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Background: This study investigated the safety, reactogenicity, and immunogenicity in healthy subjects of a Clostridioides difficile vaccine candidate with/without adjuvant, targeting toxins A and B., Methods: In this first-in-human, phase 1, observer-blind study, subjects aged 18-45 years were randomized to receive F2 antigen (n = 10) or placebo (n = 10), and subjects aged 50-70 years to receive F2 antigen plus AS01 adjuvant (n = 45), F2 antigen (n = 45), or placebo (n = 30) in 2 doses 1 month apart. A subcohort (n = 40) received a third dose 15 months later. Solicited adverse events (AEs) were recorded for 7 days and unsolicited AEs for 30 days after each dose. Immunogenicity was assessed at baseline and after each dose., Results: Solicited AEs were transient and most frequent in subjects receiving F2 antigen plus AS01. No serious AEs were considered related to study vaccine. Immunogenicity was substantially higher in subjects receiving F2 antigen plus AS01 than subjects receiving F2 antigen alone. A third dose increased the immune response in subjects with baseline neutralization titers below the assay lower limit of quantitation., Conclusions: The GSK C. difficile vaccine candidate was immunogenic, especially when given with AS01, and was well tolerated with an acceptable safety profile., Clinical Trial Registration: NCT04026009., Competing Interests: Potential conflicts of interest. M. C., B. d. W., G. S. F., A. L., S. M., C. S., and J. P. Y. are employees of GSK. M. E. I. was an employee of GSK at the time of the study. B. d. W., M. E. I., S. M., C. S., G. S. F., and J. P. Y. hold financial equities in GSK. B. d. W. also holds shares in Haleon. G. S. F. was an employee of Janssen Biologics, 3D-PharmXchange Consultancy, and Access to Medicine Foundation over the past 36 months. I. L.-R. reports funding from GSK to her institution for the conduct of this study; and funding to her institution for the conduct of various vaccine trials (non-C. difficile vaccine studies) from Janssen, MSD, Moderna, Curevac, Osivax, Vaccitech, Icosavax, OSE Immunotherapeutics, Icon Genetics, and Virometix. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Given the knowledge of the damage caused by prolonged invasive mechanical ventilation in premature newborns, withdrawing this support as quickly as possible is important to minimize morbidity. The aim of this study was to analyze the variables associated with extubation outcomes and to develop a predictive model for successful extubation in premature newborns., Methods: Data were obtained from a multicenter study involving six public maternity hospitals. The variables with the highest correlation to the extubation outcome were used to construct the predictive model through data analysis and machine learning methods, followed by training and testing of algorithms., Results: Data were collected from 405 premature newborns. The predictive model with the best metrics was trained and tested using the variables of gestational age, birth weight, weight at extubation, congenital infections, and time on invasive mechanical ventilation, based on 393 samples according to the extubation outcome (12 were discarded due to irretrievable missing data in important attributes). The model exhibited an accuracy of 77.78%, sensitivity of 79.41%, and specificity of 60%., Conclusion: These variables generated a predictive model capable of estimating the probability of successful extubation in premature newborns., Impact: Prolonged use of invasive mechanical ventilation in preterm newborns increases morbidity/mortality rates, emphasizing the importance of early withdrawal from invasive ventilatory support. However, the decision to extubate lacks tools with higher extubation outcome precision. The use of artificial intelligence through the construction of a predictive model can assist in the decision-making process for extubating preterm newborns based on real-world data. The implementation of this tool can optimize the decision to extubate preterm newborns, promoting successful extubation and reducing preterm newborns exposure to adverse events associated with extubation failure., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Introduction: CrossFit® is a physical training method that aims to promote physical fitness through the development of components such as aerobic capacity, strength and muscular endurance. Data regarding bruxism behaviors in CrossFit® practitioners are scarce, but previous studies have shown increased dental clenching behavior during weightlifting practices., Objective: The present study aimed to evaluate clinical signs of bruxism in CrossFit® practitioners., Methods: The sample comprised a convenience sample of CrossFit® practitioners (n=57), of both genders, aged 19-58 years. Outcome variables were as follows: Oral Behavior Checklist, the International Physical Activity Questionnaire and the Standardized Tool for the Assessment of Bruxism. Data were expressed in terms of absolute values and percentages. Spearman's correlation and Fisher exact tests were used for statistical analysis, and a significance level of 5% was considered., Results: The mean age was 32.82 years, with a female majority (63.15%). CrossFit® practitioners frequently reported clenching their teeth during training practice (61.40%) and presented linea alba (82.45%), lip impression (54.38%), tongue impression (26.31%), bone exostosis (19.29%), tooth wear (61.40%) and non-carious cervical lesions (35.09%)., Conclusions: No correlation was found between clinical signs of bruxism, oral behaviors and physical activity intensity; however, the results suggest that individuals who practice CrossFit® training have oral behaviors that can cause morpho-functional changes in the stomatognathic system, especially the habit of clenching their teeth during training. In addition, data emphasize the need for dental health education among CrossFit® practitioners, and more studies with a representative sample are necessary.

The turtle shell is a remarkable structure that has intrigued not only evolutionary biologists but also engineering and material scientists because of its multi-scale complexity and various functions. Although protection is its most apparent role, the carapace and plastron are also related to many physiological functions and their shape influences hydrodynamics and self-righting ability. As such, analysing the functional morphology of the shell could help understanding the ecology of Triassic stem-turtles, which will contribute to the century-long debate on the evolutionary origins of turtles. Here, we used 3D imaging techniques to digitize the shells of two of the earliest stem-turtle taxa, Proganochelys and Proterochersis, and submitted their models to biomechanical and shape analyses. We analysed the strength performance under five predation scenarios and tested the function of two morphological traits found in stem-turtles, the epiplastral processes and an attached pelvic girdle. The latter, also present in the crown-lineage of side-necked turtles, has been suggested to increase load-bearing capacity of the shell or to improve swimming in pleurodires. Our results do not confirm the shell-strengthening hypothesis and, together with the results of our shape analyses, suggest that at least one of the first stem-turtles (Proterochersis) was an aquatic animal., (© 2024. The Author(s).)

The osteology, neuroanatomy, and musculature are known for most primary clades of turtles (i.e., "families"), but knowledge is still lacking for one particular clade, the Carettochelyidae. Carettochelyids are represented by only one living taxon, the pig-nosed turtle Carettochelys insculpta. Here, we use micro-computed tomography of osteological and contrast-enhanced stained specimens to describe the cranial osteology, neuroanatomy, circulatory system, and jaw musculature of Carettochelys insculpta. The jaw-related myology is described in detail for the first time for this taxon, including m. zygomaticomandibularis, a muscular unit only found in trionychians. We also document a unique arterial pattern for the internal carotid artery and its subordinate branches and provide an extensive list of osteological ontogenetic differences. The present work provides new insights into the craniomandibular anatomy of turtles and will allow a better understanding of the evolutionary history of the circulatory system of trionychians and intraspecific variation among turtles., (© 2024 The Authors. The Anatomical Record published by Wiley Periodicals LLC on behalf of American Association for Anatomy.)

Paleopathology, the study of diseases and injuries from the fossil record, allows for a unique view into the life of prehistoric animals. Pathologies have nowadays been described in nearly all groups of fossil vertebrates, especially dinosaurs. Despite the large number of skeletons, pathologies had never been reported in the sauropodomorph Plateosaurus trossingensis. Here we describe the first pathologies of Plateosaurus using two individuals with pathologies in the chevrons of the tail, from the Upper Triassic of Trossingen, SW Germany. The two specimens each contain three consecutive pathological chevrons. Our results show that the pathologies were caused by external trauma in one individual and potentially tendinous trauma in the other. Healing of the lesions allowed survival of both animals. Using additional pathological specimens found in other collections and from multiple localities, we observe that 14.8% of all individuals of Plateosaurus contain pathologies within their chevrons, suggesting it was a vulnerable bone., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Schaeffer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Late Jurassic rhynchocephalians from the Solnhofen Archipelago have been known for almost two centuries. The number of specimens and taxa is constantly increasing, but little is known about the ontogeny of these animals. The well-documented marine taxon Pleurosaurus is one of such cases. With over 15 described (and many more undescribed) specimens, there were no unambiguous juveniles so far. Some authors have argued that Acrosaurus, another common component of the Solnhofen Archipelago herpetofauna, might represent an early ontogenetic stage of Pleurosaurus, but the lack of proper descriptions for this taxon makes this assignment tentative, at best. Here, we describe the first unambiguous post-hatchling juvenile of Pleurosaurus and tentatively attribute it to Pleurosaurus cf. P. ginsburgi. The new specimen comes from the Lower Tithonian of the Mörnsheim Formation, Germany. This specimen is small, disarticulated, and incomplete, but preserves several of its craniomandibular bones and presacral vertebrae. It shares with Pleurosaurus a set of diagnostic features, such as an elongated and triangular skull, a low anterior flange in its dentition, and an elongated axial skeleton. It can be identified as a juvenile due to the presence of an unworn dentition, well-spaced posteriormost dentary teeth, a large gap between the last teeth and the coronoid process of the dentary, and poorly ossified vertebrae with unfused neural arches. Acrosaurus shares many anatomical features with both this specimen and Pleurosaurus, which could indicate that the two genera are indeed synonyms. The early ontogenetic stage inferred for the new Pleurosaurus specimen argues for an even earlier ontogenetic placement for specimens referred to Acrosaurus, the latter possibly pertaining to hatchlings., (© 2024 American Association for Anatomy.)

The hyoid apparatus of tetrapods is highly diverse in its morphology. It plays an important role in feeding, breathing, sound production, and various other behaviors. Among turtles, the diversity of the hyoid apparatus has been recurrently linked to their habitat. The ossification of the hyoid corpus is often the main trait used in correlations with "niche" occupancy, an ossified corpus being associated with aquatic environments and a cartilaginous corpus with terrestrial life. Most studies conducted so far have focused on species belonging to Testudinoidea, the clade that occupies the biggest diversity of habitats (i.e., terrestrial, semi-terrestrial, and aquatic animals), while other turtle lineages have been largely understudied. We assessed the adult anatomy of the hyoid apparatus of 92 turtle species from all "families", together with ossification sequences from embryological series of 11 species, some described for the first time here. Using nearly 40 different discrete anatomical characters, we discuss the evolutionary patterns and the biological significance of morphological transformations in the turtle hyoid elements. Morphological changes are strongly associated to feeding modes, with several instances of convergent evolution within and outside the Testudines clade, and are not as strongly connected to habitat as previously thought. Some of the hyoid character states we describe are diagnostic of specific turtle clades, thus providing phylogenetically relevant information., Competing Interests: The authors declare no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology.)

Sepsis and acute kidney injury (AKI) are two major public health concerns that contribute significantly to illness and death worldwide. Early diagnosis and prompt treatment are essential for achieving the best possible outcomes. To date, there are no specific clinical, imaging, or biochemical indicators available to diagnose sepsis, and diagnosis of AKI based on the KDIGO criterion has limitations. To improve the diagnostic process for sepsis and AKI, it is essential to continually evolve our understanding of these conditions. Delays in diagnosis and appropriate treatment can have serious consequences. Sepsis and AKI often occur together, and patients with kidney dysfunction are more prone to developing sepsis. Therefore, identifying potential biomarkers for both conditions is crucial. In this review, we talk about the main biomarkers that evolve the diagnostic of sepsis and AKI, namely neutrophil gelatinase-associated lipocalin (NGAL), proenkephalin (PENK), and cell-free DNA.

Dihammaphora Chevrolat (Arc Nat 1:50-54, 1859) is one of the most diverse genera of Rhopalophorini, with 46 species. It is characterized mainly by species with antennae short and subserrated, with 10 or 11 antennomeres, prothorax cylindrical, and elytra punctuated. In this study, two new species of Dihammaphora are described and illustrated, new records are provided to 11 species, and taxonomic notes are given to six species of the genus. We examined 55 specimens and identified 16 species of the genus Dihammaphora, including Dihammaphora aurea sp. nov. from Honduras, and Dihammaphora cruzi sp. nov. from Brazil. The number of species of Dihammaphora is increased to 48, two of them in Central America, resulting in seven species for this region. In Brazil, 24 species are now recognized, being the country with the largest number of species of the genus. This study shows that there is still a deficit of knowledge about the diversity and distribution of Dihammaphora., (© 2024. Sociedade Entomológica do Brasil.)

Overkill of large mammals is recognized as a key driver of Pleistocene megafaunal extinctions in the Americas and Australia. While this phenomenon primarily affected mega-mammals, its impact on large Quaternary reptiles has been debated. Freshwater turtles, due to the scarcity of giant forms in the Quaternary record, have been largely neglected in such discussions. Here we present a new giant podocnemidid turtle, Peltocephalus maturin sp. nov., from the Late Pleistocene Rio Madeira Formation in the Brazilian Amazon, that challenges this assumption. Morphological and phylogenetic analyses of the holotype, a massive partial lower jaw, reveal close affinities to extant Amazonian species and suggest an omnivorous diet. Body size regressions indicate Pe. maturin possibly reached about 180 cm in carapace length and is among the largest freshwater turtles ever found. This finding presents the latest known occurrence of giant freshwater turtles, hinting at coexistence with early human inhabitants in the Amazon.

A new species, Parahephaestion mimicus sp. nov., is described. Two species are newly recorded for the Brazilian state of Minas Gerais: Sphalloeme costipennis Melzer, 1928 (Cerambycinae, Oemini) and Oreodera omissa Melzer, 1932 (Lamiinae, Acrocinini). Six species are new records for the RPPN Sanctuary of Caraa, (Brazil, Minas Gerais): Thalusia atrata (Melzer, 1918) (Cerambycinae, Rhopalophorini), Trachelissa pustulata (Audinet-Serville, 1834) (Cerambycinae, Trachyderini), Ateralphus dejeani (Lane, 1973) (Lamiinae, Acanthoderini), Phacellocera plumicornis (Klug, 1825) (Lamiinae, Anisocerini), Oncideres impluviata (Germar, 1823), and Psyllotoxus griseocinctus Thomson, 1868 (Lamiinae, Onciderini).

Metabolism, mainly driven by oxygen consumption, plays a key role in life, as it is one of the main ways to respond to extreme temperatures through internal processes. Theba pisana , a widespread Mediterranean land snail, is exposed to a wide range of ambient temperature. In this species the oxygen consumption was tested as a response variable by multiple regression modelling on the "explanatory" variables shell-free mass, temperature, and relative humidity. Our results show that the oxygen consumption of T. pisana can be well described (73.1%) by these three parameters. In the temperature range from 23 °C to 35 °C the oxygen consumption decreased with increasing temperature. Relative humidity, in the range of 67% to 100%, had the opposite effect: if it increases, oxygen consumption will increase as well. Metabolism is proportional to an individual's mass to the power of the allometric scaling exponent α , which is between 0.62 and 0.77 in the mentioned temperature range. CT scans of shells and gravimetry revealed the shell-free mass to be calculated by multiplying the shell diameter to the third power by 0.2105. Data were compared to metabolic scaling exponents for other snails reported in the literature.

Amazonian várzeas are annually flooded for at least five months, which influences the occurence of waterbirds. This study investigates the species richness and composition, and individual abundance of waterbird assemblages in 10 várzea lakes on the lower Amazon River across a seasonal cycle. A total of 7,970 birds belonging to 52 species were recorded. Of these, 25 species were present in all four phases of the cycle, 5 in three phases, 10 in two and 12 during just one phase. Families with the highest species richness were Ardeidae and Scolopacidae. In the dry season, we recorded the highest species richness and the highest total abundance values. Thirteen species showed variation in abundance across the seasonal cycle, most being more abundant in the dry season Variation in species richness, abundance, and composition suggests that research on waterbird assemblages in Amazonian várzeas should consider all phases of the seasonal cycle. Furthermore, the occurrence of several migratory species demonstrates the importance of this region for the conservation of this group. Multi-year monitoring would contribute to a better understanding of the dynamics of Amazonian várzea waterbird assemblages.

Organisms display a considerable variety of body sizes and shapes, and macroevolutionary investigations help to understand the evolutionary dynamics behind such variations. Turtles (Testudinata) show great body size disparity, especially when their rich fossil record is accounted for. We explored body size evolution in turtles, testing which factors might influence the observed patterns and evaluating the existence of long-term directional trends. We constructed the most comprehensive body size dataset for the group to date, tested for correlation with paleotemperature, estimated ancestral body sizes, and performed macroevolutionary model-fitting analyses. We found no evidence for directional body size evolution, even when using very flexible models, thereby rejecting the occurrence of Cope's rule. We also found no significant effect of paleotemperature on overall through-time body size patterns. In contrast, we found a significant influence of habitat preference on turtle body size. Freshwater turtles display a rather homogeneous body size distribution through time. In contrast, terrestrial and marine turtles show more pronounced variation, with terrestrial forms being restricted to larger body sizes, up to the origin of testudinids in the Cenozoic, and marine turtles undergoing a reduction in body size disparity after the extinctions of many groups in the mid-Cenozoic. Our results, therefore, suggest that long-term, generalized patterns are probably explained by factors specific to certain groups and related at least partly to habitat use., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Cerdocyonina is a clade composed by the South-American canids in which the bush dog (Speothos venaticus) is one of the most elusive species. Known for its unique morphology within the group, this small, bear-like faced canid is the only member of the clade adapted to hypercarnivory, an almost exclusively meat-based diet currently present only in usually large, pack-hunting canids such as the grey wolf (Canis lupus). However, much of the biology of the bush dog is poorly understood, and inferences about its ecology, hunting strategies and diet are usually based on observation of captive individuals and anecdotal records, with reduced quantitative data to offer support. Here, we investigated the craniomandibular functional morphology of the bush dog through finite element analysis (FEA). FEA was employed to model the biting behaviour and to create extrinsic and intrinsic functional scenarios with different loads, corresponding to different bites used to subdue and process the prey. For comparison, the same modelling was applied to the skull of a grey wolf and a grey fox (Urocyon cinereoargenteus). Our analysis showed that the bush dog's responses to loading are more similar to the wolf's than to the fox's in most scenarios, suggesting a convergent craniomandibular functional morphology between these two hypercarnivorous species, despite their distinct phylogenetic positions and body sizes. Differences between the three taxa are noteworthy and suggested to be related to the size of the usual prey. The modelled bite force for the bush dog is relatively strong, about half of that estimated for the wolf and about 40% stronger than the fox's bite. The results strengthen with quantitative data the inferences of the bush dog as a pack-hunting predator with prey size similar to its own, such as large rodents and armadillos, being specialised in subduing and killing its prey using multiple bites. Its similarity to the wolf also confirms anecdotal accounts of predation on mammals that are much larger than itself, such as peccaries and tapirs. These data highlight the ecological specialisation of this small canid in a continent where large, pack-hunting canids are absent., (© 2022 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.)

The primary purpose of this study was to assess the translatability of preclinical to early clinical tolerable and pharmacologically active dose ranges for central nervous system (CNS) active drugs. As a part of this, IBs were reviewed on reporting quality. Investigator's Brochures (IBs) of studies performed at the Centre for Human Drug Research (CHDR) reporting statistically significant results of CNS activity related to the drug's mechanism of action were included. The quality of IBs was assessed based on the presence of a rationale for the chosen animal model, completeness of pharmacokinetic (PK) results in reporting and internal validity information of the preclinical evidence. The IB-derisk tool was used to generate preclinical and early clinical data overviews data. For each compound, the overlap between pharmacologically active dose ranges and well-tolerated levels was calculated for three pharmacokinetic (PK) parameters: human equivalent dose (HED), maximum plasma concentration (C max ) and area under the curve (AUC). Twenty-five IBs were included. In general, the quality of reporting in IBs was assessed as poor. About a third of studies did not explore the entire concentration-effect curve (pre)clinically. Single dose tolerability ranges were most accurately predicted by C max . Human equivalent dose and AUC were the best predictors of pharmacologically active ranges. Tolerable and pharmacologically active dose ranges in healthy volunteers can be reasonably well predicted from preclinical data with the IB-derisk tool. The translatability of preclinical studies can be improved by applying a higher reporting standard in IBs including comparable PK measurements across all preclinical and clinical studies., (© 2023. The Author(s).)

Fossils of Cretaceous sea turtles adapted to an open marine lifestyle remain rare finds to date. Furthermore, the relationships between extant sea turtles, chelonioids, and other Mesozoic marine turtles are still contested, with one key species being Santanachelys gaffneyi Hirayama, 1998, long considered the earliest true sea turtle. The species is an Early Cretaceous member of Protostegidae , a controversial clade either placed within or closely related to Chelonioidea or, alternatively, along the stem lineage of hidden-neck turtles ( Cryptodira ) and representing an independent open marine radiation. Santanachelys gaffneyi is one of the most completely preserved early protostegids and is therefore critical for establishing the global phylogenetic position of the group. However, the single known specimen of this taxon is yet to be described in detail. Here we describe a second specimen of Santanachelys gaffneyi from its type horizon, the Romualdo Formation (late Aptian) of the Santana Group of the Araripe basin, NE Brazil. The skeletal elements preserved include the posterior part of the skull, neck vertebrae, shoulder girdle, anterior-most and left/central part of the carapace with few peripherals, and plastron lacking most of the hyoplastra. The remaining part of the carapace was apparently completed by fossil dealers using an anterior part of the pleurodiran Araripemydidae , tentatively identified as a shell portion of cf. Araripemys barretoi, a more common Santana fossil turtle, among other indeterminate turtle shell fragments. The purpose of this paper is to report the repatriation of the specimen to Brazil and to provide a preliminary description., Supplementary Information: The online version contains supplementary material available at 10.1186/s13358-023-00271-9., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2023.)

Successful drug discovery is like finding oases of safety and efficacy in chemical and biological deserts. Screens in disease models, and other decision tools used in drug research and development (R&D), point towards oases when they score therapeutic candidates in a way that correlates with clinical utility in humans. Otherwise, they probably lead in the wrong direction. This line of thought can be quantified by using decision theory, in which 'predictive validity' is the correlation coefficient between the output of a decision tool and clinical utility across therapeutic candidates. Analyses based on this approach reveal that the detectability of good candidates is extremely sensitive to predictive validity, because the deserts are big and oases small. Both history and decision theory suggest that predictive validity is under-managed in drug R&D, not least because it is so hard to measure before projects succeed or fail later in the process. This article explains the influence of predictive validity on R&D productivity and discusses methods to evaluate and improve it, with the aim of supporting the application of more effective decision tools and catalysing investment in their creation., (© 2022. Springer Nature Limited.)

Background: The association between lipoprotein levels and late-onset neonatal sepsis has shown controversial results. The aims are to assess lipid profile, cytokines, and Monocyte-to-HDL (M/H) ratio as diagnostic and prognostic markers for late-onset neonatal sepsis., Methods: This prospective study included 49 septic neonates and 17 controls. Cholesterol (CT), Triglyceride (TG), Very-Low-Density (VLDLc), Low-Density (LDLc), and High-Density Lipoproteins (HDLc) were measured at admission (D0) and on days 3, 7 and 10 to evaluate septic shock outcomes. Cytokines and monocytes were evaluated by flow cytometry., Results: Septic newborns showed higher IL-6 and IL-8 at D0 and CT levels on D7 and on D10, which also presented higher TG, VLDLc and non-HDL cholesterol concentrations than controls. The septic shock group (n = 22) revealed a higher number of male subjects, CRP, IL-6, IL-8 and IL-10 levels, while lower TG, HDLc, monocyte numbers and M/H ratio at admission compared to the non-shock group (n = 27). M/H ratio and non-HDL cholesterol on D0 were risk factors for septic shock (OR = 0.70, 0.49‒0.99; OR = 0.96, 0.92‒0.99, respectively). Decreasing levels from D0 to D3 of CT (OR = 0.96, 0.93‒0.99), VLDLc (OR = 0.91, 0.85‒0.98), and non-HDL cholesterol (OR = 0.92, 0.87‒0.98) were also predictors of septic shock., Conclusions: Lower M/H ratios and non-HDL cholesterol at admission and decreasing levels of cholesterol, VLDLc and non-HDL cholesterol during a hospital stay are associated with the development of septic shock in newborns with late-onset neonatal sepsis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Turtles have a highly modified body plan, including a rigid shell that constrains postcranial anatomy. Skull morphology and neck mobility may therefore be key to ecological specialization in turtles. However, the ecological signal of turtle skull morphologies has not been rigorously evaluated, leaving uncertainties about the roles of ecological adaptation and convergence. We evaluate turtle cranial ecomorphology using three-dimensional geometric morphometrics and phylogenetic comparative methods. Skull shape correlates with allometry, neck retraction capability, and different aquatic feeding ecologies. We find that ecological variables influence skull shape only, whereas a key functional variable (the capacity for neck retraction) influences both shape and size. Ecology and functional predictions from three-dimensional shape are validated by high success rates for extant species, outperforming previous two-dimensional approaches. We use this to infer ecological and functional traits of extinct species. Neck retraction evolved among crownward stem-turtles by the Late Jurassic, signaling functional decoupling of the skull and neck from the shell, possibly linked to a major episode of ecomorphological diversification. We also find strong evidence for convergent ecological adaptations among marine groups. This includes parallel loss of neck retraction, evidence for active hunting, possible grazing, and suction feeding in extinct marine groups. Our large-scale assessment of dietary and functional adaptation throughout turtle evolution reveals the timing and origin of their distinct ecomorphologies, and highlights the potential for ecology and function to have distinct effects on skull form., (© 2022 The Authors. Evolution published by Wiley Periodicals LLC on behalf of The Society for the Study of Evolution.)

The labyrinth of the vertebrate inner ear is a sensory system that governs the perception of head rotations. Central hypotheses predict that labyrinth shape and size are related to ecological adaptations, but this is under debate and has rarely been tested outside of mammals. We analyze the evolution of labyrinth morphology and its ecological drivers in living and fossil turtles, an understudied group that underwent multiple locomotory transitions during 230 million years of evolution. We show that turtles have unexpectedly large labyrinths that evolved during the origin of aquatic habits. Turtle labyrinths are relatively larger than those of mammals, and comparable to many birds, undermining the hypothesis that labyrinth size correlates directly with agility across vertebrates. We also find that labyrinth shape variation does not correlate with ecology in turtles, undermining the widespread expectation that reptilian labyrinth shapes convey behavioral signal, and demonstrating the importance of understudied groups, like turtles., (© 2022. The Author(s).)

Progressive familial intrahepatic cholestasis type 2 (PFIC2) is a rare autosomal recessive disorder caused by mutations in the ABCB11 gene. Clinical manifestations include cholestasis with low γ-glutamyltransferase (GGT), hepatosplenomegaly, and severe pruritus. Liver transplantation is required for individuals with progressive liver disease or failure of the bypass procedure and has been considered curative. However, in the case of PFIC2, although bile salt excretory pump (BSEP) deficiency is a liver-specific condition rather than a systemic disease, evidence of recurrent BSEP disease has been shown in a small proportion of allografts. We describe an unusual case of a 21-year-old individual with PFIC2 and evidence of recurrent BSEP disease after liver transplantation, with clinical and laboratory improvement after pulse therapy with methylprednisolone for 3 days and adjustment of oral immunosuppression. This case report highlights the recurrence of PFIC2 in patients post liver transplant. It also emphasizes the importance of clinical suspicion, which should be considered in cases of posttransplant cholestasis in PFIC2 patients, especially those with low γ-glutamyltransferase (GGT) and without signs of acute graft rejection. Having knowledge of the condition favors a targeted diagnostic approach and contributes to early therapeutic management and a higher success rate., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The association between ulcerative colitis (UC) and primary sclerosing cholangitis has been described for several years and can be classified as having a distinct disease phenotype from inflammatory bowel diseases (IBD). The simultaneous occurrence of decompensated liver disease requiring liver transplant and active IBD is a management challenge, considering that these patients may be at increased risk of infections, thromboembolic events, bleeding, and drug hepatotoxicity., Case Presentation: We describe a case of a 37-year-old patient with UC and sclerosing cholangitis presenting with severe decompensated rectocolitis complicated with thromboembolic phenomena and severe liver dysfunction who underwent liver transplant while using biological therapy to control bowel disease., Conclusions: This case highlights the evolution of sclerosing cholangitis to liver transplant in patients with decompensated UC. Despite the risk of recurrence, primary sclerosing cholangitis has excellent results after liver transplant. Despite the use of immunosuppression after liver transplant, biological therapy may be necessary to control IBD., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Populations of Culex quinquefasciatus Say, 1823 (Diptera: Culicidae) have shown resistance to insecticides of the carbamate and organophosphate classes. The objective of this study was to assess the susceptibility of C. quinquefasciatus larvae to essential oils from leaves of Eugenia uniflora L., Melaleuca armillaris (Sol. ex Gaertn.) Sm., and Schinus molle L and C. quinquefasciatus larvae's biochemical responses after their exposure to these leaves. The essential oils were chemically analyzed by GC and GC/MS. First, the lethal concentration for 50% (LC 50 ) values was estimated using different concentrations of essential oils and probit analysis. The larvae were exposed for 1 h at the LC 50 estimated for each essential oil. The susceptibility of the larvae to essential oils was evaluated using the following biochemical parameters: concentrations of total protein and reduced glutathione; levels of production of hydrogen peroxide and lipid peroxidation; and the activity of the enzyme acetylcholinesterase (AChE). The main chemical constituents in E. uniflora were E-β-ocimene, curzerene, germacrene B, and germacrone; in M. armillaris were 1,8-cineole and terpinolene; and in S. molle were sabinene, myrcene, and sylvestrene. The essential oils had LC 50 values between 31.52 and 60.08 mg/L, all of which were considered effective. All of them also promoted changes in biochemical parameters when compared to the control treatment. The essential oils of S. molle and E. uniflora inhibited the activity of the AChE enzyme, and the essential oil of M. armillaris increased it. All essential oils had larvicidal activity against C. quinquefasciatus, but the essential oil of E. uniflora was the most efficient. Thus, the findings of the present study suggest that the essential oil of E. uniflora can be considered promising for the development of botanical larvicides., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: This study evaluated the effects of 12 weeks of karate training on cardiometabolic parameters, oxidative stress, and inflammation in adolescents with overweight and obesity., Method: Seventy adolescents were randomized into 2 groups: control received nutritional and psychological interventions once a week for 12 weeks, and treatment received nutritional and psychological interventions once a week, plus 3 karate sessions per week, for 12 weeks. The main outcome measure was improvement in cardiometabolic parameters, oxidative stress, and inflammation., Results: After the intervention period, the treatment group showed a reduction in resting heart rate (77.86 [10.89]), high-density lipoprotein cholesterol (40.86 [8.31]), and triglycerides (75.18 [32.29]) and an increase in low-density lipoprotein cholesterol (95.64 [42.53]) in relation to pretraining. Regarding oxidative stress markers, there was a reduction in protein carbonylation (0.07 [0.06]) and nitric oxide (1.39 [1.11]) and an increase in superoxide dismutase (0.68 [0.31]) and glutathione (0.11 [0.08]) compared with pretraining. With respect to inflammation, adiponectin increased (14.54 [5.36]) after the intervention when compared with preintervention., Conclusion: The study concluded that the intervention may improve cardiometabolic parameters, oxidative stress, and inflammation in adolescents with overweight and obesity. Long-term effects need to be evaluated.

Advanced glycation end products (AGEs) are independently related to cardiovascular disease (CVD) and favor cholesterol and oxysterol accumulation in macrophage foam cells. Soluble RAGE (sRAGE) impairs cellular AGE signaling alleviating the deleterious effects of AGE in atherogenesis. The association between plasma AGEs and sRAGE with the content of cholesterol, markers of cholesterol synthesis and absorption, and oxysterols in atherosclerotic plaques was evaluated in subjects undergoing carotid endarterectomy.Plasma and carotid plaques were obtained from symptomatic ( n = 23) and asymptomatic subjects ( n = 40). Lipids from plaques were extracted and sterols (oxysterols, cholesterol, desmosterol, lathosterol, sitosterol, and campesterol) were determined by using gas chromatography/mass spectrometry. Plasma total AGEs and pentosidine were measured by using fluorimetry and sRAGE by using ELISA.In symptomatic subjects´ atherosclerotic plaques, an increased amount of cholesterol (3x) and oxysterols [7 α-hydroxycholesterol (1.4x); 7 β-hydroxycholesterol (1.2x); 25-hydroxycholesterol (1.3x); 24-hydroxycholesterol (2.7x), and 27-hydroxycholesterol, (1.15x)], with exception to 7 ketocholesterol, were found in comparison to asymptomatic individuals. Plasma total AGEs and pentosidine significantly and positively correlated to sterols accumulated in the atherosclerotic lesion, including cholesterol, desmosterol, campesterol, sitosterol, and oxysterols. On the other hand, sRAGE inversely correlated to total AGEs and pentosidine in plasma, and with major species of oxysterols, cholesterol, and markers of cholesterol synthesis and absorption in the atherosclerotic lesion. In multiple regression analyses, it was observed a significant inverse correlation between sRAGE and 24-hydroxycholesterol and desmosterol, and a positive significant correlation between pentosidine and 24-hydroxycholesterol, 27-hydroxycholesterol, and campesterol.In conclusion, the plasma concentration of AGEs and sRAGE is a tool to predict the accumulation of sterols in atherosclerotic lesions in symptomatic and asymptomatic individuals, helping to prevent and improve the management of acute cardiovascular complications.

Hibernation is a natural condition of animals that lives in the temperate zone, although some tropical lizards also experience hibernation annually, such as the lizard native from South America, Salvator merianae, or "tegu" lizard. Even though physiological and metabolic characteristic associated with hibernation have been extensively studied, possible alterations in the red blood cells (RBC) integrity during this period remains unclear. Dehydration and fasting are natural consequences of hibernating for several months and it could be related to some cellular modifications. In this study, we investigated if the osmotic tolerance of RBCs of tegu lizard under hibernation is different from the cells obtained from animals while normal activity. Additionally, we indirectly investigated if the RBCs membrane of hibernating tegus could be associated with oxidation by quantifying oxidized biomolecules and the activity of antioxidant enzymes. Our findings suggest that RBCs are more fragile during the hibernation period, although we did not find evidence of an oxidative stress scenario associated with the accentuated fragility. Even though we did not exclude the possibility of oxidative damage during hibernation, we suggested that an increased RBCs volume as a consequence of hypoosmotic blood during hibernation could also affect RBCs integrity as noted.

Many deceptive orchids present variation in floral color and fragrance. This might be advantageous for the plant, as it can disturb the associative avoidance learning of pollinators, promoting more visits to the flowers. Some studies have shown that color and fragrance can be correlated in polymorphic deceptive orchids, but these studies employed color traits based on the human visual system and not the visual perception of pollinators. Thus, we investigated the composition of the floral fragrance of Ionopsis utricularioides (Sw.) Lindl., a polymorphic deceptive orchid, and analyzed possible correlations with the floral color as seen by bees, Apis mellifera L. and Melipona quadrifasciata Lepeletier, using the color hexagon model. We found high color and fragrance intraspecific variation, as expected for deceptive species. However, we found no color-fragrance association in individuals, either by comparing fragrance profiles with the color variable saturation or by comparing them with the placement of individuals in the color hexagon for both bee species. This lack of correlation contradicts the biochemical pathway hypothesis, which proposes that associations between floral color and scent in polymorphic flowers arise from shared biochemical pathways. However, a complete absence of correlation between floral signals is consistent with selection arising through pollinator cognitive ecology. Lack of correlation would increase the floral variability perceived by bees, given their multimodal learning, and this variability could disrupt avoidance learning of deceptive flowers, thus enhancing the efficacy of the plant's deceptive pollination mechanism., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

National and international laws and regulations exist to protect animals used for scientific purposes in translational and applied research, which includes drug development. However, multiple animal models are available for each disease. We evaluated the argumentation behind the selection of a specific animal model using thematic content analysis in project applications issued in 2017-2019 in the Netherlands. In total, 125 animal models for translational and applied research from 110 project applications were assessed. Explanations to select a specific model included: the model’s availability (79%); the availability of expertise (62%); and the model showing similar disease pathology/symptoms (59%) to humans. Therefore, current selection of a specific animal model seems to be based on tradition rather than its potential predictive value for clinical outcome. The applicants’ explanations for the implementation of the 3R prin­ciples (replacement, reduction and refinement) as to the animal model were unspecific. Replacement was achieved by using data from prior in vitro studies, reduction by optimal experimental design and statistics, and refinement by reducing discomfort. Additionally, due to the stated need for a test model with high complexity (47%) and intactness (30%), the full replacement of animal models with alternative (non-live animal) approaches was thought unachievable. Without a clear, systematic and transparent justification for the selection of a specific animal model, the likelihood of poorly trans­latable research remains. It is not only up to the researcher to demonstrate this, as ethical committees and funding bodies can provide positive stimuli to drive this change.

A low-sodium (LS) diet has been shown to reduce blood pressure (BP) and the incidence of cardiovascular diseases. However, severe dietary sodium restriction promotes insulin resistance (IR) and dyslipidemia in animal models and humans. Thus, further clarification of the long-term consequences of LS is needed. Here, we investigated the effects of chronic LS on gastrocnemius gene and protein expression and lipidomics and its association with IR and plasma lipids in LDL receptor knockout mice. Three-month-old male mice were fed a normal sodium diet (NS; 0.5% Na; n = 12-19) or LS (0.06% Na; n = 14-20) over 90 days. Body mass (BM), BP, plasma total cholesterol, triacylglycerol (TG), glucose, hematocrit, and IR were evaluated. LS increased BM (9%), plasma TG (51%), blood glucose (19%), and IR (46%) when compared with the NS. RT-qPCR analysis revealed that genes involved in lipid uptake and oxidation were increased by the LS: Fabp3 (106%), Prkaa1 (46%), and Cpt1 (74%). Genes and proteins (assessed by Western blotting) involved in insulin signaling were not changed by the LS. Similarly, lipid species classically involved in muscle IR, such as diacylglycerols and ceramides detected by ultra-high-performance liquid chromatography coupled to mass spectrometry, were also unchanged by LS. Species of phosphatidylcholines (68%), phosphatidylinositol (90%), and free fatty acids (59%) increased while cardiolipins (41%) and acylcarnitines (9%) decreased in gastrocnemius in response to LS and were associated with glucose disposal rate. Together these results suggest that chronic LS alters glycerophospholipid and fatty acids species in gastrocnemius that may contribute to glucose and lipid homeostasis derangements in mice., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Theropod dinosaurs were relatively scarce in the Late Cretaceous ecosystems of southeast Brazil. Instead, hypercarnivorous crocodyliforms known as baurusuchids were abundant and probably occupied the ecological role of apex predators. Baurusuchids exhibited a series of morphological adaptations hypothesized to be associated with this ecological role, but quantitative biomechanical analyses of their morphology have so far been lacking. Here, we employ a biomechanical modelling approach, applying finite element analysis (FEA) to models of the skull and mandibles of a baurusuchid specimen. This allows us to characterize the craniomandibular apparatus of baurusuchids, as well as to compare the functional morphology of the group with that of other archosaurian carnivores, such as theropods and crocodylians. Our results support the ecological role of baurusuchids as specialized apex predators in the continental Late Cretaceous ecosystems of South America. With a relatively weak bite force (~600 N), the predation strategies of baurusuchids likely relied on other morphological specializations, such as ziphodont dentition and strong cervical musculature. Comparative assessments of the stress distribution and magnitude of scaled models of other predators (the theropod Allosaurus fragilis and the living crocodylian Alligator mississippiensis) consistently show different responses to loadings under the same functional scenarios, suggesting distinct predatory behaviors for these animals. The unique selective pressures in the arid to semi-arid Late Cretaceous ecosystems of southeast Brazil, which were dominated by crocodyliforms, possibly drove the emergence and evolution of the biomechanical features seen in baurusuchids, which are distinct from those previously reported for other predatory taxa., (© 2020 Anatomical Society.)

Previous qualitative research has suggested there are only minor differences between the db/db mouse and the Zucker Diabetic Fatty (ZDF) rat, both animal models of type 2 diabetes. However, it is not known whether these models are also comparable regarding drug response in quantitative terms (effect size). To investigate the extent of these differences, we conducted a systematic review and meta-analysis of approved drugs in these models. We searched on PubMed and Embase on July 3, 2019 for studies including either model, a monotherapy arm with an EMA/FDA approved drug for the treatment of type 2 diabetes, HbA1c assessment and a control group. Studies aimed at diabetes prevention or with surgical interventions were excluded. We calculated the Standardised Mean Difference (SMD) to compare effect sizes (HbA1c reduction) per drug and drug class across models. We included a risk of bias assessment for all included publications. A total of 121 publications met our inclusion criteria. For drugs with more than two comparisons, both models predicted the direction of the effect regarding HbA1c levels. There were no differences between the db/db mouse and ZDF rat, except for exenatide (P = 0.02) and GLP-1 agonists (P = 0.03) in which a larger effect size was calculated in the ZDF rat. Our results indicate the differences between the db/db mouse and ZDF rat are not relevant for preliminary efficacy testing. This methodology can be used to further differentiate between animal models used for the same indication, facilitating the selection of models more likely to predict human response., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Reports of a reproducibility crisis combined with a high attrition rate in the pharmaceutical industry have put animal research increasingly under scrutiny in the past decade. Many researchers and the general public now question whether there is still a justification for conducting animal studies. While criticism of the current modus operandi in preclinical research is certainly warranted, the data on which these discussions are based are often unreliable. Several initiatives to address the internal validity and reporting quality of animal studies (e.g., Animals in Research: Reporting In Vivo Experiments (ARRIVE) and Planning Research and Experimental Procedures on Animals: Recommendations for Excellence (PREPARE) guidelines) have been introduced but seldom implemented. As for external validity, progress has been virtually absent. Nonetheless, the selection of optimal animal models of disease may prevent the conducting of clinical trials, based on unreliable preclinical data. Here, we discuss three contributions to tackle the evaluation of the predictive value of animal models of disease themselves. First, we developed the Framework to Identify Models of Disease (FIMD), the first step to standardise the assessment, validation and comparison of disease models. FIMD allows the identification of which aspects of the human disease are replicated in the animals, facilitating the selection of disease models more likely to predict human response. Second, we show an example of how systematic reviews and meta-analyses can provide another strategy to discriminate between disease models quantitatively. Third, we explore whether external validity is a factor in animal model selection in the Investigator's Brochure (IB), and we use the IB-derisk tool to integrate preclinical pharmacokinetic and pharmacodynamic data in early clinical development. Through these contributions, we show how we can address external validity to evaluate the translatability and scientific value of animal models in drug development. However, while these methods have potential, it is the extent of their adoption by the scientific community that will define their impact. By promoting and adopting high quality study design and reporting, as well as a thorough assessment of the translatability of drug efficacy of animal models of disease, we will have robust data to challenge and improve the current animal research paradigm.

The origin of turtles is one of the most long-lasting debates in evolutionary research. During their evolution, a series of modifications changed their relatively kinetic and anapsid skull into an elongated akinetic structure with a unique pulley system redirecting jaw adductor musculature. These modifications were thought to be strongly correlated to functional adaptations, especially to bite performance. We conducted a series of Finite Element Analyses (FEAs) of several species, including that of the oldest fully shelled, Triassic stem-turtle Proganochelys, to evaluate the role of force distribution and to test existing hypotheses on the evolution of turtle skull architecture. We found no support for a relation between the akinetic nature of the skull or the trochlear mechanisms with increased bite forces. Yet, the FEAs show that those modifications changed the skull architecture into an optimized structure, more resistant to higher loads while allowing material reduction on specific regions. We propose that the skull of modern turtles is the result of a complex process of progressive correlation between their heads and highly flexible necks, initiated by the origin of the shell.

Clinical trial failures (>99%) in Alzheimer's disease are in stark contrast to positive efficacy data in animals. We evaluated the correlation between animal and clinical efficacy outcomes (cognition) in Alzheimer's disease using data from registered drugs as well as interventions tested in phase II or III clinical trials for Alzheimer's disease. We identified 20 interventions, which were tested in 208 animal studies in 63 different animal models. Clinical outcome was correlated with animal results in 58% of cases. But, individual animal models showed divergent results across interventions, individual interventions showed divergent results across animal models, and animal model outcomes were determined with 16 different methods. This result is unsurprising due to poor external validity (what do we model) of the animal models. Although the animal models all share Alzheimer's disease symptoms, none represents the whole syndrome. Investigators did not motivate why one model was chosen over another, and did not consider the ways the disease phenomena were generated (spontaneous, (experimentally) induced or by genetic modification), or the species characteristics, which determine the outcomes. The explanation for the lack of correlation between animal and human outcomes can be manifold: the pathogenesis of Alzheimer's disease is not reflected in the animal model or the outcomes are not comparable. Our conclusion is that currently no animal models exist which are predictive for the efficacy of interventions for Alzheimer's disease., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Noasaurines form an enigmatic group of small-bodied predatory theropod dinosaurs known from the Late Cretaceous of Gondwana. They are relatively rare, with notable records in Argentina and Madagascar, and possible remains reported for Brazil, India, and continental Africa. In south-central Brazil, the deposits of the Bauru Basin have yielded a rich tetrapod fauna, which is concentrated in the Bauru Group. The mainly aeolian deposits of the Caiuá Group, on the contrary, bear a scarce fossil record composed only of lizards, turtles, and pterosaurs. Here, we describe the first dinosaur of the Caiuá Group, which also represents the best-preserved theropod of the entire Bauru Basin known to date. The recovered skeletal parts (vertebrae, girdles, limbs, and scarce cranial elements) show that the new taxon was just over 1 m long, with a unique anatomy among theropods. The shafts of its metatarsals II and IV are very lateromedially compressed, as are the blade-like ungual phalanges of the respective digits. This implies that the new taxon could have been functionally monodactyl, with a main central weight-bearing digit, flanked by neighbouring elements positioned very close to digit III or even held free of the ground. Such anatomical adaptation is formerly unrecorded among archosaurs, but has been previously inferred from footprints of the same stratigraphic unit that yielded the new dinosaur. A phylogenetic analysis nests the new taxon within the Noasaurinae clade, which is unresolved because of the multiple alternative positions that Noasaurus leali can acquire in the optimal trees. The exclusion of the latter form results in positioning the new dinosaur as the sister-taxon of the Argentinean Velocisaurus unicus.

Sporotrichosis is an infection caused by the fungus of the Sporothrix schenckii complex and can be particularly harmful in immunocompromised patients. We report the case of a 26-year-old male patient with a previous history of pulmonary infection who underwent a liver transplant for Budd-Chiari syndrome. After the procedure, he presented with persistent fever and leukocytosis. On the 13th post-operative day, he was diagnosed with thrombosis of the hepatic artery and underwent a second liver transplant 15 days after the first procedure. After the retransplant, he presented daily episodes of fever, even after the use of several antimicrobial, antiviral, and antifungal agents. A number of negative cultures from different sites were obtained. After an acute episode of mental confusion, the growth of S schenckii was observed in cultures from cerebrospinal fluid and ascites obtained from a diagnostic paracentesis. Treatment with amphotericin B was started but the patient died on the fourth day of antifungal treatment, from a massive gastrointestinal hemorrhage. We found no previous report in the literature of spontaneous dissemination of S schenckii to the abdominal cavity causing peritonitis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Piramys auffenbergi was described as an emydine turtle based on a well-preserved skull retrieved from late Miocene deposits exposed on Piram Island, India. The description and figures provided in the original publication are vague and do not support assignment to Emydinae. This taxon has mostly been ignored by subsequent authors., Material and Methods: We reexamine the holotype specimen, provide an extensive description and diagnosis for Piramys auffenbergi , and include this taxon in a global character-taxon matrix for Pleurodira., Results: The presence of a processus trochlearis pterygoidei conclusively shows pleurodiran affinities for Piramys auffenbergi . Inclusion of this taxon in a phylogenetic analysis retrieves it within Stereogenyini closely related to the Asian taxa Shweboemys pilgrimi and Brontochelys gaffneyi ., Discussion: Our reexamination of the holotype of Piramys auffenbergi confidently rejects the original assessment of this taxon as an emydine testudinoid and conclusively shows affinities with the pleurodiran clade Stereogenyini instead. Even though most taxa from this lineage are thought to be coastal turtles, all Asian stereogenyines were collected from continental deposits, suggesting a more diverse paleoecology for the group., Competing Interests: The authors declare that they have no competing interests.