INSP-15. ITCC-P4: A sustainable platform of molecularly well-characterized PDX models of pediatric cancers for high throughputin vivo testing

alexandrossfakianakis shared this article with you from Inoreader INSP-15. ITCC-P4: A sustainable platform of molecularly well-characterized PDX models of pediatric cancers for high throughputin vivo testing via Neuro-Oncology Current Issue Abstract Thanks to state-of-the-art molecular profiling techniques we by now have a much better understanding of pediatric cancers and what is driving them. On the other hand, we have also realized that pediatric cancers are much more heterogeneous than previously thought. Many new types and subtypes of pediatric cancers have been identified with distinct molecular and clinical characteristics. However, for many if not most of these new types and subtypes there is no specific treatment available, yet. In order to develop specific treatment protocols and to increase survival rates for pediatric cancer patients further, both at diagnosis and relapse/metastasis, we need a large collection of well-characterized preclinical models representing all the different types and subtypes. These models can be used for preclinical drug testing to prioritize the pediatric development of anticancer drugs that would be best targeting pediatric tumor biology. The ITCC-P4 co nsortium, which is a collaboration between many academic centers across Europe, several companies involved in in vivo preclinical testing, and ten pharmaceutical companies, started in 2017 with the overall aim to establish a sustainable platform of >400 molecularly well-characterized PDX models of high-risk pediatric cancers and to use them for in vivo testing of novel mechanism-of-action based treatments. Currently, 340 models have been fully established, including 87 brain tumor models and 253 non-brain tumor models, together representing many different tumor types both from primary and relapsed/metastatic disease. Out of these 340 models, 252 have been fully molecularly characterized, most of them together with their matching original tumors, and almost of all these models are currently being subjected to in vivo testing using three standard of care drugs and six novel mechanism-of-action based drugs. In this presentation, an update on the current status of the ITCC-P4 platfor m and the data we collectively have generated thus far will be presented. View on Web

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Temporomandibular disorders, bite force and osseous changes of the temporomandibular joints in patients with hypermobile Ehlers‐Danlos Syndrome compared to a healthy control group

alexandrossfakianakis shared this article with you from Inoreader Temporomandibular disorders, bite force and osseous changes of the temporomandibular joints in patients with hypermobile Ehlers‐Danlos Syndrome compared to a healthy control group via Journal of Oral Rehabilitation SUMMARY Background Ehlers-Danlos syndrome (EDS) is a hereditary disorder that affects the connective tissue and collagen structures in the body characterized by joint hypermobility, skin hyperextensibility and tissue fragility. Objective The aim was to investigate temporomandibular disorders (TMD), bite force, teeth in occlusal contact and osseous changes of the temporomandibular joints (TMJs) in 26 patients with hypermobile EDS (hEDS), differentiated by a genetic test, compared to 39 healthy controls. METHODS: Clinical examination according to Diagnostic Criteria for Temporomandibular Disorders (DC/TMD), radiological examinations of the TMJs by cone-beam computed tomographic (CBCT) scans, registration of bite force and teeth in occlusal contact was performed. Statistical analyses included Fisher's Exact Test, multiple logistic and linear regression models adjusted for age, gender and Body Mass Index (BMI). Results Single symptoms and signs of TMD occurred significantly more often in hEDS (p=0.002; p=0.001; p=0.003; p=<0.0001; p=0.012) and maximum mouth opening was significantly smaller in hEDS compared to controls (p=<0.0001). The DC/TMD diagnosis myalgia, myofascial pain with referral, arthralgia, headache attributed to TMD, disc displacement disorders and degenerative joint disease occurred significantly more often in hEDS compared to controls (p=0.000; p=0.008; p=0.003; p=0.000; p=<0.0001; p=0.010, respectively). No significant differences were found in bite force and in teeth in occlusal contact between the groups (p>0.05). On CBCT of the TMJs, subcortical sclerosis occurred significantly more often in hEDS compared to controls (p=0.005). Conclusion Symptoms and signs of TMD and osseous changes of the TMJs occurred significantly more often in hEDS. Bite force and teeth in occlusal contact were comparable to controls. View on Web

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Biologic Agents in Plastic Surgery

alexandrossfakianakis shared this article with you from Inoreader Biologic Agents in Plastic Surgery via Seminars in Plastic Surgery Semin Plast Surg 2022; 36: 002-002 DOI: 10.1055/s-0042-1743454 Thieme Medical Publishers, Inc. 333 Seventh Avenue, 18th Floor, New York, NY 10001, USA Article in Thieme eJournals: Table of contents  |  Full text View on Web

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Benchmarking Feature Selection Methods in Radiomics

alexandrossfakianakis shared this article with you from Inoreader Benchmarking Feature Selection Methods in Radiomics via Investigative Radiology - Current Issue Objectives A critical problem in radiomic studies is the high dimensionality of the datasets, which stems from small sample sizes and many generic features extracted from the volume of interest. Therefore, feature selection methods are used, which aim to remove redundant as well as irrelevant features. Because there are many feature selection algorithms, it is key to understand their performance in the context of radiomics. Materials and Methods A total of 29 feature selection algorithms and 10 classifiers were evaluated on 10 publicly available radiomic datasets. Feature selection methods were compared for training times, for the stability of the selected features, and for ranking, which measures the pairwise similarity of the methods. In addition, the predictive performance of the algorithms was measured by utilizing the area under the receiver operating characteristic curve of the best-performing classifier. Results Feature selections differed largely in training times as well as stability and similarity. No single method was able to outperform another one consistently in predictive performance. Conclusion Our results indicated that simpler methods are more stable than complex ones and do not perform worse in terms of area under the receiver operating characteristic curve. Analysis of variance, least absolute shrinkage and selection operator, and minimum redundancy, maximum relevance ensemble appear to be good choices for radiomic studies in terms of predictive performance, as they outperformed most other feature selection methods. View on Web

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Fat Quantification in Dual-Layer Detector Spectral Computed Tomography: Experimental Development and First In-Patient Validation

alexandrossfakianakis shared this article with you from Inoreader Fat Quantification in Dual-Layer Detector Spectral Computed Tomography: Experimental Development and First In-Patient Validation via Investigative Radiology - Current Issue Objectives Fat quantification by dual-energy computed tomography (DECT) provides contrast-independent objective results, for example, on hepatic steatosis or muscle quality as parameters of prognostic relevance. To date, fat quantification has only been developed and used for source-based DECT techniques as fast kVp-switching CT or dual-source CT, which require a prospective selection of the dual-energy imaging mode. It was the purpose of this study to develop a material decomposition algorithm for fat quantification in phantoms and validate it in vivo for patient liver and skeletal muscle using a dual-layer detector-based spectral CT (dlsCT), which automatically generates spectral information with every scan. Materials and Methods For this feasibility study, phantoms were created with 0%, 5%, 10%, 25%, and 40% fat and 0, 4.9, and 7.0 mg/mL iodine, respectively. Phantom scans were performed with the IQon spectral CT (Philips, the Netherlands) at 120 kV and 140 kV and 3 T magnetic resonance (MR) (Philips, the Netherlands) chemical-shift relaxometry (MRR) and MR spectroscopy (MRS). Based on maps of the photoelectric effect and Compton scattering, 3-material decomposition was done for fat, iodine, and phantom material in the image space. After written consent, 10 patients (mean age, 55 ± 18 years; 6 men) in need of a CT staging were prospectively included. All patients received contrast-enhanced abdominal dlsCT scans at 120 kV and MR imaging scans for MRR. As reference tissue for the liver and the skeletal muscle, retrospectively available non–contrast-enhanced spectral CT data sets were used. Agreement between dlsCT and MR was evaluated for the phantoms, 3 hepatic and 2 muscular regions of interest per patient by intraclass correlation coefficients (ICCs) and Bland-Altman analyses. Results The ICC was excellent in the phantoms for both 120 kV and 140 kV (dlsCT vs MRR 0.98 [95% confidence interval (CI), 0.94–0.99]; dlsCT vs MRS 0.96 [95% CI, 0.87–0.99]) and in the skeletal muscle (0.96 [95% CI, 0.89–0.98]). For log-transformed liver fat values, the ICC was moderate (0.75 [95% CI, 0.48–0.88]). Bland-Altman analysis yielded a mean difference of −0.7% (95% CI, −4.5 to 3.1) for the liver and of 0.5% (95% CI, −4.3 to 5.3) for the skeletal muscle. Interobserver and intraobserver agreement were excellent (>0.9). Conclusions Fat quantification was developed for dlsCT and agreement with MR techniques demonstrated for patient liver and muscle. Hepatic steatosis and myosteatosis can be detected in dlsCT scans from clinical routine, which retrospectively provide spectral information independent of the imaging mode. View on Web

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Homoarginine Treatment of Rats Improves Cardiac Function and Remodeling in Response to Pressure Overload

alexandrossfakianakis shared this article with you from Inoreader Homoarginine Treatment of Rats Improves Cardiac Function and Remodeling in Response to Pressure Overload via Fundamental & Clinical Pharmacology Abstract Background Low serum concentrations of the amino acid homoarginine (HA) are associated with increased cardiovascular mortality by incompletely understood mechanisms. Objectives This study sought to assess the influence of HA on cardiac remodeling in rats undergoing either transaortic banding or inhibition of nitric oxide synthesis by Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME). Methods Male Wistar rats (n=136) underwent a sham operation (SH) or aortic banding (AB). Both groups were equally divided into fourteen subgroups, receiving different doses of HA alone or in combination with lisinopril, spironolactone, or L-NAME over 4 weeks. Results HA treatment in AB animals resulted in a dose-dependent improvement of cardiac function up to a concentration of 800 mg·kg-1·day-1. Combining 800 mg·kg-1·day-1 HA with spironolactone or lisinopril yielded additional effects, showing a positive correlation with LV ejection fraction (+33%, p=0.0002) and fractional shortening (+41%, p=0.0014). An inverse association was observed with collagen area fraction (-41%, p<0.0001), myocyte cross-sectional area (-22%, p<0.0001) and the molecular markers atrial natriuretic factor (-74%, p=0.0091), brain natriuretic peptide (-42%, p=0.0298), beta-myosin heavy chain (-46%, p=0.0411), and collagen type V alpha 1 chain (-73%, p=0.0257) compared to placebo-treated AB animals. Co-administration of HA and L-NAME was found to attenuate cardiac remodeling and prevent NO-deficient hypertension following AB. Conclusion HA treatment has led to a dose-dependent improvement of myocardial function and marked histological and molecular changes in cardiac remodeling following AB. Combining HA with standard heart failure medication resulted in additional beneficial effects boosting its direct impact on heart failure pathophysiology. View on Web

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Nuclear-targeted 4E-BP1 is dephosphorylated, induces nuclear translocation of eIF4E, and alters mRNA translation

alexandrossfakianakis shared this article with you from Inoreader Nuclear-targeted 4E-BP1 is dephosphorylated, induces nuclear translocation of eIF4E, and alters mRNA translation via ScienceDirect Publication: Experimental Cell Research Publication date: Available online 10 June 2022 Source: Experimental Cell Research Author(s): Sho Takahashi, Shusaku Shibutani, Hiroyuki Iwata View on Web

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Identification of multiple isoforms of glucocorticoid receptor in nasal polyps of patients with chronic rhinosinusitis

alexandrossfakianakis shared this article with you from Inoreader Identification of multiple isoforms of glucocorticoid receptor in nasal polyps of patients with chronic rhinosinusitis via Most Recent Articles: Journal of Otolaryngology - Head & Neck Surgery The conventional belief that glucocorticosteroid (GC) acts through a single brand glucocorticoid receptor (GR)α protein has changed dramatically with the discovery of multiple GR isoforms. We aimed to evaluate... View on Web

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Mendelian randomization analysis for attention deficit/hyperactivity disorder: studying a broad range of exposures and outcomes

alexandrossfakianakis shared this article with you from Inoreader Mendelian randomization analysis for attention deficit/hyperactivity disorder: studying a broad range of exposures and outcomes via International Journal of Epidemiology - Advance Access Abstract BackgroundAttention deficit/hyperactivity disorder (ADHD) is a highly prevalent neurodevelopmental disorder caused by a combination of genetic and environmental factors and is often thought as an entry point into a negative life trajectory, including risk for comorbid disorders, poor educational achievement or low income. In the present study, we aimed to clarify the causal relationship between ADHD and a comprehensive range of related traits. Methods We used genome-wide association study (GWAS) summary statistics for ADHD (n = 53 293) and 124 traits related to anthropometry, cognitive function and intelligence, early life exposures, education and employment, lifestyle and environment, longevity, neurological, and psychiatric and mental health or personality and psychosocial factors available in the MR-Base database (16 067 ≤n ≤766 345). To investigate their causal relationship with ADHD , we used two-sample Mendelian randomization (MR) with a range of sensitivity analyses, and validated MR findings using causal analysis using summary effect estimates (CAUSE), aiming to avoid potential false-positive results. Results Our findings strengthen previous evidence of a causal effect of ADHD liability on smoking and major depression, and are consistent with a causal effect on odds of decreased average total household income [odds ratio (OR) = 0.966, 95% credible interval (CrI) = (0.954, 0.979)] and increased lifetime number of sexual partners [OR = 1.023, 95% CrI = (1.013, 1.033)]. We also found evidence for a causal effect on ADHD for liability of arm predicted mass and weight [OR = 1.452, 95% CrI = (1.307, 1.614) and OR = 1.430, 95% CrI = (1.326, 1.539), respectively] and time spent watching television [OR = 1.862, 95% CrI = (1.545, 2.246)], and evidence for a bidirectional effect for age of first sexual intercourse [beta� ��= −0.058, 95% CrI = (−0.072, −0.044) and OR = 0.413, 95% CrI = (0.372, 0.457), respectively], odds of decreased age completed full-time education [OR = 0.972, 95% CrI = (0.962, 0.981) and OR = 0.435, 95% CrI = (0.356, 0.533), respectively] and years of schooling [beta = -0.036, 95% CrI = (−0.048, −0.024) and OR = 0.458, 95% CrI = (0.411, 0.511), respectively]. Conclusions Our results may contribute to explain part of the widespread co-occurring traits and comorbid disorders across the lifespan of individuals with ADHD and may open new opportunities for developing preventive strategies for ADHD and for negative ADHD trajectories. View on Web

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Isolated cerebral toxoplasmosis 17 years post renal transplant

alexandrossfakianakis shared this article with you from Inoreader Isolated cerebral toxoplasmosis 17 years post renal transplant via Transplant Infectious Disease View on Web

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