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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 -
Bone Jun 2024Greater white matter hyperintensities (WMH) in older adults have been associated with reduced bone mineral density (BMD) and increased fractures and falls. However, it...
PURPOSE
Greater white matter hyperintensities (WMH) in older adults have been associated with reduced bone mineral density (BMD) and increased fractures and falls. However, it is unclear whether there is a causal relationship between BMD reduction and WMH. In this study, Mendelian randomization (MR) was used to find the causality between WMH and estimated BMD (eBMD).
METHODS
We performed a two-sample bidirectional MR analysis using statistical data obtained from publicly available genome-wide association studies (GWAS). The main method of MR analysis is the inverse-variance weighted (IVW) method. To identify and account for the impact of horizontal pleiotropy, we also employed MR-Egger regression, MR pleiotropy residual sum, and outlier (MR-PRESSO).
RESULTS
MR analysis found a causal relationship between eBMD and WMH (IVW OR = 0.938, 95 % CI: 0.889-0.990, p = 0.020). Our causal estimates are unlikely to be distorted by horizontal pleiotropy according to heterogeneity test (both p > 0.05) and MR-Egger regression (p > 0.05). However, in the reverse MR analysis, there was no evidence that WMH was causally correlated with eBMD (IVW OR = 0.979, 95 % CI: 0.954-1.005, p = 0.109).
CONCLUSION
Our results suggest that low eBMD increased the risk of WMH; conversely, no evidence that WMH causally affects eBMD was found.
PubMed: 38914213
DOI: 10.1016/j.bone.2024.117138 -
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 -
European Spine Journal : Official... Jun 2024The role of basal metabolic rate (BMR) in intervertebral disc degeneration (IVDD) is still uncertain. To address this gap, we conducted a Mendelian randomization (MR)...
BACKGROUND
The role of basal metabolic rate (BMR) in intervertebral disc degeneration (IVDD) is still uncertain. To address this gap, we conducted a Mendelian randomization (MR) study to comprehensively explore the causal relationship between BMR and IVDD.
METHODS
BMR data were obtained from a large genome-wide association study (GWAS) database, while IVDD data were derived from the FinnGen project. The causal relationship between IVDD and BMR was investigated using MR, with inverse-variance weighting (IVW) as the primary estimate. MR-Egger weighed median and weighed mode were employed for robustness. Sensitivity analyses, including the Cochran Q test, leave-one-out analysis, and MR-Egger intercept analysis, were conducted. Furthermore, the study also identified causal relationships between IVDD and factors associated with BMR (hyperthyroidism, type 2 diabetes, standing height, weight, and body mass index). Multivariable MR was applied to further assess the direct effect of BMR on IVDD.
RESULTS
Genetic predisposition to BMR (after removing outliers OR: 1.49; 95% CI: 1.37-1.63; P = 5.073e-21) were associated with an increased risk of IVDD. Additionally, IVDD risk increased with greater height, weight, and BMI. No causal relationship was observed between hy/thy and T2D and intervertebral disc degeneration (IVDD) (P > 0.05). In multivariable MR, a significant causal association between BMR and IVDD persisted, even after adjusting for BMI, height, and weight.
CONCLUSION
In this study, we successfully identified that a higher BMR is independently and causally linked to IVDD, indicating an increased risk of developing IVDD. These findings suggest that managing BMR could potentially mitigate the risk of IVDD.
PubMed: 38910168
DOI: 10.1007/s00586-024-08367-7 -
Scientific Reports Jun 2024Type II diabetes mellitus (T2DM) is a rising global health burden due to its rapidly increasing prevalence worldwide, and can result in serious complications. Therefore,...
Type II diabetes mellitus (T2DM) is a rising global health burden due to its rapidly increasing prevalence worldwide, and can result in serious complications. Therefore, it is of utmost importance to identify individuals at risk as early as possible to avoid long-term T2DM complications. In this study, we developed an interpretable machine learning model leveraging baseline levels of biomarkers of oxidative stress (OS), inflammation, and mitochondrial dysfunction (MD) for identifying individuals at risk of developing T2DM. In particular, Isolation Forest (iForest) was applied as an anomaly detection algorithm to address class imbalance. iForest was trained on the control group data to detect cases of high risk for T2DM development as outliers. Two iForest models were trained and evaluated through ten-fold cross-validation, the first on traditional biomarkers (BMI, blood glucose levels (BGL) and triglycerides) alone and the second including the additional aforementioned biomarkers. The second model outperformed the first across all evaluation metrics, particularly for F1 score and recall, which were increased from 0.61 ± 0.05 to 0.81 ± 0.05 and 0.57 ± 0.06 to 0.81 ± 0.08, respectively. The feature importance scores identified a novel combination of biomarkers, including interleukin-10 (IL-10), 8-isoprostane, humanin (HN), and oxidized glutathione (GSSG), which were revealed to be more influential than the traditional biomarkers in the outcome prediction. These results reveal a promising method for simultaneously predicting and understanding the risk of T2DM development and suggest possible pharmacological intervention to address inflammation and OS early in disease progression.
Topics: Diabetes Mellitus, Type 2; Humans; Biomarkers; Machine Learning; Oxidative Stress; Male; Female; Middle Aged; Risk Assessment; Risk Factors; Blood Glucose; Inflammation; Algorithms
PubMed: 38909127
DOI: 10.1038/s41598-024-65044-x -
Public Health Jun 2024To describe the trends in the nature of general practices in Scotland between 2014/15 and 2023.
OBJECTIVES
To describe the trends in the nature of general practices in Scotland between 2014/15 and 2023.
STUDY DESIGN
Descriptive ecological study.
METHODS
We obtained data from Public Health Scotland and used general practitioner (GP) practice codes, practice names, and the General Medical Council (GMC) numbers of their listed GPs to describe trends in practice characteristics and to identify individual practices that were likely to be operating as a single entity.
RESULTS
Defining practice entities is difficult because different GP practice codes are often retained when GPs are performing across multiple practices. If GP practice codes alone are used, the median practice list size increased from 5094 to 5881, and the mean from 5588 to 6289, between 2013/14 and 2020/21. There was one outlier practice that grew to have over 45,000 patients registered by 2020/21. However, this underestimates the extent of this new mega-practice phenomenon. Using the GMC numbers of GPs listed as performers to identify where the same GPs are working across multiple GP practice codes, we identified a series of mega-practices that span across health board areas and which have experienced a dramatic increase in their list size (with the two largest having list sizes of over 101,000 and 77,000 patients, respectively).
CONCLUSIONS
Further research is needed to better understand: how mega-practices provide services and whether this differs from other practices; where financial rewards accumulate within mega-practices; differences in staffing between mega-practices and other models; and the impacts mega-practices have on the quality and continuity of care and on health and inequality outcomes.
PubMed: 38908308
DOI: 10.1016/j.puhe.2024.05.026 -
Aesthetic Plastic Surgery Jun 2024Plastic surgeons increasingly use social media to market their practices and educate prospective patients. Previous studies have investigated plastic surgery content on...
BACKGROUND
Plastic surgeons increasingly use social media to market their practices and educate prospective patients. Previous studies have investigated plastic surgery content on Instagram from the angle of hashtags and most popular plastic surgeons. However, very little is understood about what plastic surgeons themselves post on Instagram and what plastic surgery content average users engage with.
OBJECTIVES
The aim of this study was to analyze Instagram posts from accounts related to plastic surgeons in the USA to establish suggestions for growing one's practice with this powerful platform to reach patients.
METHODS
Board-certified plastic surgeons from all US regions that were active from February 1, 2023 to April 12, 2023 were randomly chosen. Their Instagram accounts were accessed for post analysis. For procedural posts, engagement statistics and multiple variables were collected. Dixon's outlier test was used to determine outliers in the data. ANCOVA and Tukey analysis was used to determine whether procedure type influenced engagement.
RESULTS
120 surgeon accounts were identified with 2157 posts analyzed, yielding notable differences in posts among regions. Most posts were aesthetic procedures (94.4%) and of female patients (90.3%). Surgical procedures were also predominant (86.1%). In addition, Reels had higher engagement than photograph posts. Users engaged with Body procedures at the highest rate.
CONCLUSIONS
This cross-sectional analysis shows plastic surgeons tend to overwhelmingly post female patients, aesthetic procedures, and surgical content. These insights may be used to guide social media content and improve the effectiveness of Instagram as a tool for marketing or education.
LEVEL OF EVIDENCE IV
This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
PubMed: 38907051
DOI: 10.1007/s00266-024-04144-5 -
European Journal of Vascular and... Jun 2024Complex abdominal aortic aneurysms (cAAA) pose a clinical challenge. The aim of this study was to assess the 30 day mortality and morbidity for open aneurysm repair...
OBJECTIVE
Complex abdominal aortic aneurysms (cAAA) pose a clinical challenge. The aim of this study was to assess the 30 day mortality and morbidity for open aneurysm repair (OAR) and fenestrated/branched endovascular aortic repair (F/BEVAR), and the effect of hospital volume in patients with asymptomatic cAAA in Switzerland.
METHODS
Retrospective, cohort study using data from Switzerland's national registry for vascular surgery, Swissvasc, including patients treated from 1 January 2019 to 31 December 2022. All patients with asymptomatic, true, non-infected cAAA were identified. Primary outcome was 30 day mortality and morbidity reported using the Clavien-Dindo classification. Outcomes were compared between OAR and F/BEVAR after propensity score weighting.
RESULTS
Of the 461 patients identified, 333 underwent OAR and 128 underwent F/BEVAR for cAAA. At 30 days, overall mortality rate was 3.3% after OAR and 3.1% after F/BEVAR (p = .76). Propensity scores weighted analysis indicated similar morbidity rates for both approaches: F/BEVAR (OR 0.69, 95% CI 0.45 - 1.05, p = .055); intestinal ischaemia (1.8% after OAR, 3.1% after F/BEVAR, p = .47) and renal failure requiring dialysis (1.5% after OAR, 5.5% after F/BEVAR, p = .024) were associated with highest morbidity and mortality. Treatment specific complications with high morbidity were abdominal compartment syndrome and lower limb compartment syndrome following F/BEVAR. Overall treatment volume was low for most of the hospitals treating cAAA in Switzerland; outliers with increased mortality were identified among low volume hospitals.
CONCLUSION
Comparable 30 day mortality and morbidity rates were found between OAR and F/BEVAR for cAAA in Switzerland; lack of centralisation was also highlighted. Organ specific complications driving mortality were renal failure, intestinal ischaemia, and limb ischaemia, specifically after F/BEVAR. Treatment in specialised high volume centres, alongside efforts to reduce peri procedural kidney injury and mesenteric ischaemia, offers potential to lower morbidity and mortality in elective cAAA treatment.
PubMed: 38906370
DOI: 10.1016/j.ejvs.2024.06.022