Estimating the replicability of highly cited clinical research (2004-2018).

Introduction: Previous studies about the replicability of clinical research based on the published literature have suggested that highly cited articles are often contradicted or found to have inflated effects. Nevertheless, there are no recent updates of such efforts, and this situation may have changed over time.

Methods: We searched the Web of Science database for articles studying medical interventions with more than 2000 citations, published between 2004 and 2018 in high-impact medical journals.

Open Science 2.0: Towards a truly collaborative research ecosystem.

Conversations about open science have reached the mainstream, yet many open science practices such as data sharing remain uncommon. Our efforts towards openness therefore need to increase in scale and aim for a more ambitious target. We need an ecosystem not only where research outputs are openly shared but also in which transparency permeates the research process from the start and lends itself to more rigorous and collaborative research.

Characterization of Comments About bioRxiv and medRxiv Preprints.

Importance: Preprints have been increasingly used in biomedical science, and a key feature of many platforms is public commenting. The content of these comments, however, has not been well studied, and it is unclear whether they resemble those found in journal peer review.

Objective: To describe the content of comments on the bioRxiv and medRxiv preprint platforms.

Are most published research findings false in a continuous universe?

Diagnostic screening models for the interpretation of null hypothesis significance test (NHST) results have been influential in highlighting the effect of selective publication on the reproducibility of the published literature, leading to John Ioannidis' much-cited claim that most published research findings are false. These models, however, are typically based on the assumption that hypotheses are dichotomously true or false, without considering that effect sizes for different hypotheses are not the same. To address this limitation, we develop a simulation model that overcomes this by modeling effect sizes explicitly using different continuous distributions, while retaining other aspects of previous models such as publication bias and the pursuit of statistical significance.

Memory destabilization during reconsolidation: a consequence of homeostatic plasticity?

Remembering is not a static process: When retrieved, a memory can be destabilized and become prone to modifications. This phenomenon has been demonstrated in a number of brain regions, but the neuronal mechanisms that rule memory destabilization and its boundary conditions remain elusive. Using two distinct computational models that combine Hebbian plasticity and synaptic downscaling, we show that homeostatic plasticity can function as a destabilization mechanism, accounting for behavioral results of protein synthesis inhibition upon reactivation with different re-exposure times.

Comparing quality of reporting between preprints and peer-reviewed articles in the biomedical literature.

Background: Preprint usage is growing rapidly in the life sciences; however, questions remain on the relative quality of preprints when compared to published articles. An objective dimension of quality that is readily measurable is completeness of reporting, as transparency can improve the reader's ability to independently interpret data and reproduce findings.

Methods: In this observational study, we initially compared independent samples of articles published in bioRxiv and in PubMed-indexed journals in 2016 using a quality of reporting questionnaire.

Two years into the Brazilian Reproducibility Initiative: reflections on conducting a large-scale replication of Brazilian biomedical science.

Scientists have increasingly recognised that low methodological and analytical rigour combined with publish-or-perish incentives can make the published scientific literature unreliable. As a response to this, large-scale systematic replications of the literature have emerged as a way to assess the problem empirically. The Brazilian Reproducibility Initiative is one such effort, aimed at estimating the reproducibility of Brazilian biomedical research.

Using collaboration networks to identify authorship dependence in meta-analysis results.

Meta-analytic methods are powerful resources to summarize the existing evidence concerning a given research question and are widely used in many academic fields. Meta-analyzes can also be used to study sources of heterogeneity and bias among results, which should be considered to avoid inaccuracies. Many of these sources can be related to study authorship, as both methodological heterogeneity and researcher bias may lead to deviations in results between different research groups.

Addressing selective reporting of experiments through predefined exclusion criteria.

The pressure for every research article to tell a clear story often leads researchers in the life sciences to exclude experiments that 'did not work' when they write up their results. However, this practice can lead to reporting bias if the decisions about which experiments to exclude are taken after data have been collected and analyzed. Here we discuss how to balance clarity and thoroughness when reporting the results of research, and suggest that predefining the criteria for excluding experiments might help researchers to achieve this balance.

Shifting from fear to safety through deconditioning-update.

Aversive memories are at the heart of psychiatric disorders such as phobias and post-traumatic stress disorder (PTSD). Here, we present a new behavioral approach in rats that robustly attenuates aversive memories. This method consists of 'deconditioning' animals previously trained to associate a tone with a strong footshock by replacing it with a much weaker one during memory retrieval.

A Freely Available, Self-Calibrating Software for Automatic Measurement of Freezing Behavior.

Freezing behavior is commonly used as a measure of associative fear memory. It can be measured by a trained observer, but this task is time-consuming and subject to variation. Commercially available software packages can also be used to quantify freezing; however, they can be expensive and usually require various parameters to be adjusted by the researcher, leading to additional work and variability in results.

Chronic in vivo optogenetic stimulation modulates neuronal excitability, spine morphology, and Hebbian plasticity in the mouse hippocampus.

Prolonged increases in excitation can trigger cell-wide homeostatic responses in neurons, altering membrane channels, promoting morphological changes, and ultimately reducing synaptic weights. However, how synaptic downscaling interacts with classical forms of Hebbian plasticity is still unclear. In this study, we investigated whether chronic optogenetic stimulation of hippocampus CA1 pyramidal neurons in freely moving mice could (a) cause morphological changes reminiscent of homeostatic scaling, (b) modulate synaptic currents that might compensate for chronic excitation, and (c) lead to alterations in Hebbian plasticity.

The Brazilian Reproducibility Initiative.

Most efforts to estimate the reproducibility of published findings have focused on specific areas of research, even though science is usually assessed and funded on a regional or national basis. Here we describe a project to assess the reproducibility of findings in biomedical science published by researchers based in Brazil. The Brazilian Reproducibility Initiative is a systematic, multicenter effort to repeat between 60 and 100 experiments: the project will focus on a set of common methods, repeating each experiment in three different laboratories from a countrywide network.

Different temporal windows for CB1 receptor involvement in contextual fear memory destabilisation in the amygdala and hippocampus.

Reconsolidation is a process in which re-exposure to a reminder causes a previously acquired memory to undergo a process of destabilisation followed by subsequent restabilisation. Different molecular mechanisms have been postulated for destabilisation in the amygdala and hippocampus, including CB1 receptor activation, protein degradation and AMPA receptor exchange; however, most of the amygdala studies have used pre-reexposure interventions, while those in the hippocampus have usually performed them after reexposure. To test whether the temporal window for destabilisation is similar across both structures, we trained Lister Hooded rats in a contextual fear conditioning task, and 1 day later performed memory reexposure followed by injection of either the NMDA antagonist MK-801 (0.

Effect size and statistical power in the rodent fear conditioning literature - A systematic review.

Proposals to increase research reproducibility frequently call for focusing on effect sizes instead of p values, as well as for increasing the statistical power of experiments. However, it is unclear to what extent these two concepts are indeed taken into account in basic biomedical science. To study this in a real-case scenario, we performed a systematic review of effect sizes and statistical power in studies on learning of rodent fear conditioning, a widely used behavioral task to evaluate memory.

On the transdiagnostic nature of peripheral biomarkers in major psychiatric disorders: A systematic review.

The search for biomarkers has been a leading endeavor in biological psychiatry. To analyze its evolution over the years, we performed a systematic review to evaluate (a) the most studied peripheral molecular markers in major psychiatric disorders, (b) the main features of studies proposing them as biomarkers and (c) whether their patterns of variation are similar across disorders. Of the six molecules most commonly studied as plasmatic markers of schizophrenia, major depressive disorder or bipolar disorder, five (BDNF, TNF-alpha, IL-6, C-reactive protein and cortisol) were the same across diagnoses.

On the transition from reconsolidation to extinction of contextual fear memories.

Retrieval of an associative memory can lead to different phenomena. Brief reexposure sessions tend to trigger reconsolidation, whereas more extended ones trigger extinction. In appetitive and fear cued Pavlovian memories, an intermediate "null point" period has been observed where neither process seems to be engaged.

Protocol for a Systematic Review of Effect Sizes and Statistical Power in the Rodent Fear Conditioning Literature.

The concepts of effect size and statistical power are often disregarded in basic neuroscience, and most articles in the field draw their conclusions solely based on the arbitrary significance thresholds of statistical inference tests. Moreover, studies are often underpowered, making conclusions from significance tests less reliable. With this in mind, we present the protocol of a systematic review to study the distribution of effect sizes and statistical power in the rodent fear conditioning literature, and to analyze how these factors influence the description and publication of results.

Calcineurin inhibition blocks within-, but not between-session fear extinction in mice.

Memory extinction involves the formation of a new associative memory that inhibits a previously conditioned association. Nonetheless, it could also depend on weakening of the original memory trace if extinction is assumed to have multiple components. The phosphatase calcineurin (CaN) has been described as being involved in extinction but not in the initial consolidation of fear learning.

Multifactoriality in Psychiatric Disorders: A Computational Study of Schizophrenia.

The search for biological causes of mental disorders has up to now met with limited success, leading to growing dissatisfaction with diagnostic classifications. However, it is questionable whether most clinical syndromes should be expected to correspond to specific microscale brain alterations, as multiple low-level causes could lead to similar symptoms in different individuals. In order to evaluate the potential multifactoriality of alterations related to psychiatric illness, we performed a parametric exploration of published computational models of schizophrenia.