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Multiple Sclerosis
Multiple Sclerosis is a demyelinating neurodegenerative disease that does not have a confirmed cause, but is widely considered to be an autoimmune disease in nature. It is indicated by demyelination of the nerves of the brain and spinal cord. Its symptoms are unique in nature and vary, but include those that inhibit or affect the eyes and limbs. These can present themselves as numbness or atrophy, shock like sensations, paralysis, as well as lack of coordination or tremors, within the extremities. Within the eye, Multiple Sclerosis can cause blurriness. double vision, pain, or vision loss. Multiple Sclerosis effects can be presented throughout other realms of the body but is largely characterized by these main symptoms. Some of these can include loss of sexual or excretory function and epilepsy. While there are a few subcategories of multiple sclerosis, in most instances, the disease afflicts in a relapsing nature, where relapses of symptoms might not occur for extended periods of time, yielding more to the uncertainty of the disease. There is no known cure for the disease, but measures can be taken post relapse to regain loss of function and the symptoms can be mitigated via therapeutic or medicinal means.

Epigenetic factors

Because of the outside factors that precede multiple sclerosis and the heritability typically occurring within the mother, it is thought to have an epigenetic cause. Some factors that may increase the incidence of MS are smoking, deficiency of vitamin disease, and a history of some viral infections - which are factors that can induce epigenetic change.

Human leukocyte antigen-DRB1*15 allele
Human leukocyte antigen-DRB1*15 allele is a potential risk for hereditary factors of MS. Because of the increased likelihood of the mother's human leukocyte antigen-DRB1*15 allele being passed onto their children, this contributes to the instances of MS being more prevalent from the mother. HLA-DRB1 is thought to be regulated via epigenetic means, and the correlation of MS and this allele is speculated to be due to the presence of hypomethylation in the CpG island of HLA-DRB1.

miRNA

Higher levels of expression of specific types of miRNA can be used as an indication of MS, and can often be seen in the brain of those afflicted. This is thought to be the way in which smoking can induce epigenetic changes that increase susceptibility to MS. CD4+T cell differentiation is often associated with higher expression of miR-155 and miR-326, and with this differentiation, instances of autoimmune encephalitis. Higher expression levels miR-18b, miR-493 and miR-599 are seen in those experiencing a relapse, and the instance of miR-96 is seen in remission often times. miR-145 can often be used as a reliable diagnostic tool due to its high specificity and sensitivity in whole blood testing. A symptom associated with MS patients is white matter lesions in the brain, and these lesions when biopsied showed higher expression of miR-155, miR-326 and miR-34a. These are especially notable due to the fact that these miRNA's afflict CD47 causing downregulation, leading to premature myelin phagocytosis.

DNA methylation

Indication of MS can be gathered from methylation patterns, and those observed uniquely in patients exhibiting MS. Methylation exhibits in the CpG and HLA-DRB1 sites of CD4-T cells. Hypomethylation of PAD2, a regulator of MBP which in turn regulates myellin, is also associated with higher instances of MS. While methylation is an indicator of MS, its effects are more specialized to location in MS.

Histone Modifications

Association of histone modification and MS patients can be found in lesions located in the brain, with most instances of this being observed in patients over time and in lesions located in the frontal lobe. Higher instance of histone acetylation can be seen in patients afflicted over time, but this is counteracted by lower instances of histone acetylation in lesions found on the brain early in the course of the disease. The mechanisms by which histone modifications work in the progression of MS are unconfirmed, but changes in acetylation are often associated with the disease.

Treatments

HDAC inhibitors
Trichostatin

Positive responses were observed in animal trials utilizing this HDAC inhibitor, associated with mediation of inflammatory pathways and thus resulting in lower instances of inflammatory responses in the brain.

Vorinostat

Animal trials were utilized along with the testing of human mDCs. Mediation of T-cells and Th1/Th17 were observed, thereby decreasing instances of inflammation and demyelination.

Valpropic Acid

Valpropic acid has been shown to have positive results in animal trials, in the mitigation of the disease by regulating the severity and duration of MS. Its mechanism is decreasing the presentation of miRNA.

Here, I think it would be beneficial to introduce HDACi's a bit more before talking about them. Also, it is not super clear here if these are treatments for MS. I believe so given the organization of the article; however, I do think it would be helpful to explicitly state it. I really like how you do include the mechanism of these drugs to help readers understand the significance.

Article Selection
Trevor's comments in magenta

Option 1 - Proposal
ALS Source (MND)
 * Epigenetics of neurodegenerative diseases
 * Article Evaluation
 * This article is detailed and has some good, and recent references. More findings in each area of disease discussed would be beneficial in the betterment of the article's credibility and ensuring it is the most accurate.
 * Because it would encompass more aspects of neurodegenerative and/or memory decline, dementia should be included. Dementia is not specific, but rather something caused by having some sort of condition. It may be worthwhile to include this in order to broaden the spectrum of disease that the article covers. More information could be added on (FTD). Including Alzheimers as a subcategory of dementia rather than its own might help organizationally as well.
 * Like the aspect of including dementia as a category and its associated diseases as subcategories, this can also be applied to motor neuron disease as well. For instance, ALS could be categorized under this.
 * The content is relevant but because of the fact that the topic is so broad, there needs to be more disease coverage when discussing the epigenetics of neurodegenerative disease, and more should be done to encompass recognizable conditions for the mass public. While it appears to cover a good amount of neurodegenerative diseases, more should be done in order to ensure that diseases covered are those that its readers will be familiar or somewhat familiar with. With this in mind, the article would greatly benefit from having a section dedicated to MS, a more commonly known condition.
 * Another condition that should be included would be PSP - while not well known, there should be as much information on neurodegenerative diseases that are known about and have extensive research as possible.
 * MSA should be added to this article as well, again, in order to ensure that the information on this article is broadened.
 * Ataxia is another category of neurodegenerative diseases. This can be along with Friedrich's Ataxia included in this as a subcategory as well.
 * The article is difficult to read, so likely with the categories being more broad, hopefully the reader is able to take on this read in easier strides and understand the content piece by piece, by getting introduced to the group of diseases first rather than introducing the disease on its own. This should make the read more digestible.
 * Sources
 * Sources
 * Sources

https://www.healthdirect.gov.au/motor-neurone-disease-mnd

https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Amyotrophic-Lateral-Sclerosis-ALS-Fact-Sheet

https://pubmed.ncbi.nlm.nih.gov/30391475/

MS Addition

https://pubmed.ncbi.nlm.nih.gov/24652042/

https://pubmed.ncbi.nlm.nih.gov/27382982/

SMA Addition

https://rarediseases.info.nih.gov/diseases/7674/spinal-muscular-atrophy

AD Addition

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8574196/

https://pubmed.ncbi.nlm.nih.gov/33573255/

HD Addition

https://pubmed.ncbi.nlm.nih.gov/28523552/

PD Addition

https://www.ninds.nih.gov/Disorders/All-Disorders/Parkinsons-Disease-Information-Page

Dementia Addition

https://pubmed.ncbi.nlm.nih.gov/29562532/

Impact Addition

https://pubmed.ncbi.nlm.nih.gov/30352259/

PSP Addition

https://pubmed.ncbi.nlm.nih.gov/30050033/

MSA Addition

https://pubmed.ncbi.nlm.nih.gov/32151281/

Ataxia Addition

https://pubmed.ncbi.nlm.nih.gov/29053830/

You have a wealth of excellent sources here and have clearly done a lot of research on your topic. But you need to really expand upon this outline. There's hardly enough here for me to critique and offer substantive comments on where to go from here because of how surface level your outline is. I agree on pretty much everywhere that you say the article needs improvement, but without much in the way of concrete details of how you plan to make those improvements it's difficult to give much direction.

My recommendation is to put a ton of effort into your first draft to help you get back on track. If you expand on your outline before then and want me to offer more suggestions, just let me know that it's updated and I will look over it again.

'''Sources are not enough. Read, read, read. Then get together and compare notes. Best advice - get out starting mode and finish what you think is a final draft. It won't be the final one but then at least you will have something. It is easy to edit and hard to write. So get yourself some text to edit.'''

Free to a Good Home
'''This is a good topic and it is a shape that no one chose it. You can leave it here for a while perhaps you will want to switch to it. However, I guess it is getting a bit late for that.'''


 * Epigenetic therapy
 * Article Evaluation
 * The content is relevant and tends to have about the same amount of information for each disease/condition discussed.
 * It is written in a neutral tone.
 * All claims appear to have a citation.
 * The citations appear reliable but there needs to be more recent sources.
 * It covers people with degenerative diseases and mental conditions.
 * It covers people with degenerative diseases and mental conditions.


 * Sources
 * https://pubmed.ncbi.nlm.nih.gov/30723290/
 * https://pubmed.ncbi.nlm.nih.gov/33741974/

Option 3

 * Epigenetic effects of smoking
 * Article Evaluation
 * The content is relevant but it lacks enough information.
 * There are assertive and non passive claims. It is not written in an academic manner.
 * There are citations for most claims.
 * The citations appear to be reliable but there are not very many, nor are there enough recent citations.
 * It does not tackle any underrepresented group - which is why a source on infertile men might be beneficial.
 * It does not tackle any underrepresented group - which is why a source on infertile men might be beneficial.


 * Sources
 * https://pubmed.ncbi.nlm.nih.gov/30132931/
 * https://pubmed.ncbi.nlm.nih.gov/27651444/
 * https://pubmed.ncbi.nlm.nih.gov/34064931/