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Institution

Novartis Foundation

NonprofitBasel, Switzerland
About: Novartis Foundation is a nonprofit organization based out in Basel, Switzerland. It is known for research contribution in the topics: Leprosy & Population. The organization has 99 authors who have published 85 publications receiving 3993 citations.


Papers
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Journal ArticleDOI
TL;DR: In vivo potency can be increased with little to no systemic exposure, localized innate immune activation and short in vivo residence times of SMIP-based adjuvants, and this work provides a systematic and generalizable approach to engineering small molecules for use as vaccine adjuvant.
Abstract: Adjuvants increase vaccine potency largely by activating innate immunity and promoting inflammation. Limiting the side effects of this inflammation is a major hurdle for adjuvant use in vaccines for humans. It has been difficult to improve on adjuvant safety because of a poor understanding of adjuvant mechanism and the empirical nature of adjuvant discovery and development historically. We describe new principles for the rational optimization of small-molecule immune potentiators (SMIPs) targeting Toll-like receptor 7 as adjuvants with a predicted increase in their therapeutic indices. Unlike traditional drugs, SMIP-based adjuvants need to have limited bioavailability and remain localized for optimal efficacy. These features also lead to temporally and spatially restricted inflammation that should decrease side effects. Through medicinal and formulation chemistry and extensive immunopharmacology, we show that in vivo potency can be increased with little to no systemic exposure, localized innate immune activation and short in vivo residence times of SMIP-based adjuvants. This work provides a systematic and generalizable approach to engineering small molecules for use as vaccine adjuvants.

154 citations

Journal ArticleDOI
TL;DR: This review provides insights into best practice for scaling digital health initiatives in LMICs derived from practical experience in real-life case studies, discussing how these may influence the development and implementation of health programmes in the future.
Abstract: Healthcare challenges in low and middle income countries (LMICs) have been the focus of many digital initiatives that have aimed to improve both access to healthcare and the quality of healthcare delivery. Moving beyond the initial phase of piloting and experimentation, these initiatives are now more clearly focused on the need for effective scaling and integration to provide sustainable benefit to healthcare systems. Based on real-life case studies of scaling digital health in LMICs, five key focus areas have been identified as being critical for success. Firstly, the intrinsic characteristics of the programme or initiative must offer tangible benefits to address an unmet need, with end-user input from the outset. Secondly, all stakeholders must be engaged, trained and motivated to implement a new initiative, and thirdly, the technical profile of the initiative should be driven by simplicity, interoperability and adaptability. The fourth focus area is the policy environment in which the digital healthcare initiative is intended to function, where alignment with broader healthcare policy is essential, as is sustainable funding that will support long-term growth, including private sector funding where appropriate. Finally, the extrinsic ecosystem should be considered, including the presence of the appropriate infrastructure to support the use of digital initiatives at scale. At the global level, collaborative efforts towards a less-siloed approach to scaling and integrating digital health may provide the necessary leadership to enable innovative solutions to reach healthcare workers and patients in LMICs. This review provides insights into best practice for scaling digital health initiatives in LMICs derived from practical experience in real-life case studies, discussing how these may influence the development and implementation of health programmes in the future.

149 citations

Journal ArticleDOI
TL;DR: Treatment with 0.75% LDE225 cream in NBCCS patients was very well tolerated and caused BCC regression, thus potentially offering an attractive therapeutic alternative to currently available therapies for this indication.

143 citations

Journal ArticleDOI
TL;DR: There was considerable variability at an individual level in the degree of COX-2 inhibition and selectivity attained by both drugs, suggesting sources of variability might be exploited to identify patients uniquely susceptible to benefit or at developing risk of cardiovascular complications.

136 citations

Journal ArticleDOI
TL;DR: Analysis of the two differentiated cell types, spores and stalk cells, and their precursors revealed a large number of differentially expressed genes as well as unexpected patterns of gene expression, which shed new light on the timing and possible mechanisms of cell-type divergence.
Abstract: A distinct feature of development in the simple eukaryote Dictyostelium discoideum is an aggregative transition from a unicellular to a multicellular phase. Using genome-wide transcriptional analysis we show that this transition is accompanied by a dramatic change in the expression of more than 25% of the genes in the genome. We also show that the transcription patterns of these genes are not sensitive to the strain or the nutritional history, indicating that Dictyostelium development is a robust physiological process that is accompanied by stereotypical transcriptional events. Analysis of the two differentiated cell types, spores and stalk cells, and their precursors revealed a large number of differentially expressed genes as well as unexpected patterns of gene expression, which shed new light on the timing and possible mechanisms of cell-type divergence. Our findings provide new perspectives on the complexity of the developmental program and the fraction of the genome that is regulated during development.

132 citations


Authors

Showing all 100 results

NameH-indexPapersCitations
Peter G. Schultz15689389716
Elizabeth A. Winzeler6924330083
Andrew I. Su5820220263
Diego H. Castrillon5410815087
Scott B. Ficarro5413411374
Eric C. Peters508211393
Kavita Shah461076741
Scott A. Lesley4622710590
Xu Wu42706929
Tim Wiltshire3911211960
Glen Spraggon371295172
Richard Glynne37706087
Claudio A. P. Joazeiro344810941
Mathew T. Pletcher30534704
Arnab K. Chatterjee28713251
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
20222
20218
20209
20197
20186
20174