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OBJECTIVE: We focused to analyze the time-course changes at pre- and post-flare of T peripheral helper (Tph) cells and circulating T follicular helper (Tfh) cells in the blood of patients with systemic lupus erythematosus (SLE) with lupus low disease activity state (LLDAS) before flare. METHODS: This study included inactive (n=29) and active (n=55) patients with SLE. Tph subsets, Tfh subsets, CD11chi B cells, and plasma cells in the blood were determined by flow cytometry. The blood levels of cytokines including interferons (IFNs) were measured by electrochemiluminescence assay or cytokine beads array. RESULTS: Active SLE patients exhibited the increased frequency of Tph1, Tph2, Tfh1, and Tfh2 subsets when compared to inactive patients, but no clear changes in the other subsets. During the treatment with medications, Tph1, Tph2, and Tfh2 subsets were significantly reduced along with disease activity and Tph1 and Tph2 subsets were positively correlated with SLE disease activity index (SLEDAI). The time course analysis of patients at pre- and post-flare revealed that in the patients at LLDAS before flare, Tph subsets and Tfh subsets were relatively low levels. At the flare, Tph cells, particularly Tph1 and Tph2 subsets, were increased and correlated with SLEDAI. Furthermore, the blood levels of IFN-α2a, IFN-γ, and IFN-λ1 were low in the patients with LLDAS before flare but these IFNs, particularly IFN-λ1, were increased along with flare. CONCLUSION: Increased frequency of Tph1 and Tph2 subsets and elevated levels of serum IFN-λ1 are presumably critical for triggering of flare in SLE.
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Aquaculture contributes to the sustainable development of food security, marine resource conservation, and economy. Shifting aquaculture feed from fish meal and oil to terrestrial plant derivatives may result in cost savings. However, many carnivorous fish cannot be sustained on plant-derived materials, necessitating the need for the identification of important factors for farmed fish growth and the identification of whether components derived from terrestrial plants can be used in feed. Herein, we focused on the carnivorous fish leopard coral grouper (P. leopardus) to identify the essential growth factors and clarify their intake timing from feeds. Furthermore, we evaluated the functionality of starch, which are easily produced by terrestrial plants. Results reveal that carbohydrates, which are not considered essential for carnivorous fish, can be introduced as a major part of an artificial diet. The development of artificial feed using starch offers the possibility of increasing the growth of carnivorous fish in aquaculture.
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Alimentación Animal , Acuicultura , Almidón , Almidón/metabolismo , Alimentación Animal/análisis , Acuicultura/métodos , Animales , Peces/metabolismo , Peces/crecimiento & desarrolloRESUMEN
BACKGROUND: Validation of protective associations of the lupus low disease activity state (LLDAS) against flare, irreversible damage, health-related quality of life, and mortality has enabled the adoption of treat-to-target strategies in patients with systemic lupus erythematosus (SLE). Previous validation studies were of short duration, limiting the ability to detect longer term signals in flare rate and irreversible damage. In addition, previous studies have focused on percent time at target, rather than actual periods of time that are more useful in clinical practice and trials. We assessed long-term protective associations of LLDAS and remission, and specifically examined protective thresholds of sustained LLDAS and remission. METHODS: Patients aged 18 years or older with SLE were followed up from May 1, 2013, to Dec 31, 2020 in a prospective, multinational, longitudinal cohort study. Patients were recruited from 25 centres in 12 countries. Multi-failure time-to-event analyses were used to assess the effect of sustained LLDAS on irreversible damage accrual (primary outcome; measured with the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index) and flare (key secondary outcome; measured with the SELENA Flare Index), with dose exposure and threshold effects studied. Sustained LLDAS or remission were defined as two or more consecutive visits over at least 3 months in the respective state. This study is registered with ClinicalTrials.gov, NCT03138941. FINDINGS: 3449 patients were followed up for a median of 2·8 years (IQR 1·1-5·6), totalling 37â662 visits. 3180 (92·2%) patients were women, and 3031 (87·9%) were of Asian ethnicity. 2506 (72·7%) patients had sustained LLDAS at least once. Any duration of sustained LLDAS or remission longer than 3 months was associated with reduced damage accrual (LLDAS: hazard ratio 0·60 [95% CI 0·51-0·71], p<0·0001; remission: 0·66 [0·57-0·76], p<0·0001) and flare (LLDAS: 0·56 [0·51-0·63], p<0·0001; remission: 0·66 [0·60-0·73], p<0·0001), and increasing durations of sustained LLDAS corresponded to increased protective associations. Sustained DORIS remission or steroid-free remission were less attainable than LLDAS. INTERPRETATION: We observed significant protective associations of LLDAS and remission against damage accrual and flare, establish a threshold of 3 months sustained LLDAS or remission as protective, and demonstrate deepening protection with longer durations of sustained LLDAS or remission. FUNDING: The Asia Pacific Lupus Collaboration receives project support grants from AstraZeneca, Bristol Myers Squibb, EMD Sereno, GSK, Janssen, Eli Lilly, and UCB.
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Lupus Eritematoso Sistémico , Índice de Severidad de la Enfermedad , Humanos , Femenino , Adulto , Masculino , Estudios Prospectivos , Persona de Mediana Edad , Estudios Longitudinales , Inducción de Remisión , Calidad de VidaRESUMEN
With the rapid growth of inland aquaculture worldwide, side effects such as the discharge of nutrients and antibiotics pose a threat to the global environments. A sustainable future for aquaculture requires an effective management system, including the early detection of disease through the monitoring of specific biomarkers in aquaculture tanks. To this end, we investigated whether fish feces in aquaculture tanks could be used for non-invasive health monitoring using ayu (Plecoglossus altivelis) infected with Flavobacterium psychrophilum, which causes bacterial cold-water disease worldwide. Feces that were subsequently produced in the tanks were used for metagenomic and metabolomic analyses. The relative abundances of the genera Cypionkella (0.6% ± 1.0%, 0.1% ± 0.2%), Klebsiella (11.2% ± 10.0%, 6.2% ± 5.9%), and F. psychrophilum (0.5% ± 1.0%, 0.0% ± 0.0%) were significantly higher in the feces of the infection challenge test tanks than in those of the control tanks. The abundances of cortisol, glucose, and acetate in the feces of the infection challenge test tanks were 2.4, 2.4, and 1.3 times higher, respectively, than those of the control tanks. Metagenome analysis suggested that acetate was produced by microbes such as Cypionkella. The abundances of indicated microbes or metabolites increased after day 4 of infection at the earliest, and were thus considered possible biomarkers. Our results suggest that feces produced in aquaculture tanks can potentially be used for non-invasive and holistic monitoring of fish diseases in aquaculture systems. IMPORTANCE: The aquaculture industry is rapidly growing, yet sustainability remains a challenge. One crucial task is to reduce losses due to diseases. Monitoring fish health and detecting diseases early are key to establishing sustainable aquaculture. Using metagenomic and metabolomic analyses, we found that feces of ayu infected with Flavobacterium psychrophilum contain various specific biomarkers that increased 4 days post-challenge, at the earliest. Our findings are the first step in establishing a novel, non-invasive, and holistic monitoring method for fish diseases in aquaculture systems, especially in ayu, which is an important freshwater fish species in Asia, promoting a sustainable future.
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Acuicultura , Biomarcadores , Heces , Enfermedades de los Peces , Infecciones por Flavobacteriaceae , Flavobacterium , Metabolómica , Metagenómica , Osmeriformes , Animales , Flavobacterium/genética , Flavobacterium/clasificación , Flavobacterium/aislamiento & purificación , Infecciones por Flavobacteriaceae/veterinaria , Infecciones por Flavobacteriaceae/microbiología , Heces/microbiología , Osmeriformes/microbiología , Enfermedades de los Peces/microbiología , Biomarcadores/análisis , Metagenómica/métodos , Metabolómica/métodosRESUMEN
A stereoselective N-alkenylation of azoles with alkynes and iodine(III) electrophile is reported. The reaction between various azoles and internal alkynes is mediated by benziodoxole triflate as the electrophile in a trans-fashion, affording azole-bearing vinylbenziodoxoles in moderate to good yields. The tolerable azole nuclei include pyrazole, indazole, 1,2,3-triazole, benzotriazole, and tetrazole. The iodanyl group in the product can be leveraged as a versatile synthetic handle, allowing for the preparation of hitherto inaccessible types of densely functionalized N-vinylazoles.
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OBJECTIVES: This study aimed to investigate the impact of memory function and social capital on depressive symptoms during the COVID-19 pandemic among older adults in rural Japan. METHODS: A retrospective study with longitudinal data was conducted during COVID-19 from May 2021 to November 2021 (T2) in Kurogawa, Japan. The candidate population for this study was 145 with the following requirements: (1) older individuals aged 65 years or above who were registered in the Kurogawa study, and (2) those with previous data (from November 2016 to February 2020; T1 as pre-pandemic). Memory function was assessed using the Wechsler Memory Scale-Revised Logical Memory II delayed recall part A (LM II-DR). Depressive symptoms were assessed using the Japanese version of the 15-item Geriatric Depression Scale (GDS-15). Social capital was evaluated through civic participation, social cohesion, and reciprocity. Fear of the COVID-19 infection (FCV-19S) was evaluated. RESULTS: The final analysis included 96 participants (mean age = 81.0 years, SD = 4.8) Multivariate analysis for GDS-15 score by Mixed Model Repeated Measures (MMRM) revealed significant associations between LM II-DR (ß = -0.13, 95% CI: -0.21-0.05, p = 0.002) and FCV-19S during COVID-19 (ß = 0.08, 95% CI: 0.01-0.15, p = 0.02) with GDS-15 score. However, civic participation, social cohesion and reciprocity were not associated with GDS-15 score. CONCLUSIONS: Among older adults in rural Japan, memory function and fear of the COVID-19 infection were significantly associated with depressive symptoms in MMRM analysis. However, social capital was not associated with depressive symptoms. This highlights the need to address memory function and fear of the COVID-19 infection in interventions for older adults during crises like the COVID-19 pandemic.
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COVID-19 , Depresión , Vida Independiente , Población Rural , Capital Social , Humanos , COVID-19/psicología , COVID-19/epidemiología , Femenino , Masculino , Japón/epidemiología , Anciano , Estudios Retrospectivos , Anciano de 80 o más Años , Estudios Longitudinales , Población Rural/estadística & datos numéricos , Depresión/epidemiología , Depresión/psicología , SARS-CoV-2RESUMEN
To understand the differences in degradation processes depending on the chemical properties of polymers, it is necessary to both quantify the microbiome composition and evaluate the process of microbial turnover (i.e., community assembly processes) in a variety of polymer materials. In this study, using a phylogenetic bin-based null model analysis (i.e., iCAMP), we evaluated community assembly processes from original estuary water to 37 types of polymers, which provide overwhelmingly diverse niches for microbes, in 14-day incubation experiments. First, we evaluated the polymer properties related to degradation rates. Polymers with higher adipic acid (AdA) monomer exhibited higher motility, hydrophilicity, and degradation rates, whereas those with higher aromatic monomer exhibited the opposite trends. Second, microbiome composition analysis was performed, and the microbiomes were significantly changed by the AdA or aromatic content. This was consistent with the polymer properties, suggesting that polymer motility and hydrophilicity attributable to the first-order structure modify the accessibility of the enzyme to the reaction site and hence the degradation rate, resulting in differences in microbiome community composition. Finally, we determined community assembly processes from estuary water to plastics using a phylogenetic bin-based null model analysis. The importance of heterogeneous selection was higher in mobile, hydrophilic, and fast-degrading polymers, while that of homogeneous selection was lower. This suggests that the environmental difference between before and after incubation becomes significant under rapid degradation, which select microbes adapted to biofilm environments. In addition, the more stochastic turnover prevailed, the more variation in the communities (i.e., ß-diversity) increased. This suggests that turnover processes not dictated by the environment lead to instability in community compositions.
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Biodegradación Ambiental , Microbiota , Filogenia , Contaminantes Químicos del Agua/análisis , Polímeros , Estuarios , Microbiología del AguaRESUMEN
A π-Lewis acidic metal-catalysed cyclisation/photochemical radical addition sequence was developed, which utilises in situ generated 2-benzopyrylium cation intermediates as photoredox catalysts and electrophilic substrates to form 1H-isochromene derivatives in good yields in most cases. The key 2-benzopyrylium intermediates were generated through the activation of the alkyne moiety of ortho-carbonyl alkynylbenzene derivatives by such π-Lewis acidic metal catalysts as AgNTf2 and Cu(NTf2)2, and the subsequent intramolecular cyclisation and proto-demetalation using trifluoroacetic acid. Further photo-excitation of the 2-benzopyrylium intermediates facilitated single-electron transfer from a benzyltrimethylsilane derivative as a donor molecule to promote the radical addition of arylmethyl radicals to the 2-benzopyrylium intermediates.
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Gamma heavy chain disease (gHCD) is a rare B-cell lymphoproliferative disorder that mostly occurs after childbearing age. Here we report the first case of gHCD in a pregnant patient that was diagnosed in the second trimester, and another pregnancy in the same patient after initial treatment for gHCD. The former pregnancy ended in intrauterine fetal death, believed to be caused by insufficient maternal blood flow due to multiple placental infarcts. The latter pregnancy course was uneventful. Although we cannot rule out the possibility that the poor outcome of the former pregnancy was due to an unfortunate complication independent of gHCD, the courses of these pregnancies suggest that non-lymphomatous gamma heavy chain may have a significant impact on pregnancy and that its removal by treatment may improve outcomes.
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Resultado del Embarazo , Humanos , Embarazo , Femenino , Adulto , Enfermedad de las Cadenas Pesadas/complicaciones , Cadenas gamma de Inmunoglobulina , Muerte Fetal/etiología , Resultado del TratamientoRESUMEN
T peripheral helper (Tph) cells are thought to contribute to extra-follicular B cell activation and play a pathogenic role in autoimmune diseases. However, the role of Tph subsets is not fully elucidated. Here, we investigate the immunological functions of Tph subsets and their involvement in systemic lupus erythematosus (SLE). We have defined four Tph subsets (Tph1: CXCR3+CCR6-, Tph2: CXCR3-CCR6-, Tph17: CXCR3-CCR6+, and Tph1-17: CXCR3+CCR6+) and performed RNA sequencing after cell sorting. Tph1 and Tph17 subsets express substantial levels of IL21, indicating B cell helper functions. However, Tph2 and Tph1-17 subsets express low IL21. Interestingly, we have found Tph2 subset express high levels of CX3CR1, GZMB, PRF1, GLNY, S1PR5, TBX21, EOMES, ZNF863, and RUNX3, indicating a feature of CD4+ cytotoxic T lymphocytes. In SLE patients, the frequency of Tph1 and Tph2 subsets are significantly increased and positively correlated with SLE disease activity indexes. Tph1 cells expansion has been observed in patients with cutaneous and musculoskeletal manifestations. On the other hand, Tph2 cell expansion has been found in patients with lupus nephritis in addition to the above manifestations. Our findings imply that Tph1 and Tph2 subsets exert distinct immunological functions and are contributed to the complexity of clinical manifestations in SLE.
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Antineoplásicos , Lupus Eritematoso Sistémico , Nefritis Lúpica , Humanos , Lupus Eritematoso Sistémico/genética , Ciclo Celular , Proliferación CelularRESUMEN
OBJECTIVES: Anti-IL-6 receptor antibodies are clinically efficacious in the management of rheumatoid arthritis (RA) with an associated increase in regulatory T cells (Tregs); however, the role of functional Treg subsets has yet to be clarified. This study aimed to evaluate how functional Treg subsets are altered by IL-6 receptor blockade and to analyze the relationship between these Treg subsets and the clinical outcome of RA. METHODS: We collected frozen peripheral blood mononuclear cells (PBMCs) from 40 patients with RA who started tocilizumab (TCZ) with or without MTX and 11 healthy controls (HCs). We fractionated Tregs with flow cytometry based on markers of phenotype and function and measured the proportions of detailed Treg subsets sequentially from baseline to week 52. RESULTS: The proportions of resting Tregs (rTregs) and rTregs+activated Tregs (aTregs) were significantly lower in RA patients at baseline than in HCs. The proportions of all those CD127low Tregs, rTregs, aTregs, and rTregs+aTregs were significantly increased with TCZ treatment. In patients treated with TCZ without MTX, rTreg were increased. Patients with an increase in the proportion of rTregs at week 12 had significantly less arthritis flares during the observation period. CONCLUSIONS: Blocking IL-6 receptor with TCZ increased the proportion of rTregs, a functional Treg subpopulation. Patients with an early increase in rTregs showed a favorable treatment course, and this increase in rTregs may reflect molecular remission induced by IL-6 signal inhibition.
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Surface modification using hydrophilic polymer coatings is a sustainable approach for preventing membrane clogging due to foulant adhesion to water treatment membranes and reducing membrane-replacement frequency. Typically, both molecular descriptors and time-domain nuclear magnetic resonance (TD-NMR) data, which reveal physicochemical properties and polymer-chain dynamics, respectively, are required to predict the properties and understand the mechanisms of hydrophilic polymer coatings. However, studies on the selection of essential components from high-dimensional data and their application to the prediction of surface properties are scarce. Therefore, we developed a method for selecting features from combined high-dimensional molecular descriptors and TD-NMR data. The molecular descriptors of the monomers present in polyethylene terephthalate films were calculated using RDKit, an open-source chemoinformatics toolkit, and TD-NMR spectroscopy was performed over a wide time range using five-pulse sequences to investigate the mobility of the polymer chains. The model that analyzed the data using the random forest algorithm, after reducing the features using gradient boosting machine-based recursive feature elimination, achieved the highest prediction accuracy. The proposed method enables the extraction of important elements from both descriptors of surface properties and can contribute to the development of new sustainable materials and material-specific informatics methodologies encompassing multiple information modalities.
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Sjögren's syndrome (SS) can present with extraglandular organs, such as interstitial lung disease (ILD). Anti-SS-A antibody is frequently found in SS cases, whereas anti-centromere antibody (ACA) is detected in some SS cases. Notably, the anti-SS-A and ACA double-positive cases exhibited distinct features with a higher prevalence of ILD. However, there have so far been no reports on the treatment of ILD in anti-SS-A and ACA double-positive cases. We herein present a case of ILD with anti-SS-A and ACA double-positive SS that was successfully treated with immunosuppressive therapy. Our case suggests the potential efficacy of immunosuppressive therapy for this poorly understood condition.
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OBJECTIVE: To assess whether Lupus Low Disease Activity State (LLDAS) attainment is associated with favorable outcomes in patients with recent onset systemic lupus erythematosus (SLE). METHODS: Data from a 13-country longitudinal SLE cohort were collected prospectively between 2013 and 2020. An inception cohort was defined based on disease duration < 1 year at enrollment. Patient characteristics between inception and noninception cohorts were compared. Survival analyses were performed to examine the association between LLDAS attainment and damage accrual and flare. RESULTS: Of the total 4106 patients, 680 (16.6%) were recruited within 1 year of SLE diagnosis (inception cohort). Compared to the noninception cohort, inception cohort patients were significantly younger, had higher disease activity, and used more glucocorticoids, but had less organ damage at enrollment. Significantly fewer inception cohort patients were in LLDAS at enrollment than the noninception cohort (29.6% vs 52.3%, P < 0.001), but three-quarters of both groups achieved LLDAS at least once during follow-up. Limiting analysis only to patients not in LLDAS at enrollment, inception cohort patients were 60% more likely to attain LLDAS (hazard ratio 1.37, 95% CI 1.16-1.61, P < 0.001) than noninception cohort patients and attained LLDAS significantly faster. LLDAS attainment was significantly protective against flare in both the inception and noninception cohorts. A total of 88 (13.6%) inception cohort patients accrued organ damage during a median 2.2 years of follow-up. CONCLUSION: LLDAS attainment is protective from flare in recent onset SLE. Significant protection from damage accrual was not observed because of low rates of damage accrual in the first years after SLE diagnosis. (ClinicalTrials.gov: NCT03138941).
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Lupus Eritematoso Sistémico , Índice de Severidad de la Enfermedad , Humanos , Lupus Eritematoso Sistémico/diagnóstico , Femenino , Masculino , Adulto , Persona de Mediana Edad , Estudios Longitudinales , Progresión de la Enfermedad , Glucocorticoides/uso terapéutico , Estudios Prospectivos , Adulto JovenRESUMEN
OBJECTIVES: To assess the risk of flare and damage accrual after tapering glucocorticoids (GCs) in modified serologically active clinically quiescent (mSACQ) patients with systemic lupus erythematosus (SLE). METHODS: Data from a 12-country longitudinal SLE cohort, collected prospectively between 2013 and 2020, were analysed. SLE patients with mSACQ defined as the state with serological activity (increased anti-dsDNA and/or hypocomplementemia) but without clinical activity, treated with ≤7.5 mg/day of prednisolone-equivalent GCs and not-considering duration, were studied. The risk of subsequent flare or damage accrual per 1 mg decrease of prednisolone was assessed using Cox proportional hazard models while adjusting for confounders. Observation periods were 2 years and censored if each event occurred. RESULTS: Data from 1850 mSACQ patients were analysed: 742, 271 and 180 patients experienced overall flare, severe flare and damage accrual, respectively. Tapering GCs by 1 mg/day of prednisolone was not associated with increased risk of overall or severe flare: adjusted HRs 1.02 (95% CI, 0.99 to 1.05) and 0.98 (95% CI, 0.96 to 1.004), respectively. Antimalarial use was associated with decreased flare risk. Tapering GCs was associated with decreased risk of damage accrual (adjusted HR 0.96, 95% CI, 0.93 to 0.99) in the patients whose initial prednisolone dosages were >5 mg/day. CONCLUSIONS: In mSACQ patients, tapering GCs was not associated with increased flare risk. Antimalarial use was associated with decreased flare risk. Tapering GCs protected mSACQ patients treated with >5 mg/day of prednisolone against damage accrual. These findings suggest that cautious GC tapering is feasible and can reduce GC use in mSACQ patients.
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Glucocorticoides , Lupus Eritematoso Sistémico , Prednisolona , Brote de los Síntomas , Humanos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/complicaciones , Femenino , Masculino , Glucocorticoides/administración & dosificación , Glucocorticoides/uso terapéutico , Adulto , Persona de Mediana Edad , Prednisolona/administración & dosificación , Prednisolona/uso terapéutico , Reducción Gradual de Medicamentos/métodos , Estudios Longitudinales , Progresión de la Enfermedad , Estudios de Cohortes , Modelos de Riesgos Proporcionales , Estudios ProspectivosRESUMEN
INTRODUCTION: Patients with peripheral artery disease (PAD) often complain of reduced physical activity (PA) despite improvements in intermittent claudication after successful endovascular treatment (EVT). Sarcopenia resulting from chronic ischemia can affect post-EVT PA levels. OBJECTIVE: This study aims to assess the association between sarcopenia and post-EVT PA levels. METHODS: One hundred five patients with PAD were consecutively enrolled in this study. PA was assessed using the post-EVT step count and the pre-EVT International Physical Activity Questionnaire. Sarcopenia was diagnosed based on the Asia Working Group for Sarcopenia and defined as low muscle mass and strength, and/or slow walking speed. The patients were categorized into three groups: 1) patients with sarcopenia (Sarcopenia Group); 2) patients with only low muscle mass or strength, and/or slow walking speed (Suspected-Sarcopenia Group); and 3) patients who did not fulfill all the sarcopenia criteria (No-Sarcopenia Group). RESULTS: Proportions of patients in the Sarcopenia, Suspected-Sarcopenia, and No-Sarcopenia Groups were 31.4, 38.1, and 30.5%, respectively. After controlling for potential confounders, the Sarcopenia Group demonstrated significantly lower step counts than the Suspected-Sarcopenia Group (p = .016) and No-Sarcopenia Group (p = .009). CONCLUSIONS: Our findings indicate that patients with PAD and sarcopenia require rehabilitation strategies to enhance physical performance.
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This study aims to elucidate the effectiveness and safety of SARS-CoV-2 mRNA vaccination in patients with systemic lupus erythematosus (SLE). We enrolled uninfected SLE patients who received two vaccine doses (BNT162b2 or mRNA-1273) and historical unvaccinated patients. Neutralizing antibodies, adverse reactions, and disease flares were evaluated 4 weeks after the second vaccination. Ninety patients were enrolled in each group. Among the vaccinated patients, SLE Disease Activity Index (SLEDAI), and prednisolone doses before vaccination were 2, and 5 mg/d, respectively. After the second vaccination, 19 (21.1%) had no neutralizing antibodies. Adverse reactions occurred in 88.9% within 3 d. Negative antibodies were associated with anemia and mycophenolate mofetil administration. SLEDAI increased modestly but significantly after vaccination, with 13 (14.4%) experiencing flares and 4 (4.4%) severe flares (nephritis in three and vasculitis in one). The flare rate was higher in vaccinated patients than unvaccinated controls. The mean duration between the second vaccination and flares was 35 d, and flares occurred at least 8 days after vaccination. Multivariable analysis showed that high SLEDAI and anti-dsDNA antibodies were associated with flares. The vaccine type, neutralizing antibody titer, and adverse reaction frequency did not affect flares. Therefore, residual disease activity before vaccination increases flare risk.
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Vacuna nCoV-2019 mRNA-1273 , Anticuerpos Neutralizantes , Vacuna BNT162 , COVID-19 , Lupus Eritematoso Sistémico , SARS-CoV-2 , Humanos , Lupus Eritematoso Sistémico/inmunología , Femenino , Masculino , COVID-19/prevención & control , COVID-19/inmunología , Adulto , Vacuna BNT162/administración & dosificación , Vacuna BNT162/efectos adversos , Vacuna BNT162/inmunología , SARS-CoV-2/inmunología , Vacuna nCoV-2019 mRNA-1273/administración & dosificación , Vacuna nCoV-2019 mRNA-1273/efectos adversos , Vacuna nCoV-2019 mRNA-1273/inmunología , Persona de Mediana Edad , Anticuerpos Neutralizantes/sangre , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/inmunología , Brote de los Síntomas , Vacunación/efectos adversos , Anticuerpos Antivirales/sangre , Índice de Severidad de la Enfermedad , Anticuerpos Antinucleares/sangre , Anticuerpos Antinucleares/inmunologíaRESUMEN
The development of data science has been needed in environmental fields such as marine, weather, and soil data. In general, the datasets are large in some cases, but they are often small because they contain observation data that the analyses themselves are limited. In such a case, the data are statistically evaluated by increasing or decreasing the levels of factors using differential analysis, resulting in the essential factors are estimated. However, there is no consistent approach to the means of assessing strong associations as a group between factors. Causal inference method has the possibility to output effective results for small data, and the results are expected to provide important information for understanding the potential highly association between factors, not necessarily the inference with big data. Here, we describe essential checkpoints and settings for the calculation by a direct method for learning a linear non-Gaussian structural equation model (DirectLiNGAM) and validation methods for the calculation results by using DirectLiNGAM with small-scale model data as an additional discussion of DirectLiNGAM portion of the related research article. Thus, this study provides the statistical validation methods for the association networks, treatments, and interventions for structural inference as a group of essential factors.â¢Causal inference with DirectLiNGAMâ¢Validation of correlation coefficient and feature importanceâ¢Validation using causal effect object and propensity scores.
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OBJECTIVE: Disease activity monitoring in SLE includes serial measurement of anti-double stranded-DNA (dsDNA) antibodies, but in patients who are persistently anti-dsDNA positive, the utility of repeated measurement is unclear. We investigated the usefulness of serial anti-dsDNA testing in predicting flare in SLE patients who are persistently anti-dsDNA positive. METHODS: Data were analysed from patients in a multinational longitudinal cohort with known anti-dsDNA results from 2013 to 2021. Patients were categorized based on their anti-dsDNA results as persistently negative, fluctuating or persistently positive. Cox regression models were used to examine longitudinal associations of anti-dsDNA results with flare. RESULTS: Data from 37 582 visits of 3484 patients were analysed. Of the patients 1029 (29.5%) had persistently positive anti-dsDNA and 1195 (34.3%) had fluctuating results. Anti-dsDNA expressed as a ratio to the normal cut-off was associated with the risk of subsequent flare, including in the persistently positive cohort (adjusted hazard ratio [HR] 1.56; 95% CI: 1.30, 1.87; P < 0.001) and fluctuating cohort (adjusted HR 1.46; 95% CI: 1.28, 1.66), both for a ratio >3. Both increases and decreases in anti-dsDNA more than 2-fold compared with the previous visit were associated with increased risk of flare in the fluctuating cohort (adjusted HR 1.33; 95% CI: 1.08, 1.65; P = 0.008) and the persistently positive cohort (adjusted HR 1.36; 95% CI: 1.08, 1.71; P = 0.009). CONCLUSION: Absolute value and change in anti-dsDNA titres predict flares, including in persistently anti-dsDNA positive patients. This indicates that repeat monitoring of dsDNA has value in routine testing.