Loeffler's Endocarditis- A cause of endomyocardial fibrosis in a patient of juvenile idiopathic arthritis: A Case Report.

Endomyocardial fibrosis secondary to hyper-eosinophilic syndrome also known as Loeffler's Endocarditis is a rare cause of restrictive cardiomyopathy. If left untreated, it carries a very high morbidity and mortality rate. The case of a 20 years old girl, a known case of polyarticular juvenile idiopathic arthritis since the age of 13 years was reported at Federal Government Polyclinic Hospital, Islamabad on 14th May 2022. She presented with an acute history of shortness of breath and cough for two weeks. Her initial echocardiogram showed suspicion of Loeffler's Endocarditis, which is attributed to be an adverse effect of etanercept- a tumour necrosis factor (TNF) inhibitor, which she had been prescribed for her arthritis. The patient is currently being managed with high doses of steroids, therapeutic anticoagulation with rivaroxaban, carvedilol for tachycardia and mycophenolate mofetil as an immunosuppressant.

A radiomics pipeline dedicated to Breast MRI: validation on a multi-scanner phantom study.

OBJECTIVE: Quantitative analysis in MRI is challenging due to variabilities in intensity distributions across patients, acquisitions and scanners and suffers from bias field inhomogeneity. Radiomic studies are impacted by these effects that affect radiomic feature values. This paper describes a dedicated pipeline to increase reproducibility in breast MRI radiomic studies. MATERIALS AND METHODS: T1, T2, and T1-DCE MR images of two breast phantoms were acquired using two scanners and three dual breast coils. Images were retrospectively corrected for bias field inhomogeneity and further normalised using Z score or histogram matching. Extracted radiomic features were harmonised between coils by the ComBat method. The whole pipeline was assessed qualitatively and quantitatively using statistical comparisons on two series of radiomic feature values computed in the gel mimicking the normal breast tissue or in dense lesions. RESULTS: Intra and inter-acquisition variabilities were strongly reduced by the standardisation pipeline. Harmonisation by ComBat lowered the percentage of radiomic features significantly different between the three coils from 87% after bias field correction and MR normalisation to 3% in the gel, while preserving or improving performance of lesion classification in the phantoms. DISCUSSION: A dedicated standardisation pipeline was developed to reduce variabilities in breast MRI, which paves the way for robust multi-scanner radiomic studies but needs to be assessed on patient data.

RNA-mediated gene regulation is less evolvable than transcriptional regulation.

Much of gene regulation is carried out by proteins that bind DNA or RNA molecules at specific sequences. One class of such proteins is transcription factors, which bind short DNA sequences to regulate transcription. Another class is RNA binding proteins, which bind short RNA sequences to regulate RNA maturation, transport, and stability. Here, we study the robustness and evolvability of these regulatory mechanisms. To this end, we use experimental binding data from 172 human and fruit fly transcription factors and RNA binding proteins as well as human polymorphism data to study the evolution of binding sites in vivo. We find little difference between the robustness of regulatory protein-RNA interactions and transcription factor-DNA interactions to DNA mutations. In contrast, we find that RNA-mediated regulation is less evolvable than transcriptional regulation, because mutations are less likely to create interactions of an RNA molecule with a new RNA binding protein than they are to create interactions of a gene regulatory region with a new transcription factor. Our observations are consistent with the high level of conservation observed for interactions between RNA binding proteins and their target molecules as well as the evolutionary plasticity of regulatory regions bound by transcription factors. They may help explain why transcriptional regulation is implicated in many more evolutionary adaptations and innovations than RNA-mediated gene regulation.

Mechanistic insights into the manganese-dependent phosphodiesterase activity of yeast Dbr1 with bis-p-nitrophenylphosphate and branched RNA substrates.

Saccharomyces cerevisiae Dbr1 is a manganese-dependent RNA debranching enzyme that cleaves the 2'-5' phosphodiester bond of the lariat introns formed during pre-mRNA splicing. Dbr1 is a member of the binuclear metallophosphoesterase enzyme superfamily. We showed previously via alanine scanning that RNA debranching in vivo and in vitro depends on conserved active site residues His13, Asp40, Asn85, His86, His179, His231, and His233. Here, by extending the alanine scan, we added Cys11 to the ensemble of essential active site components. We report that Dbr1 has a vigorous manganese-dependent phosphodiesterase activity with the non-RNA substrate bis-p-nitrophenylphosphate. Whereas RNA debranching requires His86, bis-p-nitrophenylphosphatase activity does not. We interpret these and other structure-activity relations reported here in light of the crystal structures of Entamoeba Dbr1 and other homologous binuclear metallophosphodiesterases. Our results suggest that (i) Dbr1 adheres to the two-metal mechanism of the enzyme superfamily, but is distinguished by its reliance on a Cys11-Xaa-His13 motif to engage one of the catalytic metals instead of the Asp-Xaa-His element typical of other clades within the superfamily; (ii) His86 is a general acid catalyst that protonates the O2' leaving group of the RNA 2'-5' phosphodiester; and (iii) the favorable pKa of p-nitrophenol elides the strict need for a general acid during hydrolysis of bis-p-nitrophenylphosphate. The Dbr1 bis-p-nitrophenylphosphatase activity is well suited for high-throughput screening for inhibitors of debranching.

Genonets server-a web server for the construction, analysis and visualization of genotype networks.

A genotype network is a graph in which vertices represent genotypes that have the same phenotype. Edges connect vertices if their corresponding genotypes differ in a single small mutation. Genotype networks are used to study the organization of genotype spaces. They have shed light on the relationship between robustness and evolvability in biological systems as different as RNA macromolecules and transcriptional regulatory circuits. Despite the importance of genotype networks, no tool exists for their automatic construction, analysis and visualization. Here we fill this gap by presenting the Genonets Server, a tool that provides the following features: (i) the construction of genotype networks for categorical and univariate phenotypes from DNA, RNA, amino acid or binary sequences; (ii) analyses of genotype network topology and how it relates to robustness and evolvability, as well as analyses of genotype network topography and how it relates to the navigability of a genotype network via mutation and natural selection; (iii) multiple interactive visualizations that facilitate exploratory research and education. The Genonets Server is freely available at http://ieu-genonets.uzh.ch.

Immediate, Short-Term, Intermediate, and Long-Term Clinical Outcomes of True Bifurcation Stenting.

INTRODUCTION: Coronary artery bifurcation lesion is an epicardial stenosis that, when compared to non-bifurcation lesions, poses a greater risk of adverse events and can compromise prognosis. This study aims to investigate the clinical efficacy of different stenting techniques, particularly in terms of their immediate, short-term, intermediate, and long-term outcomes in patients with true bifurcation lesions. METHODOLOGY: This retrospective observational cohort study was conducted in a tertiary cardiac hospital in Islamabad, from February 1, 2015, to February 28, 2021. A total of 172 patients who met the inclusion criteria and underwent percutaneous coronary intervention were selected using a consecutive sampling technique. Follow-up was maintained for three years to assess procedural outcomes. RESULTS: Of the 172 participants, the majority were males (69%) and only 4% were above 75 years of age. A significant relation between major adverse cardiac events (MACEs) with acute coronary syndrome (ACS) and previous percutaneous coronary intervention (PCI) (p < 0.000) was observed. Procedural success was good in all patients using the drug-eluting stent. The MAC rate was 6.9% and the final kissing balloon inflation, stenting technique, and bifurcation involvement were significantly associated with MACE occurrence (p < 0.01), and mortality was reported in two patients (1.16%). MACEs were associated with mortality; previous PCI and hypertension increased the risk of mortality. CONCLUSION: The two-stent strategy can be used with good long-term outcomes and low complication rates.

Outcomes of a Modified Technique for Deflation of Distal Radial Artery Occlusion Device on Radial Artery Patency After Percutaneous Coronary Intervention.

Objective: This study aimed to compare two protocols of deflation with increased intervals versus late deflation with smaller intervals for distal radial artery occlusion device (DROAD) removal to assess for radial artery occlusion (RAO). Methods: All patients who underwent PCI with distal radial access were enrolled in the study. The DROAD was applied using an occlusive hemostasis method. Patients were assigned to either protocol 1 or protocol 2 at the primary physician's discretion. Protocol 1 involved the removal of 2 ml of air starting 1 h after the sheath removal and then the removal of 2 ml every 30 min until the band came off. Protocol 2 involved the removal of 4 ml of air 2 h after the sheath removal and then a further 4 ml of air every 15 min until the band came off. Results: A total of 446 patients were enrolled in this study (mean age; 61 ± 6 (Group 1) and 60 ± 5 (Group 2); females 45.83% (Group 1) and 46.34% (Group 2)). The baseline characteristics were the same, including mean hemostasis time (256 ± 25 min (Group 1) and 254 ± 28 min (Group 2), P-value = 0.611). Primary and secondary endpoints did not reach significance in either group (RAO; 21 (8.71) Group 1 and 18 (8.78) Group 2 (P-value = 0.932)). Age (OR (95%CI): 1.07 (0.57-1.45); P-value = 0.031), female gender (OR (95%CI): 1.42 (0.93-1.74); P-value = 0.012), distal artery diameter (OR (95%CI): 0.57 (0.21-0.93); P-value = 0.005), procedure time (OR (95%CI): 2.64 (0.95-4.32); P-value = 0.001), and sheath size (OR (95%CI): 2.47 (1.43-3.76); P-value = 0.044) were predictors of RAO in our cohort. Conclusion: This investigation shows no difference in the incidence of RAO with the standard versus accelerated deflation protocol after PCI. However, local vascular complications, including hematoma were increased with the accelerated protocol.

Multimodal MRI radiomic models to predict genomic mutations in diffuse intrinsic pontine glioma with missing imaging modalities.

Purpose: Predicting H3.1, TP53, and ACVR1 mutations in DIPG could aid in the selection of therapeutic options. The contribution of clinical data and multi-modal MRI were studied for these three predictive tasks. To keep the maximum number of subjects, which is essential for a rare disease, missing data were considered. A multi-modal model was proposed, collecting all available data for each patient, without performing any imputation. Methods: A retrospective cohort of 80 patients with confirmed DIPG and at least one of the four MR modalities (T1w, T1c, T2w, and FLAIR), acquired with two different MR scanners was built. A pipeline including standardization of MR data and extraction of radiomic features within the tumor was applied. The values of radiomic features between the two MR scanners were realigned using the ComBat method. For each prediction task, the most robust features were selected based on a recursive feature elimination with cross-validation. Five different models, one based on clinical data and one per MR modality, were developed using logistic regression classifiers. The prediction of the multi-modal model was defined as the average of all possible prediction results among five for each patient. The performances of the models were compared using a leave-one-out approach. Results: The percentage of missing modalities ranged from 6 to 11% across modalities and tasks. The performance of each individual model was dependent on each specific task, with an AUC of the ROC curve ranging from 0.63 to 0.80. The multi-modal model outperformed the clinical model for each prediction tasks, thus demonstrating the added value of MRI. Furthermore, regardless of performance criteria, the multi-modal model came in the first place or second place (very close to first). In the leave-one-out approach, the prediction of H3.1 (resp. ACVR1 and TP53) mutations achieved a balanced accuracy of 87.8% (resp. 82.1 and 78.3%). Conclusion: Compared with a single modality approach, the multi-modal model combining multiple MRI modalities and clinical features was the most powerful to predict H3.1, ACVR1, and TP53 mutations and provided prediction, even in the case of missing modality. It could be proposed in the absence of a conclusive biopsy.

Firm characteristics, governance mechanisms, and ESG disclosure: how caring about sustainable concerns?

Environmental, social, and governance (ESG) pillars help determine the business organizations' sustainable business practices. Considering the same, this research examines the association between firm characteristics, governance mechanisms, and ESG for a sample of 564 firms from fifteen developed economies. For empirical analysis, ordinary least square, fixed effect, and random effect estimations techniques were applied using annual data from 2010 to 2019. The overall findings reveal that the governance structure of firms (board size, board independence, and cross-listing) play a significant role in ESG disclosure. Moreover, low corruption perception reflects higher ESG disclosure among the targeted firms. Additionally, firm characteristics; such as liquidity position shows a better reporting of ESG during the study period. When accounting for the ESG disclosure individually, the findings confirm the productive role of board size, current ratio, and low corruption towards environmental exposure. Lastly, the results demonstrate that board size and ESG disclosure promote better financial performance. These results offer valuable policy recommendations.

Impact of ComBat and a Multi-Model approach to deal with multi-scanner and missing MRI data in a small cohort study. Application to H3K27M mutation prediction in patients with DIPG.

Radiomics was proposed to identify tumor phenotypes non-invasively from quantitative imaging features. Calculating a large amount of information on images, allows the development of reliable classification models. In multi-modal imaging protocols, the question arises of adding an imaging modality to improve model performance. In addition, in the implementation of clinical protocols, some modalities are not acquired or are of insufficient quality and cannot be reliably taken into account. Furthermore, multi-scanner studies generate some variability in the acquisition and data. Some methodological solutions using ComBat and a multi-model approach were tested to take these two issues into account. It was applied to a cohort of 88 patients with Diffuse Intrinsic Pontine Glioma (DIPG). Sixteen models using radiomic features computed using 0, 1, 2, 3 or 4 MRI modalities were proposed. Based on Leave-One-Out Cross-Validation, F1 weighted scores ranged from 0.66 to 0.85. A model of majority voting using the prediction of all the models available for one given patient was finally applied, reducing drastically the number of unclassified patients.Clinical relevance- In case of patients with DIPG, the prediction of H3 mutation is of prime importance in case of inconclusive biopsy or in the absence of it. It could suggest orientations for new chemotherapy drugs associated with the radiation therapy.