathways. DLG5 and DLG5 variants has been found to have a dual role in human diseases. Although it is overexpressed in pancreatic adenocarcinoma, its expression is reduced in lung, liver, breast, prostate, and bladder cancers. However, two independent studies on glioblastoma (GBM) have shown the opposite effects of DLG5. Our study evaluates the existing literature on the role of DLG5 and DLG5 variants in disease processes, and summarizes the available data on the role of DLG5 in disease based on cell experiments, clinical samples, and animal models, while highlighting its future potential in disease treatment.

Femoral Nerve Block and Local Instillation Analgesia Associated With More Reliable Efficacy in Regional Anesthesia Interventions Within 24 Hours Following Anterior Cruciate Ligament Reconstruction: A Network Meta-analysis.

PURPOSE: To assess the relative effectiveness of different regional anesthetic techniques (peripheral nerve blocks, local instillation analgesia, including intra-articular, subcutaneous, and periarticular infiltration) in patients undergoing anterior cruciate ligament reconstruction (ACLR). METHODS: PubMed, Embase, Cochrane Library, and Web of Science databases were searched from their inception to December 31, 2020. The search was supplemented by manual review of relevant reference lists. Randomized controlled trials of participants after ACLR that compared regional anesthesia interventions were selected. The 2 coprimary outcomes were (1) rest pain scores and (2) cumulative oral morphine equivalent consumption on day 1 (24 hours) post-ACLR. Data were pooled using a Bayesian framework. RESULTS: Of 759 records identified, 46 trials were eligible, evaluating 9 interventions in 3,171 patients. Local instillation analgesia (LIA), including intra-articular, subcutaneous, and periarticular infiltration, had significant improvement in pain relief as compared with placebo (-0.91; 95% CrI -1.45 to -0.37). Femoral nerve block (FNB) also showed significant effects in relieving pain as compared with placebo (-0.70; 95% 95% credible interval [CrI] -1.28 to -0.12). Compared with placebo, a significant reduction in opioid consumption was found in LIA (mean difference -13.29 mg; 95% CrI -21.77 to -4.91) and FNB (mean difference -13.97 mg; 95% CrI -24.71 to -3.04). Femoral and sciatic nerve block showed the greatest ranking for pain relief and opioid consumption without significant evidence (P > .05) to support superiority in comparison with placebo, respectively. CONCLUSIONS: Our meta-analysis shows that FNB and LIA can significantly diminish postoperative pain and reduce opioid consumption following ACLR compared with placebo in the setting of regional anesthesia, and femoral and sciatic nerve block may be the number 1 top-ranked analgesic technique despite high uncertainty. LEVEL OF EVIDENCE: I, Systematic review of Level I studies.

Bioinformatics analysis of prognostic value and immunological role of MeCP2 in pan-cancer.

Methyl-CpG-binding protein 2(MeCP2) is an important epigenetic regulatory factor that promotes many tumor developments, such as liver cancer, breast cancer, and colorectal cancer. So far, no pan-cancer analysis has been reported. Therefore, this study aims to explore pan-cancer's prognostic value, immune infiltration pattern, and biological function. We used bioinformatics methods to analyze the expression and prognostic significance of MeCP2, and the relationship between MeCP2 and clinicopathological parameters, genetic variation, methylation, phosphorylation, immune cell infiltration, and biological function in pan-cancer from using a public database. The results showed that expression of MeCP2 was up-regulated in 8 cancers and down-regulated in 2 cancers, which was remarkably correlated with the prognosis, pathological stage, grade and subtype of cancers. The promoter methylation level of MeCP2 DNA was decreased in bladder urothelial carcinoma (BLCA), breast invasive carcinoma (BRCA), liver hepatocellular carcinoma (LIHC), prostate adenocarcinoma (PRAD), uterine corpus endometrial carcinoma (UCEC), testicular germ cell tumors (TGCT), and stomach adenocarcinoma (STAD);decreased phosphorylation of S25, S90, S92, S241, S286, S325 and S435 was found in MeCP2, such as UCEC, lung adenocarcinoma (LUAD), ovarian serous cystadenocarcinoma (OV), colon adenocarcinoma (COAD), and kidney renal clear cell carcinoma (KIRC). Furthermore, MeCP2 expression was significantly associated with multiple immunomodulators and immune cell infiltration levels across most tumors. Therefore, our pan-cancer explored the prognostic markers and immunotherapeutic value of MeCP2 in different cancers.

Significance of HOXD transcription factors family in progression, migration and angiogenesis of cancer.

The transcription factors (TFs) of the HOX family play significant roles during early embryonic development and cellular processes. They also play a key role in tumorigenesis as tumor oncogenes or suppressors. Furthermore, TFs of the HOXD geFIne cluster affect proliferation, migration, and invasion of tumors. Consequently, dysregulated activity of HOXD TFs has been linked to clinicopathological characteristics of cancer. HOXD TFs are regulated by non-coding RNAs and methylation of DNA on promoter and enhancer regions. In addition, HOXD genes modulate the biological function of cancer cells via the MEK and AKT signaling pathways, thus, making HOXD TFs, a suitable molecular marker for cancer prognosis and therapy. In this review, we summarized the roles of HOXD TFs in different cancers and highlighted its potential as a diagnostic and therapeutic target.

Clinical Outcomes of Arthroscopic Tenodesis Versus Tenotomy for Long Head of the Biceps Tendon Lesions: A Systematic Review and Meta-analysis of Randomized Clinical Trials and Cohort Studies.

BACKGROUND: Controversy exists concerning whether tenotomy or tenodesis is the optimal surgical treatment option for proximal biceps tendon lesions. PURPOSE: To evaluate the clinical outcomes after arthroscopic tenodesis and tenotomy in the treatment of long head of the biceps tendon (LHBT) lesions. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: A systematic review was performed by searching PubMed, the Cochrane Library, Web of Science, and Embase to identify randomized controlled trials (RCTs) and cohort studies that compared the clinical efficacy of tenotomy with that of tenodesis for LHBT lesions. A standardized data extraction form was predesigned to obtain bibliographic information of the study as well as patient, intervention, comparison, and outcome data. A random-effects model was used to pool quantitative data from the primary outcomes. RESULTS: A total of 21 eligible studies were separated into 3 methodological groups: (1) 4 RCTs with level 1 evidence, (2) 3 RCTs and 4 prospective cohort studies with level 2 evidence, and (3) 10 retrospective cohort studies with level 3 to 4 evidence. Analysis of the 3 groups demonstrated a significantly higher risk of the Popeye sign after tenotomy versus tenodesis (group 1: risk ratio [RR], 3.29 [95% CI, 1.92-5.49]; group 2: RR, 2.35 [95% CI, 1.43-3.85]; and group 3: RR, 2.57 [95% CI, 1.33-4.98]). Arm cramping pain remained significantly higher after tenotomy only in the retrospective cohort group (RR, 2.17 [95% CI, 1.20-3.95]). The Constant score for tenotomy was significantly worse than that for tenodesis in the prospective cohort group (standardized mean difference [SMD], -0.47 [95% CI, -0.73 to -0.21]), as were the forearm supination strength index (SMD, -0.75 [95% CI, -1.28 to -0.21]) and the Simple Shoulder Test (SST) score (SMD, -0.60 [95% CI, -0.94 to -0.27]). CONCLUSION: The results demonstrated that compared with tenodesis, tenotomy had a higher risk of a Popeye deformity in all 3 study groups; worse functional outcomes in terms of the Constant score, forearm supination strength index, and SST score according to prospective cohort studies; and a higher incidence of arm cramping pain according to retrospective cohort studies.