Intracortical microelectrodes afford researchers an effective tool to precisely monitor neural spiking activity. Additionally, intracortical microelectrodes have the ability to return function to individuals with paralysis as part of a brain computer interface. Unfortunately, the neural signals recorded by these electrodes degrade over time. Many strategies which target the biological and/or materials mediating failure modes of this decline of function are currently under investigation. The goal of this study is to identify a precise cellular target for future intervention to sustain chronic intracortical microelectrode performance. Previous work from our lab has indicated that the Cluster of Differentiation 14/Toll-like receptor pathway (CD14/TLR) is a viable target to improve chronic laminar, silicon intracortical microelectrode recordings. Here, we use a mouse bone marrow chimera model to selectively knockout CD14, an innate immune receptor, from either brain resident microglia or blood-derived macrophages, in order to understand the most effective targets for future therapeutic options. Using single-unit recordings we demonstrate that inhibiting CD14 from the blood-derived macrophages improves recording quality over the 16 week long study. We conclude that targeting CD14 in blood-derived cells should be part of the strategy to improve the performance of intracortical microelectrodes, and that the daunting task of delivering therapeutics across the blood-brain barrier may not be needed to increase intracortical microelectrode performance.

Intracortical microelectrodes record neuronal activity of individual neurons within the brain, which can be used to bridge communication between the biological system and computer hardware for both research and rehabilitation purposes. However, long-term consistent neural recordings are difficult to achieve, in large part due to the neuroinflammatory tissue response to the microelectrodes. Prior studies have identified many factors that may contribute to the neuroinflammatory response to intracortical microelectrodes. Unfortunately, each proposed mechanism for the prolonged neuroinflammatory response has been investigated independently, while it is clear that mechanisms can overlap and be difficult to isolate. Therefore, we aimed to determine whether the dual targeting of the innate immune response by inhibiting innate immunity pathways associated with cluster of differentiation 14 (CD14), and the mechanical mismatch could improve the neuroinflammatory response to intracortical microelectrodes. A thiol-ene probe that softens on contact with the physiological environment was used to reduce mechanical mismatch. The thiol-ene probe was both softer and larger in size than the uncoated silicon control probe. Cd14-/- mice were used to completely inhibit contribution of CD14 to the neuroinflammatory response. Contrary to the initial hypothesis, dual targeting worsened the neuroinflammatory response to intracortical probes. Therefore, probe material and CD14 deficiency were independently assessed for their effect on inflammation and neuronal density by implanting each microelectrode type in both wild-type control and Cd14-/- mice. Histology results show that 2 weeks after implantation, targeting CD14 results in higher neuronal density and decreased glial scar around the probe, whereas the thiol-ene probe results in more microglia/macrophage activation and greater blood–brain barrier (BBB) disruption around the probe. Chronic histology demonstrate no differences in the inflammatory response at 16 weeks. Over acute time points, results also suggest immunomodulatory approaches such as targeting CD14 can be utilized to decrease inflammation to intracortical microelectrodes. The results obtained in the current study highlight the importance of not only probe material, but probe size, in regard to neuroinflammation.

Background Development of a deep learning method to identify Barrett's esophagus (BE) scopes in endoscopic images. Methods 443 endoscopic images from 187 patients of BE were included in this study. The gastroesophageal junction (GEJ) and squamous-columnar junction (SCJ) of BE were manually annotated in endoscopic images by experts. Fully convolutional neural networks (FCN) were developed to automatically identify the BE scopes in endoscopic images. The networks were trained and evaluated in two separate image sets. The performance of segmentation was evaluated by intersection over union (IOU). Results The deep learning method was proved to be satisfying in the automated identification of BE in endoscopic images. The values of the IOU were 0.56 (GEJ) and 0.82 (SCJ), respectively. Conclusions Deep learning algorithm is promising with accuracies of concordance with manual human assessment in segmentation of the BE scope in endoscopic images. This automated recognition method helps clinicians to locate and recognize the scopes of BE in endoscopic examinations.

Background Both inflammatory bowel disease (IBD) and hepato‐pancreato‐biliary cancers (HPBC) have been established to cause a huge socioeconomic burden. Epidemiological studies have revealed a close association between IBD and HPBC. Methods Herein, we utilized inverse‐variance weighting to conduct a two‐sample Mendelian randomization analysis. We sought to investigate the link between various subtypes of IBD and HPBC. To ensure the accuracy and consistency of our findings, we conducted heterogeneity tests, gene pleiotropy tests, and sensitivity analyses. Results Compared to the general population, IBD patients in Europe exhibited a 1.22‐fold increased incidence of pancreatic cancer (PC) with a 95% confidence interval (CI) of 1.0022–1.4888 (p = 0.0475). We also found a 1.14‐fold increased incidence of PC in Crohn's disease (CD) patients with (95% CI: 1.0017–1.3073, p = 0.0472). In the East Asian population, the incidence of hepatocellular carcinoma (HCC) was 1.28‐fold higher (95% CI = 1.0709–1.5244, p = 0.0065) in IBD patients than in the general population. Additionally, ulcerative colitis (UC) patients displayed 1.12‐fold (95% CI: 1.1466–1.3334, p < 0.0001) and 1.31‐fold (95% CI: 1.0983–1.5641, p = 0.0027) increased incidences of HCC and cholangiocarcinoma (CCA), respectively. Finally, the incidence of PC was 1.19‐fold higher in CD patients than in the general population (95% CI = 1.0741–1.3132, p = 0.0008). Conclusion Our study validated that IBD is a risk factor for HPBC. This causal relationship exhibited significant heterogeneity in different European and East Asian populations.