Harnessing the spatial and transcriptional regulation of monoterpenoid indole alkaloid metabolism in Alstonia scholaris leads to the identification of broad geissoschizine cyclase activities.

Monoterpene indole alkaloids (MIAs) are valuable metabolites produced in numerous medicinal plants from the Apocynaceae family such as Alstonia scholaris, which synthesizes strictamine, a MIA displaying neuropharmacological properties of a potential importance. To get insights into the MIA metabolism in A. scholaris, we studied here both the spatial and transcriptional regulations of MIA genes by performing a robust transcriptomics analysis of the main plant organs, leaf epidermis but also by sequencing RNA from leaves transiently overexpressing the master transcriptional regulator MYC2.

Principles of Stereotactic Surgery.

Background And Objectives: Stereotactic procedures are used to manage a diverse set of patients across a variety of clinical contexts. The stereotactic devices and software used in these procedures vary between surgeons, but the fundamental principles that constitute safe and accurate execution do not. The aim of this work is to describe these principles to equip readers with a generalizable knowledge base to execute and understand stereotactic procedures.

A General Framework for Characterizing Inaccuracy in Stereotactic Systems.

Background And Objectives: Identifying and characterizing sources of targeting error in stereotactic procedures is essential to maximizing accuracy, potentially improving surgical outcomes. We aim to describe a generic framework which characterizes sources of stereotactic inaccuracy.

Methods: We assembled a list of stereotactic systems: ROSA, Neuromate, Mazor Renaissance, ExcelsiusGPS, Cirq, STarFix (FHC), Nexframe, ClearPoint, CRW, and Leksell.

Spatial and spectral changes in cortical surface potentials during pinching versusthumb and index finger flexion.

Electrocorticographic (ECoG) signals provide high-fidelity representations of sensorimotor cortex activation during contralateral hand movements. Understanding the relationship between independent and coordinated finger movements along with their corresponding ECoG signals is crucial for precise brain mapping and neural prosthetic development. We analyzed subdural ECoG signals from three adult epilepsy patients with subdural electrode arrays implanted for seizure foci identification.

Spectral Changes in Motor Thalamus Field Potentials During Movement.

Motor thalamus plays a crucial role in integrating and modulating sensorimotor information. While voltage power spectral changes in motor cortex with movement are well-characterized, corresponding activity in the motor thalamus, particularly broadband power change, remains unclear. The present study aims to characterize spectral changes in motor thalamus during hand movements of 15 subjects undergoing awake deep brain stimulation surgery targeting the ventral intermediate (Vim) nucleus of the thalamus for disabling tremor.

Debottlenecking cytochrome P450-dependent metabolic pathways for the biosynthesis of commercial natural products.

Covering: 2016 to the end of 2024This highlight article aims to provide a perspective on the challenges that novel biotechnological processes face in the biomanufacturing of natural products (NPs) whose biosynthesis pathways rely on cytochrome P450 monooxygenases. This enzyme superfamily is one of the most versatile in the biosynthesis of a plethora of NPs finding use across the food, nutrition, medicine, chemical and cosmetics industries. These enzymes often exhibit excellent regio- and stereoselectivity, but they can suffer from low activity and instability, which are serious issues impairing the development of high performing bioprocesses.

Proper reference selection and re-referencing to mitigate bias in single pulse electrical stimulation data.

Single pulse electrical stimulation experiments produce pulse-evoked potentials used to infer brain connectivity. The choice of recording reference for intracranial electrodes remains non-standardized and can significantly impact data interpretation. When the reference electrode is affected by stimulation or evoked brain activity, it can contaminate the pulse-evoked potentials recorded at all other electrodes and influence interpretation of findings.

Locoregional CAR T Cells for the Treatment of CNS Tumors in Children: Investigational Drug Service Pharmacy Activities.

Background: A major obstacle in translating the therapeutic potential of chimeric antigen receptor (CAR) T cells to children with central nervous system (CNS) tumors is the blood-brain barrier. To overcome this limitation, preclinical and clinical studies have supported the use of repeated, locoregional intracranial CAR T-cell delivery. However, there is limited literature available describing the process for the involvement of an investigational drug service (IDS) pharmacy, particularly in the setting of a children's hospital with outpatient dosing for CNS tumors.

Clinical Utility of Serum C-Peptide Concentration for Hospitalized Patients with Hyperglycemia.

Serum C-peptide concentration is often utilized for diagnostic, prognostic, or therapeutic assessment in diabetes mellitus. However, there are limited clinical data regarding diagnostic and predictive value of C-peptide measured during hospitalizations for hyperglycemia. Adults admitted to Mayo Clinic inpatient facilities due to an acute hyperglycemic emergency between January 2017 and November 2022 were included in our study.

Functional mapping of movement and speech using task-based electrophysiological changes in stereoelectroencephalography.

Objective: Stereoelectroencephalography (SEEG) has become the predominant method for intracranial seizure localization. When imaging, semiology, and scalp EEG findings are not in full agreement or definitively localizing, implanted SEEG recordings are used to test candidate seizure onset zones (SOZs). Discovered SOZs may then be targeted for resection, laser ablation, or neurostimulation.

Changes in endoscopic activity and classification of lesions with panenteric capsule endoscopy in patients treated for Crohn's disease - a prospective blinded comparison with ileocolonoscopy, faecal calprotectin and C-reactive protein.

Background And Aims: Panenteric capsule endoscopy (PCE) is a minimally invasive modality that may replace ileocolonoscopy (IC) in selected patients with Crohn's disease (CD). This study aimed to evaluate the dynamics of repeated assessment with PCE in patients receiving medical treatment for ileocolonic CD.

Methods: This prospective, blinded, multicentre study included patients with endoscopically active CD.

Dapagliflozin and Right Ventricular-Pulmonary Vascular Interaction in Heart Failure With Preserved Ejection Fraction: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Increases in pulmonary capillary wedge pressure (PCWP) during exercise reduce pulmonary artery (PA) compliance, increase pulsatile right ventricular (RV) afterload, and impair RV-PA coupling in patients with heart failure with preserved ejection fraction (HFpEF). The effects of the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin on pulmonary vascular properties and RV-PA coupling are unknown.

Objective: To test the effect of dapagliflozin on right ventricular performance and pulmonary vascular load during exertion in HFpEF.

Dielectrophoretic bead-droplet reactor for solid-phase synthesis.

Solid-phase synthesis underpins many advances in synthetic and combinatorial chemistry, biology, and material science. The immobilization of a reacting species on the solid support makes interfacing of reagents an important challenge in this approach. In traditional synthesis columns, this leads to reaction errors that limit the product yield and necessitates excess consumption of the mobile reagent phase.