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Genes Jun 2024Recent research has highlighted associations between sleep and microbial taxa and pathways. However, the causal effect of these associations remains unknown. To...
Recent research has highlighted associations between sleep and microbial taxa and pathways. However, the causal effect of these associations remains unknown. To investigate this, we performed a bidirectional two-sample Mendelian randomization (MR) analysis using summary statistics of genome-wide association studies (GWAS) from 412 gut microbiome traits (N = 7738) and GWAS studies from seven sleep-associated traits (N = 345,552 to 386,577). We employed multiple MR methods to assess causality, with Inverse Variance Weighted (IVW) as the primary method, alongside a Bonferroni correction (( < 2.4 × 10) to determine significant causal associations. We further applied Cochran's Q statistical analysis, MR-Egger intercept, and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) for heterogeneity and pleiotropy assessment. IVW estimates revealed 79 potential causal effects of microbial taxa and pathways on sleep-related traits and 45 inverse causal relationships, with over half related to pathways, emphasizing their significance. The results revealed two significant causal associations: genetically determined relative abundance of pentose phosphate decreased sleep duration ( = 9.00 × 10), and genetically determined increase in fatty acid level increased the ease of getting up in the morning ( = 8.06 × 10). Sensitivity analyses, including heterogeneity and pleiotropy tests, as well as a leave-one-out analysis of single nucleotide polymorphisms, confirmed the robustness of these relationships. This study explores the potential causal relationships between sleep and microbial taxa and pathways, offering novel insights into their complex interplay.
Topics: Humans; Mendelian Randomization Analysis; Gastrointestinal Microbiome; Genome-Wide Association Study; Sleep; Polymorphism, Single Nucleotide; Causality
PubMed: 38927705
DOI: 10.3390/genes15060769 -
Genes Jun 2024Uterine pathologies pose a challenge to women's health on a global scale. Despite extensive research, the causes and origin of some of these common disorders are not... (Comparative Study)
Comparative Study
Uterine pathologies pose a challenge to women's health on a global scale. Despite extensive research, the causes and origin of some of these common disorders are not well defined yet. This study presents a comprehensive analysis of transcriptome data from diverse datasets encompassing relevant uterine pathologies such as endometriosis, endometrial cancer and uterine leiomyomas. Leveraging the Comparative Analysis of Shapley values (CASh) technique, we demonstrate its efficacy in improving the outcomes of the classical differential expression analysis on transcriptomic data derived from microarray experiments. CASh integrates the microarray game algorithm with Bootstrap resampling, offering a robust statistical framework to mitigate the impact of potential outliers in the expression data. Our findings unveil novel insights into the molecular signatures underlying these gynecological disorders, highlighting CASh as a valuable tool for enhancing the precision of transcriptomics analyses in complex biological contexts. This research contributes to a deeper understanding of gene expression patterns and potential biomarkers associated with these pathologies, offering implications for future diagnostic and therapeutic strategies.
Topics: Female; Humans; Transcriptome; Endometriosis; Leiomyoma; Gene Expression Profiling; Endometrial Neoplasms; Uterine Neoplasms; Uterine Diseases; Algorithms
PubMed: 38927658
DOI: 10.3390/genes15060723 -
Aging Jun 2024Iridocyclitis and the use of glucocorticoid medication have been widely studied as susceptibility factors for cataracts. However, the causal relationship between them...
Iridocyclitis and the use of glucocorticoid medication have been widely studied as susceptibility factors for cataracts. However, the causal relationship between them remains unclear. This study aimed to investigate the causal relationship between the development of iridocyclitis and the genetic liability of glucocorticoid medication use on the risk of senile cataracts occurrence by performing Two-sample Mendelian randomization (MR) analyses. Instrumental variables (IVs) significantly associated with exposure factors (P < 5 × 10) were identified using published genome-wide association data from the FinnGen database and UK Biobank. Reliability analyses were conducted using five approaches, including inverse-variance weighted (IVW), MR-Egger regression, simple median, weighted median, and weighted mode. A sensitivity analysis using the leave-one-out method was also performed. Genetic susceptibility to glucocorticoid use was associated with an increased risk of developing senile cataracts (OR, 1.10; 95% CI, 1.02-1.17; P < 0.05). Moreover, iridocyclitis was significantly associated with a higher risk of developing senile cataracts (OR, 1.03; 95% CI, 1.01-1.05; P < 0.05). Nonetheless, some heterogeneity in the IVs was observed, but the MR results remained consistent after penalizing for outliers. The estimates were consistent in multivariate analyses by adjusting for body mass index (BMI) and diabetes mellitus type 2 (T2DM). This study provides new insights into the prevention and management of senile cataracts by highlighting the increased risk associated with iridocyclitis and the use of glucocorticoids.
PubMed: 38925660
DOI: 10.18632/aging.205963 -
Journal of Imaging May 2024Hyperspectral images include information from a wide range of spectral bands deemed valuable for computer vision applications in various domains such as agriculture,...
Hyperspectral images include information from a wide range of spectral bands deemed valuable for computer vision applications in various domains such as agriculture, surveillance, and reconnaissance. Anomaly detection in hyperspectral images has proven to be a crucial component of change and abnormality identification, enabling improved decision-making across various applications. These abnormalities/anomalies can be detected using background estimation techniques that do not require the prior knowledge of outliers. However, each hyperspectral anomaly detection (HS-AD) algorithm models the background differently. These different assumptions may fail to consider all the background constraints in various scenarios. We have developed a new approach called Greedy Ensemble Anomaly Detection (GE-AD) to address this shortcoming. It includes a greedy search algorithm to systematically determine the suitable base models from HS-AD algorithms and hyperspectral unmixing for the first stage of a stacking ensemble and employs a supervised classifier in the second stage of a stacking ensemble. It helps researchers with limited knowledge of the suitability of the HS-AD algorithms for the application scenarios to select the best methods automatically. Our evaluation shows that the proposed method achieves a higher average F1-macro score with statistical significance compared to the other individual methods used in the ensemble. This is validated on multiple datasets, including the Airport-Beach-Urban (ABU) dataset, the San Diego dataset, the Salinas dataset, the Hydice Urban dataset, and the Arizona dataset. The evaluation using the airport scenes from the ABU dataset shows that GE-AD achieves a 14.97% higher average F1-macro score than our previous method (HUE-AD), at least 17.19% higher than the individual methods used in the ensemble, and at least 28.53% higher than the other state-of-the-art ensemble anomaly detection algorithms. As using the combination of greedy algorithm and stacking ensemble to automatically select suitable base models and associated weights have not been widely explored in hyperspectral anomaly detection, we believe that our work will expand the knowledge in this research area and contribute to the wider application of this approach.
PubMed: 38921608
DOI: 10.3390/jimaging10060131 -
Metabolites May 2024It was pointed out to us that we had not followed exactly the IROA TruQuant IQQ Workflow Kit protocol in the experimental part of our work [...].
It was pointed out to us that we had not followed exactly the IROA TruQuant IQQ Workflow Kit protocol in the experimental part of our work [...].
PubMed: 38921481
DOI: 10.3390/metabo14060293 -
PloS One 2024This study developed and validated a surgical instrument motion measurement system for skill evaluation during practical laparoscopic surgery training. Owing to the...
This study developed and validated a surgical instrument motion measurement system for skill evaluation during practical laparoscopic surgery training. Owing to the various advantages of laparoscopic surgery including minimal invasiveness, this technique has been widely used. However, expert surgeons have insufficient time for providing training to beginners due to the shortage of surgeons and limited working hours. Skill transfer efficiency has to be improved for which there is an urgent need to develop objective surgical skill evaluation methods. Therefore, a simple motion capture-based surgical instrument motion measurement system that could be easily installed in an operating room for skill assessment during practical surgical training was developed. The tip positions and orientations of the instruments were calculated based on the marker positions attached to the root of the instrument. Because the patterns of these markers are individual, this system can track multiple instruments simultaneously and detect exchanges. However due to the many obstacles in the operating room, the measurement data included noise and outliers. In this study, the effect of this decrease in measurement accuracy on feature calculation was determined. Accuracy verification experiments were conducted during wet-lab training to demonstrate the capability of this system to measure the motion of surgical instruments with practical accuracy. A surgical training experiment on a cadaver was conducted, and the motions of six surgical instruments were measured in 36 cases of laparoscopic radical nephrectomy. Outlier removal and smoothing methods were also developed and applied to remove the noise and outliers in the obtained data. The questionnaire survey conducted during the experiment confirmed that the measurement system did not interfere with the surgical operation. Thus, the proposed system was capable of making reliable measurements with minimal impact on surgery. The system will facilitate surgical education by enabling the evaluation of skill transfer of surgical skills.
Topics: Laparoscopy; Humans; Clinical Competence; Surgical Instruments; Motion; Cadaver; Nephrectomy
PubMed: 38917181
DOI: 10.1371/journal.pone.0305693 -
Journal of Obstetrics and Gynaecology :... Dec 2024Ovarian cancer stands as a highly aggressive malignancy. The core aim of this investigation is to uncover genes pivotal to the progression and prognosis of ovarian...
BACKGROUND
Ovarian cancer stands as a highly aggressive malignancy. The core aim of this investigation is to uncover genes pivotal to the progression and prognosis of ovarian cancer, while delving deep into the intricate mechanisms that govern their impact.
METHODS
The study entailed the retrieval of RNA-seq data and survival data from the XENA database. Outliers were meticulously excluded in accordance with TCGA guidelines and through principal components analysis. The R package 'deseq2' was harnessed to extract differentially expressed genes. WGCNA was employed to prioritise these genes, and Cox regression analysis and survival analysis based on disease-specific time were conducted to identify significant genes. Immunohistochemistry validation was undertaken to confirm the distinct expression of USP43. Furthermore, the influence of USP43 on the biological functions of ovarian cancer cells was explored using techniques such as RNA interference, western blotting, scratch assays, and matrigel invasion assays. The examination of immune infiltration was facilitated via CIBERSORT.
RESULTS
The study unearthed 5195 differentially expressed genes between ovarian cancer and normal tissue, comprising 3416 up-regulated and 1779 down-regulated genes. WGCNA pinpointed 204 genes most intimately tied to tumorigenesis. The previously undisclosed gene USP43 exhibited heightened expression in tumour tissues and exhibited associations with overall survival and disease-specific survival. USP43 emerged as a driver of cell migration (43.27 ± 3.91% vs 19.69 ± 1.94%) and invasion ability (314 ± 32 vs 131 ± 12) through the mechanism of epithelial mesenchymal transition, potentially mediated by the KRAS pathway. USP43 was also identified as a booster of CD4+ T memory resting cell infiltration, while concurrently reducing M1 macrophages within cancer, thereby fostering a milieu with relatively immune suppressive traits. Interestingly, USP43 demonstrated connections with epigenetically regulated-mRNAsi, although not with mRNAsi.
CONCLUSION
This study underscores the role of USP43 in facilitating tumour migration and invasion. It postulates USP43 as a novel therapeutic target for ovarian cancer treatment.
Topics: Female; Humans; Ovarian Neoplasms; Ubiquitin-Specific Proteases; Gene Expression Regulation, Neoplastic; Cystadenocarcinoma, Serous; Cell Line, Tumor; Prognosis; Cell Movement; Epithelial-Mesenchymal Transition; Survival Analysis; Clinical Relevance
PubMed: 38916982
DOI: 10.1080/01443615.2024.2361862 -
Frontiers in Endocrinology 2024This study aims to investigate the impacts of phimosis on the health of the genitourinary system through Mendelian random analysis.
PURPOSE
This study aims to investigate the impacts of phimosis on the health of the genitourinary system through Mendelian random analysis.
MATERIAL AND METHOD
A dual-sample Mendelian randomization (MR) analysis was conducted using the publicly available genome-wide association study (GWAS) data. The inverse variance weighted based on the random effects model (Re-IVW) method was used as the main statistical analysis. Complementary methods, including weighted median, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO), were applied to detect or correct the impact of horizontal pleiotropy.
RESULT
Re-IVW showed a genetic predictive causal relationship of phimosis on glomerulonephritis (odds ratio [OR]: 1.37 [1.13-1.65], = 0.00149) and IgA glomerulonephritis (OR: 1.57 [1.18-2.09), = 0.00187). Suggestive evidence indicated that phimosis was associated with chronic nephritis syndrome (OR: 1.23 (1.00-1.51), p = 0.0481], acute nephritis syndrome (OR: 1.50 [1.13-2.01], = 0.0058), and impotence (OR: 1.39 [1.11-1.73], = 0.0035). Kidney and ureteral stone (OR: 1.14 [1.04-1.26], = 0.0069), urethral strictures (OR: 1.26 [1.07-1.48], = 0.0050), benign prostatic hyperplasia (OR: 1.07 [1.01-1.13], = 0.0242), and decreased testicular function (OR: 0.72 [0.56-0.94], = 0.0141) have genetically predictive causal relationships.
CONCLUSION
In summary, we employed a series of reliable analytical methods to investigate the association between phimosis and 26 urogenital diseases. We have reported several strong associations, but more research is needed to evaluate whether this discovery is replicated in other environments and to gain a better understanding of potential mechanisms.
Topics: Humans; Mendelian Randomization Analysis; Male; Genome-Wide Association Study; Phimosis; Female Urogenital Diseases; Polymorphism, Single Nucleotide; Genetic Predisposition to Disease
PubMed: 38915890
DOI: 10.3389/fendo.2024.1308270 -
Physics and Imaging in Radiation... Apr 2024Magnetic Resonance Imaging (MRI) guided stereotactic body radiotherapy (SBRT) of liver metastases is an upcoming high-precision non-invasive treatment. Interobserver...
BACKGROUND AND PURPOSE
Magnetic Resonance Imaging (MRI) guided stereotactic body radiotherapy (SBRT) of liver metastases is an upcoming high-precision non-invasive treatment. Interobserver variation (IOV) in tumor delineation, however, remains a relevant uncertainty for planning target volume (PTV) margins. The aims of this study were to quantify IOV in MRI-based delineation of the gross tumor volume (GTV) of liver metastases and to detect patient-specific factors influencing IOV.
MATERIALS AND METHODS
A total of 22 patients with liver metastases from three primary tumor origins were selected (colorectal(8), breast(6), lung(8)). Delineation guidelines and planning MRI-scans were provided to eight radiation oncologists who delineated all GTVs. All delineations were centrally peer reviewed to identify outliers not meeting the guidelines. Analyses were performed both in- and excluding outliers. IOV was quantified as the standard deviation (SD) of the perpendicular distance of each observer's delineation towards the median delineation. The correlation of IOV with shape regularity, tumor origin and volume was determined.
RESULTS
Including all delineations, average IOV was 1.6 mm (range 0.6-3.3 mm). From 160 delineations, in total fourteen single delineations were marked as outliers after peer review. After excluding outliers, the average IOV was 1.3 mm (range 0.6-2.3 mm). There was no significant correlation between IOV and tumor origin or volume. However, there was a significant correlation between IOV and regularity (Spearman's ρ = -0.66; p = 0.002).
CONCLUSION
MRI-based IOV in tumor delineation of liver metastases was 1.3-1.6 mm, from which PTV margins for IOV can be calculated. Tumor regularity and IOV were significantly correlated, potentially allowing for patient-specific margin calculation.
PubMed: 38912009
DOI: 10.1016/j.phro.2024.100592 -
Journal of Orthopaedic Case Reports Jun 2024The use of image-free robotic systems for total knee arthroplasty (TKA) is gaining popularity. Although the surgical transepicondylar axis (sTEA) is considered the...
Precise Calibration of Femoral Component Rotation Using the Posterior Condylar Axis as a Reference during Image-free Robot-assisted Total Knee Arthroplasty: A Technical Note.
INTRODUCTION
The use of image-free robotic systems for total knee arthroplasty (TKA) is gaining popularity. Although the surgical transepicondylar axis (sTEA) is considered the optimal femoral rotational reference during TKA, it is difficult to define intra-operatively. Conventional and image-free robot-assisted TKA (RA-TKA) therefore rely on the use of Whiteside's axis (WSA) or the posterior condylar axis (PCA) as surrogate references. The PCA is considered to be associated with less variability than the WSA. The authors present a simple technique to permit calibration of femoral component rotation (FCR) using the PCA as a reference for image-free robotic systems that do not permit this option.
TECHNIQUE
The image-free robotic systems used by the authors (Navio and CORI, Smith and Nephew, Memphis, TN, USA) permit calibration of FCR only when the perpendicular to WSA is used as a reference. When the PCA is selected as a reference, a fixed 3° of external rotation is set by the robot. The technique proposed by the authors involves the use of the former setting, followed by internal rotation of the perpendicular to the WSA to co-align it with the PCA. The planning menu subsequently permits virtual surgical planning using the PCA as the femoral rotational reference and permits adjustments in rotational positioning of the femoral component while displaying the effect of rotation on bony resection and vice versa in real time. In addition, coaligning the perpendicular to the anatomic trans-epicondylar axis (aTEA) displays the internal rotation of the PCA with respect to the aTEA. This information can be used for setting rotational boundaries with respect to the PCA while using various alternate alignment strategies, like functional alignment, since the relation between the aTEA and sTEA is less likely to be affected by dyplasia and wear when compared with the PCA or WSA.
CONCLUSION
This simple technique permits optimally calibrated rotational positioning of the femoral component during image-free RA-TKA, using the PCA as a reference. It can be applied for optimizing surgery in knees with altered or outlier anatomy, as well as routinely, especially when alternate alignment strategies are used.
PubMed: 38910981
DOI: 10.13107/jocr.2024.v14.i06.4548