September 2020 review byTheodore R. Fields, MD, FACP. SelfDecode has the strictest sourcing guidelines in the health industry and we almost exclusively link to medically peer-reviewed studies, usually on PubMed. [25] 14-3-3 (YWHAH) is also another synovial derived protein that has been reported as a citrullination target. 7. We use cookies to ensure that we give you the best experience on our website. This process may well be the cause of the inflammatory process since citrullinated proteins and the enzymes responsible for producing them are found in inmflamed synovium. Natural Factors That May Decrease Inflammation in Joint Disease, Joe Cohen flipped the script on conventional and alternative medicine and it worked. Gardette A, Ottaviani S, Tubach F, Roy C, Nicaise-Roland P, Palazzo E, Gill G, Meyer O, Dieud P. High anti-CCP antibody titres predict good response to rituximab in patients with active rheumatoid arthritis. 2023 HealthCheckUp.com. Most patients with rheumatoid arthritis have anti-cyclic citrullinated peptide (anti-CCP). Some conditions and medical procedures that can raise RF levels include: other autoimmune diseases, certain chronic infections, diabetes, bacterial endocarditis, cancer, normal aging, vaccinations and transfusions. A complete metabolic panel measures sodium (Na), potassium (K), chloride, glucose, creatinine (a measure of kidney function), and AST and ALT (markers of liver function). In case studies, higher omega-3 fatty acid levels are associated with a lower risk of anti-CCP antibody production [18, 19]. Treatment for RA is based on the whole picture, not just one score or symptom. It is fairly common to have a general feeling of not being well if rheumatoid arthritis is present as well. When a patient is positive for Anti-CCP and RF, it is likely they have RA and may be more likely to have a more rapidly progressing and severe form of the disease. Los anticuerpos nos protegen de las enfermedades combatiendo sustancias extraas como los virus y las bacterias. In July 2010, the 2010 ACR/EULAR Rheumatoid Arthritis Classification Criteria were introduced. Some research suggests that oral bacteria such as P. gingivalis directly contribute to the development of rheumatoid arthritis [9]. While a high CCP may mean a possibly aggressive disease course, it must be looked at with the amount of swelling, inflammation in the blood, and the number of joints involved. The higher the levels of anti-CCP antibody, the more likely it is to suggest RA. This usually takes less than five minutes. A blood sample is required for a CCP antibody test. This marker can indicate the level of inflammation in your body. Anti-CCP antibody may be associated with a higher incidence of ILD in SSc. Available from: University of Rochester Medical Center [Internet]. Perhaps you need to be on other medicines for this condition. Anti-CCP: Anti-Cyclic Citrullinated Peptide Antibody Also known as Anti-Citrullinated Protein Antibody (ACPA) Useful in diagnosis and prognosis of rheumatoid arthritis (RA) Newest anti-CCP assay yields a specificity of 98%, the sensitivity of 80% for RA Present in 70% of patients with established RA What is Anti-CCP? Joe Cohen flipped the script on conventional and alternative medicineand it worked. As well, it. Diagnosing and managing RA involves clinical evaluation by a rheumatologist, as well as several different laboratory tests that require blood work. While additional pulmonary evaluation was being planned, a few . This test is performed by drawing a blood sample from the patient. Underlying gum disease and poor dental hygiene are associated with rheumatoid arthritis and high anti-CCP levels. [3], In a comparative study (in 2007), various detection kits had a sensitivity between 69.6% and 77.5% and a specificity between 87.8% and 96.4%. This will allow your doctor to detect whether anti-CCP is present in your body. A CCP antibody test requires a blood sample. Epub 2014 Jul 3. Contact a health care provider if you have questions about your health. [6][17] Noteworthy are the findings of a recently published study that highly valuates anti-MCV test systems for diagnosing rheumatoid arthritis in anti-CCP-negative patients. Health Encyclopedia: CCP; [cited 2020 Feb 12]; [about 2 screens]. If high levels of anti-CCP (above 500 IU/ml) were included in the model instead of the categorical anti-CCP variable, the results became similar (data not shown). Anti-MCV titers are distributed more homogenously (from low to very high titers) and are better suited than anti-CCP to measure disease activity. They are present early in the disease process and have not been found consistently in any other autoimmune disease syndrome. A complete blood count (CBC) test looks at red and white blood cell counts. There have however been reported significant falls in patients clinically responding to infliximab and to rituximab; anti-CCP has been . my arthritis pain is VERY low. It is thought to be a combination of genetics and environmental factors. Furthermore, a positive anti-CCP does not necessarily mean a diagnosis of rheumatoid arthritis. Anti-CCPs have shown to be present in patients with other connective tissue disorders like systemic lupus erythematosus (SLE). Anti-CCP is commonly produced when you have rheumatoid arthritis. High levels of CCP antibodies have also been discovered in connective tissue diseases, autoimmune disorders, and particularly with some forms of lupus. ACPAs have proved to be powerful biomarkers that allow the diagnosis of rheumatoid arthritis (RA) to be made at a very early stage. CCP antibodies are produced by the immune system and can mistakenly attack healthy tissues. How do I move my physical server to Azure? . Autoantibodies can cause disease by attacking the body's healthy cells by mistake. Filed Under: Medical Articles and Infographics, 2023 HealthResearchFunding.org - Privacy Policy, 14 Hysterectomy for Fibroids Pros and Cons, 12 Pros and Cons of the Da Vinci Robotic Surgery, 14 Pros and Cons of the Cataract Surgery Multifocal Lens, 11 Pros and Cons of Monovision Cataract Surgery. CCP antibodies, also called anti-CCP antibodies, are a type of antibody called autoantibodies. If the sample finds the presence of anti-CCP at a certain level, the result is positive. Anti-CCP positive rheumatoid arthritis patients generally receive the most aggressive treatment options available including taking disease-modifying antirheumatic drugs (DMARDs) and supplementing withanti-inflammatory home remedies to provide symptom relief. Cyclic citrullinated peptide (CCP) antibody testing detects and measures CCP antibodies in the blood. Several studies have found that rheumatoid arthritis patients are more likely to have gum disease as well as more severe forms of the disease [4, 5, 6, 7, 8]. Often, a patient with rheumatoid arthritis and positive anti-CCP test result is called having seropositive rheumatoid arthritis. In order to reach a rheumatoid arthritis diagnosis when a patient tests positive for anti-CCPs, several other criteria must be met. Cyclic Citrullinated Peptide Ab, S. 33935-8. For this reason, only a medical provider will be able to interpret individualized test results and compare them with symptoms to determine a diagnosis. In seropositive RA, blood tests show unusually high levels of antibodies called anti-cyclic citrullinated peptides (anti-CCPs). Anti-MCV levels in the cases . The Anti-CCP Blood Test Normal Range is lower than 20 u/mL. Last month, they upped my mtx to 8 tablets due to swollen hands. He is the author of numerous health-related books and contributor to several medicine, health and wellbeing websites. Rheumatoid factor (RF) was the first autoantibody to be discovered in people with RA. A study has shown that the anti-CCP test can assist in the diagnosis of rheumatoid arthritis with a positive likelihood ratio of around 14 and a specificity of around 96 percent. Align your health hacks with your genes for optimal health & cognitive function. The anti CCP blood test is a rather new test that is becoming widely used, but the standardized RF test is generally ordered along with it or instead of it by many providers. If both . Masson-Bessiere C, Sebbag M, Girbal-Neuhauser E, et al. [26], Other ACPAs and citrullinated targets in RA. The meaning of these results may depend on the results of a rheumatoid factor (RF) test as well as a physical exam. This is useful in determining the likelihood of rheumatoid arthritis being the cause of bothersome symptoms and what course the disease is likely to take in the future. If your test result comes out positive, you must immediately consult your orthopedic doctor. Rheumatoid arthritis may progress very slowly or may progress rapidly. A plus sign next to the number [1+, 2+, etc] means that the information is found within the full scientific study rather than the abstract. CCP positivity was quantified as low (level, 1-2 the upper limit of normal [ULN]), medium (2-3 ULN), or high (>3 ULN). Hemoglobin and albumin levels were lower in the anti-CCP-positive group than in the anti-CCP/RF-negative group and . With these laboratory tests as a guide, the healthcare provider may need to make adjustments to the patients medications and RA treatment. The results will be analysed, the data proceeded and hopefully we will be able to answer the questions. What Do the Results of an Anti-CCP Test Mean? CCP is normal if 30 and below for those over 50. We keep the number of high qualtiy advertisers very low. As with rheumatoid factor, some people with positive anti-CCP antibody will not have RA, but this test is somewhat more specific forRA than the rheumatoid factor. Also, the stimulating effects of caffeine help to fight physical and mental fatigue that is common with rheumatoid arthritis. What Happens If CCP Antibody Is Positive? Patients with connective tissue disorder such as systemic lupus erythematosus may also show the presence of anti-CCP. Although this test isnt specific enough to create a diagnosis on its own, about 95% of people who have a positive test result will be able to meet the diagnostic criteria for rheumatoid arthritis at some point in the future if they do not meet them immediately. https://labtestsonline.org/understanding/analytes/ccp/tab/test/, http://www.arthritisandpainclinic.com/blood-tests.html, http://arthritis.about.com/od/radiagnosis/f/anticcp.htm, http://www.webmd.com/rheumatoid-arthritis/arthritis-test-results, http://www.medicinenet.com/citrulline_antibody/index.htm, http://patient.info/doctor/rheumatoid-arthritis-pro, http://www.arthritis.org/about-arthritis/types/rheumatoid-arthritis/articles/what-type-do-you-have.php, http://rheumatology.oxfordjournals.org/content/43/5/655.full, http://ard.bmj.com/content/64/10/1521.full.pdf. Available from. Remember that this is just the beginning. Levels of anti-MCV and RF did not change over time and disease duration or the presence of erosions had no statistically significant effect on the autoantibodies levels. Abdul Wahab A, Mohammad M, Rahman MM, Mohamed Said MS. Anti-cyclic citrullinated peptide antibody is a good indicator for the diagnosis of rheumatoid arthritis. They are present in the majority of patients with rheumatoid arthritis. The normal level of anti-CCP is less than 20 Units. Chest X-ray showed a small right pleural effusion. [1], During inflammation, arginine amino acid residues can be enzymatically converted into citrulline residues in proteins such as vimentin, by a process called citrullination. Rheumatoid factors are another type of autoantibody. Omega-3 fats help by reducing inflammation that can increase the citrullination of proteins leading to an immune system reaction and increased anti-CCP [20, 21]. They are never enough alone to diagnose RA. Your rheumatologist may be taking a conservative . These antibodies are made as a direct attack of specific proteins found naturally in the body. Antibodies protect you from disease by fighting foreign substances like viruses and bacteria. It is calculated by measuring the rate at which red blood cells sediment in a test tube in one hour. (At Hospital for Special Surgery, anti-CCP is reported in Units. Learn more here. Thats because a positive test result can mean that another autoimmune condition besides rheumatoid arthritis may be present. Joe is a thriving entrepreneur, with a mission to empower people to take advantage of the precision health revolution and uncover insights from their DNA and biomarkers so that we can all feel great all of the time. (Autoantibodies develop in response to the bodys own tissue, and are characteristic of autoimmune diseases, such as RA.) In Figure 4a-c, the self-assembled layer of the fiber was photographed using magnifications of 500, 4000, and 5000, respectively. [13][14] Unfortunately, these artificial antigens are not expressed in the affected tissue, and therefore are probably not directly involved in the pathogenesis of RA. It is hypothesized that the lung inflammation caused by smoking could possibly lead to developing the anti-CCP antibodies in patients who possess this shared epitope. A level above 20 suggests the possibility of RA. anti-CCP is very specific of RA, but you can found them in other rjeumatic diseases: - Palindromic rheumatism: 56% (Salvador G. Rheumatology 2003;42:972) - Psoriatic arthritis; 12% (worse. The Anti-CCP Blood Test Normal Range is lower than 20 u/mL. . Those given wormwood saw a nearly 10% greater reduction in anti-CCP antibodies and a greater reduction in painful and swollen joints after 48 weeks [23]. my arthritis pain is VERY low. The normal level of anti-CCP is less than 20 Units. 2. moderate, and severe) there was a highly significant difference as regard ESR, ACCP, AMCV, DAS28 score. Applies only to results expressed in units of measure originally reported by the performing laboratory. 2007. Rheumatoid Arthritis (RA); 2019 Feb [cited 2020 Feb 12]; [about 2 screens]. Epub 2014 Oct 30. Pancreatic Elastase Stool Test Purpose, Procedure, Results, Normal Range, What is Cardiac Ablation? Anti CCP antibody of > 500 means the patients body is producing high levels an antibody to CCP. [1] These include x-rays of your joints and the following blood tests: These blood tests can show signs of inflammation. PMID 29628436; PMCID: PMC6014894. They are continually monitored by our internal peer-review process and if we see anyone making material science errors, we don't let them write for us again. Vitamin D may help lower anti-CCP antibodies by suppressing overactive immune cells that attack the bodys own proteins and tissues [17]. A level above 20 suggests the possibility of RA. Clin Exp Rheumatol. Some individuals may experienced the development of nodules near the elbow. Dental treatment that removed P. gingivalis reduced the production of citrulline in 55 RA patients [3]. all my numbers look normal except my CCP Antibody IgG is > 500 (where they same normal range is < 16). If the test results indicate the presence of RF without CCP antibodies, there are antibodies without RF, or both are present but in low levels, then this may be an indication of early RA. Anti-nuclear antibody (ANA) Anti-cyclic citrullinated peptide (anti-CCP) antibodies C-reactive protein (CRP) Erythrocyte sedimentation rate (ESR, or sed rate) The amount of rheumatoid factor in your blood may also help your doctor choose the treatment approach that will work best for your situation. It is important to remember that levels of the antibody are not directly linked to disease activity, but since anti-CCP antibodies are still believed to play a role in the destruction of the joints, some studies use them to try and understand or decipher substances that might affect disease progression [2]. We do not aim to diagnose, treat, cure or prevent any illness or disease. I am hearing of that situation in areas that have govt healthcare. Mayo Foundation for Medical Education and Research; c19952020. A seropositive result could mean an overall more severe disease course than rheumatoid arthritis patients who are classified as seronegative. is a clickable link to peer-reviewed scientific studies. Diagnosing rheumatoid arthritis at its earliest stages can prevent damage and improve long-term quality of life. . Our aim was to investigate the newest generation anti-cyclic citrullinated peptide (CCP) antibody 3.1 assay in diagnosing rheumatoid arthritis (RA) compared with other autoimmune and non-autoimmune diseases. Negative levels do not exclude the disease, and positive levels do not guarantee the diagnosis. Some providers may not have the appropriate testing facilities to determine results from the anti CCP blood test. Omega-3 fats help by reducing inflammation that can increase the citrullination of proteins leading to an immune system reaction and increased anti-CCP [20, 21]. Despite these rare cases, a positive anti-CCP test is considered highly specific to rheumatoid arthritis (meaning a negative test does not rule out the disease, but a positive result rules it in). They are almost never found in people who don't have the disease. Moreover, analysis of the correlation of anti-CCP antibody titre with RA disease activity yielded conflicting results. The presence of autoantibodies against citrullinated proteins in rheumatoid arthritis patients was first described in the mid-1970s when the biochemical basis of antibody reactivity against keratin and filaggrin was investigated. You may feel a little sting when the needle goes in or out. Ann Rheum Dis. When a doctor tests for RF levels, they may also perform an anti-CCP test. The results of these tests may be used in two ways: The doctor and healthcare team use the results of these tests to guide treatment options for each patient. CCP antibodies are produced by the immune system and can mistakenly attack healthy tissues. Some individuals with a confirmed tuberculosis diagnosis have also been known to have a positive anti CCP blood test. If your results are negative for both tests (anti-CCP and RA), it is likely that the arthritis is due to a cause other than rheumatoid arthritis. More Information Juvenile idiopathic arthritis If the patients hemoglobin levels indicate anemia, this will be further investigated looking for its cause. The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. Low levels of anti-CCP can be found in the test results of certain patients but may not enough to produce a positive result. As a result, this test also helps doctors pursue specific and possibly more aggressive treatment options. Available from: Arthritis Foundation [Internet]. Positive CCP antibodies and negative RF, it may mean you are in the early stages of rheumatoid arthritis or will develop it in the future. These include: You may also need this test if other tests couldn't confirm or rule out a diagnosis of rheumatoid arthritis. Get more fiber in your diet with foods such as: fresh fruits and vegetables. Some folks actually have high RF levels, high anti-CCP, high CRP, and high ESR level, and definitely do NOT have RA." RF tests used to be the main test to help diagnose rheumatoid arthritis. Smoking increases the citrullination of proteins that can trigger an autoimmune reaction [14]. Adapted from a presentation at the Early RA Support and Education Program at Hospital for Special Surgery. Despite the name, however, RF is not specific to RA, and there are many factors that can impact RF lab results. The effects are specific of the immune cell targeted, promoting overexpression of thrombotic, inflammatory, and pro-oxidative markers in monocytes; pro-oxidative status in neutrophils; and proinflammatory profile in lymphocytes. Rochester (NY): University of Rochester Medical Center; c2020. Other diseases that can lead to increased RF levels include chronic infection, cirrhosis, or scarring of the liver, cryoglobulinemia (or abnormal proteins in the blood), dermatomyositis (an inflammatory muscle disease), inflammatory lung disease, mixed connective . There are numerous tests that a medical provider may run in addition to the anti CCP blood test. A complete metabolic panel is used to monitor kidney and liver function, in order to assesswhether changes to medicationmust be made orwhether they are working well. Result LOINC Value. It only means that even if the blood test is negative, you may still have this disease, and you may be required to undergo other tests. 2013 May-Jun [cited 2020 Feb 12]; 29(3):773-77. Other names: Cyclic citrullinated peptide antibody, anticitrullinated peptide antibody, citrulline antibody, anti-cyclic citrullinated peptide, anti-CCP antibody, ACPA. A positive result for cyclic citrullinated peptide (CCP) antibodies indicates a high likelihood of rheumatoid arthritis (RA). As we do not wish to plaster large banner ads throughout the site we have an advertising relationship with some of the offers displayed here. Be sure to tell your health care provider about all medicines, vitamins, and dietary supplements you are taking. The healthcare team orders these labs regularly to monitor the patients disease and check how his or her medications are working. A Mayo prospective clinical evaluation of the CCP antibody test showed a diagnostic sensitivity for RA of 78% with fewer than 5% false positive results in healthy controls (see Cautions). 5 Whats the normal range for an anti CCP test? I'm 29, I was diagnosed with RA about. Doctor, author and fitness enthusiast, Ahmed Zayed, MD, is a surgery resident with a passion for helping people live a happy healthy life. but is for informational and educational purposes alone. It may take 3-5 business days for full results to return. The earlier someone can be diagnosed with anti-CCP positive rheumatoid arthritis the sooner targeted treatments can be initiated. Available from: Familydoctor.org [Internet]. It's a newer, much more accurate test. Doctors will also use imaging scans to observe any signs of bone and cartilage deterioration around the affected joints. The normal level of anti-CCP is less than 20 u/ml. A blood sample is drawn from the patient and analyzed in a lab. ; 2018 Oct 27 [cited 2020 Feb 12]; [about 3 screens]. Rheumatoid arthritis is a progressive, autoimmune disease that causes pain, swelling, and stiffness in the joints. [11] The average cost of Anti-CCP test in India can be anywhere between Rs 500 to Rs . Cyclic citrullinated peptide (CCP) antibody testing detects and measures CCP antibodies in the blood. In case studies, higher omega-3 fatty acid levels are associated with a lower risk of anti-CCP antibody production [18, 19]. A positive anti-CCP usually means that you have rheumatoid arthritis. The joint is usually stiff in the morning, but will begin to loosen up during the rest of the day. Anti-CCP is an autoantibody. These attacks can produce inflammatory symptoms most commonly experienced in rheumatoid arthritis. 16 of anti-CCP antibodies or X-ray damage at first presentation, and poorer long-term 17 function as measured by HAQ; and 18 elevated CRP, elevated ESR, presence of RF, presence of anti-CCP antibodies or X-19 ray damage at first presentation, and radiological progression. Some people with RA will have negative rheumatoid factor and negative anti-CCP. Anti-CCP is thought to be present in 60% to 70% of patients with rheumatoid arthritis. Prior to the discovery and testing of anti-CCP, most doctors used rheumatoid factor (RF) another antibody as a test to help reach a rheumatoid arthritis diagnosis. This test can be used as a prognostic tool to know whether or not the symptoms are already severe. Anti-cyclic citrullinated peptide (anti- CCP) is an antibody . SelfDecode does not treat, diagnose or cure any conditions, Niewold TB, Harrison MJ, Paget SA. It is common to experience higher levels of fatigue and a fever. Sjogren syndrome, Graves disease, and lupus are all possibilities with a positive test result. It is possible to have an autoimmune disorder like rheumatoid arthritis and have a negative anti CCP blood test. Cyclic Citrullinated Peptide Antibody; [updated 2019 Dec 24; cited 2020 Feb 12]; [about 2 screens]. Anti-CCP antibodies are abundant in rheumatoid arthritis, and tests measuring anti-CCP have a specificity of about 96% [ 1 ]. Its important to note that once the RF level is elevated, it will often remain so even if the disease goes into remission. A CCP antibody test is used to help diagnose rheumatoid arthritis. If anything fails to meet your standards in any way please contact us so that we may consider removing it from our recommendations. 2003 Sep;62(9):870-874. To help in diagnosing rheumatoid arthritis, Why Fasting Is Required Before Blood Test, Right Side Abdominal Pain Symptoms, Causes, Diagnosis, Treatment, Left Side Abdominal Pain Symptoms, Causes, Diagnosis, Treatment. Washington D.C.: American Association for Clinical Chemistry; c20012020. However we do not offer any products or services that haven't been thoroughly vetted by us. Your email address will not be published. 2014 Oct;81(5):41620. The result is positive if the blood sample contains anti-CCP at a specified level. The levels of antibodies will fluctuate over time if a positive test result is received. Test Result Name. OBJECTIVE To examine the association of treatment response and disease duration with changes in rheumatoid factor (RF) and anti-cyclic . Anti-CCP is thought to be present in anywhere between 60% and 80% of rheumatoid arthritis patients. Testing for the presence of anti-CCP is a relatively new support tool in helping doctors diagnose rheumatoid arthritis. Some levels of ANA can be found even in healthy people. Since anti-MCV antibody levels at baseline predict disease activity at 2 years, anti-MCV antibodies might be superior as compared to anti-CCP an- [4][5] Subsequent studies demonstrated that autoantibodies from RA patients react with a series of different citrullinated antigens, including fibrinogen, deiminated Epstein-Barr Virus Nuclear Antigen 1 and vimentin,[6][7][8] which is a member of the intermediate filament family of proteins. These are done to check for other potential health issues, especially anemia and signs of inflammation, that are common with individuals who have rheumatoid arthritis. Another member wrote, "Just for the record, blood tests for RA are only part of the diagnosis puzzle. Objective. The cost to maintain this website grows each week. Do you all know of other sites for people with my similar issues?? Anticyclic citrullinated peptide (anti-CCP) antibody levels are characteristically elevated in rheumatoid arthritis, although they can be elevated in other rheumatologic conditions associated with inflammatory arthritis, such as systemic lupus erythematosus. These symptoms must also occur for more than six consecutive weeks and meet certain criteria such as how many joints are involved and where they are located on the body. Rheumatoid arthritis is not just a pain in your joints. when I get a cold it get a small flare up but other than that, I am able to play racquetball for a least 2 hours 6 days a week and can do regular activities (job, wife, kids, evening Early detection can help patients to maintain their quality of life and prevent the severe progression of rheumatoid arthritis. Before taking the test, the healthcare practitioner will typically require you to stop taking any medications or supplements, including dietary supplements with biotin and multivitamins at least 8 hours before the test is performed. Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects the joints, but can affect other parts of the body. The test is also known as an anti-citrulline antibody, cyclic citrullinated peptide antibody (CCPA), anti-cyclic citrullinated peptide antibody, and anti-CCP. I was just diagnosed with RA. I have the same condition // high Anti CCP (528) but very low symptom just two swollen fingers and stiffness at my ankle in the morning. The earlier you address the symptoms of rheumatoid arthritis, the earlier you can find the appropriate treatment for the same. Vimentin, fibrin, filaggrin, enolase and keratin are common citrullination targets. How to differentiate between UTI and Pregnancy Symptoms? Required fields are marked *. Where are anti CCP antibodies found in the body? Research has shown that rheumatoid arthritis patients who test positive for anti-CCP could potentially experience a more aggressive set of symptoms and more severe damage to the affected joints. These proteins are components of complement, proteolytic activity, cell recognition, endocytosis, and response to biotic stimuli amongst others.
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