Immune-inflammatory conditions in the central nervous system (CNS) rely on molecular and cellular interactions which are homeostatically maintained to protect neural tissue from harm. The CD40–CD40L interaction upregulates key proinflammatory molecules, a function best understood in the context of infection, during which B-cells are activated via CD40 signaling to produce antibodies. However, the role of CD40 in neurological disease of non-infectious etiology is unclear. We review the role of CD40–CD40L in traumatic brain injury, Alzheimer’s Disease, Parkinson’s Disease, stroke, epilepsy, nerve injury, multiple sclerosis, ALS, myasthenia gravis and brain tumors. We also highlight therapeutic advancements targeting the CD40 system to either attenuate the neuroinflammatory response or leverage the downstream effects of CD40 signaling for direct tumor cell lysis.

The control of pneumatically driven soft robots typically requires electronics. Microcontrollers are connected to power electronics that switch valves and pumps on and off. As a recent alternative, fluidic control methods have been introduced, in which soft digital logic gates permit multiple actuation states to be achieved in soft systems. Such systems have demonstrated autonomous behaviors without the use of electronics. However, fluidic controllers have required complex fabrication processes. To democratize the exploration of fluidic controllers, we developed tube-balloon logic circuitry, which consists of logic gates made from straws and balloons. Each tube-balloon logic device takes a novice five minutes to fabricate and costs $0.45. Tube-balloon logic devices can also operate at pressures of up to 200 kPa and oscillate at frequencies of up to 15 Hz. We configure the tube-balloon logic device as NOT-, NAND-, and NOR-gates and assemble them into a three-ring oscillator to demonstrate a vibrating sieve that separates sugar from rice. Because tube-balloon logic devices are low-cost, easy to fabricate, and their operating principle is simple, they are well suited for exploring fundamental concepts of fluidic control schemes while encouraging design inquiry for pneumatically driven soft robots.

Developing soft circuits from individual soft logic gates poses a unique challenge: with increasing numbers of logic gates, the design and implementation of circuits lead to inefficiencies due to mathematically unoptimized circuits and wiring mistakes during assembly. It is therefore practically important to introduce design tools that support the development of soft circuits. We developed a web-based graphical user interface, the Soft Compiler , that accepts a user-defined robot behavior as a truth table to generate a mathematically optimized circuit diagram that guides the assembly of a soft fluidic circuit. We describe the design and experimental verification of three soft circuits of increasing complexity, using the Soft Compiler as a design tool and a novel pneumatic glove as an input interface. In one example, we reduce the size of a soft circuit from the original 11 logic gates to 4 logic gates while maintaining circuit functionality. The Soft Compiler is a web-based design tool for fluidic, soft circuits and published under an open-source MIT License.

Diagnosis and longitudinal monitoring of neurological diseases are limited by the poor specificity and limited resolution of currently available techniques. Analysis of circulating cells in cerebrospinal fluid (CSF) has emerged as a promising strategy for the diagnosis, molecular characterization, and monitoring of neurological disease. In comparison to bulk sequencing analysis, single-cell sequencing studies can provide novel insights into rare cell populations and uncover heterogeneity in gene expression at a single-cell resolution, which has several implications for understanding disease pathology and treatment. Parallel development of standardized biofluid collection protocols, pre-processing strategies, reliable single-cell isolation strategies, downstream genomic analysis, and robust computational analysis is paramount for comprehensive single-cell sequencing analysis. Here we perform a comprehensive review of studies focusing on single-cell sequencing of cells in the CSF of patients with oncological or non-oncological diseases of the central nervous system.

Background Tarlov cysts are perineural collections of cerebrospinal fluid most often affecting sacral nerve roots, which may cause back pain, extremity paresthesias and weakness, bladder/bowel dysfunction, and/or sexual dysfunction. The most effective treatment of symptomatic Tarlov cysts, with options including non-surgical management, cyst aspiration and injection of fibrin glue, cyst fenestration, and nerve root imbrication, is debated. Methods Retrospective chart review was conducted for 220 patients with Tarlov cysts seen at our institution between 2006 and 2021. Logistic regression analysis was conducted to determine the association between treatment modality, patient characteristics, and clinical outcome. Results Seventy-two (43.1%) patients with symptomatic Tarlov cysts were managed non-surgically. Of the 95 patients managed interventionally, 71 (74.7%) underwent CT-guided aspiration of the cyst with injection of fibrin glue; 17 (17.9%) underwent cyst aspiration alone; 5 (5.3%) underwent blood patching; and 2 (2.1%) underwent more than one of the aforementioned procedures. Sixty-six percent of treated patients saw improvement in one or more symptoms, with the most improvement in patients after aspiration of cyst with injection of fibrin glue; however, this association was not statistically significant on logistic regression analysis. Conclusion Although the subtype of percutaneous treatment was not significantly associated with optimal or suboptimal patient outcomes, cyst aspiration both with and without injection of fibrin glue may serve as a useful diagnostic tool to (1) determine symptom etiology and (2) identify patients who might have achieved temporary improvement between the time of cyst aspiration and refill with cerebrospinal fluid as potential candidates for neurosurgical intervention of cyst fenestration and nerve root imbrication.