Melanoma cells in the brain may use similar mechanisms for adapting to injury and/or disease (that is, through continued reallocation of energy, matter, and information) as other cell types do to create an environment in which cancer cells can grow and sustain themselves within the confines of the brain. These adaptable mechanisms include the ability to reactivate dormant neural crest-derived migration and communication pathways. Unlike some other types of cancers that invade neural tissue as a simple invasion, melanomas are capable of achieving limited molecular, metabolic, and electrical similarity to the neural circuitry of the brain. Melanomas achieve this limited similarity through both vascular co-optation and mimicking synaptic functions, as well as through their engagement of redox-coupled metabolic pathways and feedback-regulated signal transduction pathways. The result is the creation of a metastable tumor–host system, where the relationship between tumor and host is defined by the interaction of stabilizing and destabilizing forces; forces that define the degree of coherence, vulnerability, and persistence of the tumor–host system. In this review, we integrate molecular, electrophysiological, and anatomical data to develop a single unifying hypothesis for the functional integration of melanoma cells into the neural tissue of the brain. Additionally, we describe how neural crest-based regulatory pathways are reactivated in the adult brain and how tumor–host coherence is developed as a function of the shared thermodynamic and informational constraints placed on both tumor and host. We also describe how our proposed conceptual model allows for the understanding of therapeutic interventions as selective disruptions of the neural, metabolic, and immunological couplings that support metastatic adaptation.

Thought processes in the brain occur as it continually modifies its use of energy. This review integrates research findings from molecular neurology, vascular physiology and non-equilibrium thermodynamics to create a comprehensive perspective on thinking as a coordinated energy process. Data shows that there is a relationship between the processing of information and metabolism throughout all scales, from the mitochondria’s electron transport chain to the rhythmic changes in the microvasculature. Through the cellular level of organization, mitochondrial networks, calcium (Ca²⁺) signals from astrocytes and the adaptive control of capillaries work together to maintain a state of balance between order and dissipation that maintains function while also maintaining the ability to be flexible. The longer-term regulatory mechanisms including redox plasticity, epigenetic programs and organelle remodeling may convert short-lived states of metabolism into long-lasting physiological “memory”. As well, data indicates that the cortical networks of the brain appear to be operating close to their critical regimes, which will allow them to respond to stimuli but prevent the brain from reaching an unstable energetic state. It is suggested that cognition occurs as the result of the brain’s ability to coordinate energy supply with neural activity over both time and space. Providing a perspective of the functional aspects of neurons as a continuous thermodynamic process creates a framework for making predictive statements that will guide future studies to measure coherence as a key link between energy flow, perception, memory and cognition.

Although there have been advancements in stroke treatment (reperfusion) therapy, and it has been shown that many individuals continue to suffer from partial recoveries and continuing decline in their neurological status as a result of suffering a stroke, a primary barrier to providing precise care to patients with stroke continues to be the inability to capture changes in molecular and cellular programs over time and in biological compartments. This review synthesizes evidence that represents the entire continuum of ischemia, beginning with acute metabolic failure and excitotoxicity, and ending with immune response in the nervous system, reprogramming of glial cells, remodeling of vessels, and plasticity at the level of networks, and organizes this evidence in a temporal framework that includes three biological compartments:central nervous system tissue, cerebrospinal fluid, and peripheral blood. Additionally, this review discusses new technologies which enable researchers to discover biomarkers at an extremely high resolution, including single-cell and spatial multi-omics, profiling of extracellular vesicles, proteoform-resolved proteomics, and glymphatic imaging, as well as new computational methods and machine-learning algorithms to integrate data from multiple modalities and predict trajectories of disease progression. The final section of this review will provide an overview of translationally relevant and ethically relevant issues regarding the deployment of predictive biomarkers, such as privacy, access, equity, and fairness, and emphasize the importance of global coordination of research efforts in order to ensure the clinical applicability and global equity of biomarker-based diagnostics and treatments.

Background: The concept of mesopancreas is frequently discussed in the surgical literature as the neural pathway for metastatic spread in pancreatic head cancer. It generally refers to a retro-pancreatic plane that should be resected to reduce the incidence of regional metastases. However, this concept remains poorly defined, both embryologically and anatomically. Our objective was to establish a clear embryological and anatomical definition of the mesopancreas, making anatomical data more applicable in surgical practice. Methods: We examined seven cadavers (5 males, 2 females, aged 62–71) with no medical or surgical history, preserved in 9% formalin at Carol Davila University’s Anatomy Department. Regional dissections were performed in successive planes, highlighting the celiac ganglia and the associated network of neural connections that comprise the mesopancreas. Results: Our study defines the “mesopancreas” as remnants of primordial mesenteries that coalesced into the Treitz fascia. We identified its functional components as nerve fibers linking the celiac ganglia and superior mesenteric plexus to the pancreas, along with vascular structures, lymphatics, and connective and adipose tissue. These components likely contribute to regional metastasis in pancreatic head cancer. While resection of the mesopancreas could help prevent metastasis, its complex anatomy and proximity to major vessels pose significant surgical challenges. Conclusions: Based on our findings, we propose a plausible definition for the term “mesopancreas”. It encompasses the structures that originated as part of the primordial mesenteries, which subsequently coalesced, resulting in the formation of the Treitz fascia. In essence, the mesopancreas is the functional content of a former mesentery.

Research shows that neurodegenerative processes do not develop from a single “broken” biochemistry process; rather, they develop when a complex multi-physics environment gradually loses its ability to stabilize the neuron via a collective action between the protein, ion, field and fluid dynamics of the neuron. The use of new technologies such as quantum-informed molecular simulation (QIMS), dielectric nanoscale mapping, fluid dynamics of the cell, and imaging of perivascular flow are allowing researchers to understand how the collective interactions among proteins, membranes and their electrical properties, along with fluid dynamics within the cell, form a highly interconnected dynamic system. These systems require fine control over the energetic, mechanical and electrical interactions that maintain their coherence. When there is even a small change in the protein conformations, the electric properties of the membrane, or the viscosity of the cell’s interior, it can cause changes in the high dimensional space in which the system operates to lose some of its stabilizing curvature and become prone to instability well before structural pathologies become apparent. AI has allowed researchers to create digital twin models using combined physical data from multiple scales and to predict the trajectory of the neural system toward instability by identifying signs of early deformation. Preliminary studies suggest that deviations in the ergodicity of metabolic–mechanical systems, contraction of dissipative bandwidth, and fragmentation of attractor basins could be indicators of vulnerability. This study will attempt to combine all of the current research into a cohesive view of the role of progressive loss of multi-physics coherence in neurodegenerative disease. Through integration of protein energetics, electrodynamic drift, and hydrodynamic irregularities, as well as predictive modeling utilizing AI, the authors will provide mechanistic insights and discuss potential approaches to early detection, targeted stabilization, and precision-guided interventions based on neurophysics.

Background and Clinical Significance: Although rupture of aneurysms at the internal carotid-posterior communicating artery (ICA-PCom) junction accounts for a small percentage of all ruptured intracranial aneurysms, they are clinically relevant due to their proximity to perforator-rich cisterns, the optic-carotid-oculomotor pathways and flow-diverting zones, as well as their high likelihood for causing early neurological instability. Additionally, ruptured ICA-PCom aneurysms that have multiple lobulations are associated with increased variability in wall shear stress, local inflammatory remodeling and higher propensity for rupture at smaller sizes compared to other types of aneurysms. Due to the rapidity of early physiological destabilization in most patients with ruptured ICA-PCom aneurysms, clinical–anatomical correlations in these cases are often obscured by neurological deterioration; therefore, the presentation of this patient provides a unique opportunity to correlate the minimal early symptoms, tri-lobulation of the aneurysm and confined cisternal hemorrhage, to better understand rupture behavior, surgical decision-making in an anatomically challenging area, and postoperative recovery. Case Presentation: A 48-year-old hypertensive female experienced an acute “thunderclap” headache accompanied by intense photophobia and focal meningeal irritation, but, unexpectedly, retained a normal neurologic examination. She did exhibit some minor ocular motor micro-latencies, early cortical attentional strain and lateralized pain sensation that suggested localized cisternal involvement despite lack of generalized neurologic impairment. Digital subtraction angiography and three-dimensional CT angiography revealed a ruptured, tri-lobulated aneurysm originating from the communicating portion of the left internal carotid artery proximal to its origin from the posterior communicating artery, oriented toward the perimesencephalic cisterns. The aneurysm was surgically clipped using a standard left pterional craniotomy with direct visualization, after careful dissection through the carotid and optic windows to preserve the anterior choroidal artery, oculomotor nerve, and surrounding perforators. The neck of the aneurysm was reconstructed with a single straight clip, without compromise to the parent vessel lumen. The patient had an uneventful postoperative course without vasospasm or neurologic deficit. At both 3 and 9 months postoperatively the patient remained free of clinical neurologic deficit, and imaging demonstrated continued aneurysm exclusion, preserved ICA-PCom anatomy, and no evidence of delayed ischemic injury or hydrocephalus. Conclusions: The goal of this report is to demonstrate how a ruptured, morphologically complex ICA-PCom aneurysm may present with preserved neurologic function, thereby enabling the study of clinical–anatomical associations before secondary injury mechanisms intervene. The relationship between the configuration of the patient’s symptoms, geometry of the aneurysm and pattern of hemorrhage within the cisterns offers insight into a rare rupture pattern observed during routine clinical experience. Through complete anatomical analysis, timely microsurgical reconstruction and consistent follow-up, the authors were able to achieve long-term recovery of this particular patient. Continued advancements in vascular imaging techniques, aneurysmal wall modeling, and postoperative monitoring will likely help clarify the underlying mechanism(s) responsible for such presentations.