Morphoelectric and transcriptomic divergence of the layer 1 interneuron repertoire in human versus mouse neocortex.

Neocortical layer 1 (L1) is a site of convergence between pyramidal-neuron dendrites and feedback axons where local inhibitory signaling can profoundly shape cortical processing. Evolutionary expansion of human neocortex is marked by distinctive pyramidal neurons with extensive L1 branching, but whether L1 interneurons are similarly diverse is underexplored. Using Patch-seq recordings from human neurosurgical tissue, we identified four transcriptomic subclasses with mouse L1 homologs, along with distinct subtypes and types unmatched in mouse L1.

Functional alteration due to structural damage is network dependent: insight from multiple sclerosis.

Little is known about how the brain's functional organization changes over time with respect to structural damage. Using multiple sclerosis as a model of structural damage, we assessed how much functional connectivity (FC) changed within and between preselected resting-state networks (RSNs) in 122 subjects (72 with multiple sclerosis and 50 healthy controls). We acquired the structural, diffusion, and functional MRI to compute functional connectomes and structural disconnectivity profiles.

Human neocortical expansion involves glutamatergic neuron diversification.

The neocortex is disproportionately expanded in human compared with mouse, both in its total volume relative to subcortical structures and in the proportion occupied by supragranular layers composed of neurons that selectively make connections within the neocortex and with other telencephalic structures. Single-cell transcriptomic analyses of human and mouse neocortex show an increased diversity of glutamatergic neuron types in supragranular layers in human neocortex and pronounced gradients as a function of cortical depth. Here, to probe the functional and anatomical correlates of this transcriptomic diversity, we developed a robust platform combining patch clamp recording, biocytin staining and single-cell RNA-sequencing (Patch-seq) to examine neurosurgically resected human tissues.

Integrated Morphoelectric and Transcriptomic Classification of Cortical GABAergic Cells.

Neurons are frequently classified into distinct types on the basis of structural, physiological, or genetic attributes. To better constrain the definition of neuronal cell types, we characterized the transcriptomes and intrinsic physiological properties of over 4,200 mouse visual cortical GABAergic interneurons and reconstructed the local morphologies of 517 of those neurons. We find that most transcriptomic types (t-types) occupy specific laminar positions within visual cortex, and, for most types, the cells mapping to a t-type exhibit consistent electrophysiological and morphological properties.

Irradiance, Photofrin Dose and Initial Tumor Volume are Key Predictors of Response to Interstitial Photodynamic Therapy of Locally Advanced Cancers in Translational Models.

The objective of the present study was to develop a predictive model for Photofrin -mediated interstitial photodynamic therapy (I-PDT) of locally advanced tumors. Our finite element method was used to simulate 630-nm intratumoral irradiance and fluence for C3H mice and New Zealand White rabbits bearing large squamous cell carcinomas. Animals were treated with light only or I-PDT using the same light settings.

Preserved network functional connectivity underlies cognitive reserve in multiple sclerosis.

Cognitive reserve is one's mental resilience or resistance to the effects of structural brain damage. Reserve effects are well established in people with multiple sclerosis (PwMS) and Alzheimer's disease, but the neural basis of this phenomenon is unclear. We aimed to investigate whether preservation of functional connectivity explains cognitive reserve.

White matter tract network disruption explains reduced conscientiousness in multiple sclerosis.

Quantifying white matter (WM) tract disruption in people with multiple sclerosis (PwMS) provides a novel means for investigating the relationship between defective network connectivity and clinical markers. PwMS exhibit perturbations in personality, where decreased Conscientiousness is particularly prominent. This trait deficit influences disease trajectory and functional outcomes such as work capacity.

Volumetric modulated arc therapy treatment planning of thoracic vertebral metastases using stereotactic body radiotherapy.

Purpose/objectives: To retrospectively evaluate the plan quality, treatment efficiency, and accuracy of volumetric modulated arc therapy (VMAT) plans for thoracic spine metastases using stereotactic body radiotherapy (SBRT).

Materials/methods: Seven patients with thoracic vertebral metastases treated with noncoplanar hybrid arcs (NCHA) (1 to 2 3D-conformal partial arcs +7 to 9 IMRT beams) were re-optimized with VMAT plans using three coplanar arcs. Tumors were located between T2 and T7 and PTVs ranged between 24.

On the use of volumetric-modulated arc therapy for single-fraction thoracic vertebral metastases stereotactic body radiosurgery.

To retrospectively evaluate quality, efficiency, and delivery accuracy of volumetric-modulated arc therapy (VMAT) plans for single-fraction treatment of thoracic vertebral metastases using image-guided stereotactic body radiosurgery (SBRS) after RTOG 0631 dosimetric compliance criteria. After obtaining credentialing for MD Anderson spine phantom irradiation validation, 10 previously treated patients with thoracic vertebral metastases with noncoplanar hybrid arcs using 1 to 2 3D-conformal partial arcs plus 7 to 9 intensity-modulated radiation therapy beams were retrospectively re-optimized with VMAT using 3 full coplanar arcs. Tumors were located between T2 and T12.

Therapeutic hyperthermia: The old, the new, and the upcoming.

Hyperthermia has long been used for cancer treatment, either alone or in combination with chemotherapy, radiation therapy, or both. Its efficacy and versatility continue to be well demonstrated in randomized trials across a number of primary cancers, but barriers to its widespread adoption persist including effective delivery and verification systems. This article describes hyperthermia, details its biological mechanisms of action and immunological effects, and summarizes select preclinical data and key clinical trials combining hyperthermia with standard cancer treatments.

GADD153 expression does not necessarily correlate with changes in culture behavior of hybridoma cells.

Background: The acute sensitivity of some hybridoma cell lines to culture-related stresses severely limits their productivity. Recent developments in the characterization of the stress signals modulating the cellular phenotype revealed that the pro-apoptotic transcription factor Gadd153 could be used as a marker to facilitate the optimization of mammalian cell cultures. In this report, we analyzed the expression of Gadd153 in Sp2/0-Ag14 murine hybridoma cells grown in stationary batch culture and subjected to two different culture optimization paradigms: L-glutamine supplementation and ectopic expression of Bcl-xL, an anti-apoptotic gene.