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This study addresses the diagnostic and therapeutic challenges in malignant melanoma (MM) and non-melanoma skin cancers (NMSC). We aim to identify circulating proteins causally linked to MM and NMSC traits using a multicenter Mendelian randomization (MR) framework. We utilized large-scale cis-MR to estimate the impact of numerous plasma proteins on MM, NMSC, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC). To ensure robustness, additional analyses like MR Steiger and Bayesian colocalization are conducted, followed by replication through meta-analytical methods. The associations between identified proteins and outcomes are also validated at the tissue level using Transcriptome-Wide Association Study methods. Furthermore, a protein-protein interaction analysis is conducted to explore the relationship between identified proteins and existing cancer medication targets. The MR analysis has identified associations of 13 plasma proteins with BCC, 2 with SCC, and 1 with MM. Specifically, ASIP and KRT5 are associated with BCC, with ASIP also potentially targeting MM. CTSS and TNFSF8 are identified as promising druggability candidates for BCC. This multidimensional approach nominates ASIP, KRT5, CTSS, and TNFSF8 as potential diagnostic and therapeutic targets for skin cancers. This study suggests that the circulating proteins ASIP, KRT5, CTSS, and TNFSF8 are causally associated with melanoma and non-melanoma skin cancer-related traits through a multicenter Mendelian randomization. [ABSTRACT FROM AUTHOR]

Previous evidence has suggested that childhood sunburn could be a risk factor for cutaneous malignant melanoma (MM) and non-melanoma skin cancer (NMSC). However, existing observational studies could not reveal the causal associations genetically. This study aimed to investigate whether there was a genetic causal relationship between childhood sunburn and skin cancers. Univariable Mendelian randomization (MR) and Causal Analysis Using Summary Effect analysis was carried out for causal estimates and evaluation for the horizontal pleiotropy. Multivariable MR and the mediation effects analysis were used to test whether the causal associations were mediated by potential confounders. A suggestively significant causal association between childhood sunburn and MM was indicated (OR = 4.74; 95% CI: 1.31–17.19; p = 1.79E-02). Genetically predicted childhood sunburn was significantly associated with increased risk of overall melanoma in situ (MIS) (OR = 4.02; 95% CI: 2.00–8.08; p = 9.40E-05), MIS of face (OR = 18.28; 95% CI: 5.28–63.35; p = 4.59E-06), and MIS of trunk (OR = 7.05; 95% CI: 2.06–24.13; p = 1.88E-03). Similar trends were found for childhood sunburn and NMSC (OR = 8.16; 95% CI: 6.07–10.99; p = 1.53E-20), including both basal cell carcinoma (BCC) (OR = 3.76; 95% CI:2.96–4.77; p = 2.19E-08) and squamous cell carcinoma (SCC) (OR = 7.44; 95% CI: 5.09–10.87; p = 2.19E-08). After adjustment for hair and skin color, facial ageing, vitamin D levels, body mass index, alcohol consumption, and smoking status, childhood sunburn showed an independent association with MIS, MIS of face, MIS of trunk, as well as NMSC, including both BCC and SCC. Mediation analysis showed no significant mediation effect. This study demonstrated a causal relationship between childhood sunburn and the risk of both MM and NMSC, which suggested that enhanced screening and prevention for childhood sunburn could contribute to the early detection and decreased risk of MM and NMSC. [ABSTRACT FROM AUTHOR]

Coronary arteries have high curvatures, and hence, flow through them causes disturbed flow patterns, resulting in stenosis and atherosclerosis. This in turn decreases the myocardial flow perfusion, causing myocardial ischemia and infarction. Therefore, in order to understand the mechanisms of these phenomena caused by high curvatures and branching of coronary arteries, we have conducted elaborate hemodynamic analysis for both (i) idealized coronary arteries with geometrical parameters representing realistic curvatures and stenosis and (ii) patient-specific coronary arteries with stenoses. Firstly, in idealized coronary arteries with approximated realistic arterial geometry representative of their curvedness and stenosis, we have computed the hemodynamic parameters of pressure drop, wall shear stress (WSS) and wall pressure gradient (WPG), and their association with the geometrical parameters of curvedness and stenosis. Secondly, we have similarly determined the wall shear stress and wall pressure gradient distributions in four patient-specific curved stenotic right coronary arteries (RCAs), which were reconstructed from medical images of patients diagnosed with atherosclerosis and stenosis; our results show high WSS and WPG regions at the stenoses and inner wall of the arterial curves. This paper provides useful insights into the causative mechanisms of the high incidence of atherosclerosis in coronary arteries. It also provides guidelines for how simulation of blood flow in patient's coronary arteries and determination of the hemodynamic parameters of WSS and WPG can provide a medical assessment of the risk of development of atherosclerosis and plaque formation, leading to myocardial ischemia and infarction. The novelty of our paper is in our showing how in actual coronary arteries (based on their CT imaging) curvilinearity and narrowing complications affect the computed WSS and WPG, associated with risk of atherosclerosis. This is very important for cardiologists to be able to properly take care of their patients and provide remedial measures before coronary complications lead to myocardial infarctions and necessitate stenting or coronary bypass surgery. We want to go one step further and provide clinical application of our research work. For that, we are offering to cardiologists worldwide to carry out hemodynamic analysis of the medically imaged coronary arteries of their patients and compute the values of the hemodynamic parameters of WSS and WPG, so as to provide them an assessment of the risk of atherosclerosis for their patients. Graphical abstract Theme and aims: Coronary arteries have high curvatures, and hence flow through them causes disturbed flow patterns, resulting in stenosis and atherosclerosis. This in turn decreases the myocardial flow perfusion, causing myocardial ischemia and infarction. Therefore, in order to understand the mechanisms of these phenomena caused by high curvatures and branching of coronary arteries, we have conducted elaborate hemodynamic analysis for both (i) idealized coronary arteries with geometrical parameters representing curvatures and stenosis, and (ii) patient-specific coronary arteries with stenoses. Methods and results: Firstly, in idealized coronary arteries with approximated realistic arterial geometry representative of their curvedness and stenosis, we have computed the hemodynamic parameters of pressure drop, wall shear stress (WSS) and wall pressure gradient (WPG), and their association with the geometrical parameters of curvedness and stenosis. Then, we have determined the wall shear stress and wall pressure gradient distributions in four patient-specific curved stenotic right coronary arteries (RCAs), that were reconstructed from medical images of patients diagnosed with atherosclerosis and stenosis, as illustrated in Figure 1, in which the locations of the stenoses are highlighted by arrows. Figure 1: Three-dimensional CT visualization of arteries in patients with suspected coronary disease. The arteries can be seen as a combination of various curved segments with stenoses at unspecific locations highlighted by arrows. Our results show high WSS and WPG regions at the stenoses and inner wall of the arterial curves, as depicted in Figure 2. Therein, the encapsulations show (i) high WSS, and (ii) high WPG regions at the stenosis and inner wall of the arterial curves. Figure 2: WSS and WPG surface plot of realistic arteries (a), (b), (c) and (d), wherein the small squared parts are enlarged to show the detailed localized contour plots at the stenotic regions. Therein, the circular encapsulations show (i) high WSS and (ii) high WPG regions at the stenosis and inner wall of the arterial curves. Conclusion and novelty: This paper provides useful insights into the causative mechanisms of the high incidence of atherosclerosis in coronary arteries. It also provides guidelines for how simulation of blood flow in patient coronary arteries and determination of the hemodynamic parameters of WSS and WPG can provide a medical assessment of the risk of development of atherosclerosis and plaque formation, leading to myocardial ischemia and infarction. The novelty of our paper is our showing how in actual coronary arteries (based on their CT imaging), curvilinearity and narrowing complications affect the computed WSS and WPG associated with risk of atherosclerosis. This is very important for cardiologists to be able to properly take care of their patients and provide remedial measures before coronary complications lead to myocardial infarctions and necessitate stenting or coronary bypass surgery. [ABSTRACT FROM AUTHOR]

Cerebral glioma is one of the most aggressive space-occupying diseases, which will exhibit midline shift (MLS) due to mass effect. MLS has been used as an important feature for evaluating the pathological severity and patients' survival possibility. Automatic quantification of MLS is challenging due to deformation, complex shape and complex grayscale distribution. An automatic method is proposed and validated to estimate MLS in patients with gliomas diagnosed using magnetic resonance imaging (MRI). The deformed midline is approximated by combining mechanical model and local symmetry. An enhanced Voigt model which takes into account the size and spatial information of lesion is devised to predict the deformed midline. A composite local symmetry combining local intensity symmetry and local intensity gradient symmetry is proposed to refine the predicted midline within a local window whose size is determined according to the pinhole camera model. To enhance the MLS accuracy, the axial slice with maximum MSL from each volumetric data has been interpolated from a spatial resolution of 1 mm to 0.33 mm. The proposed method has been validated on 30 publicly available clinical head MRI scans presenting with MLS. It delineates the deformed midline with maximum MLS and yields a mean difference of 0.61 ± 0.27 mm, and average maximum difference of 1.89 ± 1.18 mm from the ground truth. Experiments show that the proposed method will yield better accuracy with the geometric center of pathology being the geometric center of tumor and the pathological region being the whole lesion. It has also been shown that the proposed composite local symmetry achieves significantly higher accuracy than the traditional local intensity symmetry and the local intensity gradient symmetry. To the best of our knowledge, for delineation of deformed midline, this is the first report on both quantification of gliomas and from MRI, which hopefully will provide valuable information for diagnosis and therapy. The study suggests that the size of the whole lesion and the location of tumor (instead of edema or the sum of edema and tumor) are more appropriate to determine the extent of deformation. Composite local symmetry is recommended to represent the local symmetry around the deformed midline. The proposed method could be potentially used to quantify the severity of patients with cerebral gliomas and other brain pathology, as well as to approximate midsagittal surface for brain quantification. [ABSTRACT FROM AUTHOR]

Sculpting pattern onto free-form surfaces is a potential method for many applications such as jewelry, glass blowmolding, injection molding, even automatically spray painting on the surfaces, etc. In this paper, a method of tool path generation for pattern sculpting on free-form surfaces is developed. First, 2D pattern is converted into discrete data points for tool path generation from digital image using image processing technique. To map the discrete pattern onto the part surface, mesh mapping is introduced, which is used for flattening the part surfaces onto a plane. On this plane, the discrete pattern is scaled, rotated, and translated to a desirable location. Then using the mapping of the part surface to the plane as a guide, the pattern to be sculpted is inversely mapped back onto the part surface. On this basis, according to the selected cutter and the depth of cut, the tool path is generated. Since the method does not rely on processing on the surface parametric domain, it is not limited to single surface patch, and is also equally applicable to multiple trimmed surfaces and mesh surfaces, etc. During calculation of the projected pattern, the proposed method does not involve any iterative numerical procedures, thus it is also robust and efficient. Finally, the method is implemented and tested on several typical examples to verify its validity. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the clinical efficacy and feasibility of one-stage surgical treatment for upper thoracic spinal tuberculosis by internal fixation, debridement, and combined interbody and posterior fusion via a posterior-only approach. Methods: Fourteen patients (eight males, six females) with upper thoracic tuberculosis whose lesions were confined to two adjacent segments were admitted to our hospital. Their ages ranged from 23 to 72 years (average, 50 years). The American Spinal Injury Association (ASIA) impairment scale was used to assess neurological function. ASIA classification showed that preoperatively, one patient was grade A, two patients were grade B, eight patients were grade C, and three patients were grade D. All patients were treated with one-stage surgical treatment by internal fixation, debridement, and combined interbody and posterior fusion via a posterior-only approach. Patients were evaluated preoperatively and postoperatively by measurement of thoracic kyphotic angles using Cobb angle evaluation, determination of erythrocyte sedimentation rate (ESR), evaluation of ASIA impairment scale, and radiological examination. Results: Operation time ranged from 70 to 135 min, (average, 110 min). Intraoperative blood loss ranged from 200 to 950 mL (average, 450 mL). All patients were followed up for 22 to 48 months postoperatively (average, 31.5 months). No sinus tract formation, cerebrospinal meningitis, or recurrence of tuberculosis occurred. All patients had significant postoperative improvement in ASIA classification scores. The thoracic kyphotic angles were significantly decreased to 12°-26° postoperatively, and at final follow-up were 13°-28°. The ESR recovered to normal within 6 months postoperatively in all patients. Bone fusion was achieved within 3-8 months (average, 5.5 months). Conclusions: One-stage surgical treatment for upper thoracic spinal tuberculosis by internal fixation, debridement, and combined interbody and posterior fusion via a posterior-only approach can be an effective and feasible treatment method. [ABSTRACT FROM AUTHOR]

The article presents a study which proposed a technique for the automatic detection of subarachnoid hemorrhage (SAH) on clinical non-contrast head computed tomography (CT) scans. Also cited are the proposed two steps in detecting SAH, including the identification of abnormality in the approximated subarachnoid space (SAS) through support vector machine (SVM) based pattern classification, and the components of the method including image preprocessing, brain segmentation, and feature extraction.

This paper presents an accurate and efficient method for the computation of both point projection and inversion onto Bézier surfaces. First, these two problems are formulated in terms of solution of a polynomial equation with u and v variables expressed in the Bernstein basis. Then, based on subdivision of the Bézier surface and the recursive quadtree decomposition, a novel solution method is proposed. The computation of point projection is shown to be equivalent to the geometrically intuitive intersection of asurface with the u-ν plane. Finally, by comparing the distances between the test point and the candidate points, the closest point is found. Examples illustrate the feasibility of this method. [ABSTRACT FROM AUTHOR]

Background: The potential effects of insulin therapy on osteoarthritis (OA) risk are poorly understood. This study aimed to explore the causal relationship between insulin therapy and OA.Mendelian randomization (MR) analysis was performed to examine the association between genetically proxied inhibition of insulin targets and the risk of overall, hip (HOA) and knee OA (KOA). We then performed univariable MR using summary statistics regarding insulin target genes derived from the DrugBank database. Data related to blood glucose reduction levels were used as a proxy for insulin levels. Two phenotypes, type 2 diabetes, and glycosylated hemoglobin levels, were selected as positive controls to confirm the direction and validity of the proxies. The OA datasets were derived from the UK Biobank cohort. Multivariable MR was adjusted for body mass index, sedentary behavior, cigarette smoking, frequency of alcohol intake, age, and genetic sex.Genetically proxied insulin therapy was associated with an increased risk of overall OA [odds ratio (OR):1.2595; 95% confidence interval (CI):1.0810–1.4675] and HOA (OR:1.4218; 95%CI:1.1240–1.7985), which remained consistent across multiple MR methods. After adjusting for confounders, we found evidence supporting a significant causal link with a higher risk of overall OA and HOA. A further two-step MR analysis revealed no significant mediation effects from the six mediators in the associations.There was a causal association between genetically proxied insulin therapy and a higher risk of OA, especially HOA.Methods: The potential effects of insulin therapy on osteoarthritis (OA) risk are poorly understood. This study aimed to explore the causal relationship between insulin therapy and OA.Mendelian randomization (MR) analysis was performed to examine the association between genetically proxied inhibition of insulin targets and the risk of overall, hip (HOA) and knee OA (KOA). We then performed univariable MR using summary statistics regarding insulin target genes derived from the DrugBank database. Data related to blood glucose reduction levels were used as a proxy for insulin levels. Two phenotypes, type 2 diabetes, and glycosylated hemoglobin levels, were selected as positive controls to confirm the direction and validity of the proxies. The OA datasets were derived from the UK Biobank cohort. Multivariable MR was adjusted for body mass index, sedentary behavior, cigarette smoking, frequency of alcohol intake, age, and genetic sex.Genetically proxied insulin therapy was associated with an increased risk of overall OA [odds ratio (OR):1.2595; 95% confidence interval (CI):1.0810–1.4675] and HOA (OR:1.4218; 95%CI:1.1240–1.7985), which remained consistent across multiple MR methods. After adjusting for confounders, we found evidence supporting a significant causal link with a higher risk of overall OA and HOA. A further two-step MR analysis revealed no significant mediation effects from the six mediators in the associations.There was a causal association between genetically proxied insulin therapy and a higher risk of OA, especially HOA.Results: The potential effects of insulin therapy on osteoarthritis (OA) risk are poorly understood. This study aimed to explore the causal relationship between insulin therapy and OA.Mendelian randomization (MR) analysis was performed to examine the association between genetically proxied inhibition of insulin targets and the risk of overall, hip (HOA) and knee OA (KOA). We then performed univariable MR using summary statistics regarding insulin target genes derived from the DrugBank database. Data related to blood glucose reduction levels were used as a proxy for insulin levels. Two phenotypes, type 2 diabetes, and glycosylated hemoglobin levels, were selected as positive controls to confirm the direction and validity of the proxies. The OA datasets were derived from the UK Biobank cohort. Multivariable MR was adjusted for body mass index, sedentary behavior, cigarette smoking, frequency of alcohol intake, age, and genetic sex.Genetically proxied insulin therapy was associated with an increased risk of overall OA [odds ratio (OR):1.2595; 95% confidence interval (CI):1.0810–1.4675] and HOA (OR:1.4218; 95%CI:1.1240–1.7985), which remained consistent across multiple MR methods. After adjusting for confounders, we found evidence supporting a significant causal link with a higher risk of overall OA and HOA. A further two-step MR analysis revealed no significant mediation effects from the six mediators in the associations.There was a causal association between genetically proxied insulin therapy and a higher risk of OA, especially HOA.Conclusion: The potential effects of insulin therapy on osteoarthritis (OA) risk are poorly understood. This study aimed to explore the causal relationship between insulin therapy and OA.Mendelian randomization (MR) analysis was performed to examine the association between genetically proxied inhibition of insulin targets and the risk of overall, hip (HOA) and knee OA (KOA). We then performed univariable MR using summary statistics regarding insulin target genes derived from the DrugBank database. Data related to blood glucose reduction levels were used as a proxy for insulin levels. Two phenotypes, type 2 diabetes, and glycosylated hemoglobin levels, were selected as positive controls to confirm the direction and validity of the proxies. The OA datasets were derived from the UK Biobank cohort. Multivariable MR was adjusted for body mass index, sedentary behavior, cigarette smoking, frequency of alcohol intake, age, and genetic sex.Genetically proxied insulin therapy was associated with an increased risk of overall OA [odds ratio (OR):1.2595; 95% confidence interval (CI):1.0810–1.4675] and HOA (OR:1.4218; 95%CI:1.1240–1.7985), which remained consistent across multiple MR methods. After adjusting for confounders, we found evidence supporting a significant causal link with a higher risk of overall OA and HOA. A further two-step MR analysis revealed no significant mediation effects from the six mediators in the associations.There was a causal association between genetically proxied insulin therapy and a higher risk of OA, especially HOA. [ABSTRACT FROM AUTHOR]