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Abstract Computer-assisted surgery is becoming essential in modern medicine to accurately plan, guide, and perform surgeries. Similarly, Digital Twin technology is expected to be instrumental in the future of surgery, owing to its capacity to virtually replicate patient-specific interventions whilst providing real-time updates to clinicians. This perspective introduces the term Digital Twin-Assisted Surgery and discusses its potential to improve surgical precision and outcome, along with key challenges for successful clinical translation.

Abstract This study investigates the reconstruction of hyperspectral signatures from RGB data to enhance surgical imaging, utilizing the publicly available HeiPorSPECTRAL dataset from porcine surgery and an in‐house neurosurgery dataset. Various architectures based on convolutional neural networks (CNNs) and transformer models are evaluated using comprehensive metrics. Transformer models exhibit superior performance in terms of RMSE, SAM, PSNR and SSIM by effectively integrating spatial information to predict accurate spectral profiles, encompassing both visible and extended spectral ranges. Qualitative assessments demonstrate the capability to predict spectral profiles critical for informed surgical decision‐making during procedures. Challenges associated with capturing both the visible and extended hyperspectral ranges are highlighted using the MAE, emphasizing the complexities involved. The findings open up the new research direction of hyperspectral reconstruction for surgical applications and clinical use cases in real‐time surgical environments.

Background: Glioblastoma is the most common and aggressive primary brain tumour, characterised by its invasive nature and complex metabolic profile. Emerging research highlights the role of amino acids (AAs) in glioblastoma metabolism, influencing tumour growth and the surrounding microenvironment. Methods: This narrative review synthesises recent pre-clinical studies focusing on the metabolic functions of AAs in glioblastoma. Key areas include the effects of AA deprivation on tumour growth, adaptive mechanisms, and the tumour microenvironment. Results: The effects related to arginine, glutamine, methionine, and cysteine deprivation have been more extensively reported. Arginine deprivation in arginine-auxotrophic glioblastomas induces apoptosis and affects cell adhesion, while glutamine deprivation disrupts metabolic pathways and enhances autophagy. Methionine and cysteine deprivation impact lipid metabolism and ferroptosis. Tumour adaptive mechanisms present challenges, and potential compensatory responses have been identified. The response of the microenvironment to AA deprivation, including immune modulation, is critical to determining therapeutic outcomes. Conclusions: Targeting AA metabolism offers a promising approach for glioblastoma treatment, with potential targeted drugs showing clinical promise. However, the complexity of tumour adaptive mechanisms and their impact on the microenvironment necessitates further research to optimise combination therapies and improve therapeutic efficacy.

Abstract We investigated whether prestimulus alpha-band oscillatory activity and stimulus-elicited recurrent processing interact to facilitate conscious visual perception. Participants tried to perceive a visual stimulus that was perceptually masked through object substitution masking (OSM). We showed that attenuated prestimulus alpha power was associated with greater negative-polarity stimulus-evoked ERP activity that resembled the visual awareness negativity (VAN), previously argued to reflect recurrent processing related to conscious perception. This effect, however, was not associated with better perception. Instead, when prestimulus alpha power was elevated, a preferred prestimulus alpha phase was associated with a greater VAN-like negativity, which was then associated with better cue perception. Cue perception was worse when prestimulus alpha power was elevated but the stimulus occurred at a nonoptimal prestimulus alpha phase and the VAN-like negativity was low. Our findings suggest that prestimulus alpha activity at a specific phase enables temporally selective recurrent processing that facilitates conscious perception in OSM.

New approaches for the management of glioblastoma (GBM) are an urgent and unmet clinical need. Here, we illustrate that the efficacy of radiotherapy for GBM is strikingly potentiated by concomitant therapy with the arginine-depleting agent ADI-PEG20 in a non-arginine-auxotrophic cellular background (argininosuccinate synthetase 1 positive). Moreover, this combination led to durable and complete radiological and pathological response, with extended disease-free survival in an orthotopic immune-competent model of GBM, with no significant toxicity. ADI-PEG20 not only enhanced the cellular sensitivity of argininosuccinate synthetase 1–positive GBM to ionizing radiation by elevated production of nitric oxide (˙NO) and hence generation of cytotoxic peroxynitrites, but also promoted glioma-associated macrophage/microglial infiltration into tumors and turned their classical antiinflammatory (protumor) phenotype into a proinflammatory (antitumor) phenotype. Our results provide an effective, well-tolerated, and simple strategy to improve GBM treatment that merits consideration for early evaluation in clinical trials.

Abstract Objective To identify a convergent, multitarget proliferation characteristic for astrocytoma transformation that could be targeted for therapy discovery. Methods Using an integrated functional genomics approach, we prioritized networks associated with astrocytoma progression using the following criteria: differential co‐expression between grade II and grade III IDH1‐mutated and 1p/19q euploid astrocytomas, preferential enrichment for genetic risk to cancer, association with patient survival and sample‐level genomic features. Drugs targeting the identified multitarget network characteristic for astrocytoma transformation were computationally predicted using drug transcriptional perturbation data and validated using primary human astrocytoma cells. Results A single network, M2, consisting of 177 genes, was associated with glioma progression on the basis of the above criteria. Functionally, M2 encoded physically interacting proteins regulating cell cycle processes and analysis of genome‐wide gene‐regulatory interactions using mutual information and DNA–protein interactions revealed the known regulators of cell cycle processes FoxM1, B‐Myb, and E2F2 as key regulators of M2. These results suggest functional disruption of M2 via gene mutation or altered expression as a convergent pathway regulating astrocytoma transformation. By considering M2 as a multitarget drug target regulating astrocytoma transformation, we identified several drugs that are predicted to restore M2 expression in anaplastic astrocytoma toward its low‐grade profile and of these, we validated the known antiproliferative drug resveratrol as down‐regulating multiple nodes of M2 including at nanomolar concentrations achievable in human cerebrospinal fluid by oral dosing. Interpretation Our results identify M2 as a multitarget network characteristic for astrocytoma progression and encourage M2‐based drug screening to identify new compounds for preventing glioma transformation.

We present a case report of a 51-year-old left-handed male with a background of human papillomovairus 16-positive tonsil squamous cell carcinoma presenting with tonic-clonic seizure and a radiological diagnosis of secondary metastatic deposits. These were initially treated with stereotactic radiosurgery and subsequently with surgery. Surgical resection was performed under general anesthesia with right-sided temporal and parietal approaches. Both the parietal and temporal deposits were removed, while the intraventricular mass was intentionally left to avoid postoperative deficits. Adjuvant radiotherapy and chemotherapy were administered postoperatively. The patient experienced a satisfactory recovery postoperatively and was reoperated for recurrence 4 months later. He maintained a good quality of life and an excellent performance status throughout, but unfortunately he passed away in November 2018 due to septic complications. This case history stresses the difficulty in managing squamous cell carcinomas (SCC) with brain metastatic deposits. There are no current guidelines about the management of patients presenting with such a rare condition. More data are thus desirable to better define treatment guidelines and protocols when SCC brain metastases are present.

Metabolic regulation of immune cells has arisen as a critical set of processes required for appropriate response to immunological signals. While our knowledge in this area has rapidly expanded in leukocytes, much less is known about the metabolic regulation of brain-resident microglia. In particular, the role of alternative nutrients to glucose remains poorly understood. Here, we use stable-isotope (13C) tracing strategies and metabolomics to characterize the oxidative metabolism of β-hydroxybutyrate (BHB) in human (HMC3) and murine (BV2) microglia cells and the interplay with glucose in resting and LPS-activated BV2 cells. We found that BHB is imported and oxidised in the TCA cycle in both cell lines with a subsequent increase in the cytosolic NADH:NAD+ ratio. In BV2 cells, stimulation with LPS upregulated the glycolytic flux, increased the cytosolic NADH:NAD+ ratio and promoted the accumulation of the glycolytic intermediate dihydroxyacetone phosphate (DHAP). The addition of BHB enhanced LPS-induced accumulation of DHAP and promoted glucose-derived lactate export. BHB also synergistically increased LPS-induced accumulation of succinate and other key immunometabolites, such as α-ketoglutarate and fumarate generated by the TCA cycle. Finally, BHB upregulated the expression of a key pro-inflammatory (M1 polarisation) marker gene, NOS2, in BV2 cells activated with LPS. In conclusion, we identify BHB as a potentially immunomodulatory metabolic substrate for microglia that promotes metabolic reprogramming during pro-inflammatory response.

The environmental research program of the United States military has set up blind tests for detection and discrimination of unexploded ordnance. One such test consists of measurements taken with the EM-63 sensor at Camp Sibert, AL. We review the performance on the test of a procedure that combines a field-potential (HAP) method to locate targets, the normalized surface magnetic source (NSMS) model to characterize them, and a support vector machine (SVM) to classify them. The HAP method infers location from the scattered magnetic field and its associated scalar potential, the latter reconstructed using equivalent sources. NSMS replaces the target with an enclosing spheroid of equivalent radial magnetization whose integral it uses as a discriminator. SVM generalizes from empirical evidence and can be adapted for multiclass discrimination using a voting system. Our method identifies all potentially dangerous targets correctly and has a false-alarm rate of about 5%.