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Michael Williams
Many results reported in the biomedical research literature cannot be independently reproduced, undermining the basic foundations of science. This overview is intended for researchers who are committed to improving the quality and integrity of biomedical science by raising awareness of both the sources of irreproducibility, and activities specifically targeted to address the issue. The irreproducibility of biomedical research is due to a variety of factors, known and unknown, that markedly influence experimental outcomes...
May 16, 2018: Current Protocols in Pharmacology
John Ogunsola, Richard Antia
Nucleolar organizer regions (NORs) are chromosomal segments which are selectively stained by silver methods and evaluated as agyrophilic nucleolar organizer regions (AgNORs). The evaluation of AgNORs provides an insight into the level of cellular proliferation. This technique has extensively and sparsely been used in human and veterinary histopathology respectively. However, two major drawbacks have been irreproducible results and excessive staining precipitates. This study seeks to adapt the technique to canine peripheral blood smears in order to establish a routine staining protocol...
2018: Open Veterinary Journal
Samuel Kobina Annim
This paper examines the accuracy, validity and presentation of statistical evidence and also assesses the implications of irreproducibility associated with variations in sample size for academic research work and policy-making. The 2012/13 Ghana Living Standards Survey (GLSS), 10 academic publications and the Free Senior High School policy in Ghana are used to address the objectives of the paper. The data show that about 20 per cent of the tables in the Main Report of the GLSS Six is irreproducible, 10 per cent of the tables have outcomes worth re-examining, and in terms of completeness in the presentation of statistical evidence, only 3 out of the 27 sampled tables report the sample size that was used...
June 2018: Data in Brief
Damion K Corrigan, Vincent Vezza, Holger Schulze, Till T Bachmann, Andrew R Mount, Anthony J Walton, Jonathan G Terry
For analytical applications involving label-free biosensors and multiple measurements, i.e., across an electrode array, it is essential to develop complete sensor systems capable of functionalization and of producing highly consistent responses. To achieve this, a multi-microelectrode device bearing twenty-four equivalent 50 µm diameter Pt disc microelectrodes was designed in an integrated 3-electrode system configuration and then fabricated. Cyclic voltammetry and electrochemical impedance spectroscopy were used for initial electrochemical characterization of the individual working electrodes...
June 9, 2018: Sensors
Bianca Vora, Aolin Wang, Idit Kosti, Hongtai Huang, Ishan Paranjpe, Tracey J Woodruff, Tippi MacKenzie, Marina Sirota
Preterm birth (PTB) is the leading cause of newborn deaths around the world. Spontaneous preterm birth (sPTB) accounts for two-thirds of all PTBs; however, there remains an unmet need of detecting and preventing sPTB. Although the dysregulation of the immune system has been implicated in various studies, small sizes and irreproducibility of results have limited identification of its role. Here, we present a cross-study meta-analysis to evaluate genome-wide differential gene expression signals in sPTB. A comprehensive search of the NIH genomic database for studies related to sPTB with maternal whole blood samples resulted in data from three separate studies consisting of 339 samples...
2018: Frontiers in Immunology
Chen Liu, He Cheng, Kaizhou Jin, Meng Guo, Yu Lu, Zhengshi Wang, Chao Yang, Jiang Long, Quanxing Ni, Xianjun Yu, Guopei Luo
OBJECTIVES: Notable modifications have been made in the American Joint Committee on Cancer (AJCC) Staging eighth edition staging for pancreatic cancer for the consideration of the irreproducible and inapplicable of the AJCC seventh edition staging. However, the new staging classification has not been systemically verified. METHODS: A comparison was performed to evaluate the application of the AJCC seventh and eighth staging classifications using the Surveillance, Epidemiology, and End Results registry (18,450 patients) and an institutional series (2040 patients)...
May 30, 2018: Pancreas
Bor Luen Tang
Important and potentially useful findings in the sciences are under more intense public scrutiny now more than ever. Other researchers in the field dive into replicating and expanding the findings while the media swamps the community and the public with peripheral reporting and analyses. How should authors and the hosting/funding institutions respond when other workers in the field could not reproduce or replicate their published results? To illustrate the importance of author-initiated and institution-driven investigations in response to outcries of research irreproducibility, I draw on comparisons between three recent and well-publicized cases in the life sciences: betatrophin, STAP cells, and NgAgo...
May 20, 2018: Accountability in Research
Yan Wu, Tingting Jiang, Zhaoyang Wu, Ruqin Yu
A ratiometric surface-enhanced Raman scattering (SERS) aptasensor based on internal standard (IS) methods was proposed for the ultrasensitive and reproducible quantitative detection of silver ion (Ag+ ) with Au@Ag core-shell nanoparticle (Au@Ag NP) substrate. In principle, the thiolated 5'-Rox C-containing labeled aptamer probe (Rox-aptamer) is firstly immobilized on the SERS substrate surface and then hybridizes with the complementary DNA (cDNA) to form a rigid double-stranded DNA (dsDNA), in which the Rox Raman labels is used to produce the Raman signal...
August 1, 2018: Talanta
Daria Krefft, Aliaksei Papkov, Maciej Prusinowski, Agnieszka Zylicz-Stachula, Piotr M Skowron
BACKGROUND: Acoustic or hydrodynamic shearing, sonication and enzymatic digestion are used to fragment DNA. However, these methods have several disadvantages, such as DNA damage, difficulties in fragmentation control, irreproducibility and under-representation of some DNA segments. The DNA fragmentation tool would be a gentle enzymatic method, offering cleavage frequency high enough to eliminate DNA fragments distribution bias and allow for easy control of partial digests. Only three such frequently cleaving natural restriction endonucleases (REases) were discovered: CviJI, SetI and FaiI...
May 11, 2018: BMC Genomics
Gustavo Diaz, Chandler Bridges, Megan Lucas, Yong Cheng, Jeff S Schorey, Karen M Dobos, Nicole A Kruh-Garcia
Exosomes, a type of nanovesicle released from all cell types, can be isolated from any bodily fluid. The contents of exosomes, including proteins and RNAs, are unique to the cells from which they are derived and can be used as indicators of disease. Several common enrichment protocols, including ultracentrifugation, yield exosomes laden with soluble protein contaminants. Specifically, we have found that the most abundant proteins within blood often co-purify with exosomes and can confound downstream proteomic studies, thwarting the identification of low abundance biomarker candidates...
April 13, 2018: Journal of Visualized Experiments: JoVE
Katarzyna B Handing, Ewa Niedzialkowska, Ivan G Shabalin, Misty L Kuhn, Heping Zheng, Wladek Minor
Metals have crucial roles in many physiological, pathological, toxicological, pharmaceutical, and diagnostic processes. Proper handling of metal-containing macromolecule samples for structural studies is not trivial, and failure to handle them properly is often a source of irreproducibility caused by issues such as pH changes, incorporation of unexpected metals, or oxidization/reduction of the metal. This protocol outlines the guidelines and best practices for characterizing metal-binding sites in protein structures and alerts experimenters to potential pitfalls during the preparation and handling of metal-containing protein samples for X-ray crystallography studies...
May 2018: Nature Protocols
Huei-Chung Huang, Li-Xuan Qin
Background: Data artifacts due to variations in experimental handling are ubiquitous in microarray studies, and they can lead to biased and irreproducible findings. A popular approach to correct for such artifacts is through post hoc data adjustment such as data normalization. Statistical methods for data normalization have been developed and evaluated primarily for the discovery of individual molecular biomarkers. Their performance has rarely been studied for the development of multi-marker molecular classifiers-an increasingly important application of microarrays in the era of personalized medicine...
2018: PeerJ
Carl Philipp Rosenau, Benson J Jelier, Alvar D Gossert, Antonio Togni
Fluorine chemistry has taken a pivotal role in chemical reaction discovery, drug development, and chemical biology. NMR spectroscopy, arguably the most important technique for the characterization of fluorinated compounds, is rife with highly inconsistent referencing of fluorine NMR chemical shifts, producing deviations larger than 1 ppm. Herein, we provide unprecedented evidence that both spectrometer design and the current unified scale system underpinning the calibration of heteronuclear NMR spectra have unintentionally led to widespread variation in the standardization of 19 F NMR spectral data...
April 16, 2018: Angewandte Chemie
Ahmad Haeri Mazanderani, Faith Moyo, Tendesayi Kufa, Jean Maritz, Gayle G Sherman
We describe the extent of and variables associated with irreproducible HIV-1 PCR positive results within South Africa's Early Infant Diagnosis (EID) program from 2010 to 2015 and propose criteria for differentiating indeterminate from clearly positive results using the COBAS® AmpliPrep/COBAS® TaqMan HIV-1 Qualitative Test version 2.0 (CAP/CTM Qual v2.0). Fourteen percent of specimens with an instrument-positive result that were repeat-tested yielded a negative result for which cycle threshold (Ct) proved to be the only predictive variable...
March 3, 2018: Diagnostic Microbiology and Infectious Disease
Delphine R Boulbes, Tracy Costello, Keith Baggerly, Fan Fan, Rui Wang, Rajat Bhattacharya, Xiangcang Ye, Lee M Ellis
Purpose: The successful translation of laboratory research into effective therapies is dependent upon the validity of peer-reviewed publications. However, several publications in recent years suggested that published scientific findings could be reproduced only 11% to 45% of the time. Multiple surveys attempted to elucidate the fundamental causes of data irreproducibility and underscored potential solutions, more robust experimental designs, better statistics, and better mentorship. However, no prior survey has addressed the role of the review and publication process on honest reporting...
April 11, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Clare Fiala, Eleftherios P Diamandis
Irreproducibility is a widely recognized problem harming scientific progress. Here, we classify types of scientific irreproducibility based on deleteriousness using a cancer analogy: benign, pre-malignant and malignant. We discuss the difficulties of challenging potentially irreproducible papers, especially in high impact journals and/or by famous authors. We advocate for high impact journals publishing papers with large translation value, to implement mandatory author reflections on the reproducibility, utility and relevance of their work 5 to 10 years after publication...
May 2018: Clinical Biochemistry
Daiping Wang, Wolfgang Forstmeier, Malika Ihle, Mehdi Khadraoui, Sofia Jerónimo, Katrin Martin, Bart Kempenaers
Many fields of science-including behavioral ecology-currently experience a heated debate about the extent to which publication bias against null findings results in a misrepresentative scientific literature. Here, we show a case of an extreme mismatch between strong positive support for an effect in the literature and a failure to detect this effect across multiple attempts at replication. For decades, researchers working with birds have individually marked their study species with colored leg bands. For the zebra finch Taeniopygia guttata, a model organism in behavioral ecology, many studies over the past 35 years have reported effects of bands of certain colors on male or female attractiveness and further on behavior, physiology, life history, and fitness...
April 2018: Evolution; International Journal of Organic Evolution
Abha Belorkar, Rajanikanth Vadigepalli, Limsoon Wong
BACKGROUND: Transcriptomic datasets often contain undeclared heterogeneity arising from biological variation such as diversity of disease subtypes, treatment subgroups, time-series gene expression, nested experimental conditions, as well as technical variation due to batch effects, platform differences in integrated meta-analyses, etc. However, current analysis approaches are primarily designed to handle comparisons between experimental conditions represented by homogeneous samples, thus precluding the discovery of underlying subphenotypes...
March 19, 2018: BMC Systems Biology
Swapna Mohan, Robert W Barbee, Susan B Silk
The IACUC comprises the key component of animal research oversight at any institution or facility and thus has the responsibility to review and approve proposed animal activities. As the primary oversight unit that ensures the quality of animal welfare and therefore contributes to overall research quality, the IACUC can support reproducibility in research by ensuring rigorous experimental design, standardization of care and management, and assessment of the validity of research. An IACUC that is constituted as required by the Animal Welfare Act and the PHS Policy incorporates a wide range of expertise...
March 1, 2018: Journal of the American Association for Laboratory Animal Science: JAALAS
Richard M Shiffrin, Katy Börner, Stephen M Stigler
It appears paradoxical that science is producing outstanding new results and theories at a rapid rate at the same time that researchers are identifying serious problems in the practice of science that cause many reports to be irreproducible and invalid. Certainly, the practice of science needs to be improved, and scientists are now pursuing this goal. However, in this perspective, we argue that this seeming paradox is not new, has always been part of the way science works, and likely will remain so. We first introduce the paradox...
March 13, 2018: Proceedings of the National Academy of Sciences of the United States of America
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