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Vi analyserer lønforskelle mellem mandlige og kvindelige økonomer i hhv. den offentlige og private sektor to år efter dimissionstidspunktet ved brug af den klassiske OaxacaBlinder dekomponering. Lønforskellen er betydelig selv i vores meget homogene gruppe af personer (18.000 kr. i den offentlige sektor; 60.000 kr. i den private sektor). Fem år efter dimissionstidspunktet er lønforskellen steget til 49.000 kr i den offentlige sektor og 143.000 kr. i den private sektor. Forskelle i karakterer, erhvervserfaring og øvrige personlige karakteristika er ikke i stand til at forklare majoriteten af disse forskelle, hverken to eller fem år efter dimissionen. [ABSTRACT FROM AUTHOR]

In chronic myeloid leukemia (CML), combination therapies with tyrosine kinase inhibitors (TKIs) aim to improve the achievement of deep molecular remission that would allow therapy discontinuation. IFN-[alpha] is one promising candidate, as it has long-lasting effects on both malignant and immune cells. In connection with a multicenter clinical trial combining dasatinib with IFN-[alpha] in 40 patients with chronic-phase CML (NordCML007, NCT01725204), we performed immune monitoring with single-cell RNA and T cell receptor (TCR) sequencing (n = 4, 12 samples), bulk TCR[beta] sequencing (n = 13, 26 samples), flow cytometry (n = 40, 106 samples), cytokine analyses (n = 17, 80 samples), and ex vivo functional studies (n = 39, 80 samples). Dasatinib drove the immune repertoire toward terminally differentiated NK and [CD8.sup.+] T cells with dampened functional capabilities. Patients with dasatinib-associated pleural effusions had increased numbers of [CD8.sup.+] recently activated effector memory T (Temra) cells. In vitro, dasatinib prevented CD3-induced cell death by blocking TCR signaling. The addition of IFN-[alpha] reversed the terminally differentiated phenotypes and increased the number of costimulatory intercellular interactions and the number of unique putative epitope-specific TCR clusters. In vitro IFN-[alpha] had costimulatory effects on TCR signaling. Our work supports the combination of IFN-[alpha] with TKI therapy, as IFN-[alpha] broadens the immune repertoire and restores immunological function., Introduction Currently, the ultimate therapeutic goal in patients with chronic-phase chronic myeloid leukemia (CP-CML) is to achieve deep molecular remission, which would allow the discontinuation of tyrosine kinase inhibitor (TKI) [...]

In Chile, the budget for managing environmental liabilities such as abandoned tailings impoundments is limited. Using native and endemic plant species to remove heavy metals from tailings represents a low-cost alternative. Ex situ phytoremediation experiments were conducted over a period of seven months. The endemic species Lycium chilense and native species Haplopappus foliosus were used to remove copper and lead from mine tailings. The results indicate that both species can concentrate levels of Cu and Pb higher than the toxicity threshold in the roots and aerial parts, and present high removal efficiency for Cu higher than 50%. In both species, the concentrations of the target elements are higher in the roots than in the aerial parts. Haplopappus foliosus presents the best performance, accumulating higher concentrations of Cu and Pb than Lycium chilense, and presenting a bioconcentration of over one for Cu. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular senescence may be a causal factor in the development and progression of non-alcoholic steatohepatitis (NASH). The most effective currently available treatment for NASH is lifestyle intervention, including dietary modification. This study aimed to evaluate the effects of dietary intervention on hallmarks of NASH and molecular signatures of hepatocellular senescence in the Gubra-Amylin NASH (GAN) diet-induced obese (DIO) and biopsy-confirmed mouse model of NASH. Methods: GAN DIO-NASH mice with liver biopsy-confirmed NASH and fibrosis received dietary intervention by switching to chow feeding (chow reversal) for 8, 16 or 24 weeks. Untreated GAN DIO-NASH mice and chow-fed C57BL/6J mice served as controls. Pre-to-post liver biopsy histology was performed for within-subject evaluation of NAFLD Activity Score and fibrosis stage. Terminal endpoints included blood/liver biochemistry, quantitative liver histology, mitochondrial respiration and RNA sequencing. Results: Chow-reversal promoted substantial benefits on metabolic outcomes and liver histology, as demonstrated by robust weight loss, complete resolution of hepatomegaly, hypercholesterolemia, elevated transaminase levels and hepatic steatosis in addition to attenuation of inflammatory markers. Notably, all DIO-NASH mice demonstrated ≥ 2 point significant improvement in NAFLD Activity Score following dietary intervention. While not improving fibrosis stage, chow-reversal reduced quantitative fibrosis markers (PSR, collagen 1a1, α-SMA), concurrent with improved liver mitochondrial respiration, complete reversal of p21 overexpression, lowered γ-H2AX levels and widespread suppression of gene expression markers of hepatocellular senescence. Conclusions: Dietary intervention (chow reversal) substantially improves metabolic, biochemical and histological hallmarks of NASH and fibrosis in GAN DIO-NASH mice. These benefits were reflected by progressive clearance of senescent hepatocellular cells, making the model suitable for profiling potential senotherapeutics in preclinical drug discovery for NASH. [ABSTRACT FROM AUTHOR]

Background The purpose of the study was to quantify the association between body weight and health by estimating the expected lifetime with and without diabetes (diabetes-free life expectancy) at age 30 and 65. In addition, the diabetes-free life expectancy was stratified by educational level. Methods Life tables by sex, level of education and obese/not obese were constructed using nationwide register data and self-reported data on body weight and height and diabetes from the Danish National Health Survey in 2021. Diabetes-free life expectancies were estimated by Sullivan's method. Results The difference in life expectancy between not obese 30-year-old men with a long and a short education was 5.7 years. For not obese women, the difference was 4.1 years. For obese men and women, the difference in life expectancy at age 30 was 7.0 and 5.2 years. Women could expect more years without and fewer years with diabetes than men regardless of body weight and educational level. Diabetes-free life expectancy differed by 6.9 years between not obese 30-year-old men with a short and a long education and by 7.7 years for obese men with a short and a long education. For women, the differences were 5.9 and 6.6 years. Conclusion The results demonstrate an association of obesity and educational level with life expectancy and diabetes-free life expectancy. There is a need for preventive efforts to reduce educational inequality in life expectancy and diabetes-free life expectancy. Structural intervention will particularly benefit overweight people with short education. [ABSTRACT FROM AUTHOR]

The organic matter content of marine sediments is often used to infer past changes in ocean conditions. However, the organic carbon pool preserved in coastal sediments is a complex mixture derived from different sources and may not reflect in situ processes. In this study, we combine taxonomic identification of reworked palynomorphs with pyrolysis organic geochemistry and reflected‐light organic petrographic microscopy to investigate the provenance, composition and preservation of organic matter in a marine sediment core retrieved from the NE Greenland shelf. Our study reveals continuous yet variable input of land‐derived organic carbon to the marine environment throughout the late Younger Dryas–Holocene, with the highest input of inert carbon in the late Younger Dryas. Although the sediments contain some recent marine palynomorphs, there is no other evidence of fresh marine organic carbon. In contrast, our results indicate that these shelf sediments represent a significant sink of recycled organic carbon. The results of pyrolysis geochemistry revealed that ~90% of the total organic carbon in the sediments is inert. The organic petrography analyses revealed that >70–84% of the organic carbon in the sediment core is terrigenous. Reworked dinoflagellate cysts showed a continuous provenance of Cretaceous land‐derived material, most likely from the nearby Clavering Island. Our study points to the importance of constraining the organic matter origin, composition and preservation in marine sediments to achieve more accurate palaeoenvironmental reconstructions based on organic proxies. [ABSTRACT FROM AUTHOR]

Introduction There is a substantial risk of developing stenosis and dysfunction in the arteriovenous fistula (AVF) in patients on hemodialysis (HD). Far infrared radiation (FIR) is a non-invasive local intervention with a potentially beneficial effect on AVF patency. The underlying mechanism is not clear. It was hypothesized that a single FIR treatment reduces factors of inflammation and promotes endothelial vasodilators in the AVF. Methods Forty HD patients with an AVF were included in an open-label intervention study. Patients were randomized to receive either FIR (FIR group) or no FIR (control group). Blood samples were drawn directly from the AVF and from a peripheral vein in the non-AVF arm before (T0) and 40 min after (T40) treatment during a HD session. The changes [median (interquartile range)] in circulating factors of inflammation, endothelial function and vasoreactivity during FIR were measured. Results In the AVF a single FIR treatment during dialysis resulted in a significantly diminished decrease in soluble vascular cell adhesion molecule, sVCAM [−31.6 (−54.3; 22.1) vs −89.9 (−121.6; −29.3), P  = .005] and soluble intercellular adhesion molecule, sICAM [−24.2 (−43.5; 25.3) vs −49 (−79.9; −11.6), P  = .02] compared with the control group. Other factors, such as interleukins, nitrite, nitrate and tumor necrosis factor 1, also declined during dialysis, but with no significant differences related to FIR in either the AVF or the non-AVF arm. Conclusion A single FIR treatment attenuated the decrease in sVCAM and sICAM in the AVF compared with a control group during HD. Findings do not support the hypothesis of a vaso-protective effect of FIR. The long-term effects of FIR on the AVF are unknown. [ABSTRACT FROM AUTHOR]

Heavy metal exposure from wastewater is an important environmental issue worldwide. In the search for more efficient treatment technologies, biosorption has been presented as an alternative for contaminant removal from wastewaters. The aim of this work is to determine the operation parameters of copper adsorption followed by biosorbent regeneration. The algae Durvillaea antarctica and Lessonia trabeculata were used as biosorbents in batch experiments. These biosorbents were exposed to different conditions, such as pH, copper concentration, exposure time, mass-to-volume ratios and regeneration reagents. Batch sorption tests revealed an adequate pH of 4.5–5.0. The selected biosorbent was D. antarctica due to a considerably higher copper retention capacity. As a regenerating reagent, sulfuric acid was more efficient. For diluted copper solutions (10 to 100 mg L−1), a biosorbent particle size of between 1.70 and 3.36 mm showed better retention capacity than larger particles and a biosorbent mass-to-volume ratio of 10 g L−1 was desirable for these metal concentrations. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor 21 (FGF21) plays a key role in hepatic lipid metabolism and long-acting FGF21 analogs have emerged as promising drug candidates for the treatment of nonalcoholic steatohepatitis (NASH). It remains to characterize this drug class in translational animal models that recapitulate the etiology and hallmarks of human disease. To this end, we evaluated the long-acting FGF21 analog PF-05231023 in the GAN (Gubra Amylin NASH) diet-induced obese (DIO) and biopsy-confirmed mouse model of NASH. Male C57BL/6J mice were fed the GAN diet high in fat, fructose, and cholesterol for 34 wk before the start of the study. GAN DIO-NASH mice with biopsy-confirmed NAFLD Activity Score (NAS ≥5) and fibrosis (stage ≥F1) were biweekly administered with PF-05231023 (10 mg/kg sc) or vehicle (sc) for 12 wk. Vehicle-dosed chow-fed C57BL/6J mice served as healthy controls. Pre-to-post liver biopsy histopathological scoring was performed for within-subject evaluation of NAFLD Activity Score (NAS) and fibrosis stage. Terminal endpoints included quantitative liver histology and transcriptome signatures as well as blood and liver biochemistry. PF-05231023 significantly reduced body weight, hepatomegaly, plasma transaminases, and plasma/liver lipids in GAN DIO-NASH mice. Notably, PF-05231023 reduced both NAS (≥2-point improvement) and fibrosis stage (1-point improvement). Improvements in NASH and fibrosis severity were supported by reduced quantitative histological markers of steatosis, inflammation, and fibrogenesis as well as improvements in disease-associated liver transcriptome signatures. In conclusion, PF-05231023 reduces NASH and fibrosis severity in a translational biopsy-confirmed mouse model of NASH, supporting development of FGF21 analogs for the treatment of NASH. NEW & NOTEWORTHY It is unclear if long-acting FGF21 analogs have antifibrotic efficacy in NASH. We therefore profiled the clinically relevant FGF21 analog PF-05231023 in a translational diet-induced obese and biopsy-confirmed mouse model of NASH. We found PF-05231023 to exert hepatoprotective effects as indicated by notable improvements in plasma markers and histological hallmarks of NASH, including improved fibrosis stage. Collectively, the present study supports the continued exploration of long-acting FGF21 analogs for the treatment of NASH and other fibrotic diseases. [ABSTRACT FROM AUTHOR]

In the present study, the assessment of heavy metal contaminant migration from fresh mine tailings was conducted using the electrokinetic remediation technique (EKR). In this sense, a pilot EKR cell was designed to evaluate the recovery potential of copper, nickel, and cobalt species. In particular, the focus was on the impacts of electric field intensity and pH in initial mixture and testing their interaction in copper, nickel, and cobalt migration. Experiments were made using a 22 factorial experimental design with a central point, using DC electric fields from 1.0 to 2.0 V cm−1 and H2SO4 pretreatment solutions from 1.0 to 2.0 mol L−1, along with an ANOVA test with error reduction. The metal removal rates were approximately 7% for cobalt, neglectable for copper, and 6% for nickel. In the best cases, the highest concentrations by migration at the cathodic zone were 11%, 31%, and 30%, respectively. According to ANOVA tests, factor interaction was proven for each metal in the half cell near the cathode and the closest zone from the cathode specifically. Both factors affected metal concentrations, which indicates that when the goal aims for species accumulation in a narrower section, each factor has a significant effect, and their interaction makes a proven enhancement. Thus, using 2.0 V cm−1 and 2.0 mol L−1 showed a high improvement in metal concentration in the cathodic zone. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide Aim The aim of this study is to develop a reliable composite score based on simulator metrics to assess competency in virtual reality video-assisted thoracoscopic surgery lobectomy and explore the benefits of combining it with expert rater assessments. METHODS Standardized objective assessments (time, bleeding, economy of movement) and subjective expert rater assessments from 2 previous studies were combined. A linear mixed model including experience level, lobe and the number of previous simulated procedures was applied for the repeated measurements. Reliability for each of the 4 assessments was calculated using Cronbach's alpha. The Nelder–Mead numerical optimization algorithm was used for optimal weighting of scores. A pass–fail standard for the composite score was determined using the contrasting groups' method. RESULTS In total, 123 virtual reality video-assisted thoracoscopic surgery lobectomies were included. Across the 4 different assessments, there were significant effects (P  < 0.01) of experience, lobe, and simulator experience, but not for simulator attempts on bleeding (P  = 0.98). The left upper lobe was significantly more difficult compared to other lobes (P = 0.02). A maximum reliability of 0.92 could be achieved by combining the standardized simulator metrics with standardized expert rater scores. The pass/fail level for the composite score when including 1 expert rater was 0.33. CONCLUSIONS Combining simulator metrics with 1 or 2 raters increases reliability and can serve as a more objective method for assessing surgical trainees. The composite score may be used to implement a standardized and feasible simulation-based mastery training program in video-assisted thoracoscopic surgery lobectomy. [ABSTRACT FROM AUTHOR]

Non-invasive biomarkers of non-alcoholic fatty liver disease (NAFLD) supporting diagnosis and monitoring disease progression are urgently needed. The present study aimed to establish a bioinformatics pipeline capable of defining and validating NAFLD biomarker candidates based on paired hepatic global gene expression and plasma bioanalysis from individuals representing different stages of histologically confirmed NAFLD (no/mild, moderate, more advanced NAFLD). Liver secretome gene signatures were generated in a patient cohort of 26 severely obese individuals with the majority having no or mild fibrosis. To this end, global gene expression changes were compared between individuals with no/mild NAFLD and moderate/advanced NAFLD with subsequent filtering for candidate gene products with liver-selective expression and secretion. Four candidate genes, including LPA (lipoprotein A), IGFBP-1 (insulin-like growth factor-binding protein 1), SERPINF2 (serpin family F member 2) and MAT1A (methionine adenosyltransferase 1A), were differentially expressed in moderate/advanced NAFLD, which was confirmed in three independent RNA sequencing datasets from large, publicly available NAFLD studies. The corresponding gene products were quantified in plasma samples but could not discriminate among different grades of NAFLD based on NAFLD activity score. Conclusion: We demonstrate a novel approach based on the liver transcriptome allowing for identification of secreted hepatic gene products as potential circulating diagnostic biomarkers of NAFLD. Using this approach in larger NAFLD patient cohorts may yield potential circulating biomarkers for NAFLD severity. [ABSTRACT FROM AUTHOR]

Introduction: Pulmonary rehabilitation (PR) is a key standard treatment for people with chronic obstructive pulmonary disease (COPD) with documented effect on symptom relief, improved physical function, and quality of life. However, referral, uptake and adherence rates remain low. Pulmonary telerehabilitation (PTR) is a safe and effective alternative to conventional PR. This study explores associations, thoughts and attitudes towards PTR in patients with COPD who decline referral to outpatient hospital-based routine PR. Methods: A mixed-methods study with integration of survey data (n=84) and semi-structured interviews (n=9). Results: We found a significant association between belief of effect of PTR and willingness to participate. Increasing age was significantly associated with reduced odds of daily use of central processing unit (CPU) or tablet. One-third of the participants were undecided about potential participation in PTR. Qualitative findings highlight that participants perceived participating in PTR as more convenient and had preferences for individualized, supervised, and monitored rehabilitation. Conclusion: Those willing to participate in a PTR program believed in the benefits, were comfortable with technological devices, had preferences for exercising at home, and saw opportunities in the social setting. Future PTR programs should include monitoring, preferably managed by a familiar health care professional (HCP). [ABSTRACT FROM AUTHOR]

Purpose: Vitamin K deficiency and hence a high level of plasma dephosphorylated undercarboxylated matrix Gla protein (dp-ucMGP) is frequent in patients on hemodialysis. This group is recommended to restrict their potassium intake which often leads to restriction of vitamin K rich foods. A menaquinone-7 (MK-7) supplement has been shown to decrease dp-ucMGP, but it has yet to be examined if a vitamin K rich diet could be equally effective. Patients and Methods: A prospective randomized crossover intervention trial with two arms; 6 weeks of 360 μg MK-7 tablet/day and 6 weeks of a vitamin K rich diet with a 3-week washout period in between. Participants were 10 patients in hemodialysis and the primary outcome measures were changes in dp-ucMGP, total MGP (tMGP), and undercarboxylated osteocalcin (ucOC). Furthermore, the level of potassium and phylloquinone in broccoli was determined after different durations of boiling. Results: During the MK-7 intervention the dp-ucMGP and ucOC decreased significantly compared to baseline (− 0.42 [− 0.93; − 0.22] nmol/L (p=< 0.01) and − 1.85 [− 2.91; − 1.30] nmol/L (p< 0.01)), while these were unchanged during the dietary intervention (0.03 [− 0.64; 0.37] nmol/L (p=1.00) and 0.30 [− 1.71; 1.41] nmol/L (p=0.77)). Between the two interventions there was a greater decrease in ucOC (p=0.02) during the MK-7 compared to the dietary period. No significant changes in the total MGP levels were found in any of the periods. The retention of potassium following boiling for 2 minutes and 8 minutes was 76% and 49%, respectively, while for phylloquinone the retention was 92%, and independent of duration of boiling. Conclusion: A daily MK-7 supplement for 6 weeks lowered dp-ucMGP and ucOC significantly, while a vitamin K rich diet was not able to induce any significant effect. Boiled broccoli maintains a reasonable content of phylloquinone while potassium is extracted and is a reasonable source of phylloquinone for patients on hemodialysis. [ABSTRACT FROM AUTHOR]

Reducing the amount of noble metals in catalysts for electrochemical conversion devices is paramount if these devices are to be commercialized. Taking advantage of the high degree of particle property control displayed by the sonochemical method, we set out to synthesize Cu@Pt bimetallic nanocatalysts in an effort to improve the mass activity towards the hydrogen evolution reaction. At least 17 times higher mass activity was found for the carbon supported Cu@Pt bimetallic nanocatalyst (737 mA mg−1, E = − 20   m V) compared to carbon supported Pt nanocatalysts prepared with the same ultrasound conditions (44 mA mg−1, E = − 20   m V). The synthesis was found to proceed with the sonochemical formation of Cu and Cu2O nanoparticles with the addition of PtCl4 leading to galvanic displacement of the Cu-nanoparticles and the formation of a Pt-shell around the Cu-core. [ABSTRACT FROM AUTHOR]

Background: Obesity, hyperglycemia and hypertension are critical risk factors for development of diabetic kidney disease (DKD). Emerging evidence suggests that glucagon-like peptide-1 receptor (GLP-1R) agonists improve cardiovascular and renal outcomes in type 2 diabetes patients. Here, we characterized the effect of the long-acting GLP-1R agonist semaglutide alone and in combination with an ACE inhibitor (lisinopril) in a model of hypertension-accelerated, advanced DKD facilitated by adeno-associated virus-mediated renin overexpression (ReninAAV) in uninephrectomized (UNx) female diabetic db/db mice. Methods: Female db/db mice received a single intravenous injection of ReninAAV 1 week prior to UNx. Six weeks post-nephrectomy, db/db UNx-ReninAAV mice were administered (q.d.) vehicle, semaglutide (30 nmol/kg, s.c.) or semaglutide (30 nmol/kg, s.c.) + lisinopril (30 mg/kg, p.o.) for 11 weeks. Endpoints included blood pressure, plasma/urine biochemistry, kidney histopathology and RNA sequencing. Results: Vehicle-dosed db/db UNx-ReninAAV mice developed hallmarks of DKD characterized by severe albuminuria and advanced glomerulosclerosis. Semaglutide robustly reduced hyperglycemia, hypertension and albuminuria concurrent with notable improvements in glomerulosclerosis severity, podocyte filtration slit density, urine/renal kidney injury molecule-1 (KIM-1) levels and gene expression markers of inflammation and fibrogenesis in db/db UNx-ReninAAV mice. Co-administration of lisinopril further ameliorated hypertension and glomerulosclerosis. Conclusions: Semaglutide improves disease hallmarks in the db/db UNx-ReninAAV mouse model of advanced DKD. Further benefits on renal outcomes were obtained by adjunctive antihypertensive standard of care. Collectively, our study supports the development of semaglutide for management of DKD. [ABSTRACT FROM AUTHOR]

Single nucleotide polymorphisms (SNPs) in insulin and insulin receptor genes may influence the interaction between the two molecules, as may anti-insulin antibodies (IAs), commonly found in patients with type 1 diabetes mellitus (T1D) or type 2 diabetes mellitus (T2D) treated with exogenous insulin. We examined the impact of two SNPs in the human insulin gene (INS), rs3842752 and rs689, and two in the insulin receptor gene (INSR) rs2245649 and rs2229429, on disease susceptibility, glycaemic control, and IAs formation in 100 T1D patients and 101 T2D patients treated with insulin. 79 individuals without diabetes were typed as healthy controls. The minor alleles of rs3842752 and rs689 in INS protected against T1D (OR: 0.50, p = 0.01 and OR: 0.44; p = 0.002, respectively). The minor alleles of both rs2245649 and rs2229429 in INSR were risk factors for poor glycaemic control (HbA1c ≥ 80 mmol/mol) in T1D (OR: 5.35, p = 0.009 and OR: 3.10, p = 0.01, respectively). Surprisingly, the minor alleles of rs2245649 and rs2229429 in INSR associated strongly with the absence of IAs in T1D (OR = 0.28, p = 0.008 and OR = 0.30, p = 0.002, respectively). In conclusion, the minor alleles of the investigated INS SNPs protect against T1D, and the minor alleles of the investigated INSR SNPs are associated with poor glycaemic control and the absence of IAs in T1D. [ABSTRACT FROM AUTHOR]

Non‐alcoholic steatohepatitis (NASH) has emerged as a major challenge for public health because of high global prevalence and lack of evidence‐based therapies. Most animal models of NASH lack sufficient validation regarding disease progression and pharmacological treatment. The Gubra‐Amylin NASH (GAN) diet‐induced obese (DIO) mouse demonstrate clinical translatability with respect to disease etiology and hallmarks of NASH. This study aimed to evaluate disease progression and responsiveness to clinically effective interventions in GAN DIO‐NASH mice. Disease phenotyping was performed in male C57BL/6J mice fed the GAN diet high in fat, fructose, and cholesterol for 28–88 weeks. GAN DIO‐NASH mice with biopsy‐confirmed NASH and fibrosis received low‐caloric dietary intervention, semaglutide (30 nmol/kg/day, s.c.) or lanifibranor (30 mg/kg/day, p.o.) for 8 and 12 weeks, respectively. Within‐subject change in nonalcoholic fatty liver disease (NAFLD) Activity Score (NAS) and fibrosis stage was evaluated using automated deep learning‐based image analysis. GAN DIO‐NASH mice showed clear and reproducible progression in NASH, fibrosis stage, and tumor burden with high incidence of hepatocellular carcinoma. Consistent with clinical trial outcomes, semaglutide and lanifibranor improved NAS, whereas only lanifibranor induced regression in the fibrosis stage. Dietary intervention also demonstrated substantial benefits on metabolic outcomes and liver histology. Differential therapeutic efficacy of semaglutide, lanifibranor, and dietary intervention was supported by quantitative histology, RNA sequencing, and blood/liver biochemistry. In conclusion, the GAN DIO‐NASH mouse model recapitulates various histological stages of NASH and faithfully reproduces histological efficacy profiles of compounds in advanced clinical development for NASH. Collectively, these features highlight the utility of GAN DIO‐NASH mice in preclinical drug development. [ABSTRACT FROM AUTHOR]