Cancer is a complex and heterogeneous group of diseases driven by genetic mutations and molecular changes. Identifying and characterizing cancer driver gene is crucial for understanding cancer biology and guiding precision oncology. Integrating multi-omics data can reveal the intricate molecular interactions underlying cancer progression and treatment responses. We developed a graph convolutional network (GCN) framework, DriverOmicsNet, that integrates multi-omics data using STRING protein–protein interaction networks and correlation-based weighted gene correlation network analysis (WGCNA). We applied this framework to 15 cancer types, analyzing 5555 tumor samples to predict cancer-related features such as homologous recombination deficiency, cancer stemness, immune clusters, tumor stage, and survival outcomes. DriverOmicsNet demonstrated superior predictive accuracy and model performance metrics across all target labels when compared with GCN models based on STRING network alone. Gene expression emerged as the most significant feature, reflecting the dynamic and functional state of cancer cells. The combined use of STRING PPI and WGCNA networks enhanced the identification of key driver genes and their interactions. Our study highlights the effectiveness of using GCNs to integrate multi-omics data for precision oncology. The integration of STRING PPI and WGCNA networks provides a comprehensive framework that improves predictive power and facilitates the understanding of cancer biology, paving the way for more tailored treatments.

BackgroundTwo parallel cannulated screws along with an anterior wire to construct a tension band is a popular approach in transverse patellar fractures. However, the optimal screw proximity, either deep or superficial screw placements, remains controversial. Hence, a new concept of the addition of a third screw to form a triangular configuration along with the original two parallel screws was proposed in this study. Therefore, the biomechanical effect of the additional third screw on the stability of the fractured patella was investigated with finite element (FE) simulation.MethodsAn FE knee model including the distal femur, proximal tibia, and fractured patella (type AT/OTA 34-C) was developed in this study. Four different screw configurations, including two parallel cannulated screws with superficial (5-mm proximity) and deep (10-mm proximity) placements and two parallel superficial screws plus a third deep screw, and two parallel deep screws plus a third superficial screw, with or without the anterior wire, were considered for the simulation.ResultsResults indicated that the addition of a third screw increased stability by reducing the dorsal gap opening when two parallel screws were deeply placed, particularly on the fractured patella without an anterior wire. However, the third screw was of little value when two parallel screws were superficially placed. In the existence of two deep parallel screws and the anterior wire, the third screw reduced the gap opening by 23.5% (from 1.15mm to 0.88mm) and 53.6% (from 1.21mm to 0.61mm) in knee flexion 45 degrees and full extension, respectively. Furthermore, in the absence of the anterior wire, the third screw reduced the gap opening by 73.5% (from 2mm to 0.53mm) and 72.2% (from 1.33mm to 0.37mm) in knee flexion 45 degrees and full extension, respectively.ConclusionBased on the results, a third cannulated screw superficially placed (5-mm proximity) is recommended to increase stability and maintain contact of the fractured patella, fixed with two parallel cannulated screws deeply placed (10-mm proximity), particularly when an anterior wire was not used. Furthermore, the third screw deeply placed is not recommended in a fractured patella with two parallel superficial screws.

Background: Lateral hinge fracture (LHF) is associated with nonunion and plate breakage in high tibial osteotomy (HTO). Mechanical studies investigating fixation strategies for LHFs to restore stability and avoid plate breakage are absent. This study used computer simulation to compare mechanical stabilities in HTO for different LHFs fixed with medial and bilateral locking plates. Methods: A finite element knee model was created with HTO and three types of LHF, namely T1, T2, and T3 fractures, based on the Takeuchi classification. Either medial plating or bilateral plating was used to fix the HTO with LHFs. Furthermore, the significance of the locking screw at the combi hole (D-hole) of the medial TomoFix plate was evaluated. Results: The osteotomy gap shortening distance increased from 0.53 to 0.76, 0.79, and 0.72 mm after T1, T2, and T3 LHFs, respectively, with medial plating only. Bilateral plating could efficiently restore stability and maintain the osteotomy gap. Furthermore, using the D-hole screw reduced the peak stress on the medial plate by 28.7% (from 495 to 353 MPa), 26.6% (from 470 to 345 MPa), and 32.6% (from 454 to 306 MPa) in T1, T2, and T3 LHFs, respectively. Conclusion: Bilateral plating is a recommended strategy to restore HTO stability in LHFs. Furthermore, using a D-hole locking screw is strongly recommended to reduce the stress on the medial plate for lowering plate breakage risk.

The contribution of non-cancer tumoral microenvironment to cachexia is vastly unclear. Despite advances in understanding the signals involved in cancer cachexia progression, the exact time point of cachexia onset remains unpredictable. The transgenic Kras^LSL-G12D/+;Trp53^flox/flox;Pdx1-Cre (KP₂C) GEMM is a clinically relevant model, with the timing of cancer cachexia progression from the pre-cachectic, early-onset, to severe cachexia showed that the onset of cachexia was associated with differences in muscle wasting. The exact cell-of-origin in different types of non-cancer cells in the tumoral microenvironment and the circulating blood, which drives cachexia, remains unclear. Production of potent pro-cachectic substances that induce skeletal muscle wasting also requires mechanistic analysis. This study analyzed the PBMC and the mouse-derived syngeneic transplants (MDSTs) of KP₂C GEMM in recipient mice and pinpoints the cell-type changes with the timing of cachexia (>10% weight loss) by conducting single-cell expression analysis of cell-type-specific gene expression determinants of cachexia. Single-cell RNA sequencing analysis identified signals in high-quality, specific cell types of PBMC (29,615 cells) and MDST (23,151 cells). The scRNA-seq data identified differentially expressed chitinase 3 like 1 (CHI3L1 encoded by mouse Chi3l1) and chitinase-like 3 (CHI3L3, encoded by Chil3) and that macrophages are significant mediators of early-onset muscle wasting in tumor-bearing mice. C2C12 myoblasts treated with the CHI3L1 recombinant protein suppressed myotube formation and upregulated mRNA expression of Hdac3, Tlr9, Irf3, Tbk1, and Nfkb1. Skeletal muscle-specific conditional Hdac3 knockout in tumor-bearing mice decreased muscle wasting via CHI3L1-HDAC3 signaling. An anti-CHI3L1 monoclonal antibody was administered to target these macrophage populations, and the treatment resulted in suppressed tumor growth, metastatic progression, and protected body weight. Our results support the role of pancreatic tumor-associated macrophages in mediating skeletal muscle wasting and provide a clinically relevant mechanism of progression from the pre-cachectic state to the cachexia onset.

Background: Dynamic tape is one of the options for supporting the foot arch in the management of arch-related disorders. However, its mechanical effects on the foot arch remain unclear, particularly under cyclic loading. This study aims to investigate the initial effects of dynamic taping on maintaining foot arch height under cyclic loading among university students. Methods: Thirty-three asymptomatic participants were enrolled in this study. The dynamic tape was applied to the foot with the lower arch to provide support, and the other foot remained untaped as a control. The tape was applied without pre-tension and simply laid straight. Changes in bilateral foot arch height and index were measured using a commercial foot sole morphology assessment device and compared after 6 and 12 min of walking. Results: The arch height did not decrease significantly after walking for 6 or 12 min in either the taped or untaped foot. However, the arch index of the taped foot increased significantly (from 0.258 ± 0.086 to 0.273 ± 0.085) after 12 min of walking, whereas no significant change was observed in the untaped foot. Conclusions: This study is the first to evaluate the initial effect of dynamic tape applied without pre-tension on foot arch support by directly measuring sole morphology using a pin-array impression device. The results indicate that dynamic tape without pre-tension does not effectively prevent the immediate reduction in foot arch height after application. Further research is needed to determine the optimal balance between pre-tension and therapeutic efficacy.