Vagus nerve stimulation (VNS) is an established adjunctive therapy for drug-resistant epilepsy. Experimental and clinical evidence indicates that its therapeutic effects involve distributed brain networks and multiple neurochemical pathways. Electroencephalography (EEG) has been widely used to characterize VNS-related neurophysiological changes, including alterations in conventional oscillatory activity, functional connectivity, and, more recently, aperiodic spectral components such as the spectral exponent and spectral offset. However, these EEG findings are often interpreted without sufficient consideration of the neurochemical intermediates that may contribute to the observed electrophysiological changes. In this structured narrative review, primarily focused on epilepsy, we examine how VNS-related EEG findings can be interpreted in light of noradrenergic, serotonergic, cholinergic, GABAergic, and neurotrophic mechanisms. We also discuss methodological challenges in the analysis of periodic and aperiodic EEG components and outline how machine learning approaches and adaptive closed-loop neuromodulation strategies may support the development of clinically useful VNS biomarkers.
Oxygen extraction fraction is differentially associated with pathological biomarkers in Alzheimer’s disease and non-Alzheimer’s dementias
IntroductionWe aimed to understand the pathophysiological differences between 16 Alzheimer’s disease (AD) and 15 non-AD dementia patients by quantifying oxygen extraction fraction (OEF) in cortical (CGM) and deep gray matter (DGM) regions.MethodsTo achieve this, we used a novel MRI-based OEF mapping technique, QQ, which estimates OEF from routine multi-echo gradient echo data. Multiple linear regression analyses were performed to compare the associations between OEF and white matter hyperintensities (WMH) or cognitive impairment (measured by Montreal Cognitive Assessment (MoCA) between the two groups.ResultsIn the AD and non-AD group, OEF showed negative associations with WMH in DGM and positive associations with MoCA in DGM and CGM.DiscussionOur study suggests that QQ is a promising tool for differentiating between AD and non-AD dementias, by revealing abnormalities in tissue oxygen usage and their relationships to microvascular changes and cognitive impairment.
A reasonably likely surrogate endpoint for metabolic dysfunction–associated steatohepatitis
Nature Medicine, Published online: 28 April 2026; doi:10.1038/s41591-026-04267-z
A reasonably likely surrogate endpoint for metabolic dysfunction–associated steatohepatitis
<![CDATA[Adial seeks FDA priority voucher to speed AD04 review, a biomarker-guided therapy aiming to curb heavy drinking in alcohol use disorder.]]>
Electrophysiological and morphological alteration in the visual pathway of children with attention-deficit/hyperactivity disorder
IntroductionAttention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders in children. Optical Coherence Tomography (OCT) and Visual evoked potentials (VEP) are common non-invasive diagnostic techniques. Researchers can use these techniques to identify possible biomarkers and explore the neurodevelopmental mechanisms underlying ADHD.MethodsThe ADHD group (37 cases, average age 8.81 ± 1.44 years) and the healthy controls (38 cases, average age 8.97 ± 1.43 years), had the OCT and VEP. The retinal nerve fibre layer (RNFL), optic disc parameters, and macular parameters were measured through OCT. The latencies of P100 and the amplitudes of N75-P100 and P100-N135 waves at three different spatial frequencies (visual angles of 15’, 30’, and 60’) were tested through VEP.ResultsThe average RNFL and RNFL in each quadrant between the two groups were no statistically significant (all p > 0.05). The optic disc area, average cup-to-disc ratio, and cup volume in the ADHD group were all significantly larger than those in the control group (all p < 0.05). At three visual angles (15’, 30’, 60’), P100-latency in the ADHD group were all more significant than those in the control group (all p < 0.05). The amplitudes of N75-P100 and P100-N135 in the ADHD group were all statistically significantly lower than those in the control group (all p ≤ 0.001).DiscussionFrom the perspective of electroencephalophysiology, children with ADHD may have early visual information processing disorders. This provides a theoretical and practical basis for further early intervention in children with ADHD from the field of visual perception. The study protocol followed the tenets of the Declaration of Helsinki, was approved by the local ethics committee (No 2023-2240), and was registered on ClinicalTrials.gov (ChiCTR2400086223).
Targeted therapies plus radiotherapy for diffuse intrinsic pontine glioma: the randomized phase 2 BIOMEDE trial
Nature Medicine, Published online: 24 April 2026; doi:10.1038/s41591-026-04354-1
In a biomarker-driven trial evaluating radiotherapy with erlotinib, everolimus or dasatinib in patients with newly diagnosed diffuse intrinsic pontine glioma, the primary endpoint of overall survival was not met, but features associated with long-term survival were defined, and everolimus emerged as a potential candidate for further testing.
<![CDATA[How do estrogen, testosterone, and aromatase shape binge eating and bulimia risk? Let’s explore brain biomarkers and future hormone-aware treatments.]]>
Presurgery Pembrolizumab May Be the Future for Some Operable CRCs
Groundbreaking data from the Phase II NEOPRISM-CRC trial show that patients given pembrolizumab prior to surgery for certain types of high-risk, operable colorectal cancer (CRC) remain relapse-free for almost three years.
Furthermore, the response to treatment can be predicted by DNA and T cell biomarkers.
At present, the standard of care for people with high-risk stage II or III CRC with deficient DNA mismatch repair (dMMR) or microsatellite instability (MSI), like those included in the study, is surgery followed by chemotherapy, but relapse rates can range from 15% to 40% at three years.
Pembrolizumab is already given to patients with inoperable stage IV dMMR/MSI CRC to shrink the tumors and prolong life, but it is not yet available for patients with operable tumors.
The NEOPRISM-CRC trial investigated whether pembrolizumab could benefit such patients.
For the study, 32 people with large, high-risk stage II or III dMMR/MSI CRC were given three cycles of intravenous pembrolizumab 200 mg followed by surgery.
The researchers, led by Kai-Keen Shiu, from University College London (UCL) Cancer Institute, have previously reported that that 59% of participants had a pathologic complete response (pCR) to pembrolizumab, indicating that there were no cancer cells in tissue samples removed from these patients during surgery.
The data presented at the American Association for Cancer Research Annual Meeting 2026 by Yanrong Jiang, a PhD student at UCL Cancer Institute, focused on survival outcomes and whether biomarkers could predict which patients respond to pembrolizumab.
She reported that, after a mean of 33 months of follow-up, all patients were alive and relapse-free.
Shiu said: “Seeing that no patients have experienced a cancer recurrence after almost three years of follow-up is extremely encouraging and strengthens our confidence that pembrolizumab is a safe and highly effective treatment to improve outcomes in patients with high-risk bowel cancers.”
Blood samples taken throughout the study were assessed for circulating tumor (ct)DNA using the highly sensitive whole genome tumor-informed Personalis NeXT Personal assay, which can track up to 1800 patient-specific variants.
The team found that all 25 patients with evaluable data had detectable ctDNA at baseline.
Remarkably, after one round of treatment with pembrolizumab, 24% of participants no longer had detectable ctDNA. The proportion increased to 43% and 58% after rounds two and three, respectively. Post-surgery, ctDNA was undetectable in all 25 patients.
When the researchers analyzed the ctDNA clearance profiles, they identified three distinct patterns. They designated the first group “super molecular responders.” All six patients in this group had undetectable ctDNA after one cycle of pembrolizumab.
The “dynamic molecular responder” group included 11 patients who cleared ctDNA at different rates—four after cycle two of pembrolizumab, five after cycle three, and the remainder post-surgery, even though the level was decreasing rapidly during immunotherapy.
The final group, termed “poor molecular responders,” included eight patients who showed stable, high levels of ctDNA throughout immunotherapy, with levels only becoming undetectable post-surgery.
Interestingly, the pCR rate varied across the three groups: It was 100% among the super molecular responders and 82% among the dynamic molecular responders, but 0% among the poor molecular responders.
Shiu told Inside Precision Medicine that measuring ctDNA using the Next Personal assay could “potentially trump all standard tests when it comes to informing decision making.”
He suggested that the super molecular responders could potentially consider forgoing surgery altogether, while the poor molecular responders could be considered for treatment intensification, such as the addition of a second immunotherapy agent.
Although ctDNA gives information on how the tumor is responding to treatment, it doesn’t explain why some patients respond and others don’t.
The researchers, therefore, also carried out T cell receptor (TCR) sequencing, which provides a readout of the immune environment within the tumor, specifically whether there are expanded T cell populations that may recognize cancer, explained Marnix Jansen, MD, a clinician scientist and consultant histopathologist who led the translational research on the trial from UCL Cancer Institute.
“We found that patients who achieved a complete response had a higher proportion of expanded T cell clones in their tumors, suggesting a more focused and effective anti-tumor immune response at baseline,” he said.
When the team combined the ctDNA results with the TCR sequencing data, they improved the ability to predict outcomes compared with using either biomarker alone.
“The key implication is that integrating immune and tumor biomarkers in a dynamic model may allow early, data-driven treatment decisions, such as identifying patients who are highly likely to benefit or, conversely, those who may need a change in therapy,” Jansen told Inside Precision Medicine.
The post Presurgery Pembrolizumab May Be the Future for Some Operable CRCs appeared first on Inside Precision Medicine.
Monitoring Mammalian and Microbial Bioprocesses in Real Time
At the 2026 BiOS conference in San Francisco, researchers presented a biosensing platform aimed at improving how living cells and tissues are monitored during drug bioprocessing. Known as TissueSense, the system provides continuous, real-time insight into cellular behavior without disrupting the biological environment.
In biopharmaceutical manufacturing, maintaining consistent cell health and productivity is essential. Yet many monitoring approaches still rely on intermittent sampling or endpoint measurements, offering only partial visibility into dynamic biological processes. TissueSense addresses this limitation by enabling continuous, in situ observation—capturing changes as they unfold.
The platform combines resonator-based photonic sensing with phase contrast microscopy, allowing simultaneous detection of biochemical activity and structural changes in cells. This dual approach provides a more complete picture of how cells respond to process conditions, such as nutrient shifts or environmental stress, which directly impact production outcomes.
A defining feature of the system is its label-free operation. Conventional biosensing methods often require fluorescent markers or reagents that might alter cell behavior or limit long-term monitoring. By removing these constraints, TissueSense supports extended observation of living systems in conditions closer to their natural state, an advantage for prolonged bioprocesses.
Data from the platform are analyzed using machine learning to simultaneously quantify up to 18 biomarkers, linking molecular outputs—such as secreted proteins—to tissue structure and function. This multiplexed capability is particularly relevant in drug manufacturing, where small variations in cellular activity can influence yield, quality, and reproducibility.
While TissueSense focuses on mammalian tissue models, parallel advances in microbial systems highlight a broader shift toward continuous, high-resolution monitoring across bioprocessing platforms. In yeast-based systems, for example, researchers have developed microbead-based cultivation methods that enable high-throughput, label-free screening of millions of individual mutants in extremely small volumes. These approaches can enrich desirable traits, such as resistance to metabolic inhibitors, by thousands-fold, supporting strain optimization for industrial bioproduction.
Similarly, in bacterial bioreactors, automated flow cytometry techniques now allow real-time tracking of population dynamics and physiological states. By combining DNA staining with indicators of active replication, these systems provide continuous insight into growth rates and cell cycle behavior, helping optimize feed strategies and overall process performance.
Together, these developments point toward a more integrated future for bioprocess monitoring—one that spans mammalian, yeast, and bacterial systems. Continuous, non-destructive sensing technologies are enabling researchers and manufacturers to move beyond static measurements toward dynamic control of biological production.
The post Monitoring Mammalian and Microbial Bioprocesses in Real Time appeared first on GEN – Genetic Engineering and Biotechnology News.
Combination immunotherapy for colorectal cancer: Clinical applications, rationale, challenges, and future perspectives
Fei et al. review combination immunotherapy strategies for colorectal cancer, focusing on overcoming resistance in pMMR/MSS/MSI-L tumors. They highlight integrating ICIs with chemotherapy, targeted therapy, and radiotherapy and discuss insights into the tumor microenvironment and biomarkers to improve outcomes.