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Following aneurysmal subarachnoid hemorrhage (aSAH), aneurysm rebleeding leads to very poor clinical outcomes. Ruptured aneurysms must be urgently secured either by open microsurgery or endovascular techniques to prevent re-rupture. The objective of this study was to compare time-to-treatment and functional outcomes following aSAH between rural and urban patients treated at a quaternary neurosurgical centre with a large geographical catchment. We analyzed patients enrolled in the Vancouver Ruptured Aneurysm Database (VRAD) between December 2022 and September 2025. Demographic, clinical, radiographic, treatment and functional outcomes were compared between groups. Time from ictus-to-presentation, ictus-to-neurosurgical centre, ictus-to-treatment and transfer times were collected. Proportion of aneurysms treated within 24&#xa0;hours of ictus were also compared between groups. Our cohort included 124 patients: 81 (65.3%) urban and 43 (34.7%) rural. Rural patients lived farther from the neurosurgical centre (>100&#xa0;km: 79.1% vs. 9.9%; >500&#xa0;km: 30.2% vs. 0%). Rural patients had longer transfer times from outside hospital to neurosurgical centre (median 11.5 vs. 5.0&#xa0;h; p&#xa0;<&#xa0;0.001) and longer time from ictus-to-neurosurgical centre (median 13.2 vs. 5.5&#xa0;h; p&#xa0;<&#xa0;0.001). Despite rural patients having longer times from ictus-to-treatment (median 24.0 vs. 22.2&#xa0;h; p&#xa0;<&#xa0;0.001), there were no differences in proportion of patients treated within 24&#xa0;h of ictus (rural 51.2% vs urban 54.3%; p&#xa0;=&#xa0;0.737). Discharge disposition, mortality (12.1%), and mRS at discharge (mean 3.2&#xa0;&#xb1;&#xa0;1.9) and 3&#xa0;months (mean 3.1&#xa0;&#xb1;&#xa0;2.4) were comparable between groups. However, rural patients reported lower 3-month post-aSAH quality of life than urban patients (mean EQ-5D: 71.4 vs. 80.3; p&#xa0;=&#xa0;0.042). Rural patients with aSAH achieve comparable time-to-treatment, likelihood of being treated within 24&#xa0;hours of ictus and functional outcomes, to urban patients when treated at a high-volume neurosurgical centre with a robust centralized system of inter-hospital neurosurgery consultation and transfer. Rural patients, however, experience a significantly worse quality-of-life 3&#xa0;months following aneurysm treatment. Over a large geographical area, timely access to comprehensive aSAH management and treatment is possible for rural patients in a system where care delivery and transfer is coordinated and centralized. Coordinated regional hospitals and transfer protocols are essential to enable timely and equitable aSAH care.

Fish-mouthing (FM), defined as focal end convergence of a flow diverter(FD) with or without associated biological changes such as in-stent stenosis, has been increasingly reported with newer-generation devices and has gained increasing clinical attention. However, data regarding FM associated with the Surpass Evolve(SE) FD remain limited. This study aimed to evaluate the incidence, temporal changes, and risk factors of FM. We retrospectively reviewed 124 patients who underwent single SE (Stryker Neurovascular, Kalamazoo, MI, USA) implantation for the treatment of cerebral aneurysms. Serial follow-up skull X-rays or computed tomography(CT) were systematically reviewed. FM was defined as a &#x2265;25% reduction in the diameter of either end. Patient demographics, aneurysm characteristics and procedure-related factors were analyzed to identify predictors of FM. Of the 124 patients, 94 patients (with 115 aneurysms) completed 1-month follow-up. Most aneurysms (107 cases, 93%) were located in the internal carotid artery(ICA), with a median size of 10.03 mm (range, 2.39-28.61). At 1 month, FM was identified in 19 patients (20.21%). At 1 year, FM was observed in 6 patients (6.96%). One of the patients with FM experienced mild visual disturbance symptom. Complete occlusion was seen in 87.1% of cases at 1 year. Univariate analysis showed associations between proximal FM and fusiform shaped aneurysm, multiple aneurysms and middle cerebral artery located aneurysm. FM deformities were observed in 20.21% of SE cases at 1month and decreased to 6.98% at 1 year. Fusiform shaped aneurysm, multiple aneurysms and middle cerebral artery located aneurysm were identified as possible risk factors of proximal FM. Further studies investigating these biomechanical mechanisms are warranted to identify additional risk factors.

Glioblastoma (GBM) with a primitive neuronal component (PNC) is an uncommon GBM subtype. We report a rare case of GBM with PNC originating in the left frontal lobe and review the relevant literature. A 60-year-old woman with no previous medical history presented with a generalized seizure. MRI revealed a lesion with ring enhancement in the left frontal lobe, suggestive of a high-grade glioma. The patient underwent gross total tumor resection. Intraoperative pathological examination suggested a high-grade glioma; therefore, photodynamic therapy was applied to the resection cavity. Histopathological examination revealed an isocitrate dehydrogenase-wild-type GBM with PNC. The patient received chemoradiation therapy with temozolomide following the Stupp protocol. However, the tumor recurred rapidly within five months after resection, and bevacizumab was initiated. The tumor decreased in size after bevacizumab administration, and no distant metastasis was confirmed on whole-body CT for at least 25 months. GBM with PNC is a newly recognized and rare GBM subtype characterized by early onset, poor prognosis, and a higher propensity for extracranial metastasis and CSF dissemination compared with conventional GBM.

CUDC-907, referred to as Fimepinostat, functions as a dual inhibitor of PI3K and HDAC, exhibiting significant anti-tumor efficacy in a range of cancer types. However, its specific role in glioblastoma is not well understood. In this study, we investigated the effects of CUDC-907 on glioblastoma using cellular, organoid, and animal models to assess its inhibitory potential and toxicity. In vitro, we assessed glioblastoma cell proliferation, migration, invasion, and apoptosis using standard assays. glioblastoma organoids were treated to examine three-dimensional tumor growth and cellular changes. For in vivo analysis, animal models with glioblastoma received CUDC-907 to study its systemic impact and toxicity, with tumor progression closely monitored. We also tested the synergy between CUDC-907 and temozolomide to evaluate enhanced chemosensitivity. RNA sequencing was conducted to explore the fundamental molecular mechanisms involved, focusing on alterations in the cell cycle and DNA damage repair pathways. Our findings show that CUDC-907 significantly suppresses the proliferation, migration, and invasion of glioblastoma cells and promotes apoptosis, while exhibiting minimal toxicity. Additionally, CUDC-907 acts synergistically with temozolomide, a chemotherapy drug used for glioblastoma treatment, enhancing glioblastoma's chemosensitivity to temozolomide. RNA sequencing suggests that CUDC-907 achieves its effects by influencing the glioblastoma cell cycle and inhibiting DNA damage repair. Overall, the data suggest that CUDC-907 may be a promising anti-cancer agent for glioblastoma treatment.

This study compares the in vivo behavior (epidural thickness and complication rate including the development of cerebrospinal fluid fistula, CSF-fistula) of the newer dura sealant HEMOPATCH&#xae; (HP) with that of the well-established patch TACHOSIL&#xae; (TS) in early postoperative magnetic resonance imaging (MRI) and during the clinical course after supratentorial cranial surgery. This retrospective cohort study included 58 patients with complete datasets (HP group n = 39, TS group n = 19). Inclusion criteria were supratentorial surgery, use of one dura sealant (HP or TS), re-implantation of the bone flap, and MRI within 3&#xa0;months after surgery. We measured the thickness of the used dura sealant in axial T1-weighted sequences of postoperative MRI on the area of suture (central) and on two peripheral spots. Additionally, we examined the incidence of surgical revisions due to hemorrhage, infection, and wound healing disorders. The mean central thickness of HP and TS were 0.49&#xa0;cm and 0.55&#xa0;cm, respectively. This difference in size was not statistically significant (p = 0.066). The peripheral epidural thickness of HP (d = 0.36&#xa0;cm) was significantly smaller than of TS (d = 0.42&#xa0;cm; p = 0.014) in one of two points of peripheral measurement. Similarly, the two groups did not differ significantly in the complication rate needing surgical revision, including CSF fistula (HP 3/39 vs TS 3/19; p = 0.34). The biological behavior in terms of growth, swelling, induction of wound healing disorders, hemorrhage, and development of CSF-fistula showed no statistically significant difference within this small descriptive cohort.

Oncolytic virotherapy represents a promising yet under-explored approach for precision cancer treatment, particularly when tailored to tumor-specific molecular profiles. Patients with high-grade isocitrate dehydrogenase (IDH) mutant astrocytomas have limited treatment options and poor prognoses. Here, we investigate the therapeutic efficacy of rQNestin34.5&#x2009;v.2 (CAN-3110), an engineered oncolytic herpes simplex virus 1 (oHSV-1), in IDH1-R132H-mutant diffuse gliomas. We demonstrate that the IDH1-R132H mutation enhances glioma susceptibility to viral infection through upregulation of Nectin-1, the main HSV-1 entry receptor. Concurrently, IDH1-R132H-driven DNA hypermethylation suppresses interferon (IFN) signaling, creating a permissive microenvironment that facilitates viral replication and tumor cell apoptosis. In immunocompetent murine glioma models, intratumoral administration of rQNestin34.5&#x2009;v.2 induces robust antitumor immune activation, including increased immune infiltration and systemic IFN-&#x3b3; release. However, elevated expression of poliovirus receptor (PVR) and the immune checkpoint T-cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) on tumor-infiltrating leukocytes suggests a potential resistance mechanism to virotherapy. Combining rQNestin34.5&#x2009;v.2 with TIGIT blockade enhances therapeutic efficacy compared to monotherapy, identifying IDH1-R132H as a potential predictive biomarker for oncolytic virotherapy response.

Retrospective cohort. To compare morphologic anatomic features of individual with L4-L5 degenerative pathology with and without listhesis to identify predictive factors of instability. Aging-related degenerative changes in the lumbar spine can lead to instability in the form of a listhesis. Previous studies have identified elements of lumbar facet joint morphology that may be risk factors for instability when compared to an asymptomatic population. Patients with single-level L4-L5 degenerative pathology, with or without spondylolisthesis, who underwent L4-5 surgery were evaluated. Facet joint anatomic features were measured on standing radiographs and supine MRI. Multivariate stepwise regression was used to identify anatomic factors associated with L4-5 spondylolisthesis. Outcomes included: (1) change in % listhesis from standing radiographs to supine MRI, (2) change in listhesis between flexion and extension radiographs, (3) change in translation from standing radiographs to MRI, and (4) change in L4-5 disc angle between standing radiographs and MRI. Univariate Pearson correlation was performed for the strongest predictors. Among 231 L4-L5 surgical patients (100 with spondylolisthesis; mean age 64.3 &#xb1; 12.6; BMI 29.0 &#xb1; 5.9; 23.8% female), anterior disc height predicted % listhesis change from MRI to standing radiographs (&#x3b2;=-0.33, P=0.01). Middle disc height predicted change in disc angle (&#x3b2;=-1.17, P=0.01). Anterior disc height correlated with preoperative listhesis (r=-0.51, P<.001). Facet effusion width predicted flexion-extension disc angle change (&#x3b2;=0.32, P=0.05). In L4-L5 degeneration, spondylolisthesis was associated with sagittal facet orientation, greater effusion, and reduced anterior disc height, which most strongly correlated with increased translation. These features help interpret differences between standing radiographs and MRI and may assist in identifying segments where instability should influence surgical planning.

Chemotherapy resistance and intolerance present significant challenges in the effective treatment of acute myeloid leukemia (AML). However, the role of metabolic reprogramming, particularly lipid metabolic rewiring, in promoting chemotherapy resistance in leukemia has not been fully elucidated. Here, we found that multiple lipid metabolism processes are aberrantly activated in Ara-C resistant AML cells, accompanied by upregulation of JAK-STAT3 signaling and key lipid metabolic regulators, notably SREBP1 and CPT2. Additionally, we discovered W1307, a potent and highly selective STAT3 inhibitor, which demonstrated significant anti-tumor activity both in vitro and in vivo. Genetic and pharmacological inhibition of STAT3 simultaneously suppresses lipid synthesis and catabolism, leading to lipids metabolic disorder accompanied with lipids accumulation, ROS increase, lipid peroxidation and mitochondrial membrane potential decrease. Mechanistically, STAT3 binds to DNA response elements in the promoters of the lipid metabolism associated gene SREBF1 and CPT2, and regulates their expression. Furthermore, inhibition of STAT3 enhances the anti-tumor effect of Ara-C and sensitizes resistant AML cell line to Ara-C through disrupting lipid homeostasis and triggering lipotoxicity. Our findings highlight the critical role of STAT3-driven lipid metabolism reprogramming in chemoresistance. Furthermore, W1307 emerges as a promising therapeutic candidate to overcome chemoresistance in leukemia treatment.

The high incidence of in-stent restenosis (ISR) associated with bare-metal stents (BMS) undermines the viability of endovascular treatment as a treatment option for patients with severe symptomatic intracranial atherosclerotic stenosis (ICAS). The study aimed to evaluate whether durable fluoropolymer drug-eluting stents (DES) reduce the incidence of ISR compared with BMS in the treatment of severe ICAS. This prospective, multicentre, open-label, blinded outcome clinical trial was conducted at 16 centres in China, enrolling patients with ischaemic stroke or transient ischaemic attack (<90&#x2009;days) attributed to 70%-99%&#x2009;stenosis of an intracranial major artery. Eligible patients were randomly assigned to receive durable fluoropolymer DES or BMS for stenosis treatment. The primary outcome was ISR at 1 year postprocedure, which was defined as a stenosis rate of &#x2265;50% occurring within or immediately adjacent to (within 5 mm) the stent. Secondary outcomes included symptomatic ISR and stroke or death within 30 days or stroke in the target vessel territory between 31 days and 1 year. Between 20 February 2023 and 10 April 2024, 156 patients were enrolled and assigned to receive DES (n=78) or BMS (n=78). The median age was 61 years (IQR 54-67), and 129 (82.7%) of 156 patients were male. At 1 year, the primary outcome occurred in 2.9% in the DES group versus 27.9% in the BMS group (risk difference -0.25, 95% CI -0.37 to -0.13, p<0.001). No significant differences were observed between the DES and BMS groups in symptomatic ISR (0% vs 2.9%, p=0.20) or in stroke or death within 30 days or stroke in the target vessel territory between 31 days and 1 year (7.7% vs 12.3%, p=0.45). Among patients with severe ICAS, treatment with durable fluoropolymer DES resulted in a lower 1-year ISR compared with BMS. NCT05719883.

To investigate the value of interictal fast ripples (FRs; 250-500&#x202f;Hz) recorded by stereoelectroencephalography (SEEG) in identifying extra-temporal epileptogenic sites and predicting surgical outcomes in temporal plus epilepsy (TPE), using a clinically driven, neuroanatomically based categorization of patients and recording contacts. We performed a retrospective cohort study of 21 consecutive patients with electroclinically defined TPE who underwent SEEG monitoring and subsequent resective surgery at our center between January 2021 and June 2023. Interictal ripples (80-250&#x202f;Hz) and FRs (250-500&#x202f;Hz) were identified during stable non-rapid eye movement (NREM) sleep by experienced epileptologists using semi-automatic detection followed by blinded visual review. Each recording contact was assigned to one of four neuroanatomical sub-regions on the basis of post-implantation CT-MRI fusion: mesial temporal, lateral temporal, insular, or orbitofrontal cortex. Patients were categorized by the neuroanatomical distribution of the SEEG-defined SOZ into a mesial-restricted TPE group (SOZ confined to mesial temporal structures with rapid extra-temporal propagation, n&#x202f;=&#x202f;5) and a multilobar TPE group (SOZ involving the temporal lobe plus at least one extra-temporal structure at onset, n&#x202f;=&#x202f;16). Surgical resection was tailored to each patient based on the SEEG-defined SOZ, with FR-rich extra-temporal sites considered for inclusion when functional risk allowed. Patients were grouped post hoc by the actual resection extent: Group A (temporal resection alone, n&#x202f;=&#x202f;5) and Group B (temporal plus extra-temporal satellite resection, n&#x202f;=&#x202f;16). Outcomes were assessed using the Engel classification at &#x2265;&#x202f;24 months. A total of 412 contacts were analyzed. The FR positivity rate was 82.4% (34/41) at SOZ contacts versus 12.3% at non-SOZ contacts (P&#x202f;<&#x202f;0.001). In the mesial-restricted TPE group, FRs were strongly concentrated in the mesial temporal region (positivity 92.3%), with very low rates in insular (FR density 0.2&#x202f;&#xb1;&#x202f;0.1 events/min) and orbitofrontal contacts (0.1&#x202f;&#xb1;&#x202f;0.1 events/min). In the multilobar TPE group, the mesial temporal FR density was comparable (4.5&#x202f;&#xb1;&#x202f;1.0 vs. 4.8&#x202f;&#xb1;&#x202f;1.2 events/min, P&#x202f;=&#x202f;0.452), but FR density was markedly higher in the insula (3.1&#x202f;&#xb1;&#x202f;0.8 events/min, P&#x202f;<&#x202f;0.001) and the orbitofrontal cortex (2.4&#x202f;&#xb1;&#x202f;0.7 events/min, P&#x202f;=&#x202f;0.003). The Engel Class Ia rate was 81.3% (13/16) in Group B versus 20.0% (1/5) in Group A (OR=0.15, 95% CI: 0.04-0.58, P&#x202f;=&#x202f;0.006). Focal cortical dysplasia (47.6%) was the most common postoperative histopathological finding. When patients with TPE are categorized by the neuroanatomical distribution of the SOZ, interictal FRs co-localize with SOZ contacts and concentrate in the extra-temporal sub-regions (insula, orbitofrontal cortex) that define multilobar TPE. Inclusion of FR-rich extra-temporal sites in the tailored resection was associated with markedly improved postoperative seizure freedom. These findings support FRs as a clinically useful electrophysiological marker of extra-temporal epileptogenicity in TPE, while confirming that formal demonstration of a functional epileptogenic network will require dedicated spatiotemporal connectivity analyses, which we propose as the next step.

Emotional intelligence (EI) has emerged as a critical neurocognitive construct linking affective processing, social behavior, and adaptive functioning. This integrative narrative review synthesizes multidisciplinary findings to map the biological underpinnings of EI across genetic, epigenetic, neuroanatomical, and neurophysiological domains. Drawing on evidence from neuroimaging, molecular genetics, neurochemistry, and brain connectivity studies, the review suggests EI as a product of dynamic interactions between prefrontal-limbic circuits, neurotransmitter systems, and environmentally sensitive regulatory mechanisms. Key brain structures, including the prefrontal cortex, amygdala, anterior cingulate cortex, and insula, operate within coordinated networks that support the recognition, regulation, and social cognition of emotions. Neurotransmitters such as dopamine, serotonin, oxytocin, and gamma-aminobutyric acid (GABA) modulate the emotional reactivity and cognitive control essential to EI. Epigenetic modifications further explain the lifelong plasticity of emotional capacities in response to experience. Anchored in the process model of emotion regulation and the social brain hypothesis, this review provides a cohesive neuroscientific framework for EI. It outlines its translational implications in education, healthcare, and affective computing. By consolidating current advances, this review may help inform precision interventions and policy initiatives aimed at enhancing emotional resilience, empathy, and psychological well-being.

Parkinson's disease management is often complicated by motor fluctuations and dyskinesia. Although deep brain stimulation addresses these symptoms, its use is limited by invasiveness, potential device failure, and the need for ongoing maintenance. Magnetic resonance-guided focused ultrasound (MRgFUS) provides incisionless, image-guided ablation as an alternative. However, the benefits and harms of staged, bilateral MRgFUS pallidothalamic tractotomy have not been evaluated systematically in prospective multicentre studies. In this prospective, multicentre, single-arm study, adults with idiopathic, levodopa-responsive Parkinson's disease and motor complications (Movement Disorders Society Unified Parkinson's Disease Rating Scale [MDS-UPDRS] part IV item 4.2 or 4.4 score &#x2265;2) were enrolled at nine investigational centres (six in the USA, two in Spain, and one in Taiwan). Participants underwent unilateral MRgFUS pallidothalamic tractotomy to the symptom-dominant side. Contralateral pallidothalamic tractotomy followed a minimum of 6 months later for participants meeting prespecified criteria. The primary efficacy endpoint was percent change from baseline to 3 months after the second procedure in the summed MDS-UPDRS part III off-medication upper and lower extremity (ULE) motor scores. Safety outcomes were incidence, severity, and persistence of treatment-related adverse events in the 12 months after each procedure. Safety and efficacy of unilateral treatment were evaluated in the unilateral intention-to-treat (ITT) and safety populations, defined as all patients receiving one or more sonications during the first procedure. The primary outcome and safety of bilateral treatment were evaluated in the bilateral modified ITT (mITT) and safety populations, which required one or more sonications during the second procedure, a baseline motor assessment, and at least one post-bilateral motor assessment. This trial is registered at ClinicalTrials.gov, NCT04728295 and is active, not recruiting. Between July 12, 2021, and Nov 1, 2023, 54 patients received unilateral treatment and 40 proceeded to bilateral treatment (63 [67%] were male and 31 [33%] were female) and were included in the primary analysis; 36 completed 12-month follow-up after the second procedure. Median bilateral ULE motor scores decreased from 33&#xb7;0 points (IQR 28&#xb7;0-40&#xb7;5) at baseline to 21&#xb7;0 points (15&#xb7;0-25&#xb7;5) at month 3 post-bilateral treatment, a median within-patient change of 10&#xb7;5 points (5&#xb7;7-20&#xb7;0), representing a 32% (18-52) improvement (p<0&#xb7;0001). Benefits became apparent within 1 month of the first procedure and lasted through to 12 months after the second procedure. Treatment-related adverse events occurred in 21 (39%) of 54 patients after unilateral treatment; one (2%) had a persistent moderate adverse event at 6 months. After bilateral treatment, 22 (55%) of 40 patients had treatment-related adverse events; ten (25%) had persistent moderate or severe adverse events at 12 months, mainly affecting speech, gait, and balance. One (3%) patient developed severe persistent anarthria. Unilateral MRgFUS pallidothalamic tractotomy demonstrated safety and efficacy for Parkinson's disease motor complications; however, bilateral treatment offered small motor gains while increasing persistent moderate or severe adverse events. Post-bilateral treatment complications in speech, gait, and balance are consistent with historical data for bilateral ablative procedures for movement disorders. Although unilateral MRgFUS pallidothalamic tractotomy was beneficial in our study, bilateral procedures demand rigorous patient selection and counselling regarding cumulative risks. Insightec.

A 76-year-old man presented with headache, progressive left-sided visual loss, and cranial neuropathy. Initial MRI and cerebrospinal fluid findings mimicked those of hypertrophic pachymeningitis. Corticosteroid therapy provided only a transient improvement before clinical deterioration, including right-eye blindness. A re-evaluation revealed destructive sphenoid sinus disease, and surgical decompression confirmed invasive Aspergillus sinusitis. The course was complicated by a ruptured infectious internal carotid artery aneurysm, which required emergency endovascular embolization. Despite the catastrophic subarachnoid hemorrhage, the patient survived with intensive multidisciplinary treatment. This case highlights the diagnostic pitfalls of invasive fungal sinusitis and the catastrophic risks of empirical corticosteroid administration for suspected inflammatory diseases without excluding a fungal etiology.

Closed reduction is an important adjunct in the surgical management of traumatic cervical facet dislocations, particularly jumped and locked facets. By restoring normal spinal alignment, successful closed reduction allows the surgeon to proceed with surgical stabilization via an anterior-first approach, obviating the need to rotate a dislocated, biomechanically unstable cervical spine, thereby minimizing the risk of iatrogenic spinal cord injury. While closed reduction has traditionally been achieved with Gardner-Wells tongs and weights, this reduction method requires the patient to remain bedbound for prolonged periods of time, is not MRI-compatible, and is associated with inconsistent results. We present two patients with bilaterally jumped and locked cervical facets, in whom a closed manual reduction technique was used, allowing rapid spinal realignment prior to surgical stabilization. We provide a detailed video illustration of this technique, emphasizing the steps involved and relevant technical nuances. While this technique might have been previously used and rarely reported, it has not, to the best of our knowledge, been described in a detailed, step-by-step fashion. Closed manual reduction of traumatic cervical facet dislocations can be performed safely and effectively in the operating room prior to definitive surgical stabilization of the spine. This technique should not be attempted in patients with severe spinal cord compression or neurologic compromise. The importance of adequate muscle relaxation provided by general anesthesia and continuous intraoperative feedback provided by live fluoroscopy and neurophysiologic monitoring cannot be overemphasized.

Cerebrospinal fluid circulation through the glymphatic system plays a crucial role in removing metabolic waste from the central nervous system. However, the mechanism underlying the brain-wide glymphatic dynamics is not yet fully understood, in part due to the lack of glymphatic imaging technologies on deep brains. Here, we report a hybrid imaging technology that integrates three-dimensional photoacoustic tomography and ultrasound localization microscopy (3D-PAULM), enhanced by a photoacoustic dye with strong optical absorption in the second near-infrared window (NIR-II). 3D-PAULM allows for continuous, noninvasive, whole-brain imaging in mice through intact skull, providing superresolution mapping of the brain vasculature and highly sensitive tracing of the NIR-II dye in the glymphatic system. Using 3D-PAULM, we investigated the glymphatic function impaired by ischemic stroke, aging, and anesthesia. Our results provide insights into glymphatic transport under various physiological as well as pathological conditions and establish 3D-PAULM as a valuable tool for preclinical glymphatic research.

Extracapsular resection is effective for functioning pituitary adenomas, but its role in tumors with suprasellar extension remains unclear. The aim of this study was to evaluate surgical outcomes of a refined endoscopic transnasal technique for nonfunctioning pituitary adenomas with suprasellar extension, focusing on pseudocapsule-based extracapsular resection. We retrospectively analyzed 259 patients with tumors &#x2265;20 mm and &#x2265;1-year follow-up (2007-2023). Factors associated with complete pseudocapsular resection and surgical outcomes were evaluated using unadjusted and multivariable logistic regression analyses stratified by surgical period. A pseudocapsule was identified in 52.5% of cases, and complete resection was achieved in 34.4%. Total resection was achieved in 73.7%, with most residual tumors in the cavernous sinus. Complete pseudocapsular resection was associated with smaller tumor size, reduced intraoperative cerebrospinal fluid leakage, lower residual tumor rates, and fewer postoperative hemorrhages and complications in unadjusted analyses.In multivariable analyses, these associations were significant in the early period but not in the later period, whereas reduced overall complications remained significant across both periods. Tumor regrowth occurred in 22 patients and was controlled with stereotactic radiotherapy. Tumor size-but not suprasellar extension-was associated with complete pseudocapsular resection. Complete pseudocapsular resection is associated with improved outcomes, particularly during earlier phases of surgical experience, although its relative impact may decrease with increasing surgical proficiency. Careful identification and resection of the pseudocapsule should be pursued when feasible.

Humans can convey new and highly diverse information through language. This ability to form and combine words into elaborate phrases and sentences enables us to express inexhaustible meanings and is fundamental to human cognition1-5. However, understanding the microscopic&#xa0;cellular building blocks and cortical landscape that precisely&#xa0;underlie human language has remained a challenge. Here we used wide-scale single-neuronal recordings combined with natural language processing models to identify fine-grained linguistic representations across the human frontotemporal cortex during language production. We find that, whereas certain neurons represented the detailed grammatical relationships between words or their parts of speech, others tracked the sentences' higher-order syntactic structure, their phrase transitions and sequence. Collectively, these neurons reliably captured the words' syntactic and semantic properties but also dynamically incorporated their specific sentence contexts, therefore&#xa0;enabling them to encode information combinatorially and at highly granular levels of detail. We show how these cell populations were locally organized and how their microscale representations differed from that of their wider field potential patterns. We also show how these neurons were distributed broadly across the frontotemporal cortex, but how their ability to encode linguistic information was left-lateralized and varied between&#xa0;cortical regions. Together, these findings identify some of the most basic cellular building blocks by which linguistic information is encoded in humans and begin to define the cortical landscape of language at a combined micro (cellular), meso (local population) and macro (regional) scale.

Tumor treating fields (TTFields) improve survival in glioblastoma (GBM), but their clinical efficacy is limited by inefficient electric-field delivery through the high-impedance scalp and skull. This attenuation reduces intratumoral electric-field intensity and increases superficial power deposition, while external arrays remain associated with skin-interface complications. We propose an intracranial-implanted coupled-electrode TTFields strategy (ICE-TTF), in which a single depth electrode implanted in the tumor cavity is coupled with distributed extracranial counter-electrodes. Finite-element modeling was used to optimize electrode geometry and evaluate electric-field and thermal distributions. A segmented intracranial electrode was examined for directional field switching. Short-term anti-tumor activity was assessed in rat glioma models using bioluminescence imaging and histology. Impedance monitoring and electrochemical assays were performed to evaluate interface behavior, short-term electrode stability, and tissue response. In simulations, ICE-TTF generated tumor electric-field intensities within the TTFields-relevant range with substantially lower power and lower temperature rise than external TTFields under matched coverage assumptions. Segmented contacts enabled switching between predominantly radial and tangential field components. In vivo, ICE-TTF attenuated the BLI-derived tumor-burden signal and reduced proliferative activity. Electrode-tissue impedance was associated with BLI-derived tumor-burden progression, supporting its potential as a candidate monitoring signal. Electrochemical modeling, ion-release measurements, and short-term histology supported short-term electrochemical stability and peri-electrode tissue compatibility of Pt-Ir electrodes under the tested high-frequency stimulation conditions. ICE-TTF represents a candidate reduced-implant-burden intracranial TTFields delivery architecture. The current data support simulation-based field-delivery feasibility, short-term proof-of-concept anti-tumor activity, and future impedance-informed monitoring, while direct comparative efficacy, survival benefit, and closed-loop control remain to be validated.

Glioma is a highly aggressive central nervous system malignancy characterized by profound immune evasion, the underlying mechanisms of which remain incompletely defined. This study investigated how the transcription factor RBP-J drives immune suppression through activation of NNMT in cancer-associated fibroblasts (CAFs). By integrating single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST), we identified a CAF-specific NNMT-high subpopulation enriched at the tumor margin and closely associated with M2 macrophages. Bioinformatic analyses using Seurat and Monocle3 delineated a stromal-immune regulatory network and highlighted RBP-J as a potential upstream regulator of NNMT. Mechanistic experiments demonstrated that RBP-J directly binds to the NNMT promoter and activates its transcription, leading to intracellular SAM depletion, reduced H3K27me3 levels, and epigenetic upregulation of SAA3. Elevated SAA3 promoted M2 macrophage recruitment and polarization, resulting in CD8+ T cell exhaustion and immune suppression. In vivo experiments using an orthotopic glioma model confirmed that NNMT-high CAFs accelerated tumor growth, increased M2 macrophage infiltration, and diminished CD8+ T cell activity. Importantly, combined treatment with an NNMT inhibitor and &#x3b1;PD-1 partially reversed the immunosuppressive microenvironment and significantly enhanced therapeutic efficacy. Collectively, this study identifies the RBP-J/NNMT/SAA3 axis as a critical stromal-driven mechanism of immune evasion in glioma and provides a rationale for targeting metabolic-epigenetic pathways to improve immunotherapy outcomes. Schematic Diagram Illustrating the Molecular Mechanism by Which RBP-J Promotes Immune Evasion in Glioma via Activation of NNMT in CAFs, Leading to H3K27 Demethylation-Mediated Upregulation of SAA3 and Subsequent Reprogramming of M2 Macrophages.