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This document is a correction notice for an article titled "The BRD4 inhibitor JQ1 augments the antitumor efficacy of abemaciclib in preclinical models of gastric carcinoma." The authors identified minor errors in the image-typesetting in Figure 3 of the original article. The image for the NCI-N87 cell line in Figure 3C was mistakenly included, and the corresponding statistical analysis for NCI-N87 in Figure 3D needs to be corrected. The corrected figure has been provided, and the correction does not affect the results or conclusions of the paper. The correction notice is authored by Mei Feng, Hao Xu, Wenyuan Zhou, and Yisheng Pan. [Extracted from the article]

In a recent study by Mennitti et al., the authors concluded that oligofructose supplementation during pregnancy and lactation impairs offspring development. However, the data reported in this article have limitations and should be interpreted with caution. A conclusion with respect to offspring development does not seem justified. [ABSTRACT FROM AUTHOR]

Bacteriophages (phages) may be used as an alternative to antibiotic therapy for combating infections caused by multidrug-resistant bacteria. In the last decades, there have been studies concerning the use of phages and antibiotics separately or in combination both in animal models as well as in humans. The phenomenon of phage–antibiotic synergy, in which antibiotics may induce the production of phages by bacterial hosts has been observed. The potential mechanisms of phage and antibiotic synergy was presented in this paper. Studies of a biofilm model showed that a combination of phages with antibiotics may increase removal of bacteria and sequential treatment, consisting of phage administration followed by an antibiotic, was most effective in eliminating biofilms. In vivo studies predominantly show the phenomenon of phage and antibiotic synergy. A few studies also describe antagonism or indifference between phages and antibiotics. Recent papers regarding the application of phages and antibiotics in patients with severe bacterial infections show the effectiveness of simultaneous treatment with both antimicrobials on the clinical outcome. [ABSTRACT FROM AUTHOR]

300 million people live with at least one of 6,000 rare diseases worldwide. However, rare disease research is not always reviewed with scrutiny, making it susceptible to what the author refers to as nontransparent science. Nontransparent science can obscure animal model flaws, misguide medicine regulators and drug developers, delay or frustrate orphan drug development, or waste limited resources for rare disease research. Flawed animal models not only lack pharmacologic relevance, but also give rise to issue of clinical translatability. Sadly, these consequences and risks are grossly overlooked. Nontransparency in science can take many forms, such as premature publication of animal models without clinically significant data, not providing corrections when flaws to the model are discovered, lack of warning of critical study limitations, missing critical control data, questionable data quality, surprising results without a sound explanation, failure to rule out potential factors which may affect study conclusions, lack of sufficient detail for others to replicate the study, dubious authorship and study accountability. Science has no boarders, neither does nontransparent science. Nontransparent science can happen irrespective of the researcher's senority, institutional affiliation or country. As a patient-turned researcher suffering from Bietti crystalline dystrophy (BCD), I use BCD as an example to analyze various forms of nontransparent science in rare disease research. This article analyzes three papers published by different research groups on Cyp4v3−/−, high-fat diet (HFD)-Cyp4v3−/−, and Exon1-Cyp4v3−/− mouse models of BCD. As the discussion probes various forms of nontransparent science, the flaws of these knockout mouse models are uncovered. These mouse models do not mimic BCD in humans nor do they address the lack of Cyp4v3 (murine ortholog of human CYP4V2) expression in wild type (WT) mouse retina which is markedly different from CYP4V2 expression in human retina. Further, this article discusses the impact of nontransparent science on drug development which can lead to significant delays ultimately affecting the patients. Lessons from BCD research can be helpful to all those suffering from rare diseases. As a patient, I call for transparent science in rare disease research. [ABSTRACT FROM AUTHOR]

Certain polymeric materials such as polyurethanes (PUs) are the most prevalent class of used biomaterials in regenerative medicine and have been widely explored as vascular substitutes in several animal models. It is thought that PU-based biomaterials possess suitable hemo-compatibility with comparable performance related to the normal blood vessels. Despite these advantages, the possibility of thrombus formation and restenosis limits their application as artificial functional vessels. In this regard, various surface modification approaches have been developed to enhance both hemo-compatibility and prolong patency. While critically reviewing the recent advances in vascular tissue engineering, mainly PU grafts, this paper summarizes the application of preferred cell sources to vascular regeneration, physicochemical properties, and some possible degradation mechanisms of PU to provide a more extensive perspective for future research. [ABSTRACT FROM AUTHOR]

Background: Synovitis is an inflammation-related disease linked to rheumatoid arthritis, osteoarthritis, infections and trauma. This inflammation is accompanied by immune cells infiltration which initiates an inflammatory response causing pain, discomfort and affecting the normal joint function. The treatment of synovitis is based on the administration of anti-inflammatory drugs or biological agents such as platelet rich plasma and mesenchymal stem cells. However, the evaluation and validation of more effective therapies of synovitis requires the establishment of clinically relevant animal models. Results: In this study, Large White pigs were pre-immunized to evaluate an antigen-induced synovitis. The immune monitoring of synovial fluids in this model allowed us the identification of IL-12p40 and T cell subsets as immune biomarkers. Moreover, the evolution of synovitis was performed by arthroscopic procedures and kinetic analysis. In summary, this paper describes an animal model of antigen-induced synovitis to be used in the evaluation of anti-inflammatory therapies. Conclusions: The novelty of this paper lies in the development of a clinically relevant model of synovitis which permits the simultaneous evaluation of synovitis from an immunological, surgical and kinetic point of view. [ABSTRACT FROM AUTHOR]

Background: Animal models of human behavioural deficits involve conducting experiments on animals with the hope of gaining new knowledge that can be applied to humans. This paper aims to address risks, biases, and fallacies associated with drawing conclusions when conducting experiments on animals, with focus on animal models of mental illness. Conclusions: Researchers using animal models are susceptible to a fallacy known as false analogy, where inferences based on assumptions of similarities between animals and humans can potentially lead to an incorrect conclusion. There is also a risk of false positive results when evaluating the validity of a putative animal model, particularly if the experiment is not conducted double-blind. It is further argued that animal model experiments are reconstructions of human experiments, and not replications per se, because the animals cannot follow instructions. This leads to an experimental setup that is altered to accommodate the animals, and typically involves a smaller sample size than a human experiment. Researchers on animal models of human behaviour should increase focus on mechanistic validity in order to ensure that the underlying causal mechanisms driving the behaviour are the same, as relying on face validity makes the model susceptible to logical fallacies and a higher risk of Type 1 errors. We discuss measures to reduce bias and risk of making logical fallacies in animal research, and provide a guideline that researchers can follow to increase the rigour of their experiments. [ABSTRACT FROM AUTHOR]

Neohelice granulata (previously known as Chasmagnathus granulata and C. granulatus) is a burrowing semiterrestrial crab found in the intertidal zone of estuaries, salt marshes and mangroves of the South-western Atlantic Ocean. Beginning in the late 1989s, an explosion of publications appeared in international journals dealing with its ecology, physiology, toxicology and behavior. A bibliometric analysis using the Scopus database allowed detecting 309 papers that deal with this species during the period 1986–2009. The number of papers per year increased continuously, reaching a mean annual value of 22.6 during the last 5 years; a great majority of them were authored by researchers from Argentina and Brazil. Neohelice granulata has become now one of the most studied crab species, after Carcinus maenas, Callinectes sapidus, Scylla serrata and Cancer pagurus and C. magister, and it can be considered as an emergent animal model for biochemical, physiological and ecological research. [ABSTRACT FROM AUTHOR]

Background: Double injection of blood into cisterna magna using a rabbit model results in cerebral vasospasm. An unacceptably high mortality rate tends to limit the application of model. Ultrasound guided puncture can provide real-time imaging guidance for operation. The aim of this paper is to establish a safe and effective rabbit model of cerebral vasospasm after subarachnoid hemorrhage with the assistance of ultrasound medical imaging.Methods: A total of 160 New Zealand white rabbits were randomly divided into four groups of 40 each: (1) manual control group, (2) manual model group, (3) ultrasound guided control group, and (4) ultrasound guided model group. The subarachnoid hemorrhage was intentionally caused by double injection of blood into their cisterna magna. Then, basilar artery diameters were measured using magnetic resonance angiography before modeling and 5 days after modeling.Results: The depth of needle entering into cisterna magna was determined during the process of ultrasound guided puncture. The mortality rates in manual control group and model group were 15 and 23 %, respectively. No rabbits were sacrificed in those two ultrasound guided groups. We found that the mortality rate in ultrasound guided groups decreased significantly compared to manual groups. Compared with diameters before modeling, the basilar artery diameters after modeling were significantly lower in manual and ultrasound guided model groups. The vasospasm aggravated and the proportion of severe vasospasms was greater in ultrasound guided model group than that of manual group. In manual model group, no vasospasm was found in 8 % of rabbits.Conclusions: The ultrasound guided double injection of blood into cisterna magna is a safe and effective rabbit model for treatment of cerebral vasospasm. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common form of dementia. At the diagnostic stage, the AD brain is characterized by the accumulation of extracellular amyloid plaques, intracellular neurofibrillary tangles and neuronal loss. Despite the large variety of therapeutic approaches, this condition remains incurable, since at the time of clinical diagnosis, the brain has already suffered irreversible and extensive damage. In recent years, it has become evident that AD starts decades prior to its clinical presentation. In this regard, transgenic animal models can shed much light on the mechanisms underlying this "pre-clinical" stage, enabling the identification and validation of new therapeutic targets. This paper summarizes the formidable efforts to create models mimicking the various aspects of AD pathology in the rat. Transgenic rat models offer distinctive advantages over mice. Rats are physiologically, genetically and morphologically closer to humans. More importantly, the rat has a wellcharacterized, rich behavioral display. Consequently, rat models of AD should allow a more sophisticated and accurate assessment of the impact of pathology and novel therapeutics on cognitive outcomes. [ABSTRACT FROM AUTHOR]

Background: Mammalian sires participate in infant care. We previously demonstrated that sires of a strain of nonmonogamous laboratory mice initiate parental retrieval behavior in response to olfactory and auditory signals from the dam during isolation in a new environment. This behavior is rapidly lost in the absence of such signals when the sires are caged alone. The neural circuitry and hormones that control paternal behavior are not wellunderstood. CD38, a membrane glycoprotein, catalyzes synthesis of cyclic ADP-ribose and facilitates oxytocin (OT) secretion due to cyclic ADP-ribose-dependent increases in cytosolic free calcium concentrations in oxytocinergic neurons in the hypothalamus. In this paper, we studied CD38 in the nucleus accumbens (NAcc) and the role of OT on paternal pup retrieval behavior using CD38 knockout (CD38-/-) mice of the ICR strain. Results: CD38-/- sires failed to retrieve when they were reunited with their pups after isolation together with the mate dams, but not with pup, in a novel cage for 10 min. CD38-/- sires treated with a single subcutaneous injection of OT exhibited recovery in the retrieval events when caged with CD38-/- dams treated with OT. We introduced human CD38 in the NAcc of CD38-/- sires using a lentiviral infection technique and examined the effects of local expression of CD38. Pairs of knockout dams treated with OT and sires expressing CD38 in the NAcc showed more retrieval (83% of wild-type sire levels). Complete recovery of retrieval was obtained in sires with the expression of CD38 in the NAcc in combination with OT administration. Other paternal behaviors, including pup grooming, crouching and huddling, were also more common in CD38-/- sires with CD38 expression in the NAcc compared with those in CD38-/- sires without CD38 expression in the NAcc. Conclusions: CD38 in the NAcc and OT are critical in paternal behavior. [ABSTRACT FROM AUTHOR]

Simian immunodeficiency virus (SIV) infection of Indian-origin rhesus macaques (RM) has been widely used as a well-established nonhuman primate (NHP) model for HIV/AIDS research. However, there have been a growing number of studies using Chinese RM to evaluate immunopathogenesis of SIV infection. In this paper, we have for the first time reviewed and discussed the major publications related to SIV or SHIV infection of Chinese RM in the past decades. We have compared the differences in the pathogenesis of SIV infection between Chinese RM and Indian RM with regard to viral infection, immunological response, and host genetic background. Given AIDS is a disease that affects humans of diverse origins, it is of importance to study animals with different geographical background. Therefore, to examine and compare results obtained from RM models of Indian and Chinese origins should lead to further validation and improvement of these animal models for HIV/AIDS research. [ABSTRACT FROM AUTHOR]

Animal models play a central role in all areas of biomedical research. The process of animal model building, development and evaluation has rarely been addressed systematically, despite the long history of using animal models in the investigation of neuropsychiatric disorders and behavioral dysfunctions. An iterative, multi-stage trajectory for developing animal models and assessing their quality is proposed. The process starts with defining the purpose(s) of the model, preferentially based on hypotheses about brain-behavior relationships. Then, the model is developed and tested. The evaluation of the model takes scientific and ethical criteria into consideration. Model development requires a multidisciplinary approach. Preclinical and clinical experts should establish a set of scientific criteria, which a model must meet. The scientific evaluation consists of assessing the replicability/reliability, predictive, construct and external validity/generalizability, and relevance of the model. We emphasize the role of (systematic and extended) replications in the course of the validation process. One may apply a multiple-tiered 'replication battery' to estimate the reliability/replicability, validity, and generalizability of result. Compromised welfare is inherent in many deficiency models in animals. Unfortunately, 'animal welfare' is a vaguely defined concept, making it difficult to establish exact evaluation criteria. Weighing the animal's welfare and considerations as to whether action is indicated to reduce the discomfort must accompany the scientific evaluation at any stage of the model building and evaluation process. Animal model building should be discontinued if the model does not meet the preset scientific criteria, or when animal welfare is severely compromised. The application of the evaluation procedure is exemplified using the rat with neonatal hippocampal lesion as a proposed model of schizophrenia. In a manner congruent to that for improving animal models, guided by the procedure expounded upon in this paper, the developmental and evaluation procedure itself may be improved by careful definition of the purpose(s) of a model and by defining better evaluation criteria, based on the proposed use of the model. [ABSTRACT FROM AUTHOR]

Background: The development of new ultrasound contrast agents (UCAs) has become one of the most promising fields in ultrasound medicine. This paper evaluates a new self-made contrast agent enhancement effect developed to study the fibrotic stages of the liver in perfusion models in vivo. Methods: We constructed experimental models of hepatic fibrosis involving five stages from F0 to F4 via administration of CCL4 (0.01 ml/kg BW) every 3 days for 3 months. The intrahepatic circulatory time of the contrast agent was analyzed via an image and Cine-loop display. Calculations of the perfusion-related parameters including the peak signal intensity (PSI) and peak signal intensity time (PIT) of the portal vein and parenchyma were obtained from an analysis of the time-acoustic intensity curve. Results: Hepatic artery to vein transmit time (HA-HVTT) was significantly shorter at F4 stage (mean 5.1 seconds) compared with those in other stages (mean 8.3 s, 7.5 s, 6.9 s, 6.6 s, P < 0.01). The average PSI difference of PV-parenchyma was 13.62 dB in F4 stage, demonstrating significant differences between F4 stage and other early stages (P < 0.001). Conclusion: These results indicate that the new self-made contrast agent is capable of indicating intrahepatic hemodynamic changes. HA-HVTT and the PSI difference of the microbubble perfusion in liver parenchyma and PV were considered to differentiate the degree of hepatic fibrosis between F4 and other early stages. [ABSTRACT FROM AUTHOR]

Background: The concept of reserve was established to account for the observation that a given degree of neurodegenerative pathology may result in varying degrees of symptoms in different individuals. There is a large amount of evidence on epidemiological risk and protective factors for neurodegenerative diseases and dementia, yet the biological mechanisms that underpin the protective effects of certain lifestyle and physiological variables remain poorly understood, limiting the development of more effective preventive and treatment strategies. Additionally, different definitions and concepts of reserve exist, which hampers the coordination of research and comparison of results across studies.Discussion: This paper represents the consensus of a multidisciplinary group of experts from different areas of research related to reserve, including clinical, epidemiological and basic sciences. The consensus was developed during meetings of the working groups of the first International Conference on Cognitive Reserve in the Dementias (24-25 November 2017, Munich, Germany) and the Alzheimer's Association Reserve and Resilience Professional Interest Area (25 July 2018, Chicago, USA). The main objective of the present paper is to develop a translational perspective on putative mechanisms underlying reserve against neurodegenerative disease, combining evidence from epidemiological and clinical studies with knowledge from animal and basic research. The potential brain functional and structural basis of reserve in Alzheimer's disease and other brain disorders are discussed, as well as relevant lifestyle and genetic factors assessed in both humans and animal models.Conclusion: There is an urgent need to advance our concept of reserve from a hypothetical model to a more concrete approach that can be used to improve the development of effective interventions aimed at preventing dementia. Our group recommends agreement on a common dictionary of terms referring to different aspects of reserve, the improvement of opportunities for data sharing across individual cohorts, harmonising research approaches across laboratories and groups to reduce heterogeneity associated with human data, global coordination of clinical trials to more effectively explore whether reducing epidemiological risk factors leads to a reduced burden of neurodegenerative diseases in the population, and an increase in our understanding of the appropriateness of animal models for reserve research. [ABSTRACT FROM AUTHOR]

Background: The pharmaceutical industry is in the midst of a productivity crisis and rates of translation from bench to bedside are dismal. Patients are being let down by the current system of drug discovery; of the several 1000 diseases that affect humans, only a minority have any approved treatments and many of these cause adverse reactions in humans. A predominant reason for the poor rate of translation from bench to bedside is generally held to be the failure of preclinical animal models to predict clinical efficacy and safety. Attempts to explain this failure have focused on problems of internal validity in preclinical animal studies (e.g. poor study design, lack of measures to control bias). However there has been less discussion of another key factor that influences translation, namely the external validity of preclinical animal models.Review Of Problems Of External Validity: External validity is the extent to which research findings derived in one setting, population or species can be reliably applied to other settings, populations and species. This paper argues that the reliable translation of findings from animals to humans will only occur if preclinical animal studies are both internally and externally valid. We review several key aspects that impact external validity in preclinical animal research, including unrepresentative animal samples, the inability of animal models to mimic the complexity of human conditions, the poor applicability of animal models to clinical settings and animal-human species differences. We suggest that while some problems of external validity can be overcome by improving animal models, the problem of species differences can never be overcome and will always undermine external validity and the reliable translation of preclinical findings to humans.Conclusion: We conclude that preclinical animal models can never be fully valid due to the uncertainties introduced by species differences. We suggest that even if the next several decades were spent improving the internal and external validity of animal models, the clinical relevance of those models would, in the end, only improve to some extent. This is because species differences would continue to make extrapolation from animals to humans unreliable. We suggest that to improve clinical translation and ultimately benefit patients, research should focus instead on human-relevant research methods and technologies. [ABSTRACT FROM AUTHOR]

A conference paper on ZF-Human Disease Database (ZF-HDD) is presented. ZF-HDD is a database for zebrafish models of human genetic diseases. The difference in numbers between the human and zebrafish proteins, associated to genetic conditions, is due to positive selection pressure to preserve as duplication these proteins in zebrafish.