Why publish? An interview study exploring patient innovators' reasons for and experiences of scientific publishing.

BACKGROUND: Scientific publications featuring patient-driven innovations (i.e., innovations that are developed and driven by patients or informal caregivers) are increasing. By understanding patient innovators' experiences of research publication, the scientific community may be better prepared to support or partner with patient innovators. Thus, the aim of this study was to explore patient innovators' reasons for and experiences of authoring scientific publications about their innovations. METHODS: Qualitative semi-structured interviews were conducted with 15 international patient innovators from three continents who had published in scientific journals. Participants were identified through a scoping review on patient-driven innovations and snowball sampling. Interviews were conducted from June to October 2022 and the data was analyzed using the Framework Method. FINDINGS: Participants' reasons for publishing in scientific journals were to strengthen the roles and voices of patients and informal caregivers, and to get recognition for their innovations. Some published as a response to serendipitous opportunities. Several positive experiences were reported: collaborations defined by transparency, mutual respect, and meaningful participation; learning and competence development; and gained confidence regarding the value of lived experiences in research. Participants also reported negative experiences, such as cultural barriers manifested as conservatism in academia and power imbalances between participants and researchers, and structural barriers regarding academic affiliations and research funding. CONCLUSIONS: Despite progress in increasing patient and public involvement in research and publication, our study found that patient innovators still experience barriers. This suggests that continued efforts are needed to facilitate contributions from patient innovators and other public actors to the production of relevant and meaningful research.

Rapid technological advances over the past decades have resulted in many health innovations that enable persons living with chronic conditions to better manage their health conditions in self-care. Similarly, caregivers can provide more advanced informal care. Do-it-yourself health innovations, such as automatic insulin dosing for diabetes patients, have been developed by patients and informal caregivers whom we in this study defined as patient innovators. There is an increasing trend of research focusing on such patient-driven innovations. However, we know little about the driving forces of patient innovators to contribute to scientific publications about their innovations. Therefore, the aim of this study was to explore patient innovators' reasons for publishing and their experiences thereof. We interviewed 15 international patient innovators who had experience of scientific publishing. Their main driving forces were to make patients' voices heard and receive recognition for their innovations, which could facilitate spread to other patients. The patient innovators in our study had positive experiences and meaningful collaborations with researchers that contributed to developing their scientific skills. However, they also faced challenges, such as managing their health and professional occupations besides research, being questioned by peer reviewers, and difficulties tackling the research and publication system without academic affiliation or funding. Our findings suggest that despite strong driving forces and positive experiences of scientific publishing, patient innovators face barriers that need to be addressed to facilitate the publication process for contributors without academic experience.

Objectives and outcomes of patient-driven innovations published in peer-reviewed journals: a qualitative analysis of publications included in a scoping review.

OBJECTIVES: The aim of this study was to gain a deeper understanding of the objectives and outcomes of patient-driven innovations that have been published in the scientific literature, focusing on (A) the unmet needs that patient-driven innovations address and (B) the outcomes for patients and healthcare that have been reported. METHODS: We performed an inductive qualitative content analysis of scientific publications that were included in a scoping review of patient-driven innovations, previously published by our research group. The review was limited to English language publications in peer-reviewed journals, published in the years 2008-2020. RESULTS: In total, 83 publications covering 21 patient-driven innovations were included in the analysis. Most of the innovations were developed for use on an individual or community level without healthcare involvement. We created three categories of unmet needs that were addressed by these innovations: access to self-care support tools, open sharing of information and knowledge, and patient agency in self-care and healthcare decisions. Eighteen (22%) publications reported outcomes of patient-driven innovations. We created two categories of outcomes: impact on self-care, and impact on peer interaction and healthcare collaboration. CONCLUSIONS: The patient-driven innovations illustrated a diversity of innovative approaches to facilitate patients' and informal caregivers' daily lives, interactions with peers and collaborations with healthcare. As our findings indicate, patients and informal caregivers are central stakeholders in driving healthcare development and research forward to meet the needs that matter to patients and informal caregivers. However, only few studies reported on outcomes of patient-driven innovations. To support wider implementation, more evaluation studies are needed, as well as research into regulatory approval processes, dissemination and governance of patient-driven innovations.

A homeodomain feedback circuit underlies step-function interpretation of a Shh morphogen gradient during ventral neural patterning.

The deployment of morphogen gradients is a core strategy to establish cell diversity in developing tissues, but little is known about how small differences in the concentration of extracellular signals are translated into robust patterning output in responding cells. We have examined the activity of homeodomain proteins, which are presumed to operate downstream of graded Shh signaling in neural patterning, and describe a feedback circuit between the Shh pathway and homeodomain transcription factors that establishes non-graded regulation of Shh signaling activity. Nkx2 proteins intrinsically strengthen Shh responses in a feed-forward amplification and are required for ventral floor plate and p3 progenitor fates. Conversely, Pax6 has an opposing function to antagonize Shh signaling, which provides intrinsic resistance to Shh responses and is important to constrain the inductive capacity of the Shh gradient over time. Our data further suggest that patterning of floor plate cells and p3 progenitors is gated by a temporal switch in neuronal potential, rather than by different Shh concentrations. These data establish that dynamic, non-graded changes in responding cells are essential for Shh morphogen interpretation, and provide a rationale to explain mechanistically the phenomenon of cellular memory of morphogen exposure.

Axon-bearing and axon-less horizontal cell subtypes are generated consecutively during chick retinal development from progenitors that are sensitive to follistatin.

BACKGROUND: Horizontal cells are retinal interneurons that modulate the output from photoreceptors. A rich literature on the morphological classification and functional properties of HCs in different animals exists, however, the understanding of the events underlying their development is still limited. In most vertebrates including chicken, two main horizontal cell (HC) subtypes are identified based on the presence or absence of an axon. RESULTS: In this work we have molecularly characterized three HC subtypes based on Lim1, Isl1, GABA and TrkA, a classification that is consistent with three chick HC subtypes previously defined by morphology. The axon-bearing and axon-less HC subpopulations molecularly defined by Lim1 and Isl1, are born consecutively on embryonic day (E) 3-4 and E4-5, respectively, and exhibit temporally distinguishable periods of migration. Their relative numbers are not adjusted by apoptosis. A sharp decrease of high endogenous levels of the activin-inhibitor follistatin at E3 coincides with the appearance of the Lim1 positive cells. Extending the follistatin exposure of the HC retinal progenitor cells by injection of follistatin at E3 increased the number of both Lim1- and Isl1 positive HCs when analysed at E9. CONCLUSION: The results imply that the axon-bearing and axon-less HC subgroups are defined early and are generated consecutively from a retinal progenitor cell population that is sensitive to the inhibitory action of follistatin. The results are consistent with a model wherein added follistatin causes HC-generating progenitors to proliferate beyond the normal period of HC generation, thus producing extra HCs of both types that migrate to the HC layer.

Genetic elimination of Suppressor of fused reveals an essential repressor function in the mammalian Hedgehog signaling pathway.

The Hedgehog (Hh) pathway plays important roles during embryogenesis and carcinogenesis. Here, we show that ablation of the mouse Suppressor of fused (Sufu), an intracellular pathway component, leads to embryonic lethality at approximately E9.5 with cephalic and neural tube defects. Fibroblasts derived from Sufu(-/-) embryos showed high Gli-mediated Hh pathway activity that could not be modulated at the level of Smoothened and could only partially be blocked by PKA activation. Despite the robust constitutive pathway activation in the Sufu(-/-) fibroblasts, the GLI1 steady-state localization remained largely cytoplasmic, implying the presence of an effective nuclear export mechanism. Sufu(+/-) mice develop a skin phenotype with basaloid changes and jaw keratocysts, characteristic features of Gorlin syndrome, a human genetic disease linked to enhanced Hh signaling. Our data demonstrate that, in striking contrast to Drosophila, in mammals, Sufu has a central role, and its loss of function leads to potent ligand-independent activation of the Hh pathway.