Vitamin D gestation known unknowns located by a computer in pubmed publications– June 2023

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Creating an ignorance-base: Exploring known unknowns in the scientific literature

Journal of Biomedical Informatics June 2023 https://doi.org/10.1016/j.jbi.2023.104405
Mayla R. Boguslav a, Nourah M. Salem a, Elizabeth K. White a b, Katherine J. Sullivan a, Michael Bada a, Teri L. Hernandez c, Sonia M. Leach a b, Lawrence E. Hunter a (Colorado)

Highlights

• We created the first ignorance-base (knowledge-base) to capture goals for scientific knowledge.
• Our exploration methods provide analyses, summaries, and visualizations based on a query.
• Ignorance enrichment provided fruitful avenues for future research.
• Exploration by topic in vitamin D found three avenues to explore.
• Exploration by experimental results for vitamin D and preterm birth found an emerging topic.

Background:
Scientific discovery progresses by exploring new and uncharted territory. More specifically, it advances by a process of transforming unknown unknowns first into known unknowns, and then into knowns. Over the last few decades, researchers have developed many knowledge bases to capture and connect the knowns, which has enabled topic exploration and contextualization of experimental results. But recognizing the unknowns is also critical for finding the most pertinent questions and their answers. Prior work on known unknowns has sought to understand them, annotate them, and automate their identification. However, no knowledge-bases yet exist to capture these unknowns, and little work has focused on how scientists might use them to trace a given topic or experimental result in search of open questions and new avenues for exploration. We show here that a knowledge base of unknowns can be connected to ontologically grounded biomedical knowledge to accelerate research in the field of prenatal nutrition.

Results:
We present the first ignorance-base, a knowledge-base created by combining classifiers to recognize ignorance statements (statements of missing or incomplete knowledge that imply a goal for knowledge) and biomedical concepts over the prenatal nutrition literature. This knowledge-base places biomedical concepts mentioned in the literature in context with the ignorance statements authors have made about them. Using our system, researchers interested in the topic of vitamin D and prenatal health were able to uncover three new avenues for exploration (immune system, respiratory system, and brain development) by searching for concepts enriched in ignorance statements. These were buried among the many standard enriched concepts. Additionally, we used the ignorance-base to enrich concepts connected to a gene list associated with vitamin D and spontaneous preterm birth and found an emerging topic of study (brain development) in an implied field (neuroscience). The researchers could look to the field of neuroscience for potential answers to the ignorance statements.

Conclusion:
Our goal is to help students, researchers, funders, and publishers better understand the state of our collective scientific ignorance (known unknowns) in order to help accelerate research through the continued illumination of and focus on the known unknowns and their respective goals for scientific knowledge.
 Download the PDF from VitaminDWiki

Conclusion (from PDF)

Our ultimate goal was to create an ignorance-base and exploration methods to enable students, researchers, funders, and publishers to find the next important scientific questions or knowledge gaps. By augmenting and streamlining the manual work of literature reviews, we can help direct research to focus on important quesitons and possible answers. The exploration by topic method not only found new avenues for exploration for researchers interested in vitamin D using our novel method of ignorance enrichment (the immune system, respiratory system, and brain development), but also elucidated how questions were asked and how that changed over time using our novel method of ignorance-category enrichment. Our exploration by experimental results method found an emerging topic (brain development) with specific knowledge goal statements to pursue that bear on a sPTB and vitamin D gene list. Further, the findings suggested a field (neuroscience) to look to for answers. These questions (and subsequent answers) have high potential to positively impact the health of pregnant women and their offspring globally. The importance of questions and knowledge goals in research is well established, and our ignorance-base and exploration methods bring these to the forefront to help researchers explore a topic and experimental results in the context of our collective scientific ignorance. The scientific endeavor rests on our continuous ability to ask questions and push research farther as we learn more knowledge.
To paraphrase Confucius,“Real knowledge is to know the extent of one’s ignorance” (Analects 2:17). In the right context, ignorance is a source of wisdom.

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Observations by VitaminDWiki

• They appear to focus on possible Vitamin D affects during pregnancy on live births
• They used a lot of human and computer power to identify concepts that were poorly known
• They appear to ignore the 100X larger vitamin D literature that might apply to pregnancy
• They appear to ignore vitamin D effects on pergnant mother, miscarriage, still birth, pre-mature birth, etc.
• They appear to not identify the importance of the Vitamin D receptor
• They appear to not identify the importance of dose size, dose frequency, nor when Vitamin D is started
• They have URLs to the programs used and perhaps the results
• They appear to ignore the importance of other nutrients, such as Omega-3, on infant health
• Based on the 2018 ending date of their data, the analysis methods are obsolete
• Suspect that the use of CHAT-GPT or other Large Languge Models will accomplsh far more in near real-time instead of a 5 year delay

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VitaminDWiki - Pregnancy category contains

924 items in Pregnancy category

 - see also

• Overview Pregnancy and vitamin D
• Number of articles in both categories of Pregnancy and:Dark Skin 30;   Depression 21;   Diabetes 44;   Obesity 17;  Hypertension 44;   Breathing 36;  Omega-3 44;  Vitamin D Receptor 24 Click here for details
• All items in category Infant/Child 854 items
• Pregnancy needs at least 40 ng of vitamin D, achieved by at least 4,000 IU – Hollis Aug 2017
• 38+ papers with Breastfed etc, in the title
• Call to action – more Vitamin D for pregnancies, loading doses are OK – Holick Aug 2019
• 53+ preeclampsia studies
• 94+ studies with PRETERM in the title
• Fertility problem (PCOS) reduced by vitamin D, etc: many studies 15+
• 94+ Gestational Diabetes
• Caesarean birth much more likely if low Vitamin D - many studies 15+ studies
• Post-partum depression and low Vitamin D - many studies 15+ studies
• Stillbirth reduced by Vitamin D, Zinc, Omega-3 - several studies 5+ studies
• Search VitaminDWiki for "Assisted reproduction" 33 items as of Aug 2022
• Fertility and Sperm category listing has 142 items along with related searches
• (Stunting OR “low birth weight” OR LBW) 1180 items as of June 2020
• Less labor pain if higher level of vitamin D – August 2021
• Healthy pregnancies need lots of vitamin D
• Ensure a healthy pregnancy and baby - take Vitamin D before conception
  

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VitaminDWiki - Healthy pregnancies need lots of vitamin D contains

Most were taking 2,000 to 7,000 IU daily for >50% of pregnancy
   Click on hyperlinks for details

Problem	Vit. D Reduces	Evidence
0. Chance of not conceiving	3.4 times	Observe
1. Miscarriage	2.5 times	Observe
2. Pre-eclampsia	3.6 times	RCT
3. Gestational Diabetes	3 times	RCT
4. Good 2nd trimester sleep quality	3.5 times	Observe
5. Premature birth	2 times	RCT
6. C-section - unplanned	1.6 times	Observe
Stillbirth - OMEGA-3	4 times	RCT - Omega-3
7. Depression AFTER pregnancy	1.4 times	RCT
8. Small for Gestational Age	1.6 times	meta-analysis
9. Infant height, weight, head size      within normal limits		RCT
10. Childhood Wheezing	1.3 times	RCT
11. Additional child is Autistic	4 times	Intervention
12.Young adult Multiple Sclerosis	1.9 times	Observe
13. Preeclampsia in young adult	3.5 times	RCT
14. Good motor skills @ age 3	1.4 times	Observe
15. Childhood Mite allergy	5 times	RCT
16. Childhood Respiratory Tract visits	2.5 times	RCT

RCT = Randomized Controlled Trial