Functionalized chitosan hydrogel promotes osseointegration at the interface of3D printed titanium alloy scaffolds.

Autogenous bone transplantation is a prevalent clinical method for addressing bone defects. However, the limited availability of donor bone and the morbidity associated with bone harvesting have propelled the search for suitable bone substitutes. Bio-inspired scaffolds, particularly those fabricated using electron beam melting (EBM) deposition technology, have emerged as a significant advancement in this field. These 3D-printed titanium alloy scaffolds are celebrated for their outstanding biocompatibility and favorable elastic modulus. Thermosensitive chitosan hydrogel, which transitions from liquid to solid at body temperature, serves as a popular carrier in bone tissue engineering. Icariin (ICA), known for its efficacy in promoting osteoblast differentiation from bone marrow mesenchymal stem cells (BMSCs), plays a crucial role in this context. We developed a system combining a 3D-printed titanium alloy with a thermosensitive chitosan hydrogel, capable of local bone regeneration and integration through ICA delivery. Our in vitro findings reveal that this system can gradually release ICA, demonstrating excellent biocompatibility while fostering BMSC proliferation and osteogenic differentiation. Immunohistochemistry and Micro-CT analyses further confirm the effectiveness of the system in accelerating in vivo bone regeneration and enhancing osseointegration. This composite system lays a significant theoretical foundation for advancing local bone regeneration and integration.

An omics-to-omics joint knowledge association subtensor model for radiogenomics cross-modal modules from genomics and ultrasonic images of breast cancers.

The radiogenomics analysis can provide the connections between genomics and radiomics, which can infer the genomic features of tumors from their radiogenomic associations through the low-cost and non-invasiveness screening ultrasonic images. Although there are a number of pioneer approaches exploring the connections between genomic aberrations and ultrasonic features, these studies mainly focus on the relationship between ultrasonic features and only the most popular cancer genes, confronting two difficulties: missing many-to-many relationships as omics-to-omics view, and confounding group-specific associations with whole sample associations. To overcome the difficulty of omics-to-omics view and the issue of tumor heterogeneity, we propose an omics-to-omics joint knowledge association subtensor model. Specifically, the subtensor factorization framework can successfully discover the joint cross-modal module via an omics-to-omics view, while the sparse weight sample indication strategy can mine sample subgroups from the multi-omic data with tumor heterogeneity. The experimental evaluation result shows the jointness of the discovered modules across omics, their association with tumorigenesis contribution, and their relation for cancer related functions. In summary, our proposed omics-to-omics joint knowledge association subtensor model can serve as an efficient tool for radiogenomic knowledge associations, promoting the cross-modal knowledge graph construction of in explainable artificial intelligence cancer diagnosis.

Integrating multi-type aberrations from DNA and RNA through dynamic mapping gene space for subtype-specific breast cancer driver discovery.

Driver event discovery is a crucial demand for breast cancer diagnosis and therapy. In particular, discovering subtype-specificity of drivers can prompt the personalized biomarker discovery and precision treatment of cancer patients. Still, most of the existing computational driver discovery studies mainly exploit the information from DNA aberrations and gene interactions. Notably, cancer driver events would occur due to not only DNA aberrations but also RNA alternations, but integrating multi-type aberrations from both DNA and RNA is still a challenging task for breast cancer drivers. On the one hand, the data formats of different aberration types also differ from each other, known as data format incompatibility. On the other hand, different types of aberrations demonstrate distinct patterns across samples, known as aberration type heterogeneity. To promote the integrated analysis of subtype-specific breast cancer drivers, we design a "splicing-and-fusing" framework to address the issues of data format incompatibility and aberration type heterogeneity simultaneously. To overcome the data format incompatibility, the "splicing-step" employs a knowledge graph structure to connect multi-type aberrations from the DNA and RNA data into a unified formation. To tackle the aberration type heterogeneity, the "fusing-step" adopts a dynamic mapping gene space integration approach to represent the multi-type information by vectorized profiles. The experiments also demonstrate the advantages of our approach in both the integration of multi-type aberrations from DNA and RNA and the discovery of subtype-specific breast cancer drivers. In summary, our "splicing-and-fusing" framework with knowledge graph connection and dynamic mapping gene space fusion of multi-type aberrations data from DNA and RNA can successfully discover potential breast cancer drivers with subtype-specificity indication.

Circular RNAs in Parkinson's Disease: Reliable Biological Markers and Targets for Rehabilitation.

In clinical practice, the underlying pathogenesis of Parkinson's disease (PD) remains unknown. Circular RNAs (circRNAs) have good biological properties and can be used as biological marker. Rehabilitation as a third treatment alongside drug and surgery has been shown to be clinically effective, but biomarkers of rehabilitation efficiency at genetic level is still lacking. In this study, we identified differentially expressed circRNAs in peripheral blood exosomes between PD patients and health controls (HCs) and determined whether these circRNAs changed after rehabilitation, to explore the competing RNA networks and epigenetic mechanisms affected. We found that there were 558 upregulated and 609 downregulated circRNAs in PD patients compared to HCs, 3398 upregulated and 479 downregulated circRNAs in PD patients after rehabilitation compared to them before rehabilitation, along with 3721 upregulated and 635 downregulated circRNAs in PD patients after rehabilitation compared to HCs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that differentially expressed circRNAs may affect the stability of the cellular actin backbone and synaptic structure by influencing the aggregation of α-synuclein (a-syn). We selected two circRNAs overexpressed in PD patients for validation (hsa_circ_0001535 and hsa_circ_0000437); the results revealed that their expression levels were all reduced to varying degrees (p < 0.05) after rehabilitation. After network analysis, we believe that hsa_circ_0001535 may be related to the aggregation of a-syn, while hsa_circ_0000437 may act on hsa-let-7b-5p or hsa-let-7c-5p through sponge effect to cause inflammatory response. Our findings suggest that rehabilitation can mitigate the pathological process of PD by epigenetic means.

Extracellular Vesicles-Encapsulated miR-153-3p Potentiate the Survival and Invasion of Lung Adenocarcinoma.

Extracellular vesicles (EVs) play an essential role in the communication between cells and the tumor micro-environment. However, the effect of tumor-derived EVs on the growth and metastasis of lung adenocarcinoma (LUAD) remains to be explored. This study aimed to elucidate the role of miR-153-3p-EVs in the invasion and migration capabilities of LUAD cells and explore its mechanism through in vivo and in vitro experiments. We found that miR-153-3p was specifically and highly expressed in LUAD and its secreted EVs. Furthermore, the expression of BANCR was negatively regulated by miR-153-3p and identified as a target gene of miR-153-3p using luciferase reporter assays. Through further investigation, we found that the downregulation of BANCR activates the PI3K/AKT pathway and accelerates the process of epithelial-mesenchymal transition (EMT), which ultimately leads to the aggravation of LUAD. The orthotopic xenograft mouse model was established to illustrate the effect of miR-153-3p-EVs on LUAD. Animal studies showed that miR-153-3p-EVs accelerated tumor growth in mice. Besides, we found that miR-153-3p-EVs could damage the respiratory ability of mice and produce a mass of inflammatory cells around the lung tissue of mice. Nevertheless, antagomir-153-3p treatment could inhibit the deterioration of respiratory function and inhibit the growth of lung tumors in mice. In conclusion, our study reveals the potential molecular mechanism of miR-153-3p-EVs in the development of LUAD and provides a potential strategy for the treatment of LUAD.

Regional ventilation distribution in patients with scoliosis assessed by electrical impedance tomography: Is individual thorax shape required?

BACKGROUND: Electrical impedance tomography (EIT) is a non-invasive non-radiological regional lung function measurement. The aim of the study was to examine the feasibility of assessing ventilation distribution with EIT in scoliosis patients using generic and individual thorax shape. METHODS: Eight subjects were measured with EIT before scoliosis surgery. Reconstructions with two different forward models were compared: the generic shape and the individual thorax shapes. Three EIT-based parameters measuring ventilation distribution were calculated: left lung to overall ratio, center of ventilation (CoV), global inhomogeneity index. RESULTS: EIT measurements were successfully conducted in all subjects. No statistical differences were found in the EIT-based parameters using the different reconstruction models. CoV based on the generic shape was significantly correlated to the main Cobb angle (r=-0.84, p < 0.01). CONCLUSION: It was feasible to monitor regional ventilation distribution in scoliosis patients with EIT. Individual thorax shapes might not be required for reliable patient assessment in a clinical setting.

Curcumin Ameliorates White Matter Injury after Ischemic Stroke by Inhibiting Microglia/Macrophage Pyroptosis through NF-κB Suppression and NLRP3 Inflammasome Inhibition.

NLRP3 inflammasome-mediated pyroptosis is a proinflammatory programmed cell death pathway, which plays a vital role in functional outcomes after stroke. We previously described the beneficial effects of curcumin against stroke-induced neuronal damage through modulating microglial polarization. However, the impact of curcumin on microglial pyroptosis remains unknown. Here, stroke was modeled in mice by middle cerebral artery occlusion (MCAO) for 60 minutes and treated with curcumin (150 mg/kg) intraperitoneally immediately after reperfusion, followed by daily administrations for 7 days. Curcumin ameliorated white matter (WM) lesions and brain tissue loss 21 days poststroke and improved sensorimotor function 3, 10, and 21 days after stroke. Furthermore, curcumin significantly reduced the number of gasdermin D+ (GSDMD+) Iba1+ and caspase-1+Iba1+ microglia/macrophage 21 days after stroke. In vitro, lipopolysaccharide (LPS) with ATP treatment was used to induce pyroptosis in primary microglia. Western blot revealed a decrease in pyroptosis-related proteins, e.g., GSDMD-N, cleaved caspase-1, NLRP3, IL-1ß, and IL-18, following in vitro or in vivo curcumin treatment. Mechanistically, both in vivo and in vitro studies confirmed that curcumin inhibited the activation of the NF-κB pathway. NLRP3 knocked down by siRNA transfection markedly increased the inhibitory effects of curcumin on microglial pyroptosis and proinflammatory responses, both in vitro and in vivo. Furthermore, stereotaxic microinjection of AAV-based NLRP3 shRNA significantly improved sensorimotor function and reduced WM lesion following curcumin treatment in MCAO mice. Our study suggested that curcumin reduced stroke-induced WM damage, improved functional outcomes, and attenuated microglial pyroptosis, at least partially, through suppression of the NF-κB/NLRP3 signaling pathway, further supporting curcumin as a potential therapeutic drug for stroke.

Melatonin Protects Against Ischemic Brain Injury by Modulating PI3K/AKT Signaling Pathway via Suppression of PTEN Activity.

Stroke is one of the leading causes of death and disability worldwide with limited therapeutic options. Melatonin can attenuate ischemic brain damage with improved functional outcomes. However, the cellular mechanisms of melatonin-driven neuroprotection against post-stroke neuronal death remain unknown. Here, distal middle cerebral artery occlusion (dMCAO) was performed in C57BL/6j mice to develop an ischemic stroke in vivo model. Melatonin was injected intraperitoneally immediately after ischemia, and 24 and 48 hours later. Melatonin treatment, with 5 to 20 mg/kg, elicited a dose-dependent decrease in infarct volume and concomitant increase in sensorimotor function. At the molecular level, phosphorylation of PTEN and Akt were increased, whereas PTEN activity was decreased in melatonin treated animals 72 hours after dMCAO. At the cellular level, oxygenglucose deprivation (OGD) challenge of neuronal cell line Neuro-2a (N2a) and primary neurons supported melatonin's direct protection against neuronal cell death. Melatonin treatment reduced LDH release and neuronal apoptosis at various time points, markedly increased Akt phosphorylation in neuronal membrane, but significantly suppressed it in the cytoplasm of post-OGD neurons. Mechanistically, melatonin-induced Akt phosphorylation and neuronal survival was blocked by Wortmannin, a potent PIP3 inhibitor, exposing increased PI3K/Akt activation as a central player in melatonin-driven neuroprotection. Finally, PTEN knock-down through siRNA significantly inhibited PI3K/Akt activation and cell survival following melatonin treatment, suggesting that melatonin protection against ischemic brain damage, is at least partially, dependent on modulation of the PTEN/PI3K/Akt signaling axis.

Ventilation improvement after pneumonia treatment evaluated with electrical impedance tomography: an observational study.

Objective.Due to radiation exposure, not all patients with pneumonia receive chest x-rays or CT measurements to confirm treatment effectiveness. The aim of this study was to examine the ability to use electrical impedance tomography (EIT) to evaluate the treatment effectiveness in such patient group.Approach.A total of 35 consecutive patients with non-severe pneumonia were included in this prospective study. The patients received standard treatment according to our internal protocol. EIT measurements were performed in supine position before the treatment started and on day 6 of the treatment period. The EIT-based global inhomogeneity (GI) index and center of ventilation (CoV) index were calculated. The clinical pulmonary infection score (CPIS) was obtained at both time points.Main results.Clinically significant improvements inGIandCoVwere found in the patient group (ΔGI: -34% ± 17% and ΔCoV: -10% ± 11%;p<0.001). Although the CPIS was also significantly improved (ΔCPIS-0.70 ± 0.17,p<0.001), no correlations were demonstrated when compared to ΔGIor ΔCoV. Significance.EIT demonstrated individual improvement of ventilation heterogeneity after standard treatment in non-severe pneumonia, and provided different information compared to CPIS. EIT has the potential to become a routine non-invasive, non-radiative tool to assess pneumonia treatment effectiveness.

STIC: Predicting Single Nucleotide Variants and Tumor Purity in Cancer Genome.

Single nucleotide variant (SNV) plays an important role in cellular proliferation and tumorigenesis in various types of human cancer. Next-generation sequencing (NGS) has provided high-throughput data at an unprecedented resolution to predict SNVs. Currently, there exist many computational methods for either germline or somatic SNV discovery from NGS data, but very few of them are versatile enough to adapt to any situations. In the absence of matched normal samples, the prediction of somatic SNVs from single-tumor samples becomes considerably challenging, especially when the tumor purity is unknown. Here, we propose a new approach, STIC, to predict somatic SNVs and estimate tumor purity from NGS data without matched normal samples. The main features of STIC include: (1) extracting a set of SNV-relevant features on each site and training the BP neural network algorithm on the features to predict SNVs; (2) creating an iterative process to distinguish somatic SNVs from germline ones by disturbing allele frequency; and (3) establishing a reasonable relationship between tumor purity and allele frequencies of somatic SNVs to accurately estimate the purity. We quantitatively evaluate the performance of STIC on both simulation and real sequencing datasets, the results of which indicate that STIC outperforms competing methods.

CNV_IFTV: An Isolation Forest and Total Variation-Based Detection of CNVs from Short-Read Sequencing Data.

Accurate detection of copy number variations (CNVs) from short-read sequencing data is challenging due to the uneven distribution of reads and the unbalanced amplitudes of gains and losses. The direct use of read depths to measure CNVs tends to limit performance. Thus, robust computational approaches equipped with appropriate statistics are required to detect CNV regions and boundaries. This study proposes a new method called CNV_IFTV to address this need. CNV_IFTV assigns an anomaly score to each genome bin through a collection of isolation trees. The trees are trained based on isolation forest algorithm through conducting subsampling from measured read depths. With the anomaly scores, CNV_IFTV uses a total variation model to smooth adjacent bins, leading to a denoised score profile. Finally, a statistical model is established to test the denoised scores for calling CNVs. CNV_IFTV is tested on both simulated and real data in comparison to several peer methods. The results indicate that the proposed method outperforms the peer methods. CNV_IFTV is a reliable tool for detecting CNVs from short-read sequencing data even for low-level coverage and tumor purity. The detection results on tumor samples can aid to evaluate known cancer genes and to predict target drugs for disease diagnosis.

Postoperative efficacy of low-temperature plasma radiofrequency ablation in elderly patients with laryngeal carcinoma and its influences on tumor markers and COX-2 and VEGF expressions in laryngeal carcinoma tissues.

PURPOSE: To observe the postoperative efficacy of low-temperature plasma radiofrequency ablation in treating elderly patients with laryngeal carcinoma and its influence on the tumor markers, cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) expressions in laryngeal carcinoma tissues. METHODS: A total of 50 elderly laryngeal carcinoma patients undergoing low-temperature plasma radiofrequency ablation in our hospital from January 2015 to January 2018 were enrolled as observation group, and another 50 elderly laryngeal carcinoma patients receiving conventional surgical treatment as control group. At the end of the treatment course, the efficacy and postoperative complications in the patients were observed, the operation time and pain visual analogue scale (VAS) and mucosal recovery scores were recorded. Besides, the levels of the tumor markers carbohydrate antigen 125 (CA125), CA199 and carcinoembryonic antigen (CEA) were determined, and the expressions of COX-2 and VEGF in laryngeal carcinoma tissues in the two groups were detected using immunohistochemistry and quantitative polymerase chain reaction (PCR). RESULTS: The efficacy in the study group was obviously higher than in the control group (p<0.05), and the cases of postoperative complications declined evidently in the study group (p<0.05). Moreover, the study group exhibited distinctly shorter operation time and lower VAS pain and mucosal recovery scores than the control group (p<0.05). The levels of the tumor markers CA125, CEA and CA19.9 and the expression levels of COX-2 and VEGF in laryngeal carcinoma tissues were substantially lowered in the study group (p<0.05). CONCLUSIONS: Low-temperature plasma radiofrequency ablation has better efficacy in treating elderly laryngeal carcinoma patients, with few postoperative complications, and decreased expression levels of postoperative tumor markers as well as COX-2 and VEGF in laryngeal carcinoma tissues, and it offers better overall effect and notable application value, therefore it is worth trying it in clinical practice.

[Effectiveness of percutaneous injection of autologous concentrated bone marrow aspirate combined with platelet-rich plasma in treatment of delayed fracture healing].

OBJECTIVE: To analyze the effectiveness of percutaneous injection of autologous concentrated bone marrow aspirate (cBMA) combined with platelet-rich plasma (PRP) in the treatment of delayed fracture healing. METHODS: A prospective, randomized, controlled, single-blind case study was conducted. Between March 2016 and July 2018, 66 patients who met the inclusion and exclusion criteria for delayed fracture healing but had solid internal fixation of the fracture end were randomly divided into control group (31 cases, treated with percutaneous autogenous bone marrow blood injection) and study group (35 cases, treated with percutaneous autogenous cBMA+PRP injection). General data such as gender, age, body mass index, site of delayed fracture healing, length of bone defect at fracture end, and preoperative radiographic union score for tibia (RUST) showed no significant difference between the two groups ( P>0.05). Before injection, Kirschner wire was used in both groups to stimulate the fracture end and cause minor injury. The fracture healing time, treatment cost, and adverse reactions were recorded and compared between the two groups. Visual analogue scale (VAS) score was used to evaluate pain improvement. The tibial RUST score was extended to the tubular bone healing evaluation. RESULTS: No infection of bone marrow puncture needle eyes occurred in both groups. In the control group, local swelling was obvious in 5 cases and pain was aggravated at 1 day after operation in 11 cases. In the study group, postoperative swelling and pain were not obvious, but 2 cases presented local swelling and pain. All of them relieved after symptomatic treatment. Patients in both groups were followed up, the follow-up time of the control group was 16-36 months (mean, 21.8 months), and the study group lasted 14-33 months (mean, 23.2 months). The amount of bone marrow blood was significantly lower in the study group than in the control group ( t=4.610, P=0.000). The degree of postoperative pain in the study group was less than that in the control group, and the treatment cost was higher than that in the control group. But the differences between the two groups in VAS score at 1 day after operation and treatment cost were not significant ( P>0.05). Fracture healing was achieved in 19 cases (61.3%) in the control group and 30 cases (85.7%) in the study group. The difference in fracture healing rate between the two groups was significant ( χ 2=5.128, P=0.024). Fracture healing time and RUST score at last follow-up were significantly better in the study group than in the control group ( P<0.05). At last follow-up, RUST scores in both groups were significantly improved when compared with those before operation ( P<0.05). CONCLUSION: Autogenous cBMA combined with PRP percutaneous injection can provide high concentration of BMSCs and growth factors, and can improve the fracture healing rate and shorten the fracture healing time better than autogenous bone marrow blood injection.

[Application of "diamond concept" in treatment of femoral shaft fractures nonunion after intramedullary fixation].

OBJECTIVE: To investigate the effectiveness of the treatment under the guidance of "diamond concept" for femoral shaft fractures nonunion after intramedullary fixation. METHODS: Between January 2014 and December 2016, 21 cases of femoral shaft fractures nonunion after intramedullary fixation were treated with auxiliary plate fixation combined with autogenous iliac graft, and autologous bone marrow concentrate and platelet-rich plasma (PRP) gel under the guidance of the "diamond concept". There were 13 males and 8 females, with an average age of 32.5 years (range, 17-48 years). All fractures were closed femoral shaft fractures. Four patients underwent internal fixation with plate and resulted in nonunion, then they were fixed with intramedullary nails, but did not heal either. The rest 17 patients were fixed with intramedullary nailing. Fracture nonunion classification: 4 cases of hypertrophic nonunion, 17 cases of atrophic nonunion; the length of bone defect was 1-3 mm; the duration from the last treatment to the current treatment was 10-23 months (mean, 14.3 months). The operation time, intraoperative blood loss, the time between operation and full loading, fracture healing time, and complications were recorded. The visual analogue scale (VAS) score and the imaging system of fracture healing of the extremities (RUST) of patients before operation and at last follow-up were recorded to evaluate the fracture healing; the function of the affected limb was evaluated according to the Schatzker-Lambert efficacy score standard at last follow-up. RESULTS: The operation time was 105-160 minutes, with an average of 125.6 minutes; the intraoperative blood loss was 160-580 mL, with an average of 370.5 mL. All incisions healed by first intention, without vascular or nerve injury. All patients were followed up 22-46 months (mean, 26.5 months). All the fractures healed, with a fracture healing time of 3-7 months (mean, 4.8 months). During the follow-up, there was no infection, loosening, implant breakage, re-fracture, and other complications. The VAS score at last follow-up was 0.8±0.3, showing significant difference ( t=7.235, P=0.000) when compared with preoperative score (5.2±3.7); the RUST score was 3.4±0.3, which was significantly higher than the preoperative score (1.5±0.7) ( t=8.336, P=0.000). According to the Schatzker-Lambert effectiveness evaluation standard, the limb function was excellent in 16 cases, good in 4 cases, fair in 1 case, and the excellent and good rate was 95.42%. CONCLUSION: Nonunion after intramedullary fixation of femoral fracture treated with auxiliary plate combined with autogenous iliac graft, autogenous bone marrow concentration and PRP gel in accordance with the "diamond concept" can not only restore the stability of the fracture ends, but also improves the biological environment of the fracture site, and can improve the rate of fracture healing.

MiR-487a-3p suppresses the malignant development of pancreatic cancer by targeting SMAD7.

OBJECTIVE: To uncover the role of microRNA-487a-3p (miR-487a-3p) in influencing the malignant development of pancreatic cancer and the involvement of its downstream target SMAD7. METHODS: MiR-487a-3p level in 40 pancreatic cancer and paracancerous tissues was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between miR-487a-3p level and clinical indicators in pancreatic cancer patients was analyzed. Regulatory effects of miR-487a-3p on biological phenotypes of pancreatic cancer cells were assessed. At last, the involvement of miR-487a-3p and its downstream target SMAD7 in pancreatic cancer was determined. RESULTS: MiR-487a-3p was lowly expressed in pancreatic cancer tissues. Pancreatic cancer patients expressing a low level of miR-487a-3p suffered high metastasis rate and poor prognosis. Overexpression of miR-487a-3p markedly attenuated proliferative and migratory capacities in pancreatic cancer cells. SMAD7 was the downstream target of miR-487a-3p, which was highly expressed in pancreatic cancer samples. Overexpression of SMAD7 reversed the regulatory effects of miR-487a-3p on pancreatic cancer cell phenotypes. CONCLUSIONS: MiR-487a-3p is downregulated in pancreatic cancer samples, which is linked to metastasis and prognosis in pancreatic cancer. It inhibits the malignant development of pancreatic cancer by negatively regulating SMAD7.

Biomechanical Evaluation of Preoperative Rehabilitation in Patients of Anterior Cruciate Ligament Injury.

OBJECTIVES: To investigate the biomechanical characteristics of patients with anterior cruciate ligament (ACL) injury by gait analysis, surface electromyography (SEMG), and proprioception test, and provide rehabilitation suggestions according to the results. METHODS: In this retrospective cohort study, 90 adults with unilateral ACL injury, ranging in age from 19 to 45 years (66 men and 24 women, average age: 30.03 ± 7.91) were recruited for this study form May 2018 to July 2019. They were divided into three groups according to the time after the injury: group A (3-week to 1.5-month), group B (1.5-month to 1 year), and group C (more than 1 year). The SEMG signals were collected from the bilateral rectus femoris (RF), vastus medialis (VM), and vastus lateralis (VL) and the root mean square (RMS) were used to assess muscular activity. SEMG were used to analyze muscles function, gait analysis was used to evaluate the walking stability, balance and location assessment were used to analyze the proprioception. RESULTS: Through the comparison between bilateral limbs, all muscles strength shown decreased (RF: 239.94 ± 129.70 vs 364.81 ± 148.98, P = 0.001; VM: 298.88 ± 175.41 vs 515.79 ± 272.49, P = 0.001; VL:389.54 ± 157.97 vs 594.28 ± 220.31, P < 0.001) and the division of proprioception became larger (tandem position: 7.79 ± 1.57 vs 6.33 ± 1.49, P = 0.001; stance with one foot: 8.13 ± 0.84 vs 7.1 ± 0.57, P = 0.003; variance of 30°: 6.96 ± 3.15 vs 4.45 ± 1.67, P = 0.03; variance of 60°: 4.64 ± 3.38 vs 2.75 ± 1.98, P = 0.044) in the injured side when compared to the non-injured and 26 gait parameters were shown difference in group A. In group B, the muscle strength of VL shown decreased (VL: 381.23 ± 142.07 vs 603.9 ± 192.72, P < 0.001) and the division of location of 30° became larger (7.62 ± 4.98 vs 4.33 ± 3.24, P = 0.028) in the injured side when compared to the non-injured side and there were eight gait parameters that showed differences. In group C, the muscle strength and proprioception showed no differences and only 16 gait parameters showed differences between the bilateral limbs. CONCLUSION: The results proved the deterioration of proprioception in 30° of injured side will not recover and non-injury side and will become worse after 1 year from the injury; among the VL, VM, and RF, the recovery rate of VL is the slowest and bilateral straight leg raising (SLR) (30°) is the best way to train it; the gait stability will be worse after 1 year from the injury. Therefore, we suggest that the training for proprioception in 30° and VL are important for the rehabilitation, and the ACL reconstruction should be performed within 1 year.

Dual-Layer Strengthened Collaborative Topic Regression Modeling for Predicting Drug Sensitivity.

An effective way to facilitate the development of modern oncology precision medicine is the systematical analysis of the known drug sensitivities that have emerged in recent years. Meanwhile, the screening of drug response in cancer cell lines provides an estimable genomic and pharmacological data towards high accuracy prediction. Existing works primarily utilize genomic or functional genomic features to classify or regress the drug response. Here in this work, by the migration and extension of the conventional merchandise recommendation methods, we introduce an innovation model on accurate drug sensitivity prediction by using dual-layer strengthened collaborative topic regression (DS-CTR), which incorporates not only the graphic model to jointly learn drugs and cell lines feature from pharmacogenomics data but also drug and cell line similarity network model to strengthen the correlation of the prediction results. Using Genomics of Drug Sensitivity in Cancer project (GDSC) as benchmark datasets, the 5-fold cross-validation experiment demonstrates that DS-CTR model significantly improves drug response prediction performance compared with four categories of state-of-the-art algorithms as for both Receiver Operator Curve (ROC) and the Area Under Receiver Operator Curve (AUC). By uncovering the unknown cell-drug associations with advanced literature evidences, our novel model DS-CTR is validated and supported. The model also provides the possibility to make the discovery of new anti-cancer therapeutics in the preclinical trials cheaper and faster.

HetRCNA: A Novel Method to Identify Recurrent Copy Number Alternations from Heterogeneous Tumor Samples Based on Matrix Decomposition Framework.

A common strategy to discovering cancer associated copy number aberrations (CNAs) from a cohort of cancer samples is to detect recurrent CNAs (RCNAs). Although the previous methods can successfully identify communal RCNAs shared by nearly all tumor samples, detecting subgroup-specific RCNAs and their related subgroup samples from cancer samples with heterogeneity is still invalid for these existing approaches. In this paper, we introduce a novel integrated method called HetRCNA, which can identify statistically significant subgroup-specific RCNAs and their related subgroup samples. Based on matrix decomposition framework with weight constraint, HetRCNA can successfully measure the subgroup samples by coefficients of left vectors with weight constraint and subgroup-specific RCNAs by coefficients of the right vectors and significance test. When we evaluate HetRCNA on simulated dataset, the results show that HetRCNA gives the best performances among the competing methods and is robust to the noise factors of the simulated data. When HetRCNA is applied on a real breast cancer dataset, our approach successfully identifies a bunch of RCNA regions and the result is highly correlated with the results of the other two investigated approaches. Notably, the genomic regions identified by HetRCNA harbor many breast cancer related genes reported by previous researches.

Inferring subgroup-specific driver genes from heterogeneous cancer samples via subspace learning with subgroup indication.

MOTIVATION: Detecting driver genes from gene mutation data is a fundamental task for tumorigenesis research. Due to the fact that cancer is a heterogeneous disease with various subgroups, subgroup-specific driver genes are the key factors in the development of precision medicine for heterogeneous cancer. However, the existing driver gene detection methods are not designed to identify subgroup specificities of their detected driver genes, and therefore cannot indicate which group of patients is associated with the detected driver genes, which is difficult to provide specifically clinical guidance for individual patients. RESULTS: By incorporating the subspace learning framework, we propose a novel bioinformatics method called DriverSub, which can efficiently predict subgroup-specific driver genes in the situation where the subgroup annotations are not available. When evaluated by simulation datasets with known ground truth and compared with existing methods, DriverSub yields the best prediction of driver genes and the inference of their related subgroups. When we apply DriverSub on the mutation data of real heterogeneous cancers, we can observe that the predicted results of DriverSub are highly enriched for experimentally validated known driver genes. Moreover, the subgroups inferred by DriverSub are significantly associated with the annotated molecular subgroups, indicating its capability of predicting subgroup-specific driver genes. AVAILABILITY AND IMPLEMENTATION: The source code is publicly available at https://github.com/JianingXi/DriverSub. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.