Explore the vast range of titles available.

Temporal lobe adult-onset seizures (TAOS) related to autoimmunity represent an increasingly recognized disease syndrome within the spectrum of epilepsies. In this context, certain autoantibodies (autoABs) were often associated with limbic encephalitis (LE). Here, we aimed to gain insights into (a) the distribution of 'neurological' autoABs (neuroABs, defined as autoABs targeting neuronal surface structures or 'onconeuronal' ABs or anti-glutamate acid decarboxylase 65 (GAD65) autoABs) in a large consecutive TAOS patient cohort, to characterize (b) clinical profiles of seropositive versus seronegative individuals and to find (c) potential evidence for other autoABs. Blood sera/cerebrospinal fluid (CSF) of TAOS patients (n = 800) and healthy donors (n = 27) were analyzed for neuroABs and screened for other autoABs by indirect immunofluorescence on hippocampal/cerebellar sections and immunoblots of whole brain and synaptosome lysates. Serological results were correlated with clinico-neuropsychological features. 13% of TAOS patients (n = 105) were neuroAB+, with anti-GAD65 and anti-N-methyl-D-aspartate receptors (NMDAR) as most frequent autoABs in this group. In our screening tests 25% of neuroAB- patients (n = 199) were positive (screening+), whereas all control samples were negative (n = 27). Intriguingly, key clinico-neuropsychological characteristics including magnetic resonance imaging (MRI) findings, epileptiform electroencephalographic (EEG) activity, and inflammatory cellular infiltrates in CSF were shared to a greater extent by neuroAB+ with neuroAB-/screening+ patients than with neuroAB-/screening- patients. Serological testing in a large consecutive TAOS patient series revealed seropositivity for anti-GAD65 autoABs as the most frequent neuroAB. Intriguingly, neuroAB+ individuals were virtually indistinguishable from neuroAB-/screening+ patients in several major clinical features. In contrast, neuroAB-/screening- TAOS patients differed in many parameters. These data support the potential presence of so far unrecognized autoABs in patients with TAOS.

Temporal lobe epilepsy (TLE) represents a devastating neurological condition, in which approximately 4/5 of patients remain refractory for anti-convulsive drugs. Epilepsy surgery biopsies often reveal the damage pattern of “hippocampal sclerosis” (HS) characterized not only by neuronal loss but also pronounced astrogliosis and inflammatory changes. Since TLE shares distinct pathogenetic aspects with multiple sclerosis (MS), we have here scrutinized therapeutic effects in experimental TLE of the immunmodulator fingolimod, which is established in MS therapy. Fingolimod targets sphingosine-phosphate receptors (S1PRs). mRNAs of fingolimod target S1PRs were augmented in two experimental post status epilepticus (SE) TLE mouse models (suprahippocampal kainate/pilocarpine). SE frequently induces chronic recurrent seizures after an extended latency referred to as epileptogenesis . Transient fingolimod treatment of mice during epileptogenesis after suprahippocampal kainate-induced SE revealed substantial reduction of chronic seizure activity despite lacking acute attenuation of SE itself. Intriguingly, fingolimod exerted robust anti-convulsive activity in kainate-induced SE mice treated in the chronic TLE stage and had neuroprotective and anti-gliotic effects and reduced cytotoxic T cell infiltrates. Finally, the expression profile of fingolimod target-S1PRs in human hippocampal biopsy tissue of pharmacoresistant TLE patients undergoing epilepsy surgery for seizure relief suggests repurposing of fingolimod as novel therapeutic perspective in focal epilepsies.

Despite major advances in molecular profiling and classification of primary brain tumors, personalized treatment remains limited for most patients. Here, we explored the feasibility of individual molecular profiling and the efficacy of biomarker-guided therapy for adult patients with primary brain cancers in the real-world setting within the molecular tumor board Freiburg, Germany. We analyzed genetic profiles, personalized treatment recommendations, and clinical outcomes of 102 patients with 21 brain tumor types. Alterations in the cell cycle, BRAF, and mTOR pathways most frequently led to personalized treatment recommendations. Molecularly informed therapies were recommended in 71% and implemented in 32% of patients with completed molecular diagnostics. The disease control rate following targeted treatment was 50% and the overall response rate was 30%, with a progression-free survival 2/1 ratio of at least 1.3 in 31% of patients. This study highlights the efficacy of molecularly guided treatment and the need for biomarker-stratified trials in brain cancers.

Objective Kawasaki disease (KD) is an acute systemic vasculitis predominantly affecting coronary arteries of infants and children. We recently identified leucin‐rich α‐2‐glycoprotein 1 (LRG‐1) as known transforming growth factor β1 (TGFβ1) signal‐modulating molecule, orchestrating endothelial activation and cardiac remodeling, as associated with interleukin‐1β (IL‐1β) signaling in KD. In the present study, we aimed to assess the role for LRG‐1 as part of a multimediator inflammatory environment as a possible direct mediator of human coronary artery endothelial activation. Methods Human coronary artery endothelial cells (HCAECs) were treated with a blood inflammatory matrix, with or without targeted inhibition of several inflammatory mediators, including LRG‐1, and were analyzed for inflammatory activation or endothelial‐to‐mesenchymal transition (EndMT) on gene expression level. Proteomic profiling of the inflammatory matrix, treatment‐naïve KD (n = 11), or healthy control serum samples (n = 10) was performed by proximity extension assay (n = 184 markers) and Luminex. Results Proteomic analysis of KD serum samples and the inflammatory matrix revealed elevation of 37 versus 50 inflammatory proteins, respectively, with 19 significantly up‐regulated markers shared. The HCAEC culture with the inflammatory matrix resulted in inflammatory endothelial activation, which was most efficiently abrogated by IL‐1 receptor type 1 (IL‐1R1) inhibition compared to all other tested drugs. Whereas inflammatory endothelial activation can also link to TGFβ‐driven EndMT, which was supported by respective signatures in our KD serum proteomics, we observed that in vitro inflammatory matrix–induced EndMT was partly impaired by both IL‐1R1 and tumor necrosis factor inhibition compared to other tested drugs. Conclusions Collectively, our observations in the context of a multimediator inflammatory environment indicate a prominent role of a specific clinically relevant cytokine signaling axis in inflammatory coronary artery endothelial activation and EndMT in the context of KD.

As China rose to its position of global superpower, Chinese groups in the West watched with anticipation and trepidation. In this volume, international scholars examine how artists, writers, filmmakers, and intellectuals from the Chinese diaspora represented this new China to global audiences. The chapters, often personal in nature, focus on the nexus between the political and economic rise of China and the cultural products this period produced, where new ideas of nation, identity, and diaspora were forged.

This essay foregrounds the work of late nineteenth-century British painter Margaret Murray Cookesley, who may be largely forgotten today, but who in her day exhibited regularly at the Royal Academy and, it seems, also managed to sell her art to an interested public. What makes her oeuvre fascinating in the context of British Aestheticism is that she successfully combined artistic principles adopted from the Aesthetic Movement with the Eastern subject matter inherited from the Orientalist painting tradition. By analysing a number of Cookesley’s Orientalist-Aestheticist paintings of harem women this essay thus suggests that Aestheticism was by no means a well-defined or self-contained artistic movement but was open enough to invite often bizarre hybrids like Cookesley’s works into its circle.

The classical hero– and this tradition lasts into the eighteenth-century–was a mature man in the middle stages of his life; in contrast, the modern hero is young and undergoes a period of learning which sees him develop from immaturity to maturity, from self-obsession to social responsibility, from desire to ethical reasoning.1 The modern age makes youth visible and renders it a significant stage in a person's life. Because the revolutions and changes caused by new political regimes, industrialization, urbanization and modern capitalism required and desired the period to do so. [...]Masson does not only elaborate on David Copperfield as a Bildungsroman but also on the novel as a general tool for the reader's Bildung–via the novel's ability to generalize, poeticize, or idealize, within a realistic setting that reveals contemporary structures of feelings. [...]he grows through the final crisis on his path to maturity: Mr. Dick is the only free and comic character who remains in Britain, but his contrariness must be shielded: society sees him as a madman or an eccentric at best, and it is only Betsey Trotwood who gives him a chance and helps him survive in a society. Because Aunt Betsey herself has come to know the dangers of \"waywardness,\" desire, imaginings and an undisciplined heart when she put herself into the hands of a useless husband.

Writings of travelers have shaped ideas about an evolving China, while preconceived ideas about China also shaped the way they saw the country. A Century of Travels in China explores the impressions of these writers on various themes, from Chinese cities