Historical roots of the stigma of epilepsy: A review of the classic Iranian literature.

BACKGROUND: The stigma toward epilepsy is a daily challenge for people with epilepsy (PWE) and can influence the well-being and prognosis of these individuals. However, the cultural origins of such stigma have sparsely been examined. In this study, we aimed to investigate the classic Persian literature to gain insight into the historical and cultural beliefs and opinions regarding epilepsy as a determinant in developing stigma towards PWE. METHODS: In this narrative review of the classic Persian literature, we investigated the opinions and beliefs regarding epilepsy and PWE. In February 2023, we searched https://ganjoor.net (an open-access database of Iranian literature) for the relevant literary materials (poem and prose) using the Persian translation of the terms epilepsy (Sar'e) and epileptic (Masroo'e). Two clinical researchers went through the results and extracted the related materials under the supervision of two experts in Persian literature. A bilingual academic translated the included literary materials from Persian to English. RESULTS: Our search yielded 57 literature materials by 31 poets and writers from the 4th to 14th Hijri centuries, roughly coinciding with the past Gregorian millennium (1000-2000 AC). We classified the literary concepts related to epilepsy stigma into five subgroups: (i) a simile for pain and suffering; (ii) an atonement for blasphemous beliefs or a disease caused by supernatural power; (iii) a sign of madness, insanity, and lack of wisdom; (iv) a celestial observation; and (v) a subject for jokes. CONCLUSIONS: Classic Persian literature considered epilepsy as a simile for suffering and a sign of insanity that is caused by blasphemous beliefs or celestial objects, with PWE classified as insane and unwise. While such depictions became less prevalent after the 14th century CE, they can give rise to misconceptions and negative stigma toward PWE and should be addressed in modern culture. Each society should critically investigate its socio-cultural origins of stigma and rectify such misbeliefs.

Defining the condensate landscape of fusion oncoproteins.

Fusion oncoproteins (FOs) arise from chromosomal translocations in ~17% of cancers and are often oncogenic drivers. Although some FOs can promote oncogenesis by undergoing liquid-liquid phase separation (LLPS) to form aberrant biomolecular condensates, the generality of this phenomenon is unknown. We explored this question by testing 166 FOs in HeLa cells and found that 58% formed condensates. The condensate-forming FOs displayed physicochemical features distinct from those of condensate-negative FOs and segregated into distinct feature-based groups that aligned with their sub-cellular localization and biological function. Using Machine Learning, we developed a predictor of FO condensation behavior, and discovered that 67% of ~3000 additional FOs likely form condensates, with 35% of those predicted to function by altering gene expression. 47% of the predicted condensate-negative FOs were associated with cell signaling functions, suggesting a functional dichotomy between condensate-positive and -negative FOs. Our Datasets and reagents are rich resources to interrogate FO condensation in the future.