Faculty Bibliography

Widespread hyperalgesia, characterized by pain sensitivity beyond the primary pain site, is a common yet under-characterized feature across chronic pain conditions, including chronic pancreatitis (CP). In this exploratory study, we identified a candidate neural biosignature of widespread hyperalgesia using high-density electroencephalography (EEG) in patients with chronic low back pain (cLBP). Specifically, stimulus-evoked delta, theta, and alpha oscillatory activity in the bilateral medial orbitofrontal cortex (mOFC) differentiated cLBP patients with widespread hyperalgesia from healthy controls. To examine cross-condition generalizability and advance predictive biomarker development for CP, we applied this mOFC-derived EEG biosignature to an independent cohort of patients with CP. The biosignature distinguished CP patients with widespread hyperalgesia and predicted individual treatment responses to peripherally targeted endoscopic therapy. These preliminary findings provide early support for a shared cortical signature of central sensitization across pain conditions and offer translational potential for developing EEG-based predictive tools for treatment response in CP.

This collective eulogy by colleagues, co-authors and friends is a tribute to the work and life of Rudolf Nieuwenhuys. 'Neurofascination' is an apt label for his scholarly life in the sciences from the start in 1955 until his last days in 2024. In addition, he had a broad interest in Roman and Gothic architecture, the history and politics of the twentieth century, religion and the music of Johann Sebastian Bach. Extensive discussions on one or more of these topics often led to long-lasting friendships, some of which inform the following pages. Rudolf is remembered for his highly didactical and remarkably illustrated presentations and publications, including the three-volume The Central Nervous System of Vertebrates and the four editions of The Human Central Nervous System. His research interests addressed an impressively wide range of topics concerning development and evolutionary neurobiology and a systematic approach to comparative brain structures in vertebrates. His almost endless fascination for neuromorphology included the invertebrates as well. But unfortunately, even his long life was not enough to write the book on the comparative neuroanatomy of invertebrates which he long had in mind. The many years of his career spanned the remarkable histology of the gigantocerebellum of mormyrids to an exploratory synthesis of subdivisions of the human cortex, as originally mapped by the Vogt-Vogt school of cortical architectonics.

The subgenual anterior cingulate cortex (sgACC) plays a central role in the pathophysiology of major depressive disorder (MDD). Its functional interactive profile with the left dorsal lateral prefrontal cortex (DLPFC) is associated with transcranial magnetic stimulation (TMS) treatment outcomes. Previous research on sgACC functional connectivity (FC) in MDD has yielded inconsistent results, partly due to small sample sizes and limited statistical power. Furthermore, calculating sgACC-FC to target TMS individually is challenging. We used a large multi-site cross-sectional sample (1660 patients with MDD vs. 1341 healthy controls) from Phase II of the Depression Imaging REsearch ConsorTium (DIRECT) to systematically delineate case-control difference maps of sgACC-FC. We explored the potential impact of group-level abnormality profiles on TMS target localization and clinical efficacy. Next, we developed an MDD big data-guided, individualized TMS targeting algorithm to integrate group-level statistical maps with individual-level brain activity to individually localize TMS targets. We found enhanced sgACC-DLPFC FC in patients with MDD compared with healthy controls (HC). These group differences altered the position of the sgACC anti-correlation peak in the left DLPFC. We showed that the magnitude of case-control differences in the sgACC-FC was related to clinical improvement in two independent clinical samples. This targeting algorithm may generate targets demonstrating stronger associations with clinical efficiency than group-level targets. We reliably delineated MDD-related abnormalities of sgACC-FC profiles in a large, independently ascertained sample and demonstrated the potential impact of such case-control differences on FC-guided localization of TMS targets.

BACKGROUND:/calmodulin-dependent protein kinase II and selected for probe collection. RESULTS:This approach significantly reduced the amount of FFPE tissue needed for robust single population RNA-seq. We demonstrate ~20 identified L3 or L5 pyramidal neurons or one lamina-specific cortical ribbon from a single 5µm thick section is sufficient to generate robust RNA-seq reads. Bioinformatic analysis of neurons and ribbons showed notable similarities and differences reflective of the single neuron and multiple admixed cell types within the former and latter, respectively. Comparison with existing methods Protocols exist for DSP of postmortem human FFPE brain tissue. However, this new approach enables profiling small groups of ~14-21 pyramidal neurons using the GeoMx DSP platform. CONCLUSIONS:This optimized DSP assay provides high resolution RNA-seq data demonstrating utility and versatility of the GeoMx platform for individually characterized neurons and isolated cortical ribbons within postmortem FFPE human brain tissue for downstream analyses.

Developed by the Center for Robust Speech Systems at the University of Texas at Dallas, in collaboration with New York University and the University of Wisconsin-Madison, CCi-MOBILE addresses a critical challenge in optimizing cochlear implant (CI) fitting and enhancing sound coding strategies. Existing clinical CI processors and research tools often lack either the necessary computational power and flexibility or the portability required for real-world testing. CCi-MOBILE bridges this gap by enabling the implementation and evaluation of diverse real-time sound coding algorithms in both laboratory and real-world settings, including those requiring synchronized bilateral stimulation. Building upon previous publications, this paper provides new detailed discussion on parameter setting for stimulus generation with CCi-MOBILE and serves as a comprehensive resource for scientists and engineers developing novel real-time sound coding and signal processing strategies with this platform. As part of an ongoing development effort, future generations of CCi-MOBILE may offer additional functionalities beyond those described here.

BACKGROUND:Despite evidence supporting the efficacy of culturally tailored interventions in reducing stigma, such approaches are lacking for women living with HIV/AIDS (WLWHAs) in China. We conducted this study to determine the efficacy of the culturally tailored Helping Overcome Perceived Stigma (HOPES) intervention in reducing perceived stigma among WLWHAs in China. METHODS:A single-blinded, two-arm parallel-group randomized clinical trial was conducted from 2023 to 2024 in South and Southwest China. WLWHAs from four hospitals were assigned using a WeChat-embedded randomization application to the control group (usual care) or the HOPES intervention. Data analysts remained blinded. Interventions were conducted virtually using Leave No One Behind (LNOB) platform for 3 months. The primary outcome, perceived stigma score, was assessed at baseline, immediately after the intervention and at 3 months post-intervention using 7 items from the HIV/AIDS Stigma Experience Questionnaire (HASEQ), with data analyzed through repeated measures analysis. RESULTS:Of 136 WLWHAs screened, we randomized 101 WLWHAs (50 HOPES; 51 controls). The HOPES group demonstrated a statistically significant reduction in perceived stigma scores immediately after the intervention (-3.86 points, 95 % CI: 5.34 to -2.38, P < .001) and at three months post-intervention (-5.83 points, 95 % CI: 7.20 to -4.47, P < .001) compared to the control group. CONCLUSION/CONCLUSIONS:The findings demonstrate HOPES' efficacy in reducing perceived stigma in WLWHA. However, the clinical significance of these changes needs further investigation. Future research should focus on defining meaningful patient-reported thresholds, assessing long-term impact, and optimizing delivery methods.

OBJECTIVES/UNASSIGNED:To review the different analgesic modalities and benefits of non-opioid pain management options as well as their evidence-based, established superiority, compared to opioid medications. MATERIALS/UNASSIGNED:We review the updated literature about pain management of renal colic, a prevalent and painful urologic condition. Prescribers must know the efficacy, safety and possible ramifications of analgesic selections. RESULTS/UNASSIGNED:Commonly prescribed medications in the United States (US) include non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, and opioids. In the context of the current epidemic of death from overdoses of opioids in the US, the frequency of opioid prescribing for renal colic is likely excessive, problematic and potentially remediable. We also present analgesic modalities revolving around interventions with peri-procedural pain management for ureteroscopy and percutaneous nephrolithotomy. After touching on the implications of misguided opioid use, especially in the context of kidney stone disease, and despite the evidence and consensus guidelines supporting NSAIDs in renal colic, current evidence has shown that many clinicians continue to prescribe opioids as first-line treatment. Finally, we highlight current efforts targeted at the reduction of opioid use and prescription in the setting of provider education and decision aids in curbing misguided opioid use in renal colic. CONCLUSIONS/UNASSIGNED:While the evidence against treating kidney stones with opioids is clear, more work is needed to shift current practices to reflect that renal colic is a non-opioid-requiring condition.

The value of preclinical diffusion MRI (dMRI) is substantial. While dMRI enables in vivo non-invasive characterization of tissue, ex vivo dMRI is increasingly being used to probe tissue microstructure and brain connectivity. Ex vivo dMRI has several experimental advantages including higher SNR and spatial resolution compared to in vivo studies, and enabling more advanced diffusion contrasts for improved microstructure and connectivity characterization. Another major advantage of ex vivo dMRI is the direct comparison with histological data, as a crucial methodological validation. However, there are a number of considerations that must be made when performing ex vivo experiments. The steps from tissue preparation, image acquisition and processing, and interpretation of results are complex, with many decisions that not only differ dramatically from in vivo imaging of small animals, but ultimately affect what questions can be answered using the data. This work represents "Part 2" of a three-part series of recommendations and considerations for preclinical dMRI. We describe best practices for dMRI of ex vivo tissue, with a focus on the value that ex vivo imaging adds to the field of dMRI and considerations in ex vivo image acquisition. We first give general considerations and foundational knowledge that must be considered when designing experiments. We briefly describe differences in specimens and models and discuss why some may be more or less appropriate for different studies. We then give guidelines for ex vivo protocols, including tissue fixation, sample preparation, and MR scanning. In each section, we attempt to provide guidelines and recommendations, but also highlight areas for which no guidelines exist (and why), and where future work should lie. An overarching goal herein is to enhance the rigor and reproducibility of ex vivo dMRI acquisitions and analyses, and thereby advance biomedical knowledge.

RATIONALE & OBJECTIVE/OBJECTIVE:Despite national efforts, the uptake of home dialysis (peritoneal dialysis or home hemodialysis) remains low. Characteristics of the built environment may differentially impact home dialysis use. STUDY DESIGN/METHODS:Retrospective cohort study (2010-2019). SETTING & PARTICIPANTS/METHODS:1,103,695 adults (aged≥18 years) initiating dialysis in the US Renal Data System. EXPOSURE/METHODS:We examined 3 built environment domains based on residential ZIP code: (1) medically underserved areas (MUAs), defined as neighborhoods with limited primary care access; (2) distance to the nearest dialysis facility; and (3) distribution of housing characteristics (structure and overcrowding). OUTCOME/RESULTS:Uptake of home dialysis modalities at dialysis initiation. ANALYTICAL APPROACH/METHODS:We quantified associations between built environment characteristics and home dialysis initiation using multilevel logistic regression stratified by urbanicity type (urban, suburban, small-town, and rural). RESULTS:Among adults initiating dialysis, 40.8% lived in MUAs. Across ZIP codes, the mean percentage of overcrowded housing was 4.2% (SD, 4.7%), and the percentage of detached housing was 61.1% (SD, 21.1%); mean distance to the nearest dialysis facility was 5.5km (SD, 9.1km). Living in MUAs was associated with reduced home dialysis use only in urban (OR, 0.94; 95% CI, 0.91-0.96) and suburban (OR, 0.92; 95% CI, 0.89-0.94) areas. Similarly, housing overcrowding was associated with decreased home dialysis use only in urban (OR, 0.88; 95% CI, 0.86-0.89) and suburban (OR, 0.91; 95% CI, 0.90-0.93) areas. Longer distance to a dialysis facility was the most salient neighborhood factor associated with increased home dialysis use in small towns (OR, 1.14; 95% CI, 1.12-1.16) and rural areas (OR, 1.17; 95% CI, 1.15-1.19). LIMITATIONS/CONCLUSIONS:Housing characteristics were measured at the ZIP code level. CONCLUSIONS:Built environment characteristics associated with home dialysis uptake vary by urbanicity. Policies should address built environment barriers that are specific to urbanicity level. For example, increasing the frequency of dialysate delivery schedules could address housing space constraints in urban and suburban areas, and promoting home dialysis might be more effective for patients living far from dialysis centers in small-town and rural areas.

Around 40% of the US population and 1 in 6 individuals worldwide have obesity, with the incidence surging globally^1,2. Various dietary interventions, including carbohydrate, fat and, more recently, amino acid restriction, have been explored to combat this epidemic^3-6. Here we investigated the impact of removing individual amino acids on the weight profiles of mice. We show that conditional cysteine restriction resulted in the most substantial weight loss when compared to essential amino acid restriction, amounting to 30% within 1 week, which was readily reversed. We found that cysteine deficiency activated the integrated stress response and oxidative stress response, which amplify each other, leading to the induction of GDF15 and FGF21, partly explaining the phenotype^7-9. Notably, we observed lower levels of tissue coenzyme A (CoA), which has been considered to be extremely stable¹⁰, resulting in reduced mitochondrial functionality and metabolic rewiring. This results in energetically inefficient anaerobic glycolysis and defective tricarboxylic acid cycle, with sustained urinary excretion of pyruvate, orotate, citrate, α-ketoglutarate, nitrogen-rich compounds and amino acids. In summary, our investigation reveals that cysteine restriction, by depleting GSH and CoA, exerts a maximal impact on weight loss, metabolism and stress signalling compared with other amino acid restrictions. These findings suggest strategies for addressing a range of metabolic diseases and the growing obesity crisis.