Simple Alternatives Research Articles

LSBert: Lexical Simplification Based on BERT

Lexical simplification (LS) aims at replacing complex words with simpler alternatives. LS commonly consists of three main steps: complex word identification, substitute generation, and substitute ranking. Existing LS methods focus on the contextual information of the complex word in the last step (substitute ranking). However, they miss out the following two facts: (1) The word complexity of a polysemous word is very closely related to its context; (2) The step of substitute generation regardless of the context will inevitably produce a large number of spurious candidates. Therefore, we propose a novel LS system LSBert based on pretrained language model BERT to address the aforementioned issues, which is capable of making use of the wider context when both identifying the words in need of simplification and generating substitute candidates for the complex words. Specifically, LSBert consists of a network for complex word identification by fine-tuning BERT and a network for substitute generation based on BERT. Experimental results show that LSBert performs well in both complex word identification and substitute generation, achieving state-of-the-art results in three benchmarks. To facilitate reproducibility, the code of the LSBert system is available at https://github.com/qiang2100/BERT-LS.

Model Predictive Control-Based Optimized Operation of a Hybrid Charging Station for Electric Vehicles

This paper presents an energy management system (EMS) based on a novel approach using model predictive control (MPC) for the optimized operation of power sources in a hybrid charging station for electric vehicles (EVs). The hybrid charging station is composed of a photovoltaic (PV) system, a battery, a complete hydrogen system based on a fuel cell (FC), electrolyzer (EZ), and tank as an energy storage system (ESS), grid connection, and six fast charging units, all of which are connected to a common MVDC bus through Z-source converters (ZSC). The MPC-based EMS is designed to control the power flow among the energy sources of the hybrid charging station and reduce the utilization costs of the ESS and the dependency on the grid. The viability of the EMS was proved under a long-term simulation of 25 years in Simulink, using real data for the sun irradiance and a European load profile for EVs. Furthermore, this EMS is compared with a simpler alternative that is used as a benchmark, which pursues the same objectives, although using a states-based strategy. The results prove the suitability of the EMS, achieving a lower utilization cost (−25.3%), a notable reduction in grid use (−60% approximately) and an improvement in efficiency.

A Pilot Study of Detecting Individual Sleep Apnea Events Using Noncontact Radar Technology, Pulse Oximetry, and Machine Learning

The gold standard for assessing sleep apnea, polysomnography, is resource intensive and inconvenient. Thus, several simpler alternatives have been proposed. However, validations of these alternatives have focused primarily on estimating the apnea‐hypopnea index (apnea events per hour of sleep), which means information, clearly important from a physiological point of view such as apnea type, apnea duration, and temporal distribution of events, is lost. The purpose of the present study was to investigate if this information could also be provided with the combination of radar technology and pulse oximetry by classifying sleep apnea events on a second‐by‐second basis. Fourteen patients referred to home sleep apnea testing by their medical doctor were enrolled in the study (6 controls and 8 patients with sleep apnea; 4 mild, 2 moderate, and 2 severe) and monitored by Somnofy (radar‐based sleep monitor) in parallel with respiratory polygraphy. A neural network was trained on data from Somnofy and pulse oximetry against the polygraphy scorings using leave‐one‐subject‐out cross‐validation. Cohen’s kappa for second‐by‐second classifications of no event/event was 0.81, or almost perfect agreement. For classifying no event/hypopnea/apnea and no event/hypopnea/obstructive apnea/central apnea/mixed apnea, Cohen’s kappa was 0.43 (moderate agreement) and 0.36 (fair agreement), respectively. The Bland‐Altman 95% limits of agreement for the respiratory event index (apnea events per hour of recording) were ‐8.25 and 7.47, and all participants were correctly classified in terms of sleep apnea severity. Furthermore, the results showed that the combination of radar and pulse oximetry could be more accurate than the two technologies separately. Overall, the results indicate that radar technology and pulse oximetry could reliably provide information on a second‐by‐second basis for no event/event which could be valuable for management of sleep apnea. To be clinically useful, a larger study is necessary to validate the algorithm on a general population.

CO² filtration during pneumoperitoneum inflation and deflation in patients undergoing laparoscopy during the COVID-19 pandemic.

The current Covid-19 pandemic has been the most discussed topic of the year, mostly about protection and ways to avoid dissemination of the virus. In the healthcare system, especially in the operating rooms, the viability of laparoscopic surgery was questioned, mostly because of the transmission through aerosol. This article tries to suggest a way to minimize risks of laparoscopic surgery, during this situation, by using electrostatic filters, a simple, effective and low cost alternative.

Evaluation of pulping therapy in deciduous teeth using chlorhephenicol tetracycline and Zinc oxide

ABSTRACT The technique using CTZ paste (chloramphenicol, tetracycline, and zinc oxide-eugenol) in the endodontic treatment of deciduous teeth is easy to perform and requires a single session, which is an advantage with child patients. The inexistence of clinical protocols with the use of CTZ and the multifactorial endodontic repair process in deciduous teeth evidence the need for research on the subject. This study aimed to suggest a clinical protocol model for the systematization and standardization of the endodontic treatment of deciduous teeth using CTZ paste. In the case report presented, after pulp therapy, clinical-radiographical follow-up was conducted after 30, 60, 90 and 180 days. It was concluded that using CTZ paste is a simple, viable, and satisfactory alternative. Future clinical studies are needed regarding CTZ use in child clinic with strong scientific evidence.

Traffic Light Control Using Hierarchical Reinforcement Learning and Options Framework

The number of vehicles worldwide has grown rapidly over the past decade, impacting how urban traffic is managed. Traffic light control is a well-known problem and, although an increasing number of technologies are used to solve it, it still poses challenges and opportunities, especially when considering the inefficiency of the popular fixed-time traffic controllers. This study aims to apply Hierarchical Reinforcement Learning (HRL) and Options Framework to control a signalized vehicular intersection and compare its performance with that of a fixed-time traffic controller, configured using the Webster Method. HRL combines the ability to learn and make decisions while taking observations from the environment in real-time. These capabilities bring a significant adaptive power to a highly dynamic problem. The test scenarios were built using the SUMO simulation tool. According to our results, HRL presents better performance than those of its own isolated sub-policies and the fixed-time model, indicating a simple and efficient alternative.

Chinese Lexical Simplification

Lexical simplification has attracted much attention in many languages, which is the process of replacing complex words in a given sentence with simpler alternatives of equivalent meaning. Although the richness of vocabulary in Chinese makes the text very difficult to read for children and non-native speakers, there is no research work for the Chinese lexical simplification (CLS) task. To circumvent difficulties in acquiring annotations, we manually create the first benchmark dataset for CLS, which can be used for evaluating the lexical simplification systems automatically. To acquire a more thorough comparison, we present five different types of methods as baselines to generate substitute candidates for the complex word that includes synonym-based approach, word embedding-based approach, BERT-based approach, sememe-based approach, and a hybrid approach. Finally, we design the experimental evaluation of these baselines and discuss their advantages and disadvantages. To our best knowledge, this is the first study for CLS task.

Florida Sleeve Operative Technique

The Florida sleeve is a useful aortic root remodeling technique for cardiothoracic surgeons to have in their armamentarium that entails encompassing the sinuses while narrowing the aortic annulus and sinotubular junction to preserve the aortic valve. This technique is a valuable alternative to root replacement in appropriately chosen patients. The Florida sleeve is particularly advantageous for aortic valve salvage in cases of offset coronary arteries and bicuspid aortic valve. It has even become a useful option in carefully selected aortic dissection patients. Specific attention must be paid to inspection of the coronary artery relationship to commissures, circumferential dissection below the coronaries to allow passage of the sleeve graft and subcommissural suture placement to secure the graft in place. The Florida sleeve is a useful aortic root remodeling technique for cardiothoracic surgeons to have in their armamentarium that entails encompassing the sinuses while narrowing the aortic annulus and sinotubular junction to preserve the aortic valve. This technique is a valuable alternative to root replacement in appropriately chosen patients. The Florida sleeve is particularly advantageous for aortic valve salvage in cases of offset coronary arteries and bicuspid aortic valve. It has even become a useful option in carefully selected aortic dissection patients. Specific attention must be paid to inspection of the coronary artery relationship to commissures, circumferential dissection below the coronaries to allow passage of the sleeve graft and subcommissural suture placement to secure the graft in place. Aortic Sinuses Resection or External Support to Treat Aortic Root Aneurysm?Operative Techniques in Thoracic and Cardiovascular SurgeryVol. 26Issue 2PreviewThe modified Bentall procedure was the standard surgical treatment for aortic root aneurysm until 3 decades ago when an operation was introduced to preserve the aortic valve in these patients.1 We coined the term “aortic valve sparing operations” to differentiate them from aortic valve repair and proposed a classified in 2 basic types: reimplantation of the aortic valve and remodeling of the aortic root.2 Aortic valve sparing operations became increasingly more popular over time but were deemed complex and surgeons continued to search for simpler alternatives to preserve the native aortic valve in patients with aortic root aneurysms. Full-Text PDF

Biobleaching: An eco-friendly approach to reduce chemical consumption and pollutants generation

Abstract The pulp and paper industry is known to be a large contributor to environmental pollution due to the huge consumption of chemicals and energy. Several chemicals including H2SO4, Cl2, ClO2, NaOH, and H2O2 are used during the bleaching process. These chemicals react with lignin and carbohydrates to generate a substantial amount of pollutants in bleach effluents. Environmental pressure has compelled the pulp and paper industry to reduce pollutant generation from the bleaching section. Enzymes have emerged as simple, economical, and eco-friendly alternatives for bleaching of pulp. The pretreatment of pulp with enzymes is termed as biobleaching or pre-bleaching. Different microbial enzymes such as xylanases, pectinases, laccases, manganese peroxidases (MnP), and lignin peroxidases are used for biobleaching. Xylanases depolymerize the hemicelluloses precipitated on pulp fiber surfaces and improves the efficiency of bleaching chemicals. Xylanase treatment also increases the pulp fibrillation and reduces the beating time of the pulp. Pectinases hydrolyze pectin available in the pulp fibers and improve the papermaking process. Laccase treatment is found more effective along with mediator molecules (as a laccase-mediator system). Biobleaching of pulp results in the superior quality of pulp along with lower consumption of chlorine-based chemicals and lower generation of adsorbable organic halidesadsorbable organic halides (AOX. An enzyme pretreatment reduces the kappa number of pulp and improves ISO brightness significantly. Better physical strength properties and pulp viscosity have also been observed during biobleaching of pulp.

Bispectral analysis of overnight airflow to improve the pediatric sleep apnea diagnosis

Pediatric Obstructive Sleep Apnea (OSA) is a respiratory disease whose diagnosis is performed through overnight polysomnography (PSG). Since it is a complex, time-consuming, expensive, and labor-intensive test, simpler alternatives are being intensively sought. In this study, bispectral analysis of overnight airflow (AF) signal is proposed as a potential approach to replace PSG when indicated. Thus, our objective was to characterize AF through bispectrum, and assess its performance to diagnose pediatric OSA. This characterization was conducted using 13 bispectral features from 946 AF signals. The oxygen desaturation index ≥3% (ODI3), a common clinical measure of OSA severity, was also obtained to evaluate its complementarity to the AF bispectral analysis. The fast correlation-based filter (FCBF) and a multi-layer perceptron (MLP) were used for subsequent automatic feature selection and pattern recognition stages. FCBF selected 3 bispectral features and ODI3, which were used to train a MLP model with ability to estimate apnea-hypopnea index (AHI). The model reached 82.16%, 82.49%, and 90.15% accuracies for the common AHI cut-offs 1, 5, and 10 events/h, respectively. The different bispectral approaches used to characterize AF in children provided complementary information. Accordingly, bispectral analysis showed that the occurrence of apneic events decreases the non-gaussianity and non-linear interaction of the AF harmonic components, as well as the regularity of the respiratory patterns. Moreover, the bispectral information from AF also showed complementarity with ODI3. Our findings suggest that AF bispectral analysis may serve as a useful tool to simplify the diagnosis of pediatric OSA, particularly for children with moderate-to-severe OSA.

Magnetic nanocatalysts as multifunctional platforms in cancer therapy through the synthesis of anticancer drugs and facilitated Fenton reaction

BackgroundHeterocyclic compounds have always been used as a core portion in the development of anticancer drugs. However, there is a pressing need for developing inexpensive and simple alternatives to high-cost and complex chemical agents-based catalysts for large-scale production of heterocyclic compounds. Also, development of some smart platforms for cancer treatment based on nanoparticles (NPs) which facilitate Fenton reaction have been widely explored by different scientists. Magnetic NPs not only can serve as catalysts in the synthesis of heterocyclic compounds with potential anticancer properties, but also are widely used as smart agents in targeting cancer cells and inducing Fenton reactions. Aim of ReviewTherefore, in this review we aim to present an updated summary of the reports related to the main clinical or basic application and research progress of magnetic NPs in cancer as well as their application in the synthesis of heterocyclic compounds as potential anticancer drugs. Afterwards, specific tumor microenvironment (TME)-responsive magnetic nanocatalysts for cancer treatment through triggering Fenton-like reactions were surveyed. Finally, some ignored factors in the design of magnetic nanocatalysts- triggered Fenton-like reaction, challenges and future perspective of magnetic nanocatalysts-assisted synthesis of heterocyclic compounds and selective cancer therapy were discussed.Key Scientific Concepts of Review:This review may pave the way for well-organized translation of magnetic nanocatalysts in cancer therapy from the bench to the bedside.

Alzheimer's Gone Viral: Could Herpes Simplex Virus Type-1 Be Stealing Your Memories?

Alzheimer's disease (AD) is one of the principal causes of disability and morbidity. It is one of the most expensive illnesses. Despite this, there are no significant data regarding its etiology and optimal treatment. This review concentrates on the viral hypothesis of AD. After a comprehensive PubMed literature search, we analyzed the studies associating herpes simplex virus type-1 (HSV1) infection to AD from the previous 10 years. Molecular mechanisms whereby HSV1 induces AD-related pathophysiology, including neuronal production and accumulation of amyloid-beta (amyloid-β), abnormal phosphorylation of tau proteins, impaired calcium homeostasis, and autophagy, are addressed. The virus also imitates the disease in other ways, showing increased neuroinflammation, oxidative stress, synaptic dysfunction, and neuronal apoptosis. Serological studies correlate HSV1 infection with AD and cognitive impairment. A causal link between HSV1 and AD raises the concept of a simple, efficient, and preventive treatment alternative. Anti-viral agents impede brain degeneration by preventing HSV1 spread and its replication, decreasing hyperphosphorylated tau and amyloid-β; thus providing an efficacious treatment for AD. We also mention brown algae, intravenous immunoglobulin (IVIG), and a synthetic drug, BAY57-1293, with anti-viral properties, as options for treating AD. We want to recommend future researchers to look for more affordable, non-invasive, and swifter techniques to identify HSV1 in the brain and assist in the early detection and prevention of AD.

A new similarity measure for vector space models in text classification and information retrieval

There are various models, methodologies and algorithms that can be used today for document classification, information retrieval and other text mining applications and systems. One of them is the vector space–based models, where distance metrics or similarity measures lie at the core of such models. Vector space–based model is one of the fast and simple alternatives for the processing of textual data; however, its accuracy, precision and reliability still need significant improvements. In this study, a new similarity measure is proposed, which can be effectively used for vector space models and related algorithms such as k-nearest neighbours ( k-NN) and Rocchio as well as some clustering algorithms such as K-means. The proposed similarity measure is tested with some universal benchmark data sets in Turkish and English, and the results are compared with some other standard metrics such as Euclidean distance, Manhattan distance, Chebyshev distance, Canberra distance, Bray–Curtis dissimilarity, Pearson correlation coefficient and Cosine similarity. Some successful and promising results have been obtained, which show that this proposed similarity measure could be alternatively used within all suitable algorithms and models for information retrieval, document clustering and text classification.

Confidence regions and other tools for an extension of correspondence analysis based on cumulative frequencies

Over the past 50 years, correspondence analysis (CA) has increasingly been used by data analysts to examine the association structure of categorical variables that are cross-classified to form a contingency table. However, the literature has paid little attention to the case where the variables are ordinal. Indeed, Pearson’s chi-squared statistic $$X^{2}$$ can perform badly in studying the association between ordinal categorical variables (Agresti in An introduction to categorical data analysis, Wiley, Hoboken, 1996; Barlow et al. in Statistical inference under order restrictions, Wiley, New York, 1972). Taguchi’s (Nair in Technometrics 28(4):283–291, 1986; Nair in J Am Stat Assoc 82:283–291, 1987) and Hirotsu’s (Biometrika 73: 165–173, 1986) statistics have been introduced in the literature as simple alternatives to Pearson’s index for contingency tables with ordered categorical variables. Taguchi’s statistic takes into account the presence of an ordinal categorical variable by considering the cumulative sum of the cell frequencies across the variable. An extension of correspondence analysis using a decomposition of Taguchi’s statistic has been introduced to accommodate this feature of the variables. This considers the impact of differences between adjacent ordered categories on the association between row and column categories. Therefore, the main aim of this paper is to introduce a confidence region for each of the ordered categories so that one may determine the statistical significance of a category with respect to the null hypothesis of independence. We highlight that the construction of these circles has not been considered in the literature for this approach to CA. We also introduce a suitable decomposition of Taguchi’s statistic to test the statistical significance of each column category.

Alternative fabrication methodologies for two-dimensional self-assembled Inorganic-Organic hybrid semiconductors

This report presents the structural and optical properties of(R-NH 3 ) 2 PbI 4 type Inorganic-Organic (IO) hybrids, prepared from alternative fabrication techniques, without any excess usage of Iodine. The fabrication relies on common deposition techniques viz., thermal vacuum deposition, electrochemical deposition, and spincoating. The resulting two-dimensional (2D) structures are alternatively stacked-up along c-axis by inorganic (PbI 6 extended network) layers with organic (R–NH 3 ) - moieties as spacers. These hybrids show strong room-temperature exciton features confined within the lowest inorganic bandgap. The proposed methodologies are simple alternatives to the conventional multi-step fabrication methodologies and are directly applicable to varieties of IO hybrids of different dimensionalities for various optoelectronic applications. • Novel methodologies for IO hybrids without metal halide and excess of halide usage. • Efficient direct conversion of pure Pb metal films into perfect layered 2D IO hybrids. • Nano and microcrystal fabrication from lead acetate based electrodeposition. • Strong room-temperature exciton photoluminescence from IO hybrids is demonstrated.

Propriedades físicas de óleos essenciais: Uma ferramenta experimental no ensino de Química

As atividades experimentais representam recurso indiscutível no processo ensino – aprendizagem. Para alunos de graduação essas práticas se tornam mais eficientes quando tratadas de forma contextualizada. Métodos físicos de análises são alternativas simples, de baixo custo e rápidas na verificação da autenticidade de óleos essenciais com alto valor comercial, além de oferecer didática experimental que facilita o aprendizado de discentes dos cursos de química e áreas afins. Entre os parâmetros físicos destacam-se densidade, índice de refração e rotação óptica, que regulamentam a comercialização de fitoterápicos no Brasil. O presente estudo tem como objetivo fornecer alternativas de atividade experimental no ensino de química voltado para aplicação prática relacionada a regulamentação na comercialização de óleo essencial com alto valor agregado e produção científica na área. Os óleos essenciais foram obtidos por hidrodestilação. A densidade, o índice de refração e a rotação específica foram medidos em aparelhos específicos. O óleo essencial de candeeiro obteve maior rotação específica (-58,75° à -59,25°). O índice de refração foi maior para o pau-de-óleo (1,501560 ± 0,000000 nD). A densidade foi superior para o óleo essencial da marangaba vermelha (0,98 ±0,015 g/mL). Alterações na composição química de óleos essenciais apresentam mudanças significativas nas suas propriedades físicas, estas podem ser facilmente identificadas com a ajuda de aparelhos de fácil acesso e manuseio, garantindo eficiência das suas propriedades biológicas. Os estudantes, podem desenvolver habilidades profissionais para identificação dessas características, possibilidade esta, que representa motivação no processo de ensino-aprendizagem.

Triglyceride-to-high density lipoprotein cholesterol ratio and triglyceride-glucose index in the perinatal period of neonates

Background Environmental factors and growth disturbances, either intra-uterine, or post-natal, can result in permanent changes in tissues and also long-term effects that may present themselves as pathological conditions in adulthood, including increased incidence of insulin resistance, impaired glucose tolerance, and also higher likelihood for diabetes mellitus. The triglyceride to glucose index (TyG) and triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-c) have been proposed as reliable and simple alternatives for the evaluation of insulin resistance. To date, there was limited data regarding the TyG index and TG/HDL-c ratio in the perinatal period of neonates. We aimed to investigate the possible relationships between HOMA-IR, TyG index, and TG/HDL-c in the cord blood of neonates.Materials-Methods One hundred and six pregnant women with singleton gestation who gave birth to full-term, normal-weight Turkish neonates without fetal distress were included in the study. The samples of maternal serum and cord blood in neonates were obtained after delivery.Results Mean TyG index was 3.71 ± 0.38 and the mean TG/HDL-c ratio was 3.12 ± 3.00 in this group. Correlations were found between maternal age and neonate glucose levels and HOMA-IR (p < .05). HOMA-IR was negatively correlated with triglyceride, TG/HDL-c ratio, TyG index + TG/HDL, and positively correlated with HDL and TyG index.Conclusions Our study indicates that the TyG index and TG/HDL-C may be used as an indicator of insulin sensitivity in the perinatal period of neonates. However, the validity of these results should be tested in other centers with a larger neonate population in order to evaluate whether ethnic and racial diversity influence these relationships.

Electroporation-Based Treatments in Small Animal Veterinary Oral and Maxillofacial Oncology.

Electroporation is a method of inducing an increase in permeability of the cell membrane through the application of an electric field and can be used as a delivery method for introducing molecules of interest (e.g., chemotherapeutics or plasmid DNA) into cells. Electroporation-based treatments (i.e., electrochemotherapy, gene electrotransfer, and their combinations) have been shown to be safe and effective in veterinary oncology, but they are currently mostly recommended for the treatment of those solid tumors for which clients have declined surgery and/or radiotherapy. Published data show that electroporation-based treatments are also safe, simple, fast and cost-effective treatment alternatives for selected oral and maxillofacial tumors, especially small squamous cell carcinoma and malignant melanoma tumors not involving the bone in dogs. In these patients, a good local response to treatment is expected to result in increased survival time with good quality of life. Despite emerging evidence of the clinical efficacy of electroporation-based treatments for oral and maxillofacial tumors, further investigation is needed to optimize treatment protocols, improve clinical data reporting and better understand the mechanisms of patients' response to the treatment.

Hopf superpolynomial from topological vertices

Link/knot invariants are series with integer coefficients, and it is a long-standing problem to get them positive and possessing cohomological interpretation. Constructing positive “superpolynomials” is not straightforward, especially for colored invariants. A simpler alternative is a multi-parametric generalization of the character expansion, which leads to colored “hyperpolynomials”. The third construction involves branes on resolved conifolds, which gives rise to still another family of invariants associated with composite representations. We revisit this triality issue in the simple case of the Hopf link and discover a previously overlooked way to produce positive colored superpolynomials from the DIM-governed four-point functions, thus paving a way to a new relation between super- and hyperpolynomials.

Inhibitors of Tumor Necrosis Factor Synthesis as a New Approach for theTreatment of Rheumatoid Arthritis

Objective: The treatment of rheumatoid arthritis (RA) is based on the inhibition of TNF. Here we evaluated whether drugs that might inhibit TNF, such as pentoxifylline (PTX), rupatadine (RUP), rolipram (ROL) and thalidomide (THA), could be an alternative for RA treatment. Methods: In wistar male rats the changes in paw thickness, plasma TNF and by the activity of basic aminopeptidase (APB) in soluble fraction of synovial tissue and peripheral blood mononuclear cells (PBMC) evaluated after daily injection for 30 days were taken as anti-inflammatory outputs, while hepatotoxicity was assessed by measuring plasma alanine transaminase (ALT) and aspartate transaminase (AST) activity. The content of IL1-?, IL-6 in serum and synovial fluid and the histology of the injured tissue were determined only for ROL, THA and ROL+THA. Prednisolone was used as a standard drug. Results: Collagen treatment induced paw thickness, histological changes in the tibiotarsal joint, increase in synovial fluid of both cytokines and synovial tissue of APB activity. Furthermore, the APB activity in PBMC was reduced and ALT and AST activity were enhanced. The most effective drug schedule in reducing arthritis induced changes described above, as well as recovering from control levels TNF, IL1-β, APB in synovial tissue and AST activities were THA and the association of ROL and THA. However, only THA alone reduced the levels of ALT. Conclusion: The synthesis of TNF in RA models can be blocked by drugs acting at different targets. We show that THA and THA+ROL emerges as simple and effective therapeutic alternatives for RA.