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OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disease resulting in debilitating clinical manifestations that vary in severity by race and ethnicity with a disproportionate burden in African American, Mestizo, and Asian populations compared with populations of European descent. Differences in global and local genetic ancestry may shed light on the underlying mechanisms contributing to these disparities, including increased prevalence of lupus nephritis, younger age of symptom onset, and presence of autoantibodies. METHODS: A total of 1,139 European, African American, and Mestizos patients with SLE were genotyped using the Affymetrix LAT1 World array. Global ancestry proportions were estimated using ADMIXTURE, and local ancestry was estimated using RFMIXv2.0. We investigated associations between lupus nephritis, age at onset, and autoantibody status with both global and local ancestry proportions within the Major Histocompatibility Complex region. RESULTS: Our results showed small effect sizes that did not meet the threshold for statistical significance for global or local ancestry proportions in either African American or Mestizo patients with SLE who presented with the clinical manifestations of interest compared with those who did not. CONCLUSION: These findings suggest that local genetic ancestry within the Major Histocompatibility Complex region is not a major contributor to these SLE manifestations among patients with SLE from admixed populations.

We report a case of persistent disseminated mpox evolving over >6 months in an HIV/hepatitis B virus co-infected patient in France who had By November 2023, the global mpox outbreak [...]

Background: Oncocytic thyroid carcinoma (OTC) was previously considered a variant of follicular thyroid carcinoma (FTC) but has recently been reclassified as a separate form of thyroid cancer. This study aimed to demonstrate that FTC and OTC are fundamentally distinct entities that can potentially be differentiated preoperatively through cytology and/or molecular testing. Methods: A retrospective chart review of patients diagnosed with FTC and OTC operated upon at two university health centers from January 2016 to September 2023 (n = 3219) was conducted. Molecular testing results were correlated with histopathologic diagnosis. Results: Fifty patients met the inclusion criteria. FTC was identified in 27 (54.0%) patients, and OTC in 23 (46.0%) patients. Patients with OTC were older (61.8 years) than FTC patients (51.2 years) (p = 0.013). Moreover, aggressive tumors were found in 39.1% (9/23) of OTCs compared to 11.1% (3/27) of FTCs (p = 0.021). Amongst Bethesda category III and IV nodules, 17 out of 20 (85.0%) OTC cytology reports demonstrated an oncocytic subtype compared to only 5 out of 24 FTC cytology reports (20.8%) (p = 0.002). On molecular testing, the EIF1AX alteration was exclusively present in OTCs while the PAX8/PPARy and PTEN alterations were exclusively found in FTCs. Copy number alterations (CNAs) were found to be more prevalent in OTC (66.7%) compared to FTC (33.3%), and they were not indicative of tumor aggressiveness. Within the OTC group, all three patients who had a TP53 alteration were diagnosed with aggressive cancer. Lastly, the OTCs exhibited a higher frequency of multiple alterations on molecular testing (66.7%) compared to FTCs (33.3%). Conclusion: To our knowledge, this is the largest study to date comparing the clinical application of abnormalities found on molecular testing for FTC and OTC. It further demonstrates the distinct clinicopathological and molecular characteristics of OTC.

Objective Disease activity both between and within patients with SLE is highly variable, yet factors driving this variability remain unclear. This study aimed to identify predictors of variability in SLE disease activity over time.Methods We analysed data from 2930 patients with SLE across 13 countries, collected over 38 754 clinic visits between 2013 and 2020. Clinic visit records were converted to panel data with 1-year intervals. The time-adjusted mean disease activity, termed AMS, was calculated. The yearly change in AMS, denoted as ΔAMSt, was regressed onto AMSt−1 and other potential predictors using random-effects models. Some variables were split into a person-mean component to assess between-patient differences and a demeaned component to assess within-patient variability.Results Overall, variability in SLE disease activity exhibited stabilisation over time. A significant inverse relationship emerged between a patient’s disease activity in a given year and variability in disease activity in the subsequent year: a 1-point increase in person-mean disease activity was associated with a 0.27-point decrease (95% CI −0.29 to –0.26, p

Objectives Systemic lupus erythematosus (SLE) is a disease with heterogeneous treatment patterns largely based on organ involvement and disease severity. The SLE Prospective Observational Cohort Study (SPOCS) collected data worldwide over 3 years from patients with moderate-to-severe SLE. We report real-world patterns of medication use in patients enrolled in SPOCS.Methods Data were collected at study entry; patients were followed twice annually according to local practice. Disease activity (SLE Disease Activity Index 2000 (SLEDAI-2K)), average oral glucocorticoid dose and use of other treatments—specifically antimalarials, biologics and immunosuppressants—were measured over time. Subgroup analyses were stratified by baseline interferon gene signature (IFNGS) status and disease activity (SLEDAI-2K) status.Results Patient demographics and baseline characteristics were similar among subgroups; the majority of patients were on antimalarials (n=670; 81.1%), followed by glucocorticoids (n=537; 65.0%), immunosuppressants (n=453; 54.8%) and biologics (n=175; 21.2%). In the overall population, median (IQR) SLEDAI-2K scores decreased within 12 months (baseline: 8.0 (6.0–12.0); 12 months: 4.0 (2.0–8.0)) and remained stable thereafter. The mean (SD) daily oral glucocorticoid dose increased by 6 months (baseline: 6.0 (7.09); 6 months: 9.8 (8.67)) and remained stable thereafter. The proportion of patients who were on glucocorticoid doses >5 mg/day ranged from ~20% to 33% throughout the study. In subgroup analyses, patients with high IFNGS and high disease activity state (HDAS) at baseline used more immunosuppressants and glucocorticoids compared with those with low IFNGS and non-HDAS at baseline.Conclusions These findings underscore that SLE therapy is still often unable to reach goals as recommended by the European Alliance of Associations for Rheumatology, both with regard to glucocorticoid use and disease activity, suggesting that there is an unmet need for new treatment options for patients with SLE.Trial registration number NCT03189875; 16 June 2017.

Forest cover has undergone significant changes accelerating over recent decades. Acari vectors such as ticks and chigger mites are intricately linked to forest ecosystems because of the suitable hosts and microclimates provided. However, the implications of forest cover change on Acari vectors and their pathogens remain poorly understood. This study investigates the impacts of forest cover dynamics on Acari-borne diseases risk worldwide through a comprehensive review of the literature.We conducted a scoping review following the PRISMA Method to retrieve citations related to forest cover dynamics and Acari-borne diseases. Eligibility criteria were predefined and relevant data were extracted from selected articles. The analysis employed a descriptive approach and thematic narrative synthesis.Our review revealed that the influence of forest cover dynamics on Acari-borne diseases and vectors was predominantly discussed within a Western context, especially regarding Ixodes ticks and Lyme disease. Four types of forest cover dynamics have been identified in the literature: deforestation, fragmentation, conversion and reforestation. However, there was no consensus on their impacts on vectors and pathogens. Studies reported conflicting findings including: protective or risk effects, nonlinear relationships, dependent effects influenced by additional factors altering relationships or no significant effects. Although, there is limited empirical evidence on tropical contexts as well as for reforestation and conversion dynamics. Differences in results trends emerge according to the article type, with literature reviews often overestimating the dilution effect, which assumes that species diversity reduces disease risk, observed in empirical research. Finally, our review identifies a notable absence of studies on scrub typhus.This scoping review provides a novel and comprehensive overview of global literature on the impacts of forest cover dynamics on Acari vectors and the infectious agents they transmit. It highlights the need for future research targeting specific forest cover dynamics on chigger mite vectors in a tropical context.

Objective To estimate the prevalence of organ damage (damage) and flare and to examine longitudinal associations between flares and subsequent damage accrual, in patients with systemic lupus erythematosus (SLE).Methods Patients enrolled in the Asia Pacific Lupus Collaboration cohort with ≥3 years of prospectively captured data were studied. Flares were assessed at routine visits, while damage ((Systemic Lupus International Collaborating Clinics/American College of Rheumatology) Damage Index) was assessed annually. Multivariable, multifailure survival analyses were carried out to quantify the association between flares and damage accrual.Results 1556 patients with SLE with a median (IQR) of 5.7 (3.9, 7.0) years of follow-up were studied. 39.5% (n=614) of patients had damage at enrolment, and 31.9% (n=496) accrued damage during the study observation period. The incidence of damage accrual during observation was ~58/1000 person-years. Overall, 74.1% (n=1153) of patients experienced a flare of any severity (mild/moderate or severe) at least once; 56.9% (n=885) experienced recurrent (≥2) flares. The risk of subsequent damage accrual in patients who experienced mild-to-moderate flare, after controlling for confounders, was 32% greater than in patients without flares (adjusted HR) (95% CI 1.32 (1.17 to 1.72)). The risk of damage accrual was greater if patients had severe flares (HR (95% CI) 1.58 (1.18 to 2.11)). For each additional flare, the risk of damage accrual increased by 7% (HR (95% CI) 1.07 (1.02 to 1.13)).Conclusions Flares independently increased the risk of damage accrual. Prevention of flares should be considered a necessary goal of SLE disease management to minimise permanent damage.

ABSTRACT Neutralizing antibody titers and binding antibody levels are considered correlates of protection against severe SARS-CoV-2 infection. The clinical utility of serology should be reevaluated in light of the emergence of escape variants, as commercial antibody-binding assays have not been adapted to the virus’ antigenic evolution. We compared anti-SARS-CoV-2 antibody titers in four quantitative serological tests based on variable ancestral spike antigens (three in-house ELISAs and the prototype VIDAS SARS-CoV-2 IgG QUANT assay) and neutralization assays against the pseudotyped Wuhan, BA.2, BA.4/5, BQ.1.1, and XBB.1.1 viruses in a cohort of 100 patients infected in 2020 or during the Omicron waves. Binding antibody levels correlated well with neutralizing antibody titers for Wuhan, BA.2, and BA.4/5, but the association decreased for BQ.1.1 and XBB.1 (for the VIDAS assay, Spearman’s correlation was 0.82 [95% CI 0.74–0.88] and 0.61 [0.46–0.72] for BA.2 and XBB.1, respectively). In 15% of patients with no neutralizing antibodies against XBB.1, the VIDAS assay still yielded binding antibody levels ranging from 74 to 7,652 binding antibody units/mL. Using an adjusted threshold based on receiver operating characteristic (ROC) curve analysis, the specificity of neutralizing antibody detection increased from 0.15 (95% CI 0.02–0.45) and 0.17 (0.04–0.41) to 0.92 (0.64–1.00) and 0.83 (0.59–0.96) against BQ.1.1 and XBB.1, respectively. Serological tests based on receptor-binding domain antigens from the ancestral virus fail to predict neutralizing activity against the latest circulating Omicron variants. Adapting serological tests may improve their clinical utility in immunocompromised patients.IMPORTANCEAnti-SARS-CoV-2 serology was developed in 2020 in response to the COVID-19 pandemic to diagnose SARS-CoV-2 infection and monitor an individual’s immunity following natural infection or vaccination. Given the relationship between neutralizing antibody titers and protection against severe infection, many studies have evaluated the correlation between serology tests and neutralization assays in the pre-Omicron era. An important potential clinical use of serology, which explores binding antibodies, is estimating an individual’s level of protection against new infection, particularly in immunosuppressed individuals and those at risk of severe COVID. However, in the Omicron era, as new viruses evade the immunity induced by previous infections and vaccination, the correlation between binding antibody levels determined by serological assays developed from ancestral antigens and neutralizing antibody titers against new viruses should be re-examined in order to determine whether these assays should be optimized by adapting antigens to the circulating SARS-CoV-2 strains.

Bats play key roles in ecosystem functions and provide services to human populations. There is a need to protect bat populations and to mitigate the risks associated with pathogen spillover. Caves are key habitats for many bat species, which use them as roosting and breeding sites. Caves, bats and their guano also attract many other animals along trophic chains which might favor direct or indirect interspecies interactions. Two caves hosting colonies of insectivorous bats have been investigated in the Republic of Congo to characterize habitat sharing and interactions between bats, humans and animals. We set up a camera-trap monitoring protocol during 19 months at the entrance of and inside each cave. Our results demonstrated the richness and complexity of the species interactions around and within these caves. We identified and/or quantified mainly rodents, but also numerous categories of animals such as insects, birds, reptiles and carnivores using the caves. We investigated the temporal variation in the use of caves and the potential interactions between humans, wild animals and bat colonies. Our study contributes to the understanding of the interface and interactions, for the first time quantified, between cave-dwelling animal species, including humans. This knowledge is important to promote the conservation of cave ecosystems and better understand the ecology of infectious diseases.

In recent years, there has been a growing interest in accelerated materials innovation in the context of the process-structure-property chain. In this regard, it is essential to take into account manufacturing processes and tailor materials design approaches to support downstream process design approaches. As a major step into this direction, we present a holistic and generic optimization approach that covers the entire process-structure-property chain in materials engineering. Our approach specifically employs machine learning to address two critical identification problems: a materials design problem, which involves identifying near-optimal material microstructures that exhibit desired properties, and a process design problem that is to find an optimal processing path to manufacture these microstructures. Both identification problems are typically ill-posed, which presents a significant challenge for solution approaches. However, the non-unique nature of these problems offers an important advantage for processing: By having several target microstructures that perform similarly well, processes can be efficiently guided towards manufacturing the best reachable microstructure. The functionality of the approach is demonstrated at manufacturing crystallographic textures with desired properties in a simulated metal forming process.

The incidence of diphtheria has been rising over the past decade, particularly in its cutaneous form. A clinical review of the case series was therefore required. We reviewed the epidemiological, clinical, microbiological and therapeutic data of cutaneous diphtheria cases, in adult patients living in metropolitan France with a skin sample positive for corynebacteria of the diphtheriae complex between 2018 and 2022. Of the 132 cases identified, 63 met the inclusion criteria. The mean age was 53.8 years, 68.3% were men and 56.7% had travelled outside mainland France. Immunization rate was 44%. Lesions involved the lower limbs (86.9%), corresponded to ulcerations in 82% of cases. Two species were identified in the study: C. diphtheriae (77%) and C. ulcerans (23%). 39% were toxigenic. Other bacteria were present in 88.9% of cases: Staphylococcus aureus (54.7%) and Streptococcus pyogenes (49.1%). 17.5% of clinicians ignored the presence of Corynebacteria of the diphtheriae species complex. Clinicians seem to be unfamiliar with this disease due to under-reporting and a lack of knowledge and awareness among clinicians, and rarely mention it, which explains the frequent failure to comply with French recommendations. Clinical data are consistent with the literature. Continued epidemiological surveillance, increased vaccination coverage in high-risk populations and better information of clinicians are essential to prevent and control this preventable disease.