Drug-Induced Fatty Liver Disease (DIFLD): A Comprehensive Analysis of Clinical, Biochemical, and Histopathological Data for Mechanisms Identification and Consistency with Current Adverse Outcome Pathways.

Drug induced fatty liver disease (DIFLD) is a form of drug-induced liver injury (DILI), which can also be included in the more general metabolic dysfunction-associated steatotic liver disease (MASLD), which specifically refers to the accumulation of fat in the liver unrelated to alcohol intake. A bi-directional relationship between DILI and MASLD is likely to exist: while certain drugs can cause MASLD by acting as pro-steatogenic factors, MASLD may make hepatocytes more vulnerable to drugs. Having a pre-existing MASLD significantly heightens the likelihood of experiencing DILI from certain medications. Thus, the prevalence of steatosis within DILI may be biased by pre-existing MASLD, and it can be concluded that the genuine true incidence of DIFLD in the general population remains unknown. In certain individuals, drug-induced steatosis is often accompanied by concomitant injury mechanisms such as oxidative stress, cell death, and inflammation, which leads to the development of drug-induced steatohepatitis (DISH). DISH is much more severe from the clinical point of view, has worse prognosis and outcome, and resembles MASH (metabolic-associated steatohepatitis), as it is associated with inflammation and sometimes with fibrosis. A literature review of clinical case reports allowed us to examine and evaluate the clinical features of DIFLD and their association with specific drugs, enabling us to propose a classification of DIFLD drugs based on clinical outcomes and pathological severity: Group 1, drugs with low intrinsic toxicity (e.g., ibuprofen, naproxen, acetaminophen, irinotecan, methotrexate, and tamoxifen), but expected to promote/aggravate steatosis in patients with pre-existing MASLD; Group 2, drugs associated with steatosis and only occasionally with steatohepatitis (e.g., amiodarone, valproic acid, and tetracycline); and Group 3, drugs with a great tendency to transit to steatohepatitis and further to fibrosis. Different mechanisms may be in play when identifying drug mode of action: (1) inhibition of mitochondrial fatty acid ß-oxidation; (2) inhibition of fatty acid transport across mitochondrial membranes; (3) increased de novo lipid synthesis; (4) reduction in lipid export by the inhibition of microsomal triglyceride transfer protein; (5) induction of mitochondrial permeability transition pore opening; (6) dissipation of the mitochondrial transmembrane potential; (7) impairment of the mitochondrial respiratory chain/oxidative phosphorylation; (8) mitochondrial DNA damage, degradation and depletion; and (9) nuclear receptors (NRs)/transcriptomic alterations. Currently, the majority of, if not all, adverse outcome pathways (AOPs) for steatosis in AOP-Wiki highlight the interaction with NRs or transcription factors as the key molecular initiating event (MIE). This perspective suggests that chemical-induced steatosis typically results from the interplay between a chemical and a NR or transcription factors, implying that this interaction represents the primary and pivotal MIE. However, upon conducting this exhaustive literature review, it became evident that the current AOPs tend to overly emphasize this interaction as the sole MIE. Some studies indeed support the involvement of NRs in steatosis, but others demonstrate that such NR interactions alone do not necessarily lead to steatosis. This view, ignoring other mitochondrial-related injury mechanisms, falls short in encapsulating the intricate biological mechanisms involved in chemically induced liver steatosis, necessitating their consideration as part of the AOP's map road as well.

Novel clinical phenotypes, drug categorization, and outcome prediction in drug-induced cholestasis: Analysis of a database of 432 patients developed by literature review and machine learning support.

BACKGROUND: Serum transaminases, alkaline phosphatase and bilirubin are common parameters used for DILI diagnosis, classification, and prognosis. However, the relevance of clinical examination, histopathology and drug chemical properties have not been fully investigated. As cholestasis is a frequent and complex DILI manifestation, our goal was to investigate the relevance of clinical features and drug properties to stratify drug-induced cholestasis (DIC) patients, and to develop a prognosis model to identify patients at risk and high-concern drugs. METHODS: DIC-related articles were searched by keywords and Boolean operators in seven databases. Relevant articles were uploaded onto Sysrev, a machine-learning based platform for article review and data extraction. Demographic, clinical, biochemical, and liver histopathological data were collected. Drug properties were obtained from databases or QSAR modelling. Statistical analyses and logistic regressions were performed. RESULTS: Data from 432 DIC patients associated with 52 drugs were collected. Fibrosis strongly associated with fatality, whereas canalicular paucity and ALP associated with chronicity. Drugs causing cholestasis clustered in three major groups. The pure cholestatic pattern divided into two subphenotypes with differences in prognosis, canalicular paucity, fibrosis, ALP and bilirubin. A predictive model of DIC outcome based on non-invasive parameters and drug properties was developed. Results demonstrate that physicochemical (pKa-a) and pharmacokinetic (bioavailability, CYP2C9) attributes impinged on the DIC phenotype and allowed the identification of high-concern drugs. CONCLUSIONS: We identified novel associations among DIC manifestations and disclosed novel DIC subphenotypes with specific clinical and chemical traits. The developed predictive DIC outcome model could facilitate DIC prognosis in clinical practice and drug categorization.

New insights into the regulation of bile acids synthesis during the early stages of liver regeneration: A human and experimental study.

BACKGROUND AND AIMS: Liver regeneration is essential for the preservation of homeostasis and survival. Bile acids (BAs)-mediated signaling is necessary for liver regeneration, but BAs levels need to be carefully controlled to avoid hepatotoxicity. We studied the early response of the BAs-fibroblast growth factor 19 (FGF19) axis in healthy individuals undergoing hepatectomy for living donor liver transplant. We also evaluated BAs synthesis in mice upon partial hepatectomy (PH) and acute inflammation, focusing on the regulation of cytochrome-7A1 (CYP7A1), a key enzyme in BAs synthesis from cholesterol. METHODS: Serum was obtained from twelve human liver donors. Mice underwent 2/3-PH or sham-operation. Acute inflammation was induced with bacterial lipopolysaccharide (LPS) in mice fed control or antoxidant-supplemented diets. BAs and 7α-hydroxy-4-cholesten-3-one (C4) levels were measured by HPLC-MS/MS; serum FGF19 by ELISA. Gene expression and protein levels were analyzed by RT-qPCR and western-blot. RESULTS: Serum BAs levels increased after PH. In patients with more pronounced hypercholanemia, FGF19 concentrations transiently rose, while C4 levels (a readout of CYP7A1 activity) dropped 2 h post-resection in all cases. Serum BAs and C4 followed the same pattern in mice 1 h after PH, but C4 levels also dropped in sham-operated and LPS-treated animals, without marked changes in CYP7A1 protein levels. LPS-induced serum C4 decline was attenuated in mice fed an antioxidant-supplemented diet. CONCLUSIONS: In human liver regeneration FGF19 upregulation may constitute a protective response from BAs excess during liver regeneration. Our findings suggest the existence of post-translational mechanisms regulating CYP7A1 activity, and therefore BAs synthesis, independent from CYP7A1/Cyp7a1 gene transcription.

Effects of mirror neuron activation therapies on functionality in older adults: Systematic review and meta-analysis.

PURPOSE: To identify the effects of mirror neuron activation (MNAT) combined or not with physical exercise (PE) in healthy older adults, on functionality, balance, gait velocity and risk of falls. METHODS: A systematic electronic search was performed in PubMed/MEDLINE, Cochrane, and Embase databases. RESULTS: Thirteen randomized controlled trials were included in the qualitative analysis, and eleven in the quantitative analysis. All studies showed fair to high quality and the most frequent high-risk bias was "Blinding of participants and personnel". Compared to the control condition, higher improvement was shown in older people who received MNAT, on functionality (1.57 [0.57, 2.62], balance (1.95 [1.32, 2.572]), and gait velocity (1.20 [0.30, 2.11]). Compared to PE, MNAT combined with PE does not improve functionality. More studies are needed to assess MNAT effectiveness in the rest of the outcomes. CONCLUSIONS: Neuron system activation through MNAT improves relevant abilities in older adults, with better results when including functional activities. However, the beneficial effects on these variables of adding MNAT to a PE program are controversial.

Comprehensive analysis of epigenetic and epitranscriptomic genes’ expression in human NAFLD

Non-alcoholic fatty liver disease (NAFLD) is a multifactorial condition with a complex etiology. Its incidence is increasing globally in parallel with the obesity epidemic, and it is now considered the most common liver disease in Western countries. The precise mechanisms underlying the development and progression of NAFLD are complex and still poorly understood. The dysregulation of epigenetic and epitranscriptomic mechanisms is increasingly recognized to play pathogenic roles in multiple conditions, including chronic liver diseases. Here, we have performed a comprehensive analysis of the expression of epigenetic and epitranscriptomic genes in a total of 903 liver tissue samples corresponding to patients with normal liver, obese patients, and patients with non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH), advancing stages in NAFLD progression. We integrated ten transcriptomic datasets in an unbiased manner, enabling their robust analysis and comparison. We describe the complete landscape of epigenetic and epitranscriptomic genes’ expression along the course of the disease. We identify signatures of genes significantly dysregulated in association with disease progression, particularly with liver fibrosis development. Most of these epigenetic and epitranscriptomic effectors have not been previously described in human NAFLD, and their altered expression may have pathogenic implications. We also performed a comprehensive analysis of the expression of enzymes involved in the metabolism of the substrates and cofactors of epigenetic and epitranscriptomic effectors. This study provides novel information on NAFLD pathogenesis and may also guide the identification of drug targets to treat this condition and its progression towards hepatocellular carcinoma. (AU)

Bridging Evolutionary History and Conservation of New World Vultures.

The New World Vultures (Cathartidae) include seven species of obligate scavengers that, despite their ecological relevance, present critical information gaps around their evolutionary history and conservation. Insights into their phylogenetic relationships in recent years has enabled the addressing of such information gaps through approaches based on phylogeny. We reconstructed the ancestral area in America of the current species using two regionalization schemes and methods: Biogeography with Bayesian Evolutionary Analysis (BioGeoBears) and Bayesian Binary Model-Monte Carlo Markov Chains (BBM-MCMC). Then, we identified the priority species and areas for conservation by means of the Evolutionary Distinctiveness index (ED), as a proxy of the uniqueness of species according to phylogeny, and the Global Endangerment index (GE), mapping phylogenetic diversity. We found that the ancestral area of New World Vultures in America corresponds to South America, with dispersal processes that led to a recolonization of North America by Coragyps atratus, Gymnogyps californianus and Cathartes aura. We identified the Black Vulture, G. californianus and Vultur gryphus as priority species based on ED and "Evolutionary Distinct Globally Endangered" (EDGE) indexes, and the lowlands of Amazon River basin and the Orinoco basin and some tributaries areas of the Guiana Shield were identified as the priority areas when mapping the phylogenetic diversity. This study highlights the importance of filling knowledge gaps of species of conservation concern through the integration of evolutionary and ecological information and tools and, thus, developing adequate strategies to enhance the preservation of these species in the face of the current loss of biodiversity.

Comprehensive analysis of epigenetic and epitranscriptomic genes' expression in human NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is a multifactorial condition with a complex etiology. Its incidence is increasing globally in parallel with the obesity epidemic, and it is now considered the most common liver disease in Western countries. The precise mechanisms underlying the development and progression of NAFLD are complex and still poorly understood. The dysregulation of epigenetic and epitranscriptomic mechanisms is increasingly recognized to play pathogenic roles in multiple conditions, including chronic liver diseases. Here, we have performed a comprehensive analysis of the expression of epigenetic and epitranscriptomic genes in a total of 903 liver tissue samples corresponding to patients with normal liver, obese patients, and patients with non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH), advancing stages in NAFLD progression. We integrated ten transcriptomic datasets in an unbiased manner, enabling their robust analysis and comparison. We describe the complete landscape of epigenetic and epitranscriptomic genes' expression along the course of the disease. We identify signatures of genes significantly dysregulated in association with disease progression, particularly with liver fibrosis development. Most of these epigenetic and epitranscriptomic effectors have not been previously described in human NAFLD, and their altered expression may have pathogenic implications. We also performed a comprehensive analysis of the expression of enzymes involved in the metabolism of the substrates and cofactors of epigenetic and epitranscriptomic effectors. This study provides novel information on NAFLD pathogenesis and may also guide the identification of drug targets to treat this condition and its progression towards hepatocellular carcinoma.

The Reliability and Accuracy of a Fall Risk Assessment Procedure Using Mobile Smartphone Sensors Compared with a Physiological Profile Assessment.

Falls in older people are a major health concern as the leading cause of disability and the second most common cause of accidental death. We developed a rapid fall risk assessment based on a combination of physical performance measurements made with an inertial sensor embedded in a smartphone. This study aimed to evaluate and validate the reliability and accuracy of an easy-to-use smartphone fall risk assessment by comparing it with the Physiological Profile Assessment (PPA) results. Sixty-five participants older than 55 performed a variation of the Timed Up and Go test using smartphone sensors. Balance and gait parameters were calculated, and their reliability was assessed by the (ICC) and compared with the PPAs. Since the PPA allows classification into six levels of fall risk, the data obtained from the smartphone assessment were categorised into six equivalent levels using different parametric and nonparametric classifier models with neural networks. The F1 score and geometric mean of each model were also calculated. All selected parameters showed ICCs around 0.9. The best classifier, in terms of accuracy, was the nonparametric mixed input data model with a 100% success rate in the classification category. In conclusion, fall risk can be reliably assessed using a simple, fast smartphone protocol that allows accurate fall risk classification among older people and can be a useful screening tool in clinical settings.

Classification of Parkinson's disease stages with a two-stage deep neural network.

Introduction: Parkinson's disease is one of the most prevalent neurodegenerative diseases. In the most advanced stages, PD produces motor dysfunction that impairs basic activities of daily living such as balance, gait, sitting, or standing. Early identification allows healthcare personnel to intervene more effectively in rehabilitation. Understanding the altered aspects and impact on the progression of the disease is important for improving the quality of life. This study proposes a two-stage neural network model for the classifying the initial stages of PD using data recorded with smartphone sensors during a modified Timed Up & Go test. Methods: The proposed model consists on two stages: in the first stage, a semantic segmentation of the raw sensor signals classifies the activities included in the test and obtains biomechanical variables that are considered clinically relevant parameters for functional assessment. The second stage is a neural network with three input branches: one with the biomechanical variables, one with the spectrogram image of the sensor signals, and the third with the raw sensor signals. Results: This stage employs convolutional layers and long short-term memory. The results show a mean accuracy of 99.64% for the stratified k-fold training/validation process and 100% success rate of participants in the test phase. Discussion: The proposed model is capable of identifying the three initial stages of Parkinson's disease using a 2-min functional test. The test easy instrumentation requirements and short duration make it feasible for use feasible in the clinical context.

Effect of virtual running with exercise on functionality in pre-frail and frail elderly people: randomized clinical trial.

BACKGROUND: Virtual mirror therapies could increase the results of exercise, since the mirror neuron system produces an activation of motor execution cortical areas by observing actions performed by others. In this way, pre-frail and frail people could use this system to reach an exercise capacity threshold and obtain health benefits. AIM: The aim of this study is to evaluate the effects of a virtual running (VR) treatment combined with specific physical gait exercise (PE) compared to placebo VR treatment combined with PE on functionality, pain, and muscular tone in pre-frail and frail older persons. METHODS: A single blinded, two-arm, randomised controlled trial design was employed. Thirty-eight participants were divided into two intervention arms: Experimental Intervention (EI) group, in which VR and gait-specific physical exercises were administered and Control Intervention (CI) group, in which a placebo virtual gait and the same exercise programme was administered. Functionality, pain, and tone were assessed. RESULTS: EI group improved in aerobic capacity, functional lower-limb strength, reaction time, and pain, while CI group remained the same. Regarding static balance and muscle tone, no differences were found for either group. Further analysis is needed to asses VR effectiveness for improving gait, stand-up and sit-down performance and velocity. CONCLUSIONS: Virtual running therapy appears to enhance capacities related with voluntary movements (i.e., aerobic capacity, functional lower-limb strength, and reaction time) and reduce pain.

Detection of moisture ratio and carotenoid compounds in mamey (Pouteria sapota) fruit during dehydration process using spectroscopic techniques.

This work presents the study of the moisture ratio and carotenoid compounds in dried mamey (Pouteria sapota) using non-invasive spectroscopic techniques. The drying behavior of mamey at 64 °C by a homemade solar dryer is analyzed by fitting the experimental data to four different mathematical drying models. In addition, this result is compared with other drying techniques, namely by heat chamber with natural convection at temperatures of 50 °C and 60 °C. The results show that the Lewis model is the one that best fits the experimental moisture ratio curve of mamey. On the other hand, Near-Infrared and Terahertz spectroscopic techniques are used to estimate the moisture ratio, since water absorption is most sensitive at these frequencies. Fourier Transform Infrared-attenuated total reflectance and Raman spectroscopy are performed to detect the carotenoid compounds in dried mamey. This compound has important applications in the food industry and health benefits. To our knowledge, there are few studies on the dehydration of Pouteria sapota as well as its characterization using spectroscopic techniques for the detection of moisture ratio and carotenoid content; therefore, this study can be useful in agriculture and food sectors when detailed information about the cited parameters is needed.

Non-Invasive Sex Determination of Nestlings and Adult Bonelli's Eagles Using Morphometrics.

Biometric analysis allows the sexing of most vertebrates, particularly birds. Birds of prey, and, especially, the Bonelli's eagle (Aquila fasciata), show reverse sexual dimorphism (i.e., females are usually larger than males). In contrast to blood sampling, the use of morphometrics allows sex determination using a non-invasive method, and, therefore, it facilitates fieldwork. By means of a linear discriminant analysis of biometric variables, we obtained different equations that allow the sexing of nestlings and adult Bonelli's eagles. We sampled 137 Bonelli's eagles, 82 nestlings and 55 adults in eastern Spain during the period 2015-2022. The sexes obtained after linear discriminant analysis were compared with their molecular sexing. The validation procedure of the linear discriminant equations facilitated the reduction of the number of variables used and, consequently, optimised working time and sexing accuracy. After validation, some equations showed a 100% sexing efficiency for Bonelli's eagles, particularly for adults. Our results showed that the variables with smaller overlap between the sexes were the lateral tarsus length and dorso-ventral tarsus length, particularly in nestlings. The rest of the variables showed some overlap between the sexes in both age classes. The results we obtained enable the sexing of juvenile and adult Bonelli's eagles in the field using just these two measurements. Hence, this is an easy, accurate, quick and non-invasive method with multiple applications, including in studies on population dynamics, survival analysis or extinction risk assessments, which, ultimately, could contribute to the improvement of the conservation status of this endangered species.

Pancreatic microexons regulate islet function and glucose homeostasis.

Pancreatic islets control glucose homeostasis by the balanced secretion of insulin and other hormones, and their abnormal function causes diabetes or hypoglycaemia. Here we uncover a conserved programme of alternative microexons included in mRNAs of islet cells, particularly in genes involved in vesicle transport and exocytosis. Islet microexons (IsletMICs) are regulated by the RNA binding protein SRRM3 and represent a subset of the larger neural programme that are particularly sensitive to SRRM3 levels. Both SRRM3 and IsletMICs are induced by elevated glucose levels, and depletion of SRRM3 in human and rat beta cell lines and mouse islets, or repression of particular IsletMICs using antisense oligonucleotides, leads to inappropriate insulin secretion. Consistently, mice harbouring mutations in Srrm3 display defects in islet cell identity and function, leading to hyperinsulinaemic hypoglycaemia. Importantly, human genetic variants that influence SRRM3 expression and IsletMIC inclusion in islets are associated with fasting glucose variation and type 2 diabetes risk. Taken together, our data identify a conserved microexon programme that regulates glucose homeostasis.

A socioeconomic approach to the profile of microcredit holders from the Hispanic minority in the USA.

The subject of this study is the microcredit market in the USA, more specifically in Florida. The justification for choosing this specific state is the massive presence of the Hispanic population. This will facilitate a generalization of the obtained results to the microcredit market in Latin American countries. Thus, the objective of this study is to analyze the profile of microcredit holders and their companies from socioeconomic and financial points of view. As our data also consider the degree of repayment of the microloans included in the sample, the clients' profile is related to the punctuality or default of their corresponding loan repayments using the methodology of multinomial logit regression. The variables used in this study refer to personal information concerning borrowers (gender, age, education level, and marital status), the economic situation of their respective companies (closeness to the lender, number of workers, and revenues), and the characteristics of granted loans (principal, term, and purpose). However, the results of the regression show that only two variables are significant at the 5% significance level: the borrower's age, which has a positive effect on repayment punctuality, and the loan term, which exhibits a negative effect. The findings of this study have clear implications, as they can help lenders design suitable microloans adjusted to customer profiles. Finally, future research should include other demographics and characteristics of affected companies.

Potential negative effects of the installation of video surveillance cameras in raptors' nests.

Video surveillance cameras installed on birds' nests are a cost-effective tool to study many aspects of ecology and behaviour that would otherwise be practically impossible to obtain. However, although most studies report neutral effects of cameras on birds, very few studies analyse in detail the potential negative effects of their use, particularly on raptors. Here, using a long-term database of a population of Bonelli's eagle (Aquila fasciata) collected from 2000 to 2022, I show how the inappropriate use of video surveillance cameras could result in negative effects on the reproduction of a threatened species through a before-and-after control-impact study design. Pairs under video surveillance showed lower productivity, lower breeding success and unusual delayed laying dates. The installation of cameras close to the laying date, coinciding with the mating phase of individuals, most of them subadult inexperienced birds; in combination to the reiteration of visits to the nests once the cameras were installed to check the system, particularly during the incubation period and early stages of breeding; and the installation of cameras in a particular area subject to constant human disturbance, might explain these results. Potential management actions to mitigate the effect of the installation of video cameras on birds' behaviour should include the need to plan the intervention dates, testing the systems beforehand under controlled conditions and adequate post-installation monitoring to avoid unnecessary disturbance to animals. Finally, I urge the scientific community to report the potential negative effects observed in their studies, especially if the target species are threatened with extinction.

Impact of Parkinson's Disease on Functional Mobility at Different Stages.

Introduction: Specific functional assessments to determine the progression of Parkinson's Disease (PD) are important to slow down such progression and better plan rehabilitation. This study aimed to explore possible differences in the performance of different functional tasks included in a mobility test using sensors embedded in an Android device, in people at different PD stages. Materials and Methods: Eighty-seven participants with PD agreed to participate in this cross-sectional study. They were assessed once using an inertial sensor and variables related to functional status were recorded (i.e., MLDisp, APDisp, DispA, Vrange, MLRange, PTurnSit, PStand, TTime, and RTime). Results: There was significant impairment of the vertical range during gait between stages I and II. Further, when stages II and III were compared, the sit-to-stand power was significantly impaired, and the total time required to complete the test increased significantly (p < 0.05). Even more significant differences were obtained when stages I and III were compared, in particular, dysfunction in postural control, vertical range, sit to stand power and total time. Finally, there were no significant differences between stages in the medial-lateral displacements and reaction time (p > 0.05). Conclusion: Functional mobility becomes more significantly impaired in the PD population as the PD stages progress. This implies impaired postural control, decreased ability to sit down or stand up from a chair, increased metabolic cost during walking, and overall slowing-down of motor function.

Accuracy of a 3D temporal scanning system for gait analysis: Comparative with a marker-based photogrammetry system.

BACKGROUND: Combining the accuracy of marker-based stereophotogrammetry and the usability and comfort of markerless human movement analysis is a difficult challenge. 3D temporal scanners are a promising solution, since they provide moving meshes with thousands of vertices that can be used to analyze human movements. RESEARCH QUESTION: Can a 3D temporal scanner be used as a markerless system for gait analysis with the same accuracy as traditional, marker-based stereophotogrammetry systems? METHODS: A comparative study was carried out using a 3D temporal scanner synchronized with a marker-based stereophotogrammetry system. Two gait cycles of twelve healthy adults were measured simultaneously, extracting the positions of key anatomical points from both systems, and using them to analyze the 3D kinematics of the pelvis, right hip and knee joints. Measurement differences of marker positions and joint angles were described by their root mean square. A t-test was performed to rule out instrumental errors, and an F-test to evaluate the amplifications of marker position errors in dynamic conditions. RESULTS: The differences in 3D landmark positions were between 1.9 and 2.4 mm in the reference pose. Marker position errors were significantly increased during motion in the medial-lateral and vertical directions. The angle relative errors were between 3% and 43% of the range of motion, with the greatest difference being observed in hip axial rotation. SIGNIFICANCE: The differences in the results obtained between the 3D temporal scanner and the marker-based system were smaller than the usual errors due to lack of accuracy in the manual positioning of markers on anatomical landmarks and to soft-tissue artefacts. That level of accuracy is greater than other markerless systems, and proves that such technology is a good alternative to traditional, marker-based motion capture.