Explainable machine learning approach for cancer prediction through binarilization of RNA sequencing data.

In recent years, researchers have proven the effectiveness and speediness of machine learning-based cancer diagnosis models. However, it is difficult to explain the results generated by machine learning models, especially ones that utilized complex high-dimensional data like RNA sequencing data. In this study, we propose the binarilization technique as a novel way to treat RNA sequencing data and used it to construct explainable cancer prediction models. We tested our proposed data processing technique on five different models, namely neural network, random forest, xgboost, support vector machine, and decision tree, using four cancer datasets collected from the National Cancer Institute Genomic Data Commons. Since our datasets are imbalanced, we evaluated the performance of all models using metrics designed for imbalance performance like geometric mean, Matthews correlation coefficient, F-Measure, and area under the receiver operating characteristic curve. Our approach showed comparative performance while relying on less features. Additionally, we demonstrated that data binarilization offers higher explainability by revealing how each feature affects the prediction. These results demonstrate the potential of data binarilization technique in improving the performance and explainability of RNA sequencing based cancer prediction models.

Effects of Nd: YAG LASER irradiation and O2 plasma on the adhesive performance of poly-ether-ether-ketone (PEEK).

PURPOSE: To evaluate the effects of neodymium-doped yttrium aluminum garnet (Nd: YAG) LASER irradiation and oxygen (O2) plasma on the adhesive performance of polyether ether ketone (PEEK) and resin adhesive. METHODS: Nd: YAG LASERs of varying powers and O2 plasma for different durations were used to modify PEEK. A total of 168 PEEK specimens were randomly divided into seven groups (n = 24/group): (A) Control group: untreated PEEK, (B) L0.75 group: PEEK modified with 0.75 W Nd: YAG LASER, (C) L1 group: PEEK modified with 1.0 W Nd: YAG LASER, (D) L1.25 group: PEEK modified with 1.25 W Nd: YAG LASER, (E) P15 group: PEEK modified with 15 min of O2 plasma, (F) P25 group: PEEK modified with 25 min of O2 plasma, and (G) P35 group: PEEK modified with 35 min of O2 plasma. The surface characteristics of the materials were comprehensively analyzed using a scanning electron microscope (SEM), profilometer, energy-dispersive spectrometer (EDS), and contact angle tester. The adhesive specimens were bonded with Variolink N resin adhesive in all groups and each group was further divided into two subgroups (n = 12/group): (a) water storage for 56 h at 37 °C and (b) thermal cycling 5000 times. Shear bond strength (SBS) was tested using a universal testing machine, and the fracture modes were observed using an automated chemiluminescence analysis system to assess the effects of Nd: YAG LASER and O2 plasma on the bond strength of PEEK to resin adhesive. RESULTS: Both Nd: YAG LASER and O2 plasma treatments altered the surface characteristics of PEEK and significantly increased the SBS between PEEK and Variolink N resin adhesive. The L0.75 group (Nd: YAG LASER) and the P35 group (O2 plasma) achieved the highest SBS, respectively. Furthermore, the SBS of the L0.75 group was higher than that of the P35 group. Following thermal cycling, SBS values decreased compared to the water storage subgroups. The fracture modes of the specimens in each group were predominantly interfacial and mixed, with no cohesive fractures observed. CONCLUSIONS: Nd: YAG LASER irradiation and O2 plasma treatments can improve the SBS between PEEK and resin adhesive, with the 0.75 W Nd: YAG LASER being the preferred treatment method.

Synergistic Effect of Nano Strontium Titanate Coating and Ultraviolet C Photofunctionalization on Osteogenic Performance and Soft Tissue Sealing of poly(ether-ether-ketone).

This study aimed to evaluate the bioactivity of poly(ether ether ketone) (PEEK) after surface modification by persistent photoconductive strontium titanate (SrTiO3) magnetron sputtering and ultraviolet (UV) C irradiation. According to the different modifications, the PEEK specimens were randomly divided into five groups (n = 38/group): PEEK, Sr100-PEEK, Sr200-PEEK, UV/PEEK, and UV/Sr200-PEEK. Then, the specimens of Sr100-PEEK and Sr200-PEEK groups were, respectively, coated with 100 and 200 nm thickness photocatalyst SrTiO3 on the PEEK surface by magnetron sputtering. Subsequently, UV-C light photofunctionalized the specimens of PEEK and Sr200-PEEK groups to form UV/PEEK and UV/Sr200-PEEK groups. The specimens were characterized by a step meter, scanning electron microscopy (SEM), atomic force microscopy (AFM), energy dispersive X-ray spectroscopy (EDX), and a water contact angle meter. The release test of the Sr ion was performed by inductively coupled plasma mass spectrometry (ICP-MS). In vitro study, osteogenic activity (MC3T3-E1 osteoblast-like cells) and epithelial and connective tissue attachment (gingival epithelial cells GE1 and fibroblasts NIH3T3) were analyzed in five groups. Surface morphology of the specimens was changed after coating, and the Sr content on the Sr-PEEK surface was increased with increasing coating thickness. In addition, the contact angle was increased significantly after magnetron sputtering. After UV-C photofunctionalization, the content of surface elements changed and the contact angle was decreased. The release of Sr ion was sustained, and the final cumulative release amount did not exceed the safety limit. In vitro experiments showed that SrTiO3 improved the cell activity of MC3T3-E1 and UV-C irradiation further enhanced the osteogenic performance of PEEK. Besides, UV-C irradiation also significantly promoted the cell viability, development, and expression of adhesion proteins of GE1 and NIH3T3 on PEEK. The present investigation demonstrated that nano SrTiO3 coating with UV-C photofunctionalization synergistically enhanced the osteogenic properties and soft tissue sealing function of PEEK in vitro.

Endoscopic-Directed Trans-Gastric Retrograde Cholangiopancreatography in Patients With Roux-en-Y gastric Bypasses: A Meta-Analysis.

BACKGROUND AND AIM: Endoscopic ultrasound-directed trans-gastric retrograde cholangiopancreatography (EDGE) is a new procedure for treating pancreaticobiliary diseases in patients with Roux-en-Y gastric bypass (RYGB). The aim of this meta­analysis was to determine the overall outcomes and safety of EDGE. MATERIALS AND METHODS: We performed a computerized search of the main databases, including PubMed, EMBASE, Cochrane Library, and Science Citation Index, through October 2022. The main outcome measures examined in the meta-analysis were technical and clinical success rates and overall adverse event (AE) rate, especially the lumen-apposing metal stent (LAMS) dislodgement rate. AE rates were assessed according to LAMS size (15 vs. 20 mm), number of stages (single vs. two) and access route (gastrogastric vs. jejuno-gastric). RESULTS: Fourteen trials with a total of 574 patients who had undergone 585 EDGE procedures were included in this study. The cumulative technical and clinical success and AE rates were 98%, 94%, and 14%, respectively. The commonest AE was LAMS dislodgement (rate 4%). The overall AE rate was lower in the 20-mm LAMS than in the 15-mm LAMS group (odds ratio [OR]=5.79; 95% confidence interval [CI]: 2.35 to 14.29). There were no significant differences in AE rate between number of stages (OR=1.36; 95% CI: 0.51 to 3.64) or differing access routes (OR=1.03; 95% CI 0.48 to 2.22). CONCLUSION: We here provide evidence that EDGE for endoscopic retrograde cholangiopancreatography yields good treatment outcomes in patients with RYGBs. The AE rate is significantly lower with 20-mm versus 15-mm LAMS; thus, the former is likely preferable.

Current surface modification strategies to improve the binding efficiency of emerging biomaterial polyetheretherketone (PEEK) with bone and soft tissue: A literature review.

PURPOSE: The aim of this study was to review the literature on current surface modification strategies used to improve the binding efficiency of an emerging biological material, polyetheretherketone (PEEK), with bone and soft tissues. STUDY SELECTION: This review was based on articles retrieved from PubMed, Google Scholar, Web of Science, and ScienceDirect databases. The main keywords used during the search were "polyetheretherketone (PEEK)," "implant," "surface modification," "biomaterials," "bone," "osseointegration," and "soft tissue." RESULTS: The suitability of PEEK surface modification strategies has been critically analyzed and summarized here. Many cell and in vivo experiments in small animals have shown that the use of advanced modification technologies with appropriate surface modification strategies can effectively improve the surface inertness of PEEK, thereby improving its binding efficiency with bone and soft tissues. CONCLUSIONS: Surface modifications of PEEK have revealed new possibilities for implant treatment; however, most results are based on in vitro or short-term in vivo evaluations in small animals. To achieve a broad application of PEEK in the field of oral implantology, more in vivo experiments and long-term clinical evaluations are needed to investigate the effects of various surface modifications on the tissue integration ability of PEEK to develop an ideal implant material.

Corrigendum: Effect of Monoacylglycerol Lipase Inhibition on Intestinal Permeability of Rats With Severe Acute Pancreatitis.

[This corrects the article DOI: 10.3389/fphar.2022.869482.].

Effect of Monoacylglycerol Lipase Inhibition on Intestinal Permeability of Rats With Severe Acute Pancreatitis.

Background: Endocannabinoid 2-arachidonoylglycerol (2-AG) is an anti-nociceptive lipid that is inactivated through cellular uptake and subsequent catabolism by monoacylglycerol lipase (MAGL). In this study, we investigated the effects of MAGL inhibition on intestinal permeability and explored the possible mechanism. Methods: A rat model of severe acute pancreatitis (SAP) was established. Rats were divided into three groups according to treatment. We analyzed intestinal permeability to fluorescein isothiocyanate-dextran and the levels of inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and 2-AG. Hematoxylin and eosin staining was used to assess histological tissue changes. In vivo intestinal permeability was evaluated by transmission electron microscopy. We obtained ileum tissues, extracted total RNA, and applied RNA-sequencing. Sequencing data were analyzed by bioinformatics. Results: Inflammatory factor levels were higher, while 2-AG levels were lower in the SAP group compared with the control group. Administration of JZL184 to rats with SAP increased the levels of 2-AG and lowered the levels of IL-6 and TNF-α. Notably, intestinal permeability was improved by JZL184 as demonstrated by fluorescein isothiocyanate-dextran measurement, hematoxylin and eosin staining, and transmission electron microscopy. RNA-sequencing showed significant transcriptional differences in SAP and JZL184 groups compared with the control group. KEGG analysis showed that the up- or downregulated genes in multiple comparison groups were enriched in two pathways, focal adhesion and PI3K-Akt signaling pathways. Differential alternative splicing (AS) genes, such as Myo9b, Lsp1, and Git2, have major functions in intestinal diseases. A total of 132 RNA-binding proteins (RBPs) were screened by crossing the identified abnormally expressed genes with the reported RBP genes. Among them, HNRNPDL coexpressed the most AS events as the main RBP. Conclusion: MAGL inhibition improved intestinal mucosal barrier injury in SAP rats and induced a large number of differentially expressed genes and alternative splicing events. HNRNPDL might play an important role in improving intestinal mucosal barrier injury by affecting alternative splicing events.

Construction of a BMP-2 gene delivery system for polyetheretherketone bone implant material and its effect on bone formation in vitro.

Polyetheretherketone (PEEK) has been widely investigated for improving its biological inert to enable it to achieve stronger osteogenic capability and to be a promising material in implant fields. The most important mechanism that makes a successful implantation is osteointegration. Surface modification is an appropriate method to maintain the excellent mechanical properties of PEEK and simultaneously endow PEEK certain biological characters. In this work, we attempted to shape the nano-topography of PEEK surface by nitrogen low-temperature plasma and polydopamine coating on the surface as a secondary reaction platform to bond the aminated poly (lactic-co-glycolic acid) (PLGA) microspheres encapsulating the BMP-2 gene for enhancing the biological activity. Scanning electron microscope, atomic force microscopy, X-ray photoelectron spectroscopy and water contact angle (CA) measurements were applied to characterize the surface of modified or untreated PEEK. Surface characterization showed that the modification was successfully performed on PEEK including a rougher and more hydrophilic surface with nanotopographic features. The influence on cell adhesion, proliferation and differentiation was evaluated by culturing of rat bone marrow mesenchymal stem cells on different modified PEEK substrates in vitro. The biological results indicated that the low-temperature plasma treatment and PDA-coating on PEEK significantly promoted cell adhesion and proliferation. And the osteogenic differentiation was effectively improved by BMP-2 gene releasing from PLGA-NH2 microspheres. The results showed that this novel biological surface modification endowed PEEK with outstanding bioactivity and osteogenic ability, providing a theoretical basis for application in the field of implantation.

An Efficient Parallelized Ontology Network-Based Semantic Similarity Measure for Big Biomedical Document Clustering.

Semantic mining is always a challenge for big biomedical text data. Ontology has been widely proved and used to extract semantic information. However, the process of ontology-based semantic similarity calculation is so complex that it cannot measure the similarity for big text data. To solve this problem, we propose a parallelized semantic similarity measurement method based on Hadoop MapReduce for big text data. At first, we preprocess and extract the semantic features from documents. Then, we calculate the document semantic similarity based on ontology network structure under MapReduce framework. Finally, based on the generated semantic document similarity, document clusters are generated via clustering algorithms. To validate the effectiveness, we use two kinds of open datasets. The experimental results show that the traditional methods can hardly work for more than ten thousand biomedical documents. The proposed method keeps efficient and accurate for big dataset and is of high parallelism and scalability.

Construction and performance evaluation of a sustained release implant material polyetheretherketone with antibacterial properties.

OBJECTIVE: This study aimed to construct a tightly binding antibiotic sustained release system on the polyetheretherketone (PEEK) surface and investigate the cellular activity and antibacterial properties of the new oral implant materials. METHODS: Low-temperature argon plasma under certain parameters was used to prepare P-PEEK with nano-topology, and chemical deposition technology was adopted to form a polydopamine (PDA) coating on the PEEK surface to build a biological binding platform, PDA/P-PEEK. Subsequently, vancomycin gelatin nanoparticles (Van-GNPs) were prepared by two-step desolvation method. Finally, Van-GNPs were combined with PEEK implant material surface to form a new composite material, Van-GNPs/PEEK. scanning electron microscope (SEM), atomic force microscope (AFM), energy dispersive spectrometer (EDS), and contact angle tester were used to comprehensively characterize the materials. The in vitro release test of Van was performed by dynamic dialysis with ultraviolet spectrophotometer. The cell cytotoxicity and adhesion tests were studied by mouse embryonic osteoblasts. The antibacterial properties were evaluated by bacterial adhesion test, plate colony counting, and antimicrobial ring test with Staphylococcus aureus and Streptococcus mutans. RESULTS: PEEK was treated with low-temperature argon plasma and attached to PDA to form a biological binding platform. The synthesized Van-GNPs were smooth, round, with uniform particle size distribution, and bound to PEEK to form a new composite material, which can release Van constantly. Cell experiments showed that Van-GNPs/PEEK had no cytotoxicity and had good interaction with osteoblasts. Bacterial experiments showed that surface conjugation with Van-GNPs could significantly improve the antibacterial performance of PEEK against S. aureus and S. mutans. SIGNIFICANCE: This study demonstrated that Van-GNPs/PEEK have good cellular compatibility and autonomous antibacterial properties, which provide a theoretical basis for the wide application of PEEK in the field of stomatology.

Preparation and characterization of general-purpose gelatin-based co-loading flavonoids nano-core structure.

Flavonoids (FLAs) possess anti-cancer, anti-viral, anti-bacterial, and anti-oxidant properties. In this study, gelatin nanoparticles (GNPs) with controllable surface potential and diameter was prepared through a modified two-step desolvation. Two well-known flavonoids, namely, low-molecular weight Genistein (GEN) and high-molecular weight Icariin (ICA), were adsorbed onto the surface of GNPs (FLA@GNPs). The characteristics of GNPs and the main parameters affecting flavonoid adsorption were studied to evaluate the adsorption capacity and structural stability of FLA@GNPs. Furthermore, co-adsorption of GEN and ICA was detected. The adsorption mechanism of GNPs with FLA was further discussed. Results showed that the low-molecular weight GEN could be effectively adsorbed by GNPs, and their entrapment efficiencies were over 90% under optimized conditions. The total drug loading of the co-adsorbed FLA@GNPs was significantly higher than that of the single drug loaded (GEN or ICA). GEN@GNPs could maintain its structural stability under acidic conditions (pH = 2) at room temperature (25 °C). This protective function enables both ICA and GEN to be bioactive at room temperature for at least 180 days. The characteristics of GNPs adsorption indicate that the hydrogen bonding theory of the combination of gelatin molecules with polyphenols cannot sufficiently explain the binding of GNPs with polyphenols. FLA@GNPs is a promising general-purpose gelatin-based co-loading preload structure with simplified operation and storage condition.

Antibacterial properties of nano-silver coated PEEK prepared through magnetron sputtering.

OBJECTVE: We aimed to investigate the cytotoxicity and antibacterial properties of nano-silver-coated polyetheretherketone (PEEK) produced through magnetron sputtering and provide a theoretical basis for its use in clinical applications. METHODS: The surfaces of PEEKs were coated with nano-silver at varying thicknesses (3, 6, 9, and 12nm) through magnetron sputtering technology. The resulting coated PEEK samples were classified into the following groups according to the thickness of the nano-silver coating: PEEK-3 (3nm), PEEK-6 (6nm), PEEK-9 (9nm), PEEK-12 (12nm), and PEEK control group. The surface microstructure and composition of each sample were observed by scanning electron microscopy (SEM), atomic force microscopy (AFM), and energy dispersive spectrum (EDS) analysis. The water contact angle of each sample was then measured by contact angle meters. A cell counting kit (CCK-8) was used to analyze the cytotoxicity of the mouse fibroblast cells (L929) in the coated groups (n=5) and group test samples (n=6), negative control (polyethylene, PE) (n=6), and positive control group (phenol) (n=6). The antibacterial properties of the samples were tested by co-culturing Streptococcus mutans and Straphylococcus aureus. The bacteria that adhered to the surface of samples were observed by SEM. The antibacterial adhesion ability of each sample was then evaluated. RESULTS: SEM and AFM analysis results showed that the surfaces of control group samples were smooth but compact. Homogeneous silver nano-particles (AgNPs) and nano-silver coating were uniformly distributed on the surface of the coated group samples. Compared with the control samples, the nano-silver coated samples had a significant increase in surface roughness (P<0.05) as the thickness of their nano-silver coating increased. EDS analysis showed that not only C and O but also Ag were present on the surface of the coated samples. Moreover, the water contact angle of modified samples significantly increased after nano-silver coating modification (P<0.01). CCK-8 cytotoxicity test results showed that coated samples did not exhibit cytotoxicity. The antibacterial experimental results showed that the nano-silver coating can significantly improve the antibacterial activity and bacterial adhesion ability of the PEEK samples. SIGNIFICANCE: The compact and homogeneous nano-silver coating was successfully prepared on the surface of PEEK through magnetron sputtering. The nano-silver coated PEEKs demonstrated enhanced antibacterial activities and bacterial adhesion abilities and had no cytotoxic effects.

Bioactivity and antibacterial effect of nitrogen plasma immersion ion implantation on polyetheretherketone.

OBJECTIVE: We aimed to investigate the bioactivity and antibacterial effect of nitrogen plasma immersion ion implantation (PIII) on polyetheretherketone (PEEK). METHODS: According to the different modified parameters, the PEEK specimens were randomly divided into four main groups (n=49/group): PEEK-C, PEEK-I, PEEK-L, and PEEK-H. Then, N2-PIII surface modification was conducted using the corresponding parameters. The microstructure and composition of the modified PEEK surface was observed by scanning electron microscope (SEM), atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS). The water contact angle of the PEEK surface was also studied by contact angle meters. The bioactive ability of PEEK samples was evaluated by observing the attachment, proliferation, and differentiation of MG63 cells cultured on the PEEK samples. Antibacterial property of the samples against Staphylococcus aureus was detected with the plate colony-counting methods. RESULTS: SEM and AFM analysis shows that PEEK-C surface is relatively smooth with the Ra value of 50.6±2.52nm. PEEK-I and PEEK-L surface is rough with the Ra value of 435.9±6.47nm and 443.23±5.49nm, respectively, and the PEEK-H surface is the most rough with the Ra value of 608.4±3.14nm. XPS element analysis demonstrated that nitrogen functional groups were successfully introduced into the surface of PIII-modified PEEK. Biological evaluation and the antibacterial results showed that nitrogen PIII treatment can significantly improve the biological activity of PEEK, and samples showed antibacterial properties against S. aureus. SIGNIFICANCE: PEEK surface subjected to the N2-PIII treatment showed better biological activity and antibacterial effect. Therefore, N2-PIII-treated PEEK surface is promising in bone tissue engineering and dental applications.

Electrodynamics analysis on coherent perfect absorber and phase-controlled optical switch.

A coherent perfect absorber is essentially a specially designed Fabry-Perot interferometer, which completely extinguishes the incident coherent light. The one- and two-beam coherent perfect absorbers have been analyzed using classical electrodynamics by considering index matching in layered structures to totally suppress reflections. This approach presents a clear and physically intuitive picture for the principle of operation of a perfect absorber. The results show that the incident beam(s) must have correct phases and amplitudes, and the real and imaginary parts of the refractive indices of the media in the interferometer must satisfy a well-defined relation. Our results are in agreement with those obtained using the S-matrix analysis. However, the results were obtained solely based on the superposition of waves from multiple reflections without invoking the concept of time reversal as does the S-matrix approach. Further analysis shows that the two-beam device can be configured to function as a phase-controlled three-state switch.