**5. Domain-Specific Knowledge**

To extend current knowledge into new knowledge using the synthesis method introduced in this perspective article, possessing a solid foundational base of expert knowledge in one's field, called domain-specific knowledge [64], is vital. Most narrative reviews are written by experts [65], and research in memory and learning has revealed some important clues about how expertise is acquired. Practicing repeated retrieval of memorized information over a period of time strengthens knowledge storage and recall from long-term memory, developing the kind of deep learning possessed by experts which enables them to comprehend complex concepts, solve di fficult problems, and infer new associations [66]. This finding implies that knowledge synthesis can be strengthened by repeated readings and practiced memory recall of relevant selected literature that lies outside the scope of one's domain-specific knowledge. Nevertheless, opportunities to form novel, potentially ground-breaking transdisciplinary theories and theses appear remote unless one is willing to investigate research outside of one's domain of expertise during the process of new knowledge synthesis.

Logan [67] criticized the disconnect between specialized knowledge and meaningful context, quoting Konrad Lorenz:

"Philosophers are people who know less and less about more and more, until they know nothing about everything. Scientists are people who know more and more about less and less, until they know everything about nothing."

In other words, a proper balance of both knowledge depth and scope is necessary for meaningful context and new knowledge synthesis. Research confirms that boundary-spanning knowledge search methods, which expand beyond one's domain-specific range, promote the discovery of new pathways and new combinations of knowledge that lead to breakthroughs [68]. For example, based on my web-based synthesis of phosphate toxicity and cancer, my awareness of the e fficacy of a reduced-phosphate diet to treat chronic kidney disease patients led to a boundary-spanning proposal to test a similar phosphate-reduced diet as a novel intervention for cancer prevention and treatment [69].

## **6. Association, Causation, and Mediation**

An essential function of scientific inquiry is the ability to recognize patterns that connect discrete pieces of data and provide new meaning to the investigation [70]. Connecting pieces of evidence together in a synthesis is analogous to assembling pieces of a jigsaw puzzle to create a coherent big picture. The graphical abstract in Figure 2 uses the analogy of a jigsaw puzzle to illustrate how current, prior, qualitative, and quantitative knowledge are pieced together from various domains during knowledge synthesis. This section of the article provides an elementary explanation of relationships by which research concepts are logically combined during synthesis into new knowledge. The strengths and weaknesses of linked concepts can strengthen or weaken one's synthesis. I provide further examples from my web-based syntheses in the field of epidemiology, and the strengths and limitations of three common types of linked relationships are discussed: association, causation, and mediation.
