Hospital de Cruces

Recurrence patterns in OPC differ by HPV status and smoking history. HPV-positive heavy smokers represent a distinct high-risk subgroup characterized by increased distant metastasis and inferior survival, warranting refined stratification beyond p16 status alone.

Abstract Brain tumours invade neural tissue, disrupting the functional organisation of neural networks. This disruption can trigger compensatory neuroplastic mechanisms that help preserve cognitive function despite pathological burden. Resting-state functional connectivity (rs-FC) provides a valuable approach for examining these alterations, yet the scope and trajectory of network-level changes remain unclear. In this study, we used rs-FC to characterise compensatory responses induced by left-hemisphere brain tumours affecting the integrity of the language network. The comparison of connectivity patterns at diagnosis and after surgery allowed us to track the temporal progression of these patterns. Relative to healthy participants, patients showed significant deviations in pre-surgical rs-FC, with widespread changes involving the dorsal attention, sensorimotor, frontoparietal, default mode, and cerebellar networks. These differences persisted post-surgically, with no significant longitudinal modifications. Network-level alterations also influenced topological properties: patients showed increased segregation while preserving global integration relative to controls. These properties changed significantly from pre- to postoperative period, with a postoperative increase in segregation and integration towards a pattern more closely resembling that of healthy controls. Furthermore, preoperative network segregation was identified as a predictor of postoperative cognitive recovery. These findings suggest that brain tumours induce network remapping, affecting functional connectivity far beyond the regions strictly related to the affected region. The observed changes in network topological organisation likely reflect the adaptive role of domain-general networks in facilitating homeostatic processes. Surgical strategies aimed at preserving these changes seem to promote sustained cognitive function, regardless of malignancy grade or lesion extent. Key points Presurgical patients show widespread inter- and intrahemispheric rs-FC alterations, reflecting tumour-driven network remapping. Network integration and segregation show longitudinal recovery, approaching neurotypical topology four months post-surgery. Preoperative network segregation predicts postoperative cognitive recovery. Importance of the Study Brain tumours disrupt large-scale brain networks, yet the extent, temporal dynamics, and cognitive relevance of these alterations remain poorly understood. Using resting-state functional connectivity, this study provides a longitudinal, network-level characterisation of tumour-induced neuroplasticity in patients with left-hemisphere lesions affecting language-related regions. Compared with prior work focused on local effects or single networks, our results demonstrate widespread inter- and intrahemispheric connectivity changes involving multiple domain-general resting-state networks, highlighting extensive network remapping beyond lesion boundaries. Importantly, we show that postoperative recovery is accompanied by a rebalancing of network integration and segregation toward a neurotypical configuration. Critically, preoperative network segregation emerges as a predictor of postoperative cognitive recovery, identifying a potential biomarker of resilience. These findings have direct translational relevance, suggesting that preserving and supporting large-scale network organisation during surgical planning may promote cognitive outcomes independently of tumour grade or lesion extent.

N6-methyladenosine (m6A) RNA modifications and reovirus infections have recently been implicated in the development of celiac disease. While viral infections are known to alter the RNA modification machinery of the host, their interplay in autoimmune tissue damage remains unexplored. In this study we employed an in vitro model combining a viral mimic with gliadin peptides to simulate celiac disease conditions, alongside the analysis of serum and intestinal biopsies from controls and patients to investigate the link between m6A methylation and viral infections in inducing autoimmune inflammation. We found elevated anti-reovirus reactivity in patients, increased antiviral gene expression and enhanced m6A levels. Notably, the expression of IRF7 was synergistically induced by the combined exposure to the viral mimic and gliadin peptides, and this is mediated through m6A methylation in its coding region and interaction with the reader protein YTHDC2. Furthermore, the reduction of m6A through METTL3 silencing or simvastatin treatment reduced IRF7 mRNA methylation and downstream proinflammatory gene expression both in vitro and ex vivo. These findings highlight m6A methylation as a modulator of antiviral responses and a potential therapeutic target in autoimmune disorders.