Pay It Forward is a major study conducted by the University of California, Davis, and the California Digital Library, on behalf of the University of California Libraries, and with collaborating libraries at Harvard University, Ohio State University, and the University of British Columbia addressed the financial ramifications for the types of research institutions whose affiliated scholars generate a preponderance of the scholarly literature. The project focused on large, research-intensive universities in North America and defined sustainability as costing those institutions roughly no more than, and ideally considerably less than, current journal subscription costs for comparable journals today, with a rate of growth that will be possible for these institutions to support over time. The project sheds new light on the financial viability of the article processing charge business model to create open access at a much larger scale.

Pay It Forward is a major study conducted by the University of California, Davis, and the California Digital Library, on behalf of the University of California Libraries, and with collaborating libraries at Harvard University, Ohio State University, and the University of British Columbia addressed the financial ramifications for the types of research institutions whose affiliated scholars generate a preponderance of the scholarly literature. The project focused on large, research-intensive universities in North America and defined sustainability as costing those institutions roughly no more than, and ideally considerably less than, current journal subscription costs for comparable journals today, with a rate of growth that will be possible for these institutions to support over time. The project sheds new light on the financial viability of the article processing charge business model to create open access at a much larger scale.

Background

Chronic fatigue syndrome (CFS) remains poorly understood. Although infections are speculated to trigger the syndrome, a specific infectious agent and underlying pathophysiological mechanism remain elusive. In a previous study, we described similar clinical phenotypes in CFS patients and alternatively diagnosed chronic Lyme syndrome (ADCLS) patients—individuals diagnosed with Lyme disease by testing from private Lyme specialty laboratories but who test negative by reference 2-tiered serologic analysis.

Methods

Here, we performed blinded RNA-seq analysis of whole blood collected from 25 adults diagnosed with CFS and 13 ADCLS patients, comparing these cases to 25 matched controls and 11 patients with well-controlled systemic lupus erythematosus (SLE). Samples were collected at patient enrollment and not during acute symptom flares. RNA-seq data were used to study host gene expression, B-cell/T-cell receptor profiles (BCR/TCR), and potential viral infections.

Results

No differentially expressed genes (DEGs) were found to be significant when CFS or ADCLS cases were compared to controls. Forty-two DEGs were found when SLE cases were compared to controls, consistent with activation of interferon signaling pathways associated with SLE disease. BCR/TCR repertoire analysis did not show significant differences between CFS and controls or ADCLS and controls. Finally, viral sequences corresponding to anelloviruses, human pegivirus 1, herpesviruses, and papillomaviruses were detected in RNA-seq data, but proportions were similar (P = .73) across all genus-level taxonomic categories.

Conclusions

Our observations do not support a theory of transcriptionally mediated immune cell dysregulation in CFS and ADCLS, at least outside of periods of acute symptom flares.