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PubMed2026

Quality assessment, prognostic factors, and biomarkers for brain tumor analysis: a comprehensive systematic review.

The brain tumors possess different causative factors and properties, making their diagnosis and treatment difficult. Growth of these cancers usually leads to compression of the adjacent nerves and obstruction of the flow of cerebrospinal fluid, thus leading to increase in intracranial pressure. This affects the working of brain in many ways; thus, the difficulty involved in its treatment. With the improvements in technology in neuroimaging, including Diffusion Tensor Imaging (DTI), Positron Emission Tomography (PET), and multiparametric Magnetic Resonance Imaging (mpMRI), the diagnosis process has become easy. The effectiveness of any form of therapy in such patients depends primarily on their prognosis. While it is a common practice that physicians determine the prognosis of the disease by considering the age of the patient, histological grade of the tumor, and resection status, now this method has become more comprehensive by adding molecular signature and genetic analyses to the list of criteria. Next-generation sequencing (NGS) allows a reliable molecular classification. It increases the level of risk stratification, facilitating the application of therapies tailored to individual patients. Thus, molecular oncology has greatly changed our views on brain tumors' pathology and prognosis while neoadjuvant treatments aim at increasing the survival rate. On the other hand, radiogenomics is a field of study that combines non-invasive imaging phenotypes and genomic information in order to find unique molecular signatures of tumors without collecting samples from tumors. Molecular biomarkers are absolutely essential in the diagnosis of cancer, treatment monitoring, and recurrence of cancer. Advances in liquid biopsy technology, particularly the methods for circulating tumor DNA (ctDNA) and Extracellular Vesicle (EV) based analysis, have enabled the possibility of non-invasive monitoring of the progression of the tumors over time. This review highlights key studies and important scientific works about imaging technologies, biomarkers, and prognostic factors of malignant brain tumors.

Humans↗

PubMed2026

The Efficacy of Pharmacotherapy Intervention on Anthropometric Outcomes in Survivors of Childhood Brain Tumors: An Updated Systematic Review and Meta-Analysis.

INTRODUCTION: Many survivors of childhood brain tumors face long-term adverse health outcomes like obesity. Uncertainties surround the effect of interventions to manage obesity-related outcomes in survivors of childhood brain tumors. The goal of this updated systematic review and meta-analysis was to provide the best estimate of the treatment efficacy of pharmacotherapy intervention on anthropometric outcomes in this pediatric population. METHODS: We searched CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, PubMed, ClinicalTrials.gov, and ProQuest for articles published from January 1, 2015, to January 31, 2025. A meta-analysis was performed using the generic inverse-variance method in RevMan 5.4. Heterogeneity was assessed using the Cochrane Q test and the I2 statistic. We used the GRADE approach to determine the certainty of evidence. RESULTS: A total of six studies met the inclusion criteria: four newly identified studies published after January 1, 2015 (125 participants), and two from the previously published review (23 participants). The pooled estimate showed no significant change in body mass index z-score after intervention (mean difference = -0.02; 95% CI: -0.06 to 0.02, I2 = 0%; 4 studies, 94 participants; low certainty of evidence). Similar pooled effects were observed across other outcomes; however, individual studies reported significant changes in some outcomes within the treatment groups after the intervention. CONCLUSION: Pharmacological agents showed no significant change in anthropometric outcomes for survivors of childhood brain tumors. Further trials are needed to assess the efficacy of pharmacological agents and to identify subgroups most likely to benefit.

Humans↗

PubMed2026

Assessment of the role and effectiveness of nurse-led multimodal intervention in the rehabilitation of dysphagia in patients with brain tumors.

BACKGROUND: Dysphagia is a common complication in patients with brain tumors, which has a profound adverse impact on patients' health status and quality of life. However, there is a relative lack of research on the rehabilitation of dysphagia in brain tumor patients, especially regarding the role and effectiveness of nurse-led multimodal interventions in the rehabilitation of dysphagia in brain tumor patients, which lacks systematic assessment and in-depth discussion. AIM: This study aimed to evaluate the role and effectiveness of a nurse-led multimodal intervention in improving swallowing function and quality of life in brain tumor patients with dysphagia. METHODS: In this study, a randomized controlled trial (RCT) design was used to select 120 dysphagia patients among brain tumor patients admitted to our hospital during the period of January 2024 to May 2024 as the study subjects, and they were stratified and randomly divided into an intervention group (n = 60) and a control group (n = 60). While the control group received conventional nursing care and treatment protocols, the intervention group received a nurse-led multimodal intervention program, including personalized swallowing training, nutritional support, psychological care, and a family-participatory rehabilitation program, which was developed and dynamically adjusted by nurses, rehabilitation therapists, and dietitians. Differences in data before and after the intervention were analyzed using the paired t-test or Wilcoxon signed-rank test, and between-group comparisons were made using the independent samples t-test or Mann-Whitney U test. RESULTS: Both the intervention and control groups showed improvement in swallowing function among the patients. The Kubota drinking test score, Saito's swallowing function grading, and the quality of life scores for patients in the intervention group showed a significant enhancement compared to those in the control group (P < 0.05), indicating that the intervention was more effective than the control. When compared within groups, all scores in both the intervention and control groups improved gradually with the time of intervention (P < 0.05). The improvement was significantly higher in the intervention group than in the control group. CONCLUSION: This study demonstrates that a nurse-led multimodal intervention is significantly effective in improving swallowing function and quality of life in patients with brain tumors. The intervention provides comprehensive rehabilitation support for patients through multidisciplinary collaboration and personalized care and has certain clinical promotion value.

Humans↗

PubMed2026

Understanding specificity in immune-brain pathways: A systematic review of differential associations between individual cytokines and brain structure and function measured through magnetic resonance imaging in humans.

Research shows that cytokines are associated with psychiatric disorders, including major depression, and multiple aspects of brain structure and function. Accumulating data suggest that different cytokines may have unique profiles of biological activity, particularly in their neuromodulatory roles, but it is currently unclear whether they have unique associations with specific neural circuits in humans. In this paper, we systematically review magnetic resonance imaging studies conducted with depressed or healthy control human participants under age 65 that examine associations between peripheral cytokines and brain structure and function, with the goal of evaluating evidence for the specificity of these cytokine-brain associations. We find that across multiple measures of brain structure and function, the majority of studies reviewed reported unique associations between individual cytokines and brain outcomes. A synthesis of findings across studies also suggests a preliminary hypothesis of specific associations of interleukin-6 levels in circulation with the default mode network and tumor necrosis factor-alpha with the salience network, which could be tested in future research. We conclude the review with future directions for research that can strengthen understanding of these associations.

Humans↗

PubMed2026

Awake Craniotomy for Eloquent Region Glioblastoma Classified by Tumor Location-A Retrospective and Prospective Cohort Study.

INTRODUCTION: The efficacy of awake craniotomy (AC) with intraoperative mapping for glioblastoma (GBM) in eloquent regions remains debated. This study aims to evaluate functional and survival outcomes of GBM patients undergoing AC stratified by tumor locations. METHODS: A combined retrospective (2015-2023, n = 114: 43 AC vs. 71 standard craniotomy) and prospective cohort (2023-2025, n = 28: 13 AC vs. 15 standard craniotomy) of GBM patients with motor/language-eloquent tumors was analyzed. Tumors were classified into motor subtypes (I: precentral gyrus; II: premotor/supplementary motor; III: internal capsule posterior limb; IV: other) and language subtypes (I: Broca's/precentral; II: postcentral/supramarginal gyrus; III: Wernicke's; IV: insular; V: other). Outcomes included extent of resection (EOR), postoperative motor/language recovery, overall survival (OS), and progression-free survival (PFS). RESULTS: The retrospective cohort demonstrated that AC has advantages in functional preservation across various motor/language subtypes. However, AC was associated with significantly deteriorated survival outcomes specifically in precentral gyrus GBMs. A prospective cohort study, enrolling only precentral gyrus GBMs for validation, yielded results consistent with the retrospective findings: worsened OS and PFS (OS: HR = 3.223, p = 0.0450; PFS: HR = 2.374, p = 0.0476); reduced EOR (AC: 74.3% ± 5.3%; standard craniotomy: 86.9% ± 12.3%, p = 0.0470); and better motor recovery. CONCLUSIONS: Functional preservation and survival outcomes of AC in GBM exhibited subtype-specific correlations with tumor locations. AC with intraoperative mapping effectively preserves neurological function in GBM patients. However, for tumors involving the precentral gyrus, the AC approach carries greater risks than benefits and should be considered with caution. TRIAL REGISTRATION: Strategic Intervention on Preserving Motor Function During Awake Craniotomy: NCT05143788. Strategic Intervention on Preserving Language Function During Awake Craniotomy: NCT05143775.

Adult↗

PubMed2026

Sex-dependent protective effects of microglial tumor necrosis factor on post-stroke inflammation and myelin injury.

Tumor necrosis factor (TNF) is rapidly induced after ischemic stroke, but its proposed cell-specific and sex-dependent functions during post-stroke inflammation remain insufficiently understood. Here, we investigated the role of microglia-derived TNF in the acute and subacute response to permanent middle cerebral artery occlusion (pMCAO). Tnf expression was transiently upregulated after stroke, becoming significant at 4 h, peaking at 12-24 h, and returning to baseline by 5 days. In situ hybridization confirmed strong Tnf expression in the infarct and peri-infarct regions. Whole-brain transcriptomic profiling showed that global TNF deficiency reshaped the early post-ischemic response, shifting it from microglia-associated phagocytic and wound-healing pathways toward an interferon-related inflammatory signature. To define the specific contribution of microglial TNF, we used inducible Cx3cr1CreER:Tnffl/fl mice. Microglial TNF deletion had no effect on infarct volume in males at 24 h or 5 days after pMCAO, but significantly increased infarct size in females at both time points. In both sexes, brain TNF levels peaked at 24 h and were significantly reduced in Cx3cr1CreER:Tnffl/fl mice, confirming microglia as a major source of early post-ischemic TNF. However, downstream consequences diverged by sex. At 5 days, male Cx3cr1CreER:Tnffl/fl mice showed reduced microglial reactivity and 18 kDa translocator protein (TSPO) signal, with no change in T-cell infiltration, and exhibited increased density of mature oligodendrocytes. In contrast, female Cx3cr1CreER:Tnffl/fl mice displayed enhanced microglial reactivity, increased TSPO binding, higher peri-infarct T-cell infiltration, and reduced oligodendrocyte density and myelin integrity. Together, these findings identify microglial TNF as a sex-dependent regulator of post-stroke inflammation and myelin injury.

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PubMed2026

Artificial intelligence (AI) uses in stereotactic radiosurgery (SRS): diagnosis with brain metastasis (BM) - A systematic review.

BACKGROUND: Brain metastases (BM) are the most common intracranial tumors in adults, and stereotactic radiosurgery (SRS) has become a mainstay of management. However, several diagnostic challenges persist in the SRS pathway, particularly the differentiation of radiation necrosis (RN) from true tumor progression, which conventional MRI and even advanced imaging techniques often cannot reliably resolve. Recent advances in artificial intelligence (AI) offer the potential to address these diagnostic limitations. This systematic review synthesizes current literature on AI applications for MRI-based diagnostic decision support in BM patients undergoing SRS, with a focus on radiomics and deep learning tools for distinguishing RN from progression, classifying molecular and histologic subtypes, and predicting treatment response. METHODS: A systematic review was performed in accordance with PRISMA guidelines. PubMed, Web of Science, and Scopus were searched using a targeted query combining terms related to AI, brain metastasis, diagnosis or imaging, and SRS. After screening 483 records and applying strict inclusion and exclusion criteria, 18 studies published between 2015 and 2025 were included. Data were extracted on study design, cohort characteristics, imaging modality, AI methodology, validation strategy, and reported diagnostic performance. RESULTS: Among the 18 included studies, AI models demonstrated strong performance across diagnostic tasks in the BM-SRS pathway. The differentiation of RN from true tumor progression was the most extensively studied application, addressed by 14 of 18 studies, with reported AUCs ranging from 0.71 to 0.94. Support vector machines, random-forest ensembles, convolutional neural networks, and transformer-based multimodal architectures were widely used. The literature evolved from single-sequence radiomic classifiers in 2018 to multimodal deep learning frameworks fusing imaging with clinical and genomic data in 2025. Contrast-enhanced T1-weighted MRI was the dominant imaging input, and texture-based radiomic features (GLCM, GLSZM, GLDM, and wavelet-derived features) were the most consistently predictive. The highest-performing models reached AUCs of 0.85-0.91 through multimodal integration of imaging with clinical and genomic features, and consistently outperformed expert neuroradiologist read on matched cases. Remaining studies addressed longitudinal segmentation-based detection of local failure and adverse radiation effects, BRAF mutation status in melanoma BM, early Gamma Knife treatment response, and primary tumor histology classification, with more variable performance. CONCLUSION: AI models, particularly those integrating MRI-derived radiomic features with clinical and genomic data, show high accuracy in supporting diagnostic decisions for BM patients treated with SRS. The post-SRS differentiation of radiation necrosis from true tumor progression has reached the greatest level of maturity and is closest to clinical translation, with potential to reduce unnecessary biopsies, personalize surveillance intervals, and rationalize treatment-pathway decisions. Other diagnostic applications, including molecular subtyping and primary tumor histology classification, remain exploratory and require further multicenter validation. Integration of AI tools into multidisciplinary tumor-board workflows, combined with prospective validation and standardized reporting, will be essential to realize the full clinical benefits of AI in SRS for brain metastases.

Humans↗

PubMed2026

A multicenter randomized phase II/III trial of salvage treatment for refractory primary central nervous system lymphoma using tirabrutinib: JCOG2314 (ReSTART).

Primary central nervous system lymphoma (PCNSL) is an aggressive malignancy. Patients refractory to high-dose methotrexate-based induction therapy have an extremely poor prognosis. Although whole-brain radiotherapy (WBRT) is the standard salvage treatment and provides potent tumor control, early functional deterioration and late neurocognitive toxicity remain major concerns. A phase I/II trial on relapsed or refractory PCNSL demonstrated favorable efficacy and tolerability of tirabrutinib, a second-generation selective Bruton's tyrosine kinase inhibitor. Tirabrutinib's oral administration has enabled outpatient management. However, its clinical value for induction-refractory PCNSL remains uncertain. We designed a multicenter, randomized phase II/III trial (JCOG2314) to assess the non-inferiority of tirabrutinib to WBRT in overall survival and its potential to reduce functional deterioration and cognitive impairment. A total of 94 patients from 49 institutions will be enrolled over 4 years. The trial has been registered in the Japan Registry of Clinical Trials (study number: jRCT1031250645).

Humans↗

PubMed2026

Hope is linked with more favorable tumor molecular signatures in serous ovarian cancer.

INTRODUCTION: Hope has been associated with improved quality of life and lower mortality in cancer, but the underlying biological mechanisms are poorly characterized. We previously reported that hope was associated with less inflammation and more normalized diurnal cortisol pre-treatment among women with ovarian cancer. We also reported associations of socio-environmental factors with pro-metastatic processes. Here, we used genome-wide transcriptional profiling to quantify associations between hope and tumor molecular signatures reflecting invasiveness, inflammation, and cellular immunity. METHOD: Participants were 74 women with serous ovarian cancer who provided demographic information and completed surveys pre-surgery. Hope was assessed using a face-valid item from the Center for Epidemiological Studies Depression Scale (CES-D). Depression was assessed using the full CES-D without the hope item. Illumina HT12 microarrays were used to assay tumor RNA, and associations between hope and tumor gene expression were quantified, adjusting for depression, age, BMI, grade, and stage. RESULTS: Adjusting for covariates, hope was associated with multiple favorable differences in RNA expression, including lower levels of mesenchymal differentiation (p = 0.008) and pro-inflammatory gene regulation (NF-κB: p < 0.001; IRF1: p = 0.024; STAT: p = 0.018), elevated epithelial differentiation (p = 0.011), and elevated activity of the IRF7 transcription factor which promotes cellular immunity (p = 0.016). CONCLUSIONS: These data suggest that hope is associated with an ovarian tumor gene expression profile characterized by reduced epithelial-mesenchymal transition (EMT) and inflammatory activity, and increased activity of a transcription factor promoting cellular immunity. These findings highlight potential biological implications of a resilience factor such as hope, but need replication with more robust assessments of hope.

Epithelial mesenchymal transition↗

PubMed2026

Extent of resection as an independent predictor of survival for patients with glioblastoma as defined by the new WHO 2021 classification.

OBJECTIVE: Extent of resection (EOR) has previously been demonstrated to have an impact on survival in patients with glioblastoma (GBM). However, with the World Health Organization (WHO) 2021 reclassification of GBMs based on IDH-mutation status, patients with "IDH-mutant GBMs," who typically survive long term, were reclassified as WHO grade 4 IDH-mutant astrocytomas and removed from the GBM taxonomy. Therefore, it is unknown whether the previously reported impact of resection on survival was a false-positive result due to the inclusion of the less aggressive IDH-mutant tumors in previous datasets. This study aimed to determine the extent to which EOR remains an independent predictor of survival in patients with WHO 2021 GBM after the reclassification of IDH-mutant grade 4 astrocytomas. METHODS: All cases of GBM tumors (based on the pre-2021 GBM classification) that were newly diagnosed between 2005 and 2021 were identified in our institutional database and subsequently reclassified based on the updated WHO 2021 criteria using IDH status. Multivariable statistical analyses of demographic information, survival time, and EOR based on volumetric MRI were performed to determine the independent predictors of survival for the whole group of patients and for IDH-wildtype GBM patients exclusively. Additional analyses were performed to identify an EOR threshold for improvement in survival. RESULTS: Of the 523 tumors classified as GBM based on the pre-2021 taxonomy, 52 (9.9%) cases were reclassified as WHO grade 4 IDH-mutant astrocytomas, and the median survival of patients in this group was 7.9 years, whereas median survival of the IDH-wildtype GBM patients was 1.4 years. Multivariate analyses of the whole group demonstrated that IDH-mutant astrocytomas were associated with reduced hazard of death. In both the whole group (n = 523) and in IDH-wildtype GBMs (n = 471), higher EOR of the contrast-enhancing (CE) tumor was associated with reduced hazard of death, whereas older age or male sex was associated with increased hazard of death. Because most patients (90%) had high EOR values (> 81%), a statistically meaningful EOR threshold could not be established. CONCLUSIONS: These analyses demonstrated that EOR of the CE tumor is an independent predictor of survival and that greater EOR is associated with improved survival in WHO 2021 IDH-wildtype GBMs even after excluding grade 4 IDH-mutant astrocytomas. However, an absolute EOR threshold below which resection did not improve survival could not be established, raising concerns about prior cutoff assessments.

Humans↗

PubMed2026

One Year After a Cyberattack: Lessons Learned and Dosimetric Analysis of Contingency Radiotherapy Plans.

PURPOSE: Cyberattacks on health care institutions pose significant risks to patient care, particularly in radiotherapy departments, which are heavily reliant on digital systems. This study examines the impact of a ransomware attack on our hospital and evaluates the effectiveness of the contingency measures implemented to resume radiotherapy treatments. METHODS AND MATERIALS: Following the cyberattack, our radiotherapy department faced a complete shutdown. After an initial estimate considering a shutdown of several weeks, a contingency plan was executed, including manual patient data retrieval and collaboration with a backup hospital. Contingency plans were prepared and delivered within hours, despite a partial lack of information. These plans allowed some patients to restart treatment 3 days after the attack. A dosimetric analysis was performed for the contingency plans, including various pathologies, mainly glioblastoma, head and neck cancers, and lung cancer. We compared the original and contingency plans in terms of dose coverage to the clinical target volume, biological effective dose, and their clinical impact as assessed at the 1‑year follow‑up after the cyberattack. RESULTS: Treatments resumed within 12 days at our hospital. Patients with glioblastoma showed good target coverage because of generous margins, resulting in favorable outcomes. In head and neck cases, the lack of detailed imaging led to significant target volume misses, suggesting that more conservative initial treatments could have been beneficial. Lung cases demonstrated accurate peripheral lesion targeting but faced challenges in central lesions because of the absence of positron emission tomography information. In most cases, the approach of using a contingency plan, even with limited information, led to a higher biological effective dose than would have been achieved if treatment had been stopped until full recovery at our hospital. CONCLUSIONS: The study highlights the critical importance of robust contingency planning in radiotherapy departments, emphasizing the need for backup systems and tailored approaches based on tumor location and available diagnostic information. These lessons emphasize that preparedness for digital disruptions should not focus exclusively on information and technology infrastructure.

Humans↗

PubMed2026

Quantification of appetite-regulating hormones in children with hypothalamic and common obesity.

CONTEXT: The pathophysiology of hypothalamic obesity (HyOb) remains incompletely understood with no effective treatments. OBJECTIVE: We examined differences in appetite-regulating hormone concentrations between patients with HyOb, common obesity, and lean controls. DESIGN: Multiway cross-sectional case-control study of patients aged 2 through 19 years. SETTING: Two tertiary pediatric endocrinology centers. PATIENTS: Cases were obese (body mass index [BMI] > +2 SD score [SDS], "HyOb") and lean ("HyLean") patients with congenital (septo-optic dysplasia) or acquired (suprasellar brain tumor) hypothalamic disorders. Controls had common obesity ("Ob") or nonhypothalamic disorders and normal BMI ("Lean"). MAIN OUTCOME MEASURES: Relationships between the Dykens' Hyperphagia Questionnaire Score (DHQS), plasma or serum concentrations of leptin, insulin, α-melanocyte stimulating hormone (αMSH), brain-derived neurotrophic factor, oxytocin, acylated ghrelin, agouti-related peptide and copeptin, and BMI SDS. RESULTS: Dykens' Hyperphagia Questionnaire Score did not differ between HyOb and Ob patients (24 [17-34] vs 24 [18-31]) but correlated with BMI SDS in patients with hypothalamic disorders (P = 0.02). HyOb and Ob patients exhibited similarly increased anorexigens (insulin, leptin) and decreased orexigens (ghrelin, agouti-related peptide) compared to HyLean and Lean patients. The rate of BMI increase was independently associated with lower αMSH (β = -0.23 [-0.36 to -0.11], P = .0007) and ghrelin (β=-0.004 [-0.01 to 0.00], P = .001) concentrations, suggesting that αMSH replacement may be a therapeutic target for HyOb. HyLean patients demonstrated intermediate insulin responses to glucose compared to other subcohorts. CONCLUSION: In our cohort, patients with HyOb appeared indistinguishable from Ob in terms of their appetite and appetite-regulating neuroendocrine circuitry. Higher αMSH concentrations are associated with reduced weight gain and may be a target for therapeutic intervention.

alpha-MSH↗

PubMed2026

Osimertinib With or Without Chemotherapy in Advanced Non-Small Cell Lung Cancer With EGFR and Concurrent TP53 Mutations: A Randomized Clinical Trial.

IMPORTANCE: Combination therapy has emerged as a promising therapeutic approach for patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). However, its clinical benefit-risk profile remains a focus of ongoing debate. Identifying patients most likely to derive benefit from such regimens remains an unmet clinical need. OBJECTIVE: To prospectively compare the efficacy and safety of first-line osimertinib plus chemotherapy with osimertinib monotherapy for patients with EGFR-mutated advanced NSCLC harboring concurrent TP53 mutations. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, randomized, open-label, phase 3 study conducted at 17 sites in China. Between March 25, 2021, and July 11, 2024, a total of 294 eligible patients with treatment-naive, stage IV or recurrent nonsquamous NSCLC harboring concurrent TP53 and EGFR-sensitizing mutations were enrolled. INTERVENTIONS: Patients were randomized (1:1) to receive osimertinib plus chemotherapy (pemetrexed and carboplatin every 3 weeks for 4 cycles, followed by maintenance therapy of osimertinib plus pemetrexed; n = 146) or osimertinib monotherapy (n = 148). MAIN OUTCOMES AND MEASURES: The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival, response, safety, and quality of life. RESULTS: Among 294 enrolled patients, the median age was 57 years (range, 26-79 years), and 159 (54.1%) were female. The data cutoff date was November 11, 2025. At a median follow-up of 25.1 months for the osimertinib-chemotherapy group and 26.1 months for the osimertinib monotherapy group, median progression-free survival was significantly longer with osimertinib plus chemotherapy than with osimertinib monotherapy (34.0 vs 15.6 months; difference, 18.4 months [95% CI, 9.9-22.3]; hazard ratio, 0.44 [95% CI, 0.32-0.60]; P < .001). This benefit was consistent across prespecified subgroups, including those with brain metastases and L858R mutations. The overall survival data remained immature (30.6% maturity); however, a trend toward overall survival benefit with combination therapy was observed. The incidence of grade 3 or higher treatment-related adverse events was higher in the combination group, with no new safety signal identified. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, osimertinib plus chemotherapy significantly increased progression-free survival among patients with EGFR-mutated advanced NSCLC harboring concurrent TP53 mutations. These findings provided a clinical rationale for individualized combination strategies in the management of patients with EGFR-mutated NSCLC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04695925.

Adult↗

PubMed2026

Accurate quantification of canine mitochondrial DNA copy number from canine blood and brain samples.

Acute brain injury is difficult to evaluate in veterinary medicine and tools to investigate the potential involvement of mitochondrial involvement are limited. The brain is highly enriched in mitochondria and contains thousands of copies of mitochondrial DNA (mtDNA) per cell, but robust methods for quantifying mitochondrial DNA copy number (mtDNA-CN) in canine tissues are lacking. We describe the development of a quantitative real-time PCR assay for absolute measurement of mtDNA-CN which was validated in canine blood and brain tissue. To minimize amplification of nuclear mitochondrial insertion sequences (NumtS) and repetitive regions, species-specific oligonucleotide primers were designed following in silico genomic filtering. The assay was applied to a small pilot cohort comprising blood samples from dogs with and without acute brain injury (n = 4-6 per group) and cerebral cortex samples (n = 1 per group) to assess feasibility and biological plausibility. In non-brain injury dogs, blood mtDNA-CN ranged from 98 to 288 copies per nuclear genome (mean 193 ± 72), while values in brain-injured cases ranged from 163 to 228 copies per genome (mean 200 ± 33). Cerebral cortex samples exhibited higher mtDNA-CN than blood, consistent with known tissue-specific mitochondrial enrichment. In a single brain-injured case with serial sampling, mtDNA-CN increased over five days. This study presents a validated assay and pilot data for mtDNA-CN quantification in canine samples. While not powered for biomarker evaluation, this method may enable future studies of mitochondrial dynamics in canine brain injury and metabolic disease.

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PubMed2026

The role of artificial intelligence in the diagnosis and prognosis of traumatic brain injury based on brain CT scans: a systematic review.

Traumatic brain injury (TBI) is a leading cause of emergency department visits and a major contributor to injury-related mortality and long-term neurological disability. Non-contrast computed tomography (CT) is the gold-standard imaging modality for the rapid diagnosis of TBI. Clinical outcomes depend strongly on early detection and prompt acute management. Artificial intelligence (AI)-based models may support faster automated identification of traumatic findings and early prediction of patient prognosis. A systematic literature search was conducted in PubMed/MEDLINE, Scopus, IEEE Xplore, ACM Digital Library, and the Cochrane Library in accordance with PRISMA 2020 guidelines to evaluate AI-based models for automated detection of TBI-related findings on CT and for prediction of clinical outcomes. Risk of bias and applicability were assessed using QUADAS-2 for diagnostic accuracy studies and PROBAST + AI for prediction model studies. Twenty-two studies were included. Sixteen studies evaluated diagnostic tasks and 10 evaluated prognostic outcomes, with four studies contributing to both categories. Diagnostic performance was generally high, with many studies reporting AUC values approaching or exceeding 0.90, particularly for larger lesion volumes.Prognostic performance was more variable, with moderate to high discrimination and substantial heterogeneity. Only 9 studies incorporated independent external validation, and performance was frequently lower in external cohorts. All prognostic model studies were judged to be at high overall risk of bias using PROBAST + AI, and most diagnostic accuracy studies also demonstrated high or unclear risk of bias in at least one QUADAS-2 domain, most frequently in patient selection. AI-based models applied to brain CT demonstrate strong technical performance for both diagnostic and prognostic tasks in TBI. However, most studies relied on retrospective designs and lacked independent external validation which limits models generalizability and raises concern for potential overfitting. Prospective, multicenter studies with standardized methodologies and rigorous external validation are required before widespread clinical implementation.

Humans↗

PubMed2026

A systematic review of macaque brain stimulation: Trends and future directions.

Neurostimulation techniques can powerfully modulate neural circuit activity and provide causal insights into the relationship between brain function and behavior. Macaque monkeys have long been a key animal model for brain stimulation studies. While stimulating the macaque brain with one or a few electrodes has already taught us much about brain function and dysfunction, recent technological advances promise a future with more precise stimulation using many more electrodes. However, such possibilities also increase the number of choices an experimenter has when designing their study. We can learn from a rich past, but a comprehensive overview of which brain regions have been studied and with what stimulation parameters is lacking. Here, we present a PRISMA-compliant systematic review of 734 macaque brain stimulation studies using electrical and/or optogenetic stimulation. We find a striking bias in which brain areas have traditionally been stimulated: a mere 10 brain regions account for half of all studies, with the remainder of studies investigating approximately 150 other areas. Across studies, stimulation frequency robustly predicted direct behavioral effects independent of brain region, while amplitude did not. Future studies could more systematically explore less studied regions through lower stimulation frequencies (e.g., 20-50 Hz) alongside established ranges (∼200 Hz). Tools such as fMRI or optical imaging can capture neural circuit engagement evoked by these frequencies, even when behavioral effects are absent or remain subtle. Our synthesis offers a guide towards the next steps in high-channel-count, high-precision stimulation approaches.

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PubMed2026

Somatic mutations: recent advances in brain aging and neurodegeneration.

Somatic mutations are genetic variants that occur after the single-cell phase of development and have been implicated in disease pathogenesis. While most DNA lesions are detected and repaired, examination of healthy tissue has revealed that some lesions escape repair, leading to somatic mutations that accumulate at a consistent rate, including in human brain tissue and postmitotic neurons. Emerging methodological and analytical advances have revealed the presence of persistent mutagenic mechanisms during healthy brain aging as well as mutational pattern shifts in the context of neurodegenerative diseases. Here, we highlight recent methodological advances, summarize our current understanding of somatic mutagenesis in neurotypical brain aging, and examine the role of somatic mutations in neurodegenerative diseases.

Humans↗

PubMed2026

Origins and timing of somatic variants in the brain.

Somatic variants accumulate in human brain cells throughout the lifespan. Variant allele fraction has traditionally been used as a proxy for both the developmental timing of somatic variants and their functional effect, based on the assumption that earlier mutations are shared by larger cell populations and therefore have greater potential for severe phenotypes. However, recent discoveries challenge this simplified model. Variables such as developmental bottlenecks, lineage restriction, and cellular and molecular context play critical roles in shaping the distribution and functional impact of somatic variants in the brain. These insights support a shift toward a context-dependent framework for interpreting somatic mosaicism.

Humans↗