Microgravity analogue literature review

dr.richard.barker · June 19, 2024, 3:43pm

Mining the Microgravity Analogue Literature: Help Needed!

Hey everyone,

With so many open-source microgravity platforms available, I figured it’s time to review the existing literature and i need your help sifting through a massive pile of research papers!

Here’s the challenge: I’ve pulled 17,411 papers from NCBI related to 3 groups of microgravity analogues (RPMs, 2D clinostats, slow rotating wall vessels). The tables listing these papers are in a GitHub repository along with the code used to find them and a summary of some initial findings.

The question is: How many of these papers are truly relevant to microgravity analogue experiments? There are likely to be some false positives in this dataset (my manual inspection of a small fraction of the slow wall rotating vessel group was promising but i’m not use if its just because i’m relying on the title and not the abstract?).

Can you lend a hand? I'm looking for clever ways to analyze this list of papers (titles, abstracts, journals) to identify the real deal and remove any irrelevant studies/ false positives.

Does this require a human(s) to read all titles and abstracts to pass judgment? Or is it more time-effective to find a way to make the initial search more precise? How do we assess the accuracy of this initial NCBI search?

I’ve put the code and lists of papers (& related meta-data such as author, abstract, title, publication year, journal), along with the code and a summary in this GitHub repo (GitHub - dr-richard-barker/Microgravity_analogue_review)

If this sounds interesting to you please let me know and we could create a focus group to help assess or enhance your solution or strategy.

Thanks for your time and consideration
Cheers DRB

@PlantAWG @ALSDAawg @AnimalAWG

Oracle009 · June 19, 2024, 4:21pm

Hi Richard,

This sounds interesting. I would love to be part of it. Anything I can do?

angel · June 19, 2024, 4:33pm

For sure, give me examples in csv of false positives and I could help you with this task.

dr.richard.barker · June 19, 2024, 4:36pm

Sure, here’s the link to the .csv in the repo that contains all the papers.
The same repo also contains a python note book that was used to create each of the groups.

github.com

dr-richard-barker/Microgravity_analogue_review/blob/main/RPM_clinostat_literature_combined_4_ai.csv

Group,PMID,Title,Abstract,Authors,Keywords,Publication Year,Journal Title,Publication Type,
RPM,37662695,Technology using simulated microgravity.,"The human body experiences constant stimulation from Earth's gravity, and the absence of gravity leads to various impacts at the cellular and tissue levels. Simulated microgravity (s-μg) has been employed on Earth to investigate these effects, circumventing the challenges of conducting experiments in space and providing an opportunity to understand the influence of microgravity on living organisms. Research focusing on stem cells and utilizing s-μg has enhanced our understanding of how microgravity affects stem cell morphology, migration, proliferation, and differentiation. Studies have used systems such as rotating wall vessels, random positioning machines, and clinostats. By uncovering the mechanisms underlying the observed changes in these studies, there is potential to identify therapeutic targets that regulate stem cell function and explore a range of applications, including stem cell-based regenerative medicine. This review will focus on the features of each device designed to simulate microgravity on Earth, as well as the stem cell experiments performed with those devices. Elsevier B.V.",Nishimura Y,Random positioning machine; Regenerative therapy; Rotating wall vessel; Simulated microgravity; Stem cells,2023,Regenerative therapy,Journal Article; Review,
RPM,34833068,Biological and Mechanical Characterization of the Random Positioning Machine (RPM) for Microgravity Simulations.,"The rapid improvement of space technologies is leading to the continuous increase of space missions that will soon bring humans back to the Moon and, in the coming future, toward longer interplanetary missions such as the one to Mars. The idea of living in space is charming and fascinating; however, the space environment is a harsh place to host human life and exposes the crew to many physical challenges. The absence of gravity experienced in space affects many aspects of human biology and can be reproduced in vitro with the help of microgravity simulators. Simulated microgravity (s-μg) is applied in many fields of research, ranging from cell biology to physics, including cancer biology. In our study, we aimed to characterize, at the biological and mechanical level, a Random Positioning Machine in order to simulate microgravity in an in vitro model of Triple-Negative Breast Cancer (TNBC). We investigated the effects played by s-μg by analyzing the change of expression of some genes that drive proliferation, survival, cell death, cancer stemness, and metastasis in the human MDA-MB-231 cell line. Besides the mechanical verification of the RPM used in our studies, our biological findings highlighted the impact of s-μg and its putative involvement in cancer progression.",Calvaruso M; Militello C; Minafra L; La Regina V; Torrisi F; Pucci G; Cammarata FP; Bravatà V; Forte GI; Russo G,TNBC; cancer biology; random positioning machine; simulated microgravity; space biology,2021,"Life (Basel, Switzerland)",Journal Article,GeSeTON project grant 489 of 21/02/2018/Italian MISE/
RPM,32735428,Different Foot Positioning During Calf Training to Induce Portion-Specific Gastrocnemius Muscle Hypertrophy.,"Nunes, JP, Costa, BDV, Kassiano, W, Kunevaliki, G, Castro-e-Souza, P, Rodacki, ALF, Fortes, LS, and Cyrino, ES. Different foot positioning during calf training to induce portion-specific gastrocnemius muscle hypertrophy. J Strength Cond Res 34(8): 2347-2351, 2020-The aim of this study was to compare the changes in gastrocnemius muscle thickness (MT) between conditions such as which foot was pointed outward (FPO), foot was pointed inward (FPI), or foot was pointed forward (FPF). Twenty-two young men (23 ± 4 years) were selected and performed a whole-body resistance training program 3 times per week for 9 weeks, with differences in the exercise specific for calves. The calf-raise exercise was performed unilaterally, in a pin-loaded seated horizontal leg-press machine, in 3 sets of 20-25 repetitions for training weeks 1-3 and 4 sets for weeks 4-9. Each subject's leg was randomly assigned for 1 of the 3 groups according to the foot position: FPO, FPI, and FPF. Measurements with a B-mode ultrasound were performed to assess changes in MT of medial and lateral gastrocnemius heads. After the training period, there were observed increases in MT of both medial (FPO = 8.4%, FPI = 3.8%, and FPF = 5.8%) and lateral (FPO = 5.5%, FPI = 9.1%, and FPF = 6.4%) gastrocnemius heads, and significant differences for magnitude of the gains were observed between FPO and FPI conditions (p < 0.05). Positioning FPO potentiated the increases in MT of the medial gastrocnemius head, whereas FPI provided greater gains for the lateral gastrocnemius head. Our results suggest that head-specific muscle hypertrophy may be obtained selectively for gastrocnemius after 9 weeks of calf training in young male adults.",Nunes JP; Costa BDV

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botanynerd · June 19, 2024, 4:36pm

I was an author on a similar paper in recent years. It was nowhere near this exhaustive.

This led to the development of the NASA Space Life Science Library. Many interns contributed to this work over the years.
https://public.ksc.nasa.gov/nslsl/

angel · June 19, 2024, 4:41pm

In this case RPM.csv and rotating_wall.csv are partially clean and RPM_clinostat_literature_combined_4_ai.csv is combined with false positives?

dr.richard.barker · June 19, 2024, 4:44pm

None of the .csv files have been cleaned.
Each was pulled separately and then merged into one with a new “Group” designation.
The paper provided @Botanynerd and the references inside it are the closest thing we have to a “cleaned” dataset.

angel · June 19, 2024, 4:45pm

ok, can you send me false positives?

dr.richard.barker · June 19, 2024, 4:58pm

Not a comprehensive list but here’s 168 (not evenly distributed amount the 3 groups)…

github.com

dr-richard-barker/Microgravity_analogue_review/blob/main/false_possitives_v1_168.csv

Group,PMID,Title,Abstract,Authors,Keywords,Publication Year,Journal Title,Publication Type,
2D,15664956,A549 lung epithelial cells grown as three-dimensional aggregates: alternative tissue culture model for Pseudomonas aeruginosa pathogenesis.,"A three-dimensional (3-D) lung aggregate model was developed from A549 human lung epithelial cells by using a rotating-wall vessel bioreactor to study the interactions between Pseudomonas aeruginosa and lung epithelial cells. The suitability of the 3-D aggregates as an infection model was examined by immunohistochemistry, adherence and invasion assays, scanning electron microscopy, and cytokine and mucoglycoprotein production. Immunohistochemical characterization of the 3-D A549 aggregates showed increased expression of epithelial cell-specific markers and decreased expression of cancer-specific markers compared to their monolayer counterparts. Immunohistochemistry of junctional markers on A549 3-D cells revealed that these cells formed tight junctions and polarity, in contrast to the cells grown as monolayers. Additionally, the 3-D aggregates stained positively for the production of mucoglycoprotein while the monolayers showed no indication of staining. Moreover, mucin-specific antibodies to MUC1 and MUC5A bound with greater affinity to 3-D aggregates than to the monolayers. P. aeruginosa attached to and penetrated A549 monolayers significantly more than the same cells grown as 3-D aggregates. Scanning electron microscopy of A549 cells grown as monolayers and 3-D aggregates infected with P. aeruginosa showed that monolayers detached from the surface of the culture plate postinfection, in contrast to the 3-D aggregates, which remained attached to the microcarrier beads. In response to infection, proinflammatory cytokine levels were elevated for the 3-D A549 aggregates compared to monolayer controls. These findings suggest that A549 lung cells grown as 3-D aggregates may represent a more physiologically relevant model to examine the interactions between P. aeruginosa and the lung epithelium during infection.",Carterson AJ; Höner zu Bentrup K; Ott CM; Clarke MS; Pierson DL; Vanderburg CR; Buchanan KL; Nickerson CA; Schurr MJ,NASA Discipline Cell Biology; Non-NASA Center,2005,Infection and immunity,"Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.",R01 AI050812/AI/NIAID NIH HHS/United States; R01 AI050812-02/AI/NIAID NIH HHS/United States
2D,11893073,Secondary metabolism in simulated microgravity.,"We have studied microbial secondary metabolism in a simulated microgravity (SMG) environment provided by NASA rotating-wall bioreactors (RWBs). These reactors were designed to simulate some aspects of actual microgravity that occur in space. Growth and product formation were observed in SMG in all cases studied, i.e., Bacillus brevis produced gramicidin S (GS), Streptomyces clavuligerus made beta-lactam antibiotics, Streptomyces hygroscopicus produced rapamycin, and Escherichia coli produced microcin B17 (MccB17). Of these processes, only GS production was unaffected by SMG; production of the other three products was inhibited. This was determined by comparison with performance in an RWB positioned in a different mode to provide a normal gravity (NG) environment. Carbon source repression by glycerol of the GS process, as observed in shaken flasks, was not observed in the RWBs, whether operated in the SMG or NG mode. The same phenomenon occurred in the case of MccB17 production, with respect to glucose repression. Thus, the negative effects of carbon source on GS and beta-lactam formation are presumably dependent on shear, turbulence, and/or vessel geometry, but not on gravity. Stimulatory effects of phosphate and the precursor L-lysine on beta-lactam antibiotic production, as observed in flasks, also occurred in SMG. An almost complete shift in the localization of produced MccB17 from cells to extracellular medium was observed when E. coli was grown in the RWB under SMG or NG. If a plastic bead was placed in the RWB, accumulation became cellular, as it is in shaken flasks, indicating that sheer stress favors a cellular location. In the case of rapamycin, the same type of shift was observed, but it was less dramatic, i.e., growth in the RWB under SMG shifted the distribution of produced rapamycin from 2/3 cellular:1/3 extracellular to 1/3 cellular:2/3 extracellular. Stress has been shown to induce or promote secondary metabolism in a number of other microbial systems. RWBs provide a low stress SMG environment, which, however, supports only poor production of MccB17, as compared to production in shaken flasks. We wondered whether the poor production in RWBs under SMG is due to the low level of stress, and whether increasing stress in the RWBs would raise the amount of MccB17 formed. We found that increasing shear stress by adding a single Teflon bead to the RWB improved MccB17 production. Although shear stress seems to have a marked

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dr.richard.barker · June 19, 2024, 5:01pm

Looking through the titles and abstracts i think ideally they should mention the species, the tissue, (sometimes) the assay name and the microgravity analogue type/description → that enables grouping for the meta-analysis. I think finding a way to pull this information into columns in the table may help identify false positives. Possibly?

MarshallPorterfield · June 19, 2024, 5:03pm

Hey Richard I am really interested in developing the biophysical assessments of these treatments in terms of mechanical and thermal systems, and developing some quantitative models of these factors within these treatment systems…

angel · June 19, 2024, 5:05pm

Yes, it is. I’m going to check the information and develop something, hold on.

Mustare_Madobe · June 19, 2024, 5:14pm

I am interested to be a part of it.

angel · June 19, 2024, 7:05pm

I found 108 automatically (2D case), but I require you to check if it is correct while I search for matches with slightly more complex methods:

https://www.grupoalianzaempresarial.biz/nasa/awg/microgravityanalogueliteraturereview/identified_false_positives_2D.csv

angel · June 19, 2024, 7:27pm

RPM case:

https://www.grupoalianzaempresarial.biz/nasa/awg/microgravityanalogueliteraturereview/identified_false_positives_rpm.csv

angel · June 19, 2024, 9:01pm

I found 153 in 2D using a more complex method, but it consumes considerably more resources:

https://www.grupoalianzaempresarial.biz/nasa/awg/microgravityanalogueliteraturereview/identified_false_positives_2D_a.csv

Tell me if you consider any of the results useful so I can share the code with you. I have several meetings but when I return I can explore other approaches that might be useful to you.

dr.richard.barker · June 19, 2024, 10:07pm

Hello, this is really interesting… Yes, this is really helpful, i just ned help understand what happened?
It’s hard to be sure what happened with just these .csv files.
I’m a bit confused as for the RPM analysis there were ~9958 papers but this filtered list only contains 683 entries. I can see there are new columns entitled “is_false_positive_2D” or “predicted_false_positive” which is exactly what we want to see! Awesome, is it possible to do it will all 17411 papers in the combined list? Thanks for your help with this

angel · June 20, 2024, 12:18am

I’m back. Sorry for not being specific, the files I gave you are false positives, you have to delete them from your database, what I need to know is if I deleted them correctly with the processes I developed (I check the first 20 and it’s ok), we can make an hybrid (humans labeling) or full automatic process (but it can be less rigorous).

In the first case I developed a non intensive method and I got:

2D (found 108 to exclude):
https://www.grupoalianzaempresarial.biz/nasa/awg/microgravityanalogueliteraturereview/identified_false_positives_2D.csv

RPM (found 684 to exclude):
https://www.grupoalianzaempresarial.biz/nasa/awg/microgravityanalogueliteraturereview/identified_false_positives_rpm.csv

I developed a more intensive method but I only tested in 2D (found 153 to exclude):

https://www.grupoalianzaempresarial.biz/nasa/awg/microgravityanalogueliteraturereview/identified_false_positives_2D_a.csv

In the case that humans can label if we can discard a paper, I can develop a recursive process to simpify the task and you can multiply the human capacity, but we need a server (maybe a NASA server with linux and ssh, I can host this process but maybe you want to use this methods for other task in the future) for the interface, for example, if a human label 1 paper, we have more cases to discard more papers, in this case with your csv with false positives I discard these elements (2D: 163 and RPM:684).

Except for some meetings I have this week, I have time to help you label, maybe we can end up with a hybrid approach this week, but the result might not be perfect, I can develop another interface to label if someone finds an irrelevant document and maybe one label could help to discard more documents.

angel · June 20, 2024, 12:29am

These false positives are from the 17411 papers, but we need more human labeling to discard more, maybe I can do that, but maybe you have a team doing this that we can use to finish with this task faster.

angel · June 20, 2024, 12:42am

Bad news: the false positives are the same that you sent me (168, if you have more, could be better), the difference was only PMID repeated.
Good news: With the more intensive process, I discard 1392 in RPM.

https://www.grupoalianzaempresarial.biz/nasa/awg/microgravityanalogueliteraturereview/identified_false_positives_rpm_a.csv

Now I can exclude 1392+108=1500.

Now I’m going to work with:

RPM: 8565.
https://www.grupoalianzaempresarial.biz/nasa/awg/microgravityanalogueliteraturereview/RPM_w.csv

2D: 6320.
https://www.grupoalianzaempresarial.biz/nasa/awg/microgravityanalogueliteraturereview/2d_w.csv

In this moment: 14,885. I’m going to develop something, maybe I can discard a lot more… when I finish this first approach I can develop a platform to label with humans if you have a team, we can divide by sections, I can put options, for example, human reviwed (positive or false positive) and automatically labeled (for these false positives to be reviewed by humans) this can help to obtain a rigorous result, but could be an easy way to work.

I’m showing the process in the case someone find errors or want to participate, I will publish the methods at the end.

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Microgravity analogue literature review

Mining the Microgravity Analogue Literature: Help Needed!

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