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David Bergman,1 Bjorn Roelstraete,1 Jiangwei Sun,1 Fahim Ebrahimi,1,2 Rickard Lidström,3 Axel Svedbom,4,5 Mona Ståhle,4 Jonas F Ludvigsson1,6,7 1Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; 2Department of Gastroenterology and Hepatology, Clarunis University Center for Gastrointestinal and Liver Diseases, Basel, Switzerland; 3Diagnostiskt Centrum Hud, Stockholm, Sweden; 4Division of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; 5Dermatology and Venereology Clinic, Karolinska University Hospital, Stockholm, Sweden; 6Department of Pediatrics, Orebro University Hospital, Orebro, Sweden; 7Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USACorrespondence: David Bergman, Email David.bergman.1@ki.seBackground: Microscopic colitis (MC) has been associated with several immune-mediated diseases including psoriasis, but earlier research has been limited to psoriasis occurring before MC. Data from large-scale cohort studies investigating MC and risk of future psoriasis are lacking.Objective: To examine the association between MC and psoriasis.Methods: In a nationwide, population-based, matched cohort study in Sweden from 2007 to 2021, we identified 8404 patients with biopsy-verified MC (diagnosed in 2007– 2017), 37,033 matched reference individuals, and 8381 siblings without MC. Information on MC was obtained through the ESPRESSO cohort (a Swedish histopathology database with nationwide coverage). Using Cox regression, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for psoriasis up until 2021.Results: During a median follow-up of 9.2 years (interquartile range = 6.7– 11.7), 179 MC patients and 440 reference individuals were diagnosed with psoriasis (241.1 vs 131.8 events per 100,000 person-years), corresponding to one extra case of psoriasis in 91 patients with MC over 10 years. After adjustment for the matching variables (birth year, sex, county of residence, and calendar period) and level of education, we computed an adjusted hazard ratio (aHR) of 1.82 (95% CI = 1.53– 2.17). Stratified by sex, estimates were similar and when examining the aHR across different lengths of follow-up, we found significantly elevated estimates up to 10 years after MC diagnosis. Compared to MC-free siblings, the aHR was 1.85 (95% CI = 1.36– 2.51).Conclusion: Patients with MC are at an almost doubled risk of psoriasis compared to the general population. Clinicians need to consider psoriasis in MC patients with skin lesions.Keywords: microscopic colitis, psoriasis, epidemiology

Background: Patients treated with systemics for moderate‐to‐severe psoriasis have increased risk of cardiovascular disease (CVD). However, to the best of our knowledge, there are no data on the association between clinical disease activity and future cardiovascular events in this population. Such data could help identify patients at increased CVD risk and inform the potential for CVD prevention with effective psoriasis treatment. Objective: To estimate the association between the Psoriasis Area and Severity Index (PASI) and cardiovascular events defined as hospitalization for CVD and cardiovascular death. Methods: We linked prospectively collected data on PASI and CVD risk factors to population‐based administrative data on hospitalizations and causes of death. We estimated the association between PASI and cardiovascular events using Cox proportional hazard models with PASI and Framingham 10‐year cardiovascular risk as time‐varying covariates. Results: A total of 767 patients with 6264 PASI scores were included. After adjusting for 10‐year cardiovascular risk and prior CVD, a one‐point increase in PASI was associated with a hazard ratio of 1.04 (95% CI: 1.01–1.07) for cardiovascular events. The findings were robust in sensitivity analyses. Conclusion: PASI is an independent marker for future cardiovascular events in patients with moderate‐to‐severe psoriasis. [ABSTRACT FROM AUTHOR]

Psoriasis and inflammatory bowel disease (IBD) are immune‐mediated diseases occurring in barrier organs whose main task is to protect the organism from attack. These disorders are highly prevalent especially in northern Europe where psoriasis has a prevalence of around 3–4% and IBD around 0.3%. The prevalence of IBD in North America has been estimated at around 0.4%. The total incidence rates in northern Europe have been estimated at around 6 for Crohn's disease and 11 for ulcerative colitis per 100 000 person‐years, compared with an incidence rate of around 280 per 100 000 person‐years for psoriasis. Both diseases are less common in countries with a lower index of development. The rise in IBD appears to occur as populations adopt a westernized lifestyle, whereas psoriasis seems more stable and prevalence differences may derive more from variation in genetic susceptibility. The gut microbiota is clearly an important driver of IBD pathogenesis; in psoriasis, changes in gut and skin microbiota have been reported, but it is less clear whether and how these changes contribute to the pathogenesis. Large studies show that most identified genes are involved in the immune system. However, psoriasis and IBD are highly heterogeneous diseases and there is a need for more precise and deeper phenotyping to identify specific subgroups and their genetic, epigenetic and molecular signatures. Epigenetic modifications of DNA such as histone modifications, noncoding RNA effects on transcription and translation and DNA methylation are increasingly recognized as the mechanism underpinning much of the gene–environment interaction in the pathogenesis of both IBD and psoriasis. Our understanding of underlying pathogenetic mechanisms has deepened fundamentally over the past decades developing hand in hand with novel therapies targeting pathways and proinflammatory cytokines incriminated in disease. There is not only substantial overlap between psoriasis and IBD, but also there are differences with implication for therapy. In psoriasis, drugs targeting interleukin‐23 and interleukin‐17 have shown superior efficacy compared with anti‐TNFs, whilst in IBD, drugs targeting interleukin‐17 may be less beneficial. The therapeutic toolbox for psoriasis is impressive and is enlarging also for IBD. Still, there are unmet needs reflecting the heterogeneity of both diseases and there is a need for closer molecular diagnostics to allow for the development of precise therapeutics. [ABSTRACT FROM AUTHOR]

Background: APPRECIATE is a multinational, observational, retrospective, cross‐sectional study in patients treated for psoriasis with apremilast, an oral phosphodiesterase 4 inhibitor. Objectives: To describe the characteristics of patients with psoriasis treated with apremilast in the clinical setting, to evaluate real‐world outcomes of psoriasis treatment with apremilast and to better understand the perspectives of patients and physicians on treatment outcomes. Methods: In six European countries, patients with chronic plaque psoriasis treated in clinical practice who could be contacted 6 (±1) months after apremilast initiation were enrolled. Patient characteristics, Dermatology Life Quality Index (DLQI) and Psoriasis Area and Severity Index (PASI) were obtained from medical records when available. Outcomes were evaluated using patient/physician questionnaires. Results: In 480 patients at treatment initiation, mean [median; 95% confidence interval (CI)] PASI and DLQI scores were 12.5 (10.7; 11.6–13.4) and 13.4 (13.0; 11.4–14.2), respectively. At 6 (±1) months, 72.3% of patients (n = 347) continued apremilast treatment [discontinuations: lack of efficacy (13.5%), safety (11.7%), other (2.5%)]. In patients continuing treatment, 48.6% achieved a ≥75% reduction in PASI score; mean (95% CI) DLQI score was 5.7 (4.5–6.9), and mean (SD) Patient Benefit Index score was 2.8 (1.2). Physicians perceived clinical improvement in 75.6% of patients. Physicians' perspective on overall success of apremilast in meeting expectations correlated with patients' perception of treatment benefit (r = 0.691). Most commonly reported adverse events (>5% of patients) were diarrhoea, nausea and headache. Conclusions: Patients in APPRECIATE reported high disease burden despite more moderate skin involvement than those who enrolled in clinical trials of apremilast. Findings from APPRECIATE demonstrate the real‐world value of apremilast for psoriasis treatment, as 7 of 10 patients continued therapy and showed notable improvement in disease severity and quality of life 6 (±1) months after apremilast initiation. Linked Commentary: P. Gisondi et al. J Eur Acad Dermatol Venereol 2021; 35: 13. https://doi.org/10.1111/jdv.17067. [ABSTRACT FROM AUTHOR]

Background: Psoriatic arthritis (PsA) develops in ~30% of patients with psoriasis. The diagnosis of PsA is challenging, and there are no reliable molecular markers in clinical use. MicroRNAs are short non‐coding regulatory RNAs, which can be actively packaged into extracellular vesicles (EVs) and secreted to the circulation. Objectives: To explore whether plasma‐derived EV microRNAs may serve as biomarkers for PsA in patients with psoriasis. Methods: Plasma samples were obtained from patients with cutaneous‐only psoriasis (PsC) and patients with psoriasis and PsA. Plasma EVs were isolated using miRCURY™ Exosome Isolation Kit. RNA sequencing was used to identify differentially expressed EV miRNAs in the discovery phase (PsC, n = 15; PsA, n = 14). In the validation phase (PsC, n = 29; PsA, n = 28), 41 selected miRNAs were analysed in plasma EVs by qPCR. The association of the identified miRNAs with PsA was assessed by logistic regression analysis. Results: RNA sequencing identified 19 plasma EV miRNAs with significantly different levels between PsA and PsC in the discovery cohort. Significantly lower levels of plasma EV let‐7b‐5p and miR‐30e‐5p in PsA vs. PsC were confirmed in the validation cohort, and their decreased levels were found to be associated with the presence of PsA. ROC analysis revealed an AUC of 0.68 (95% CI 0.53–0.83) for let‐7b‐5p and 0.69 (95% CI 0.55–0.84) for miR‐30e‐5p. Conclusions: Circulating EV microRNA levels are altered in patients with PsA as compared with PsC. Findings of this exploratory study suggest that circulating EV microRNAs may serve as biomarkers for arthritis in psoriasis patients. [ABSTRACT FROM AUTHOR]

Background: The advent of biosimilars may render etanercept (ETN) and adalimumab (ADA) viable alternatives to methotrexate (MTX) as first‐line systemics in psoriasis. However, real‐world relative effectiveness data comparing ADA and ETN to MTX are limited. Objective: To estimate the relative effectiveness of ADA and ETN compared to MTX. Methods: We analysed data from DermaReg, a regional register in Stockholm, Sweden, to estimate drug survival and mean Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) during maintenance treatment. Results: A total of 524 patients initiated 727 treatment episodes with ADA, ETN or MTX. After adjusting for confounders, patients treated with ADA had better drug survival (HR: 0.67; P = 0.003), lower mean PASI (−2.0; P < 0.001) and lower mean DLQI (−0.9; P < 0.001) during maintenance treatment compared to patients treated with MTX. The results for ETN compared to MTX were mixed. After adjusting for confounding, there was no significant difference in drug survival (HR 1.23; P = 0.082), but patients on ETN had lower mean PASI (−0.7; P = 0.006) during maintenance treatment. Conclusion: Adalimumab is superior to MTX in clinical practice whereas the relative effectiveness between ETN and MTX is less clear. This study also highlights the importance of appropriate confounding control in effectiveness analysis. [ABSTRACT FROM AUTHOR]

Summary: Background: As lipids are known to regulate macrophage functions, it is reasonable to suppose that a sebocyte–macrophage axis mediated by sebum lipids may exist. Objectives: To investigate if sebocytes could contribute to the differentiation, polarization and function of macrophages with their secreted lipids. Methods: Oil Red O lipid staining and Raman spectroscopy were used to assess the dermal lipid content and penetration. Immunohistochemistry was used to analyse the macrophage subsets. Human peripheral blood monocytes were differentiated in the presence of either supernatant from human SZ95 sebocytes or major sebum lipid components and activated with Propionibacterium acnes. Macrophage surface markers and their capacity to uptake fluorescein isothiocyanate‐conjugated P. acnes were detected by fluorescence‐activated cell sorting measurements. Cytokine protein levels were evaluated by enzyme‐linked immunosorbent assay and Western blot analysis. Results: Sebaceous gland‐rich skin had an increased dermal lipid content vs. sebaceous gland‐poor skin to which all the tested sebum component lipids could contribute by penetrating the dermoepidermal barrier. Of the lipids, oleic acid and linoleic acid promoted monocyte differentiation into alternatively activated macrophages. Moreover, linoleic acid also had an anti‐inflammatory effect in P. acnes‐activated macrophages, inhibiting the secretion of interleukin (IL)‐1β, IL‐6 and tumour necrosis factor (TNF)‐α. Squalene, palmitic acid, stearic acid and oleic acid augmented the secretion of IL‐1β, even in the absence of P. acnes, whereas oleic acid had a selective effect of inducing IL‐1β but downregulating IL‐6 and TNF‐α secretion. Conclusions: Our results suggest a role for sebaceous glands in modulating innate immune responses via their secreted lipids that are of possible pathological and therapeutic relevance. [ABSTRACT FROM AUTHOR]

Objective: To describe the social status and health-related quality of life of patients with psoriatic arthritis mutilans (PAM) in the Nordic countries.Method: Patients with at least one mutilated joint confirmed by radiology were studied. Disease activity involving joints and skin, physician-assessed disease activity, and patient's education and work status were recorded. Data from the 36-item Short Form Health Survey, Health Assessment Questionnaire and Dermatology Life Quality Index questionnaire were gathered and correlated with disease duration, pain, and general well-being (visual analogue scale). The controls were 58 Swedish patients with long-standing psoriatic arthritis sine PAM.Results: Sixty-seven patients were included. Patients with PAM had a protracted disease history (33 ± 14 years) and disease onset at a relatively early age (30 ± 12 years). Overall inflammatory activity at inclusion was mild to moderate. The mean number of mutilated joints was 8.2 and gross deformity was found in 16% of patients. Forty per cent were treated with biological and 32% with conventional synthetic disease-modifying anti-rheumatic drugs. Forty-two per cent had retired early or were on sick leave. Impaired functional capacity with little or no ability to perform self-care or everyday tasks was reported by 21% of the patients. Patients between 45 and 60 years of age reported the most impaired quality of life in comparison to the control group.Conclusion: PAM seriously affects social functioning. Whether early recognition of PAM and new forms of therapy can improve disease outcome and quality of life remains to be studied. [ABSTRACT FROM AUTHOR]

Objective: To determine the prevalence and clinical characteristics of psoriatic arthritis mutilans (PAM) in the Nordic countries. Method: Patients with putative PAM aged ≥ 18 years were recruited. Fifty-nine patients were included after clinical examination. Results: The prevalence of PAM in the adult Nordic population was estimated to be 3.69 per million inhabitants [95% confidence interval (CI) 2.75-4.63]. The female to male ratio was close to 1:1. The mean age of skin disease onset was 25 years and the mean age of onset of joint disease was 30 years. The onset of skin disease was 2 years earlier among female patients. At inclusion, the mean duration of arthritis was 27 ± 11 years for male patients and 33 ± 11 years for female patients. PAM was most frequently seen in the distal interphalangeal (DIP) joints of the toes, followed by the IP joint of the thumb and the DIP joint of the little finger on the left hand. Female and male patients had similar numbers of painful and swollen joints. Enthesitis was found in 19 patients (32%), while 38 patients (64%) had a history of dactylitis. Twenty-three of these 38 patients (61%) had a history of dactylitis in the same finger/toe as they had PAM. At the time of inclusion, 45% of the patients were found to have clear or almost clear skin. Conclusions: PAM in the Nordic countries has a low prevalence, with only three to five cases per million inhabitants. The majority of the patients present with mild skin disease. [ABSTRACT FROM AUTHOR]

Background Micro RNAs (mi RNAs) are endogenous, nonprotein-coding, regulatory RNAs with important roles in health and disease. mi RNAs are present in the circulation in a stable form and their levels are altered in diseases. Objectives To determine whether antitumour necrosis factor ( TNF)-α therapy affects serum mi RNA levels in patients with psoriasis. Methods Serum samples were obtained from healthy donors and from patients with chronic plaque psoriasis before and 12 weeks after the initiation of treatment with the TNF-inhibitor etanercept or methotrexate. mi RNA expression profiling was utilized to identify miRNAs with altered serum level in psoriasis, as well as anti- TNF-α-regulated mi RNAs in patients' sera. The expression of five miRNAs regulated by etanercept was measured by quantitative polymerase chain reaction (q PCR) in sera from patients and controls. Results Etanercept significantly suppressed a panel of 38 mi RNAs, which were found to be predominantly immune-cell derived and which have been implicated in inflammation and autoimmunity. Validation by q PCR showed that serum levels of miR-106b, mi R-26b, mi R-142-3p, mi R-223 and mi R-126 were significantly downregulated by etanercept in responders (Psoriasis Area and Severity Index change > 50%). By contrast, methotrexate did not significantly affect the levels of these miRNAs. Serum levels of these miRNAs were not upregulated in patients with psoriasis compared with healthy controls. The level of four circulating mi RNAs was significantly different (increased: mi R-128a; decreased: let-7d, miR-142-3p, miR-181a) in psoriasis and healthy serum. Conclusions The level of circulating mi RNAs is altered in psoriasis. Anti- TNF-α therapy has a profound effect on the serum level of mi RNAs; however, these are not related to disease severity. Our results suggest that changes in the mi RNA level may reflect a previously unknown effect of anti- TNF-α therapy. Our results suggest the involvement of mi RNAs in pathways affected by anti- TNF-α therapy and warrant further investigation of serum mi RNAs as potential biomarkers for therapy response in psoriasis. [ABSTRACT FROM AUTHOR]

Summary Background: Psoriasis is associated with several comorbidities and behavioural risk factors. Objectives: To evaluate demographic and disease characteristics in patients enrolled in the Psoriasis Longitudinal Assessment and Registry (PSOLAR). Methods: PSOLAR is a global, prospective, longitudinal, disease-based registry that includes a postmarketing commitment to evaluate safety in patients with psoriasis. Enrolled patients had to be receiving, or be eligible to receive, conventional systemic or biological agents. Demographic/disease characteristics, medical histories, lifestyle risk factors and previous treatments are collected at enrolment. Efficacy and safety data are collected every 6 months for 8 years, and data are extracted annually. Selected parameters are evaluated by age quartile using post hoc analyses. Results: As of 23 August 2012, 11 900 patients were enrolled at 301 sites in North America, Europe and Latin America. Over half of the PSOLAR population (54·7%) is male, with a mean age of 48·6 years and mean body mass index of 30·9 kg m−2 at enrolment. Mean duration of disease at enrolment was 17·5 years, and mean Physician's Global Assessment score was 2·0. Psoriatic arthritis (35·5%) and cardiovascular diseases (38·2%) were highly prevalent. Diabetes mellitus type II was reported in 11·4% of patients. Depression and anxiety were noted in 14·7% and 11·1% of patients, respectively; 79·0% reported any alcohol use and 56·7% reported smoking or a history of smoking. The occurrence of most comorbidities, including cardiovascular disease and risk factors, increased with age. Conclusions: In the PSOLAR population, multiple and age-appropriate comorbidities are associated with psoriasis and may affect the selection of psoriasis treatments. What's already known about this topic? Psoriasis is a complicated disorder, often accompanied by multiple comorbidities. Demographic and disease characteristics of patients with psoriasis reported from large claims datasets may be affected by misclassification bias or coding errors. In clinical trials, many patients are excluded owing to strict inclusion criteria. What does this study add? Data collected by the Psoriasis Longitudinal Assessment and Registry reveal that the demographics and disease characteristics of patients with psoriasis who are receiving, or are candidates for, systemic therapy in actual clinical care resemble those reported in clinical trials. Most comorbidities occur more frequently in older patients, who, in turn, may require more comprehensive overall medical care.

Linked article: C. Blegvad et al. J Eur Acad Dermatol Venereol 2020; 34: 1516–1523. https://doi.org/10.1111/jdv.16229. [ABSTRACT FROM AUTHOR]

Abstract Background Most of the many computer resources used in clinical teaching of dermatology and venereology for medical undergraduates are information-oriented and focus mostly on finding a "correct" multiple-choice alternative or free-text answer. We wanted to create an interactive computer program, which facilitates not only factual recall but also clinical reasoning. Methods Through continuous interaction with students, a new computerised interactive case simulation system, NUDOV, was developed. It is based on authentic cases and contains images of real patients, actors and healthcare providers. The student selects a patient and proposes questions for medical history, examines the skin, and suggests investigations, diagnosis, differential diagnoses and further management. Feedback is given by comparing the user's own suggestions with those of a specialist. In addition, a log file of the student's actions is recorded. The program includes a large number of images, video clips and Internet links. It was evaluated with a student questionnaire and by randomising medical students to conventional teaching (n = 85) or conventional teaching plus NUDOV (n = 31) and comparing the results of the two groups in a final written examination. Results The questionnaire showed that 90% of the NUDOV students stated that the program facilitated their learning to a large/very large extent, and 71% reported that extensive working with authentic computerised cases made it easier to understand and learn about diseases and their management. The layout, user-friendliness and feedback concept were judged as good/very good by 87%, 97%, and 100%, respectively. Log files revealed that the students, in general, worked with each case for 60–90 min. However, the intervention group did not score significantly better than the control group in the written examination. Conclusion We created a computerised case simulation program allowing students to manage patients in a non-linear format supporting the clinical reasoning process. The student gets feedback through comparison with a specialist, eliminating the need for external scoring or correction. The model also permits discussion of case processing, since all transactions are stored in a log file. The program was highly appreciated by the students, but did not significantly improve their performance in the written final examination.

Molecular imaging can detect and quantify pathophysiological processes underlying heart failure, complementing evaluation of cardiac structure and function with other imaging modalities. Targeted tracers have enabled assessment of various cellular and subcellular mechanisms of heart failure aiming for improved phenotyping, risk stratification, and personalized therapy. This review outlines the current status of molecular imaging in heart failure, accompanied with discussion on novel developments. The focus is on radionuclide methods with data from clinical studies. Imaging of myocardial metabolism can identify left ventricle dysfunction caused by myocardial ischemia that may be reversible after revascularization in the presence of viable myocardium. In vivo imaging of active inflammation and amyloid deposition have an established role in the detection of cardiac sarcoidosis and transthyretin amyloidosis. Innervation imaging has well documented prognostic value in predicting heart failure progression and arrhythmias. Tracers specific for inflammation, angiogenesis and myocardial fibrotic activity are in earlier stages of development, but have demonstrated potential value in early characterization of the response to myocardial injury and prediction of cardiac function over time. Early detection of disease activity is a key for transition from medical treatment of clinically overt heart failure towards a personalized approach aimed at supporting repair and preventing progressive cardiac dysfunction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The advent of biosimilars may increase the frequency of dose escalation with biologics in psoriasis., Objective: To explore the frequency and outcomes of dose escalation with adalimumab etanercept, and ustekinumab., Methods: Data were extracted from DermaReg-Pso, a psoriasis register in Stockholm, Sweden. The main exposure was treatment, and the main outcome was dose escalation. We describe outcomes with dose escalation by estimating drug survival and changes in the Psoriasis Area and Severity Index (PASI)., Results: 554 patients had 946 treatment episodes with adalimumab, etanercept, or ustekinumab. The cumulative incidence of dose escalation was 4.1 per 100 treatment years. The Hazard Ratios (HRs) for dose escalation with ustekinumab vs adalimumab and ustekinumab vs etanercept were 1.93 (95% CI: 1.25-2.98), and 2.20 (95% CI: 1.42-3.41), respectively. After dose escalation, the HRs for treatment discontinuation with adalimumab and etanercept compared with ustekinumab were 3.10 (95% CI: 1.56-6.18) and 7.15 (95% CI: 3.96-12.94), respectively. PASI was higher after compared to before dose escalation for etanercept ( p  = 0.036), but not for adalimumab ( p  = 0.832) or ustekinumab ( p  = 0.300)., Conclusions: Dose escalation was comparatively more frequent with ustekinumab than with adalimumab or etanercept; however, treatment discontinuation after dose escalation was more common with adalimumab and etanercept than ustekinumab.

The world's oceans are challenged by climate change linked warming with typically highly populated coastal areas being particularly susceptible to these effects. Many studies of climate change on the marine environment use large, short-term temperature manipulations that neglect factors such as long-term adaptation and seasonal cycles. In this study, a Baltic Sea 'heated' bay influenced by thermal discharge since the 1970s from a nuclear reactor (in relation to an unaffected nearby 'control' bay) was used to investigate how elevated temperature impacts surface water microbial communities and activities. 16S rRNA gene amplicon based microbial diversity and population structure showed no difference in alpha diversity in surface water microbial communities, while the beta diversity showed a dissimilarity between the bays. Amplicon sequencing variant relative abundances between the bays showed statistically higher values for, e.g., Ilumatobacteraceae and Burkholderiaceae in the heated and control bays, respectively. RNA transcript-derived activities followed a similar pattern in alpha and beta diversity with no effect on Shannon's H diversity but a significant difference in the beta diversity between the bays. The RNA data further showed more elevated transcript counts assigned to stress related genes in the heated bay that included heat shock protein genes dnaKJ , the co-chaperonin groS , and the nucleotide exchange factor heat shock protein grpE . The RNA data also showed elevated oxidative phosphorylation transcripts in the heated (e.g., atpHG ) compared to control (e.g., atpAEFB ) bay. Furthermore, genes related to photosynthesis had generally higher transcript numbers in the control bay, such as photosystem I ( psaAC ) and II genes ( psbABCEH ). These increased stress gene responses in the heated bay will likely have additional cascading effects on marine carbon cycling and ecosystem services., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Seidel, Broman, Ståhle, Bergström, Forsman, Hylander, Ketzer and Dopson.)

Psoriatic arthritis mutilans (PAM) is the rarest and most severe form of psoriatic arthritis, characterized by erosions of the small joints and osteolysis leading to joint disruption. Despite its severity, the underlying mechanisms are unknown, and no susceptibility genes have hitherto been identified. We aimed to investigate the genetic basis of PAM by performing massive parallel sequencing in sixty-one patients from the PAM Nordic cohort. We found rare variants in the NADPH oxidase 4 (NOX4) in four patients. In silico predictions show that the identified variants are potentially damaging. NOXs are the only enzymes producing reactive oxygen species (ROS). NOX4 is specifically involved in the differentiation of osteoclasts, the cells implicated in bone resorption. Functional follow-up studies using cell culture, zebrafish models, and measurement of ROS in patients uncovered that these NOX4 variants increase ROS levels both in vitro and in vivo. We propose NOX4 as the first candidate susceptibility gene for PAM. Our study links high levels of ROS caused by NOX4 variants to the development of PAM, offering a potential therapeutic target., (© 2024. The Author(s).)