Over the past decade there has been an exponential increase in the number of research papers utlising nanoparticles for biological applications such as intracellular sensing [1, 2], theranostics [3-5] and more recently drug delivery and precision medicine [6, 7]. Despite the success stories, there is a disconnect regarding current dogma on issues such as nanoparticle uptake and trafficking, nanoparticle delivery via the enhanced permeability and retention (EPR) effect, and endosomal escape. Critical re-evaluation of these concepts both conceptually and experimentally is needed for continued advancement in the field.

 

For this preregistration, Said et al. (2024) focus on nanoparticle intracellular trafficking, specifically endosomal escape [8]. The current consensus in the literature is that nanoparticles enter cells via endocytosis [9, 10] but reportedly just 1-2% of nanoparticles/ nanoparticle probes escape endosomes and enter the cytoplasm [11-13]. There is therefore an apparent paradox over how sensing nanoparticles can detect their intended targets in the cytoplasm if they are trapped within the cell endosomes. To address this fundamental issue of nanoparticle endosomal escape, Lévy and coworkers are carrying out replication studies to thoroughly and transparently replicate the most influential papers in the field of nanoparticle sensing. The aim of these replication studies is twofold: to establish a robust methodology to study endosomal escape of nanoparticles, and to encourage discussions, transparency and a step-change in the field.  

 

 

For this replication study, the authors classified papers on the topic of nanoparticle sensing and subsequently ranked them by number of citations.  Based on this evaluation they selected a paper by Zhu and colleagues [14] entitled “Carbon-Dot-Based Dual-Emission Nanohybrid Produces a Ratiometric Fluorescent Sensor for In Vivo Imaging of Cellular Copper Ions” for their seminal replication study.  To determine the reproducibility of the results from Zhu et al., the authors aim to establish the proportion of endosomal escape of the nanoparticles, and to examine the data in a biological context relevant to the application of the probe.

 

 

The authors plan to replicate the exact conditions reported in the materials and methods section of the selected paper such as nanoparticle probe synthesis of CdSe@C-TPEA nanoparticles, assessment of particle size, stability and reactivity and effect on cells (TEM, pH experiments, fluorescent responsivity to metal ions and cell viability). In addition, Said et al., plan to include further experimental characterisation to complement the existing study by Zhu and colleagues. They will incorporate additional controls and methodology to determine the intracellular location of nanoparticle probes in cells including: quantifying excess fluorescence in the culture medium, live cell imaging analysis, immunofluorescence with endosomal and lysosomal markers, and electron microscopy of cell sections. The authors will also include supplementary viability studies to assess the impact of the nanoparticles on HeLa cells as well as an additional biologically relevant cell line (for use in conjunction with the HeLa cells as per the original paper).

 

The Stage 1 manuscript underwent two rounds of thorough in-depth review. After considering the detailed responses to the reviewers' comments, the recommenders  determined that the manuscript met the Stage 1 criteria and awarded in-principle acceptance (IPA).  

 

The authors have thoughtfully considered their experimental approach to the replication study, whilst acknowledging any potential limitations. Given that conducting such a replication study is novel in the field of Nanotechnology and there is currently no ‘gold standard’ approach in doing so, the authors have showed thoughtful regard of statistical analysis and unbiased methodology where possible.

 

Based on current information, this study is the first use of preregistration via Peer Community in Registered Reports and the first formalised replication study in Nanotechnology for Biosciences. The outcomes of this of this study will be significant both scientifically and in the wider context in discussion of the scientific method.

 

 
Level of bias control achieved: Level 6. No part of the data or evidence that will be used to answer the research question yet exists and no part will be generated until after IPA.
 
List of eligible PCI RR-friendly Journals:

 

 

1. Howes, P. D., Chandrawati, R., & Stevens, M. M. (2014). Colloidal nanoparticles as advanced biological sensors. Science, 346(6205), 1247390. https://doi.org/10.1126/science.1247390

 

2. Liu, C. G., Han, Y. H., Kankala, R. K., Wang, S. B., & Chen, A. Z. (2020). Subcellular performance of nanoparticles in cancer therapy. International Journal of Nanomedicine, 675-704. https://doi.org/10.2147/IJN.S226186

 

3. Tang, W., Fan, W., Lau, J., Deng, L., Shen, Z., & Chen, X. (2019). Emerging blood–brain-barrier-crossing nanotechnology for brain cancer theranostics. Chemical Society Reviews, 48(11), 2967-3014. https://doi.org/10.1039/C8CS00805A

 

4. Yoon, Y. I., Pang, X., Jung, S., Zhang, G., Kong, M., Liu, G., & Chen, X. (2018). Smart gold nanoparticle-stabilized ultrasound microbubbles as cancer theranostics. Journal of Materials Chemistry B, 6(20), 3235-3239. https://doi.org/10.1039%2FC8TB00368H

 

5. Lin, H., Chen, Y., & Shi, J. (2018). Nanoparticle-triggered in situ catalytic chemical reactions for tumour-specific therapy. Chemical Society Reviews, 47(6), 1938-1958. https://doi.org/10.1039/C7CS00471K

 

6. Hou, X., Zaks, T., Langer, R., & Dong, Y. (2021). Lipid nanoparticles for mRNA delivery. Nature Reviews Materials, 6(12), 1078-1094. https://doi.org/10.1038/s41578-021-00358-0

 

7. Mitchell, M. J., Billingsley, M. M., Haley, R. M., Wechsler, M. E., Peppas, N. A., & Langer, R. (2021). Engineering precision nanoparticles for drug delivery. Nature Reviews Drug Discovery, 20(2), 101-124. https://doi.org/10.1038/s41573-020-0090-8

 

8. Said, M., Gharib, M., Zrig, S., & Lévy, R. (2024). Replication of “Carbon-Dot-Based Dual-Emission Nanohybrid Produces a Ratiometric Fluorescent Sensor for In Vivo Imaging of Cellular Copper Ions”. In principle acceptance of Version 3 by Peer Community in Registered Reports. https://osf.io/qbxpf

 

9. Behzadi, S., Serpooshan, V., Tao, W., Hamaly, M. A., Alkawareek, M. Y., Dreaden, E. C., ... & Mahmoudi, M. (2017). Cellular uptake of nanoparticles: Journey inside the cell. Chemical Society Reviews, 46(14), 4218-4244. https://doi.org/10.1039/C6CS00636A

 

10. de Almeida, M. S., Susnik, E., Drasler, B., Taladriz-Blanco, P., Petri-Fink, A., & Rothen-Rutishauser, B. (2021). Understanding nanoparticle endocytosis to improve targeting strategies in nanomedicine. Chemical society reviews, 50(9), 5397-5434. https://doi.org/10.1039/D0CS01127D

 

11. Smith, S. A., Selby, L. I., Johnston, A. P., & Such, G. K. (2018). The endosomal escape of nanoparticles: toward more efficient cellular delivery. Bioconjugate Chemistry, 30(2), 263-272. http://dx.doi.org/10.1021/acs.bioconjchem.8b00732

 

12. Cupic, K. I., Rennick, J. J., Johnston, A. P., & Such, G. K. (2019). Controlling endosomal escape using nanoparticle composition: current progress and future perspectives. Nanomedicine, 14(2), 215-223. https://doi.org/10.2217/nnm-2018-0326

 

13. Wang, Y., & Huang, L. (2013). A window onto siRNA delivery. Nature Biotechnology, 31(7), 611-612. https://doi.org/10.1038/nbt.2634

 

14. Zhu, A., Qu, Q., Shao, X., Kong, B., & Tian, Y. (2012). Carbon-dot-based dual-emission nanohybrid produces a ratiometric fluorescent sensor for in vivo imaging of cellular copper ions. Angewandte Chemie (International ed. in English), 51(29), 7185-7189. https://doi.org/10.1002/anie.201109089

In neurostimulation research, the parameters of a stimulation protocol crucially impact on the effects of the stimulation. Transcranial direct current stimulation (tDCS) is a neurostimulation technique that typically uses current intensities about 1-2 mA in human research to modulate motor and cognitive behavior. The current sham-controlled study by Hsu et al. (2024) applies current intensities not only of 2 mA but also of 4 mA and 6 mA and thus extends our understanding of stimulation parameters while ethical standards are preserved.

 

The influence of tDCS over the primary motor cortex will be evaluated for neural plasticity during motor learning. Stimulation effects will be tested not only behaviorally but also physiologically by motor evoked potentials elicited by transcranial magnetic stimulation (TMS). The presented pilot data are promising and underline the feasibility of the proposed research design. The study will contribute to tDCS research by uncovering reasons for controversial findings and thus increase reproducibility.

 

The Stage 1 manuscript was evaluated over two rounds of in-depth review. Based on detailed responses to the reviewers' comments, the recommender judged that the manuscript met the Stage 1 criteria and therefore awarded in-principle acceptance (IPA).

 

URL to the preregistered Stage 1 protocol: https://osf.io/jyuev
 
Level of bias control achieved: Level 2. At least some data/evidence that will be used to answer the research question has been accessed and partially observed by the authors, but the authors certify that they have not yet observed the key variables within the data that will be used to answer the research question.
 
List of eligible PCI RR-friendly journals:

 

• Brain and Neuroscience Advances
• Imaging Neuroscience
• NeuroImage: Reports
• Peer Community Journal
• PeerJ
• Royal Society Open Science
• Studia Psychologica

 

 

Hsu, G., Edwards, D. J., Cohen, L. G., & Parra, L. C. (2024). Dose-response of tDCS effects on motor learning and cortical excitability: a preregistered study. In principle acceptance of Version 1.3 by Peer Community in Registered Reports. https://osf.io/jyuev

Attachment and interpersonal relationships are a major subject of research and clinical work in psychology. There are, accordingly, a proliferation of measurement instruments to tap into these broad constructs. The emphasis in these measures tends to be on the emotional dimensions of the relationships—how people feel about their partners and the support that they receive. However, that is not all there is to relationship quality. Increasing attention has been paid to the physical and physiological aspects of relationships, but there are few psychometrically sound measures available to assess these dimensions.

 

In the current study, Dujols et al. (2024) assessed the psychometric properties of the Social Thermoregulation and Risk Avoidance Questionnaire (STRAQ-1), a measure of physical relationships that targets social thermoregulation, or how physical proximity is used to promote warmth and closeness. The project consists of a thorough assessment of the measure’s reliability over time—that is, the degree to which the measure assesses the construct similarly across administrations, in a sample of 183 French university students.

 

The authors assessed the longitudinal measurement invariance and test-restest reliability of the STRAQ-1. Longitudinal measurement invariance across two time points was only found for two of the four subscales. Similarly, test-retest reliability varied by subscale, ranging from poor to good. Taken together, the study suggests caution in using the STRAQ-1 scale as a reliable measure of physical relationships. The study highlights the need for continued assessment of the reliability of widely used measures, particularly reliability over time, and serves as a model for a rigorous analytic approach for doing so.

 

The Stage 2 manuscript was evaluated over two rounds of in-depth review, the first round consisting of comments from two reviewers and the second round consisting of a close read by the recommender. Based on detailed responses to the reviewers' comments, the recommender judged that the manuscript met the Stage 2 criteria and therefore awarded a positive recommendation.

 

URL to the preregistered Stage 1 protocol: https://osf.io/pmnk2
 
Level of bias control achieved: Level 3. At least some data/evidence that was used to the answer the research question was accessed by the authors prior to Stage 1 IPA (e.g. downloaded or otherwise received) but the authors certify that they had not observed ANY part of the data/evidence until after Stage 1 IPA.
 
List of eligible PCI RR-friendly journals:
 

 

 

1. Dujols, O., Klein, R. A., Lindenberg, S., Van Lissa, C. J., & IJzerman, H. (2024). Test-Retest Reliability of the STRAQ-1: A Registered Report [Stage 2]. Acceptance of Version 10 by Peer Community in Registered Reports. https://osf.io/preprints/psyarxiv/392g6

When we familiarise with new faces over repeated exposures, it is generally in situations that have meaning for us. Seeing a face more often tends to go along with learning more about the person, and their likely contexts and actions. In this Registered Report, Noad and Andrews (2024) tested whether meaningful context during exposure improves the consolidation of faces into long-term memory. Participants were shown video clips from the TV series Life on Mars, either in their original chronological sequence, which provides meaningful context, or in a scrambled sequence. It was expected that the original sequence would provide a better conceptual understanding, and this was confirmed by free recall and structured question tests. Face recognition memory was tested with images of the actor from the original clips (‘in show’) and the same actor from another show (‘out-of-show’), to test whether memory was modulated by the similarity of appearance to that at encoding. Face recognition was tested immediately after exposure and after four weeks, to allow time for consolidation. As expected, recognition memory was better for participants in the meaningful context condition, and for in-show faces. However, meaningful context did not lead to less forgetting of the faces at the follow up test, even for in-show faces, which did not support the original predictions. An exploratory analysis found that a metric of overlap between pairs of participants’ conceptual understanding was related to overlap in the set of faces they recognised. This relationship was stronger after four weeks, which suggests increased interaction of conceptual knowledge and face recognition after consolidation.

 

The Stage 2 manuscript was assessed over two rounds of review, and the recommender judged that the manuscript met the Stage 2 criteria for recommendation.

 

URL to the preregistered Stage 1 protocol: https://osf.io/8wp6f
 
Level of bias control achieved: Level 6. No part of the data or evidence that was used to answer the research question was generated until after IPA. 
 
List of eligible PCI RR-friendly journals:

 

 

References
 
1. Noad, K. & Andrews, T. J. (2024). The importance of conceptual knowledge when becoming familiar
with faces during naturalistic viewing [Stage 2]. Acceptance of Version 4 by Peer Community in Registered Reports. https://osf.io/thgrz

This study seeks to understand cultural and age differences in the effort moralization effect, a phenomenon in which people who put more effort into a task are considered more moral, regardless of the quality or the morality associated with the task. This is shown in common phrases such as the “great resignation” or “quiet quitting”, which are mostly used against younger members of the population, in particular generation Z.

 

Tissot and Roth (2024) propose to conduct a replication of a study from Celniker et al. (2023) which found evidence for this effect, with new samples from Mexico and Germany to test potential cultural differences. They will also test the effect of age on the effort moralization effect. Therefore, the study will be a quantitative analysis.
 
The authors included an adequate power analysis, alternatives for non-supported hypotheses, and filtering to ensure a high quality of data collection. They already provided an R script and dummy data to ensure the quality of the analysis.

 

The Stage 1 manuscript was evaluated over three rounds of in-depth review. Based on ​detailed responses to reviewers’ and the recommender’s comments, the recommender judged that the manuscript met the Stage 1 criteria and therefore awarded in-principle acceptance.​​​

 

 

Level of bias control achieved: Level 6. No part of the data or evidence that will be used to answer the research question yet exists and no part will be generated until after IPA.

 

List of eligible PCI RR-friendly journals:
 

 
References

 

1. Celniker, J. B., Gregory, A., Koo, H. J., Piff, P. K., Ditto, P. H., & Shariff, A. F. (2023). The moralization of effort. Journal of Experimental Psychology: General, 152, 60–79. https://doi.org/10.1037/xge0001259

 

2. Tissot, T. T. & Roth, L. H. O. (2024). Is it Worth the Hustle? A Multi-Country Replication of the Effort Moralization Effect and an Extension to Generational Differences in the Appreciation of Effort. In principle acceptance of Version 4 by Peer Community in Registered Reports. https://osf.io/tvgw2