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Abstract Age-related microangiopathy, also known as small vessel disease (SVD), causes damage to the brain, retina, liver, and kidney. Based on the DNA damage theory of aging, we reasoned that genomic instability may underlie an SVD caused by dominant C-terminal variants in TREX1, the most abundant 3′−5′ DNA exonuclease in mammals. C-terminal TREX1 variants cause an adult-onset SVD known as retinal vasculopathy with cerebral leukoencephalopathy (RVCL or RVCL-S). In RVCL, an aberrant, C-terminally truncated TREX1 mislocalizes to the nucleus due to deletion of its ER-anchoring domain. Since RVCL pathology mimics that of radiation injury, we reasoned that nuclear TREX1 would cause DNA damage. Here, we show that RVCL-associated TREX1 variants trigger DNA damage in humans, mice, and Drosophila, and that cells expressing RVCL mutant TREX1 are more vulnerable to DNA damage induced by chemotherapy and cytokines that up-regulate TREX1, leading to depletion of TREX1-high cells in RVCL mice. RVCL-associated TREX1 mutants inhibit homology-directed repair (HDR), causing DNA deletions and vulnerablility to PARP inhibitors. In women with RVCL, we observe early-onset breast cancer, similar to patients with BRCA1/2 variants. Our results provide a mechanistic basis linking aberrant TREX1 activity to the DNA damage theory of aging, premature senescence, and microvascular disease.

Electroencephalography (EEG) is a non-intrusive and powerful tool for understanding the complex nature of the brain. Epileptic seizures, a neurological disorder, are characterized by excessively synchronized neuronal activity within the brain. This abnormal synchronization disrupts the normal functioning of neural networks, leading to seizures. This work proposes to use the Gaussian-based Stockwell Transform (GST) to segment EEG signals into various frequency bands such as delta, theta, alpha, beta, and gamma band for analysis. The feature extraction process on these sub-band signals generates a feature set, encompassing the fluctuation index, relative amplitude, holoentropy, logarithmic band power, and the newly introduced Hermite polynomial-based delta amplitude modulation spectrogram. To differentiate between epileptic and non-epileptic events in EEG signals, the previous features have been applied to the Random Forest Classifier (RFC) algorithm. The effectiveness of our proposed method is validated using a benchmark EEG dataset, with GST and RFC demonstrating accurate results in distinguishing seizure activity. Experimental results show an optimal classification accuracy of 96.4 %, a sensitivity of 97 %, and a specificity of 96.4 %.

This study investigates the feasibility of using grape biodiesel from the wine industry as a sustainable and cost-effective alternative to traditional fuels. The research focuses on optimizing key parameters like blend ratio, injection timing, injection pressure, engine load, and exhaust gas recirculation in a Common Rail Direct Injection engine to achieve low emissions without compromising performance. Due to grape biodiesel's higher viscosity, different energy content, and varying ignition delays compared to diesel, precise adjustments are essential for complete combustion and reduced emissions. This study uses response surface methodology and a Central Composite Design matrix to find the best values for a number of parameters in modern CRDI engines that use advanced electronic control units. Through fifty input combinations, the study aims to minimize specific fuel consumption, hydrocarbons, nitrogen oxides, and carbon monoxide while maximising brake thermal efficiency, brake mean effective pressure, and mechanical efficiency. The optimal configuration includes a fuel injection timing of 6° bTDC, an engine load of 82 %, 6.7 % EGR, 1000 bar injection pressure, and a 33 % grape biodiesel blend. These optimum input conditions yielded outputs of 3.55 bar BMEP, 31.85 % BTE, 64 % mechanical efficiency, 0.278 kg/kWh SFC, 0.127 % CO, 357 ppm NOx, and 8 ppm of HC. These adjustments ensure low emissions and efficient engine operation, highlighting grape biodiesel's potential as a viable alternative fuel.

Abstract Background Congenital dyserythropoietic anemias (CDAs) are a very rare and heterogeneous group of disorders characterized by ineffective erythropoiesis. CDA II is caused by mutations in the SEC23B gene. The most common mutation reported in India is c.1385 A > G, p.Y462C. There is no simple and cost-effective confirmatory diagnostic test available for CDA, and therefore, many patients remain undiagnosed. High-resolution melting curve (HRM) analysis is a polymerase chain reaction (PCR) based technique applied to identify genetic differences and scan nucleic acid sequences. HRM can be used to rapidly screen the common mutation causing CDA II in the Indian population. Thus, we studied the use of High-Resolution Melting Curve Analysis to detect common mutation causing CDA II in the Indian population. Method 11 patients having SEC23B (Y462C) mutation causing CDA II are considered for this study. HRM was used to check the presence of Y462C mutation. To verify the accuracy of the HRM analysis, we compared HRM results with the results of Sanger sequencing. This helped us to confirm the diagnosis. Results We have described the clinical, hematological, and genetic data of eleven patients suffering from CDAII. According to HRM and Sanger sequencing, a homozygous SEC23B (Y462C) mutation was present in all patients, whereas a heterozygous Y462C mutation was present in their parents. Conclusion Our data showed that High-Resolution Melting (HRM) analysis could be used to rapidly screen common SEC23B mutation that causes CDA II in the Indian population.

Summary: Demyelination is a hallmark of multiple sclerosis, leukoencephalopathies, cerebral vasculopathies, and several neurodegenerative diseases. The cuprizone mouse model is widely used to simulate demyelination and remyelination occurring in these diseases. Here, we present a high-resolution single-nucleus RNA sequencing (snRNA-seq) analysis of gene expression changes across all brain cells in this model. We define demyelination-associated oligodendrocytes (DOLs) and remyelination-associated MAFBhi microglia, as well as astrocytes and vascular cells with signatures of altered metabolism, oxidative stress, and interferon response. Furthermore, snRNA-seq provides insights into how brain cell types connect and interact, defining complex circuitries that impact demyelination and remyelination. As an explicative example, perturbation of microglia caused by TREM2 deficiency indirectly impairs the induction of DOLs. Altogether, this study provides a rich resource for future studies investigating mechanisms underlying demyelinating diseases.

Purpose: A dual‐source CT system can be operated in a high‐pitch helical mode to provide a temporal resolution of 66 ms, which reduces motion artifacts in CT pulmonary angiography (CTPA). It can also be operated in a multi‐energy (ME) mode to provide iodine maps, beneficial in the evaluation of pulmonary embolism (PE). No energy‐integrating detector (EID) CT can perform simultaneous ME and high‐pitch acquisition. This phantom study aimed to evaluate the ability of a photon‐counting‐detector (PCD) CT to perform simultaneous high‐pitch and ME imaging for CTPA. Methods: A motion phantom was used to mimic the respiratory motion. Two tubes filled with iodine with intravascular thrombus mimicked by injecting glue within the tubes were placed along with 5, 10, and 15 mg/mL iodine samples, on a motion phantom at 20 and 30 revolutions per minute. Separate high‐pitch and ME EID‐CT scans and a single high‐pitch ME PCD scan were acquired and virtual monoenergetic images and iodine maps reconstructed. Percent thrombus occlusion was measured and compared between static and moving images. Results: When there was motion, EID‐CT ME suffered from significant motion artifacts. The measured iodine concentrations with PCD‐CT in high‐pitch ME were more stable when there was a motion, with a lower standard deviation than EID‐CT in ME mode. The estimated percent thrombus occlusion dropped significantly with applied motion on EID‐CT, while PCD‐CT high‐pitch ME mode showed good agreement between measurements on static or moving images. Conclusion: PCD‐CT with combined ME and high‐pitch mode facilitates simultaneous accurate iodine quantification and assessment of intravascular occlusion. [ABSTRACT FROM AUTHOR]

This study describes the Casson (a non-Newtonian fluid) nanofluid bioconvection flow across a spinning disc in the presence of gyrotactic microorganisms, many slips and thermal radiation. Also, the flow is considered as a reversible flow. The esterification process is taken into account. Using the proper variables, a system of extremely nonlinear PDEs is converted into a system of ODEs. To arrive to the solution of such equations, a numerical approach is used. Using the bvp4c approach, nonlinear flow equations can be numerically solved. Investigated are the effects of different numbers on the thermal field, volumetric concentration of nanoparticles and microbiological field. The key characteristics of the parameters in relation to the profiles of the velocity, temperature, concentration and microorganisms are graphically assessed with appropriate physical effects. A graphical explanation is provided for the wall shear stress, local Nusselt number, local Sherwood number and local motile density number. Rate of motile density number shows a prominent difference between reversible and irreversible flows for Brownian motion and Peclet number. The results of the theoretical simulations have dynamic applications in the fields of biotechnology and thermal engineering. [ABSTRACT FROM AUTHOR]