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Background Animal models of non-alcoholic steatohepatitis (NASH) are important tools in preclinical research and drug discovery. Gubra-Amylin NASH (GAN) diet-induced obese (DIO) mice represent a model of fibrosing NASH. The present study directly assessed the clinical translatability of the model by head-to-head comparison of liver biopsy histological and transcriptome changes in GAN DIO-NASH mouse and human NASH patients. Methods C57Bl/6 J mice were fed chow or the GAN diet rich in saturated fat (40%), fructose (22%) and cholesterol (2%) for ≥38 weeks. Metabolic parameters as well as plasma and liver biomarkers were assessed. Liver biopsy histology and transcriptome signatures were compared to samples from human lean individuals and patients diagnosed with NASH. Results Liver lesions in GAN DIO-NASH mice showed similar morphological characteristics compared to the NASH patient validation set, including macrosteatosis, lobular inflammation, hepatocyte ballooning degeneration and periportal/perisinusoidal fibrosis. Histomorphometric analysis indicated comparable increases in markers of hepatic lipid accumulation, inflammation and collagen deposition in GAN DIO-NASH mice and NASH patient samples. Liver biopsies from GAN DIO-NASH mice and NASH patients showed comparable dynamics in several gene expression pathways involved in NASH pathogenesis. Consistent with the clinical features of NASH, GAN DIO-NASH mice demonstrated key components of the metabolic syndrome, including obesity and impaired glucose tolerance. Conclusions The GAN DIO-NASH mouse model demonstrates good clinical translatability with respect to the histopathological, transcriptional and metabolic aspects of the human disease, highlighting the suitability of the GAN DIO-NASH mouse model for identifying therapeutic targets and characterizing novel drug therapies for NASH.

Travel literature and travel of literature both resonate with the movements of literatures in different literary spaces, traditions, and geographies, through which works of literature gain and lose in a process of thrivingness and flourishment. Central to these tectonic movements raises the question of hospitality of literatures in new literary spaces and homes by ways of translation, mistranslation, adaptation, acculturation, and finally localization. The debates taking place in the discipline of comparative and world literature over the newly emerged concept “Untranslatability” as a driving force in projecting an alternative “world literature” coincide consistently with the debate of hospitality in languages and literatures. The question of translation comes to fore since “world literature” was viewed as “literature in translation,” which invokes the possibilities and limitations of translating literature into different literary and aesthetic spaces. As such, this research investigates the way literatures move and circulate through different transnational channels, with the Mediterranean space as its focal point, by extending the postulates of world literature through a close reading of Della Descrizione dell’Africa and Leon L’Africain as two samples of Mediterranean literatures that project new spectrums of theorizing world literature.

RationaleThe rodent Continuous Performance Test (rCPT) is a novel rodent paradigm to assess attention and impulsivity that resembles the human CPT. This task measures the rodents’ ability to discriminate between target and non-target stimuli. The effect of attention-deficit/hyperactivity disorder (ADHD) medication on rCPT performance in mice remains to be fully characterized.ObjectiveTo investigate the predictive validity of the mouse rCPT by studying the effects of ADHD medication methylphenidate, atomoxetine, amphetamine, guanfacine, and modafinil in four behavioral subgroups based on performance and impulsivity levels.MethodsTwo cohorts of male C57BL/6J mice were used, and the effect of treatment was tested in a variable stimulus duration probe. Performance and impulsive subgroups were made based on discriminability and percentage premature responses, respectively.ResultsMethylphenidate, atomoxetine, and amphetamine improved performance in the low-performing animals, with no effect in the high-performers. These improvements were a result of increased hit rate and/or decreased false-alarm rate. Furthermore, these drugs decreased percentage premature responses in the high-impulsive group. Methylphenidate, guanfacine, and modafinil increased premature responses in the low-impulsive group. Modafinil impaired performance in the high-performers by increasing false-alarm rate.ConclusionThe effect of ADHD treatment was dependent on baseline, as seen by increases in performance for the low-performers and decreases in impulsivity for the high-impulsive animals. These results agree with clinical data and may support the inverted U-shaped arousal-performance theory. The rCPT combined with behavioral separation into subgroups has high predictive validity, and our study is a step forward towards establishing the clinical translatability of the rCPT.

Anti‐aging research has made significant strides in identifying treatments capable of extending lifespan across a range of organisms, from simple invertebrates to mammals. This review showcases the current state of anti‐aging interventions, highlighting the lifespan extensions observed in animal models through various treatments and the challenges encountered in translating these findings to humans. Despite promising results in lower organisms, the translation of anti‐aging treatments to human applications presents a considerable challenge. This discrepancy can be attributed to the increasing complexity of biological systems, species‐specific metabolic and genetic differences, and the redundancy of metabolic pathways linked to longevity. Our review focuses on analyzing these challenges, offering insights into the efficacy of anti‐aging mechanisms across species and identifying key barriers to their translation into human treatments. By synthesizing current knowledge and identifying gaps in translatability, this review aims to underscore the importance of advancing these therapies for human benefit. Bridging this gap is essential to assess the potential of such treatments in extending the human healthspan. Despite promising results in lower organisms, translating anti‐aging treatments to human applications presents a considerable challenge. The effectiveness or significance of a targeted molecule from a pathway might differ across species‐specific metabolic scenarios. The importance of targeted signaling pathways varies with the general metabolism of a species. Species of increasing complexity also exhibit higher redundancy in pathways controlling metabolism. The increasing complexity of species reminds us that, much like many aspects of biology and medicine, there exists a law of diminishing returns.

Reproducibility is recognized as essential to scientific progress and integrity. Replication studies and large-scale replication projects, aiming to quantify different aspects of reproducibility, have become more common. Since no standardized approach to measuring reproducibility exists, a diverse set of metrics has emerged and a comprehensive overview is needed. We conducted a scoping review to identify large-scale replication projects that used metrics and methodological papers that proposed or discussed metrics. The project list was compiled by the authors. For the methodological papers, we searched Scopus, MedLine, PsycINFO and EconLit. Records were screened in duplicate against pre-defined inclusion criteria. Demographic information on included records and information on reproducibility metrics used, suggested or discussed was extracted. We identified 49 large-scale projects and 97 methodological papers and extracted 50 metrics. The metrics were characterized based on type (formulas and/or statistical models, frameworks, graphical representations, studies and questionnaires, algorithms), input required and appropriate application scenarios. Each metric addresses a distinct question. Our review provides a comprehensive resource in the form of a ‘live’, interactive table for future replication teams and meta-researchers, offering support in how to select the most appropriate metrics that are aligned with research questions and project goals.

BackgroundThe ongoing pandemic of severe acute respiratory syndrome coronavirus 2 has led to an enormous surge of clinical research. So far, the speed and success rate of related drug development projects, especially of vaccines, is unprecedented. For the first time, this situation allowed for the opportunistic evaluation of a translatability score, originally proposed in 2009, in a prospective manner.MethodsSeveral vaccines and treatments under development in clinical phase III trials were selected for translational scoring with the translatability score. Six prospective and six retrospective case studies were performed. The scores had to be determined for a fictive date before any results of the phase III trial were reported in any media. Spearman correlation analysis and a Kruskal Wallis test were performed for statistical evaluation.ResultsA significant correlation between the translatability scores and the clinical outcomes in translation was found, as judged on the basis of positive/intermediate/negative endpoint studies or market approval. The Spearman correlation analysis of all cases (r = 0.91, p < 0.001), the prospective cases alone (r = 0.93, p = 0.008), and the retrospective cases alone (r = 0.93, p = 0.008) showed a strong correlation between the score and outcome; R2 demonstrated a score-derived determination of outcomes by 86%.ConclusionsThe score detects strengths and weaknesses of a given project, resulting in the opportunity of selective amelioration of a project, as well as prospective portfolio risk balancing. Its substantial predictive value that has been demonstrated here for the first time could be of particular interest for biomedical industry (pharmaceutical and device manufacturers), funding agencies, venture capitalists, and researchers in the area. Future evaluations will have to address the generalizability of results obtained in an exceptional pandemic situation, and the potential adaptations of weighing factors/items to particular therapeutic areas.

PurposeThe purpose of this paper is to investigate accounting as first visible-sign statement form, and also as the first writing, and analyse its systematic differences, syntactic and semantic, from subsequent speech-following (glottographic) writing forms. The authors consider how accounting as non-glottographic (and so “unspeakable”) writing form renders “glottography” a “subsystem of writing” (Hyman, 2006), while initiating a mode of veridiction which always and only names and counts, silently and synoptically. The authors also consider the translation of this statement form into the graphs, charts, equations, etc., which are central to the making of modern scientific truth claims, and to remaking the boundaries of “languaging” and translatability.Design/methodology/approachAs a historical–theoretical study, this draws on work reconceptualising writing vs speech (e.g. Harris, 1986; 2000), the statement vs the word (e.g. Foucault, 1972/2002) and the parameters of translation (e.g. Littau, 2016) to re-think the conceptual significance of accounting as constitutive of our “literate modes” of thinking, acting and “languaging in general”.FindingsSpecific reflections are offered on how the accounting statement, as mathematically regularised naming of what “ought” to be counted, is then evaluated against what is counted, thus generating a first discourse of the norm and a first accounting-based apparatus for governing the state. The authors analyse how the non-glottographic statement is constructed and read not as linear flow of signs but as simulacrum; and on how the accounting statement poses both the practical issue of how to translate non-linear flow statements, and the conceptual problem of how to think this statement form’s general translatability, given its irreducibility to the linear narrative statement form.Originality/valueThe paper pioneers in approaching accounting as statement form in a way that analyses the differences that flow from its non-glottographic status.

Sex bias in biomedical and natural science research has been prevalent for decades. In many cases, the female estrous cycle was thought to be too complex an issue to model for, and it was thought to be simpler to only use males in studies. At times, particularly when studying efficacy and safety of new therapeutics, this sex bias has resulted in over- and under-medication with associated deleterious side effects in women. Many sex differences have been recognized that are unrelated to hormonal variation occurring during the estrous cycle. Sex bias also creates animal welfare challenges related to animal over-production and wastage, insufficient consideration of welfare (and scientific) impact related to differential housing of male vs female animals within research facilities, and a lack of understanding regarding differential requirements for pain recognition and alleviation in male versus female animals. Although many funding and government agencies require both sexes to be studied in biomedical research, many disparities remain in practice. This requires further enforcement of expectations by the Institutional Animal Care and Use Committee when reviewing protocols, research groups when writing grants, planning studies, and conducting research, and scientific journals and reviewers to ensure that sex bias policies are enforced.

This paper aims at studying the impact and translatability of modality in legal contracts and agreements from English into Arabic, and vice versa. It is an attempt to examine how modal verbs used in legalese can affect and be translated between the study two languages, Arabic and English. Randomly twenty legal texts covering the commonly used modal verbs in contracts and agreements were selected and translated into Arabic. The modality used in such contracts and agreements had different meanings and scopes where directly or indirectly brought about its impact on the contexts and extent of translatability. As a result of such attempt, it has become definitely clear that modal verbs play a significant role in shaping the degree of relationship between those concerned in a certain legal text. Also, it is necessary to pinpoint that modal auxiliary verbs used in daily conversation and writing are not as same as the ones used in legal domain. In daily English language, the function of shall is to make a reference to futurity, while may make a reference to permissions. This study came up with results disclosing that the use of modality has a wide range of impact on the content of legal texts within a certain contract or agreement. Legal modality is an indication to rights and duties, hence there shall be a good mastery of the function of modality, to know its impact and translatability between the study languages.

Any pentagonal quasigroup is proved to have the product , where is an Abelian group, is its regular automorphism satisfying and is the identity mapping. All Abelian groups of order inducing pentagonal quasigroups are determined. The variety of commutative, idempotent, medial groupoids satisfying the pentagonal identity is proved to be the variety of commutative, pentagonal quasigroups, whose spectrum is . We prove that the only translatable commutative pentagonal quasigroup is . The parastrophes of a pentagonal quasigroup are classified according to well-known types of idempotent translatable quasigroups. The translatability of a pentagonal quasigroup induced by the group and its automorphism is proved to determine the value of and the range of values of