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https://www.readbyqxmd.com/read/28328894/laboratory-environmental-factors-and-pain-behavior-the-relevance-of-unknown-unknowns-to-reproducibility-and-translation
#1
Jeffrey S Mogil
The poor record of basic-to-clinical translation in recent decades has led to speculation that preclinical research is "irreproducible", and this irreproducibility in turn has largely been attributed to deficiencies in reporting and statistical practices. There are, however, a number of other reasonable explanations of both poor translation and difficulties in one laboratory replicating the results of another. This article examines these explanations as they pertain to preclinical pain research. I submit that many instances of apparent irreproducibility are actually attributable to interactions between the phenomena and interventions under study and "latent" environmental factors affecting the rodent subjects...
March 22, 2017: Lab Animal
https://www.readbyqxmd.com/read/28295910/an-analysis-of-nitroxide-based-distance-measurements-in-cell-extract-and-in-cell-by-pulsed-esr-spectroscopy
#2
Sunil Kumar Saxena, Matthew J Lawless, Amit Shimshi, Timothy F Cunningham, Monica N Kinde, Pei Tang
Distance measurements in-cell by pulsed ESR present tremendous opportunities to study proteins in a more native environment that is irreproducible in vitro. However, the in-cell environment is harsh towards the typical nitroxide radical used in DEER experiments. We perform a systematic examination of the loss of the DEER signal including contributions from nitroxide decay and nitroxide side chain cleavage. In addition, we examine whether the lifetime of the nitroxide radical can be extended by use of an oxidizing agent...
March 13, 2017: Chemphyschem: a European Journal of Chemical Physics and Physical Chemistry
https://www.readbyqxmd.com/read/28279477/the-evolution-of-differentiated-thyroid-cancer
#3
Sylvia L Asa
Differentiated thyroid tumours of follicular cell derivation have traditionally been classified based on architecture, cytology, or both. The features that distinguish the various entities are controversial and diagnostic criteria are inconsistent and often irreproducible. The complexity of classification schemes has not been substantiated by molecular profiling. In this review, a simplistic approach to the diagnosis of well differentiated thyroid neoplasia is provided to challenge the dogma. The proposed classification matches the molecular profiles of these lesions and simplifies the criteria for diagnosis...
March 6, 2017: Pathology
https://www.readbyqxmd.com/read/28266620/two-dimensional-electrophysiological-characterization-of-human-pluripotent-stem-cell-derived-cardiomyocyte-system
#4
Huanqi Zhu, Kelsey S Scharnhorst, Adam Z Stieg, James K Gimzewski, Itsunari Minami, Norio Nakatsuji, Haruko Nakano, Atsushi Nakano
Stem cell-derived cardiomyocytes provide a promising tool for human developmental biology, regenerative therapies, disease modeling, and drug discovery. As human pluripotent stem cell-derived cardiomyocytes remain functionally fetal-type, close monitoring of electrophysiological maturation is critical for their further application to biology and translation. However, to date, electrophysiological analyses of stem cell-derived cardiomyocytes has largely been limited by biologically undefined factors including 3D nature of embryoid body, sera from animals, and the feeder cells isolated from mouse...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28257086/high-throughput-screening-methodology-to-identify-alpha-synuclein-aggregation-inhibitors
#5
Jordi Pujols, Samuel Peña-Díaz, María Conde-Giménez, Francisca Pinheiro, Susanna Navarro, Javier Sancho, Salvador Ventura
An increasing number of neurodegenerative diseases are being found to be associated with the abnormal accumulation of aggregated proteins in the brain. In Parkinson's disease, this process involves the aggregation of alpha-synuclein (α-syn) into intraneuronal inclusions. Thus, compounds that inhibit α-syn aggregation represent a promising therapeutic strategy as disease-modifying agents for neurodegeneration. The formation of α-syn amyloid aggregates can be reproduced in vitro by incubation of the recombinant protein...
March 2, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28254630/hydrodynamic-gene-delivery-in-human-skin-using-a-hollow-microneedle-device
#6
M Dul, M Stefanidou, P Porta, J Serve, C O'Mahony, B Malissen, S Henri, Y Levin, E Kochba, F S Wong, C Dayan, S A Coulman, J C Birchall
Microneedle devices have been proposed as a minimally invasive delivery system for the intradermal administration of nucleic acids, both plasmid DNA (pDNA) and siRNA, to treat localised disease or provide vaccination. Different microneedle types and application methods have been investigated in the laboratory, but limited and irreproducible levels of gene expression have proven to be significant challenges to pre-clinical to clinical progression. This study is the first to explore the potential of a hollow microneedle device for the delivery and subsequent expression of pDNA in human skin...
February 27, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28207468/significant-differences-in-the-bone-of-an-isogenic-inbred-versus-nonisogenic-outbred-murine-mandible-a-study-in-rigor-and-reproducibility
#7
Edward G Carey, Sagar S Deshpande, Kevin M Urlaub, Alexander R Zheutlin, Noah S Nelson, Alexis Donneys, Stephen Y Kang, Kathleen K Gallagher, Peter A Felice, Catherine N Tchanque-Fossuo, Steven R Buchman
Inattention to differences between animal strains is a potential cause of irreproducibility of basic science investigations. Accordingly, the authors' laboratory sought to ensure that cross-comparisons of results generated from studies of mandibular physiology utilizing the Sprague Dawley and Lewis rat strains are valid. The authors specifically investigated baseline histomorphometrics, bone mineral density, and biomechanical strength of the unaltered endogenous mandibles of the inbred, isogenic Lewis rat, and the outbred, nonisogenic Sprague Dawley rat to determine if they are indeed equal...
February 15, 2017: Journal of Craniofacial Surgery
https://www.readbyqxmd.com/read/28151827/ethics-of-research-for-patients-in-pain
#8
David B Waisel
PURPOSE OF REVIEW: This review describes advances in rising and continuing ethical issues in research in patients in pain. Although some of the issues focus directly on pain research, such as research in neonatal pain management, others focus on widespread ethical issues that are relevant to pain research, such as scientific misconduct, deception, placebo use and genomics. RECENT FINDINGS: Scientific misconduct is more widespread than realized and requires greater awareness of the markers of misconduct like irreproducibility...
April 2017: Current Opinion in Anaesthesiology
https://www.readbyqxmd.com/read/28144217/subtle-scientific-fallacies-undermine-the-validity-of-neuroendocrinological-research-do-not-draw-premature-conclusions-on-the-role-of-female-sex-hormones
#9
Michael P Hengartner
Major scientific flaws such as reporting and publication biases are well documented, even though acknowledgment of their importance appears to be lacking in various psychological and medical fields. Subtle and less obvious biases including selective reviews of the literature and empirically unsupported conclusions and recommendations have received even less attention. Using the literature on the association between transition to menopause, hormones and the onset of depression as a guiding example, I outline how such scientific fallacies undermine the validity of neuroendocrinological research...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28123930/irreproducibility-of-published-bioscience-research-diagnosis-pathogenesis-and-therapy
#10
Jeffrey S Flier
No abstract text is available yet for this article.
January 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28121685/predatory-publishing-an-emerging-threat-to-the-medical-literature
#11
H Benjamin Harvey, Debra F Weinstein
The quality of medical literature is increasingly threatened by irresponsible publishing, leading to rising retraction rates, irreproducible results, and a flood of inconsequential publications that distract readers from more meaningful scholarship. "Predatory publishers" offer rapid publication with loose peer review, exploiting a system in which faculty seek longer bibliographies to achieve academic promotion. In this Commentary, the authors highlight some of the evidence that this problem exists and suggest actions to address it...
February 2017: Academic Medicine: Journal of the Association of American Medical Colleges
https://www.readbyqxmd.com/read/28117563/patent-law-s-reproducibility-paradox
#12
Jacob S Sherkow
Clinical research faces a reproducibility crisis. Many recent clinical and preclinical studies appear to be irreproducible--their results cannot be verified by outside researchers. This is problematic for not only scientific reasons but also legal ones: patents grounded in irreproducible research appear to fail their constitutional bargain of property rights in exchange for working disclosures of inventions. The culprit is likely patent law’s doctrine of enablement. Although the doctrine requires patents to enable others to make and use their claimed inventions, current difficulties in applying the doctrine hamper or even actively dissuade reproducible data in patents...
January 2017: Duke Law Journal
https://www.readbyqxmd.com/read/28098867/-retracted-nuclear-import-of-prototype-foamy-virus-transactivator-bel1-is-mediated-by-kpna1-kpna6-and-kpna7
#13
Jihui Duan, Zhiqin Tang, Hong Mu, Guojun Zhang
We would like to retract the article entitled "Nuclear import of prototype foamy virus transactivator Bel1 is mediated by KPNA1, KPNA6 and KPNA7" published in International Journal of Molecular Medicine 38: 339-406, 2016. The results presented in Fig. 6 have been demonstrated to be unreproducible, and we cannot provide an explanation for this. Furthermore, we have recently identified that the cell cultures used in our experiments were partly contaminated with Mycoplasma, which could have contributed to the irreproducibility of the results...
March 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28088185/igc-an-integrated-analysis-package-of-gene-expression-and-copy-number-alteration
#14
Yi-Pin Lai, Liang-Bo Wang, Wei-An Wang, Liang-Chuan Lai, Mong-Hsun Tsai, Tzu-Pin Lu, Eric Y Chuang
BACKGROUND: With the advancement in high-throughput technologies, researchers can simultaneously investigate gene expression and copy number alteration (CNA) data from individual patients at a lower cost. Traditional analysis methods analyze each type of data individually and integrate their results using Venn diagrams. Challenges arise, however, when the results are irreproducible and inconsistent across multiple platforms. To address these issues, one possible approach is to concurrently analyze both gene expression profiling and CNAs in the same individual...
January 14, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28061006/confirmation-of-promise-a-simple-genomics-based-clinical-classifier-for-endometrial-cancer
#15
Aline Talhouk, Melissa K McConechy, Samuel Leung, Winnie Yang, Amy Lum, Janine Senz, Niki Boyd, Judith Pike, Michael Anglesio, Janice S Kwon, Anthony N Karnezis, David G Huntsman, C Blake Gilks, Jessica N McAlpine
BACKGROUND: Classification of endometrial carcinomas (ECs) by morphologic features is irreproducible and imperfectly reflects tumor biology. The authors developed the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE), a molecular classification system based on The Cancer Genome Atlas genomic subgroups, and sought to confirm both feasibility and prognostic ability in a new, large cohort of ECs. METHODS: Immunohistochemistry (IHC) for the presence or absence of mismatch repair (MMR) proteins (to identify MMR deficiency [MMR-D]), sequencing for polymerase-ɛ (POLE) exonuclease domain mutations (POLE EDMs), and IHC for tumor protein 53 (p53) (wild type vs null/missense mutations; p53 wt and p53 abn, respectively) were performed on 319 new EC samples...
January 6, 2017: Cancer
https://www.readbyqxmd.com/read/28009490/exploring-the-chemical-reaction-space-at-the-formation-of-chalcogenidometalate-superspheres-in-ionic-liquids
#16
Silke Santner, Sivathmeehan Yogendra, Jan J Weigand, Stefanie Dehnen
The synthesis of anionic chalcogenidometalate superspheres can be achieved from [Ge4 Se10 ](4-) salts and SnCl4 in ionic liquids with 1-alkyl-(2,)3-(di)methylimidazolium cations, denoted as (Cn (C1 )C1 Im)(+) (alkyl = butyl for n=4, hexyl for n=6, octyl for n=8). Their formation is apparently independent from the lengths of the Cn chain, and the presence or absence of a second methyl group at the ionic liquid cation (that are exchanged for alkali metal cations in precursor compounds during the reactions), although this may appear counterintuitive...
December 23, 2016: Chemistry: a European Journal
https://www.readbyqxmd.com/read/27990689/resetting-the-bar-statistical-significance-in-whole-genome-sequencing-based-association-studies-of-global-populations
#17
Sara L Pulit, Sera A J de With, Paul I W de Bakker
Genome-wide association studies (GWAS) of common disease have been hugely successful in implicating loci that modify disease risk. The bulk of these associations have proven robust and reproducible, in part due to community adoption of statistical criteria for claiming significant genotype-phenotype associations. As the cost of sequencing continues to drop, assembling large samples in global populations is becoming increasingly feasible. Sequencing studies interrogate not only common variants, as was true for genotyping-based GWAS, but variation across the full allele frequency spectrum, yielding many more (independent) statistical tests...
December 18, 2016: Genetic Epidemiology
https://www.readbyqxmd.com/read/27988499/the-effect-of-storage-temperature-fluctuations-on-the-stability-of-biochemical-analytes-in-blood-serum
#18
Helmuth Haslacher, Thomas Szekeres, Marlene Gerner, Elisabeth Ponweiser, Manuela Repl, Oswald F Wagner, Thomas Perkmann
BACKGROUND: Irreproducibility of scientific results constitutes an undesirably onerous economic burden and is in many cases caused by low-quality materials. Therefore, researchers are increasingly devoting their attention to the bioresources they use. In turn, those bioresources are required to validate their preanalytical processes in order to ensure best possible quality. The present study thus aimed to evaluate the impact of repeated temperature fluctuations, as they occur in most research biobanks due to repetitive opening and closing of freezer doors, on the stability of 26 biochemical analytes...
December 19, 2016: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/27988358/feature-selection-in-clinical-proteomics-with-great-power-comes-great-reproducibility
#19
REVIEW
Wei Wang, Andrew C-H Sue, Wilson W B Goh
In clinical proteomics, reproducible feature selection is unattainable given the standard statistical hypothesis-testing framework. This leads to irreproducible signatures with no diagnostic power. Instability stems from high P-value variability (p_var), which is inevitable and insolvable. The impact of p_var can be reduced via power increment, for example increasing sample size and measurement accuracy. However, these are not realistic solutions in practice. Instead, workarounds using existing data such as signal boosting transformation techniques and network-based statistical testing is more practical...
December 15, 2016: Drug Discovery Today
https://www.readbyqxmd.com/read/27959516/interlaboratory-reproducibility-of-a-targeted-metabolomics-platform-for-analysis-of-human-serum-and-plasma
#20
Alexandros P Siskos, Pooja Jain, Werner Römisch-Margl, Mark Bennett, David Achaintre, Yasmin Asad, Luke Marney, Larissa Richardson, Albert Koulman, Julian L Griffin, Florence Raynaud, Augustin Scalbert, Jerzy Adamski, Cornelia Prehn, Hector C Keun
A critical question facing the field of metabolomics is whether data obtained from different centers can be effectively compared and combined. An important aspect of this is the interlaboratory precision (reproducibility) of the analytical protocols used. We analyzed human samples in six laboratories using different instrumentation but a common protocol (the AbsoluteIDQ p180 kit) for the measurement of 189 metabolites via liquid chromatography (LC) or flow injection analysis (FIA) coupled to tandem mass spectrometry (MS/MS)...
December 13, 2016: Analytical Chemistry
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