Gold N-Heterocyclic Carbene Catalysts for the Hydrofluorination of Alkynes Using Hydrofluoric Acid: Reaction Scope, Mechanistic Studies and the Tracking of Elusive Intermediates.

An efficient and chemoselective methodology deploying gold-N-heterocyclic carbene (NHC) complexes as catalysts in the hydrofluorination of terminal alkynes using aqueous HF has been developed. Mechanistic studies shed light on an in situ generated catalyst, formed by the reaction of Brønsted basic gold pre-catalysts with HF in water, which exhibits the highest reactivity and chemoselectivity. The catalytic system has a wide alkyl substituted-substrate scope, and stoichiometric as well as catalytic reactions with tailor-designed gold pre-catalysts enable the identification of various gold species involved along the catalytic cycle. Computational studies aid in understanding the chemoselectivity observed through examination of key mechanistic steps for phosphine- and NHC-coordinated gold species bearing the triflate counterion and the elusive key complex bearing a bifluoride counterion.

Body size interacts with the structure of the central nervous system: A multi-center in vivo neuroimaging study.

Clinical research emphasizes the implementation of rigorous and reproducible study designs that rely on between-group matching or controlling for sources of biological variation such as subject's sex and age. However, corrections for body size (i.e. height and weight) are mostly lacking in clinical neuroimaging designs. This study investigates the importance of body size parameters in their relationship with spinal cord (SC) and brain magnetic resonance imaging (MRI) metrics. Data were derived from a cosmopolitan population of 267 healthy human adults (age 30.1±6.6 years old, 125 females). We show that body height correlated strongly or moderately with brain gray matter (GM) volume, cortical GM volume, total cerebellar volume, brainstem volume, and cross-sectional area (CSA) of cervical SC white matter (CSA-WM; 0.44≤r≤0.62). In comparison, age correlated weakly with cortical GM volume, precentral GM volume, and cortical thickness (-0.21≥r≥-0.27). Body weight correlated weakly with magnetization transfer ratio in the SC WM, dorsal columns, and lateral corticospinal tracts (-0.20≥r≥-0.23). Body weight further correlated weakly with the mean diffusivity derived from diffusion tensor imaging (DTI) in SC WM (r=-0.20) and dorsal columns (-0.21), but only in males. CSA-WM correlated strongly or moderately with brain volumes (0.39≤r≤0.64), and weakly with precentral gyrus thickness and DTI-based fractional anisotropy in SC dorsal columns and SC lateral corticospinal tracts (-0.22≥r≥-0.25). Linear mixture of sex and age explained 26±10% of data variance in brain volumetry and SC CSA. The amount of explained variance increased at 33±11% when body height was added into the mixture model. Age itself explained only 2±2% of such variance. In conclusion, body size is a significant biological variable. Along with sex and age, body size should therefore be included as a mandatory variable in the design of clinical neuroimaging studies examining SC and brain structure.

Pontomedullary junction as a reference for spinal cord cross-sectional area: validation across neck positions.

Spinal cord cross-sectional area (CSA) is an important MRI biomarker to assess spinal cord atrophy in various neurodegenerative and traumatic spinal cord diseases. However, the conventional method of computing CSA based on vertebral levels is inherently flawed, as the prediction of spinal levels from vertebral levels lacks reliability, leading to considerable variability in CSA measurements. Computing CSA from an intrinsic neuroanatomical reference, the pontomedullary junction (PMJ), has been proposed in previous work to overcome limitations associated with using a vertebral reference. However, the validation of this alternative approach, along with its variability across and within participants under variable neck extensions, remains unexplored. The goal of this study was to determine if the variability of CSA across neck flexions/extensions is reduced when using the PMJ, compared to vertebral levels. Ten participants underwent a 3T MRI T2w isotropic scan at 0.6 mm3 for 3 neck positions: extension, neutral and flexion. Spinal cord segmentation, vertebral labeling, PMJ labeling, and CSA were computed automatically while spinal segments were labeled manually. Mean coefficient of variation for CSA across neck positions was 3.99 ± 2.96% for the PMJ method vs. 4.02 ± 3.01% for manual spinal segment method vs. 4.46 ± 3.10% for the disc method. These differences were not statistically significant. The PMJ method was slightly more reliable than the disc-based method to compute CSA at specific spinal segments, although the difference was not statistically significant. This suggests that the PMJ can serve as a valuable alternative and reliable method for estimating CSA when a disc-based approach is challenging or not feasible, such as in cases involving fused discs in individuals with spinal cord injuries.

Automatic measure and normalization of spinal cord cross-sectional area using the pontomedullary junction.

Spinal cord cross-sectional area (CSA) is a relevant biomarker to assess spinal cord atrophy in neurodegenerative diseases. However, the considerable inter-subject variability among healthy participants currently limits its usage. Previous studies explored factors contributing to the variability, yet the normalization models required manual intervention and used vertebral levels as a reference, which is an imprecise prediction of the spinal levels. In this study we implemented a method to measure CSA automatically from a spatial reference based on the central nervous system (the pontomedullary junction, PMJ), we investigated factors to explain variability, and developed normalization strategies on a large cohort (N = 804). Following automatic spinal cord segmentation, vertebral labeling and PMJ labeling, the spinal cord CSA was computed on T1w MRI scans from the UK Biobank database. The CSA was computed using two methods. For the first method, the CSA was computed at the level of the C2-C3 intervertebral disc. For the second method, the CSA was computed at 64 mm caudally from the PMJ, this distance corresponding to the average distance between the PMJ and the C2-C3 disc across all participants. The effect of various demographic and anatomical factors was explored, and a stepwise regression found significant predictors; the coefficients of the best fit model were used to normalize CSA. CSA measured at C2-C3 disc and using the PMJ differed significantly (paired t-test, p-value = 0.0002). The best normalization model included thalamus, brain volume, sex and the interaction between brain volume and sex. The coefficient of variation went down for PMJ CSA from 10.09 (without normalization) to 8.59%, a reduction of 14.85%. For CSA at C2-C3, it went down from 9.96 to 8.42%, a reduction of 15.13 %. This study introduces an end-to-end automatic pipeline to measure and normalize cord CSA from a neurological reference. This approach requires further validation to assess atrophy in longitudinal studies. The inter-subject variability of CSA can be partly accounted for by demographics and anatomical factors.