Musculoskeletal disorders prediagnosis by infrared thermography in CNC machinery operators: Regression models approaches.

BACKGROUND: Musculoskeletal System Disorders (MSDs) are a group of injuries that represent common occupational diseases and should be evaluated for prevention purposes because an increase has been observed due to the repetitive movements performed in the industry. This research was carried out in a manufacturing industry where metal parts are manufactured, and workers experience back and wrist pain. OBJECTIVE: To prediagnose Musculoskeletal System Disorders (MSDs) and examine the relationship between temperature, demographic, and physiological factors in workers through predictive models, contributing to MSD prevention. METHODS: Information from 36 operators was used to obtain vital signs and somatometry data, and thermograms of their hands in the dorsal, palmar, and back areas were collected and analyzed to determine the relationship between temperature and demographic and physiological factors. RESULTS: The ergonomic evaluations proved that the operators were at high risk owing to repetitive movements and postures adopted during work. Eighty-six percent of cases with injuries were identified using infrared thermograms, proving their high level of effectiveness. When studying the relationship between temperature behavior during recovery from repetitive activities and demographic and physiological factors, it was determined that age, dominant hand, respiratory frequency, and BMI were the most significant. CONCLUSIONS: Nine regression models were obtained, with coefficients of determination between 0.17 and 0.71. The significant factors for worker injuries were age, dominant hand, respiratory rate, and BMI. However, the sample size and variability in work activities should be extended to generalize the findings.

Effect of pemvidutide, a GLP-1/glucagon dual receptor agonist, on MASLD: A randomized, double-blind, placebo-controlled study.

BACKGROUND & AIMS: This was a randomized, double-blind, placebo-controlled study to assess the effects of pemvidutide, a glucagon-like peptide-1 (GLP-1)/glucagon dual receptor agonist, on liver fat content (LFC) in subjects with metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: Subjects with a BMI ≥28.0 kg/m2 and LFC ≥10% by magnetic resonance imaging-proton density fat fraction were randomized 1:1:1:1 to pemvidutide at 1.2 mg, 1.8 mg, or 2.4 mg, or placebo administered subcutaneously once weekly for 12 weeks. Participants were stratified according to a diagnosis of type 2 diabetes mellitus (T2DM). The primary efficacy endpoint was relative reduction (%) from baseline in LFC after 12 weeks of treatment. RESULTS: 94 subjects were randomized and dosed. Median baseline BMI and LFC across the study population were 36.2 kg/m2 and 20.6%; 29% of subjects had T2DM. At Week 12, relative reductions in LFC from baseline were (1.2 mg) 46.6% [95% CI -63.7 to -29.6], (1.8 mg) 68.5% [95% CI -84.4 to -52.5], and (2.4 mg) 57.1% [95% CI -76.1 to -38.1] versus 4.4% [95% CI -20.2 to 11.3] in placebo subjects (p <0.001 vs. placebo, all treatment groups), with 94.4% and 72.2% of subjects achieving 30% and 50% reductions in LFC and 55.6% achieving normalization (≤5% LFC) at the 1.8 mg dose. Maximal responses for weight loss (-4.3%; p <0.001), alanine aminotransferase (-13.8 IU/L; p = 0.029), and corrected cT1 (-75.9 ms; p = 0.002) were all observed at the 1.8 mg dose. Pemvidutide was well-tolerated at all doses with no severe or serious adverse events. CONCLUSIONS: In subjects with MASLD, weekly pemvidutide treatment yielded significant reductions in LFC, markers of hepatic inflammation, and body weight compared to placebo. IMPACT AND IMPLICATIONS: MASLD, and MASH, are strongly associated with overweight and obesity and it is believed that the excess liver fat associated with obesity is an important driver of these diseases. Glucagon-like peptide-1 receptor (GLP-1R) agonists elicit weight loss through centrally and peripherally mediated effects on appetite. Unlike GLP-1R agonists, glucagon receptor (GCGR) agonists act directly on the liver to stimulate fatty acid oxidation and inhibit lipogenesis, potentially providing a more potent mechanism for liver fat content (LFC) reduction than weight loss alone. This study demonstrated the ability of once-weekly treatment with pemvidutide, a dual GLP-1R/GCGR agonist, to significantly reduce LFC, hepatic inflammatory activity, and body weight, suggesting that pemvidutide may be an effective treatment for both MASH and obesity. CLINICAL TRIAL NUMBER: NCT05006885.

PARP1, DIDO3, and DHX9 Proteins Mutually Interact in Mouse Fibroblasts, with Effects on DNA Replication Dynamics, Senescence, and Oncogenic Transformation.

The regulated formation and resolution of R-loops is a natural process in physiological gene expression. Defects in R-loop metabolism can lead to DNA replication stress, which is associated with a variety of diseases and, ultimately, with cancer. The proteins PARP1, DIDO3, and DHX9 are important players in R-loop regulation. We previously described the interaction between DIDO3 and DHX9. Here, we show that, in mouse embryonic fibroblasts, the three proteins are physically linked and dependent on PARP1 activity. The C-terminal truncation of DIDO3 leads to the impairment of this interaction; concomitantly, the cells show increased replication stress and senescence. DIDO3 truncation also renders the cells partially resistant to in vitro oncogenic transformation, an effect that can be reversed by immortalization. We propose that PARP1, DIDO3, and DHX9 proteins form a ternary complex that regulates R-loop metabolism, preventing DNA replication stress and subsequent senescence.

State of the Art: Test all for Anti-Hepatitis D Virus and Reflex to Hepatitis D Virus RNA Polymerase Chain Reaction Quantification.

Diagnosis of HDV exposure is based on clinical assays of anti-hepatitis D antibody and current infection with hepatitis D RNA PCR. The role of hepatitis D antigen testing is not yet defined. RT-qPCR is the gold standard for measuring HDV RNA viral load, which is used to assess response to the treatment of HDV infection. Gaps in testing include poor sensitivity of antigen testing and quantitative HDV RNA accuracy can be affected by the genotypic variability of the virus and variation in laboratory techniques. There is also a limitation in HDV testing due to access, cost, and limited knowledge of testing indications. Droplet digital PCR promises to be a more accurate method to quantify HDV RNA. Also, the recent development of a rapid HDV detection test could prove useful in resource-limited areas.

Transcriptional Activation of a Pro-Inflammatory Response (NF-κB, AP-1, IL-1ß) by the Vibrio cholerae Cytotoxin (VCC) Monomer through the MAPK Signaling Pathway in the THP-1 Human Macrophage Cell Line.

This study describes, to some extent, the VCC contribution as an early stimulation of the macrophage lineage. Regarding the onset of the innate immune response caused by infection, the ß form of IL-1 is the most important interleukin involved in the onset of the inflammatory innate response. Activated macrophages treated in vitro with VCC induced the activation of the MAPK signaling pathway in a one-hour period, with the activation of transcriptional regulators for a surviving and pro-inflammatory response, suggesting an explanation inspired and supported by the inflammasome physiology. The mechanism of IL-1ß production induced by VCC has been gracefully outlined in murine models, using bacterial knockdown mutants and purified molecules; nevertheless, the knowledge of this mechanism in the human immune system is still under study. This work shows the soluble form of 65 kDa of the Vibrio cholerae cytotoxin (also known as hemolysin), as it is secreted by the bacteria, inducing the production of IL-1ß in the human macrophage cell line THP-1. The mechanism involves triggering the early activation of the signaling pathway MAPKs pERK and p38, with the subsequent activation of (p50) NF-κB and AP-1 (cJun and cFos), determined by real-time quantitation. The evidence shown here supports that the monomeric soluble form of the VCC in the macrophage acts as a modulator of the innate immune response, which is consistent with the assembly of the NLRP3 inflammasome actively releasing IL-1ß.

Psychosocial risk factors identification in Mexican workers and RGIII validation.

BACKGROUND: Since 2018, NOM-035-STPS-2018 has been applied in Mexico, focused on measuring psychosocial risk factors (PRFs) in workers and the Reference Guide III (RGIII) has been presented, however, research focused on its validation has been scarce, in very specific sectors and with small samples. OBJECTIVE: Determine the levels of PRFs of five work centers and reliability and validity aspects of RGIII. METHOD: The RGIII was applied to 1458 workers (806 women and 652 men) from five workplace in the industrial sector of Ensenada (Mexico), and the level of risk of the PRFs was analyzed, as well as their reliability and validity through Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA). RESULTS: The PRFs with medium, high and very high-risk levels are Workload, Lack of control over work and Workday. The RGIII presents adequate reliability with Cronbach's α, Alpha ordinal RHO and Omega of 0.93, 0.95 and 0.95, respectively. The EFA shows all five subscales maintain factor loadings greater than 0.43, although Leadership and relationships at work has better saturation values, and Work environment ended with only three items. The CFA indicates Leadership and work relationships with a Root Mean Square Error of Approximation (RMSEA) goodness of fit index of 0.072. CONCLUSION: The RGIII allows the identification and evaluation of the level of risk of PRFs. It complies with sufficient internal consistency. It does not have a clear factorial structure, because it does not meet the minimum values of goodness-of-fit indexes that would allow confirming the structure proposed in RGIII.

Individuals in Collaborative Governance for Environmental Management.

Analyzing the effect of individual participants on collaborative governance processes in environmental management has been elusive due to lack of theoretical frameworks and data limitations. This study uses pattern matching to contrast identity theory with original data from 7 individuals participating in waste management and urban agriculture collaboration in Florianópolis, Brazil. What started as a self-organized initiative to manage an environmental problem, due to precarious waste management services, was scaled up to a citywide policy. Findings demonstrate that as the collaboration evolved over time, individual participants in municipal government transitioned between roles, organizations, and departments which affected their influence on the collaboration according to two transition styles: integrators (overlapping different roles) and segmenters (aligning roles with contexts without ambiguity). While the integrator-style participants were key to increasing sectoral diversity during the activation stage of the collaboration to produce innovative actions, segmenters contributed to formalizing the collaboration with appropriate institutional designs. However, the success of the collaboration after the institutionalization stage depended on the individual transition style and the power of municipal agents to have agency for influencing the collaboration. These findings have implications for adapting collaborative settings to respond to contextual changes that involve urban environmental issues.

Hepatitis C Virus Elimination in the United States: Challenges, Progress, and Future Steps.

Hepatitis C virus (HCV) infection is a major public health challenge with a simple, highly efficacious, all-oral therapy (direct-acting antivirals) that can achieve cure. Owing to the ease of treatment, the World Health Organization outlined goals to eliminate HCV by the year 2030. However, unforeseen challenges have hampered progress, and few countries are on track to meet these goals. Significant disparities remain among priority populations because of barriers to care on the systemic, provider, and patient levels. In turn, many local, state, and national organizations have been persistent in tackling these barriers, the greatest of which is linkage to care. In 2023, the White House launched a multipronged national initiative to eliminate HCV infection. The resulting economic impact of the national HCV elimination program is estimated to yield a significant net cost savings of $18.1 billion within a 10-year period. This article addresses the barriers to HCV care in different priority populations and discusses innovative models of HCV care that have been introduced in the United States.

Temperature Asymmetry Analysis between Left and Right Wrist with Sensory and Infrared Thermography.

This article reports a thermal analysis of the wrists to analyze the behavior and recovery of skin temperature after 20 min when performing a highly repetitive movement, and two thermography methods (sensory and infrared) and research groups were compared. The tests were carried out with 44 participants who performed a repetitive task for 10 min and integrated into two groups, of which 22 were trained workers from a maquiladora company and were analyzed with sensory thermography, and the other 22 were in the laboratory with infrared thermography with undergraduate students. The study area is the left and right hand, specifically the wrists. The proposed hypothesis is that people with some musculoskeletal problems have a decrease in temperature when starting repetitive tasks and thermal asymmetries, which measurements were recorded at 0, 10, 15, and 20 min after the task was finished. Findings indicate that the temperatures in both wrists behave similarly. The workers reached higher temperatures, and the centigrade degrees of asymmetry difference were also higher. The variable with influence on the temperature was fractured in the arm. After thermally analyzing the temperature behavior between the wrists of both hands, it is concluded that there is an increase in temperature after finishing a repetitive task, and it does not stabilize after 20 min. Both thermography methods observed that the asymmetries are greater than 0.5 °C, detecting the possible pathology of carpal tunnel syndrome.

Closing the disparity gap and optimizing advanced hepatocellular carcinoma care in the hispanic community.

Content available: Author Interview and Audio Recording.

Hepatitis, testicular degeneration, and ataxia in DIDO3-deficient mice with altered mRNA processing.

BACKGROUND: mRNA processing is an essential step of gene expression; its malfunction can lead to different degrees of physiological disorder from subclinical disease to death. We previously identified Dido1 as a stemness marker and a gene involved in embryonic stem cell differentiation. DIDO3, the largest protein encoded by the Dido1 gene, is necessary for accurate mRNA splicing and correct transcription termination. The deletion of Dido1 exon16, which encodes the carboxy-terminal half of DIDO3, results in early embryonic lethality in mouse. RESULTS: We obtained mice bearing a Cre-LoxP conditional version of that deletion and studied the effects of inducing it ubiquitously in adult stages. DIDO3-deficient mice survive the deletion but suffer mild hepatitis, testicular degeneration, and progressive ataxia, in association with systemic alterations in mRNA splicing and transcriptional readthrough. CONCLUSIONS: These results offer insight into the distinct vulnerabilities in mouse organs following impairment of the mRNA processing machinery, and could aid understanding of human health dependence on accurate mRNA metabolism.

Benign Peripheral Non-cranial Nerve Sheath Tumors of the Neck.

Benign peripheral non-cranial nerve sheath tumors are rare lesions, including both schwannomas and neurofibromas. These tumors arise from Schwann cells, and may originate from any peripheral, cranial, or autonomic nerve. Most of them are localized and sporadic but multifocal systemic forms can occur. Cervical sympathetic chain, brachial plexus, cervical plexus and spinal roots and nerves are the major nerve systems commonly affected. Dumbbell-shaped intra- and extradural tumors occur most commonly in the cervical spine, as well as purely extradural and paravertebral tumors. The management of these tumors has improved greatly owing to the developments in imaging techniques and surgical innovations such as endoscopically assisted approaches and robotic surgery. Microsurgical intracapsular excision of the tumor helped by the use of intraoperative fluorescent dyes and intraoperative neurophysiological monitoring minimize postoperative neural deficit, since most schwannomas are encapsulated. Most tumors can be removed with a low rate of complications and recurrence. Radiotherapy should be considered for growing lesions that are not amenable to surgery. In asymptomatic patients, observation and serial scans is an option for elderly infirm patients.

Adipose tissue measurement in clinical research for obesity, type 2 diabetes and NAFLD/NASH.

INTRODUCTION: Excess body fat is linked to higher risks for metabolic syndrome, type 2 diabetes mellitus (T2DM), and cardiovascular disease (CV), among other health conditions. However, it is not only the level but also the distribution of body fat that contributes to increased disease risks. For example, an increased level of abdominal fat, or visceral adipose tissue (VAT), is associated with a higher risk of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). METHODS: A review of the most relevant primary and secondary sources on body composition from the last 25 years was conducted. Relevant articles were identified using PUBMED and Google Scholar. Narrative synthesis was performed as statistical pooling was not possible due to the heterogeneous nature of the studies. RESULTS: The body mass index (BMI) is commonly used as a proxy measure of body fatness. However, BMI does not reflect the level and distribution of body fat. Other anthropometric methods such as waist circumference measurement and waist-hip ratio, as well as methodologies like hydro densitometry, bioelectrical impedance, and isotope dilution are also limited in their ability to determine body fat distribution. Imaging techniques to define body composition have greatly improved performance over traditional approaches. Ultrasound (US), computed tomography (CT), dual-energy X-ray absorptiometry (DXA), magnetic resonance imaging (MRI), are now commonly used in clinical research. Of these, MRI can provide the most accurate and high-resolution measure of body composition. In addition, MRI techniques are considered the best for the determination of fat at the organ level. On the other hand, imaging modalities require specialized, often expensive equipment and expert operation. CONCLUSIONS: Anthropometric methods are suitable for rapid, high-volume screening of subjects but do not provide information on body fat distribution. Imaging techniques are more accurate but are expensive and do not lend themselves for high throughput. Therefore, successful trial strategies require a tiered approach in which subjects are first screened using anthropometric methods followed by more sophisticated modalities during the execution of the trial. This article provides a brief description of the most clinically relevant adipose tissue measurement techniques and discusses their value in obesity, diabetes, and NAFLD/NASH clinical research.

Factores asociados a bronquiolitis en pacientes menores de 2 años atendidos en un hospital de referencia del Perú

RESUMEN Introducción: La bronquiolitis se considera una patología respiratoria de etiología viral, frecuente a nivel de infantes. Existen diversos determinantes que contribuyen a su desarrollo dentro de esta población. El conocer dichos factores permitirá ejecutar medidas preventivas, así como disminuir el número de casos. Objetivo: Determinar los factores asociados a bronquiolitis en pacientes menores de 2 años atendidos en un hospital de referencia del Perú. Materiales y Métodos: se realizó un diseño de tipo casos y controles no emparejado, con una muestra representativa, con un tamaño muestral de 174 casos y 174 controles por muestreo probabilístico aleatorio simple, se realizó un modelo de regresión logística para los factores asociados al lactante y la madre para el cálculo del Odds Ratio e intervalo de confianza al 95% respecto a la variable dependiente bronquiolitis aguda Resultados: se reportó una asociación para la bronquiolitis aguda con las variables prematuridad 3.02 (IC95% 1.54 - 5.92), bajo peso al nacer 1.85 (IC95% 1.07 - 3.20), género femenino 2.89 (IC95% 1.72 - 4.86), madre adolescente 3.82 (IC95% 2.13 - 6.86) y madre sin grado de instrucción 3.02 (IC95% 1.83 - 11.87). Conclusión: los factores de prematuridad, bajo peso al nacer y género femenino del lactante y el grado de instrucción y condición adolescente de la madre se asocian al bronquiolitis aguda en pacientes menores de 2 años.

ABSTRACT Introduction: Bronchiolitis is considered a respiratory pathology of viral etiology that is frequent in infants. There are several determinants that contribute to its development within this population. Knowledge of these factors will allow preventive measures to be in place, as well as reduce the number of cases. Objective: To determine the factors associated with bronchiolitis in patients under 2 years of age treated at a reference hospital in Peru. Materials and Methods: an unpaired case-control type design was carried out, with a representative sample, with a sample size of 174 cases and 174 controls by simple random probabilistic sampling, a logistic regression model was carried out for the factors associated with the infant. and the mother for the calculation of the Odds Ratio and 95% confidence interval regarding the dependent variable acute bronchiolitis. Results: an association was reported for acute bronchiolitis with the following variables: prematurity 3.02 (95% CI 1.54 - 5.92), low birth weight 1.85 (95% CI 1.07 - 3.20), female gender 2.89 (95% CI 1.72 - 4.86), teenage mother 3.82 (95% CI 2.13 - 6.86) and mother with low educational level 3.02 (95% CI 1.83 - 11.87). Conclusion: prematurity, low birth weight, female gender, birth to an adolescent mother and maternal low educational levels are associated with acute bronchiolitis in patients under 2 years of age.

Factor structure and measurement invariance of the psychosocial risk factors inventory of NOM-035-STPS-2018.

The primary objective of this study was to analyze the psychometric properties of the Inventory for the Identification and Analysis of Psychosocial Risk Factors (IIA-PRF) of Reference Guide III proposed in NOM-035-STPS-2018. A total of 2,149 workers in Baja California, Mexico's industrial and education-government sectors, were administered an online inventory version. Preliminary analyses were performed, as well as a Confirmatory Factor Analysis (CFA) based on two models proposed by the standard itself: an eight-factor model (8-FM) and a four-factor model (4-FM). Likewise, based on the results and with the recommendations of the specialists, a threefactor model (3-FM) was proposed. In addition, nested model sequencing methods were subsequently applied to validate the invariance between the origin of the activity. The dimensionality of 3-FM was found to have adequate fit values according to a-priori established criteria. It is concluded that the IIAPRF does not have the reliability and validity parameters necessary to support interpretations, uses and consequences based on the theoretical structure established by NOM-035-STPS-2018 and that, although the 3-FM presents better reliability and validity indices, it is not invariant in terms of the origin of the activity. Finally, we discuss the implications and recommend reviewing and adjusting the design of the IIAPRF items to extend the measurement of invariance to other groups of relevance for decision making in the improvement of the work environment.

A Trypanosoma cruzi strain from southern Mexico is more virulent for male mice in part by blocking the immune response.

INTRODUCTION: Chagas disease is a neglected disease in the American continent. The southern Mexican state of Chiapas has the highest incidence rate of Chagas disease in the country. The disease, mainly caused by Tripanosoma cruzi in Mexico, is more prevalent in males than in females but the scientific basis for the sex-related tropism is not completely understood. The objective of this study was to evaluate the pathogenicity of a T. cruzi strain in mice of both sexes and to assess certain elements of the immune response in the infected animals. METHODOLOGY: Triatomines bugs were searched at Los Mezcales, Chiapas, Mexico and T. cruzi was identified by PCR and sequencing. A T. cruzi strain was isolated from the feces of triatomines bugs. Mice were infected with the strain and the virulence of the T. cruzi strain as well as the immune response against the infection was compared in male versus female mice. RESULTS: T. dimidiata was identified in all dwellings. 42.9% of the bugs were infected with T. cruzi lineage TcI. Male mice exhibited higher parasitemia than females, and developed leukopenia and lower levels of anti-T. cruzi antibodies compared to female mice. CONCLUSIONS: The identification of the T. cruzi strain in this endemic region of Mexico revealed that male mice are prone to this infectious protozoo, in addition to manifesting a deficient immune response against infection. These findings may explain the greater number of cases of Chagas disease among men in this endemic region of Latin America.

Positive predictive value of sustained virologic response 4 weeks posttreatment for achieving sustained virologic response 12 weeks posttreatment in patients receiving glecaprevir/pibrentasvir in Phase 2 and 3 clinical trials.

Sustained virologic response at posttreatment Week 12 (SVR12) is the widely accepted efficacy endpoint for direct-acting antiviral agents. Those with hepatitis C virus (HCV) are presenting younger with milder liver disease, potentially reducing need for long-term liver posttreatment monitoring. This analysis aimed to determine the positive predictive value (PPV) of SVR at posttreatment Week 4 (SVR4) for achieving SVR12 in patients with HCV, without cirrhosis or with compensated cirrhosis, receiving glecaprevir/pibrentasvir (G/P) in clinical trials. An integrated dataset from 20 Phase 2 and 3 clinical trials of G/P was evaluated in patients with 8-, 12- or 16-week treatment duration consistent with the current label (label-consistent group), and in all patients regardless of treatment duration consistency with the current label (overall group). Sensitivity analyses handled missing data either by backward imputation or were excluded. SVR4 PPV, negative predictive value (NPV), sensitivity and specificity were calculated for achieving SVR12 in both groups, and by treatment duration in the label-consistent group. SVR was defined as HCV ribonucleic acid 99% in both groups regardless of treatment duration. Not achieving SVR4 had 100% NPV and sensitivity for all groups. SVR4 measure had 79.5% specificity for identifying patients who did not achieve SVR12. Across 20 Phase 2/3 clinical trials of G/P, SVR4 was highly predictive of SVR12. Long-term follow-up to confirm SVR may not be necessary for certain populations of patients with HCV.

TVB-2640 (FASN Inhibitor) for the Treatment of Nonalcoholic Steatohepatitis: FASCINATE-1, a Randomized, Placebo-Controlled Phase 2a Trial.

BACKGROUND & AIMS: Increased de novo lipogenesis creates excess intrahepatic fat and lipotoxins, propagating liver damage in nonalcoholic steatohepatitis. TVB-2640, a fatty acid synthase inhibitor, was designed to reduce excess liver fat and directly inhibit inflammatory and fibrogenic pathways. We assessed the safety and efficacy of TVB-2640 in patients with nonalcoholic steatohepatitis in the United States. METHODS: 3V2640-CLIN-005 (FASCINATE-1) was a randomized, placebo-controlled, single-blind study at 10 US sites. Adults with ≥8% liver fat, assessed by magnetic resonance imaging proton density fat fraction, and evidence of liver fibrosis by magnetic resonance elastography ≥2.5 kPa or liver biopsy were eligible. Ninety-nine patients were randomized to receive placebo or 25 mg or 50 mg of TVB-2640 (orally, once-daily for 12 weeks). The primary end points of this study were safety and relative change in liver fat after treatment. RESULTS: Liver fat increased in the placebo cohort by 4.5% relative to baseline; in contrast TVB-2640 reduced liver fat by 9.6% in the 25-mg cohort (n = 30; least squares mean: -15.5%; 95% confidence interval, -31.3 to -0.23; P = .053), and 28.1% in the 50-mg cohort (n = 28; least squares mean: -28.0%; 95% confidence interval, -44.5 to -11.6; P = .001). Eleven percent of patients in the placebo group achieved a ≥30% relative reduction of liver fat compared to 23% in the 25-mg group, and 61% in the 50-mg group (P < .001). Secondary analyses showed improvements of metabolic, pro-inflammatory and fibrotic markers. TVB-2640 was well tolerated; adverse events were mostly mild and balanced among the groups. CONCLUSIONS: TVB-2640 significantly reduced liver fat and improved biochemical, inflammatory, and fibrotic biomarkers after 12 weeks, in a dose-dependent manner in patients with nonalcoholic steatohepatitis. ClinicalTrials.gov, Number NCT03938246.