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Through a process called “bioturbation,” burrowing macrofauna have altered the seafloor habitat and modified global carbon cycling since the Cambrian. However, the impact of macrofauna on the community structure of microorganisms is poorly understood. Here, we show that microbial communities across bioturbated, but geochemically and sedimentologically divergent, continental margin sites are highly similar but differ clearly from those in nonbioturbated surface and underlying subsurface sediments. Solidand solute-phase geochemical analyses combined with modeled bioturbation activities reveal that dissolved O₂ introduction by burrow ventilation is the major driver of archaeal community structure. By contrast, solid-phase reworking, which regulates the distribution of fresh, algal organic matter, is the main control of bacterial community structure. In nonbioturbated surface sediments and in subsurface sediments, bacterial and archaeal communities are more divergent between locations and appear mainly driven by sitespecific differences in organic carbon sources.

Janus kinase (JAK) inhibitors, including tofacitinib, baricitinib, upadacitinib and filgotinib, are increasingly used in the treatment of rheumatoid arthritis (RA). There has been debate about their safety, particularly following the issuance of guidance by regulatory agencies advising caution in their use in certain patients. The registrational clinical trials and registry data of JAK inhibitors did not identify a difference in the risk of major adverse cardiovascular events (MACEs), venous thromboembolism, malignancies or infections (other than herpes zoster) with a JAK inhibitor versus a biologic DMARD. In the ORAL Surveillance trial, which enrolled patients >50 years of age with ≥1 cardiovascular risk factor, tofacitinib was statistically not non-inferior to TNF inhibitors for the occurrence of MACEs and malignancy. Further post hoc analysis of the data revealed that an age of ≥65 years, a high baseline cardiovascular risk, a history of smoking, sustained inflammation, disease activity and suboptimal treatment of cardiovascular comorbidities all increase the risk of these outcomes. The guidance issued by regulatory agencies should be carefully considered to ensure appropriate and safe treatment of patients with RA without undertreatment of patients who might benefit from JAK inhibitor, as well as biologic, treatment. As always, the risks associated with the use of these agents, treatment goals, costs and patient preferences should be discussed with the patient.Concerns have been raised about the safety of Janus kinase (JAK) inhibitors. This Review summarizes the evidence regarding the risks and benefits of JAK inhibitors to clarify which patients are most at risk of adverse events and guide clinical decision-making.

Diet composition of leaf-eating mangrove crabs is a puzzle among mangrove ecologists. Nutrient-poor leaf litter can in most cases not support animal growth. Food partitioning (mangrove leaves, animal tissue, and microphytobenthos [MPB]) of sesarmid and ucidid mangrove crabs from eight locations in four countries was assessed using the concentration-dependent stable isotope mixing model, IsoConc. While stable C and N isotopes have the potential to track the origin and proportion of food sources for these crabs, only few values of trophic discrimination are available. This problem was addressed here for crabs foraging on leaf litter to identify discrimination values that provide a balanced diet with sufficient nutrients (i.e., N) when combined with other food sources. The data from all mangrove locations suggest that sesarmid and ucidid crabs ingest and assimilate mixtures of available food items. Leaf litter in the form of brown leaves was always the most important C source, while animal tissue in the form live and dead “prey” or MPB in the form of diatoms at the sediment surface were the dominant N sources. Model scenarios were generated to obtain the upper thresholds of trophic 13C discrimination between the examined crab species and leaf litter, while complying with the molar C/N < 20 requirement for sustainable invertebrate nutrition. The model predicts litter 13C discrimination thresholds of +1.5‰ to +6.0‰ for sesarmid crabs and -0.3‰ to +0.6‰ for ucidid crabs. The difference is probably caused by metabolic disparities between these two crab families. Deviations in 15N discrimination have in most cases only minor influence on the model-based 13C discrimination thresholds. The present findings lead us to suggest a modified Optimal Foraging Theory for leaf-eating mangrove crabs.

The influence of mangrove saplings (Avicennia marina) and fiddler crabs (Uca vocans) on carbon, iron, and sulfur biogeochemistry in mangrove sediment was studied using outdoor mesocosms with and without plants ($21 m^{-2}$) and crabs ($68 m^{-2}$). Saplings grew more leaves and pneumatophores in the presence of crabs. Dense microalgal mats lead to two to six times higher benthic production and about two times higher benthic respiration in the absence of crabs. Particle mixing by crabs increased the reactive oxidized iron (Fe(III)) in the upper 2 cm of the sediment, whereas oxygen leaching by roots maintained the deeper rhizosphere oxidized and enriched in Fe(III). The highest microbial activity, measured as carbon dioxide production and iron reduction, occurred within the upper 2 cm of ungrazed sediment and was fueled by the large near-surface biomass of microalgae. Leaching of dissolved organic carbon (DOC) from roots stimulated bulk sulfate reduction and caused an upward cascading reduction of the sediment as indicated by low Fe(III) and high Fe(II) between 2-cm and 6-cm depth. The effect DOC was also evident as increased microbial abundance at all depths in the sediment. Fe(III) was the most important electron acceptor for microbial carbon oxidation in ungrazed sediment (63-70%), whereas sulfate reduction was more important in grazed sediment (36-44%), particularly in the presence of plants. Aerobic respiration always accounted for <20%. Fiddler crabs and roots of A. marina have complementary effects on the biogeochemistry of mangrove sediment. Their association seems to be mutually beneficial with respect to growth and food availability.

How will coastal soils in areas newly flooded with seawater function as habitat for benthic marine organisms? This research question is highly relevant as global sea level rise and coastal realignment will cause flooding of soils and form new marine habitats. In this study, we tested experimentally the capacity of common marine polychaetes, Marenzelleria viridis, Nereis (Hediste) diversicolor and Scoloplos armiger to colonize and modify the biogeochemistry of the newly established Gyldensteen Coastal Lagoon, Denmark. All tested polychaetes survived relatively well (28-89%) and stimulated carbon dioxide release (TCO2) by 97-105% when transferred to newly flooded soils, suggesting that soil characteristics are modified rapidly by colonizing fauna. A field survey showed that the pioneering benthic community inside the lagoon was structurally different from the marine area outside the lagoon, and M. viridis and S. armiger were not among the early colonizers. These were instead N. diversicolor and Polydora cornuta with an abundance of 1603 and 540 ind m-2, respectively. Considering the species-specific effects of N. diversicolor on TCO2 release and its average abundance in the lagoon, we estimate that organic carbon degradation was increased by 219% in the first year of flooding. We therefore conclude that early colonizing polychaetes modify the soils and may play an important role in the ecological and successional developments, e.g. C cycling and biodiversity, in newly flooded coastal ecosystems. Newly flooded soils have thus a strong potential to develop into well-functioning marine ecosystems.

The effects of organic enrichment on sediment biogeochemistry was studied in diffusion controlled sediment mesocosms, where labile organic matter (OM) (fish feed) pulses were added once a week to the sediment surface. Two types of sediments, differing mainly in content of reactive Fe, were used. The aim of this experiment was two-fold, (1) to evaluate the importance of Fe-driven sulfide buffering for sulfide accumulation in surface enriched sediments, and (2) to estimate the diagenetic capacity for degradation of labile OM near the sediment surface. The simulated OM loading rate of 375 mmol C m⁻² day⁻¹ led to a 5-6 times increase in CO₂-production and a 4-5 times increase in O₂-uptake. Sulfate reduction estimated by radiotracer experiments and CO₂-release was 105-131 mmol m⁻² day⁻¹, but accumulation of porewater sulfide was low in both sediment types. Instead 99% of sulfide was oxidized with O₂ at the sediment water interface in the low Fe treatment, whereas 46% of produced sulfide precipitated as Fe-S compound in the high Fe treatment resulting in significantly lower O₂-uptake. Furthermore, the accumulation of up to 30% of added OM by the end of the experiment indicated a saturation of the heterotrophic microbial communities in the upper enriched surface layer. These results suggest a maximum diagenetic capacity for OM degradation in the range of ~25 μmol C cm⁻³ day⁻¹ or 260 mmol m⁻² day⁻¹ for the present sediment types.

Marine invasive species may modify their host environment by altering ecosystem biogeochemistry. We hypothesized that the invasive polychaete Marenzelleria viridis in Baltic Sea areas increases sulfate reduction (SR) in sediment micro-zones surrounding its burrow. Consequently, higher free porewater sulfide (H2S) is expected in sediments dominated by M. viridis than in corresponding sediments inhabited by the native polychaete Hediste diversicolor. In a thin-aquaria experiment, we found high SR rates (220 to 539 nmol cm−3 d−1) around the burrow walls of M. viridis as well as in surface and subsurface sediments with overall rates 2-fold higher than in defaunated control sediment. Similarly, an in situ survey revealed subsurface porewater H2S peaks moving upward towards the sediment surface in M. viridis inhabited areas. Accordingly, 50–85% higher porewater H2S was found almost year-round in these areas compared with H. diversicolor inhabited areas, suggesting that the invasion of M. viridis probably led to a substantial change in sediment biogeochemistry. In conclusion, M. viridis stimulates SR in sediment micro-zones and increases H2S in coastal sediments. Such change to more reducing conditions after the invasion may have critical environmental implications on, e.g., the distribution of H2S intolerant flora and fauna species.

Introduction Synovitis and enthesitis are key manifestations in psoriatic arthritis (PsA). This descriptive analysis investigated the association between improvement in synovitis and enthesitis, individually and combined, and improvement in patient-reported outcomes (PROs) including health-related quality of life (HRQoL) for patients with PsA from the SPIRIT-P1, SPIRIT-P2, and SPIRIT-H2H trials who presented with synovitis and enthesitis at baseline and received ixekizumab (IXE) treatment. Methods In this post hoc analysis, data are presented from patients with PsA treated with IXE every 4 weeks from two phase III studies (SPIRIT-P1 and SPIRIT-P2) and one phase IIIb/IV study (SPIRIT-H2H) who had both synovitis and enthesitis at baseline. Associations between improvements in synovitis and improvements in enthesitis were explored using Pearson analyses through week 52. Associations between improvements in both, either, and neither condition with improvements in PROs (36-item Short Form Health Survey Physical Component Score [SF-36 PCS], the European Quality-of-Life 5 Dimensions 5 Levels [EQ-5D-5L] including the EQ-5D Visual Analogue Score [VAS] and the EQ-health index, Patient’s Global Assessment [PtGA], and pain VAS) were assessed descriptively through week 52. Results Results demonstrated the synergistic improvements in synovitis and enthesitis, individually or combined, and improvements in PROs including HRQoL, for patients treated with IXE through week 52. An association between improvements in synovitis and enthesitis symptoms was observed through week 52. Patients who achieved resolution of both synovitis and enthesitis reported highest improvements in SF-36 PCS, EQ-5D-5L, pain VAS, and PtGA. Conclusion Synergistic improvements in two key PsA domains, namely synovitis and enthesitis, and improvements in PROs including HRQoL, were observed for patients with PsA treated with IXE through week 52. These findings support PsA treatment goal aiming to achieve the lowest possible level of disease activity in all disease domains. Trial registration numbers SPIRIT-P1 (NCT01695239), SPIRIT-P2 (NCT02349295), and SPIRIT-H2H (NCT03151551).

Background Based on clinical and genetic associations, axial spondyloarthritis (axSpA) and inflammatory bowel disease (IBD) are suspected to have a linked pathogenesis. Gut dysbiosis, intrinsic to IBD, has also been observed in axSpA. It is, however, not established to what degree gut dysbiosis is associated with axSpA disease severity. The objective of this study was to compare gut dysbiosis frequency between controls, non-radiographic axial spondyloarthritis (nr-axSpA), and ankylosing spondylitis (AS) patients and investigate whether gut dysbiosis is cross-sectionally associated with axSpA disease activity, physical function, mobility, or pain. Methods Gut dysbiosis was assessed by 16SrRNA analysis of feces from 44/88 nr-axSpA/AS patients (ASAS/mNY criteria) without inflammatory bowel disease (IBD) and 46 controls without IBD or rheumatic disease. The GA-map™ Dysbiosis Test was used, grading gut microbiota aberrations on a 1-5 scale, where ≥3 denotes dysbiosis. Proportions with dysbiosis were compared between the groups. Furthermore, standard axSpA measures of disease activity, function, mobility, and pain were compared between patients (nr-axSpA and AS combined) with and without dysbiosis, univariately, and adjusted for relevant confounders (ANCOVA). Results Gut dysbiosis was more frequent in AS than controls (36% versus 17%, p =0.023), while nr-axSpA (25% dysbiosis) did not differ significantly from either AS or controls. Univariately, most axSpA measures were significantly worse in patients with dysbiosis versus those without: ASDAS-CRP between-group difference 0.6 (95% CI 0.2–0.9); BASDAI 1.6 (0.8–2.4); evaluator’s global disease activity assessment (Likert scale 0–4) 0.3 (0.1–0.5), BASFI 1.5 (0.6–2.4), and VAS pain (cm) 1.3 (0.4–2.2). Differences remained significant after adjustment for demographics, lifestyle factors, treatments, gut inflammation (fecal calprotectin ≥50 mg/kg), and gut symptoms, except for VAS pain. BASMI and CRP were not associated with dysbiosis. Conclusion Gut dysbiosis, more frequent in AS patients than controls, is associated with worse axSpA disease activity and physical function, seemingly irrespective of both gut inflammation and treatments. This provides further evidence for an important link between disturbances in gastrointestinal homeostasis and axSpA.

Background Psoriatic Arthritis (PsA) is an immune-mediated disease with heterogenous symptoms indicating differences in the underlying immunopathogenesis. The primary objective of the study explored the dynamic mechanisms and interplay between immune cell subtypes constituting the immune response driving PsA to evaluate possible differences in immune cellular phenotypes, and secondary examined associations between emerging immune cellular phenotypes and disease outcomes. Methods Peripheral blood was collected from 70 PsA patients. Frequencies of nine immune cell subtypes were determined by multicolor flow cytometry. The interplay between immune cells were examined with principal component analysis (PCA) to establish immune cellular phenotypes. Disease characteristics, Disease Activity in Psoriatic Arthritis (DAPSA) and Psoriasis Area Severity Index (PASI) were retrieved to examine associations to individual cellular phenotypes. Results Four components were identified using PCA resembling four immune cellular phenotypes. Component 1, explaining 25.6% of the variance with contribution from T-helper 17 cells (Th17), memory T regulatory cells (mTregs), dendritic cells and monocytes, was associated with longer disease duration and higher DAPSA. Component 2, driven by Th1, naïve Tregs and mTregs, was associated with shorter disease duration. Component 3 was driven by both Th1, Th17 and CD8+ T cells, while component 4 was characterized by a reverse correlation between CD8+ T cells and natural killer cells. Conclusion Four immune cellular phenotypes of PsA were suggested at baseline demonstrating complex immune cellular mechanisms in PsA implying the possibility of improving PsA patient stratification based on both clinical and immune cellular phenotypes.