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We introduce a novel type of assessment that allows for efficient grading of higher order thinking skills. In this assessment, a student reviews and corrects a technical memo that has errors in its formulation or process. To overcome the grading challenges imposed by essay-type responses in large undergraduate courses, we provide a Visual Basic for Applications Excel tool for instructors, ensuring efficient grading of student submissions. We report our experience using this type of assessment in a multisection introductory business analytics course over several years and present survey-based evidence indicating that students perceive it to be clear and beneficial for learning.

BackgroundTo determine the clinical importance of pneumatosis intestinalis (PI) on surgical decision-making and patient outcomes.MethodsA matched cohort observational study was conducted including all clinical encounters for both ambulatory and inpatient care at UCLA Health between February 15, 2006 and January 31, 2023. Patients were initially identified using encounter diagnostic codes for "other specified diseases of intestine." A radiologic diagnosis of PI was then assessed using natural language processing techniques followed by confirmation using manual chart review. Patients who did not have PI served as a control group. Patient comorbidity was assessed using Elixhauser comorbidity scores. Logistic regression and Cox hazard analyses were used to assess associations between PI and mortality. The main outcome was 90-day all-cause mortality. Secondary outcomes were the proportion of patients undergoing surgery and, of those, how many required bowel resections.ResultsOf the 16,728 patients identified by diagnostic coding, 315 were confirmed to have a diagnosis of PI. The 90-day mortality rate for all patients with PI was 29%. Surgery was performed for 62 patients (20%), of whom 46 (72%) underwent bowel resection and 16 (28%) underwent abdominal exploration alone. Most patients underwent surgery for peritonitis (37%), bowel obstruction (31%), and/or pneumoperitoneum (23%) in association with PI; whereas only 8% of patients received surgery exclusively for PI. There was no statistically significant association between PI and mortality with logistic regression conditioned on other risk factors for mortality. In contrast, survival analysis of a matched cohort demonstrated a small effect of PI on mortality (hazard ratio = 1.24: 95% confidence interval = 1.16-1.32, P = 0.021).ConclusionsMost patients with a diagnosis of PI survive without requiring surgery. Of those who undergo surgery, nearly all have indications for laparotomy exclusive of PI. Mortality in patients who have pneumatosis is strongly associated with comorbid disease, with little to no independent association with PI. Our findings suggest that the presence of PI should not be a primary indication for surgical intervention.

Adenosine Deaminases Acting on RNA (ADARs) are enzymes that catalyze the conversion of adenosine to inosine in RNA duplexes. These enzymes can be harnessed to correct disease-causing G-to-A mutations in the transcriptome because inosine is translated as guanosine. Guide RNAs (gRNAs) can be used to direct the ADAR reaction to specific sites. Chemical modification of ADAR guide strands is required to facilitate delivery, increase metabolic stability, and increase the efficiency and selectivity of the editing reaction. Here, we show the ADAR reaction is highly sensitive to ribose modifications (e.g. 4'-C-methylation and Locked Nucleic Acid (LNA) substitution) at specific positions within the guide strand. Our studies were enabled by the synthesis of RNA containing a new, ribose-modified nucleoside analog (4'-C-methyladenosine). Importantly, the ADAR reaction is potently inhibited by LNA or 4'-C-methylation at different positions in the ADAR guide. While LNA at guide strand positions -1 and -2 block the ADAR reaction, 4'-C-methylation only inhibits at the -2 position. These effects are rationalized using high-resolution structures of ADAR-RNA complexes. This work sheds additional light on the mechanism of ADAR deamination and aids in the design of highly selective ADAR guide strands for therapeutic editing using chemically modified RNA.

Epistemic injustice is a condition where knowers and knowledge claims are unduly dismissed. Philosophers suggest that epistemic injustice manifests in three forms: testimonial, hermeneutical, and contributory. Although distinct, all forms of epistemic injustice stem from relations of power, privilege, and positionality -- where some have the opportunity and authority to legitimize the knowledge contributions of others. The purpose of this study was to explore the presence of epistemic injustice in U.S. doctoral education through a systematic review of literature. We methodically searched hundreds of peer-reviewed journals for studies focused on teaching, advising, peer interaction, doctoral socialization, and other experiences concerning doctoral education across the humanities, social science, and science disciplines. We retained, reviewed, and analyzed 107 manuscripts. Our analysis revealed epistemic injustice in doctoral education as well as rules that foster the conditions for epistemic injustice. Implications for doctoral education and future research are offered.

CONTENTS I. INTRODUCTION 333 II. OVERVIEW OF VENTURE CAPITAL 336 A. What is Venture Capital? 336 B. How are Venture Capital Funds Organized? 337 C. How do Venture Capital Funds [...]

BackgroundCurrent minimally invasive fat reduction modalities use equipment that can cost thousands of U.S. dollars. Electrochemical lipolysis (ECLL), using low-cost battery and electrodes (approximately $10), creates acid/base within fat (width, approximately 3 mm), damaging adipocytes. Longitudinal effects of ECLL have not been studied. In this pilot study, the authors hypothesize that in vivo ECLL induces fat necrosis, decreases adipocyte number/viability, and forms lipid droplets.MethodsTwo female Yorkshire pigs (50 to 60 kg) received ECLL. In pig 1, 10 sites received ECLL, and 10 sites were untreated. In pig 2, 12 sites received ECLL and 12 sites were untreated. For ECLL, two electrodes were inserted into dorsal subcutaneous fat and direct current was applied for 5 minutes. Adverse effects of excessive pain, bleeding, infection, and agitation were monitored. Histology, live-dead (calcein, Hoechst, ethidium homodimer-1), and morphology (Bodipy and Hoechst) assays were performed on day 0 and postprocedure days 1, 2, 7, 14 (pig 1 and pig 2), and 28 (pig 2). Average particle area, fluorescence signal areas, and adipocytes and lipid droplet numbers were compared.ResultsNo adverse effects occurred. Live-dead assays showed adipocyte death on the anode on days 0 to 7 and the cathode on days 1 to 2 (not significant). Bodipy showed significant adipocyte loss at all sites ( P < 0.001) and lipid droplet formation at the cathode site on day 2 ( P = 0.0046). Histology revealed fat necrosis with significant increases in average particle area at the anode and cathode sites by day 14 (+277.3% change compared with untreated, P < 0.0001; +143.4%, P < 0.0001) and day 28 (+498.6%, P < 0.0001; +354.5%, P < 0.0001).ConclusionsIn vivo ECLL induces fat necrosis in pigs. Further studies are needed to evaluate volumetric fat reduction.Clinical relevance statementIn vivo ECLL induces adipocyte death and fat necrosis. ECLL has the potential to be utilized in body fat contouring.

BackgroundmTORC1 activity is dependent on the presence of micronutrients, including Asparagine (Asn), to promote anabolic cell signaling in many cancers. We hypothesized that targeting Asn metabolism would inhibit tumor growth by reducing mTORC1 activity in well-differentiated (WD)/dedifferentiated (DD) liposarcoma (LPS).MethodsHuman tumor metabolomic analysis was utilized to compare abundance of Asn in WD vs. DD LPS. Gene set enrichment analysis (GSEA) compared relative expression among metabolic pathways upregulated in DD vs. WD LPS. Proliferation assays were performed for LPS cell lines and organoid models by using the combination treatment of electron transport chain (ETC) inhibitors with Asn-free media. 13C-Glucose-labeling metabolomics evaluated the effects of combination treatment on nucleotide synthesis. Murine xenograft models were used to assess the effects of ETC inhibition combined with PEGylated L-Asparaginase (PEG-Asnase) on tumor growth and mTORC1 signaling.ResultsAsn was enriched in DD LPS compared to WD LPS. GSEA indicated that mTORC1 signaling was upregulated in DD LPS. Within available LPS cell lines and organoid models, the combination of ETC inhibition with Asn-free media resulted in reduced cell proliferation. Combination treatment inhibited nucleotide synthesis and promoted cell cycle arrest. In vivo, the combination of ETC inhibition with PEG-Asnase restricted tumor growth.ConclusionsAsn enrichment and mTORC1 upregulation are important factors contributing to WD/DD LPS tumor progression. Effective targeting strategies require limiting access to extracellular Asn and inhibition of de novo synthesis mechanisms. The combination of PEG-Asnase with ETC inhibition is an effective therapy to restrict tumor growth in WD/DD LPS.

Epigenetics refers to the molecules and mechanisms that modify gene expression states without changing the nucleotide context. These modifications are what encode the cell state during differentiation or epigenetic memory in mitosis. Epigenetic modifications can alter gene expression by changing the chromatin architecture by altering the affinity for DNA to wrap around histone octamers, forming nucleosomes. The higher affinity the DNA has for the histones, the tighter it will wrap and therefore induce a heterochromatin state, silencing gene expression. Several groups have shown the ability to harness the cell's natural epigenetic modification pathways to engineer proteins that can induce changes in epigenetics and consequently regulate gene expression. Therefore, epigenetic modification can be used to target and treat disorders through the modification of endogenous gene expression. The use of epigenetic modifications may prove an effective path towards regulating gene expression to potentially correct or cure genetic disorders.

Abstract Aeromonas salmonicida and Yersinia ruckeri are common pathogenic bacteria that impact salmonid aquaculture. Although vaccinations are available against both organisms, large-scale vaccination efforts can be expensive, cumbersome, and are not always reliable. Alternatively, these pathogens have been effectively inactivated using UV radiation from mercury-based systems. These systems are energy intensive and fragile which currently limits their use to closed and semi-closed production systems. UV light emitting diodes (UV LEDs) have recently emerged as a novel alternative to traditional mercury-based treatment. UV LEDs have durable housing, a relatively low energy draw, can be powered by a battery source and are adaptable to challenging environments. This study examined the effectiveness of three UV LED wavelengths for disinfection of A. salmonicida and Y. ruckeri in pure culture and resuspended in a wastewater matrix. All tested UV LEDs were effective in disinfecting both organisms. 267 and 279 nm wavelengths outperformed 255 nm disinfection in both test matrices. Particulate matter from wastewater reduced the upper limit of treatment for A. salmonicida but results still indicated that all wavelengths were effective for disinfection in a challenging matrix. This study represents the first use of UV LEDs for disinfection of A. salmonicida and Y. ruckeri and provides impact to aquaculture producers looking to implement novel technologies for disease control.

Abstract Background The introduction of Emergency Medicine in Rwanda in 2015 has been associated with a mortality reduction in patients presenting to Kigali University Teaching Hospital (KUTH). In the context of increasing numbers of critically ill patients presenting to Emergency Departments (ED) globally, the aim of this study was to describe the characteristics of critically ill patients, the critical care interventions performed, and the outcomes of critically ill patients presenting to the KUTH ED with the goal of informing future research into the root causes of mortality of critically ill ED patients and of identifying high yield topics for didactic and procedural training. Methods A descriptive observational prospective cohort pilot study analyzed all patients ≥15 years who presented to KUTH between April and June 2022 with modified South African Triage Scores of Red with alarm, Red without alarm, and Orange. Results Of 320 patients, 66.9% were male and median age was 40 years. Patients were triaged as Orange (65.3%), Red without alarm (22.8%), and Red with alarm (11.9%). Presentations were categorized as: medical emergencies (48.0%), traumatic injury (44.5%), and surgical emergencies (7.6%). Median length of stay was 31 h (IQR 28, 56) and boarding was 23 h (IQR 8, 48). Overall mortality was 12.2% and highest among medical emergencies (16.5%, p = 0.048) and increased significantly with triage color: Red with alarm (47.4%), Red without alarm (16.4%), and Orange (4.3%, p

Abstract Understanding the physical and chemical response of materials to impulsive deformation is crucial for applications ranging from soft robotic locomotion to space exploration to seismology. However, investigating material properties at extreme strain rates remains challenging due to temporal and spatial resolution limitations. Combining high-strain-rate testing with mechanochemistry encodes the molecular-level deformation within the material itself, thus enabling the direct quantification of the material response. Here, we demonstrate a mechanophore-functionalized block copolymer that self-reports energy dissipation mechanisms, such as bond rupture and acoustic wave dissipation, in response to high-strain-rate impacts. A microprojectile accelerated towards the polymer permanently deforms the material at a shallow depth. At intersonic velocities, the polymer reports significant subsurface energy absorption due to shockwave attenuation, a mechanism traditionally considered negligible compared to plasticity and not well explored in polymers. The acoustic wave velocity of the material is directly recovered from the mechanochemically-activated subsurface volume recorded in the material, which is validated by simulations, theory, and acoustic measurements. This integration of mechanochemistry with microballistic testing enables characterization of high-strain-rate mechanical properties and elucidates important insights applicable to nanomaterials, particle-reinforced composites, and biocompatible polymers.

Aerobic ribonucleotide reductases (RNRs) initiate synthesis of DNA building blocks by generating a free radical within the R2 subunit; the radical is subsequently shuttled to the catalytic R1 subunit through proton-coupled electron transfer (PCET). We present a high-resolution room temperature structure of the class Ie R2 protein radical captured by x-ray free electron laser serial femtosecond crystallography. The structure reveals conformational reorganization to shield the radical and connect it to the translocation path, with structural changes propagating to the surface where the protein interacts with the catalytic R1 subunit. Restructuring of the hydrogen bond network, including a notably short O-O interaction of 2.41 angstroms, likely tunes and gates the radical during PCET. These structural results help explain radical handling and mobilization in RNR and have general implications for radical transfer in proteins.

Abstract Background Human patients with Ehlers‐Danlos syndrome (EDS) are categorized into subtypes based on causative genetic variants and phenotypes. The classical form of EDS, primarily caused by variants in COL5A1 or COL5A2, is a very common subtype in people but is poorly characterized in dogs. Objective Describe likely causal COL5A1 variants in dogs with classical EDS, summarize clinical histories, discuss potential disease mechanisms, and draw conclusions about disease prognosis. Animals Seven client‐owned dogs that exhibited clinical signs of classical EDS. Methods Clinical information was recorded from medical records and communication with attending veterinarians and dog owners. To identify potential causal gene sequence variants whole‐genome sequence analyses (n = 6) or Sanger sequencing (n = 1) were performed on DNA isolated from the probands. Pathological abnormalities in skin biopsy samples were assessed using histology and electron microscopy in 3 dogs. Results Six distinct heterozygous COL5A1 sequence variants were identified. The most common clinical signs included fragile skin (n = 7), hyperextensible skin (n = 7), joint hypermobility (n = 6), and atrophic scars (n = 5). The median age at last follow‐up or death was 12 years (range, 6.5‐14 years). Ultrastructural abnormalities in dermal collagen differed among dogs with different COL5A1 variants. Conclusion and Clinical Importance We describe the genotypic and phenotypic spectrum of the classical subtype of EDS by identifying 6 novel COL5A1 variants in conjunction with detailed clinical histories that included long‐term follow‐up information in 7 dogs.

UV light emitting diode (LED) disinfection technologies have advanced over the last decade and expanded the design space for applications in point of use, industrial, and now full-scale water treatment. This literature review examines the progression of UV LED technologies from 2007 to 2023 using key features such as total optical power, price, and wall-plug efficiency. The review found that optical power is increasing while the price per Watt is decreasing; however, the wall plug energy (WPE) is slowly improving over the last decade. These factors govern the feasibility of many UV LEDs applications and establish the current state of the art for these technologies. An analysis of inactivation rate constants for low-pressure, medium-pressure, and UV LED sources was undertaken and provides a comprehensive view of how current UV LED technologies compare to traditional technologies. This comparison found that UV LEDs perform comparably vs conventional UV technologies when disinfecting bacteria and viruses. Furthermore, comparison of reported reduction equivalent fluences for UV LED flow-through reactors at the bench-, pilot-, and full-scale were explored in this review, and it was found that LED treatment is becoming more effective at handling increased flowrates and has been proven to work at full-scale. UV LEDs do however require additional research into the impacts of water matrices at different wavelengths and the impact that each available LED wavelength has on disinfection. Overall, this work provides a broad assessment of UV disinfection technologies and serves as a state-of-the-art reference document for those who are interested in understanding this rapidly developing technology.

Background: Articular cartilage is a fiber reinforced hydrated solid that serves a largely mechanical role of supporting load and enabling low friction joint articulation. Daily activities that load cartilage, lead to fluid exudation and compressive axial strain. To date, the only mechanism shown to recover this cartilage strain in vivo is unloading (e.g., lying supine). Based on recent work in cartilage explants, we hypothesized that loaded joint activity (walking) would also be capable of strain recovery in cartilage. Methods: Eight asymptomatic young adults performed a fixed series of tasks, each of which was followed by magnetic resonance imaging to track changes in their knee cartilage thickness. The order of tasks was as follows: 1) stand for 30 ​min, 2) walk for 10 ​min, 3) stand for 30 ​min, and 4) lie supine for 50 ​min. The change in cartilage thickness was used to compute the axial cartilage strain. Results: Standing produced an average axial strain of −5.1 ​% (compressive) in the tibiofemoral knee cartilage, while lying supine led to strain recovery. In agreement with our hypothesis, walking also led to cartilage strain recovery. Interestingly, the recovery rate during walking (0.19 ​% strain/min) was nearly 3-fold faster than lying supine (0.07 ​% strain/min). Conclusions: This study represents the first in vivo demonstration that joint activity is capable of recovering compressive strain in cartilage. These findings indicate that joint activities such as walking may play a key role in maintaining and recovering cartilage strain, with implications for maintaining cartilage health and preventing or delaying cartilage degeneration.

Comensal Bacteroidota (Bacteroidota) and Enterobacteriacea are often linked to gut inflammation. However, the causes for variability of pro-inflammatory surface antigens that affect gut commensal/opportunistic dualism in Bacteroidota remain unclear. By using the classical lipopolysaccharide/O-antigen ‘rfb operon’ in Enterobacteriaceae as a surface antigen model (5-rfb-gene-cluster rfbABCDX), and a recent rfbA-typing strategy for strain classification, we characterized the integrity and conservancy of the entire rfb operon in Bacteroidota. Through exploratory analysis of complete genomes and metagenomes, we discovered that most Bacteroidota have the rfb operon fragmented into nonrandom patterns of gene-singlets and doublets/triplets, termed ‘rfb-gene-clusters’, or rfb-‘minioperons’ if predicted as transcriptional. To reflect global operon integrity, contiguity, duplication, and fragmentation principles, we propose a six-category (infra/supra-numerary) cataloging system and a Global Operon Profiling System for bacteria. Mechanistically, genomic sequence analyses revealed that operon fragmentation is driven by intra-operon insertions of predominantly Bacteroides-DNA (thetaiotaomicron/fragilis) and likely natural selection in gut-wall specific micro-niches or micropathologies. Bacteroides-insertions, also detected in other antigenic operons (fimbriae), but not in operons deemed essential (ribosomal), could explain why Bacteroidota have fewer KEGG-pathways despite large genomes. DNA insertions, overrepresenting DNA-exchange-avid (Bacteroides) species, impact our interpretation of functional metagenomics data by inflating by inflating gene-based pathway inference and by overestimating ‘extra-species’ abundance. Of disease relevance, Bacteroidota species isolated from cavitating/cavernous fistulous tract (CavFT) microlesions in Crohn’s Disease have supra-numerary fragmented operons, stimulate TNF-alpha from macrophages with low potency, and do not induce hyperacute peritonitis in mice compared to CavFT Enterobacteriaceae. The impact of ‘foreign-DNA’ insertions on pro-inflammatory operons, metagenomics, and commensalism/opportunism requires further studies to elucidate their potential for novel diagnostics and therapeutics, and to elucidate the role of co-existing pathobionts in Crohn’s disease microlesions.

IntroductionClimate change poses a significant threat to bird communities, especially forest-dwelling and narrowly distributed species, which are expected to experience severe range contractions and higher extinction risks compared to widely distributed and open-area species. The Chocó region in southwestern Colombia, known for its rich bird endemism, is particularly vulnerable.MethodsWe analyzed potential distribution shifts for 27 endemic and near-endemic bird species in the Chocó region using eBird occurrence records and climate projections. We modeled species distributions under low and high greenhouse gas emission scenarios for 2050 and 2070, comparing these projected distributions to current forested and protected areas to evaluate future conservation needs.ResultsOur findings indicate that nearly all species are projected to lose climate-suitable areas under at least one future scenario, resulting in a regional decline in species richness. Changes in species richness are most pronounced near the Colombia-Ecuador border, suggesting a shift to higher elevations. Notably, the Scarlet-and-white Tanager (Chrysothlypis salmoni) is predicted to suffer the greatest losses in climate-suitable area, both within protected and forested regions.DiscussionThese results highlight the urgency of expanding the protected area network and conserving key forested regions to help species adapt to climate change. By providing projected distribution maps and potential range shifts, our study underscores the importance of modeling future distributions to support conservation strategies for at-risk species and the ecological services they provide in tropical montane regions.

Purpose of Review: Diabetes is the most common cause of kidney disease in individuals that receive a kidney transplant, and those without pre-existing diabetes are at greater risk of developing diabetes following kidney transplant. A class of diabetes treatment medications called glucagon-like peptide-1 receptor agonists (GLP-1RA) has seen recent widespread use for people with diabetes or obesity, with efficacy for improved glycemic control, weight loss, and reduced risk of cardiovascular events. Given these benefits, and indications for use that often co-occur in kidney transplant recipients, use of GLP-1RAs warrants consideration in this population. Therefore, we sought to review the current literature to better understand the mechanisms of action, clinical application, and person-centred considerations of GLP-1RAs in kidney transplant recipients. Sources of Information: Original articles were identified between December 2023 and July 2024 from electronic databases including the Ovid MEDLINE database, PubMed, and Google Scholar using terms “kidney transplant,” “GLP-1,” “glucagon-like peptide-1 receptor agonist,” and “diabetes.” Methods: A comprehensive review of the literature was conducted to explore the relationship between GLP-1RAs and kidney transplant recipients. We reviewed the current state of evidence across the research disciplines of basic or fundamental science, clinical and health services research, and person-centred equity science, and highlighted important knowledge gaps that offer opportunities for future research. Key Findings: Numerous clinical studies have demonstrated the benefit of GLP-1RAs in people with and without diabetic kidney disease, including decreased risk of cardiovascular events. However, there is a paucity of high-quality randomized controlled trials and observational studies analyzing use of GLP-1RAs in kidney transplant recipients. Evidence of benefit in this population is therefore limited to small studies or inferred from research conducted in nontransplant populations. Growing evidence from preclinical and clinical studies may elucidate renoprotective mechanisms of GLP-1RAs and remove barriers to application of these drugs in the transplant recipient population. Individuals who are female, non-white, have lower socioeconomic status, and live in rural communities are at greater risk of diabetes and have lower uptake of GLP-1RAs. There is a need for clinical trials across diverse kidney transplant populations to estimate the efficacy of GLP-1RAs on important health outcomes. Limitations: The search strategy for this narrative review may not have been sensitive to identify all relevant articles. Our search was limited to English language articles.

Light echoes occur when light from a luminous transient is scattered by dust back into our line of sight with a time delay due to the extra propagation distance. We introduce a novel approach to estimating the distance to a source by combining light echoes with recent three-dimensional dust maps. We identify light echoes from the historical supernovae Cassiopeia A and SN 1572 (Tycho) in nearly a decade of imaging from the All-Sky Automated Survey for Supernovae (ASAS-SN). Using these light echoes, we find distances of $3.6\pm0.1$ kpc and $3.2^{+0.1}_{-0.2}$ kpc to Cas A and Tycho, respectively, which are generally consistent with previous estimates but are more precise. These distance uncertainties are primarily dominated by the low distance resolution of the 3D dust maps, which will likely improve in the future. The candidate single degenerate explosion donor stars B and G in Tycho are clearly foreground stars. Finally, the inferred reddening towards each SN agrees well with the intervening \ion{H}{I} column density estimates from X-ray analyses of the remnants.

Angelman syndrome (AS) is a neurogenetic disorder caused by the loss of ubiquitin ligase E3A (UBE3A) gene expression in the brain. The UBE3A gene is paternally imprinted in brain neurons. Clinical features of AS are primarily due to the loss of maternally expressed UBE3A in the brain. A healthy copy of paternal UBE3A is present in the brain but is silenced by a long non-coding antisense transcript (UBE3A-ATS). Here, we demonstrate that an artificial transcription factor (ATF-S1K) can silence Ube3a-ATS in an adult mouse model of Angelman syndrome (AS) and restore endogenous physiological expression of paternal Ube3a. A single injection of adeno-associated virus (AAV) expressing ATF-S1K (AAV-S1K) into the tail vein enabled whole-brain transduction and restored UBE3A protein in neurons to ∼25% of wild-type protein. The ATF-S1K treatment was highly specific to the target site with no detectable inflammatory response 5 weeks after AAV-S1K administration. AAV-S1K treatment of AS mice showed behavioral rescue in exploratory locomotion, a task involving gross and fine motor abilities, similar to low ambulation and velocity in AS patients. The specificity and tolerability of a single injection of AAV-S1K therapy for AS demonstrate the use of ATFs as a promising translational approach for AS.