Glioma promotes macrophage immunosuppressive phenotype through ANXA1 in a methionine metabolism-dependent manner

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In a Translational research with bulk RNA sequencing analysis, scRNA-seq, and in vitro validation Hong Hu *et al.* from the Harbin Medical University published in the Journal: Discover Oncology to elucidate how methionine metabolism contributes to the immunosuppressive tumor microenvironment in gliomas, with a focus on macrophage polarization mediated by ANXA1. Elevated methionine metabolism in glioma cells correlates with higher WHO tumor grade and an immunosuppressive microenvironment. High methionine metabolic activity fosters M2 macrophage polarization via ANXA1, which is downregulated upon methionine deprivation 1).

Critical Review

This study leverages multi-omics datasets, particularly MMA-scoring and scRNA-seq, to draw a novel link between methionine metabolism and the immune suppressive phenotype in gliomas, focusing on macrophage polarization. The authors make a credible case for metabolic reprogramming as a driver of glioma malignancy. However, there are caveats:

– Strengths: The integration of bulk and single-cell RNA-seq enhances resolution, and the use of in vitro validation lends support to mechanistic claims. The correlation between MMA-scores and glioma grade is statistically compelling.

– Limitations: Despite the innovative premise, the study relies heavily on correlative data. Functional validation, particularly in vivo or using clinical samples, is lacking. The assertion that ANXA1-mediated macrophage polarization is solely Met-dependent needs further biochemical interrogation. Furthermore, patient sample heterogeneity and potential confounders are not adequately addressed.

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Modulation of mitochondrial dysfunction: Mechanisms and strategies for the use of natural products to treat stroke

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In a review article (mechanistic overview on mitochondrial regulation by natural products) Qin et al. from the Qingdao Medical College & Qingdao University, Pharmaceutical University, Nanjing published in the Neural Regeneration Research journal to summarize how natural products modulate mitochondrial dysfunction (biogenesis, dynamics, transport, mitophagy, apoptosis, oxidative stress) for stroke treatment, and identify barriers to clinical translation. Natural products act via multi-target mechanisms on mitochondrial processes to exert neuroprotection in both ischemic and hemorrhagic stroke models, but clinical translation is impeded by product complexity, lack of standardization, insufficient multicenter data, and unclear long-term safety. Future directions include advanced technologies (single-cell sequencing, organoid models) and multicenter trials 1).

Critical review

*✅ Strengths*

  • Comprehensive mechanistic mapping: the article clearly organizes effects into six mitochondrial regulatory domains and links specific natural compounds (e.g., Cordyceps, ginsenosides, Gypenoside XVII, Ginkgolide K, Scutellarin, Chrysophanol) to distinct pathways of protection.
  • Provides molecular insights: for instance, Cordyceps activates PGC‑1α/NRF‑1 to enhance biogenesis; Gypenoside XVII activates PINK1/Parkin mitophagy to protect the BBB.
  • Identifies translational challenges—standardization issues, safety gaps, and absent systemic trials are analyzed realistically, demonstrating awareness of clinical hurdles.

*❌ Weaknesses*

  • Lacks summary of methodological rigor: no discussion of dosage, sample sizes, or statistical quality of cited in‑vivo/in‑vitro studies.

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Silencing NRBP1 Gene with shRNA Improves Cognitive Function and Pathological Features in AD Rat Model

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In a preclinical animal study–rat model

Xinxue Wei et al.

from the Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi

published in Biochemical Genetics Journal to investigate whether silencing the NRBP1 gene using shRNA can enhance cognitive performance and reduce pathological hallmarks of Alzheimer’s disease (AD) in a rat model induced by D-galactose and AlCl3. Silencing NRBP1 led to measurable improvements in spatial learning and memory, decreased Aβ1-42 burden, and reduced amyloid plaque pathology in the hippocampus. The intervention restored performance close to non-AD control levels, suggesting that NRBP1 may play a critical role in Alzheimer’s disease pathogenesis and could be a therapeutic target 1)

Critical Review:

This study explores a promising molecular target, NRBP1, in a standard AD animal model. The use of both behavioral (Morris water maze) and molecular (ELISA, Thioflavin-S, qPCR) assessments strengthens the internal consistency of the findings. However, it suffers from several critical limitations:

1. Lack of Mechanistic Depth: No molecular pathway analysis or downstream effectors of NRBP1 silencing are evaluated. Is NRBP1 affecting tau phosphorylation, inflammation, or synaptic signaling?

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Failure to replace removed growth friendly implants results in deteriorating radiographic outcomes

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In a registry-based comparative cohort study (early onset scoliosis patients after implant removal) Matan S Malka et al. from the Morgan Stanley Children’s Hospital (Columbia Univ, New York). Arkansas Children’s Hospital; Shriners Philadelphia; Seattle Children’s Hosp. published in Spine Deformity Journal, to evaluate if re-implanting growth-friendly constructs within 12 months after implant removal (ROI) stabilizes deformity compared to observation-only. Early re-implantation (< 12 mo post-ROI) significantly reduces 2‑year coronal Cobb progression compared to no replacement 1).

Critical Review

– Strengths:

Multicenter registry with well-defined exposure groups.

Radiographic outcomes measured at a meaningful 2‑year follow-up.

Statistically robust with p-values: Cobb 81° vs 53° (p=0.003); progression ≥5°: 64% vs 30% (p=0.04)

– Limitations:

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Evaluation of Interstitial Fluid Volume and Diffusivity in Patients With Idiopathic Normal Pressure Hydrocephalus Using Spectral Diffusion Analysis

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In a retrospective cohort Ishida *et al.* from the University hospitals—centres in Tokyo, (e.g., Tokyo Metropolitan Geriatric Center) published in the *Journal of Magnetic Resonance Imaging* to compare interstitial fluid volume fraction (Fint) and diffusivity (Dint), derived via spectral diffusion analysis, between idiopathic normal pressure hydrocephalus (iNPH) patients and healthy controls (HCs). In iNPH patients, spectral diffusion analysis revealed increased Fint and Dint in periventricular hyperintensity (PVH) regions of the centrum semiovale (CSO) and frontal white matter (FWM), while regions outside PVH did not differ from HCs 1).

Critical Review

* Strengths:

  • Utilizes advanced spectral diffusion with non‑negative least squares to separate Interstitial Fluid Dynamics an innovative approach.
  • Well‑defined region‑based ROI analysis including CSO, FWM, lenticular nucleus (LN).
  • Robust statistical treatment via Kruskal–Wallis with Dunn’s test; Spearman’s for correlations.

* Limitations & Concerns:

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The modified Brain Injury Guidelines: safe, sensitive, but not yet specific

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In a retrospective cohort review, Freeman et al. from the University of Colorado, Aurora published in the Journal of Neurosurgery analyzed the sensitivity and specificity of the modified Brain Injury Guidelines (mBIG)—especially mBIG 3 criteria—to predict neurosurgical intervention, and explored the predictive value of individual radiographic parameters.

→ mBIG 3 criteria showed 99.5% sensitivity, and combined mBIG 2+3 reached 100% sensitivity. → Specificity remains low:

  • mBIG 3: 37.2%

  • mBIG 2+3: 18.1%

→ Isolated IPH or SAH in mBIG 3 with GCS 13–15 are poor predictors of intervention. → Authors propose eliminating routine repeat head CT in mBIG 1–2 cases.

1)

🧠 Critical Review

➤ Strengths:

  • Large sample (n = 1128) over 3.5 years (May 2020–Dec 2023).
  • Addresses key clinical issue: reducing unnecessary repeat CTs.
  • High sensitivity makes mBIG a safe exclusion tool, especially mBIG 2+3.

➤ Limitations:

  • Retrospective design → risk of selection bias and unmeasured confounding.
  • Low specificity → risk of overtriage, especially in mBIG 3.
  • Single-center → limits external generalizability.
  • Sparse detail on intervention timing and type.
  • No external validation; subgroup analyses were post hoc.

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Comparative assessment of stereoelectroencephalography and subdural electrodes in invasive epilepsy monitoring: a systematic review and meta‑analysis

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In a systematic review and metaanalysis of double‑arm comparative studies Bandopadhay et al. from the Houston Methodist Hospital published in the Journal of Neurosurgery to compare safety and seizure‑outcome profiles of stereoelectroencephalography (SEEG) vs. subdural electrodes (SDE) in pharmacoresistant epilepsy using quantitative double‑arm data SEEG demonstrated a higher rate of favorable seizure outcomes (RR 1.14, 95% CI 1.02–1.27; p=0.02) and lower complication rates overall (RR 0.49, 95% CI 0.37–0.66; p<0.00001). The benefit was significant in general adult cohorts but less pronounced in pediatric or older groups 1).

 

Critical Appraisal

* Strengths:

  • Restricting to double‑arm designs reduces cross‑study heterogeneity.
  • Large pooled cohort: 1,632 SEEG vs. 1,482 SDE patients.
  • Age‑stratified subgroup analysis adds nuance to applicability.

* Limitations:

  • Potential for publication bias—likely underreporting of negative or null comparative studies.

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Management of patients discharged from the hospital after VPS surgery

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In a Letter to the Editor Lu et al. published in the Journal of Neurosurgery to discuss ventriculoperitoneal shunt management strategies for discharged patients 1).

Critical Appraisal

– Strengths:

  1. Highlights a clinically important gap—post-discharge VPS care.
  2. Sparks important discussion on outpatient monitoring and follow-up protocols.

– Limitations:

  1. Absence of abstract/data: no study design, patient numbers, follow-up length or outcomes described.

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Autologous rib graft augmentation for occipitocervical fusion in pediatric patients and a novel radiographic grading scale

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In a retrospective cohort study Shahin et al. from the Doernbecher Children’s Hospital and Oregon Health & Science University, Portland published in the Journal of Neurosurgery Pediatrics to assess whether screw‑fixed autologous rib grafts improve fusion rates in pediatric occipitocervical fusion (OCF), and validate a novel imaging-based fusion grading scale independent of graft type. Screw‑anchored rib autograft achieved 100 % solid fusion at ≥3 months (n=16), compared to 57 % fusion (4/7) and 43 % resorption/pseudarthrosis in standard allograft/BMP group (p=0.0066). The new 0–2 radiographic grade correlated well with CT-defined outcomes 11)

Critical review

1. Study design & cohort: Retrospective, single‑institution, relatively small sample (n=21 total; final rib‑graft cohort n=17 minus one without CT). Comparison spans two eras (2015–2016 vs. 2016–2022), risks secular trends or surgeon learning‑curve bias.

2. Intervention vs. control: Cohort 1 received standard instrumentation with allograft/BMP; cohort 2 received screw‑fixed rib graft. But several cohort 2 cases were revisions from cohort 1, confounding the groups. No randomization.

3. Outcomes & follow-up: Fusion assessed at ≥3 months by blinded neuroradiologists with a 0–2 grading scale—clear and reproducible. However, mid / long‑term (>1 year) follow-up beyond early fusion rate not well characterized.

4. Results interpretation: Dramatic fusion improvement is compelling, but may reflect both graft technique and instrumentation changes over time. Lack of halo/BMP/lab comparisons limiting.

5. Radiographic grading scale: Solid concept, but needs external validation across graft types and institutions.

6. Safety & complications: No donor‑site morbidity or hardware failures reported over 5+ years. But small sample limits detection of rare complications.

7. Limitations:

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Multi‑institutional recommendations on the use of 7T MRI in deep brain stimulation

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Middlebrooks EH et al. Mayo Clinic, Jacksonville; Amsterdam UMC; University of Minnesota, Minneapolis; Western University, London (ON)

Published in the Journal of Neurosurgery 1)

A Consensus/Technique article presenting multi-institutional expert consensus on the clinical application and technical optimization of 7‑Tesla MRI in deep brain stimulation (DBS) planning.

7T MRI enables superior visualization of DBS targets—subthalamic nucleus, globus pallidus internus (GPi), and thalamus—due to increased spatial resolution, enhanced contrast, and higher signal-to-noise ratio.

The paper outlines:

  • Standardized imaging sequences
  • Distortion correction methods
  • Artifact mitigation strategies
  • Post‑processing workflows

All recommendations are grounded in experience across >1000 DBS cases.

🔍 Critical Appraisal

➕ Strengths

  • Extensive real‑world experience from multiple high‑volume centers (>1 000 cases)
  • Provides reproducible and practical imaging protocols
  • Addresses technical pitfalls specific to ultrahigh‑field MRI (e.g., geometric distortion, susceptibility artifacts)
  • Multi‑institutional consensus improves external validity

➖ Weaknesses

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