Comparing artificial intelligence to humans for endoscopic diagnosis of gastric neoplasia: An external validation study.

OBJECTIVES: Artificial intelligence (AI) uses deep learning functionalities that may enhance the detection of early gastric cancer during endoscopy. An AI-based endoscopic system for upper endoscopy was recently developed in Japan. We aim to validate this AI-based system in a Singaporean cohort. METHODS: There were 300 de-identified still images prepared from endoscopy video files obtained from subjects that underwent gastroscopy in National University Hospital (NUH). Five specialists and 6 non-specialists (trainees) from NUH were assigned to read and categorize the images into "neoplastic" or "non-neoplastic." Results were then compared with the readings performed by the endoscopic AI system. RESULTS: The mean accuracy, sensitivity, and specificity for the 11 endoscopists were 0.847, 0.525, and 0.872, respectively. These values for the AI-based system were 0.777, 0.591, and 0.791, respectively. While AI in general did not perform better than endoscopists on the whole, in the subgroup of high-grade dysplastic lesions, only 29.1% were picked up by the endoscopist rating, but 80% were classified as neoplastic by AI (P = 0.0011). The average diagnostic time was also faster in AI compared with endoscopists (677.1 s vs 42.02 s (P < 0.001). CONCLUSION: We demonstrated that an AI system developed in another health system was comparable in diagnostic accuracy in the evaluation of static images. AI systems are faster and not fatigable and may have a role in augmenting human diagnosis during endoscopy. With more advances in AI and larger studies to support its efficacy it would likely play a larger role in screening endoscopy in future.

Ceria Nanoparticle Systems for Selective Scavenging of Mitochondrial, Intracellular, and Extracellular Reactive Oxygen Species in Parkinson's Disease.

Oxidative stress induced by reactive oxygen species (ROS) is one of the critical factors that involves in the pathogenesis and progression of many diseases. However, lack of proper techniques to scavenge ROS depending on their cellular localization limits a thorough understanding of the pathological effects of ROS. Here, we demonstrate the selective scavenging of mitochondrial, intracellular, and extracellular ROS using three different types of ceria nanoparticles (NPs), and its application to treat Parkinson's disease (PD). Our data show that scavenging intracellular or mitochondrial ROS inhibits the microglial activation and lipid peroxidation, while protecting the tyrosine hydroxylase (TH) in the striata of PD model mice. These results indicate the essential roles of intracellular and mitochondrial ROS in the progression of PD. We anticipate that our ceria NP systems will serve as a useful tool for elucidating the functions of various ROS in diseases.

Ceria-Zirconia Nanoparticles as an Enhanced Multi-Antioxidant for Sepsis Treatment.

The two oxidation states of ceria nanoparticles, Ce3+ and Ce4+ , play a pivotal role in scavenging reactive oxygen species (ROS). In particular, Ce3+ is largely responsible for removing O2- and . OH that are associated with inflammatory response and cell death. The synthesis is reported of 2 nm ceria-zirconia nanoparticles (CZ NPs) that possess a higher Ce3+ /Ce4+ ratio and faster conversion from Ce4+ to Ce3+ than those exhibited by ceria nanoparticles. The obtained Ce0.7 Zr0.3 O2 (7CZ) NPs greatly improve ROS scavenging performance, thus regulating inflammatory cells in a very low dose. Moreover, 7CZ NPs are demonstrated to be effective in reducing mortality and systemic inflammation in two representative sepsis models. These findings suggest that 7CZ NPs have the potential as a therapeutic nanomedicine for treating ROS-related inflammatory diseases.

Consumer acceptance of dishes in which beef has been partially substituted with mushrooms and sodium has been reduced.

We tested the hypothesis that because of their flavor-enhancing properties, mushrooms could be used as a healthy substitute for meat and a mitigating agent for sodium (salt) reduction without reduction in sensory appeal among consumers. In a fully-randomized design for each product, 147 consumers evaluated blind two carne asada and six taco blend recipes in which beef had been partially substituted with mushrooms and/or salt had been reduced by 25%, for overall liking, liking of appearance, flavor, texture and mouth feel on the 9-point hedonic scale, and adequacy of level of saltiness, spiciness and moistness on 5-point just-about-right (JAR) scales. Overall consumer acceptance of the carne asada, and liking for its appearance, flavor and texture/mouth feel decreased significantly when half the steak was substituted with mushrooms. The taco blend recipes with full sodium were also liked more overall than those with 25% less sodium. But there was no significant difference in overall liking among the three full-salt recipes, nor among the three reduced-salt recipes, indicating that across the consumer population we tested, acceptance of the mushroom-containing recipes was on par with that of the 100% beef recipe. The preference mapping analysis of the overall liking ratings of the taco blends uncovered four preference segments, two of which, representing a majority of the consumers, gave higher acceptance scores to the mushroom-substituted recipes. Furthermore, the largest preference segment liked the full- and reduced-sodium recipes equally, and another liked the reduced-sodium recipes significantly more. This research demonstrates that through their flavor enhancing properties, mushrooms can be used successfully to substitute for beef and even possibly mitigate sodium reduction without significant change in acceptance for a majority of consumers.

Age and gender differences in the influence of extrinsic product information on acceptability for RTD green tea beverages.

BACKGROUND: The introduction of ready-to-drink (RTD) green tea beverage has allowed diverse consumers to consume green teas and related products. Green tea that has been traditionally consumed for its delicate flavor characteristics is also widely consumed for its recognition as a healthy product. Because it is reported that age difference exists in consideration of health-related information, the objective of the study was to investigate how sensory and non-sensory factors, in particular health-related information, price and packaging, would affect the flavor acceptability of green tea beverages, depending on consumers' age and gender. RESULTS: Regardless of the product information, old consumers preferred products that provided an indication of health beneficial effect. On the other hand, young consumers tended to be influenced by extrinsic product information such as packaging, brand/manufacturer and/or price, though these consumers were not so much influenced by health beneficial information as were the old consumers. CONCLUSION: The findings of the study implied that the influence of non-sensory information such as health beneficial information in flavor liking differed depending mostly on consumers' age, and little on gender, for RTD green tea beverages.

Modified complete mesocolic excision with central vascular ligation for the treatment of right-sided colon cancer: long-term outcomes and prognostic factors.

OBJECTIVE: To investigate the long-term oncologic outcomes and risk factors for adverse effects in right-sided colon cancer patients who underwent modified complete mesocolic excision (mCME). BACKGROUND: Complete mesocolic excision (CME) with central vascular ligation has recently been found to improve oncological outcomes in patients with colon cancer. Our institution has established mCME on the basis of the original concept of CME for the treatment of right-sided colon cancer. METHODS: Between January 2000 and July 2009, 773 patients who underwent mCME for right-sided colon cancer were eligible for this retrospective study. The prognostic factors for survival/recurrence and the risk factors for postoperative complications were investigated. RESULTS: The mean follow-up period was 61.9 ± 34.7 months. The 5-year overall survival and 5-year disease-free survival rates were 84.0% and 82.8%, respectively. Pathologic stage III disease, postoperative complications, age more than 60 years, and minimally invasive surgery were found to be independent prognostic factors. The 5-year locoregional recurrence (LRR) and 5-year systemic recurrence rates (SRRs) were 4.9% and 13.7%, respectively. The risk of LRR and SRR increased with pathologic stage III disease. An American Society of Anesthesiology score of higher than II was an independent predictive factor of postoperative complications. CONCLUSIONS: We have successfully established the mCME technique, on the basis of the same principle as CME, but with a more tailored approach. The long-term oncologic outcomes and risk of postoperative morbidity were found to be comparable with those seen with the original CME procedure.

Ceria-Based Therapeutic Antioxidants for Biomedical Applications.

The growing interest in nanomedicine over the last 20 years has carved out a research field called "nanocatalytic therapy," where catalytic reactions mediated by nanomaterials are employed to intervene in disease-critical biomolecular processes. Among many kinds of catalytic/enzyme-mimetic nanomaterials investigated thus far, ceria nanoparticles stand out from others owing to their unique scavenging properties against biologically noxious free radicals, including reactive oxygen species (ROS) and reactive nitrogen species (RNS), by exerting enzyme mimicry and nonenzymatic activities. Much effort has been made to utilize ceria nanoparticles as self-regenerating antioxidative and anti-inflammatory agents for various kinds of diseases, given the detrimental effects of ROS and RNS therein that need alleviation. In this context, this review is intended to provide an overview as to what makes ceria nanoparticles merit attention in disease therapy. The introductory part describes the characteristics of ceria nanoparticles as an oxygen-deficient metal oxide. The pathophysiological roles of ROS and RNS are then presented, as well as their scavenging mechanisms by ceria nanoparticles. Representative examples of recent ceria-nanoparticle-based therapeutics are summarized by categorization into organ and disease types, followed by the discussion on the remaining challenges and future research directions.

Ceria Nanoparticles as Copper Chaperones that Activate SOD1 for Synergistic Antioxidant Therapy to Treat Ischemic Vascular Diseases.

All exogenous nanomaterials undergo rapid biotransformation once injected into the body and fall short of executing the intended purpose. Here, it is reported that copper-deposited ceria nanoparticles (CuCe NPs) exhibit enhanced antioxidant effects over pristine ceria nanoparticles, as the released copper buffers the depletion of glutathione while providing the bioavailable copper as a cofactor for the antioxidant enzyme, superoxide dismutase 1. The upregulated intracellular antioxidants along with the ceria nanoparticles synergistically scavenge reactive oxygen species and promote anti-inflammation and M2 polarization of macrophages by modulating signal transducer and activator of transcription 1 and 6 (STAT1 and STAT6). The therapeutic effect of CuCe NPs is demonstrated in ischemic vascular diseases (i.e., murine models of hindlimb ischemia and myocardial infarction) in which the copper-deposition affords increased perfusion and alleviation in tissue damage. The results provide rationale that metal oxide nanomaterials can be designed in a way to induce the upregulation of specific biological factors for optimal therapeutic performance.

Ceria-vesicle nanohybrid therapeutic for modulation of innate and adaptive immunity in a collagen-induced arthritis model.

Commencing with the breakdown of immune tolerance, multiple pathogenic factors, including synovial inflammation and harmful cytokines, are conjointly involved in the progression of rheumatoid arthritis. Intervening to mitigate some of these factors can bring a short-term therapeutic effect, but other unresolved factors will continue to aggravate the disease. Here we developed a ceria nanoparticle-immobilized mesenchymal stem cell nanovesicle hybrid system to address multiple factors in rheumatoid arthritis. Each component of this nanohybrid works individually and also synergistically, resulting in comprehensive treatment. Alleviation of inflammation and modulation of the tissue environment into an immunotolerant-favourable state are combined to recover the immune system by bridging innate and adaptive immunity. The therapy is shown to successfully treat and prevent rheumatoid arthritis by relieving the main symptoms and also by restoring the immune system through the induction of regulatory T cells in a mouse model of collagen-induced arthritis.

Ceria nanoparticles that can protect against ischemic stroke.

Uniform 3 nm-sized ceria nanoparticles can protect against ischemic stroke by scavenging reactive oxygen species (ROS) and reducing apoptosis. PEGylated ceria nanoparticles showed protective effects against ROS-induced cell death in vitro. Optimal doses of ceria nanoparticles reduced infarct volumes and the rate of ischemic cell death in vivo.

Evaluation of the Cadi ThermoSENSOR wireless skin-contact thermometer against ear and axillary temperatures in children.

The Cadi ThermoSENSOR skin-contact thermometer measures body temperature continuously and transmits readings wirelessly to a central server. This study evaluated the ThermoSENSOR against ear temperatures (ETs) measured by a Braun ThermoScan ear thermometer and axillary temperatures (ATs) measured by a Terumo digital clinical thermometer. The test participants consisted of 109 children aged 6 months to 16 years from a pediatric ward. The sensor was attached to the lower abdomen at least 15 minutes before the first measurement. ET, AT, and ThermoSENSOR temperatures (TTs) were recorded up to three times at the usual measurement times. The TTs differed from ETs by -0.23 degrees C +/- 0.47 degrees C (mean +/- standard deviation, n = 271) and from ATs by +0.21 degrees C +/- 0.46 degrees C (n = 270). The ETs differed from ATs by +0.43 degrees C +/- 0.42 degrees C (n = 315). These results suggest that the TTs were comparable to the ETs and ATs.

Detection of Malingering Using Wechsler Adult Intelligence Scale-IV for Psychiatric Patients.

OBJECTIVE: Psychiatric patients sometimes show poor performance or exaggerated symptoms as malingering for secondary gain. The aim of this study was to introduce cut-off scores for detecting poor performance using Wechsler Adult Intelligence Scale (WAIS) in psychiatric patients. METHODS: Participants were 261 in- and out-patients who visited psychiatry department. They were classified into 4 group- 1) military service, 2) traumatic brain injury (TBI), 3) psychosis, 4) neurosis. A Digit Span subtest (called as Reliable Digit Span, RDS) of WAIS was used to detect malingering. This study considered a score of 10% base rate as RDS cut-off score. RESULTS: The RDS cut-off score was shown at 7 pts for military service group, at 3 pts for TBI group, at 6 pts for psychosis group, and at 6 pts for neurosis group. CONCLUSION: This study first introduced RDS cut-off scores for malingering psychiatric patients in South Korea. In clinical practice, clinicians may be able to utilize the RDS cut-off scores for malingering-suspected patients. In particular, for patients with military service issues, 7 or less pts of RDS can be used for detecting and inferring their malingering.

Epitaxially Strained CeO2 /Mn3 O4 Nanocrystals as an Enhanced Antioxidant for Radioprotection.

Nanomaterials with antioxidant properties are promising for treating reactive oxygen species (ROS)-related diseases. However, maintaining efficacy at low doses to minimize toxicity is a critical for clinical applications. Tuning the surface strain of metallic nanoparticles can enhance catalytic reactivity, which has rarely been demonstrated in metal oxide nanomaterials. Here, it is shown that inducing surface strains of CeO2 /Mn3 O4 nanocrystals produces highly catalytic antioxidants that can protect tissue-resident stem cells from irradiation-induced ROS damage. Manganese ions deposited on the surface of cerium oxide (CeO2 ) nanocrystals form strained layers of manganese oxide (Mn3 O4 ) islands, increasing the number of oxygen vacancies. CeO2 /Mn3 O4 nanocrystals show better catalytic activity than CeO2 or Mn3 O4 alone and can protect the regenerative capabilities of intestinal stem cells in an organoid model after a lethal dose of irradiation. A small amount of the nanocrystals prevents acute radiation syndrome and increases the survival rate of mice treated with a lethal dose of total body irradiation.

Cognitive Decline in Korean Patients with Neurocognitive Disorder due to Traumatic Brain Injury: A Control for Premorbid Intelligence.

OBJECTIVE: Previous studies of cognitive decline in patients with neurocognitive disorder due to traumatic brain injury (NCD-TBI) have often failed to control for baseline factors such as premorbid intelligence. The purpose of the current study was to estimate and compare cognitive function among three groups (controls, complicated mild/moderate TBI, and severe TBI) after controlling for premorbid intelligence. METHODS: Severity of TBI was classified as complicated mild/moderate or severe based on duration of loss of consciousness and brain neuroimaging results. Premorbid intelligence quotients (IQs) were estimated with the Oklahoma Premorbid Intelligence Estimate. There were no differences in premorbid intelligence between the groups, which were also matched for age and education. Current cognitive function was evaluated with the Wechsler Adult Intelligence Scale-Fourth Edition. RESULTS: Comparison of current cognitive function among the three groups indicated significant group differences for all indexes and subtest scores. Processing speed showed the highest effect size. However, only working memory differed significantly between the two NCD-TBI groups. CONCLUSION: The present findings suggest that mental memory manipulation processes seem to be more sensitive to TBI severity than are perceptual-motor processes. Specifically, both auditory rehearsal/discrimination and mental alertness/manipulation will be most strongly influenced by TBI severity.

Investigation on the Intrinsic Potential of Using Potassium Chloride for Partially Replacing NaCl in Kimchi and the Effect of Information on Consumer Acceptance of Sodium-Reduced Kimchi According to Age.

The high sodium content of kimchi is a contradicting factor from its fame as a healthy food. With the aim of reducing the sodium content of kimchi, the objective of this study was to understand the effect of providing "sodium-reduced" information on the acceptance of kimchi according to the age of consumption. Six sodium-reduced kimchi samples, prepared with different percentages of sodium reduction (25% and 50%) and potassium chloride concentration (none, 0.47%, and 0.93%), were compared to control kimchi (2.0% w/v NaCl). Sensory characterization of the samples was obtained using descriptive analysis. A total of 167 kimchi consumers with balanced proportion of the young (below 40) and the old (above 40) evaluated seven kimchi samples in either of the two conditions: blind testing condition or informed testing condition where each of the samples was provided with a label that informed about "sodium reduction percentage" and "whether a salt replacer was used or not." The results showed that in terms of healthiness perception, Korean female consumers believed that kimchi with a high sodium reduction rate would contribute to health in general, though an unfavorable notion of using a salt replacer was also observed. Also, the results suggested that promoting information about sodium reduction in kimchi would generally increase consumer acceptance. However, this phenomenon was influenced not only by the sample for which the information was provided, but also by the age of consumers with different health interests and kimchi experience. PRACTICAL APPLICATION: The findings of this study showed simply reducing sodium and promoting it with a health claim showed limitation in achieving a high level of sodium reduction, such as a 50% reduction rate, which implied the importance of using supplementary material such as potassium chloride that can fulfill the missing saltiness and flavors of the original product. Promotion of "sodium-reduced" claims in kimchi generally results in increased consumer acceptance. However, the effectiveness of the information was dependent on which sample was provided and the age of the consumers, among whom health interests and kimchi experience differ.

Sensory Properties and Consumer Acceptance of Cantaloupe Melon Cultivars.

This research measured the sensory characteristics and consumer acceptance of 15 cultivars of cantaloupe. Eleven trained panelists assessed melons by descriptive analysis. Northern California consumers (n = 171) evaluated the melons for overall, appearance, flavor, and texture liking on the 9-point hedonic scale and the adequacy of ripeness, sweetness, and firmness on a 5-point just-about-right (JAR) scale. Twenty-two sensory attributes differed significantly among the melons. CaldeoDF, Caldeo, Globstar, RML0499, and Caribbean Gold showed higher firmness, crunchiness, and denser textures. Impac presented higher watermelon flavor, bitterness, and sourness. Caldeo, CaldeoDF, Globstar, Magellan, and Sol Real had higher overall intensity, sweetness and oversweet flavor, longer-lasting aftertaste, and salivating mouthfeel. Consumers liked Magellan, Acclaim, and Primo most, and Aphrodite and Impac least, and the harvesting period was not critical to consumer acceptance. Sweet, oversweet flavor, and intense orange and richness of color were drivers of overall liking. Preference clustering identified three groups of consumers with distinct sensory preferences and favorite cultivars. JAR data showed Acclaim, Magellan, Primo, and Saguaro were just right for ripeness and so was Acclaim for firmness. All melons were judged not sweet enough. Growers and distributors could use the information from this research to improve the quality and appeal of the cantaloupe melon offering in the United States. PRACTICAL APPLICATION: We profiled the sensory attributes and measured consumer liking of 15 cantaloupe cultivars. Our findings should benefit producers and consumers equally as they identified those cultivars with the most promising sensory traits and they uncovered preference segments among a population of Northern California consumers as well as drivers of liking for those segments.

Highly selective microglial uptake of ceria-zirconia nanoparticles for enhanced analgesic treatment of neuropathic pain.

Neuropathic pain is a chronic and pathological pain caused by injury or dysfunction in the nervous system. Pro-inflammatory microglial activation with aberrant reactive oxygen species (ROS) generation in the spinal cord plays a critical role in the development of neuropathic pain. However, the efficacy of current therapeutic methods for neuropathic pain is limited because only neurons or neural circuits involved in pain transmission are targeted. Here, an effective strategy to treat pain hypersensitivity using microglia-targeting ceria-zirconia nanoparticles (CZ NPs) is reported. The CZ NPs are coated with microglia-specific antibodies to promote their delivery to microglia, and thus to improve their therapeutic efficacy. The targeted delivery facilitates the elimination of both pro-inflammatory cytokines and ROS in microglia, enabling the rapid and effective inhibition of microglial activation. As a result, greatly ameliorated mechanical allodynia is achieved in a spinal nerve transection (SNT)-induced neuropathic pain mouse model, proving the potent analgesic effect of the microglia-targeting CZ NPs. Given the generality of the approach used in this study, the microglia-targeting CZ NPs are expected to be useful for the treatment of not only neuropathic pain but also other neurological diseases associated with the vicious activation of microglia.

Large scale and integrated platform for digital mass culture of anchorage dependent cells.

Industrial applications of anchorage-dependent cells require large-scale cell culture with multifunctional monitoring of culture conditions and control of cell behaviour. Here, we introduce a large-scale, integrated, and smart cell-culture platform (LISCCP) that facilitates digital mass culture of anchorage-dependent cells. LISCCP is devised through large-scale integration of ultrathin sensors and stimulator arrays in multiple layers. LISCCP provides real-time, 3D, and multimodal monitoring and localized control of the cultured cells, which thereby allows minimizing operation labour and maximizing cell culture performance. Wireless integration of multiple LISCCPs across multiple incubators further amplifies the culture scale and enables digital monitoring and local control of numerous culture layers, making the large-scale culture more efficient. Thus, LISCCP can transform conventional labour-intensive and high-cost cell cultures into efficient digital mass cell cultures. This platform could be useful for industrial applications of cell cultures such as in vitro toxicity testing of drugs and cosmetics and clinical scale production of cells for cell therapy.

[Standardized access options for colorectal surgery with the da Vinci Xi system]. / Standardisierte Zugangsoptionen für die kolorektale Chirurgie mit dem Da-Vinci-Xi-System.

BACKGROUND: Performing colorectal surgery with previous da Vinci system generations presented some limitations that caused uncertainty for surgeons as they began to apply robotic technologies. The da Vinci Xi system is designed to overcome these limitations and to enable multiquadrant colorectal surgery. OBJECTIVE: The design concept of the da Vinci Xi system and the standardized access for colorectal surgery are explained. MATERIAL AND METHODS: The da Vinci Xi system applies an overhead boom that maximizes the arm workspace, minimizes interference and makes the port placement universal for standardized access. Colorectal approaches have been validated in numerous cadaver models confirming the reproducibility of the standardized access. RESULTS: Standardized access with a straight-line port placement is possible in all colorectal applications. For right-sided hemicolectomy, a transverse abdominal approach as well as a suprapubic port placement are possible. Utilizing the same principles, left-sided colectomy, sigmoid colectomy and low anterior resections can be performed. Proctocolectomy is enabled through boom rotation and a second docking. Only minor arm-to-arm interferences occurred and were easily manageable by the bedside assistant. None of the approaches required rearrangement of the patient cart or swapping arms to different port locations. CONCLUSION: The da Vinci Xi system enables a standardized access for colorectal surgery through a universal straight-line port placement. Learning this standard principle once enables the surgeon to apply it to all colorectal surgeries and shorten the learning curve as well as minimizing stress for both novices and experienced robotic surgeons learning a new surgical robotic platform.

Synergistic Oxygen Generation and Reactive Oxygen Species Scavenging by Manganese Ferrite/Ceria Co-decorated Nanoparticles for Rheumatoid Arthritis Treatment.

Poor O2 supply to the infiltrated immune cells in the joint synovium of rheumatoid arthritis (RA) up-regulates hypoxia-inducible factor (HIF-1α) expression and induces reactive oxygen species (ROS) generation, both of which exacerbate synovial inflammation. Synovial inflammation in RA can be resolved by eliminating pro-inflammatory M1 macrophages and inducing anti-inflammatory M2 macrophages. Because hypoxia and ROS in the RA synovium play a crucial role in the induction of M1 macrophages and reduction of M2 macrophages, herein, we develop manganese ferrite and ceria nanoparticle-anchored mesoporous silica nanoparticles (MFC-MSNs) that can synergistically scavenge ROS and produce O2 for reducing M1 macrophage levels and inducing M2 macrophages for RA treatment. MFC-MSNs exhibit a synergistic effect on O2 generation and ROS scavenging that is attributed to the complementary reaction of ceria nanoparticles (NPs) that can scavenge intermediate hydroxyl radicals generated by manganese ferrite NPs in the process of O2 generation during the Fenton reaction, leading to the efficient polarization of M1 to M2 macrophages both in vitro and in vivo. Intra-articular administration of MFC-MSNs to rat RA models alleviated hypoxia, inflammation, and pathological features in the joint. Furthermore, MSNs were used as a drug-delivery vehicle, releasing the anti-rheumatic drug methotrexate in a sustained manner to augment the therapeutic effect of MFC-MSNs. This study highlights the therapeutic potential of MFC-MSNs that simultaneously generate O2 and scavenge ROS, subsequently driving inflammatory macrophages to the anti-inflammatory subtype for RA treatment.