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Incomplete congenital stationary night blindness associated with a novel variant in the CACNA1F gene
No full textPurpose: Incomplete congenital stationary night blindness (icCSNB) is a subtype of inherited, nonprogressive retinal diseases. Most cases of icCSNB result from mutations in the X-linked gene CACNA1F. We describe the clinical findings of two male siblings diagnosed with icCSNB, both carrying a novel variant c.4008 + 5G > T in CACNA1F inherited from their mother.
Methods: We carried out a comprehensive ophthalmic assessment, including fundus imaging, optical coherence tomography (OCT) scanning and electroretinography. We performed genetic testing with next generation sequencing, in-silico and functional analyses to further characterise the novel variant.
Results: Two male siblings presented with high myopia and reduced visual acuities at age three. Examination and OCT demonstrated no significant abnormalities in both siblings. Full-field electroretinogram (ffERG) testing demonstrated markedly reduced amplitude to weak flashes and an electronegative waveform to strong flashes in dark-adapted ERGs, resembling that of icCSNB, leading to its diagnosis in both children. Next generation sequencing in the older sibling identified a novel hemizygous c.4008 + 5G > T variant in CACNA1F. In-silico analysis of this variant predicted that it would disrupt normal splicing of CACNA1F, though it was not possible to confirm this by RNA sequencing. This same variant was found in the younger sibling, as well as in their mother who had normal examination and ffERG f indings.
Conclusions: We report a novel CACNA1F variant not previously identified in the literature in three patients. Although functional analyses were unable to confirm pathogenicity of this variant, in-silico tools predicted that its effect is consistent with the pathogenesis of icCSNB. Reporting of this family further widens the genotypic spectrum of icCSNB
Anisotropic behaviour of rooted soils: constitutive modelling
No full textPlant roots enhance soil stability, offering sustainable solutions for mitigating slope failure, erosion, and liquefaction. Experimental studies on rooted soils have revealed anisotropic and stress-dependent reinforcement effects. However, the theoretical understanding of this anisotropic behaviour remains limited. To interpret these behaviours, an anisotropic constitutive model was developed within the anisotropic critical state theory framework, incorporating two independent fabric tensors to represent the evolving structures of soil and roots. New anisotropic variables (AB, AR) and a root network evolution rule were introduced to capture the progressive mobilisation of root tensile strength as roots reoriented toward the direction perpendicular to the major principal stress. The model successfully reproduced key features of rooted soil behaviour under monotonic loadings, providing a unified framework for predicting the complex mechanical response of rooted soils
Cosmogenic 10Be and 26Al dating of the fluvial terraces in the Sichuan Basin, SW China: implications for the drainage evolution of the middle Yangtze River
No full textThe fluvial development in the Sichuan Basin of southwestern China plays a significant role in the drainage evolution of the Yangtze River. The assumed initially west-flowing middle Yangtze River in the basin was reversed through gradual headward erosion by the lower Yangtze River via the Three Gorges area, resulting in a significant reorganization of the East Asian fluvial system. However, fluvial terrace chronology in the Sichuan Basin is poorly constrained, and the related drainage network development of the middle Yangtze River remains vague. Five distinct terrace levels of the Yangtze River were identified in the field, which could be efficiently correlated with terrace sequences from three major tributaries in the basin: Jialing Jiang, Tuo Jiang, and Min Jiang. This study presents in-situ cosmogenic nuclide 26Al and 10Be ages from these terraces to construct a robust chronology among different rivers, and more importantly, to build a reliable fluvial evolution relationship in the basin. Temporal and spatial variations in the terrace formation ages indicate that: (1) Five terrace levels from the Yangtze River in the southern basin were dated between 1.68 (+1.18/-0.56) Ma and 20.84 (+4.30/-5.03) ka. (2) The formation age of five terrace levels derived from the Jialing Jiang in the eastern basin is concentrated between 0.61 (+0.14/-0.13) Ma and 0.22 ± 0.20 Ma. (3) The highest terrace T5 of the Tuo Jiang in the middle basin was deposited at 1.24 (+2.86/-0.22) Ma. (4) Three terrace levels from the lower Min Jiang in the western basin were deposited between 0.81(+0.28/-0.26) Ma and 15.24 ± 1.21 ka.
Our new cosmogenic nuclide chronologies provide the first evidence for the Yangtze drainage network evolution in the Sichuan Basin. The Yangtze River and Min Jiang had been aggraded during 1.02–0.14 Ma in the western basin margin with an accumulation rate of 125 m/Ma and then incised after 0.14 Ma. The aggradation in front of the mountain may be attributed to both the active tectonics of the eastern Tibetan Plateau and climate cooling during the Middle Pleistocene Transition. Conversely, the Yangtze River and Jialing Jiang in the eastern basin and the Tuo Jiang in the middle basin cut down into bedrock more than 100 m since 1.68 Ma. The average incision rate of Jialing Jiang (360 m/Ma) in the last 0.6 Ma is higher than those of the Yangtze River (67 m/Ma) and Tuo Jiang (74 m/Ma) over longer timescales. Moreover, we conclude that the present-day eastward-flowing Yangtze River was established in the Sichuan Basin before 1.68 Ma, which further suggests that the downstream Three Gorges connection should have occurred before this point in time
New kidneys, old risks: cardiovascular challenges after transplantation
Get PDFKidney transplantation markedly improves survival and quality of life in patients with kidney failure, yet cardiovascular disease remains the leading cause of morbidity and mortality in kidney transplant recipients (KTRs). This review outlines the complex interplay of traditional, transplant-specific, and recipient- and donor-related risk factors that sustain a high cardiovascular burden post-transplantation. While kidney function restoration reduces uremic toxins and improves cardiometabolic parameters, new challenges arise from immunosuppressive therapies, persistent hypertension, post-transplant diabetes mellitus, and chronic inflammation. Common cardiovascular complications include coronary artery disease, heart failure, valvular disease, peripheral artery disease, and refractory hypertension. Risk stratification tools and guidelines often fail to account for transplant-specific variables, resulting in suboptimal management. Although some pharmacological strategies and careful antihypertensive regimens show promise, most evidence is extrapolated from non-transplant populations due to the lack of dedicated randomized controlled trials. Emerging therapies like SGLT2 inhibitors, GLP-1 receptor agonists and non-steroidal mineralocorticoid receptor antagonists hold potential but require further validation in this population. Moreover, sex disparities persist in access to transplantation and in post-transplant outcomes, with men generally experiencing higher cardiovascular risk but women potentially facing greater relative mortality. The review underscores the urgent need for transplant-specific cardiovascular research, personalized therapeutic strategies including precision medicine, and greater inclusion of women in research. Optimizing cardiovascular outcomes in KTRs will require multidisciplinary collaboration, rigorous evidence generation, and an integrated approach to risk prediction, prevention, and treatment
Is iron dysregulation in the mirror motor cortex associated with misophonia?
No full textIron homeostasis plays a critical role in brain function and mental health, yet its dysregulation in specific psychiatric conditions remains underexplored. In this article, we propose iron accumulation in the brains of individuals with misophonia—a condition characterized by intense emotional and physiological reactions to specific human-generated sounds. Based on the known involvement of the mirror neuron system in misophonia, we hypothesize that excessive iron concentration in the mirror motor cortex is a result of abnormal hyperactivity in this region. We propose that chronic overactivation of mirror motor cortex leads to increased metabolic demand and elevated cerebral blood flow, facilitating excessive iron influx. This may trigger low-grade chronic neuroinflammation, promoting maladaptive synaptic plasticity and long-term potentiation. The resulting impaired inhibitory control and heightened functional connectivity with primary sensory areas may further exacerbate hyper-mirroring. We propose future studies should confirm the existence of this self-perpetuating cycle which would imply that interventions aimed at reducing mirror system hyperactivity could disrupt this cycle and offer a promising therapeutic strategy for misophonia
Principios para los indicadores liderados por la juventud para la Agenda de Juventud, Paz y Seguridad
Get PDFNo abstract available
Hollow-core polydopamine nanocarriers for ultarsound-enhanced drug delivery
Get PDFOn-demand drug release is one of the main challenges in nanocarrier design and a key step toward enhancing the efficacy of novel therapeutic formulations. Compared to conventional methods such as pH- or light-driven release, ultrasound-guided drug release offers a cost-effective strategy with improved tissue penetration making it particularly suitable for applications in hard-to-access tissues such as pancreas. In this study, hollow nanoparticles (hPDA) were developed and evaluated for ultrasound-enhanced drug delivery, focusing on pancreatic ductal adenocarcinoma (PDAC). The hPDA nanoparticles, prepared employing non-toxic reagents, measured approximately 120 nm and were successfully loaded with SN-38, a potent yet challenging-to-formulate chemotherapeutic agent. Ultrasound-triggered drug release experiments at 60 kHz and 1.1 MHz demonstrated significant enhancements in drug release, with an increase of 54% and 19% respectively, compared to controls. Cytotoxicity studies under ultrasound exposure revealed a 20% reduction in cell viability, underscoring the synergistic potential of hPDA and ultrasound technology. These findings establish hPDA nanocarriers as a promising platform for ultrasound-responsive, targeted drug delivery in cancer therapy, with high potential for improved spatiotemporal control and reduced systemic toxicity
Graph anomaly detection algorithm based on multi-view heterogeneity resistant network
Get PDFGraph anomaly detection (GAD) aims to identify nodes or edges that deviate from normal patterns. However, the presence of heterophilic edges in graphs leads to feature over-smoothing issues. To overcome this limitation, this paper proposes the multi-view heterogeneity resistant network (MV-GHRN) model, which progressively purifies heterophilic edges through multi-view collaboration. First, to address the noise sensitivity of single predictions, the method computes post-aggregation (PA) scores for both the original graph and its perturbed versions and performs weighted fusion, leveraging the consistency of multiple prediction perspectives to enhance the reliability of heterophilic edge identification. Second, a cosine similarity view is introduced as a complementary structural perspective, with both views independently completing heterophilic edge pruning to clean the graph structure from both topological and feature dimensions. Finally, a cross-view self-distillation mechanism is designed, using the fused predictions from the two purified views as teacher signals to guide the optimization of each view in reverse, correcting feature biases caused by heterophilic edges. Experiments on benchmark datasets such as YelpChi and Amazon demonstrate that the framework significantly outperforms existing methods. For instance, on the YelpChi dataset, MV-GHRN surpasses the best baseline by 16.8% and 5.2% in F1-Macro and AUC, respectively, validating the effectiveness of the progressive multi-view purification mechanism
Exploring Advanced Deep Learning Models for Super Resolution of 3D Dental CBCT Volumes
Get PDFHigh Resolution plays an important role in digital imaging, but it is even more important in medical imaging. However, due to certain constraints, medical imaging is often captured in low dose radiation which causes noise and lower resolution. As high resolution plays a vital role in diagnostics and model training, we compare efficiency and accuracy of state-of-the-art deep learning models for super-resolution reconstruction in 3D volumes. We have employed various deep learning models, such as CNN, SR-GAN, UNet and Auto-Encoder for super resolution-reconstruction of 3D Dental CBCT volumes. To optimize their performance, we have combined different architectural enhancements such as multipath structure in CNN and SR-GAN for enhanced features extraction, Mamba with UNet to capture global dependencies, and Diffusion with Auto-En-coder for feature refinement. The performance of CNN is highest with Peak Sig-nal-to-Noise Ratio and Structural Similarity Index of 35.35 and 0.952 respec-tively; however, Auto-Encoder is the fastest with training time of 28.63 hours
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