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Saleh, A. A.

Publications and source records attributed to Saleh, A. A..

2 recordsLinked to original sources

The Research Landscape of Dynamic Functional Connectivity in Parkinson's Disease: Systematic Review and Interactive Tool

Dynamic functional connectivity (dFC) analysis of functional Magnetic Resonance Imaging (fMRI) data has emerged as a powerful framework for characterizing the time-varying network disintegration and topological transitions underlying Parkinsons disease (PD). However, the rapid expansion of this field introduces methodological heterogeneity, creating a fragmented landscape that complicates knowledge synthesis and informed decision-making for future study designs. To address this, we performed a scoping review to map the conceptual and methodological diversity of dFC research in PD. Beyond a traditional static synthesis, we developed DynaPD, an open-source interactive application that allows researchers to dynamically explore study designs, analytical pipelines, and reported findings. Our synthesis of 37 eligible studies reveals divergence in preprocessing strategies but a convergence on core analytical pipelines, notably sliding-window techniques coupled with k-means clustering. Empirically, studies converge on the importance of neural flexibility assessed via dwell times and topological transitions between strongly and sparsely connected states. However, specific network interpretations remain variable. Common limitations included cross-sectional designs, limited spatial resolution for subcortical networks, and short scan duration. By providing a scoping evidence synthesis and a living interactive tool, this work functions as a decision-support resource to consolidate the literature and guide the methodological design of future studies.

neuroscience↗

Colorectal cancer detection and treatment with engineered probiotics

Bioengineered probiotics enable new opportunities to improve colorectal cancer (CRC) screening, prevention and treatment strategies. Here, we demonstrate the phenomenon of selective, long-term colonization of colorectal adenomas after oral delivery of probiotic E. coli Nissle 1917 (EcN) to a genetically-engineered murine model of CRC predisposition. We show that, after oral administration, adenomas can be monitored over time by recovering EcN from stool. We also demonstrate specific colonization of EcN to solitary neoplastic lesions in an orthotopic murine model of CRC. We then exploit this neoplasia-homing property of EcN to develop early CRC intervention strategies. To detect lesions, we engineer EcN to produce a small molecule, salicylate, and demonstrate that oral delivery of this strain results in significantly increased levels of salicylate in the urine of adenoma-bearing mice, in comparison to healthy controls. We also assess EcN engineered to locally release immunotherapeutics at the neoplastic site. Oral delivery to mice bearing adenomas, reduced adenoma burden by [~]50%, with notable differences in the spatial distribution of T cell populations within diseased and healthy intestinal tissue, suggesting local induction of robust anti-tumor immunity. Together, these results support the use of EcN as an orally-delivered platform to detect disease and treat CRC through its production of screening and therapeutic molecules.

bioengineering↗