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MSTPublications: August 2023

Posted by on Wednesday, August 30, 2023 in New Publications .

Deep Learning Segmentation of the Nucleus Basalis of Meynert on 3T MRI.
Doss DJ, Johnson GW, Narasimhan S, Shless JS, Jiang JW, González HFJ, Paulo DL, Lucas A, Davis KA, Chang C, Morgan VL, Constantinidis C, Dawant BM, Englot DJ.
AJNR Am J Neuroradiol. 2023 Aug 10. doi: 10.3174/ajnr.A7950. Online ahead of print.

Background and purpose: The nucleus basalis of Meynert is a key subcortical structure that is important in arousal and cognition and has been explored as a deep brain stimulation target but is difficult to study due to its small size, variability among patients, and lack of contrast on 3T MR imaging. Thus, our goal was to establish and evaluate a deep learning network for automatic, accurate, and patient-specific segmentations with 3T MR imaging.
Materials and methods: Patient-specific segmentations can be produced manually; however, the nucleus basalis of Meynert is difficult to accurately segment on 3T MR imaging, with 7T being preferred. Thus, paired 3T and 7T MR imaging data sets of 21 healthy subjects were obtained. A test data set of 6 subjects was completely withheld. The nucleus was expertly segmented on 7T, providing accurate labels for the paired 3T MR imaging. An external data set of 14 patients with temporal lobe epilepsy was used to test the model on brains with neurologic disorders. A 3D-Unet convolutional neural network was constructed, and a 5-fold cross-validation was performed.
Results: The novel segmentation model demonstrated significantly improved Dice coefficients over the standard probabilistic atlas for both healthy subjects (mean, 0.68 [SD, 0.10] versus 0.45 [SD, 0.11], P = .002, t test) and patients (0.64 [SD, 0.10] versus 0.37 [SD, 0.22], P < .001). Additionally, the model demonstrated significantly decreased centroid distance in patients (1.18 [SD, 0.43] mm, 3.09 [SD, 2.56] mm, P = .007).
Conclusions: We developed the first model, to our knowledge, for automatic and accurate patient-specific segmentation of the nucleus basalis of Meynert. This model may enable further study into the nucleus, impacting new treatments such as deep brain stimulation.


Temporal modelling of the biofilm lifecycle (TMBL) establishes kinetic analysis of plate-based bacterial biofilm dynamics.
Enriquez KT, Plummer WD, Neufer PD, Chazin WJ, Dupont WD, Skaar EP.
J Microbiol Methods. 2023 Aug 17;212:106808. doi: 10.1016/j.mimet.2023.106808. Online ahead of print.

Bacterial biofilms are critical to pathogenesis and infection. They are associated with rising rates of antimicrobial resistance. Biofilms are correlated with worse clinical outcomes, making them important to infectious diseases research. There is a gap in knowledge surrounding biofilm kinetics and dynamics which makes biofilm research difficult to translate from bench to bedside. To address this gap, this work employs a well-characterized crystal violet biomass accrual and planktonic cell density assay across a clinically relevant time course and expands statistical analysis to include kinetic information in a protocol termed the TMBL (Temporal Mapping of the Biofilm Lifecycle) assay. TMBL’s statistical framework quantitatively compares biofilm communities across time, species, and media conditions in a 96-well format. Measurements from TMBL can reliably be condensed into response features that inform the time-dependent behavior of adherent biomass and planktonic cell populations. Staphylococcus aureus and Pseudomonas aeruginosa biofilms were grown in conditions of metal starvation in nutrient-variable media to demonstrate the rigor and translational potential of this strategy. Significant differences in single-species biofilm formation are seen in metal-deplete conditions as compared to their controls which is consistent with the consensus literature on nutritional immunity that metal availability drives transcriptomic and metabolomic changes in numerous pathogens. Taken together, these results suggest that kinetic analysis of biofilm by TMBL represents a statistically and biologically rigorous approach to studying the biofilm lifecycle as a time-dependent process. In addition to current methods to study the impact of microbe and environmental factors on the biofilm lifecycle, this kinetic assay can inform biological discovery in biofilm formation and maintenance.


Hallmarks of CD8+ T cell dysfunction are established within hours of tumor antigen encounter before cell division.
Rudloff MW, Zumbo P, Favret NR, Roetman JJ, Detrés Román CR, Erwin MM, Murray KA, Jonnakuti ST, Dündar F, Betel D, Philip M.
Nat Immunol. 2023 Sep;24(9):1527-1539. doi: 10.1038/s41590-023-01578-y. Epub 2023 Aug 3.

Tumor-specific CD8+ T cells (TST) in patients with cancer are dysfunctional and unable to halt cancer progression. TST dysfunction, also known as exhaustion, is thought to be driven by chronic T cell antigen receptor (TCR) stimulation over days to weeks. However, we know little about the interplay between CD8+ T cell function, cell division and epigenetic remodeling within hours of activation. Here, we assessed early CD8+ T cell differentiation, cell division, chromatin accessibility and transcription in tumor-bearing mice and acutely infected mice. Surprisingly, despite robust activation and proliferation, TST had near complete effector function impairment even before undergoing cell division and had acquired hallmark chromatin accessibility features previously associated with later dysfunction/exhaustion. Moreover, continued tumor/antigen exposure drove progressive epigenetic remodeling, ‘imprinting’ the dysfunctional state. Our study reveals the rapid divergence of T cell fate choice before cell division in the context of tumors versus infection.


Nonviral In Vivo Delivery of CRISPR-Cas9 Using Protein-Agnostic, High-Loading Porous Silicon and Polymer Nanoparticles.
Fletcher RB, Stokes LD, Kelly IB 3rd, Henderson KM, Vallecillo-Viejo IC, Colazo JM, Wong BV, Yu F, d’Arcy R, Struthers MN, Evans BC, Ayers J, Castanon M, Weirich MJ, Reilly SK, Patel SS, Ivanova YI, Silvera Batista CA, Weiss SM, Gersbach CA, Brunger JM, Duvall CL.
ACS Nano. 2023 Aug 15. doi: 10.1021/acsnano.2c12261. Online ahead of print.

Surgical Management and Outcomes of Pediatric Congenital Head and Neck Teratomas: A Scoping Review.
Patel S, Kunnath AJ, Gallant JN, Belcher RH.
OTO Open. 2023 Aug 9;7(3):e66. doi: 10.1002/oto2.66. eCollection 2023 Jul-Sep.

The immunology of heart failure with preserved ejection fraction.
Smart CD, Madhur MS.
Clin Sci (Lond). 2023 Aug 31;137(16):1225-1247. doi: 10.1042/CS20230226.