Understanding ion-transfer reactions in silver electrodissolution and electrodeposition from first-principles calculations and experiments.

The electrified aqueous/metal interface is critical in controlling the performance of energy conversion and storage devices, but an atomistic understanding of even basic interfacial electrochemical reactions challenges both experiment and computation. We report a combined simulation and experimental study of (reversible) ion-transfer reactions involved in anodic Ag corrosion/deposition, a model system for interfacial electrochemical processes generating or consuming ions. With the explicit modeling of the electrode potential and a hybrid implicit-explicit solvation model, the density functional theory calculations produce free energy curves predicting thermodynamics, kinetics, partial charge profiles, and reaction trajectories. The calculated (equilibrium) free energy barriers (0.2 eV), and their asymmetries, agree with experimental activation energies (0.4 eV) and transfer coefficients, which were extracted from temperature-dependent voltage-step experiments on Au-supported, Ag-nanocluster substrates. The use of Ag nanoclusters eliminates the convolution of the kinetics of Ag+(aq.) generation and transfer with those of nucleation or etch-pit formation. The results indicate that the barrier is controlled by the bias-dependent competition between partial solvation of the incipient ion, metal-metal bonding, and electrostatic stabilization by image charge, with the latter two factors weakened by stronger positive biases. We also report simulations of the bias-dependence of defect generation relevant to nucleating corrosion by removing an atom from a perfect Ag(100) surface, which is predicted to occur via a vacancy-adatom intermediate. Together, these experiments and calculations provide the first validated, accurate, molecular model of the central steps that govern the rates of important dissolution/deposition reactions broadly relevant across the energy sciences.

Examining surgeon stress in robotic and laparoscopic surgery.

Robotic surgery may decrease surgeon stress compared to laparoscopic. To evaluate intraoperative surgeon stress, we measured salivary alpha-amylase and cortisol. We hypothesized robotic elicited lower increases in surgeon salivary amylase and cortisol than laparoscopic. Surgical faculty (n = 7) performing laparoscopic and robotic operations participated. Demographics: age, years in practice, time using laparoscopic vs robotic, comfort level and enthusiasm for each. Operative data included operative time, WRVU (surgical "effort"), resident year. Saliva was collected using passive drool collection system at beginning, middle and end of each case; amylase and cortisol measured using ELISA. Standard values were created using 7-minute exercise (HIIT), collecting saliva pre- and post-workout. Linear regression and Student's t test used for statistical analysis; p values < 0.05 were significant. Ninety-four cases (56 robotic, 38 laparoscopic) were collected (April-October 2022). Standardized change in amylase was 8.4 ± 4.5 (p < 0.001). Among operations, raw maximum amylase change in laparoscopic and robotic was 23.4 ± 11.5 and 22.2 ± 13.4; raw maximum cortisol change was 44.21 ± 46.57 and 53.21 ± 50.36, respectively. Values normalized to individual surgeon HIIT response, WRVU, and operative time, showing 40% decrease in amylase in robotic: 0.095 ± 0.12, vs laparoscopic: 0.164 ± 0.16 (p < 0.02). Normalized change in cortisol was: laparoscopic 0.30 ± 0.44, robotic 0.22 ± 0.4 (p = NS). On linear regression (p < 0.001), surgeons comfortable with complex laparoscopic cases had lower change in normalized amylase (p < 0.01); comfort with complex robotic was not significant. Robotic may be less physiologically stressful, eliciting less increase in salivary amylase than laparoscopic. Comfort with complex laparoscopic decreased stress in robotic, suggesting laparoscopic experience is valuable prior to robotic.

Predictors of endobronchial forceps utilization for inferior vena cava filter retrieval: when snare retrieval fails.

BACKGROUND: Endobronchial forceps are commonly used for complex IVC filter removal and after initial attempts at IVC filter retrieval with a snare have failed. Currently, there are no clear guidelines to help distinguish cases where primary removal should be attempted with standard snare technique or whether attempts at removal should directly be started with forceps. This study is aimed to identify clinical and imaging predictors of snare failure which necessitate conversion to endobronchial forceps. METHODS: Retrospective analysis of 543 patients who underwent IVC filter retrievals were performed at three large quaternary care centers from Jan 2015 to Jan 2022. Patient demographics and IVC filter characteristics on cross-sectional images (degree of tilt, hook embedment, and strut penetration, etc.) were reviewed. Binary multivariate logistic regression was used to identify predictors of IVC filter retrieval where snare retrieval would fail. RESULTS: Thirty seven percent of the patients (n = 203) necessitated utilization of endobronchial forceps. IVC filter hook embedment (OR:4.55; 95%CI: 1.74-11.87; p = 0.002) and strut penetration (OR: 56.46; 95% CI 20.2-157.7; p = 0.001) were predictors of snare failure. In contrast, total dwell time, BMI, and degree of filter tilt were not associated with snare failure. Intraprocedural conversion from snare to endobronchial forceps was significantly associated with increased contrast volume, radiation dose, and total procedure times (p < 0.05). CONCLUSION: IVC filter hook embedment and strut penetration were predictors of snare retrieval failure. Intraprocedural conversion from snare to endobronchial forceps increased contrast volume, radiation dose, and total procedure time. When either hook embedment or strut penetration is present on pre-procedural cross-sectional images, IVC filter retrieval should be initiated using endobronchial forceps. LEVEL OF EVIDENCE: Level 3, large multicenter retrospective cohort.

Analysis of Clinical Outcomes After Robotic Hepatectomy Applying the Western-Model Southampton Laparoscopic Difficulty Scoring System. An Experience From a Tertiary US Hepatobiliary Center.

BACKGROUND: Identification of resections with high risk of intraoperative complications is critical in guiding case selection for minimally invasive liver surgery. Several Japanese and European difficulty scoring systems have been proposed for laparoscopic liver surgery. However, the applicability of these systems for robotic liver resections has not been fully investigated. This study considers the Southampton system and examines its validity when applied to robotic hepatectomies. METHODS: We undertook a retrospective review of 372 patients who underwent robotic hepatectomies for various indications between 2013 and 2022. Of these patients, 63 operations were classified as low risk, 91 as moderate risk, 198 as high risk and 20 as extremely high risk based on Southampton criteria. Patient outcomes were compared by utilizing an ANOVA of repeated measures. Data are presented as median (mean ± SD). RESULTS: The Southampton difficulty scoring system was a strong predictor of intraoperative variables including tumor size, operative duration, estimated blood loss (EBL), and incidence of major vs minor resection (all P < .0001). In contrast, the Southampton system was a weaker predictor of postoperative outcomes including 30-day mortality (P = .15), length of stay (P = .13), and readmissions within 30 days (P = .38). CONCLUSION: The Southampton difficulty scoring system is a valid system for classifying robotic liver resections and is a strong predictor of intraoperative outcomes. However, the system was found to be a weaker predictor of postoperative outcomes. This finding may suggest the need for proposal of a new difficulty scoring system for robotic hepatectomies.

Validity of the Institut Mutualiste Montsouris classification system for robotic liver resection.

BACKGROUND: The Institut Mutualiste Montsouris (IMM) classification system is one of several widely accepted difficulty scoring systems for laparoscopic liver resections. Nothing is yet known about the applicability of this system for robotic liver resections. METHODS: We conducted a retrospective review of 359 patients undergoing robotic hepatectomies between 2016 and 2022. Resections were classified into low, intermediate, and high difficulty level. Data were analyzed utilizing ANOVA of repeated measures, 3 x 2 contingency tables, and area under the receiving operating characteristic (AUROC) curves. Data are presented as median (mean ± SD). RESULTS: Of the 359 patients, 117 were classified as low-difficulty level, 92 as intermediate, and 150 as high. The IMM system correlates well with tumor size (p = 0.002). The IMM system was a strong predictor of intraoperative outcomes including operative duration (p<0.001) and estimated blood loss (EBL) (p<0.001). The IMM system also showed a strong calibration for predicting an open conversion (AUC=0.705) and intraoperative complications (AUC=0.79). In contrast, the IMM system was a poor predictor of postoperative complications, mortality, and readmission. CONCLUSION: The IMM system provides a strong correlation with intraoperative, but not postoperative outcomes. A dedicated difficulty scoring system should be developed for robotic hepatectomy.

Safety and feasibility of a novel bi-directional portal vein access kit during transjugular intrahepatic portosystemic shunt creation.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) creation remains as one of the more technically challenging endovascular procedures. Portal vein access from the hepatic vein often requires multiple needle passes, which increases procedure times, risk of complications, and radiation exposure. With its bi-directional maneuverability, the Scorpion X access kit may be a promising tool for easier portal vein access. However, the clinical safety and feasibility of this access kit has yet to be determined. MATERIALS AND METHODS: In this retrospective study, 17 patients (12 male, average age 56.6 ± 9.01) underwent TIPS procedure using Scorpion X portal vein access kits. The primary endpoint was time taken to access the portal vein from the hepatic vein. The most common indications for TIPS were refractory ascites (47.1%) and esophageal varices (17.6%). Radiation exposure, total number of needle passes, and intraoperative complications were recorded. Average MELD Score was 12.6 ± 3.39 (range: 8-20). RESULTS: Portal vein cannulation was successfully achieved in 100% of patients during intracardiac echocardiography-assisted TIPS creation. Total fluoroscopy time was 39.31 ± 17.97 min; average radiation dose was 1036.76 ± 644.15 mGy, while average contrast dose was 120.59 ± 56.87 mL. The average number of passes from the hepatic vein to the portal vein was 2 (range: 1-6). Average time to access the portal vein once the TIPS cannula was positioned in the hepatic vein was 30.65 ± 18.64 min. There were no intraoperative complications. CONCLUSIONS: Clinical utilization of the Scorpion X bi-directional portal vein access kit is both safe and feasible. Utilizing this bi-directional access kit resulted in successful portal vein access with minimal intraoperative complications. LEVEL OF EVIDENCE: Retrospective cohort.

Patient satisfaction and cost savings analysis of the telemedicine program within a neuro-oncology department.

PURPOSE: Unique challenges exist in the utilization of telemedicine for neurological and surgical specialties. We examined the differences in patient satisfaction for telemedicine versus in-person visits within a Neuro-Oncology Program to assess whether there was a difference between surgical and medical specialties. We also examined the potential cost savings benefits of utilizing telemedicine. METHODS: 1189 Press Ganey surveys in the Department of Neuro-Oncology (982 in-person and 207 telemedicine) by surgical and medical neuro-oncology patients between 04/01/2020 and 06/30/2021 were reviewed. Survey results were divided into 4 categories (Access, Provider, Technology (telemedicine only), and Overall Satisfaction). Results were analyzed for the impact of telemedicine versus in-person visits, and gender, age, insurance, and specialty. Cost savings were calculated based on potential travel distance and lost productivity. RESULTS: Survey results from telemedicine visits demonstrated that patients with private insurance returned higher scores in the Provider (p = 0.0089), Technology (p = 0.00187), and Overall (p = 0.00382) categories. Surgical patients returned higher scores for Access (p = 0.0015), Technology (p = 0.0002), and Overall (p = 0.0019). When comparing telemedicine to in-person scores, in-person scored higher in Provider (p = 0.0092) for all patients, while in-person scored higher in Access (p = 0.0252) amongst surgical patients. Cost analysis revealed that telemedicine allowed patients to save an average of 4.1 to 5.6 h per visit time and a potential cost savings of up to $223.3 ± 171.4. CONCLUSION: Telemedicine yields equivalent patient satisfaction when employed in surgical as compared to medical Neuro-Oncology patients with the potential to lessen the financial and time burden on neuro-oncology patients.

Effects of Lovastatin on Brain Cancer Cells.

Although brain tumors occur less frequently than other forms of cancer, they have one of the bleakest prognoses with low survival rates. The conventional treatment for brain tumors includes surgery, radiotherapy, and chemotherapy. However, resistance to treatment remains a problem with recurrence shortly following. The resistance to treatment may be caused by cancer stem cells (CSCs), a subset of brain tumor cells with the affinity for self-renewal and differentiation into multiple cell lineages. An emerging approach to targeting CSCs in brain tumors is through repurposing the lipid-lowering medication, lovastatin. Lovastatin is a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor that impacts the mevalonate pathway. The inhibition of intermediates in the mevalonate pathway affects signaling cascades and oncogenes associated with brain tumor stem cells (BTSC). In this review, we show the possible mechanisms where lovastatin can target BTSC for different varieties of malignant brain tumors.

Relativistic Orbital-Optimized Density Functional Theory for Accurate Core-Level Spectroscopy.

Core-level spectra of 1s electrons of elements heavier than Ne show significant relativistic effects. We combine advances in orbital-optimized density functional theory (OO-DFT) with the spin-free exact two-component (X2C) model for scalar relativistic effects to study K-edge spectra of third period elements. OO-DFT/X2C is found to be quite accurate at predicting energies, yielding a ∼0.5 eV root-mean-square error versus experiment with the modern SCAN (and related) functionals. This marks a significant improvement over the >50 eV deviations that are typical for the popular time-dependent DFT (TDDFT) approach. Consequently, experimental spectra are quite well reproduced by OO-DFT/X2C, sans empirical shifts for alignment. OO-DFT/X2C combines high accuracy with ground state DFT cost and is thus a promising route for computing core-level spectra of third period elements. We also explored K and L edges of 3d transition metals to identify limitations of the OO-DFT/X2C approach in modeling the spectra of heavier atoms.

Hypoxia-ischemia-mediated effects on neurodevelopmentally regulated cold-shock proteins in neonatal mice under strict temperature control.

BACKGROUND: Neonates have high levels of cold-shock proteins (CSPs) in the normothermic brain for a limited period following birth. Hypoxic-ischemic (HI) insults in term infants produce neonatal encephalopathy (NE), and it remains unclear whether HI-induced pathology alters baseline CSP expression in the normothermic brain. METHODS: Here we established a version of the Rice-Vannucci model in PND 10 mice that incorporates rigorous temperature control. RESULTS: Common carotid artery (CCA)-ligation plus 25 min hypoxia (8% O2) in pups with targeted normothermia resulted in classic histopathological changes including increased hippocampal degeneration, astrogliosis, microgliosis, white matter changes, and cell signaling perturbations. Serial assessment of cortical, thalamic, and hippocampal RNA-binding motif 3 (RBM3), cold-inducible RNA binding protein (CIRBP), and reticulon-3 (RTN3) revealed a rapid age-dependent decrease in levels in sham and injured pups. CSPs were minimally affected by HI and the age point of lowest expression (PND 18) coincided with the timing at which heat-generating mechanisms mature in mice. CONCLUSIONS: The findings suggest the need to determine whether optimized therapeutic hypothermia (depth and duration) can prevent the age-related decline in neuroprotective CSPs like RBM3 in the brain, and improve outcomes during critical phases of secondary injury and recovery after NE. IMPACT: The rapid decrease in endogenous neuroprotective cold-shock proteins (CSPs) in the normothermic cortex, thalamus, and hippocampus from postnatal day (PND) 11-18, coincides with the timing of thermogenesis maturation in neonatal mice. Hypoxia-ischemia (HI) has a minor impact on the normal age-dependent decline in brain CSP levels in neonates maintained normothermic post-injury. HI robustly disrupts the expected correlation in RNA-binding motif 3 (RBM3) and reticulon-3 (RTN3). The potent neuroprotectant RBM3 is not increased 1-4 days after HI in a mouse model of neonatal encephalopathy (NE) in the term newborn and in which rigorous temperature control prevents the manifestation of endogenous post-insult hypothermia.

Lovastatin Inhibits RhoA to Suppress Canonical Wnt/ß-Catenin Signaling and Alternative Wnt-YAP/TAZ Signaling in Colon Cancer.

Statins are first-line drugs used to control patient lipid levels, but there is recent evidence that statin treatment can lower colorectal cancer (CRC) incidence by 50% and prolong CRC patient survival through mechanisms that are poorly understood. In this study, we found that the treatment of APCmin mice by the mevalonate pathway inhibitor lovastatin significantly reduced the number of colonic masses and improved hypersplenism and peripheral anemia. Furthermore, reverse transcription polymerase chain reaction (RT-PCR) analysis of colonic mass tissues showed a potent inhibitory effect in both Wnt/ß-catenin signaling and YAP/TAZ signaling in the lovastatin treatment group. The results of our transcriptomic analyses in RKO indicated that lovastatin regulated several proliferation-related signaling pathways. Moreover, lovastatin suppressed important genes and proteins related to the canonical Wnt/ß-catenin and alternative Wnt-YAP/TAZ signaling pathways in RKO and SW480 cells, and these effects were rescued by mevalonic acid (MVA), as confirmed through a series of Western blotting, RT-PCR, and reporter assays. Given that statins suppress oncogenic processes primarily through the inhibition of Rho GTPase in the mevalonate pathway, we speculate that lovastatin can inhibit certain Rho GTPases to suppress both canonical Wnt/ß-catenin signaling and alternative Wnt-YAP/TAZ signaling. In RKO cells, lovastatin showed similar inhibitory properties as the RhoA inhibitor CCG1423, being able to inhibit ß-catenin, TAZ, and p-LATS1 protein activity. Our results revealed that lovastatin inhibited RhoA activity, thereby suppressing the downstream canonical Wnt/ß-catenin and alternative Wnt-YAP/TAZ pathways in colon cancer cells. These inhibitory properties suggest the promise of statins as a treatment for CRC. Altogether, the present findings support the potential clinical use of statins in non-cardiovascular contexts and highlight novel targets for anticancer treatments.

Targeting the IL-17 Receptor Using Liposomal Spherical Nucleic Acids as Topical Therapy for Psoriasis.

The activation of T helper 17 signaling plays a critical role in psoriasis pathogenesis, and systemically-administered IL-17 inhibitors are highly effective therapy for moderate-to-severe disease. We generated topically-delivered gene-regulating nanoconstructs, comprised of spherically-arrayed antisense DNA (liposomal spherical nucleic acids [L-SNAs]), which are able to penetrate human skin to knock down cutaneous gene targets. Topically-applied L-SNAs targeting the gene encoding the mouse IL-17A receptor (Il17ra) reversed the development of psoriasis clinically, histologically, and transcriptionally in imiquimod-treated psoriasis-like mouse skin. Il17ra L-SNAs reduced the modified PASI by 74% versus controls and decreased epidermal thickness by 56%. Il17ra L-SNA reduced Il17ra protein expression by 75% and significantly decreased the mRNA expression of psoriasis markers, including Defb4, Il17c, S100a7, Pi3, Krt16, and Tnfa versus scrambled spherical nucleic acid (Scr SNA) controls. A human IL17RA L-SNA penetrates 3-dimensional cultures and normal human explants to knock down IL17RA mRNA by 63% and 66%, respectively. After topical application to psoriatic 3-dimensional rafts, anti-human IL17RA L-SNAs reduced the expression of IL17RA (by 72%) and the IL-17-induced genes IL17C (by 85%), DEFB4 (by 83%), TNFA (by 77%), and PI3 (by 65%) versus scrambled L-SNA and vehicle controls (all P < 0.001). Taken together, these data suggest that targeted suppression of IL17RA is a promising new topical treatment strategy for psoriasis.

The Presence of a Psychiatric Condition is Associated With Undergoing Hip Arthroscopy for Femoroacetabular Impingement: A Matched Case-Controlled Study.

BACKGROUND: We sought to examine the association between having a psychiatric condition and undergoing hip arthroscopy for femoroacetabular impingement (FAI). METHODS: A matched case-control study was performed to control for age and gender. All patients over 16 years of age with FAI treated with hip arthroscopy by a single surgeon were randomly matched to a patient of the same age and gender undergoing knee arthroscopy for any diagnosis other than infection by the same surgeon during the same period. Conditional logistic regression was used to compare the odds of having a psychiatric condition between groups. RESULTS: Fifty-one matched pairs of patients undergoing hip and knee arthroscopy were identified. Each group contained 35 females (69%) and had a mean age of 33.6 years. Of the 51 hip arthroscopy cases, 23 (45.1%) had a psychiatric condition. Of the 51 knee arthroscopy controls, 11 (21.6%) had a psychiatric condition. Patients undergoing hip arthroscopy were statistically significantly more likely to have a psychiatric condition compared to patients undergoing knee arthroscopy with an odds ratio of 3.4 (95% confidence interval 1.3-9.2, P < .01). CONCLUSION: There was a strong association between having a psychiatric condition and undergoing hip arthroscopy for FAI. More research should be done investigating psychiatric conditions among patients with FAI and whether this association can identify strategies to optimize patient outcomes.

Arthroscopic Anterior Cruciate Ligament Femoral Tunnel Visualization for Button Fixation.

Arthroscopic reconstruction of the anterior cruciate ligament (ACL) remains one of the most commonly performed procedures in orthopaedic surgery. We describe a technique to visualize the button being advanced through the femoral tunnel using an arthroscope placed in the anteromedial portal. Looking into the femoral tunnel in line with the sutures, this technique allows the surgeon to directly visualize the femoral button as it traverses the femoral tunnel and confirms that it is engaged over the femoral cortex. Certain complications can arise, however, with the use of a suspensory fixation with a button on the femoral cortex. This method can decrease operative time and complication rates.

Immortalized Mouse Achilles Tenocytes Demonstrate Long-Term Proliferative Capacity While Retaining Tenogenic Properties.

Investigating the cellular processes underlying tendon healing can allow researchers to improve long-term outcomes after injury. However, conducting meaningful studies to uncover the injury healing mechanism at cellular and molecular levels remains challenging. This is due to the inherent difficulty in isolating, culturing, and expanding sufficient primary tenocytes, due to their limited proliferative capacity and short lifespan. In this study, we sought to establish a novel line of immortalized mouse Achilles tenocytes (iMATs) with primary tenocyte properties, but increased proliferative capacity suitable for extensive in vitro experimentation. We show that isolated primary mouse Achilles tenocytes (pMATs) can be effectively immortalized using a piggyBac transposon expressing SV40 large T antigen flanked by FLP recombination target site (FRT). The resulting iMATs exhibit markedly greater proliferation and survival, which can be reversed with FLP recombinase. Furthermore, iMATs express the same set of tendon-specific markers as that of primary cells, although in lower levels, and respond similarly to exogenous stimulation with bone morphogenetic protein 13 (BMP13) as has been previously reported with pMATs. Taken together, our results suggest that iMATs acquire long-term proliferative capacity while maintaining tenogenic properties. We believe that iMATs are a suitable model for studying not only the native cellular processes involved in injury and healing, but also potential therapeutic agents that may augment the stability of tendon repair.

Academic-community partnerships improve outcomes in pediatric trauma care.

BACKGROUND: To address the specialized needs of injured children, pediatric trauma centers (PTCs) were established at many large, academic hospitals. This study explores clinical outcomes observed for injured children treated at an academic-sponsored community facility. METHODS: In partnership with an academic medical center in a major metropolitan area, a not-for-profit community hospital became a designated Level II PTC in October 2010. Data for injured children <15 years old treated prior to PTC designation from January 2000 to September 2010 were prospectively collected using the Trauma and Emergency Medicine Information System and compared to data collected after PTC designation from January 2011 to December 2013. RESULTS: Overall, 681 injured children were treated at the community hospital from January 2011 to December 2013. Children treated after PTC designation were less likely to undergo computed tomography (CT) (50.9% vs. 81.3%, p<0.01), even when controlling for age, gender, injury type, injury severity, and year (OR 0.18, 95%CI 0.08-0.37). Specifically, fewer head (45.7% vs. 68.7%, p<0.01) and abdominal CTs (13.2% vs. 26.5%, p<0.01) were performed. Hospital length of stay was significantly shorter (2.8 ± 3.7 days vs. 3.7 ± 5.9 days, p<0.01). Mortality was low overall, but also decreased after PTC designation (0.4% vs. 2.0%, p=0.02). CONCLUSIONS: These results indicate that academic-community partnerships in pediatric trauma care are a feasible alternative and may lead to improved outcomes for injured children.

Immunomodulatory spherical nucleic acids.

Immunomodulatory nucleic acids have extraordinary promise for treating disease, yet clinical progress has been limited by a lack of tools to safely increase activity in patients. Immunomodulatory nucleic acids act by agonizing or antagonizing endosomal toll-like receptors (TLR3, TLR7/8, and TLR9), proteins involved in innate immune signaling. Immunomodulatory spherical nucleic acids (SNAs) that stimulate (immunostimulatory, IS-SNA) or regulate (immunoregulatory, IR-SNA) immunity by engaging TLRs have been designed, synthesized, and characterized. Compared with free oligonucleotides, IS-SNAs exhibit up to 80-fold increases in potency, 700-fold higher antibody titers, 400-fold higher cellular responses to a model antigen, and improved treatment of mice with lymphomas. IR-SNAs exhibit up to eightfold increases in potency and 30% greater reduction in fibrosis score in mice with nonalcoholic steatohepatitis (NASH). Given the clinical potential of SNAs due to their potency, defined chemical nature, and good tolerability, SNAs are attractive new modalities for developing immunotherapies.