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Literature-related discovery: common factors for Parkinson’s Disease and Crohn’s Disease

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Abstract

Literature-related discovery (LRD) is the linking of two or more literature concepts that have heretofore not been linked (i.e., disjoint), in order to produce novel, interesting, and intelligible knowledge (i.e., potential discovery). The mainstream software for assisting LRD is Arrowsmith. It uses text-based linkage to connect two disjoint literatures, and it generates intermediate linking literatures by matching Title phrases from two disjoint literatures (literatures that do not share common records). Arrowsmith then prioritizes these linking phrases through a series of text-based filters. The present study examines citation-based linkage in addition to text-based linkage to link disjoint literatures through a process called bibliographic coupling. Two disjoint literatures were selected for the demonstration: Parkinson’s Disease (PD) (neurodegeneration) and Crohn’s Disease (CD) (autoimmune). Three cases were examined: (1) matching phrases in records with no shared references (text-based linkage only); (2) shared references in records with no matching phrases (citation-based linkage only); (3) matching phrases in records with shared references (text-based and citation-based linkages). In addition, the main themes in the body of shared references were examined through grouping techniques to identify the common themes between the two literatures. All the high-level concepts in the Case 1) records could be found in Case 3) records Some new concepts (at the sub-set level of the main themes) not found in the Case 3) records were identified in the Case 2) records. The synergy of matching phrases and shared references provides a strong prioritization to the selection of promising matching phrases as discovery mechanisms. There were three major themes that unified the PD and CD literatures: Genetics; Neuroimmunology; Cell Death. However, these themes are not completely independent. For example, there are genetic determinants of the inflammatory response. Naturally occurring genetic variants in important inflammatory mediators such as TNF-alpha appear to alter inflammatory responses in numerous experimental and a few clinical models of inflammation. Additionally, there is a strong link between neuroimmunology and cell death. In PD, for example, neuroinflammatory processes that are mediated by activated glial and peripheral immune cells might eventually lead to dopaminergic cell death and subsequent disease progression.

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Acknowledgments

This project was supported by MITRE internal research funding.

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  1. Ronald N. Kostoff

    Present address: School of Public Policy, Georgia Institute of Technology, Atlanta , GA, USA

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Appendix: Sample new concepts from shared references with no matching phrases

Appendix: Sample new concepts from shared references with no matching phrases

List of concepts

Anthocyanins (water-soluble vacuolar pigments that may appear red, purple, or blue according to pH. They belong to a parent class of molecules called flavonoids)

Wogonin; Scutellaria rivularis extracts (Wogonin, a major component isolated from the flavonoid-rich Scutellaria rivularis species)

Trichothecenes (a very large family of chemically related mycotoxins produced by various species of Fusarium, Myrothecium, Trichoderma, Trichothecium, Cephalosporium, Verticimonosporium, and Stachybotrys. Trichothecenes belong to sesquiterpene compounds)

Pyroptosis (Pyroptosis is a form of programmed cell death associated with antimicrobial responses during inflammation. In contrast to apoptosis, pyroptosis requires the function of caspase-1)

Adalimumab (a TNF inhibitor that binds to TNFα, preventing it from activating TNF receptors; however, because TNFα is part of the immune system that protects the body from infection, adalimumab can lead to fatal infections.)

Cooked foods

Flippases (enzymes located in the membrane responsible for aiding the movement of phospholipid molecules between the two leaflets that compose a cell’s membrane (transverse diffusion)).

  1. 1.

    Anthocyanins

LINKAGE

The shared reference (Wang and Mazza 2002) showed anthocyanins induced TNF-alpha production and modulated the immune response. The PD paper (Dreiseitel et al. 2009) showed anthocyanins inhibited monamine oxidases (whose elevated activity has been implicated in neurodegenerative diseases), and the CD paper (Osman et al. 2008) showed that anthocyanins (blueberries) reduced inflammation in colitis.

  1. 2.

    Wogonin, baicalin, baicalein; Scutellaria rivularis extracts

LINKAGE

The shared reference (Lin and Shieh 1996) described the anti-inflammatory activity of Scutellaria rivularis extracts. The PD paper (Cheng et al. 2008) described the neuroprotective effect of baicalein, and surmised its cause as increasing the levels of DA and 5-HT in the striatum, increasing the counts of dopaminergic neurons, inhibiting oxidative stress and the astroglia response. The CD paper (Latella et al. 2008) showed antifibrotic Scutellaria extracts are effective in preventing colonic fibrosis in TNBS-induced colitis, with the antifibrotic mechanism of action mediated by the inhibition of TGF-beta 1/Smad3 pathway.

  1. 3.

    Trichothecenes

LINKAGE

The shared reference (Pestka et al. 2004) states that trichothecenes are mycotoxins that can be immunostimulatory or immunosuppressive depending on dose, exposure frequency and timing of functional immune assay, and can induce MAPK-activation. The PD paper (Islam et al. 2008) shows that Satratoxin G (a macrocyclic trichothecene mycotoxin) induced apoptosis (in PC-12 neuronal cells) mediated by RNA-activated protein kinase. The CD papers (Maresca et al. 2008; Pinton et al. 2009) showed that the pro-inflammatory activity of enteropathogenic mycotoxins on human intestinal epithelial cells is mediated by both direct and indirect effects.

  1. 4.

    Diversity of cell death processes, including pyroptosis (Pyroptosis is a form of programmed cell death associated with antimicrobial responses during inflammation. In contrast to apoptosis, pyroptosis requires the function of caspase-1)

LINKAGE

The shared reference (Fink and Cookson 2005) describes the different types of cell death and the different mechanisms involved. The Parkinson’s citing paper (Paris et al. 2009) showed that the copper–dopamine complex induces mitochondrial autophagy preceding caspase-independent (non-pyroptosis) apoptotic cell death. The Crohn’s citing paper (Franchi et al. 2009) describes inflammasomes in caspase-1 activation (a pre-condition for pyroptosis) and subsequent release of proinflammatory cytokines such as interleukin-1 beta. The common theme is mechanisms other than pure necrosis or apoptosis cell death, and their subsequent role in neurodegenerative and inflammatory diseases.

  1. 5.

    Adalimumab

LINKAGE

The shared reference (Scheinfeld 2004) focuses on side effects from tnf-alpha blockers, including Adalimumab. The Parkinson’s citing paper (McCoy et al. 2008) showed that inhibition of tnf through nigral infusion of dominant-negative (DN-TNF) protein attenuates dopaminergic neuron loss and behavioral deficits resulting from striatal dopamine depletion. The Crohn’s citing paper(s) (Jacobi et al. 2006; Biancone et al. 2007) describe the use of tnf-alpha blockers for (1) treating inflammatory skin disorders, including undesirable side effects, and (2) treating inflammatory bowel disorders despite potential side-effects of increased cancer risk.

  1. 6.

    Cooked foods

LINKAGE

The shared reference (Layton et al. 1995) describes the cancer risk of heterocyclic amines (pyrolysis products formed during the cooking of meats/fish). The Parkinson’s citing paper (Louis et al. 2008) showed that elevated blood concentrations of the co-mutagenic beta-carboline harmane, also found in cooked meats, are associated with elevated levels of essential tremor. The Crohn’s citing paper (Forte et al. 2008) describes the increased risk of colorectal cancer associated with consumption of meat, and suggests that mutagenic compounds such as heterocyclic amines could be a possible causative factor.

  1. 7.

    Flippases (enzymes located in the membrane responsible for aiding the movement of phospholipid molecules between the two leaflets that compose a cell’s membrane (transverse diffusion)).

LINKAGE

The shared reference (Higgins and Gottesman 1992) addresses the transport of drugs out of cells. The Parkinson’s citing paper (Pahnke et al. 2009) proposes that the activation of the excretion function of the blood-brain barrier might help to achieve better results in trials targeting the dissolution of cerebral amyloid-beta aggregates in Alzheimer’s Disease. The Crohn’s citing paper (Annese et al. 2006) examines two SNP polymorphisms of the MDR1 gene (whose product the P-glycoprotein (P-gp) functions as a transmembrane efflux pump thus influencing disposition and response of many drugs, some of whom (i.e. glucocorticoids) are central to IBD therapy. In addition P-gp is highly expressed in many epithelial surfaces, including the gastrointestinal tract (G-I) with a putative role in decreasing the absorption of endogenous or exogenous toxins, and perhaps host-bacteria interaction), and shows that a significant association between one allele and geneotype has been found with ulcerative colitis, whereas none could be found with CD.

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Kostoff, R.N. Literature-related discovery: common factors for Parkinson’s Disease and Crohn’s Disease. Scientometrics 100, 623–657 (2014). https://doi.org/10.1007/s11192-014-1298-3

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