The tumor microenvironment (TME) plays a pivotal role in cancer progression, yet its establishment and functionality remain poorly understood due to its intricate cellular composition. A study utilizing a mouse genetic system, mosaic analysis with double markers (MADMs), revealed insights into TME evolution in sonic hedgehog (SHH)-activated medulloblastomas, highlighting the importance of astrocytic trans-differentiation in sustaining tumor growth through a multicellular paracrine feedback loop (ref: Yao doi.org/10.1016/j.cell.2019.12.024/). In the context of atypical teratoid/rhabdoid tumors (ATRTs), an international consensus was reached on the molecular subgrouping of these tumors, identifying three distinct subgroups that exhibit genetic, epigenetic, and clinical heterogeneity, emphasizing the need for standardized nomenclature and classification in future studies (ref: Ho doi.org/10.1093/neuonc/). Furthermore, Erdheim-Chester disease (ECD), characterized by MAPK pathway alterations, demonstrated varied responses to conventional versus targeted therapies, with targeted treatments yielding significantly higher rates of complete metabolic responses (ref: Bhatia doi.org/10.1093/neuonc/). The integration of machine learning workflows for DNA methylation data has emerged as a promising approach for precision cancer diagnostics, enhancing molecular tumor classification through unbiased class probability estimation (ref: Maros doi.org/10.1038/s41596-019-0251-6/). Lastly, the modulation of microglial function by VGF-derived peptides was shown to reduce neuropathology in Alzheimer's disease models, indicating potential therapeutic avenues for neurodegenerative conditions (ref: El Gaamouch doi.org/10.1186/s13024-020-0357-x/).

Neurodegenerative diseases are characterized by complex molecular and pathological changes that often mirror clinical deterioration. A study found that gene expression trajectories in blood and brain tissues are predictive of disease evolution, with 85-90% of the most predictive pathways identified in the brain also being significant in blood samples, highlighting the potential for blood-based biomarkers in early detection (ref: Iturria-Medina doi.org/10.1093/brain/). Additionally, the use of pine bark polyphenolic extract demonstrated a capacity to attenuate amyloid-β and tau misfolding in Alzheimer's disease models, suggesting that plant-derived compounds may offer therapeutic benefits in managing neurodegenerative pathology (ref: Ono doi.org/10.3233/JAD-190543/). In the context of dementia with Lewy bodies (DLB), genetic analyses revealed limited pathogenic mutations, indicating a distinct genetic profile compared to other neurodegenerative disorders, which complicates the understanding of DLB's etiology (ref: Orme doi.org/10.1186/s40478-020-0879-z/). Furthermore, the effects of risperidone on the default-mode network in first-episode schizophrenia patients revealed heterogeneity in the posteromedial cortex, suggesting that antipsychotic treatment may influence functional connectivity and symptom improvement (ref: Duan doi.org/10.1016/j.schres.2020.01.001/). Lastly, the expression patterns of purinergic receptor P2RY12 in aged and Alzheimer's disease brains were characterized, providing insights into the role of microglial activation in neuroinflammation (ref: Walker doi.org/10.3390/ijms21020678/).

Research into human adult hippocampal neurogenesis has provided valuable insights into the persistence of immature neurons in the human brain throughout life. A comprehensive methodology was established to detect these neurons, emphasizing the need for standardized reporting in studies of adult neurogenesis (ref: Flor-García doi.org/10.1038/s41596-019-0267-y/). In the realm of infectious diseases, a study on Streptococcus pneumoniae demonstrated that this pathogen triggers hierarchical autophagy through reprogramming of LAPosome-like vesicles, which are crucial for eliminating intracellular pathogens, thus revealing the complexities of innate immunity (ref: Ogawa doi.org/10.1038/s42003-020-0753-3/). Additionally, the neuropathology of speech networks in amyotrophic lateral sclerosis (ALS) was investigated, revealing distinct signatures between bulbar and nonbulbar forms of the disease, which may inform clinical management and prognostication (ref: Shellikeri doi.org/10.1093/jnen/). The ghrelin/growth hormone secretagogue receptor axis was also implicated in promoting tumor growth in primary central nervous system lymphomas, suggesting a potential target for therapeutic intervention (ref: Muta doi.org/10.1111/neup.12634/). Overall, these studies underscore the intricate interplay between genetic, molecular, and pathological factors in neurodegenerative diseases and tumor biology.

Neuroinflammation is a critical component of various neurological disorders, with recent studies elucidating the immune response mechanisms involved. A study investigating antibody signatures in multiple sclerosis revealed significant differences in reactivity to specific peptides among different histopathological patterns, suggesting that immune responses may vary based on the underlying pathology (ref: Stork doi.org/10.1007/s00401-019-02120-x/). Additionally, the identification of CNS injury-related microRNAs as novel Toll-like receptor 7/8 signaling activators highlights the role of microRNAs in modulating neuroinflammatory responses, potentially serving as biomarkers or therapeutic targets (ref: Wallach doi.org/10.3390/cells9010186/). The contribution of mTOR and PTEN to radioresistance in vestibular schwannomas was also explored, indicating that molecular alterations post-radiation could inform treatment strategies for these tumors (ref: Gugel doi.org/10.3390/cancers12010177/). Furthermore, the effects of risperidone on the default-mode network in schizophrenia patients were examined, revealing alterations in functional connectivity that correlate with symptom improvement, thereby linking neuroinflammation to psychiatric manifestations (ref: Duan doi.org/10.1016/j.schres.2020.01.001/). Lastly, the characterization of purinergic receptor P2RY12-positive microglia in aging and Alzheimer's disease provides insights into the role of microglial activation in neurodegenerative processes (ref: Walker doi.org/10.3390/ijms21020678/).

Research into neurodevelopment and synaptic plasticity has revealed critical insights into the mechanisms underlying psychiatric disorders. A study demonstrated that overexpression of the schizophrenia-associated gene C4 in mouse prefrontal cortex neurons leads to hypoconnectivity and impaired social interaction, suggesting that altered C4 expression may contribute to the pathogenesis of schizophrenia (ref: Comer doi.org/10.1371/journal.pbio.3000604/). The application of machine learning workflows for DNA methylation data has emerged as a powerful tool for precision cancer diagnostics, enhancing molecular tumor classification and providing insights into synaptic plasticity in the context of cancer (ref: Maros doi.org/10.1038/s41596-019-0251-6/). Additionally, the study of adult neurogenesis in the human hippocampus has provided a framework for understanding the persistence of neurogenesis throughout life, which may have implications for cognitive function and neuroplasticity (ref: Flor-García doi.org/10.1038/s41596-019-0267-y/). These findings collectively underscore the importance of genetic and molecular factors in shaping neurodevelopmental trajectories and their implications for neuropsychiatric disorders.

Prion diseases, characterized by protein misfolding and aggregation, have been the focus of recent investigations into their underlying mechanisms. A study demonstrated that glycans on prion proteins can reduce intracerebral fibril formation and spongiosis, suggesting that posttranslational modifications play a significant role in disease progression (ref: Sevillano doi.org/10.1172/JCI131564/). Additionally, feline irradiated diet-induced demyelination was explored as a model for understanding the neuropathology of sub-acute combined degeneration, revealing insights into the early stages of demyelination and its long-term consequences (ref: Radcliff doi.org/10.1371/journal.pone.0228109/). Furthermore, a postmortem analysis of prion seeding activity in the digestive system highlighted the presence of prion infectivity in non-neuronal organs, expanding the understanding of prion disease transmission and pathology (ref: Satoh doi.org/10.3390/molecules24244601/). These studies emphasize the complexity of prion diseases and the need for continued research into their molecular and pathological underpinnings.

Recent advances in clinical and diagnostic neuropathology have provided new insights into various neurological conditions. A systematic neuropathologic investigation of sudden unexplained death in childhood (SUDC) revealed hippocampal abnormalities in affected children, underscoring the importance of comprehensive autopsy protocols in understanding unexplained deaths (ref: McGuone doi.org/10.1093/jnen/). The use of dynamic functional connectivity methods in studying adolescent-onset schizophrenia has highlighted alterations in the mirror neuron system and mentalizing networks, suggesting that these changes may be state-specific and relevant to symptomatology (ref: Sun doi.org/10.1016/j.neures.2020.01.003/). Additionally, a retrospective review of primary skull base chordomas identified prognostic factors that could inform clinical decision-making and improve patient outcomes (ref: La Corte doi.org/10.1007/s00701-020-04219-7/). These findings reflect the ongoing efforts to enhance diagnostic accuracy and therapeutic strategies in neuropathology.