tbuckley/cabot-search huggingface dataset:
P127 Treatment of concomitant psoriasis, Crohn’s disease and hidradenitis suppurativa: exploring potential associations in their immunopathogenesis
Journal: British Journal of Dermatology (2024)

Abstract Background The immunopathogenesis of several chronic inflammatory skin diseases includes the axis of IL-23/IL-17. Case Report We present the case of a 36-year-old man with Psoriasis, Crohn’s disease, and Hidradenitis suppurativa who showed an adequate response to Ustekinumab after failure to infliximab and adalimumab. Conclusion This case highlights the importance of a personalized approach and the potential of Ustekinumab as an effective treatment option for patients with concomitant Psoriasis, Crohn’s disease, and Hidradenitis Suppurativa. The shared pathways involved in the immunopathogenesis of these inflammatory diseases may provide insights into their treatment.
P63 Effectiveness of biologics in clinical practice: Month 12 absolute psoriasis area and severity index outcomes from an international observational Psoriasis Study of Health Outcomes
Journal: British Journal of Dermatology (2024)

Abstract Introduction Absolute psoriasis area and severity index (PASI) may be an alternative to relative PASI for treatment comparisons because it reflects both clinically meaningful improvements in disease activity and informs treatment decisions based on actual disease severity, regardless of baseline score. The Psoriasis Study of Health Outcomes (PSoHO) is a 3-year, international, prospective, non-interventional study comparing the effectiveness of anti-IL-17A biologics [ixekizumab (IXE) and secukinumab (SEC)] to other approved biologics in patients with moderate-to-severe psoriasis (PsO) undergoing routine medical care. While relative PASI effectiveness has been reported at 12 months, absolute PASI responses have not yet been shown. This analysis aims to report the effectiveness measured by absolute PASI through 12 months. Methods PSoHO included patients with moderate-to-severe plaque PsO, initiating or switching to a new approved biologic treatment (including biosimilars). This analysis reports the percentage of patients receiving EMA-approved on-label dosing (n = 1678), who achieved absolute PASI scores ≤1, ≤2 and ≤3 at Months 6 and 12. Unadjusted response rates for absolute PASI scores are reported as percentages for each outcome and time point. Non-responder imputation (NRI) was used for missing outcomes and reported here. Results At Month 6, higher response rates for absolute PASI ≤1, ≤2 and ≤3 were achieved by 62.2, 72.1 and 77.8% of patients in the anti-IL-17A cohort compared with 47.4, 61.3 and 69.7% of patients in the other biologics cohort respectively. At Month 12, higher response rates for absolute PASI ≤1, ≤2 and ≤3 were achieved by 56.5, 66.2 and 71.2% of patients in the anti-IL-17A cohort compared with 50.3, 62.6 and 69.0% in the other biologics cohort respectively. At Month 6, across individual treatments, IXE provided the highest response rates in absolute PASI ≤1, ≤2 and ≤3 with 65.2, 74.0 and 79.2%, respectively. At Month 12, IXE showed the highest response rates in absolute PASI ≤1 with 59.6%, followed by risankizumab, guselkumab, tildrakizumab, secukinumab, brodalumab, adalimumab, and ustekinumab with 57.5, 51.5, 51.2, 50.0, 46.7, 44.8, and 42.4% respectively. Conclusion This analysis indicates that the anti-IL-17A cohort of the EMA-approved on-label population had a higher response rate in absolute PASI through Month 12, in a real-world setting. Across individual drug treatments, IXE indicated the highest percentage of patients achieving key endpoints at both 6 and 12 months.
P50 Metagenomic insights into gut microbiome dysbiosis and biomarker discovery in psoriasis
Journal: British Journal of Dermatology (2024)

Abstract Psoriasis is a chronic inflammatory skin disease with an incompletely understood aetiology. Emerging evidence suggests a potential role of the gut microbiome in psoriasis pathogenesis, but existing studies have yielded inconsistent results. We performed shotgun metagenomic sequencing on faecal samples from 98 psoriasis patients and 45 healthy controls, including 28 patient-relative pairs. We found decreased species evenness in psoriasis patients, with lower alpha diversity indices compared with healthy controls. The disease status and living environment influenced microbiome composition. Notably, the microbiome composition of patient-relative controls was more similar to psoriasis patients than to non-familial healthy controls. We observed reduced interspecies interactions and increased localization in the gut microbial correlation network of psoriasis patients. Functional analysis identified altered microbial pathways, particularly those related to carbohydrate metabolism, nucleotide metabolism, and immune function. A poorly characterized species, s__GGB51647_SGB4348, was identified as a candidate biomarker for discriminating psoriasis by machine learning methods. Functionally, this species was enriched in carbohydrate and nucleotide metabolism pathways. In males, s__GGB51647_SGB4348 positively correlated with disease severity and CD4+ T-cell count. Collectively, these findings illuminate the multifaceted alterations in the gut microbiome associated with psoriasis and pave the way for novel diagnostic and therapeutic strategies targeting microbial dysbiosis.
P65 Clinical characteristics of pruritus in Bangladeshi psoriasis patients
Journal: British Journal of Dermatology (2024)

Abstract Background Psoriasis is a chronic systemic autoimmune disease associated with pruritus and seriously affects the quality of life of patients, but published data on its frequency and characteristics are limited. Objectives The purpose of this study is to find out the characteristics of pruritus in patients with different types of psoriasis and its impacts on the quality of life in Bangladesh. Materials and Methods This descriptive cross-sectional study was carried out in the Department of Dermatology and Venereology of Chittagong Medical College Hospital, Bangladesh for the period between March 2021 and August 2022 by using various validated tools like Visual Analog Scale, body surface area (BSA), psoriasis area and severity index (PASI), palmoplantar pustulosis severity index, severity of generalized pustular psoriasis, Static Physician Global Assessment Scale, Dermatology Life Quality Index (DLQI) and Family Reported Outcome Measure (FROM). After developing a questionnaire assessing various aspects of pruritus, we have surveyed 270 patients of psoriasis with different varieties regarding the presence and intensity of pruritus and life quality assessment. Results The mean age of the patients was 38.86 (±14.32) years, and males 182 (67.4%) outnumber females 88 (32.6%). A total of 210 (77.8%) patients reported having pruritus, 110 (40.74%) had moderate pruritus, 82 (30.37%) had mild pruritus, and 18 (6.7%) had severe pruritus. Pruritus was more common in the 21–40 years age group (35%), male sex (53%), low-income group (51%), outside field workers (23%), winter and spring exacerbation (31%), BSA &amp;lt;9% group (45%), palmoplantar psoriasis types (19%) and mild PASI (38%) group. In regards to DLQI, the majority 91 (33.7%) patients had a small effect, 68 (25.2%) had a large effect, 54 (20%) had a moderate effect, 53 (19.6%) had extremely large effect, and 4 (1.5%) had no effect. Conclusion Though pruritus is not specific to psoriasis, this study conveys the severity of pruritus in psoriasis patients in which a physician may encounter in clinical practice to monitor disease severity and optimization of treatment as well as take proper steps to improve the quality of life of patients.
P88 Spatial transcriptomic profiling reveals body site-specific inflammatory differences in psoriasis lesions
Journal: British Journal of Dermatology (2024)

Abstract Psoriasis is a common chronic inflammatory skin disease. A variety of treatment options lead to substantial improvement of most psoriasis plaques; however, recurrence of psoriasis in previously affected areas is common. Additionally, it can be challenging to reach disease resolution in certain hard-to-treat areas such as scalp and lower extremity (LE). Here, we map histologic and spatial transcriptomic differences between psoriasis lesions across different anatomical locations, to understand if differences in the inflammatory profile can be linked to plaque-site-specific treatment resistance. Quantitative immunohistochemical analysis and transcriptomic digital spatial profiling were performed on skin punch biopsies obtained from unaffected areas on the trunk, lesional areas of the scalp, upper extremity, and LE of 12 patients with psoriasis. Histological analysis showed no significant differences in epidermal thickness among lesional (LS) skin from different body locations. Immunohistochemical markers (CD3, CD4, CD8, CD103, CD207, RORγt, FOXP3 and MPO) were higher in LS skin compared with non-lesional (NL) skin but did not differ significantly between LS sites. Whole transcriptome spatial RNA profiling identified several differentially expressed genes that distinguished LS from NL skin and revealed site-specific transcriptomic differences. Notably, IL-23 signalling was significantly enriched in the LE epidermis, and IL-17 signalling was more pronounced in the epidermis of LS samples. These findings highlight minimal histological and immunohistochemical variation, yet significant transcriptomic and pathway differences between psoriasis body locations, suggesting potential future targets for site-specific therapeutic strategies.
P72 The role of the transcription factor Bcl11b in IL-17, IL-23 and/or TNF-induced activation of the canonical and non-canonical NF-κB pathways in psoriatic keratinocytes
Journal: British Journal of Dermatology (2024)

Abstract Bcl11b (CTIP2) is a crucial transcription factor involved in the differentiation processes across various cell types, including T cells and keratinocytes. It functions both as a transcriptional repressor and activator, interacting with complexes such as NuRD and proteins like p300. Bcl11b is significantly expressed in skin and immune cells suggesting its potential involvement in diseases like psoriasis, which is characterized by hyperproliferation and aberrant differentiation of keratinocytes alongside immune cell infiltration and cytokine release. However, the mechanism underlying the role of Bcl11b in the pathogenesis of psoriasis remains unidentified. To elucidate Bcl11b’s role in psoriasis by analysing its expression and correlated pathways through meta-analysis of sequencing-based transcriptome profiles and by functional assays in normal and genetically engineered keratinocytes under inflammatory conditions. RNA-sequencing datasets from psoriatic and healthy skin samples were processed and analysed for differential expression of transcription factors, with a focus on Bcl11b. Pearson correlation analysis identified genes correlated with Bcl11b expression. Enrichment and pathway analyses were conducted using Enrichr. Functional studies involved Bcl11b knockdown in HaCaT keratinocytes via CRISPRi, followed by cytokine stimulation including IL-17A, IL-23, TNF-α and the combinations. The activation of canonical and non-canonical NF-κB pathways was assessed. Downregulation of Bcl11b in psoriatic lesions was confirmed. Correlated genes were enriched in pathways involving IL-17A, IL-23 and TNF-α signalling. Knockdown of Bcl11b in keratinocytes resulted in morphological changes indicative of incomplete differentiation and reduced proliferation. Under cytokine-driven inflammatory conditions, canonical NF-κB pathway activation was impaired in Bcl11b KD cells, while non-canonical NF-κB pathway activation was dependent on IL-17A and the combination of IL-23/TNF-α in these KD cells. These data highlight the pivotal role of Bcl11b in the proinflammatory cytokine-induced regulation of the NF-κB signalling pathways. Absence of Bcl11b results in abnormal keratinocyte behaviour associated with psoriasis. Our data suggest that key proinflammatory cytokines in psoriasis act differently on Bcl11b associated activation of the NF-kB pathways.
FC01 Higher IL-10+ T-cell and Treg-cell counts in psoriatic skin are associated with super-response to guselkumab: data from the Phase 3b GUIDE trial
Journal: British Journal of Dermatology (2024)

Abstract Interleukin-10 (IL-10) and regulatory T (Treg) cells are immunosuppressive mediators with key roles in autoimmunity. Their increased presence is believed to counter-regulate pathogenic tissue-resident memory (TRM) and T-helper (Th)17 cells in psoriasis. The ongoing randomized, double-blinded, controlled Phase 3b GUIDE trial (NCTO3818035) examines the clinical and immunological impact of an extended guselkumab [an interleukin (IL)-23p19 subunit inhibitor] dosing interval in patients with moderate-to-severe plaque-type psoriasis. Patients who achieved a psoriasis area and severity index (PASI) = 0 at both Week [W]20 and W28 with guselkumab treatment were defined as super-responders (SRes). In this mechanistic substudy of GUIDE, we aimed to determine whether SRes show immunological differences in skin T-cell composition vs. non-SRes, using flow cytometry analysis of non-lesional (at W0) and lesional (at W0, W4, W28 and W68) skin cells taken from 63 patients. At ­baseline, IL-10+ T-cell counts were higher in both non-lesional and lesional skin of SRes vs. non-SRes (with an SRe to non-SRe ratio of 3.1:1 in non-lesional skin, and a 3.0:1 ratio in lesional skin; P &amp;lt; 0.05). This trend was maintained in lesional skin after treatment with guselkumab, with higher IL-10+ T-cell counts observed in SRes than non-SRes at W4 (with an SRe to non-SRe ratio of 4.6:1; P &amp;lt; 0.05) and at W28 (with a ratio of 4.4:1; P &amp;lt; 0.05). Treg-cell (CD4+CD25+FoxP3+) counts were also higher in SRes at W4 and W28 (with an SRe to non-SRe ratio of 3.1:1 at W4, and a ratio of 2.9:1 at W28; P &amp;lt; 0.05). Further analysis of effector T-cell subsets showed that CD8+ TRM and IL-17A+ T-cell counts in lesional skin were reduced by guselkumab up to W68. Normalization of these T-cell populations in lesional skin to non-lesional skin levels appeared to be earlier in SRes (W28) compared with non-SRes (W68). These findings from GUIDE suggest that clinical super-response to guselkumab may be characterized by higher IL-10+ T-cell and Treg-cell counts, and faster normalization of CD8+ TRM and IL-17A+ T-cell counts. Therefore, higher IL-10+ T-cell and Treg-cell counts may act as predictive biomarkers for a better response to guselkumab in patients with moderate-to-severe plaque-type psoriasis.
FC07 Transcriptomic profiling across tissues and machine learning reveal molecular endotypes of psoriasis phenotypes and signatures of disease severity during biologic therapy
Journal: British Journal of Dermatology (2024)

Abstract Despite advances in understanding the pathogenesis of psoriasis, important knowledge gaps exist including (i) whether molecular endotypes of stable plaque psoriasis underlie distinct clinical phenotypes (e.g. subjects with specific comorbidities) and (ii) the positive drivers and negative molecular regulators of disease severity across tissue compartments. We performed a comprehensive RNA-seq study of skin and blood samples (n = 718) from deeply phenotyped discovery (n = 89) and refinement (n = 57) psoriasis cohorts, during targeted treatment with a TNF inhibitor (adalimumab) or an interleukin (IL)-12/23 inhibitor (ustekinumab). As gene expression is controlled by multiple factors across different cell types, network analysis of bulk RNAseq data across large numbers of clinical samples takes into account the underlying latent factors and modules that result in the coordination of gene expression and can more accurately reflect the relationship between transcriptional signatures and clinical phenotypes compared with analysis of individual genes. Using two complementary methods for dimensionality reduction, weighted gene correlation network analysis (WGCNA) and Independent Component Analysis (ICA), we defined distinct but interconnected gene modules and factors within skin and blood that were significantly positively or negatively associated with disease severity as measured by Psoriasis Area Severity Index (PASI). To understand which modules and factors in lesional psoriasis skin contribute to the prediction of disease severity, we applied Gaussian process regression followed by SHAP (SHapley Additive exPlanations). This analysis highlighted 2 principal gene modules [cytokine signalling (267 genes) and Wnt signalling (207 genes)] that explained ∼50% of the variance of PASI during clinical response to both adalimumab and ustekinumab. We derived a further gene signature (14 genes), linked to body mass index in nonlesional skin at baseline, that in lesional skin was significantly negatively associated with PASI. Notably, PASI-associated signatures in blood were only seen following exposure to adalimumab whereas ustekinumab PASI-associated signatures were confined to skin. These highly drug-specific tissue compartmentalization effects indicate a differential systemic impact of adalimumab compared with ustekinumab, in line with differences in side-effect profiles. In contrast, a gene signature in blood closely linked to HLA-C*06:02 status was independent of disease severity (PASI). The systematic nature of the dataset across skin and blood and its integration with key clinical features and outcomes to therapy provides a comprehensive and global perspective of psoriasis that are not apparent from previous studies. Specifically, our findings delineate, across skin and blood, distinct gene-environmental and genetic effects on the psoriasis transcriptome linked to clinical phenotypes and disease severity endotypes.
Bridging Innovation and Equity: Advancing Public Health Through Just-in-Time Adaptive Interventions
Authors: Nur Hani Zainal, Xueqing Liu, Utek Leong, Xiaoxi Yan, Bibhas Chakraborty
Journal: Annual Review of Public Health (2024)

This review explores the transformative potential of just-in-time adaptive interventions (JITAIs) as a scalable solution for addressing health disparities in underserved populations. JITAIs, delivered via mobile health technologies, could provide context-aware personalized interventions based on real-time data to address public health challenges such as addiction, chronic disease, and mental health management. JITAIs can dynamically adjust intervention strategies, enhancing accessibility and engagement for marginalized communities. We highlight the utility of JITAIs in reducing opportunity costs associated with traditional in-person health interventions. Examples from various health domains demonstrate the adaptability of JITAIs in tailoring interventions to meet diverse needs. The review also emphasizes the need for community involvement, robust evaluation frameworks, and ethical considerations in implementing JITAIs, particularly in low- and middle-income countries. Sustainable funding models and technological innovations are necessary to ensure equitable access and effectively scale these interventions. By bridging the gap between research and practice, JITAIs could improve health outcomes and reduce disparities in vulnerable populations.
Adapting Public Health and Health Services Interventions in Diverse, Real-World Settings: Documentation and Iterative Guidance of Adaptations
Authors: Borsika A. Rabin, Kelli L. Cain, Russell E. Glasgow
Journal: Annual Review of Public Health (2024)

When complex public health and health services interventions are implemented in real-world settings, adaptations should be expected, embraced, and studied rather than suppressed and ignored. A substantial amount of recent research has been conducted on the assessment of some types of adaptations, and interest in guiding adaptations to both interventions and implementation strategies is growing. However, there is still a need to investigate the optimal ways to systematically and pragmatically document, analyze, and iteratively guide adaptations as well as to measure the impact of those adaptations on implementation and effectiveness outcomes. This article reviews key findings from the adaptations assessment literature, frameworks to guide classification of adaptations, and methodologies to study adaptations and their impact. We summarize research from diverse settings and populations from public health and health services research on the use of these methodologies and make recommendations for research, practice research, and practice.
Strategies for Effective Public Health Communication in a Complex Information Environment
Authors: Jeff Niederdeppe, Amanda D. Boyd, Andy J. King, Rajiv N. Rimal
Journal: Annual Review of Public Health (2024)

Development and amplification of effective, culturally resonant, trustworthy, and evidence-based public health communication are urgently needed. Research evidence, theory, and practical experience from within and beyond the interdisciplinary field of health communication are well-positioned to help public health authorities, researchers, and advocates navigate the complex societal challenges that influence health and well-being in global contexts. This review offers a broad overview of the field, considers what constitutes “effectiveness” versus “effects” in public health communication, and describes core concepts of public health communication as a process rather than a product. We review domains and dominant foci of public health communication research, articulate challenges for health communication to advance health and social equity and address mis-/disinformation, and offer practical guidance on message development, audience segmentation, multilevel intervention, and evaluation of communication programs. We conclude by identifying important questions for future public health communication research, interventions, and funding.
P123 Plaque psoriasis and diabetes mellitus in the context of psychosis
Journal: British Journal of Dermatology (2024)

Abstract Psoriasis is an autoimmune autoinflammatory skin disease which may affect any body area. The disease may be accompanied by metabolic syndrome, which in some cases may manifest itself as frank diabetes mellitus. Psychosis, particularly schizophrenia may also be related to the development of diabetes mellitus. The aim was to describe the case of a patient who developed plaque psoriasis at the age of 32 and diabetes mellitus Type 2 thereafter in the context of schizophrenia. A male patient aged 35 presented with plaque psoriasis. Local measures were applied to treat the disease. The patient had been diagnosed at the age of 20 with psychosis, in this particular case schizophrenia. He was on antipsychotic drug treatment. He did not require hospitalization for his mental health issue. At the age of 37, he was diagnosed with diabetes mellitus Type 2. Metformin was administered. However, the patient developed obesity and diabetes mellitus required combined treatment with metformin and vildagliptin. Plaque psoriasis requires only local measures to be controlled with. The presence of metabolic syndrome in the context of psoriatic disease is well described. However, we present the case of a patient with schizophrenia and diabetes mellitus Type 2 in the context of overt metabolic syndrome. Schizophrenia is also known to be associated with the development of diabetes mellitus Type 2. The development of diabetes mellitus in the context of schizophrenia may be related to genetic reasons. In our case, it may be related either to genetic reasons or to environmental pressures or it may be the exhibition of severe stress which the patient cannot properly handle. Severe stress and the inability to cope with it may be related to the development of an autoimmune disease, such as plaque psoriasis in the context of schizophrenia. The presence of diabetes mellitus Type 2 may be related both to schizophrenia as well as to the metabolic syndrome described within the context of psoriatic disease.