scholarly journals Design and Reporting of Targeted Anticancer Preclinical Studies: A Meta-Analysis of Animal Studies Investigating Sorafenib Antitumor Efficacy

2016 ◽  
Vol 76 (16) ◽  
pp. 4627-4636 ◽  
Author(s):  
James Mattina ◽  
Nathalie MacKinnon ◽  
Valerie C. Henderson ◽  
Dean Fergusson ◽  
Jonathan Kimmelman
Keyword(s):  
Animal Studies ◽  
Meta Analysis ◽  
Antitumor Efficacy ◽  
Preclinical Studies

scholarly journals Large scale meta-analysis of preclinical toxicity data for target characterisation and hypotheses generation

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252533
Author(s):  
Jordi Munoz-Muriedas
Keyword(s):  
Animal Studies ◽  
Large Scale ◽  
Meta Analysis ◽  
Preclinical Studies ◽  
Technological Advances ◽  
Consistent Manner ◽  
Critical Components ◽  
Meta Analyses ◽  
And Control

Recent technological advances in the field of big data have increased our capabilities to query large databases and combine information from different domains and disciplines. In the area of preclinical studies, initiatives like SEND (Standard for Exchange of Nonclinical Data) will also contribute to collect and present nonclinical data in a consistent manner and increase analytical possibilities. With facilitated access to preclinical data and improvements in analytical algorithms there will surely be an expectation for organisations to ensure all the historical data available to them is leveraged to build new hypotheses. These kinds of analyses may soon become as important as the animal studies themselves, in addition to being critical components to achieve objectives aligned with 3Rs. This article proposes the application of meta-analyses at large scale in corporate databases as a tool to exploit data from both preclinical studies and in vitro pharmacological activity assays to identify associations between targets and tissues that can be used as seeds for the development of causal hypotheses to characterise of targets. A total of 833 in-house preclinical toxicity studies relating to 416 compounds reported to be active (pXC50 ≥ 5.5) against a panel of 96 selected targets of interest for potential off-target non desired effects were meta-analysed, aggregating the data in tissue–target pairs. The primary outcome was the odds ratio (OR) of the number of animals with observed events (any morphology, any severity) in treated and control groups in the tissue analysed. This led to a total of 2139 meta-analyses producing a total of 364 statistically significant associations (random effects model), 121 after adjusting by multiple comparison bias. The results show the utility of the proposed approach to leverage historical corporate data and may offer a vehicle for researchers to share, aggregate and analyse their preclinical toxicological data in precompetitive environments.

scholarly journals Impaired learning, memory, and extinction in posttraumatic stress disorder: translational meta-analysis of clinical and preclinical studies

2021 ◽  
Author(s):  
Milou S. C. Sep ◽  
Elbert Geuze ◽  
Marian Joëls
Keyword(s):  
Animal Models ◽  
Animal Studies ◽  
Stress Disorder ◽  
Meta Analysis ◽  
Emotional Memory ◽  
Fear Extinction ◽  
Current Evidence ◽  
Preclinical Studies ◽  
Post Traumatic Stress ◽  
Trauma Memory

Background. Current evidence-based treatments for post-traumatic stress disorder (PTSD) are efficacious in only part of PTSD patients. Therefore, novel neurobiologically-informed approaches are urgently needed. Clinical and translational neuroscience point to altered learning and memory processes as key in (models of) PTSD psychopathology. We extended this notion by clarifying at a meta-level i) the role of information valence, i.e. neutral versus emotional/fearful, and ii) comparability between clinical and preclinical phenotypes. We hypothesized that, cross-species, neutral versus emotional/fearful information processing is, respectively, impaired and enhanced in PTSD. Methods. This preregistered meta-analysis involved a literature search on PTSD+Learning/Memory+Behavior, performed in PubMed. First, the effect of information valence was estimated with a random-effects meta-regression. Then sources of variation were explored with a random forest-based analysis. Results. The analyses included 92 clinical (N=6732 humans) and 182 preclinical (N=6834 animals) studies. A general impairment of learning, memory and extinction processes was observed in PTSD patients, regardless of information valence. Impaired neutral learning/memory and fear extinction were also present in animal models of PTSD. Yet, PTSD enhanced fear/trauma memory in preclinical studies and impaired emotional memory in patients. Clinical data on fear/trauma memory was limited. Mnemonic phase and valence explained most variation in rodents but not humans. Conclusions. Impaired neutral learning/memory and fear extinction show very stable cross-species PTSD phenotypes. These could be targeted for novel PTSD treatments, building on neurobiological animal studies. We argue that seemingly cross-species discrepancies in emotional/fearful memory deserve further study; until then animal models targeting this phenotype should be applied with care.

scholarly journals Mitochondrial transplantation therapy for ischemia reperfusion injury: a systematic review of animal and human studies

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Kei Hayashida ◽  
Ryosuke Takegawa ◽  
Muhammad Shoaib ◽  
Tomoaki Aoki ◽  
Rishabh C. Choudhary ◽  
...  
Keyword(s):  
Systematic Review ◽  
Reperfusion Injury ◽  
Animal Studies ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Dysfunction ◽  
Ischemia Reperfusion ◽  
Meta Analysis ◽  
Relevant Literature ◽  
Human Studies ◽  
Cochrane Library

Abstract Background Mitochondria are essential organelles that provide energy for cellular functions, participate in cellular signaling and growth, and facilitate cell death. Based on their multifactorial roles, mitochondria are also critical in the progression of critical illnesses. Transplantation of mitochondria has been reported as a potential promising approach to treat critical illnesses, particularly ischemia reperfusion injury (IRI). However, a systematic review of the relevant literature has not been conducted to date. Here, we systematically reviewed the animal and human studies relevant to IRI to summarize the evidence for mitochondrial transplantation. Methods We searched MEDLINE, the Cochrane library, and Embase and performed a systematic review of mitochondrial transplantation for IRI in both preclinical and clinical studies. We developed a search strategy using a combination of keywords and Medical Subject Heading/Emtree terms. Studies including cell-mediated transfer of mitochondria as a transfer method were excluded. Data were extracted to a tailored template, and data synthesis was descriptive because the data were not suitable for meta-analysis. Results Overall, we identified 20 animal studies and two human studies. Among animal studies, 14 (70%) studies focused on either brain or heart IRI. Both autograft and allograft mitochondrial transplantation were used in 17 (85%) animal studies. The designs of the animal studies were heterogeneous in terms of the route of administration, timing of transplantation, and dosage used. Twelve (60%) studies were performed in a blinded manner. All animal studies reported that mitochondrial transplantation markedly mitigated IRI in the target tissues, but there was variation in biological biomarkers and pathological changes. The human studies were conducted with a single-arm, unblinded design, in which autologous mitochondrial transplantation was applied to pediatric patients who required extracorporeal membrane oxygenation (ECMO) for IRI–associated myocardial dysfunction after cardiac surgery. Conclusion The evidence gathered from our systematic review supports the potential beneficial effects of mitochondrial transplantation after IRI, but its clinical translation remains limited. Further investigations are thus required to explore the mechanisms of action and patient outcomes in critical settings after mitochondrial transplantation. Systematic review registration The study was registered at UMIN under the registration number UMIN000043347.

scholarly journals Comparison of the efficacy of hematopoietic stem cell mobilization regimens: a systematic review and network meta-analysis of preclinical studies

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Chengxin Luo ◽  
Li Wang ◽  
Guixian Wu ◽  
Xiangtao Huang ◽  
Yali Zhang ◽  
...  
Keyword(s):  
Standard Dose ◽  
Meta Analysis ◽  
Secondary Outcome ◽  
Preclinical Studies ◽  
Mice Model ◽  
Short Term ◽  
Hematopoietic Stem ◽  
Support Unit ◽  
Meta Analyses

Abstract Background Mobilization failure may occur when the conventional hematopoietic stem cells (HSCs) mobilization agent granulocyte colony-stimulating factor (G-CSF) is used alone, new regimens were developed to improve mobilization efficacy. Multiple studies have been performed to investigate the efficacy of these regimens via animal models, but the results are inconsistent. We aim to compare the efficacy of different HSC mobilization regimens and identify new promising regimens with a network meta-analysis of preclinical studies. Methods We searched Medline and Embase databases for the eligible animal studies that compared the efficacy of different HSC mobilization regimens. Primary outcome is the number of total colony-forming cells (CFCs) in per milliliter of peripheral blood (/ml PB), and the secondary outcome is the number of Lin− Sca1+ Kit+ (LSK) cells/ml PB. Bayesian network meta-analyses were performed following the guidelines of the National Institute for Health and Care Excellence Decision Support Unit (NICE DSU) with WinBUGS version 1.4.3. G-CSF-based regimens were classified into the SD (standard dose, 200–250 μg/kg/day) group and the LD (low dose, 100–150 μg/kg/day) group based on doses, and were classified into the short-term (2–3 days) group and the long-term (4–5 days) group based on administration duration. Long-term SD G-CSF was chosen as the reference treatment. Results are presented as the mean differences (MD) with the associated 95% credibility interval (95% CrI) for each regimen. Results We included 95 eligible studies and reviewed the efficacy of 94 mobilization agents. Then 21 studies using the poor mobilizer mice model (C57BL/6 mice) to investigate the efficacy of different mobilization regimens were included for network meta-analysis. Network meta-analyses indicated that compared with long-term SD G-CSF alone, 14 regimens including long-term SD G-CSF + Me6, long-term SD G-CSF + AMD3100 + EP80031, long-term SD G-CSF + AMD3100 + FG-4497, long-term SD G-CSF + ML141, long-term SD G-CSF + desipramine, AMD3100 + meloxicam, long-term SD G-CSF + reboxetine, AMD3100 + VPC01091, long-term SD G-CSF + FG-4497, Me6, long-term SD G-CSF + EP80031, POL5551, long-term SD G-CSF + AMD3100, AMD1300 + EP80031 and long-term LD G-CSF + meloxicam significantly increased the collections of total CFCs. G-CSF + Me6 ranked first among these regimens in consideration of the number of harvested CFCs/ml PB (MD 2168.0, 95% CrI 2062.0−2272.0). In addition, 7 regimens including long-term SD G-CSF + AMD3100, AMD3100 + EP80031, long-term SD G-CSF + EP80031, short-term SD G-CSF + AMD3100 + IL-33, long-term SD G-CSF + ML141, short-term LD G-CSF + ARL67156, and long-term LD G-CSF + meloxicam significantly increased the collections of LSK cells compared with G-CSF alone. Long-term SD G-CSF + AMD3100 ranked first among these regimens in consideration of the number of harvested LSK cells/ml PB (MD 2577.0, 95% CrI 2422.0–2733.0). Conclusions Considering the number of CFC and LSK cells in PB as outcomes, G-CSF plus AMD3100, Me6, EP80031, ML141, FG-4497, IL-33, ARL67156, meloxicam, desipramine, and reboxetine are all promising mobilizing regimens for future investigation.

scholarly journals A Review of the Major Prosthetic Factors Influencing the Prognosis of Implant Prosthodontics

2021 ◽  
Vol 10 (4) ◽  
pp. 816
Author(s):  
Javier Montero
Keyword(s):  
Animal Studies ◽  
Treatment Approach ◽  
Treatment Plan ◽  
Meta Analysis ◽  
Good Prognosis ◽  
Cochrane Library ◽  
Review Of The Literature ◽  
Hand Search ◽  
Related Risk

Background: The treatment plan of prosthetic restorations supported by dental implants requires comprehensive scientific knowledge to deliver prostheses with good prognosis, even before the implant insertion. This review aims to analyze the main prosthetic determinants of the prognosis of implant-supported prostheses. Methods: A comprehensive review of the literature was conducted with a PICO (Patient Intervention Comparison Outcomes) question: “For partially or complete edentulous subjects treated with implant-supported prostheses, which prosthetic factors could affect clinical outcomes?”. A literature search was performed electronically in PubMed (MEDLINE), Scopus and Cochrane Library with the following equation [PROGNOS * OR RISK] FACTOR IMPLANT DENTAL, and by hand search in relevant journals and throughout the selected papers. Results: This revision was carried out based on 50 papers focused on several prosthodontics-related risk factors that were grouped as follows: implant-connection, loading protocol, transmucosal abutments, prosthetic fit, provisionalization, type of retention, impression technique, fabrication technique, and occlusion. More than a half of the studies were systematic reviews (30%), meta-analysis (16%), or prospective evaluations of prosthesis with various kinds of events (18%). However, narrative reviews of literature (14%) and in vitro/animal studies (16%) were also found. Conclusions: The current literature provides insufficient evidence for most of the investigated topics. However, based on the accumulated data, it seems reasonable to defend that the best treatment approach is the use of morse taper implants with transmucosal abutments, recorded by means of rigidly splinted copings through the pick-up technique, and screwed by milled prosthesis occlusally adjusted to minimize functional overloading.

Towards effective cutaneous leishmaniasis treatment with light-based technologies. A systematic review and meta-analysis of preclinical studies

2021 ◽  
pp. 112236
Author(s):  
Fernanda Viana Cabral ◽  
Tiago Henrique dos Santos Souza ◽  
Fábio Parra Sellera ◽  
Adriana Fontes ◽  
Martha Simões Ribeiro
Keyword(s):  
Systematic Review ◽  
Cutaneous Leishmaniasis ◽  
Meta Analysis ◽  
Preclinical Studies

Anterior Cruciate Ligament Mechanoreceptors and their Potential Importance in Remnant-Preserving Reconstruction: A Review of Basic Science and Clinical Findings

2017 ◽  
Vol 31 (08) ◽  
pp. 736-746 ◽  
Author(s):  
Jonathan Kosy ◽  
Vipul Mandalia
Keyword(s):  
Anterior Cruciate Ligament ◽  
Posterior Cruciate Ligament ◽  
Clinical Studies ◽  
Basic Science ◽  
Animal Studies ◽  
Cruciate Ligament ◽  
Meta Analysis ◽  
Future Research ◽  
Remnant Preservation ◽  
Anterior Cruciate

AbstractMechanoreceptors, within the anterior cruciate ligament (ACL), are believed to have importance in proprioception, contributing to dynamic knee stability. The potential for reinnervation of the ACL graft is one of the proposed advantages of remnant-preserving reconstruction. The aim of this review is to summarize advances in the basic science underpinning this function, alongside recent clinical studies, to define the current role for remnant-preservation.A comprehensive systematic review was performed using PubMed and Medline searches. Studies were analyzed with particular focus placed on the methodology used to either identify mechanoreceptors or test proprioception.Contemporary work, using immunohistological staining, has shown mechanoreceptors primarily within proximity to the bony attachments of the ACL (peripherally in the subsynovial layer). The number of these receptors has been shown to decrease rapidly, following rupture, with adhesion to the posterior cruciate ligament slowing this decline. Recent studies have shown proprioceptive deficits, in both the injured and contralateral knees, with the clinical relevance of findings limited by testing methodology and the small differences found. The advantages of remnant-preservation, seen primarily in animal studies, have not been shown in systematic reviews or meta-analysis of clinical studies.The potential for reinnervation of the graft is likely time-dependent and reliant on continued loading of the remnant. Therefore, current clinical use and future research should focus on preserving remnants within 6 months of injury that remain loaded by adherence to the posterior cruciate ligament. Subsequent testing should account for central neurological changes and focus on clinically relevant outcomes.

The Effect of Plantago major on Wound Healing in Preclinical Studies: A Systematic Review

2021 ◽  
Vol 67 (1) ◽  
pp. 27-34
Author(s):  
Fernanda Cardoso ◽  
Jéssica Breder ◽  
Priscila Apolinário ◽  
Henrique Oliveia ◽  
Maria Saidel ◽  
...  
Keyword(s):  
Systematic Review ◽  
Wound Healing ◽  
Meta Analysis ◽  
Experimental Studies ◽  
Risk Of Bias ◽  
Preclinical Studies ◽  
Plantago Major ◽  
Best Response ◽  
Meta Analyses

BACKGROUND: Plantago major is a medicinal plant that has been used for centuries to treat various health conditions including wounds. PURPOSE: To investigate the effectiveness of the topical use of P major in healing skin wounds in animal models. METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review was conducted. Seven (7) electronic databases (Virtual Health Library, Public/Publisher MEDLINE, Scopus, Web of Science, Embase, Cumulative Index of Nursing and Allied Health Literature, and CAB Direct) were searched for controlled studies published in English from January 2006 to March 2020. The Collaborative Approach to Meta Analysis and Review of Animal Data from Experimental Studies tools guided the evaluation of the studies and determined their quality. The Systematic Review Center for Laboratory Animal Experimentation was used to assess the risk of bias. RESULTS: Of the 176 publications identified, 4 met the inclusion criteria. Studies included 20 to 100 animals and varying concentrations of P major. There were no reports of losses during research. Wound healing was assessed between 17 and 21 days following wounding. The best response in terms of wound contraction rate occurred with 10%, 20%, and 50% concentrations when compared with control groups. One (1) study did not have an animal ethics committee review. All studies had a high risk of bias and a lack of methodological rigor. CONCLUSION: The results of this review did not find evidence about the in vivo effectiveness of P major for wound healing. More rigorous preclinical studies with adequate sample sizes are required to identify the best concentrations and formulations as well as increase understanding about the mechanisms of action of P major in wound healing.

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