What benefit-risk trade-offs are acceptable to rheumatoid arthritis patients during treatment selection? Evidence from a multicountry choice experiment.

OBJECTIVE: Understanding preferences of patients with rheumatoid arthritis (RA) can facilitate tailored patient-centric care. This study elicited trade-offs that patients with RA were willing to make during treatment selection. METHODS: Patients with RA completed an online discrete choice experiment, consisting of a series of choices between hypothetical treatments. Treatment attributes were selected based on literature review and qualitative patient interviews. Eligible patients were ≥18 years old, diagnosed with RA, receiving systemic disease-modifying antirheumatic drug therapy, and residents of Europe or USA. Male patients were oversampled for subgroup analyses. Data were analysed using a correlated mixed logit model. RESULTS: Of 2090 participants, 42% were female; mean age was 45.2 years (range 18-83). Estimated effects were significant for all attributes (p<0.001) but varied between patients. Average relative attribute importance scores revealed different priorities (p<0.001) between males and females. While reducing pain and negative effect on semen parameters was most important to males, females were most concerned by risk of blood clots and serious infections. No single attribute explained treatment preferences by more than 30%. Preferences were also affected by patients' age: patients aged 18-44 years placed less importance on frequency and mode of treatment administration (p<0.05) than older age groups. Patients were willing to accept higher risk of serious infections and blood clots in exchange for improvements in pain, daily activities or administration convenience. However, acceptable trade-offs varied between patients (p<0.05). CONCLUSION: Treatment preferences of patients with RA were individual-specific, but driven by benefits and risks, with no single attribute dominating the decision-making.

Longevity of the humoral and cellular responses after SARS-CoV-2 booster vaccinations in immunocompromised patients.

We assessed the humoral and cellular immune responses after two booster mRNA vaccine administrations [BNT162b2 (Pfizer-BioNTech vaccine)] in cohorts of immunocompromised patients (n = 199) and healthy controls (HC) (n = 54). All patients living with HIV (PLWH) and chronic kidney disease (CKD) patients and almost all (98.2%) of the primary immunodeficiency (PID) patients had measurable antibodies 3 and 6 months after administration of the third and fourth vaccine dose, comparable to the HCs. In contrast, only 53.3% and 83.3% of the multiple sclerosis (MS) and rheumatologic patients, respectively, developed a humoral immune response. Cellular immune response was observed in all PLWH after administration of four vaccine doses. In addition, cellular immune response was positive in 89.6%, 97.8%, 73.3% and 96.9% of the PID, MS, rheumatologic and CKD patients, respectively. Unlike the other groups, only the MS patients had a significantly higher cellular immune response compared to the HC group. Administration of additional vaccine doses results in retained or increased humoral and cellular immune response in patients with acquired or inherited immune disorders.

Transport by circulating myeloid cells drives liposomal accumulation in inflamed synovium.

The therapeutic potential of liposomes to deliver drugs into inflamed tissue is well documented. Liposomes are believed to largely transport drugs into inflamed joints by selective extravasation through endothelial gaps at the inflammatory sites, known as the enhanced permeation and retention effect. However, the potential of blood-circulating myeloid cells for the uptake and delivery of liposomes has been largely overlooked. Here we show that myeloid cells can transport liposomes to inflammatory sites in a collagen-induced arthritis model. It is shown that the selective depletion of the circulating myeloid cells reduces the accumulation of liposomes up to 50-60%, suggesting that myeloid-cell-mediated transport accounts for more than half of liposomal accumulation in inflamed regions. Although it is widely believed that PEGylation inhibits premature liposome clearance by the mononuclear phagocytic system, our data show that the long blood circulation times of PEGylated liposomes rather favours uptake by myeloid cells. This challenges the prevailing theory that synovial liposomal accumulation is primarily due to the enhanced permeation and retention effect and highlights the potential for other pathways of delivery in inflammatory diseases.

Fade In, Fade Out: Do Shifts in Visual Perspective Predict the Consistency of Real-World Memories?

Memories of our personal past are not exact accounts of what occurred. Instead, memory reconstructs the past in adaptive-though not always faithful-ways. Using a naturalistic design, we asked how the visual perspective adopted in the mind's eye when recalling the past-namely, an "own eyes" versus "observer" perspective-relates to the stability of autobiographical memories. We hypothesized that changes in visual perspective over time would predict poorer consistency of memories. Young adults (N = 178) rated the phenomenology of and freely recalled self-selected memories of everyday events at two time points (10 weeks apart). Multilevel linear modeling revealed, as expected, that greater shifts in visual perspective over time predicted lower memory consistency, particularly for emotional details. Our results offer insight into the factors that predict the fidelity of memories for everyday events. Moreover, our results may elucidate new metrics that are useful in interpreting eyewitness testimony or experiences relayed in clinical contexts.

Distinct immune modulatory roles of regulatory T cells in gut versus joint inflammation in TNF-driven spondyloarthritis.

OBJECTIVES: Gut and joint inflammation commonly co-occur in spondyloarthritis (SpA) which strongly restricts therapeutic modalities. The immunobiology underlying differences between gut and joint immune regulation, however, is poorly understood. We therefore assessed the immunoregulatory role of CD4+FOXP3+ regulatory T (Treg) cells in a model of Crohn's-like ileitis and concomitant arthritis. METHODS: RNA-sequencing and flow cytometry was performed on inflamed gut and joint samples and tissue-derived Tregs from tumour necrosis factor (TNF)∆ARE mice. In situ hybridisation of TNF and its receptors (TNFR) was applied to human SpA gut biopsies. Soluble TNFR (sTNFR) levels were measured in serum of mice and patients with SpA and controls. Treg function was explored by in vitro cocultures and in vivo by conditional Treg depletion. RESULTS: Chronic TNF exposure induced several TNF superfamily (TNFSF) members (4-1BBL, TWEAK and TRAIL) in synovium and ileum in a site-specific manner. Elevated TNFR2 messenger RNA levels were noted in TNF∆ARE/+ mice leading to increased sTNFR2 release. Likewise, sTNFR2 levels were higher in patients with SpA with gut inflammation and distinct from inflammatory and healthy controls. Tregs accumulated at both gut and joints of TNF∆ARE mice, yet their TNFR2 expression and suppressive function was significantly lower in synovium versus ileum. In line herewith, synovial and intestinal Tregs displayed a distinct transcriptional profile with tissue-restricted TNFSF receptor and p38MAPK gene expression. CONCLUSIONS: These data point to profound differences in immune-regulation between Crohn's ileitis and peripheral arthritis. Whereas Tregs control ileitis they fail to dampen joint inflammation. Synovial resident Tregs are particularly maladapted to chronic TNF exposure.

Common and distinct correlates of construction and elaboration of episodic-autobiographical memory: An ALE meta-analysis.

The recollection of episodic-autobiographical memories (EAMs) entails a complex temporal dynamic, from initial "construction" to subsequent "elaboration" of memories. While there is consensus that EAM retrieval involves a distributed network of brain regions, it is still largely debated which regions specifically contribute to EAM construction and/or elaboration. To clarify this issue, we conducted an Activation Likelihood Estimation (ALE) meta-analysis based on the Preferred Reporting Items for Systematic-Reviews and Meta-Analyses (PRISMA) method. We found common recruitment of the left hippocampus and posterior cingulate cortex (PCC) during both phases. Additionally, EAM construction led to activations in the ventromedial prefrontal cortex, left angular gyrus (AG), right hippocampus, and precuneus, while the right inferior frontal gyrus was activated by EAM elaboration. Although most of these regions are distributed over the default mode network, the current findings highlight a differential contribution according to early (midline regions, left/right hippocampus, and left AG) versus later (left hippocampus, and PCC) recollection. Overall, these findings contribute to clarify the neural correlates that support the temporal dynamics of EAM recollection.

How shifting visual perspective during autobiographical memory retrieval influences emotion: A change in retrieval orientation.

Visual perspective during autobiographical memory (AM) retrieval influences how people remember the emotional aspects of memories. Prior research in emotion regulation has also shown that shifting from an own eyes to an observer-like perspective is an efficient way of regulating the affect elicited by emotional AMs. However, the impact of shifting visual perspective is also dependent on the nature of the emotion associated with the event. The current review synthesizes behavioral and functional neuroimaging findings from the event memory and emotion regulation literature that examine how adopting particular visual perspectives and actively shifting across them during retrieval alters emotional experience, by primarily focusing on emotional intensity. We review current theories explaining why shifts in perspectives may or may not change the emotional characteristics of memories, then propose a new theory, suggesting that the own eyes and observer-like perspectives are two different retrieval orientations supported by differential neural activations that lead episodic details to be reconstructed in specific ways.

IgA rheumatoid factor in rheumatoid arthritis.

OBJECTIVES: Rheumatoid factor (RF) is a well-established marker for the diagnosis and classification of rheumatoid arthritis (RA). Most studies evaluated IgM RF or isotype-nonspecific total RF assays. We evaluated the added value of IgA RF in this context. METHODS: An international sample cohort consisting of samples from 398 RA patients and 1073 controls was tested for IgA RF with 3 commercial assays. For all RA patients and 100 controls essential clinical and serological data for ACR/EULAR classification were available. RESULTS: The sensitivity of IgA RF for diagnosing RA was lower than the sensitivity of IgM RF. Differences in numerical values between IgA RF assays were observed. With all assays, the highest IgA RF values were found in patients with primary Sjögren's syndrome. Double positivity for IgM RF and IgA RF had a higher specificity for RA than either IgM RF or IgA RF. The sensitivity of double positivity was lower than the sensitivity of either IgA RF or IgM RF. Single positivity for IgA RF was at least as prevalent in controls than in RA patients. Adding IgA RF to IgM RF and anti-citrullinated protein antibodies (ACPA) did not affect RA classification. However, combined positivity for IgA RF, IgM RF and IgG ACPA had a higher specificity and lower sensitivity for RA classification than positivity for either of the antibodies. CONCLUSIONS: IgA RF showed a lower sensitivity than IgM RF. Combining IgA RF with IgM RF and ACPA did not improve sensitivity of RA classification. Combined positivity (IgA-RF/IgM-RF/ACPA) increased specificity.

Standardisation of ACPA tests: evaluation of a new candidate reference preparation.

INTRODUCTION: Commercial assays measuring antibodies to citrullinated protein/peptide (ACPA) show poor quantitative agreement. The diagnostic industry has never adopted the International Union of Immunological Societies-Centers for Disease Control and Prevention (IUIS-CDC) ACPA reference standard. Recently, the National Institute for Biological Standards and Control (NIBSC) prepared a new candidate ACPA standard (18/204). We evaluated both reference materials using different commercially available ACPA assays. MATERIALS AND METHODS: This is an international study in which the NIBSC candidate ACPA standard and the IUIS-CDC ACPA reference material were analysed together with 398 diagnostic samples from individuals with rheumatoid arthritis (RA) and in 1073 individuals who did not have RA using nine commercial ACPA assays. RESULTS: For both reference materials and samples from individuals with RA and individuals who did not have RA, there were large differences in quantitative ACPA results between assays. For most assays, values for the IUIS-CDC standard were lower than values for NIBSC 18/204 and the IUIS-CDC/NIBSC ratio was comparable for several, but not all assays. When NIBSC 18/204 was used as a calibrator, an improvement in alignment of ACPA results across several of the evaluated assays was obtained. Moreover, NIBSC 18/204 could align clinical interpretation for some but not all assays. CONCLUSION: Adoption of an international standard for ACPA determination is highly desirable. The candidate NIBSC 18/204 standard improved the standardisation and alignment of most ACPA assays and might therefore be recommended to be used as reference in commercial assays.

Remembering a Virtual Museum Tour: Viewing Time, Memory Reactivation, and Memory Distortion.

A variety of evidence demonstrates that memory is a reconstructive process prone to errors and distortions. However, the complex relationship between memory encoding, strength of memory reactivation, and the likelihood of reporting true or false memories has yet to be ascertained. We address this issue in a setting that mimics a real-life experience: We asked participants to take a virtual museum tour in which they freely explored artworks included in the exhibit, while we measured the participants' spontaneous viewing time of each explored artwork. In a following memory reactivation phase, participants were presented again with explored artworks (reactivated targets), followed by novel artworks not belonging to the same exhibit (activated lures). For each of these objects, participants provided a reliving rating that indexed the strength of memory reactivation. In the final memory recognition phase, participants underwent an old/new memory task, involving reactivated vs. baseline (i.e., non-reactivated) targets, and activated and baseline lures. The results showed that those targets that were spontaneously viewed for a longer amount of time were more frequently correctly recognized. This pattern was particularly true for reactivated targets associated with greater memory strength (a higher reliving rating). Paradoxically, however, lures that were presented after targets associated with higher reliving ratings in the reactivation phase were more often erroneously recognized as artworks encountered during the tour. This latter finding indicates that memory intrusions, irrespective of the viewing time, are more likely to take place and be incorporated into true memories when the strength of target memory is higher.

The influence of shifting perspective on episodic and semantic details during autobiographical memory recall.

Shifting to a novel visual perspective during retrieval influences autobiographical memories (AM) and can lead to persistent changes in memories. Adopting an observer-like compared to an own eyes perspective reduces episodic information during AM recall, but less is known regarding how viewpoint influences semantic information. In the current study, we investigated how shifting from an own eyes to an observer-like perspective during narrative recall of AMs influences episodic and semantic information. Shifting perspective reduced the number of episodic details associated with emotions and thoughts, and also led to similar reductions in personal semantics. We replicated prior research showing that shifting perspective reduces emotional intensity in subsequent memories, but these subjective changes were not coupled with objective changes in a narrative recall. Our findings suggest that shifting perspective influences the interplay between episodic and semantic information during proximate recall and subjective changes when memories are later recalled.

Evaluation of Humoral and Cellular Responses in SARS-CoV-2 mRNA Vaccinated Immunocompromised Patients.

Background: Immunocompromised patients are at increased risk of severe COVID-19 and impaired vaccine response. In this observational prospective study, we evaluated immunogenicity of the BNT162b2 mRNA vaccine in cohorts of primary or secondary immunocompromised patients. Methods: Five clinical groups of immunocompromised patients [primary immunodeficiency (PID) (n=57), people living with HIV (PLWH) (n=27), secondary immunocompromised patients with a broad variety of underlying rheumatologic (n=23) and homogeneous (multiple sclerosis) neurologic (n=53) conditions and chronic kidney disease (CKD) (n=39)] as well as a healthy control group (n=54) were included. Systemic humoral and cellular immune responses were evaluated by determination of anti-SARS-CoV-2 Spike antibodies using a TrimericS IgG assay (Diasorin) and through quantification of interferon gamma release in response to SARS-CoV-2 antigen with QuantiFERON SARS-CoV-2 assay (Qiagen), respectively. Responses were measured at pre-defined time-points after complete vaccination. Results: All healthy controls, PLWH and CKD-patients had detectable antibodies 10 to 14 days (T2) and 3 months (T3) after administration of the second vaccination. In contrast, only 94.5% of the PID, 50.0% of the rheumatologic and 48.0% of neurologic patients developed antibodies at T2 and only 89.1% of the PID, 52.4% of the rheumatologic and 50.0% of neurologic patients developed antibodies at T3. At T3 no significant differences in cellular response between the healthy control group and the PLWH and CKD groups were found, while proportions of reactive subjects were lower in PID and rheumatologic patients and higher in neurologic patients. Humoral and cellular immune responses significantly correlated in the healthy control, PID, PLWH groups for all 3 antigens. Conclusion: Patients with acquired or inherited immune disorders may show variable immune responses to vaccination with the BNT162b2 mRNA vaccine against SARS-CoV-2. Whether humoral, cellular or both immune responses are delayed depends on the patient group, therapy and individual risk factors. These data may guide the counselling of patients with immune disorders regarding vaccination of SARS-CoV-2.

Multicentre study to improve clinical interpretation of rheumatoid factor and anti-citrullinated protein/peptide antibodies test results.

BACKGROUND: Rheumatoid factor (RF) and anti-citrullinated protein/peptide antibodies (ACPA) are important biomarkers for diagnosis of rheumatoid arthritis (RA). However, there is poor harmonisation of RF and ACPA assays. The aim of this study was to refine RF and ACPA interpretation across commercial assays. MATERIALS AND METHODS: Six total RF isotype-non-specific assays, 3 RF IgM isotype-specific assays and 9 ACPA immunoglobulin G assays of 13 different companies were evaluated using 398 diagnostic samples from patients with RA and 1073 disease controls. RESULTS: Using cut-offs proposed by the manufacturer, there was a large variability in diagnostic sensitivity and specificity between assays. Thresholds of antibody levels were determined based on predefined specificities and used to define test result intervals. Test result interval-specific likelihood ratios (LRs) were concordant across the different RF and ACPA assays. For all assays, the LR for RA increased with increasing antibody level. Higher LRs were found for ACPA than for RF. ACPA levels associated with LRs >80 were found in a substantial fraction (>22%) of patients with RA. CONCLUSION: Defining thresholds for antibody levels and assigning test result interval-specific LRs allows alignment of clinical interpretation for all RF and ACPA assays.

Episodic-semantic interactions in spontaneous thought.

The distinction between a semantic memory system, encompassing conceptual knowledge, and an episodic memory system, characterized by specific episodes, is one of the most important theoretical proposals in cognitive science. However, the distinction between systems has rarely been discussed in relation to spontaneous thought that comes to mind with reduced cognitive effort and intentionality. In this review, we propose that the growing research on spontaneous thought can contribute to current discussions on the interaction between the episodic and semantic systems. Firstly, we review research that shows that, as in deliberate retrieval, spontaneous thoughts are influenced by both episodic and semantic memory, as reflected by the mix of semantic and episodic elements in descriptions of spontaneous thoughts, as well as semantic priming effects in spontaneous thoughts. We integrate the current evidence based on the interplay between cues and semantic activation. Namely, we suggest that cues are key to access episodic memory and modulate the frequency of spontaneous thought, while semantic activation modulates the content of spontaneous thought. Secondly, we propose that spontaneous retrieval is a privileged area to explore the question of functional independence between systems, because it provides direct access to the episodic system. We review the evidence for spontaneous thought in semantic dementia, which suggests that episodic and semantic systems are functionally independent. We acknowledge the scarcity of evidence and suggest that future studies examine the contents of spontaneous thought descriptions and their neural correlates to test the functional relationship and inform the interaction between episodic and semantic systems.

Laser speckle contrast analysis in rheumatoid arthritis: a pilot study.

OBJECTIVES: Early diagnosis and treatment is paramount in rheumatoid arthritis (RA). Nowadays, there is a need for quick and non-invasive imaging modalities, for which laser speckle contrast analysis (LASCA), a technique that assesses the peripheral blood perfusion (PBP) on a microvascular level, seems to be a promising candidate. The goal of this pilot study was to examine whether the expected increased PBP in active synovitis in RA patients can be detected by LASCA. METHODS: Thirty RA patients with active synovitis in a finger joint and 44 healthy controls (HC) underwent LASCA examination. The PBP measured over the finger joints was expressed in perfusion units (PU). For the final analysis, all 30 RA patients were matched by age and gender to 30 HC. For the primary analysis the mean difference in PU between joints with active synovitis compared to matched HC, adjusted for type of joint (MCP/PIP), finger, surface and side of hand and for the matching variables (age and gender), was calculated using a multilevel linear model. For the secondary analysis this mean difference in PU was calculated on a monoarticular level. RESULTS: The primary analysis showed an estimated mean difference of 8.79 PU (95%CI -7.79-25.37 PU; p=0.299). For the secondary analysis on a monoarticular level, none of the estimated mean differences differed significantly. CONCLUSIONS: In this pilot study examining the use of LASCA in RA, no significant difference in estimated mean PBP between joints with active synovitis in RA and joints without active synovitis in HC could be detected.

Efficacy of a tight-control and treat-to-target strategy in axial spondyloarthritis: results of the open-label, pragmatic, cluster-randomised TICOSPA trial.

OBJECTIVES: To compare the benefits of a tight-control/treat-to-target strategy (TC/T2T) in axial spondyloarthritis (axSpA) with those of usual care (UC). METHODS: Pragmatic, prospective, cluster-randomised, controlled, open, 1-year trial (NCT03043846). 18 centres were randomised (1:1). Patients met Axial Spondylo Arthritis International Society (ASAS) criteria for axSpA, had an Ankylosing Spondylitis Disease Activity Score (ASDAS) ≥2.1, received non-optimal treatment by non-steroidal anti-inflammatory drugs and were biologic-naive. INTERVENTIONS: (1) TC/T2T: visits every 4 weeks and prespecified strategy based on treatment intensification until achieving target (ie, ASDAS <2.1); (2) UC: visits every 12 weeks and treatment at the rheumatologist's discretion. MAIN OUTCOME: Percentage of patients with a ≥30% improvement on the ASAS-Health Index (ASAS-HI). Other efficacy outcomes and adverse events were recorded. A health economic evaluation was performed. STATISTICAL ANALYSIS: Two-level mixed models were used to estimate efficacy outcomes. Cost-effectiveness was assessed by the incremental cost per quality-adjusted life-year (QALY) gained for TC/T2T versus UC. RESULTS: 160 patients were included (80/group). Mean (SD) age was 37.9 (11.0) years and disease duration was 3.7 (6.2) years; 51.2% were men. ASDAS at inclusion was 3.0 (0.7), and ASAS-HI was 8.6 (3.7). ASAS-HI improved by ≥30% in 47.3% of the TC/T2T arm and in 36.1% of those receiving UC (non-significant). All secondary efficacy outcomes were more frequent in the TC/T2T arm, although not all statistically significant. Safety was similar in both arms. From a societal perspective, TC/T2T resulted in an additional 0.04 QALY, and saved €472 compared with UC. CONCLUSION: TC/T2T was not significantly superior to UC for the primary outcome, while many secondary efficacy outcomes favoured it, had a similar safety profile and was favourable from a societal health economic perspective. TRIAL REGISTRATION NUMBER: NCT03043846.

Memories for third-person experiences in immersive virtual reality.

We typically experience the world from a first-person perspective (1PP) but can sometimes experience events from a third-person perspective (3PP) much as an observer might see us. Little is known about how visual perspective influences the formation of memories for events. We developed an immersive virtual reality paradigm to examine how visual perspective during encoding influences memories. Across two studies, participants explored immersive virtual environments from first-person and third-person avatar perspectives while wearing an Oculus Rift headset. Memory was tested immediately (Study One and Study Two) and following a one-week delay (Study Two). We assessed the accuracy of visual memory using cued recall questions and spatial memory by asking participants to draw maps of the layout of each environment (Study One and Study Two). Additional phenomenological ratings were included to assess visual perspective during remembering (Study Two). There were no differences in the accuracy of visual information across the two studies, but 3PP experiences were found to increase spatial memory accuracy due to their wider camera field of view when compared to 1PP experiences. Our results also demonstrate that 3PP experiences create 3PP memories, as reflected by an increase in subjective ratings of observer-like perspectives during remembering. In sum, visual perspective during memory formation influences the accuracy of spatial but not visual information, and the vantage point of memories during remembering.

MRI-based Synthetic CT in the Detection of Structural Lesions in Patients with Suspected Sacroiliitis: Comparison with MRI.

Background Evaluation of structural lesions in the sacroiliac (SI) joints can improve the accuracy for diagnosis of spondyloarthritis. However, structural lesions, such as erosions, are difficult to assess on routine T1-weighted MRI scans. Purpose To determine the diagnostic performance of MRI-based synthetic CT (sCT) in the depiction of erosions, sclerosis, and ankylosis of the SI joints compared with T1-weighted MRI, with CT as the reference standard. Materials and Methods A prospective study (clinical trial registration no. B670201837885) was performed from February 2019 to November 2019. Adults were referred from a tertiary hospital rheumatology outpatient clinic with clinical suspicion of inflammatory sacroiliitis. MRI and CT of the SI joints were performed on the same day. SCT images were generated from MRI scans using a commercially available deep learning-based image synthesis method. Two readers independently recorded if structural lesions (erosions, sclerosis, and ankylosis) were present on T1-weighted MRI, sCT, and CT scans in different reading sessions, with readers blinded to clinical information and other images. Diagnostic performance of sCT and T1-weighted MRI scans were analyzed using generalized estimating equation models, with consensus results of CT as the reference standard. Results Thirty participants were included (16 men, 14 women; mean age, 40 years ± 10 [standard deviation]). Diagnostic accuracy of sCT was higher than that of T1-weighted MRI for erosion (94% vs 86%, P = .003), sclerosis (97% vs 81%, P < .001), and ankylosis (92% vs 84%, P = .04). With sCT, specificity for erosion detection (96% [95% CI: 90, 98] vs 89% [95% CI: 81, 94], P = .01] and sensitivity for detection of sclerosis [94% [95% CI: 87, 97] vs 20% [95% CI: 10, 35], P < .001] and ankylosis (93% [95% CI: 78, 98] vs 70% [95% CI: 47, 87], P = .001) were improved. Conclusion With CT as the reference standard, synthetic CT of the sacroiliac joints has better diagnostic performance in the detection of structural lesions in individuals suspected of having sacroiliitis compared with routine T1-weighted MRI. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Fritz in this issue.

Charting Extracellular Transcriptomes in The Human Biofluid RNA Atlas.

Extracellular RNAs present in biofluids have emerged as potential biomarkers for disease. Where most studies focus on blood-derived fluids, other biofluids may be more informative. We present an atlas of messenger, circular, and small RNA transcriptomes of a comprehensive collection of 20 human biofluids. By means of synthetic spike-in controls, we compare RNA content across biofluids, revealing a 10,000-fold difference in concentration. The circular RNA fraction is increased in most biofluids compared to tissues. Each biofluid transcriptome is enriched for RNA molecules derived from specific tissues and cell types. Our atlas enables an informed selection of the most relevant biofluid to monitor particular diseases. To verify the biomarker potential in these biofluids, four validation cohorts representing a broad spectrum of diseases were profiled, revealing numerous differential RNAs between case and control subjects. Spike-normalized data are publicly available in the R2 web portal for further exploration.

The effects of aging and an episodic specificity induction on spontaneous task-unrelated thought.

When voluntarily describing their past or future, older adults typically show a reduction in episodic specificity (e.g., including fewer details reflecting a specific event, time and/or place). However, aging has less impact on other types of tasks that place minimal demands on strategic retrieval such as spontaneous thoughts. In the current study, we investigated age-related differences in the episodic specificity of spontaneous thoughts using experimenter-based coding of thought descriptions. Additionally, we tested whether an episodic specificity induction, which increases episodic detail during deliberate retrieval of events in young and older adults, has the same effect under spontaneous retrieval. Twenty-four younger and 24 healthy older adults performed two counterbalanced sessions including a video, the episodic specificity or control induction, and a vigilance task. In the episodic specificity induction, participants recalled the details of the video while in the control they solved math exercises. The impact of this manipulation on the episodic specificity of spontaneous thoughts was assessed in the subsequent vigilance task, in which participants were randomly stopped to describe their thoughts and classify them as deliberate/spontaneous. We found no differences in episodic specificity between age groups in spontaneous thoughts, supporting the prediction that automatic retrieval attenuates the episodic specificity decrease in aging. The lack of age differences was present regardless of the induction, showing no interactions. For the induction, we also found no main effect, indicating that automatic retrieval bypasses event construction and accesses pre-stored events. Overall, our evidence suggests that spontaneous retrieval is a promising strategy to support episodic specificity in aging.