Advancing precision rheumatology: applications of machine learning for rheumatoid arthritis management

Rheumatoid arthritis (RA) is an autoimmune disease causing progressive joint damage. Early diagnosis and treatment is critical, but remains challenging due to RA complexity and heterogeneity. Machine learning (ML) techniques may enhance RA management by identifying patterns within multidimensional biomedical data to improve classification, diagnosis, and treatment predictions. In this review, we summarize the applications of ML for RA management. Emerging studies or applications have developed diagnostic and predictive models for RA that utilize a variety of data modalities, including electronic health records, imaging, and multi-omics data. High-performance supervised learning models have demonstrated an Area Under the Curve (AUC) exceeding 0.85, which is used for identifying RA patients and predicting treatment responses. Unsupervised learning has revealed potential RA subtypes. Ongoing research is integrating multimodal data with deep learning to further improve performance. However, key challenges remain regarding model overfitting, generalizability, validation in clinical settings, and interpretability. Small sample sizes and lack of diverse population testing risks overestimating model performance. Prospective studies evaluating real-world clinical utility are lacking. Enhancing model interpretability is critical for clinician acceptance. In summary, while ML shows promise for transforming RA management through earlier diagnosis and optimized treatment, larger scale multisite data, prospective clinical validation of interpretable models, and testing across diverse populations is still needed. As these gaps are addressed, ML may pave the way towards precision medicine in RA

Study on time effect of bearing capacity of Offshore Large Diameter Monopiles

In order to improve the evaluation ability of bearing capacity of offshore large-diameter monopile, the initial high strain detection and repeated high strain detection with an interval of 10-84 days were carried out on 6 large-diameter monopiles with a diameter of 7.2m-7.4m in the offshore wind field dominated by cohesive soil layer. The results show that the time-dependent increase of tip resistance, pile side resistance and total resistance of large-diameter monopiles in the same offshore wind farm has great discreteness, and the axial force increment of pile has a consistent change trend. This paper puts forward the prediction interval of 95% guarantee rate of bearing capacity increment of offshore large-diameter single pile based on depth, which provides a basis for the design of large-diameter monopile

Study on the mechanism of mechanical property strengthening of Beishan granite under mild temperature condition

Many researches found that mechanical properties of granite were strengthened under the mild temperature range (within 300 °C), which is positive for the long-term safety of the high-level radioactive waste (HLW) geological disposal engineering. To study the thermal strengthening mechanism of granite under elevated temperature by the decay heat of the HLW, a novel experiment was carried out which stress loaded firstly to cause stress damage, then thermal loaded to study the temperature effect on stress damaged granite. Results show: (1) the deformation memory effect and the Kaiser effect existed after stress loaded for non-thermal treated and 120 °C treated on granite, while the deformation memory effect (DME) was significantly faded after 250 °C treated. (2) The volume of pores/cracks in Beishan granite increased after stress loaded, then decreased significantly after 120 °C and 250 °C treated. (3) The deformation behavior, AE activity and pores/cracks closure all showed that the stress induced damage could be healed at elevated temperature, which is positive for the HLW disposal engineering. (4) A viscoelastic frictional sliding model was used to analyze the mechanism of DME fading and the mechanical property strengthening

CS12192, a Novel JAK3/JAK1/TBK1 Inhibitor, Synergistically Enhances the Anti-Inflammation Effect of Methotrexate in a Rat Model of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a common disease worldwide and is treated commonly with methotrexate (MTX). CS12192 is a novel JAK3 inhibitor discovered by Chipscreen Biosciences for the treatment of autoimmune diseases. In the present study, we examined the therapeutic effect of CS12192 against RA and explored if the combinational therapy of CS12192 and MTX produced a synergistic effect against RA in rat collagen-induced arthritis (CIA). Arthritis was induced in male Sprague-Dawley rats by two intradermal injections of bovine type II collagen (CII) and treated with MTX, CS12192, or the combination of CS12192 and MTX daily for two weeks. Effects of different treatments on arthritis score, X-ray score, pathology, and expression of inflammatory cytokines and biomarkers were examined. We found that treatment with either CS12192 or MTX produced a comparable therapeutic effect on CIA including: (1) significantly lowering the arthritis score, X-ray score, serum levels of rheumatic factor (RF), C-reactive protein (CRP), and anti-nuclear antibodies (ANA); (2) largely alleviating histopathological damage, reducing infiltration of Th17 cells while promoting Treg cells; (3) inhibiting the expression of inflammatory cytokines and chemokines such as IL-1β, TNF-α, IL-6, CCL2, and CXCL1. All these inhibitory effects were further improved by the combinational therapy with MTX and CS12192. Of importance, the combinational treatment also resulted in a marked switching of the Th17 to Treg and the M1 to M2 immune responses in synovial tissues of CIA. Thus, when compared to the monotherapy, the combination treatment with CS12192 and MTX produces a better therapeutic effect against CIA with a greater suppressive effect on T cells and macrophage-mediated joint inflammation

Differential Expression and Prognostic Value of Cytoplasmic and Nuclear Cyclin D1 in Prostate Cancer

Cyclin D1 (CCND1) has been revealed as a key regulating protein in cell cycle (G1 phase) and plays a critical role in promoting tumor development. The purpose of our study was to investigate the associations between CCND1 and biochemical recurrence of prostate cancer (PCa). We performed immunostaining of CCND1 on a tissue microarray and evaluated the CCND1 expression levels based on the intensity and extent of staining. The clinical data was collected, and the follow-up data was received by searching our follow-up database called “PC-follow”. We revealed that CCND1 expression patterns were different between cytoplasm and nucleus in this study, and the expression of CCND1 in adjacent normal tissues was higher than that in PCa tissues (P<0.001), while nuclear CCND1 showed the opposite distribution characteristic (P<0.001). The cytoplasmic CCND1 also showed correlation with several clinical factors, e.g., tumor T stage (P<0.001), Gleason score (P=0.028), positive surgical margin (P=0.037), and capsule invasion (P=0.04). We also revealed that cytoplasmic CCND1 is a protective prognostic factor in the biochemical recurrence (BCR) free time analysis (P=0.002). However, the nuclear CCND1 showed no correlation with clinical factors or prognostic value in this study. This study found that cytoplasmic and nuclear CCND1 have significant different expression patterns in PCa tissues, and cytoplasmic CCND1 has a certain prognostic value in the BCR analysis

A Novel Urine Exosomal lncRNA Assay to Improve the Detection of Prostate Cancer at Initial Biopsy: A Retrospective Multicenter Diagnostic Feasibility Study

Purpose: This study aimed at developing and validating a novel noninvasive urinary exosome-based post-DRE (digital rectal examination) lncRNA assay to diagnose PCa (prostate cancer) and clinically significant PCa (Gleason score ≥ 7) from the initial prostate biopsy. Methods: A total of 602 urine samples from eligible participants were collected. The expression levels of urinary exosomal PCA3 (prostate cancer antigen 3) and MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) were detected by qPCR (quantitative real-time PCR). Receiver operating characteristic (ROC) analysis was applied to evaluate the diagnostic performance of PCA3, MALAT1 and the lncRNA assay. A decision curve analysis (DCA) and waterfall plots were used to assess the clinical value of the lncRNA assay. Results: Urinary exosomal PCA3 and MALAT1 were overexpressed in PCa and clinically significant PCa (p &lt; 0.001). The lncRNA assay combining PCA3 and MALAT1 had a better diagnostic performance (AUC 0.828) than the current clinical parameters in detecting PCa. More importantly, the lncRNA assay yielded an AUC of 0.831 to detect clinically significant PCa, which is much higher than that of the current clinical parameters. The lncRNA assay was superior to PSA, f/tPSA and the base model for detecting PCa and clinically significant PCa, with a higher net benefit for almost all threshold probabilities. At the cutoff value of 95% sensitivity, the lncRNA assay could avoid 24.2% unnecessary biopsies while only missing 1.2% of the cases of clinically significant PCa. Conclusion: We developed and validated a novel noninvasive post-DRE urine-based lncRNA assay that presented good diagnostic power and clinical utility for the early diagnosis of PCa and high-grade PCa

A new phase of solid iodine with different molecular covalent bonds

There is a great interest in the behavior of diatomic molecular solids under extremely high-pressure conditions that lead to pressure-induced metallization, molecular dissociation, and formation of atomic phase. The consensus has been that the phase-transition sequence that happened in both solid bromine and iodine is from a molecular phase (phase I), to an incommensurate phase (phase V), and then to an atomic phase (phase II), with increasing pressure. However, a puzzle remains unresolved for both solids: pressure-induced X and Y bands were observed in the Raman spectra in the molecular phase at low pressures, even before the onset of phase V. Here, we suggest a phase for solid iodine in such a low-pressure range (designated as phase I′) in which two different covalent intramolecular bonds coexist, based on first-principles calculations and later corroborated by x-ray diffraction experiments. The pressure dependence of the X and Y bands and other vibrational frequencies measured experimentally can be explained nicely by combining the vibrational modes of phase I and phase I′. These results help improve our understanding on the pressure-induced molecular dissociation and metallization in diatomic solids and may shed some light on the investigation of similar phenomena in solid H2

FASN Protein Overexpression Indicates Poor Biochemical Recurrence-Free Survival in Prostate Cancer

Backgrounds. Fatty acid synthase (FASN) has been regarded as a prognostic marker in prostate cancer (PCa). In this study, we evaluated FASN expression at both mRNA and protein levels and assessed the association between FASN expression and prognosis in male Han Chinese with PCa treated with radical prostatectomy (RP). Methods. Expression profile and prognostic value of FASN were analyzed in tissue microarray (TMA) and data retrieved from databases including TCGA public database, GEO database, and our sequencing data with whole clinicopathological characteristics. Results. FASN expression was associated with clinical parameters and biochemical recurrence of prostate cancer. The relative expression of FASN mRNA was higher in the tumor tissue in all public databases and our sequencing data (p<0.001). A similar result was seen in tissue microarray (TMA) (p<0.001). Analysis of our sequencing data indicated that FASN’s relative expression was associated with tumor stage (p=0.048), and FASN expression was positively associated with the Gleason score (p=0.004) and seminal vesicle invasion (p=0.011) in TMA. We found that high FASN expression was an independent predictor of shorter BCR-free survival with univariate and multivariate survival analysis (p<0.05), rendering FASN an optimal prognostic biomarker in male Han Chinese with prostate cancer. Conclusions. Our study demonstrated that FASN was overexpressed at mRNA and protein levels in PCa. We found that patients with high FASN expression had a shorter BCR-free survival, showing its value as a prognostic biomarker in male Han Chinese with PCa

Oncogenic Roles of Laminin Subunit Gamma‐2 in Intrahepatic Cholangiocarcinoma via Promoting EGFR Translation

Abstract Intrahepatic cholangiocarcinoma (iCCA) is a highly lethal biliary epithelial cancer in the liver. Here, Laminin subunit gamma‐2 (LAMC2) with important oncogenic roles in iCCA is discovered. In a total of 231 cholangiocarcinoma patients (82% of iCCA patients) across four independent cohorts, LAMC2 is significantly more abundant in iCCA tumor tissue compared to normal bile duct and non‐tumor liver. Among 26.3% of iCCA patients, LAMC2 gene is amplified, contributing to its over‐expression. Functionally, silencing LAMC2 significantly blocks tumor formation in orthotopic iCCA mouse models. Mechanistically, it promotes EGFR protein translation via interacting with nascent unglycosylated EGFR in the endoplasmic reticulum (ER), resulting in activated EGFR signaling. LAMC2‐mediated EGFR translation also depends on its interaction with the ER chaperone BiP via their C‐terminus. Together LAMC2 and BiP generate a binding “pocket” of nascent EGFR and facilitate EGFR translation. Consistently, LAMC2‐high iCCA patients have poor prognosis in two iCCA cohorts. LAMC2‐high iCCA cells are highly sensitive to EGFR tyrosine kinase inhibitors (TKIs) treatment both in vitro and in vivo. Together, these data demonstrate LAMC2 as an oncogenic player in iCCA by promoting EGFR translation and an indicator to identify iCCA patients who may benefit from available EGFR‐targeted TKIs therapies