Bioinformatics analysis of oxidative stress genes in the pathogenesis of ulcerative colitis based on a competing endogenous RNA regulatory network.

Background: Ulcerative colitis (UC) is a common chronic disease associated with inflammation and oxidative stress. This study aimed to construct a long noncoding RNA (lncRNA)-microRNA (miRNA)-messenger RNA (mRNA) network based on bioinformatics analysis and to explore oxidative stress-related genes underlying the pathogenesis of UC. Methods: The GSE75214, GSE48959, and GSE114603 datasets were downloaded from the Gene Expression Omnibus database. Following differentially expressed (DE) analysis, the regulatory relationships among these DERNAs were identified through miRDB, miRTarBase, and TargetScan; then, the lncRNA-miRNA-mRNA network was established. The Molecular Signatures Database (MSigDB) was used to search oxidative stress-related genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed for functional annotation and enrichment analyses. Based on the drug gene interaction database DGIdb, drugs that interact with oxidative stress-associated genes were explored. A dextran sulfate sodium (DSS)-induced UC mouse model was used for experimental validation. Results: A total of 30 DE-lncRNAs, 3 DE-miRNAs, and 19 DE-mRNAs were used to construct a lncRNA-miRNA-mRNA network. By comparing these 19 DE-mRNAs with oxidative stress-related genes in MSigDB, three oxidative stress-related genes (CAV1, SLC7A11, and SLC7A5) were found in the 19 DEM sets, which were all negatively associated with miR-194. GO and KEGG analyses showed that CAV1, SLC7A11, and SLC7A5 were associated with immune inflammation and steroid hormone synthesis. In animal experiments, the results showed that dexamethasone, a well-known glucocorticoid drug, could significantly decrease the expression of CAV1, SLC7A11, and SLC7A5 as well as improve UC histology, restore antioxidant activities, inhibit inflammation, and decrease myeloperoxidase activity. Conclusion: SLC7A5 was identified as a representative gene associated with glucocorticoid therapy resistance and thus may be a new therapeutic target for the treatment of UC in the clinic.

Comparing Ultrasound and MRI Evaluations of the Hamstring Tendon for Predicting Autograft Size in Anterior Cruciate Ligament Reconstruction.

Background: Adequate graft size and length are crucial factors in anterior cruciate ligament (ACL) reconstruction. Accurate identification of patients who may be at risk for an insufficient length or size of the hamstring tendon (HT) can aid surgeons in preoperative planning. Purpose: To evaluate whether magnetic resonance imaging (MRI) or ultrasound could more accurately predict the size of the semitendinosus tendon (ST) and gracilis tendon (GT) and to investigate the correlation between anthropometry, graft size, and imaging measurements to find a predictive formula. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Included in the study were 36 patients who underwent ACL reconstruction with HT autograft at our institution between July 2021 and May 2022. Anthropometric data and MRI and ultrasound measurements were collected preoperatively. The length and diameter of the HT were recorded intraoperatively. Correlations between anthropometry, graft size, and imaging measurements were analyzed. Linear regression analysis was performed to construct a prediction formula. Results: The intraoperative graft diameters of the ST and GT were weakly to moderately associated with their cross-sectional areas as measured by MRI and ultrasound. MRI and ultrasound interpreted 11.9% to 15.7% and 18.4% to 41.7% of the variation in the graft diameter of the HT, with an accuracy of 50.0% to 55.6% and 69.4% to 86.1%, respectively. The intraoperative lengths of the ST and GT were both associated with patient height and tendon lengths as measured by ultrasound. Additionally, intraoperative GT length was associated with patient weight. Four formulas combining relevant anthropometric parameters and imaging measurements were calculated from multilinear regression analysis, explaining up to 46.3% of the variance in the size of HT. Conclusion: Ultrasound and MRI alone showed limited ability to predict the graft diameter of the ST and GT, while ultrasound could more accurately predict the graft size than MRI. Among the different anthropometric variables, height was the most influential in predicting tendon length.

An Integrated Solution to FIB-Induced Hydride Artifacts in Pure Zirconium.

The preparation method of transmission electron microscopy (TEM) samples for pure zirconium was successfully executed using a focused ion beam (FIB) system. These samples unveiled artifact hydrides induced during the FIB sample preparation process, which resulted from stress damage, ion implantation, and ion irradiation. An innovative solution was proposed to effectively reduce the effect of artifact hydrides for FIB-prepared samples of hydrogen-sensitive materials, such as zirconium alloys. This development lays the groundwork for further research on the micro/nanostructures of zirconium alloys after ion irradiation, thereby facilitating the study of corrosion mechanisms and the prediction of service life for nuclear fuel cladding materials. Furthermore, the solution proposed in this study is also applicable to TEM sample preparation using FIB for other hydrogen-sensitive materials such as titanium, magnesium, and palladium.

Enhancing lymph node metastasis prediction in adenocarcinoma of the esophagogastric junction: A study combining radiomic with clinical features.

BACKGROUND: The incidence of adenocarcinoma of the esophagogastric junction (AEJ) is increasing, and with poor prognosis. Lymph node status (LNs) is particularly important for planning treatment and evaluating the prognosis of patients with AEJ. However, the use of radiomic based on enhanced computed tomography (CT) to predict the preoperative lymph node metastasis (PLNM) status of the AEJ has yet to be reported. PURPOSE: We sought to investigate the value of radiomic features based on enhanced CT in the accurate prediction of PLNM in patients with AEJ. METHODS: Clinical features and enhanced CT data of 235 patients with AEJ from October 2017 to May 2023 were retrospectively analyzed. The data were randomly assigned to the training cohort (n = 164) or the external testing cohort (n = 71) at a ratio of 7:3. A CT-report model, clinical model, radiomic model, and radiomic-clinical combined model were developed to predict PLNM in patients with AEJ. Univariate and multivariate logistic regression were used to screen for independent clinical risk factors. Least absolute shrinkage and selection operator (LASSO) regression was used to select the radiomic features. Finally, a nomogram for the preoperative prediction of PLNM in AEJ was constructed by combining Radiomics-score and clinical risk factors. The models were evaluated by area under the receiver operating characteristic curve (AUC-ROC), calibration curve, and decision curve analyses. RESULTS: A total of 181 patients (181/235, 77.02%) had LNM. In the testing cohort, the AUC of the radiomic-clinical model was 0.863 [95% confidence interval (CI) = 0.738-0.957], and the radiomic model (0.816; 95% CI = 0.681-0.929), clinical model (0.792; 95% CI = 0.677-0.888), and CT-report model (0.755; 95% CI = 0.647-0.840). CONCLUSION: The radiomic-clinical model is a feasible method for predicting PLNM in patients with AEJ, helping to guide clinical decision-making and personalized treatment planning.

Recent Innovations and Technical Advances in High-Throughput Parallel Single-Cell Whole-Genome Sequencing Methods.

Single-cell whole-genome sequencing (scWGS) detects cell heterogeneity at the aspect of genomic variations, which are inheritable and play an important role in life processes such as aging and cancer progression. The recent explosive development of high-throughput single-cell sequencing methods has enabled high-performance heterogeneity detection through a vast number of novel strategies. Despite the limitation on total cost, technical advances in high-throughput single-cell whole-genome sequencing methods are made for higher genome coverage, parallel throughput, and level of integration. This review highlights the technical advancements in high-throughput scWGS in the aspects of strategies design, data efficiency, parallel handling platforms, and their applications on human genome. The experimental innovations, remaining challenges, and perspectives are summarized and discussed.

PGD: Shared gene linking polycystic ovary syndrome and endometrial cancer, influencing proliferation and migration through glycometabolism.

The relationship among polycystic ovary syndrome (PCOS), endometrial cancer (EC), and glycometabolism remains unclear. We explored shared genes between PCOS and EC, using bioinformatics to unveil their pathogenic connection and influence on EC prognosis. Gene Expression Omnibus datasets GSE226146 (PCOS) and GSE196033 (EC) were used. A protein-protein interaction (PPI) network was constructed to identify the central genes. Candidate markers were screened using dataset GSE54250. Differences in marker expression were confirmed in mouse PCOS and human EC tissues using RT-PCR and immunohistochemistry. The effect of PGD on EC proliferation and migration was explored using Ki-67 and Transwell assays. PGD's impact on the glycometabolic pathway within carbon metabolism was assessed by quantifying glucose content and lactic acid production. R software identified 31 common genes in GSE226146 and GSE196033. Gene Ontology functional classification revealed enrichment in the "purine nucleoside triphosphate metabolism process," with key Kyoto Encyclopedia of Genes and Genomes pathways related to "carbon metabolism." The PPI network identified 15 hub genes. HK2, NDUFS8, PHGDH, PGD, and SMAD3 were confirmed as candidate markers. The RT-PCR analysis validated distinct HK2 and PGD expression patterns in mouse PCOS ovarian tissue and human EC tissue, as well as in normal and EC cells. Transfection experiments with Ishikawa cells further confirmed PGD's influence on cell proliferation and migration. Suppression of PGD expression impeded glycometabolism within the carbon metabolism of EC cells, suggesting PGD as a significant PCOS risk factor impacting EC proliferation and migration through modulation of single carbon metabolism. These findings highlight PGD's pivotal role in EC onset and prognosis.

The Distribution and Host-Association of the Vector Chigger Species Leptotrombidium imphalum in Southwest China.

Leptotrombidium imphalum is a species of chigger mites, and it can serve as a transmitting vector of scrub typhus. Southwest China is an important focus of scrub typhus. Based on the field investigation in southwest China from 2001 to 2022, this article presents the first report on the distribution and infestation of L. imphalum on rodents and other sympatric small mammals in the region. A total of 2161 L. imphalum were identified from 218 small mammal hosts in 21 of 114 survey sites. The 17 host species of L. imphalum crossed 13 genera and 5 families in 3 orders (Rodentia, Eulipotyphla, and Scandentia), indicating the low host specificity of the mite. The Asian house rat (Rattus tanezumi) was the dominant host species in the 21 sites where L. imphalum were collected, and 49.38% of mites were found on R. tanezumi. Different small mammals had different susceptibility to the infestation of L. imphalum. The prevalence (PM = 27.66%), infestation mean abundance (MA = 6 mites/per examined host), and mean intensity (MI = 21.69 mites/per infested host) for L. imphalum on the shrew gymnure (Neotetracus sinensis) were much higher than those on other host species (p < 0.05), indicating N. sinensis had a high susceptibility to the infestation of L. imphalum. The infestation indices for L. imphalum on small mammal hosts varied along different altitude and latitude gradients (p < 0.05), indicating the environmental heterogeneity of the mite infestation. Leptotrombidium imphalum exhibited an aggregated distribution among different individuals of its hosts. Besides the low host specificity of L. imphalum, the prevalence of the mite was positively correlated with the occurrence of scrub typhus, indicating the potential risk of the mite.

Knowledge mapping of exosomes in prostate cancer from 2003 to 2022: a bibliometric analysis.

BACKGROUND: Prostate cancer (PCa) is highly prevalent among males worldwide. The investigation of exosomes in PCa has emerged as a dynamic and important research area. To visually depict the prominent research areas and evolutionary patterns of exosomes in PCa, we performed a comprehensive analysis via bibliometric methods. METHODS: Studies were retrieved from the Web of Science Core Collection. CiteSpace, VOSviewers, and the R package "bibliometrix" were employed to analyze the relationships and collaborations among countries/regions, organizations, authors, journals, references, and keywords. RESULTS: Over the past 20 years (2003-2022), 995 literatures on exosomes in PCa have been collected. The findings indicate a consistent upward trend in annual publications with the United States being the leading contributor. Cancers is widely recognized as the most prominent journal in this area. In total, 5936 authors have contributed to these publications, with Alicia Llorente being the most prolific. The primary keywords associated with research hotspots include "liquid biopsy", "identification", "growth", "microRNAs", and "tumor-derived exosomes". CONCLUSION: Our analysis reveals that investigating the intrinsic mechanisms of exosomes in PCa pathogenesis and exploring the potential of exosomes as biomarkers of PCa constitute the principal focal points in this domain of research.

Global trends and insights in ethical statements regarding the utilization of human cadaveric tissues for biomechanical research from 2017 to 2022: a bibliometric analysis.

Human cadaveric tissues are essential for biomechanical research, however, omitting statements regarding the ethical implications remains very common in many recent articles of biomechanics. We systematically searched PubMed for research articles published from 2017 to 2022 to identify all relevant studies (n=1850). Information on the characteristics of the cadaveric specimens and the acquisition of ethical approval was collected. The included articles were categorized as grade A (n=757), grade B (n=308), and grade C (n=785) according to our predetermined criteria. Additionally, we analyzed whether the reporting status of ethical approval varied based on publishing year, journals, regions, and research settings. No significant improvement was observed over the study period. Disparities in ethical reporting standards were identified among different regions and journals. This is the first bibliometric analysis that offers an overview of publications in biomechanical research that use human cadaveric samples. It serves as a reference for interested researchers and journal readers to discuss the associated ethical issues.

Validity of stem cell-loaded scaffolds to facilitate endometrial regeneration and restore fertility: a systematic review and meta-analysis.

Objective: Various stem cell-loaded scaffolds have demonstrated promising endometrial regeneration and fertility restoration. This study aimed to evaluate the efficacy of stem cell-loaded scaffolds in treating uterine injury in animal models. Methods: The PubMed, Embase, Scopus, and Web of Science databases were systematically searched. Data were extracted and analyzed using Review Manager version 5.4. Improvements in endometrial thickness, endometrial glands, fibrotic area, and number of gestational sacs/implanted embryos were compared after transplantation in the stem cell-loaded scaffolds and scaffold-only group. The standardized mean difference (SMD) and confidence interval (CI) were calculated using forest plots. Results: Thirteen studies qualified for meta-analysis. Overall, compared to the scaffold groups, stem cell-loaded scaffolds significantly increased endometrial thickness (SMD = 1.99, 95% CI: 1.54 to 2.44, P < 0.00001; I² = 16%) and the number of endometrial glands (SMD = 1.93, 95% CI: 1.45 to 2.41, P < 0.00001; I² = 0). Moreover, stem cell-loaded scaffolds present a prominent effect on improving fibrosis area (SMD = -2.50, 95% CI: -3.07 to -1.93, P < 0.00001; I² = 36%) and fertility (SMD = 3.34, 95% CI: 1.58 to 5.09, P = 0.0002; I² = 83%). Significant heterogeneity among studies was observed, and further subgroup and sensitivity analyses identified the source of heterogeneity. Moreover, stem cell-loaded scaffolds exhibited lower inflammation levels and higher angiogenesis, and cell proliferation after transplantation. Conclusion: The evidence indicates that stem cell-loaded scaffolds were more effective in promoting endometrial repair and restoring fertility than the scaffold-only groups. The limitations of the small sample sizes should be considered when interpreting the results. Thus, larger animal studies and clinical trials are needed for further investigation. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42024493132.

Oral appliance therapy vs. positional therapy for managing positional obstructive sleep apnea; a systematic review and meta-analysis of randomized control trials.

AIM: To assess the efficacy of positional therapy and oral appliance therapy for the management of positional obstructive sleep apnea. METHODS: We searched PubMed, Web of Science, Cochrane, and SCOPUS for relevant clinical trials. Quality assessment of the included trials was evaluated according to Cochrane's risk of bias tool. We included the following outcomes: The apnea-hypopnea index (AHI), AHI non-supine, AHI supine, sleep efficiency, percentage of supine sleep, Adherence (≥ 4 h/night, ≥ 5 days/week), Oxygen desaturation Index, Arousal Index, Epworth Sleepiness Scale score (ESS), Mean SpO2, and Functional Outcomes of Sleep Questionnaire. RESULTS: The AHI non-supine and the ESS scores were significantly lower in the OAT cohort than in the PT cohort. The PT cohort was associated with a significantly decreased percentage of supine sleep than the OAT cohort (MD= -26.07 [-33.15, -19.00], P = 0.0001). There was no significant variation between PT cohort and OAT cohort regarding total AHI, AHI supine, ODI, sleep efficiency, arousal index, FOSQ, adherence, and mean SpO2. CONCLUSION: Both Positional Therapy and Oral Appliance Therapy effectively addressed Obstructive Sleep Apnea. However, Oral Appliance Therapy exhibited higher efficiency, leading to increased supine sleep percentage and more significant reductions in the Apnea Hypopnea Index during non-supine positions, as well as lower scores on the Epworth Sleepiness Scale.

The Integration of Systematic Pharmacology and Experimental Validation to Explain the Mechanism of Action of Wuling Capsule in the Treatment of NAFLD.

BACKGROUND: Wuling capsule is a traditional Chinese medicine composed of four herbals. It has been widely used to treat chronic active hepatitis and has shown significant efficacy in hyperlipidemia. However, the treatment of NAFLD disease has not been studied in depth. METHODS: Firstly, the potential bioactive compounds in Wuling capsules were identified by TCMSP (https://old.tcmsp-e.com/tcmsp.php). Secondly， the pathway and GO function were analyzed by using the DAVID database (https://david.ncifcrf.gov/). Then, the molecular docking techniques were used to confirm the accuracy of binding between key targets and components. Furthermore, the experimental pharmacology validation was conducted using RT-qPCR and WB of the NAFLD model. RESULTS: A total of 138 active compounds and 40 common potential targets associated with NAFLD were identified through network pharmacology. The pathway and functional enrichment analysis showed that the Wuling capsule was associated with the PI3K-AKT and HIF-1α signaling pathways. In vivo experiments showed that the Wuling capsule could reduce IL-6, TNF-α, and HIF-1α proteins and up-regulate STAT3 and VEGFA levels (P < 0.05), thus alleviating liver inflammation. CONCLUSIONS: With the support of network pharmacology and animal experiments, the study preliminarily investigated the effect of the Wuling capsule on liver inflammation by regulating the HIF-1α signaling pathway, thereby protecting liver function and treating NAFLD.

Double-Level Knee Derotational Osteotomy Yields Better Postoperative Outcomes Than Tibial Tubercle Transfer Combined With Medial Patellofemoral Ligament Reconstruction in Patients With Recurrent Patellar Instability and Severe Malrotation.

PURPOSE: To assess the postoperative outcomes of double-level knee derotational osteotomy (KDRO) combined with medial patellofemoral ligament reconstruction (MPFLR) and to compare it with tibial tuber transfer (TTT) and MPFLR without derotational osteotomy in patients with recurrent patellar instability and a marked torsional deformity. METHODS: From March 2020 to December 2021, patients with torsion deformity (combined femoral torsion [FT] and tibial torsion [TTn] ≥30°) were retrospectively included. The minimum follow-up time was 18 months. Patients who received KDRO and MPFLR were categorized as the KDRO group and patients who received a combined TTT and MPFLR were categorized as the control group. Preoperative and postoperative clinical symptoms, patient-reported outcomes (Kujala, visual analog scale, Lysholm, International Knee Documentation Committee, Tegner, and Knee Injury and Osteoarthritis Outcome scores), and imaging parameters (FT, TTn, patellar height, femoral trochlear dysplasia, congruence angle, patellar tilt angle, lateral patellar angle, lateral patellar translation, and tibial tubercle-trochlear groove distance) were analyzed. RESULTS: In all, 36 patients were included with 18 in KDRO group and 18 in control group. The mean follow-up time was 30 (range 21-39) months. At the latest follow-up, no patient experienced redislocation in either group. Except for the FT and TTn in the control group, postoperative imaging parameters were significantly reduced to the normal range. KDRO group had a lower patellar tilt angle (P = .043, effect size 0.64). All clinical scores in both groups significantly improved postoperatively. The KDRO group had better functional scores than control group except the KOOS daily living activities subscore and the KOOS sports and recreation subscore. More patients in the KDRO group met the minimal clinically important difference for most patient-reported outcomes than the control group. Eight patients (44%) in the control group complained of postoperative anterior knee pain, compared with 1 patient (6%) in the KDRO group (P = .018). CONCLUSIONS: KDRO combined with MPFLR was associated with better postoperative outcomes than TTT combined with MPFLR in patients with recurrent patellar instability and a torsion deformity. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Fibroblast expression of transmembrane protein smoothened governs microenvironment characteristics after acute kidney injury.

The smoothened (Smo) receptor facilitates hedgehog signaling between kidney fibroblasts and tubules during acute kidney injury (AKI). Tubule-derived hedgehog is protective in AKI, but the role of fibroblast-selective Smo is unclear. Here, we report that Smo-specific ablation in fibroblasts reduced tubular cell apoptosis and inflammation, enhanced perivascular mesenchymal cell activities, and preserved kidney function after AKI. Global proteomics of these kidneys identified extracellular matrix proteins, and nidogen-1 glycoprotein in particular, as key response markers to AKI. Intriguingly, Smo was bound to nidogen-1 in cells, suggesting that loss of Smo could affect nidogen-1 accessibility. Phosphoproteomics revealed that the 'AKI protector' Wnt signaling pathway was activated in these kidneys. Mechanistically, nidogen-1 interacted with integrin ß1 to induce Wnt in tubules to mitigate AKI. Altogether, our results support that fibroblast-selective Smo dictates AKI fate through cell-matrix interactions, including nidogen-1, and offers a robust resource and path to further dissect AKI pathogenesis.

Intra-Articular Platelet-Rich Plasma Injection After Anterior Cruciate Ligament Reconstruction: A Randomized Clinical Trial.

Importance: Platelet-rich plasma (PRP) has been considered a promising treatment for musculoskeletal disorders. The effects of PRP on clinical outcomes of anterior cruciate ligament reconstruction (ACLR) are controversial. Objective: To compare subjective outcomes and graft maturity in patients undergoing ACLR with and without postoperative intra-articular PRP injection. Design, Setting, and Participants: This surgeon- and investigator-masked randomized clinical trial included patients treated at a national medical center in China who were aged 16 to 45 years and scheduled to undergo ACLR. Participants were enrolled between March 21, 2021, and August 18, 2022, and followed up for 12 months, with the last participant completing follow-up on August 28, 2023. Interventions: Participants were randomized 1:1 to the PRP group (n = 60), which received 3 doses of postoperative intra-articular PRP injection at monthly intervals, or to the control group (n = 60), which did not receive postoperative PRP injection. Both groups had the same follow-up schedule. Main Outcomes and Measures: The primary outcome was the mean score for 4 subscales of the Knee Injury and Osteoarthritis Outcome Score (KOOS4) (range, 0-100, with higher scores indicating better knee function and fewer symptoms) at 12 months postoperatively. Secondary outcomes were patient-reported outcomes, graft maturity (on magnetic resonance imaging), and physical examinations at 3, 6, and 12 months. Results: Among the 120 randomized participants (mean [SD] age, 29.0 [8.0] years; 84 males [70%]), 114 (95%) were available for the primary outcome analysis. The mean KOOS4 scores at 12 months were 78.3 (SD, 12.0; 95% CI, 75.2-81.4) in the PRP group and 76.8 (SD, 11.9; 95% CI, 73.7-79.9) in the control group (adjusted mean between-group difference, 2.0; 95% CI, -2.3 to 6.3; P = .36). Secondary outcomes were not statistically significantly different between the 2 groups except for sports and recreation level and graft maturity at 6 months. Intervention-related adverse events included pain at the injection site and knee swelling after injection. Conclusions and Relevance: In this randomized clinical trial among patients undergoing ACLR, the addition of postoperative intra-articular PRP injection did not result in superior improvement of knee symptoms and function at 12 months compared with no postoperative injection. Further studies are required to determine appropriate indications for PRP in musculoskeletal disorders. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2000040262.

Application of Deferoxamine in Tissue Regeneration Attributed to Promoted Angiogenesis.

Deferoxamine, an iron chelator used to treat diseases caused by excess iron, has had a Food and Drug Administration-approved status for many years. A large number of studies have confirmed that deferoxamine can reduce inflammatory response and promote angiogenesis. Blood vessels play a crucial role in sustaining vital life by facilitating the delivery of immune cells, oxygen, and nutrients, as well as eliminating waste products generated during cellular metabolism. Dysfunction in blood vessels may contribute significantly to the development of life-threatening diseases. Anti-angiogenesis therapy and pro-angiogenesis/angiogenesis strategies have been frequently recommended for various diseases. Herein, we describe the mechanism by which deferoxamine promotes angiogenesis and summarize its application in chronic wounds, bone repair, and diseases of the respiratory system. Furthermore, we discuss the drug delivery system of deferoxamine for treating various diseases, providing constructive ideas and inspiration for the development of new treatment strategies.

Development and validation of a nomogram to predict lymph node metastasis in patients with progressive muscle-invasive bladder cancer.

Purpose: To develop and validate a nomogram for preoperative prediction of lymph node metastasis in patients with progressive muscle-invasive bladder cancer. Materials and methods: We retrospectively recruited patients, divided them into training and validation cohorts, and gathered patient demographics, pathology data of transurethral bladder tumor resection specimens, imaging findings, and laboratory information. We performed logistic regression analyses, both single-variable and multi-variable, to investigate independent preoperative risk variables and develop a nomogram. Both internal and external validations were conducted to evaluate the predictive performance of this nomogram. Results: The training cohort consisted of 144 patients with advanced muscle-invasive bladder cancer, while the validation cohort included 62 individuals. The independent preoperative risk factors identified were tumor pathology grade, platelet count, tumor size on imaging, and lymph node size, which were utilized to develop the nomogram. The model demonstrated high predictive accuracy, as evidenced by the area under the receiver operating characteristic curve values of 0.898 and 0.843 for the primary and external validation cohorts, respectively. Calibration curves and decision curve analysis showed a good performance of the nomogram in both cohorts, indicating its high clinical applicability. Conclusion: A nomogram for preoperative prediction of lymph node metastasis in patients with advanced muscle-invasive bladder cancer was successfully developed; its accuracy, reliability, and clinical value were demonstrated. This new tool would facilitate better clinical decisions regarding whether to perform complete lymph node dissection in cases of radical cystectomy.

T2-weighted imaging-based radiomic-clinical machine learning model for predicting the differentiation of colorectal adenocarcinoma.

BACKGROUND: The study on predicting the differentiation grade of colorectal cancer (CRC) based on magnetic resonance imaging (MRI) has not been reported yet. Developing a non-invasive model to predict the differentiation grade of CRC is of great value. AIM: To develop and validate machine learning-based models for predicting the differentiation grade of CRC based on T2-weighted images (T2WI). METHODS: We retrospectively collected the preoperative imaging and clinical data of 315 patients with CRC who underwent surgery from March 2018 to July 2023. Patients were randomly assigned to a training cohort (n = 220) or a validation cohort (n = 95) at a 7:3 ratio. Lesions were delineated layer by layer on high-resolution T2WI. Least absolute shrinkage and selection operator regression was applied to screen for radiomic features. Radiomics and clinical models were constructed using the multilayer perceptron (MLP) algorithm. These radiomic features and clinically relevant variables (selected based on a significance level of P < 0.05 in the training set) were used to construct radiomics-clinical models. The performance of the three models (clinical, radiomic, and radiomic-clinical model) were evaluated using the area under the curve (AUC), calibration curve and decision curve analysis (DCA). RESULTS: After feature selection, eight radiomic features were retained from the initial 1781 features to construct the radiomic model. Eight different classifiers, including logistic regression, support vector machine, k-nearest neighbours, random forest, extreme trees, extreme gradient boosting, light gradient boosting machine, and MLP, were used to construct the model, with MLP demonstrating the best diagnostic performance. The AUC of the radiomic-clinical model was 0.862 (95%CI: 0.796-0.927) in the training cohort and 0.761 (95%CI: 0.635-0.887) in the validation cohort. The AUC for the radiomic model was 0.796 (95%CI: 0.723-0.869) in the training cohort and 0.735 (95%CI: 0.604-0.866) in the validation cohort. The clinical model achieved an AUC of 0.751 (95%CI: 0.661-0.842) in the training cohort and 0.676 (95%CI: 0.525-0.827) in the validation cohort. All three models demonstrated good accuracy. In the training cohort, the AUC of the radiomic-clinical model was significantly greater than that of the clinical model (P = 0.005) and the radiomic model (P = 0.016). DCA confirmed the clinical practicality of incorporating radiomic features into the diagnostic process. CONCLUSION: In this study, we successfully developed and validated a T2WI-based machine learning model as an auxiliary tool for the preoperative differentiation between well/moderately and poorly differentiated CRC. This novel approach may assist clinicians in personalizing treatment strategies for patients and improving treatment efficacy.

Long-read single-cell RNA sequencing enables the study of cancer subclone-specific genotype and phenotype in chronic lymphocytic leukemia.

Bruton's tyrosine kinase (BTK) inhibitors are effective for the treatment of chronic lymphocytic leukemia (CLL) due to BTK's role in B cell survival and proliferation. Treatment resistance is most commonly caused by the emergence of the hallmark BTKC481S mutation that inhibits drug binding. In this study, we aimed to investigate whether the presence of additional CLL driver mutations in cancer subclones harboring a BTKC481S mutation accelerates subclone expansion. In addition, we sought to determine whether BTK-mutated subclones exhibit distinct transcriptomic behavior when compared to other cancer subclones. To achieve these goals, we employ our recently published method (Qiao et al. 2024) that combines bulk DNA sequencing and single-cell RNA sequencing (scRNA-seq) data to genotype individual cells for the presence or absence of subclone-defining mutations. While the most common approach for scRNA-seq includes short-read sequencing, transcript coverage is limited due to the vast majority of the reads being concentrated at the priming end of the transcript. Here, we utilized MAS-seq, a long-read scRNAseq technology, to substantially increase transcript coverage across the entire length of the transcripts and expand the set of informative mutations to link cells to cancer subclones in six CLL patients who acquired BTKC481S mutations during BTK inhibitor treatment. We found that BTK-mutated subclones often acquire additional mutations in CLL driver genes, leading to faster subclone proliferation. When examining subclone-specific gene expression, we found that in one patient, BTK-mutated subclones are transcriptionally distinct from the rest of the malignant B cell population with an overexpression of CLL-relevant genes.

Prevalent arbuscular mycorrhizae in roots and highly variable mycobiome in leaves of epiphytic subtropical fern Ophioderma pendulum.

PREMISE: Endophytic and mycorrhizal fungi are crucial in facilitating plant nutrition acquisition and stress tolerance. In epiphytic habitats, plants face nutrition and water stress, but their roots are mostly nonmycorrhizal and especially lacking in arbuscular mycorrhizal associations. Ophioderma pendulum is an epiphytic fern with a partially mycoheterotrophic lifestyle, likely heavily reliant on symbiotic fungi. To characterize fungal associations in the sporophyte of O. pendulum, we focused on leaves and roots of O. pendulum, seeking to reveal the fungal communities in these organs. METHODS: Roots and leaves from O. pendulum in a subtropical forest were examined microscopically to observe the morphology of fungal structures and determine the percentage of various fungal structures in host tissues. Fungal composition was profiled using metabarcoding techniques that targeted ITS2 of the nuclear ribosomal DNA. RESULTS: Roots were consistently colonized by arbuscular mycorrhizal fungi (Glomeromycota), especially Acaulospora. Unlike previous findings on epiphytic ferns, dark septate endophytes were rare in O. pendulum roots. Leaves were predominantly colonized by Ascomycota fungi, specifically the classes Dothideomycetes (46.88%), Eurotiomycetes (11.51%), Sordariomycetes (6.23%), and Leotiomycetes (6.14%). Across sampling sites, fungal community compositions were similar in the roots but differed significantly in the leaves. CONCLUSIONS: Ophioderma pendulum maintains stable, single-taxon-dominant communities in the roots, primarily featuring arbuscular mycorrhizal fungi, whereas the leaves may harbor opportunistic fungal colonizers. Our study underlines the significance of mycorrhizal fungi in the adaptation of epiphytic ferns.