TLR7 modulates extramedullary splenic erythropoiesis in P. yoelii NSM-infected mice through the regulation of iron metabolism of macrophages with IFN-γ

Splenomegaly is a prominent clinical manifestation of malaria and the causes remain incompletely clear. Anemia is induced in malaria and extramedullary splenic erythropoiesis is compensation for the loss of erythrocytes. However, the regulation of extramedullary splenic erythropoiesis in malaria is unknown. An inflammatory response could facilitate extramedullary splenic erythropoiesis in the settings of infection and inflammation. Here, when mice were infected with rodent parasites, Plasmodium yoelii NSM, TLR7 expression in splenocytes was increased. To explore the roles of TLR7 in splenic erythropoiesis, we infected wild-type and TLR7-/- C57BL/6 mice with P. yoelii NSM and found that the development of splenic erythroid progenitor cells was impeded in TLR7-/- mice. Contrarily, the treatment of the TLR7 agonist, R848, promoted extramedullary splenic erythropoiesis in wild-type infected mice, which highlights the implication of TLR7 on splenic erythropoiesis. Then, we found that TLR7 promoted the production of IFN-γ that could enhance phagocytosis of infected erythrocytes by RAW264.7. After phagocytosis of infected erythrocytes, the iron metabolism of RAW264.7 was upregulated, evidenced by higher iron content and expression of Hmox1 and Slc40a1. Additionally, the neutralization of IFN-γ impeded the extramedullary splenic erythropoiesis modestly and reduced the iron accumulation in the spleen of infected mice. In conclusion, TLR7 promoted extramedullary splenic erythropoiesis in P. yoelii NSM-infected mice. TLR7 enhanced the production of IFN-γ, and IFN-γ promoted phagocytosis of infected erythrocytes and the iron metabolism of macrophages in vitro, which may be related to the regulation of extramedullary splenic erythropoiesis by TLR7

Interpretable surface-based detection of focal cortical dysplasias:a Multi-centre Epilepsy Lesion Detection study

One outstanding challenge for machine learning in diagnostic biomedical imaging is algorithm interpretability. A key application is the identification of subtle epileptogenic focal cortical dysplasias (FCDs) from structural MRI. FCDs are difficult to visualize on structural MRI but are often amenable to surgical resection. We aimed to develop an open-source, interpretable, surface-based machine-learning algorithm to automatically identify FCDs on heterogeneous structural MRI data from epilepsy surgery centres worldwide. The Multi-centre Epilepsy Lesion Detection (MELD) Project collated and harmonized a retrospective MRI cohort of 1015 participants, 618 patients with focal FCD-related epilepsy and 397 controls, from 22 epilepsy centres worldwide. We created a neural network for FCD detection based on 33 surface-based features. The network was trained and cross-validated on 50% of the total cohort and tested on the remaining 50% as well as on 2 independent test sites. Multidimensional feature analysis and integrated gradient saliencies were used to interrogate network performance. Our pipeline outputs individual patient reports, which identify the location of predicted lesions, alongside their imaging features and relative saliency to the classifier. On a restricted 'gold-standard' subcohort of seizure-free patients with FCD type IIB who had T1 and fluid-attenuated inversion recovery MRI data, the MELD FCD surface-based algorithm had a sensitivity of 85%. Across the entire withheld test cohort the sensitivity was 59% and specificity was 54%. After including a border zone around lesions, to account for uncertainty around the borders of manually delineated lesion masks, the sensitivity was 67%. This multicentre, multinational study with open access protocols and code has developed a robust and interpretable machine-learning algorithm for automated detection of focal cortical dysplasias, giving physicians greater confidence in the identification of subtle MRI lesions in individuals with epilepsy

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Metabolism and Intracranial Epileptogenicity in Temporal Lobe Long-Term Epilepsy-Associated Tumor

Brain tumors are common in epilepsy surgery and frequently occur in the temporal lobe, but the optimal surgical strategies to remove the tumor and epileptogenic zone remain controversial. We aim at illustrating the positron emission tomography (PET) metabolism and the stereoelectroencephalography (SEEG) epileptogenicity of temporal lobe long-term epilepsy-associated tumors (LEAT). In this study, 70 patients and 25 healthy controls were included. Our analysis leveraged group-level analysis to reveal the whole-brain metabolic pattern of temporal lobe LEATs. The SEEG-based epileptogenicity mapping was performed to verify the PET findings in the epileptic network. Compared to controls, patients with a temporal lobe LEAT showed a more widespread epileptic network based on 18FDG-PET in patients with a mesial temporal lobe LEAT than in those with a lateral temporal lobe LEAT. The significant brain clusters mainly involved the paracentral lobule (ANOVA F = 9.731, p < 0.001), caudate nucleus (ANOVA F = 20.749, p < 0.001), putamen (Kruskal–Wallis H = 19.258, p < 0.001), and thalamus (ANOVA F = 4.754, p = 0.011). Subgroup analysis and SEEG-based epileptogenicity mapping are similar to the metabolic pattern. Our findings demonstrate the metabolic and electrophysiological organization of the temporal lobe LEAT epileptic network, which may assist in a patient-specific surgical strategy

Altered Metabolic Networks in Mesial Temporal Lobe Epilepsy with Focal to Bilateral Seizures

This study was designed to identify whether the metabolic network changes in mesial temporal lobe epilepsy (MTLE) patients with focal to bilateral tonic-clonic seizures (FBTCS) differ from changes in patients without FBTCS. This retrospective analysis enrolled 30 healthy controls and 54 total MTLE patients, of whom 27 had FBTCS. Fluorodeoxyglucose positron emission tomography (FDG-PET) data and graph theoretical analyses were used to examine metabolic connectivity. The differences in metabolic networks between the three groups were compared. Significant changes in both local and global network topology were evident in FBTCS+ patients as compared to healthy controls, with a lower assortative coefficient and altered betweenness centrality in 15 brain regions. While global network measures did not differ significantly when comparing FBTCS− patients to healthy controls, alterations in betweenness centrality were evident in 13 brain regions. Significantly altered betweenness centrality was also observed in four brain regions when comparing patients with and without FBTCS. The study revealed greater metabolic network abnormalities in MTLE patients with FBTCS as compared to FBTCS− patients, indicating the existence of distinct epileptogenic networks. These findings can provide insight into the pathophysiological basis of FBTCS

Magnetic Resonance-Guided Laser Interstitial Thermal Therapy for Hypothalamic Hamartoma: Surgical Approach and Treatment Outcomes

Hypothalamic hamartoma (HH) is a rare lesion consisting of normal neurons and neuroglia arranged in an abnormal pattern which usually causes gelastic seizures (GS). Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) has been developed as a minimally invasive approach to treat HH and gradually become a first-line treatment. In total, this study enrolled 47 consecutive HH patients that underwent one round of ablation. Patients were followed for at least one year. Patients’ medical records and surgical information were carefully reviewed, and univariate analyses were performed. Of the treated patients, 72.3% remained GS-free in this study, with an overall Engel class I rate of 68.1%. Long-term postoperative complications occurred in six patients. Factors associated with GS prognosis included Delalande classification (p = 0.033), HH volume (p = 0.01), and the ablation rate of the HH body (p = 0.035). The disconnection rate was 0.73 ± 0.14 in the Engel class Ia group as compared to 0.62 ± 0.13 in the Engel Ib–Engel IV group (p = 0.046). MRgLITT represents a safe and effective surgical procedure. Patients with larger or Delalande type IV HH may require multiple rounds of ablation. In addition to assessing the degree of disconnection, ablation volume should also be carefully considered for patients undergoing this procedure