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The generation of synthetic data can be used for anonymization, regularization, oversampling, semi-supervised learning, self-supervised learning, and several other tasks. Such broad potential motivated the development of new algorithms, specialized in data generation for specific data formats and Machine Learning (ML) tasks. However, one of the most common data formats used in industrial applications, tabular data, is generally overlooked; Literature analyses are scarce, state-of-the-art methods are spread across domains or ML tasks and there is little to no distinction among the main types of mechanism underlying synthetic data generation algorithms. In this paper, we analyze tabular and latent space synthetic data generation algorithms. Specifically, we propose a unified taxonomy as an extension and generalization of previous taxonomies, review 70 generation algorithms across six ML problems, distinguish the main generation mechanisms identified into six categories, describe each type of generation mechanism, discuss metrics to evaluate the quality of synthetic data and provide recommendations for future research. We expect this study to assist researchers and practitioners identify relevant gaps in the literature and design better and more informed practices with synthetic data.

The objective of this study is to propose and evaluate a set of modifications to enhance a machine-learning-based method for forecasting day-ahead solar irradiation. To assess the proposed modifications, they were implemented in an initial forecast method, and their effectiveness was analyzed using two years of data on a national scale in Japan. In addition, the accuracy of the modified method was compared with one of the forecast methods for solar irradiation used by the Japan Meteorological Agency (JMA), namely, the mesoscale model (MSM). Such forecasts were made publicly available only recently, which makes this study one of the first ones to compare them with machine-learning-based forecasts. The annual root-mean-square error (RMSE) of local forecasts of the JMA-MSM varied from 0.1 to 0.14 kW h m−2; the regional equivalent varied from 0.062 to 0.091 kW h m−2. In comparison with these results, the modified model achieved an average RMSE reduction of 7.5% on the local scale and 16% on the regional scale. The modified model also had a skill score that was 23% higher than that of the JMA model. Furthermore, the performance of the JMA model had strong spatial and seasonal dependencies, which were reduced in the machine-learning-based forecasts. The results show that the proposed modifications are effective in reducing large forecasts errors, but they cannot compensate for situations in which the input data used to make the forecasts are highly inaccurate.

Autoantibodies are produced within germinal centers (GC), in a process regulated by interactions between B, T follicular helper (Tfh), and T follicular regulatory (Tfr) cells. The GC dysregulation in human autoimmunity has been inferred from circulating cells, albeit with conflicting results due to diverse experimental approaches. We applied a consistent approach to compare circulating Tfr and Tfh subsets in patients with different autoimmune diseases. We recruited 97 participants, including 72 patients with Hashimoto’s thyroiditis (HT, n = 18), rheumatoid arthritis (RA, n = 16), or systemic lupus erythematosus (SLE, n = 32), and 31 matched healthy donors (HD). We found that the frequency of circulating T follicular subsets differed across diseases. Patients with HT had an increased frequency of blood Tfh cells ( p  = 0.0215) and a reduced Tfr/Tfh ratio ( p  = 0.0338) when compared with HD. This was not observed in patients with systemic autoimmune rheumatic diseases (RA, SLE), who had a reduction in both Tfh ( p  = 0.0494 and p  = 0.0392, respectively) and Tfr ( p  = 0.0003 and p  = 0.0001, respectively) cells, resulting in an unchanged Tfr/Tfh ratio. Activated PD-1 + ICOS + Tfh and CD4 + PD-1 + CXCR5 – Tph cells were raised only in patients with SLE ( p  = 0.0022 and p  = 0.0054), without association with disease activity. Our data suggest that GC dysregulation, assessed by T follicular subsets, is not uniform in human autoimmunity. Specific patterns of dysregulation may become potential biomarkers for disease and patient stratification.

ObjectivesTo provide an update of the EULAR rheumatoid arthritis (RA) management recommendations addressing the most recent developments in the field.MethodsAn international task force was formed and solicited three systematic literature research activities on safety and efficacy of disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids (GCs). The new evidence was discussed in light of the last update from 2019. A predefined voting process was applied to each overarching principle and recommendation. Levels of evidence and strengths of recommendation were assigned to and participants finally voted on the level of agreement with each item.ResultsThe task force agreed on 5 overarching principles and 11 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); GCs; biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab including biosimilars), abatacept, rituximab, tocilizumab, sarilumab and targeted synthetic (ts) DMARDs, namely the Janus kinase inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib. Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target) and tapering in sustained clinical remission is provided. Safety aspects, including risk of major cardiovascular events (MACEs) and malignancies, costs and sequencing of b/tsDMARDs were all considered. Initially, MTX plus GCs is recommended and on insufficient response to this therapy within 3–6 months, treatment should be based on stratification according to risk factors; With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD should be added to the csDMARD; after careful consideration of risks of MACEs, malignancies and/or thromboembolic events tsDMARDs may also be considered in this phase. If the first bDMARD (or tsDMARD) fails, any other bDMARD (from another or the same class) or tsDMARD (considering risks) is recommended. With sustained remission, DMARDs may be tapered but should not be stopped. Levels of evidence and levels of agreement were high for most recommendations.ConclusionsThese updated EULAR recommendations provide consensus on RA management including safety, effectiveness and cost.

Although targeted biological treatments have transformed the outlook for patients with rheumatoid arthritis, 40% of patients show poor clinical response, which is mechanistically still unexplained. Because more than 50% of patients with rheumatoid arthritis have low or absent CD20 B cells—the target for rituximab—in the main disease tissue (joint synovium), we hypothesised that, in these patients, the IL-6 receptor inhibitor tocilizumab would be more effective. The aim of this trial was to compare the effect of tocilizumab with rituximab in patients with rheumatoid arthritis who had an inadequate response to anti-tumour necrosis factor (TNF) stratified for synovial B-cell status. This study was a 48-week, biopsy-driven, multicentre, open-label, phase 4 randomised controlled trial (rituximab vs tocilizumab in anti-TNF inadequate responder patients with rheumatoid arthritis; R4RA) done in 19 centres across five European countries (the UK, Belgium, Italy, Portugal, and Spain). Patients aged 18 years or older who fulfilled the 2010 American College of Rheumatology and European League Against Rheumatism classification criteria for rheumatoid arthritis and were eligible for treatment with rituximab therapy according to UK National Institute for Health and Care Excellence guidelines were eligible for inclusion in the trial. To inform balanced stratification, following a baseline synovial biopsy, patients were classified histologically as B-cell poor or rich. Patients were then randomly assigned (1:1) centrally in block sizes of six and four to receive two 1000 mg rituximab infusions at an interval of 2 weeks (rituximab group) or 8 mg/kg tocilizumab infusions at 4-week intervals (tocilizumab group). To enhance the accuracy of the stratification of B-cell poor and B-cell rich patients, baseline synovial biopsies from all participants were subjected to RNA sequencing and reclassified by B-cell molecular signature. The study was powered to test the superiority of tocilizumab over rituximab in the B-cell poor population at 16 weeks. The primary endpoint was defined as a 50% improvement in Clinical Disease Activity Index (CDAI50%) from baseline. The trial is registered on the ISRCTN database, ISRCTN97443826, and EudraCT, 2012-002535-28. Between Feb 28, 2013, and Jan 17, 2019, 164 patients were classified histologically and were randomly assigned to the rituximab group (83 [51%]) or the tocilizumab group (81 [49%]). In patients histologically classified as B-cell poor, there was no statistically significant difference in CDAI50% between the rituximab group (17 [45%] of 38 patients) and the tocilizumab group (23 [56%] of 41 patients; difference 11% [95% CI −11 to 33], p=0·31). However, in the synovial biopsies classified as B-cell poor with RNA sequencing the tocilizumab group had a significantly higher response rate compared with the rituximab group for CDAI50% (rituximab group 12 [36%] of 33 patients vs tocilizumab group 20 [63%] of 32 patients; difference 26% [2 to 50], p=0·035). Occurrence of adverse events (rituximab group 76 [70%] of 108 patients vs tocilizumab group 94 [80%] of 117 patients; difference 10% [–1 to 21) and serious adverse events (rituximab group 8 [7%] of 108 vs tocilizumab group 12 [10%] of 117; difference 3% [–5 to 10]) were not significantly different between treatment groups. The results suggest that RNA sequencing-based stratification of rheumatoid arthritis synovial tissue showed stronger associations with clinical responses compared with histopathological classification. Additionally, for patients with low or absent B-cell lineage expression signature in synovial tissue tocilizumab is more effective than rituximab. Replication of the results and validation of the RNA sequencing-based classification in independent cohorts is required before making treatment recommendations for clinical practice. Efficacy and Mechanism Evaluation programme from the UK National Institute for Health Research.

Citation counts are frequently used for assessing the scientific impact of articles. Current approaches for forecasting future citations counts have important limitations. This study aims to analyse and predict the trajectories of citation counts of systematic reviews (SR) based on their citation profiles in the previous years and predict quantiles of future citation counts. We included all SR published between 2010 and 2012 in medical journals indexed in the Web of Science. A longitudinal k-means (KML) clustering approach was applied to identify trajectories of citations counts 10 years after publication, according to the yearly citation count, the proportion of all cites attained in a specific year and the annual variation in citation counts. Finally, we built multinomial logistic regression models aiming to predict in what tercile or quartile of citation counts a SR would be 10 years after publication. Using clustering approaches, we obtained 24 groups of SR. Two groups (7.9% of the articles) had an average of > 200 citations, while two other groups (10.4% of the articles) presented an average of < 10 citations. The model predicting terciles of citation counts attained an accuracy of 72.8% (95%CI = 71.1–74.3%) and a kappa coefficient of 0.59 (95%CI = 0.57–0.62). Prediction of citation quartiles (combining the second and third quartiles into a single group) attained a accuracy of 76.2% (95%CI = 74.7–77.8%) and a kappa coefficient of 0.62 (95%CI = 0.59–0.64). This study provides an approach for predicting of future citations of SR based exclusively on citation counts from the previous years, with the models developed displaying an encouraging accuracy and agreement.

The Crato Formation (Aptian, Lower Cretaceous) is a fossiliferous deposit of global significance, representing a lacustrine palaeoenvironment which offers insights into aquatic insect taphonomy. Despite its importance, prior studies lacked an actualistic approach. Here, we analyze the preservation of mayflies (Ephemeroptera) and dragonflies (Odonata) from this formation using experimental taphonomy on 253 extant Ephemeroptera and 236 Odonata, alongside 306 fossil specimens. Disarticulation experiments showed that the thorax of modern mayfly larvae disarticulated first, yet Crato Hexagenitidae larvae retained intact thoraces, indicating minimal disturbance and autochthonous deposition. Fossil alate specimens rarely exhibited decay-related wing damage, aligning with short decay times. Dragonfly carcasses exhibited a characteristic leg posture in death, also preserved in Crato fossils, further suggesting minimal transport. Additionally, fossil dragonflies retained labial masks, the first structure to disarticulate experimentally, consistent with parautochthonous assemblages. Mayfly larvae exposed to low salinity during experiments exhibited excessive defecation before death, hinting at possible low salinity conditions in the Crato palaeoenvironment, though preservational challenges obscure confirmation. During experimentation, we also noticed that all carcasses immediately floated under hypersaline conditions, while carcasses immersed in non-hypersaline conditions went through slower decomposition. Thus, we can safely propose with experimental data that microbial biofilms on the surface of the water were acting during carcass sinking in this deposit.

Nanoindentation was used to probe the local slip resistance in CP-Ti deformed in compression to different extents. Changes in hardness in the deformed grains and twins were compared with the change in flow stress measured during deformation, with the aim to elucidate the relative contribution of slip and twinning to the work hardening of Ti alloys. The hardness values were calibrated with measurements on binary Ti–Al alloys. The hardness increased only slightly with deformation and cannot explain the observed work hardening. Although twinned regions were found to be harder than the parent grains, this increase was found to be small once the effect of crystal orientation was accounted for. The increase in hardness in the twins was slightly higher for compressive twins than for tensile twins. It is proposed that this modest hardness increase in the twins is more consistent with the presence of twinning stresses than with a change in the local flow stress caused by dislocation interactions. The implications of these findings to the work hardening of CP titanium are discussed.

Fixed airflow obstruction (FAO) can complicate asthma. Inflammation is a proposed underlying mechanism. Our aim in this cross-sectional investigation was to evaluate the blood leucocyte pattern and level of exhaled nitric oxide in asthmatics and non-asthmatics with or without FAO. A total of 11,579 individuals aged ≥20 years from the US National Health and Nutrition Examination Survey were included. They were grouped as: controls without asthma and FAO (n = 9,935), asthmatics without FAO (n = 674), asthmatics with FAO (n = 180) and non-asthmatics with FAO (n = 790). FAO was defined as post-bronchodilator FEV1/FVC < lower limit of normal. Exhaled nitric oxide ≥ 25ppb, blood eosinophil levels ≥300 cells/μL, and blood neutrophil levels ≥5100 cells/μL were defined as elevated. Stratified analyses for smoking and smoking history were performed. Elevated blood eosinophil levels were more common in all groups compared to the controls, with the highest prevalence in the group with asthma and fixed airflow obstruction (p<0.01). In a multiple logistic regression model adjusted for potential confounders including smoking, the asthma groups had significantly higher odds ratios for elevated B-Eos levels compared to the control group (odds ratio 1.4, (confidence interval: 1.1-1.7) for the asthma group without fixed airflow obstruction and 2.5 (1.4-4.2) for the asthma group with fixed airflow obstruction). The group with fixed airflow obstruction without asthma had higher odds ratio for elevated blood neutrophil levels compared to the controls: 1.4 (1.1-1.8). Smoking and a history of smoking were associated to elevated B-Neu levels. Fixed airflow obstruction in asthma was associated with elevated blood eosinophil levels, whereas fixed airflow obstruction without asthma was associated with elevated blood neutrophil levels.

ObjectivesSince the 2007 recommendations for the management of early arthritis have been presented, considerable research has been published in the field of early arthritis, mandating an update of the 2007 European League Against Rheumatism (EULAR) recommendations for management of early arthritis.MethodsIn accordance with the 2014 EULAR Standardised Operating Procedures, the expert committee pursued an approach that was based on evidence in the literature and on expert opinion. The committee involved 20 rheumatologists, 2 patients and 1 healthcare professional representing 12 European countries. The group defined the focus of the expert committee and target population, formulated a definition of ‘management’ and selected the research questions. A systematic literature research (SLR) was performed by two fellows with the help of a skilled librarian. A set of draft recommendations was proposed on the basis of the research questions and the results of the SLR. For each recommendation, the categories of evidence were identified, the strength of recommendations was derived and the level of agreement was determined through a voting process.ResultsThe updated recommendations comprise 3 overarching principles and 12 recommendations for managing early arthritis. The selected statements involve the recognition of arthritis, referral, diagnosis, prognostication, treatment (information, education, pharmacological and non-pharmacological interventions), monitoring and strategy. Eighteen items were identified as relevant for future research.ConclusionsThese recommendations provide rheumatologists, general practitioners, healthcare professionals, patients and other stakeholders with an updated EULAR consensus on the entire management of early arthritis.