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64-509: The ABO blood group system is used to denote the presence of one, both, or neither of the A and B antigens on erythrocytes (red blood cells). For human blood transfusions , it is the most important of the 44 different blood type (or group) classification systems currently recognized by the International Society of Blood Transfusions (ISBT) as of December 2022. A mismatch in this serotype (or in various others) can cause

128-633: A combination of 27 loci, including the ABO gene, identified individuals at increased risk for both incident and recurrent coronary artery disease events, as well as an enhanced clinical benefit from statin therapy. The study was based on a community cohort study (the Malmo Diet and Cancer study) and four additional randomized controlled trials of primary prevention cohorts (JUPITER and ASCOT) and secondary prevention cohorts (CARE and PROVE IT-TIMI 22). In April 2007, an international team of researchers announced in

192-428: A definitive observation that blood serum of an individual would agglutinate with only those of certain individuals. Based on this he classified human blood into three groups, namely group A, group B, and group C. He defined that group A blood agglutinates with group B, but never with its own type. Similarly, group B blood agglutinates with group A. Group C blood is different in that it agglutinates with both A and B. This

256-409: A high predicted MHC binding affinity. Minor histocompatibility antigens, a conceptually similar antigen class are also correctly identified by MHC binding algorithms. Another potential filter examines whether the mutation is expected to improve MHC binding. The nature of the central TCR-exposed residues of MHC-bound peptides is associated with peptide immunogenicity. A native antigen is an antigen that

320-436: A potentially fatal adverse reaction after a transfusion, or an unwanted immune response to an organ transplant. Such mismatches are rare in modern medicine. The associated anti-A and anti-B antibodies are usually IgM antibodies, produced in the first years of life by sensitization to environmental substances such as food, bacteria, and viruses. The ABO blood types were discovered by Karl Landsteiner in 1901; he received

384-453: A relative down-regulation of GTA and GTB occurs in oral carcinomas in association with tumor development. More recently, a genome wide association study (GWAS) has identified variants in the ABO locus associated with susceptibility to pancreatic cancer. In addition, another large GWAS study has associated ABO-histo blood groups as well as FUT2 secretor status with the presence in the intestinal microbiome of specific bacterial species. In this case

448-530: A single parent. The distribution of the blood groups A, B, O and AB varies across the world according to the population. There are also variations in blood type distribution within human subpopulations. In the UK, the distribution of blood type frequencies through the population still shows some correlation to the distribution of placenames and to the successive invasions and migrations including Celts , Norsemen , Danes , Anglo-Saxons , and Normans who contributed

512-472: A special dominance relationship: codominance , which means that type A and B parents can have an AB child. A couple with type A and type B can also have a type O child if they are both heterozygous ( Ii and Ii ). The cis-AB phenotype has a single enzyme that creates both A and B antigens. The resulting red blood cells do not usually express A or B antigen at the same level that would be expected on common group A 1 or B red blood cells, which can help solve

576-468: A two-sentence footnote: The serum of healthy human beings not only agglutinates animal red cells, but also often those of human origin, from other individuals. It remains to be seen whether this appearance is related to inborn differences between individuals or it is the result of some damage of bacterial kind. This was the first evidence that blood variations exist in humans — it was believed that all humans have similar blood. The next year, in 1901, he made

640-428: A type O child can be born to an AB parent—due to rare situations, such as Bombay phenotype and cis AB . The A blood type contains about 20 subgroups, of which A1 and A2 are the most common (over 99%). A1 makes up about 80% of all A-type blood, with A2 making up almost all of the rest. These two subgroups are not always interchangeable as far as transfusion is concerned, as some A2 individuals produce antibodies against

704-633: Is a popular belief in Blood type personality theory , which claims that blood types predict or influence personality. This claim is not scientifically based, and there is scientific consensus that no such link exists; the scientific community considers it a pseudoscience and a superstition . The belief originated in the 1930s, when it was introduced as part of Japan's eugenics program. Its popularity faded following Japan's defeat in World War 2 and Japanese support for eugenics faltered, but it resurfaced in

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768-448: Is also expressed on the von Willebrand factor (vWF) glycoprotein , which participates in hemostasis (control of bleeding). In fact, having type O blood predisposes to bleeding, as 30% of the total genetic variation observed in plasma vWF is explained by the effect of the ABO blood group, and individuals with group O blood normally have significantly lower plasma levels of vWF (and Factor VIII ) than do non-O individuals. In addition, vWF

832-465: Is called the antigen-antibody reaction . Antigen can originate either from within the body (" self-protein " or "self antigens") or from the external environment ("non-self"). The immune system identifies and attacks "non-self" external antigens. Antibodies usually do not react with self-antigens due to negative selection of T cells in the thymus and B cells in the bone marrow . The diseases in which antibodies react with self antigens and damage

896-534: Is degraded more rapidly due to the higher prevalence of blood group O with the Cys1584 variant of vWF (an amino acid polymorphism in VWF): the gene for ADAMTS13 (vWF-cleaving protease ) maps to human chromosome 9 band q34.2, the same locus as ABO blood type. Higher levels of vWF are more common amongst people who have had ischemic stroke (from blood clotting) for the first time. The results of this study found that

960-486: Is found worldwide, and likely predates human migration from Africa . The O01 allele is considered to predate the O02 allele. Some evolutionary biologists theorize that there are four main lineages of the ABO gene and that mutations creating type O have occurred at least three times in humans. From oldest to youngest, these lineages comprise the following alleles: A101/A201/O09 , B101 , O02 and O01 . The continued presence of

1024-487: Is insufficient to exclude many false positives from the pool of peptides that may be presented by MHC molecules. Instead, algorithms are used to identify the most likely candidates. These algorithms consider factors such as the likelihood of proteasomal processing, transport into the endoplasmic reticulum , affinity for the relevant MHC class I alleles and gene expression or protein translation levels. The majority of human neoantigens identified in unbiased screens display

1088-429: Is named "enzyme converted to O" (ECO blood) but despite the early success of converting B- to O-type RBCs and clinical trials without adverse effects transfusing into A- and O-type patients, the technology has not yet become clinical practice. Another approach to the blood antigen problem is the manufacture of artificial blood , which could act as a substitute in emergencies. In Japan and other parts of East Asia, there

1152-403: Is not yet processed by an APC to smaller parts. T cells cannot bind native antigens, but require that they be processed by APCs, whereas B cells can be activated by native ones. Antigenic specificity is the ability of the host cells to recognize an antigen specifically as a unique molecular entity and distinguish it from another with exquisite precision. Antigen specificity is due primarily to

1216-516: Is usually a self-protein or protein complex (and sometimes DNA or RNA) that is recognized by the immune system of patients with a specific autoimmune disease . Under normal conditions, these self-proteins should not be the target of the immune system, but in autoimmune diseases, their associated T cells are not deleted and instead attack. Neoantigens are those that are entirely absent from the normal human genome. As compared with nonmutated self-proteins, neoantigens are of relevance to tumor control, as

1280-478: The ABO gene that produce one's blood type: The same study also identified 18 rare alleles, which generally have a weaker glycosylation activity. People with weak alleles of A can sometimes express anti-A antibodies, though these are usually not clinically significant as they do not stably interact with the antigen at body temperature. Cis AB is another rare variant, in which A and B genes are transmitted together from

1344-851: The Nobel Prize in Physiology or Medicine in 1930 for this discovery. ABO blood types are also present in other primates such as apes , monkeys and Old World monkeys . The ABO blood types were first discovered by an Austrian physician, Karl Landsteiner , working at the Pathological-Anatomical Institute of the University of Vienna (now Medical University of Vienna ). In 1900, he found that red blood cells would clump together ( agglutinate ) when mixed in test tubes with sera from different persons, and that some human blood also agglutinated with animal blood. He wrote

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1408-651: The Rockefeller Institute for Medical Research in New York. As a member of a committee of the National Research Council concerned with blood grouping, he suggested to substitute Janský's and Moss's systems with the letters O, A, B, and AB. (There was another confusion on the use of figure 0 for German null as introduced by Hirszfeld and von Dungern, because others used the letter O for ohne , meaning without or zero; Landsteiner chose

1472-441: The morphemes to the placenames and the genes to the population. The native Celts tended to have more type O blood, while the other populations tended to have more type A. The two common O alleles, O01 and O02, share their first 261 nucleotides with the group A allele A01. However, unlike the group A allele, a guanosine base is subsequently deleted. A premature stop codon results from this frame-shift mutation . This variant

1536-406: The red blood cell antigens. The gene is located on the long arm of the ninth chromosome (9q34). The I allele gives type A, I gives type B, and i gives type O. As both I and I are dominant over i , only ii people have type O blood. Individuals with II or Ii have type A blood, and individuals with II or Ii have type B. II people have both phenotypes , because A and B express

1600-881: The 1970s by a journalist named Masahiko Nomi . Despite its status as a pseudoscience, it remains widely popular throughout East Asia. Other popular ideas are blood type-specific dietary needs , that group A causes severe hangovers , that group O is associated with better teeth, and that those with group A2 have the highest IQ scores . As with blood type personality theory, these and other popular ideas lack scientific evidence, and many are discredited or pseudoscientific. Antigen Antigens can be proteins , peptides (amino acid chains), polysaccharides (chains of simple sugars), lipids , or nucleic acids . Antigens exist on normal cells , cancer cells , parasites , viruses , fungi , and bacteria . Antigens are recognized by antigen receptors, including antibodies and T-cell receptors. Diverse antigen receptors are made by cells of

1664-410: The A, B and O epitopes. Blood groups are inherited from both parents. The ABO blood type is controlled by a single gene (the ABO gene ) with three types of alleles inferred from classical genetics : i , I , and I . The I designation stands for isoagglutinogen , another term for antigen . The gene encodes a glycosyltransferase —that is, an enzyme that modifies the carbohydrate content of

1728-520: The A1 antigen. Complications can sometimes arise in rare cases when typing the blood. With the development of DNA sequencing , it has been possible to identify a much larger number of alleles at the ABO locus, each of which can be categorized as A, B, or O in terms of the reaction to transfusion, but which can be distinguished by variations in the DNA sequence. There are six common alleles in white individuals of

1792-543: The ABH substances were all attached to glycosphingolipids, Finne et al . (1978) found that the human erythrocyte glycoproteins contain polylactosamine chains that contains ABH substances attached and represent the majority of the antigens. The main glycoproteins carrying the ABH antigens were identified to be the Band 3 and Band 4.5 proteins and glycophorin. Later, Yamamoto's group showed the precise glycosyl transferase set that confers

1856-663: The First World War (1914–1915) when citric acid began to be used for blood clot prevention . Felix Bernstein demonstrated the correct blood group inheritance pattern of multiple alleles at one locus in 1924. Watkins and Morgan, in England, discovered that the ABO epitopes were conferred by sugars, to be specific, N-acetylgalactosamine for the A-type and galactose for the B-type. After much published literature claiming that

1920-658: The O alleles is hypothesized to be the result of balancing selection . Both theories contradict the previously held theory that type O blood evolved first. It is possible that food and environmental antigens (bacterial, viral, or plant antigens) have epitopes similar enough to A and B glycoprotein antigens. The antibodies created against these environmental antigens in the first years of life can cross-react with ABO-incompatible red blood cells that it comes in contact with during blood transfusion later in life. Anti-A antibodies are hypothesized to originate from immune response towards influenza virus , whose epitopes are similar enough to

1984-547: The Phipps Tuberculosis Dispensary in 1910. Landsteiner had identified three blood groups in 1901 and added a fourth in 1902 (AB). Jan Jansky also developed a classification in 1907 in Prague. Moss used Roman numbers for his groups and identified compatibility of the groups to avoid agglutination during blood transfers. He also contributed to anesthetic management. He later taught at Yale, Harvard and

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2048-530: The Roman numerical I, II, III, and IV (corresponding to modern O, A, B, and AB). Unknown to Janský, an American physician William L. Moss devised a slightly different classification using the same numerical; his I, II, III, and IV corresponding to modern AB, A, B, and O. These two systems created confusion and potential danger in medical practice. Moss's system was adopted in Britain, France, and US, while Janský's

2112-579: The adjuvant component of vaccines plays an essential role in the activation of the innate immune system. An immunogen is an antigen substance (or adduct ) that is able to trigger a humoral (innate) or cell-mediated immune response. It first initiates an innate immune response, which then causes the activation of the adaptive immune response. An antigen binds the highly variable immunoreceptor products (B-cell receptor or T-cell receptor) once these have been generated. Immunogens are those antigens, termed immunogenic , capable of inducing an immune response. At

2176-508: The agglutinins which are present in the same serum. Thus, he discovered two antigens ( agglutinogens A and B) and two antibodies (agglutinins — anti-A and anti-B). His third group (C) indicated absence of both A and B antigens, but contains anti-A and anti-B. The following year, his students Adriano Sturli and Alfred von Decastello discovered the fourth type (but not naming it, and simply referred to it as "no particular type"). In 1910, Ludwik Hirszfeld and Emil Freiherr von Dungern introduced

2240-406: The antigens; depending on the antigen and the type of the histocompatibility molecule, different types of T cells will be activated. For T-cell receptor (TCR) recognition, the peptide must be processed into small fragments inside the cell and presented by a major histocompatibility complex (MHC). The antigen cannot elicit the immune response without the help of an immunologic adjuvant . Similarly,

2304-406: The association was with Bacteroides and Faecalibacterium spp . Bacteroides of the same OTU (operational taxonomic unit) have been shown to be associated with inflammatory bowel disease, thus the study suggests an important role for the ABO histo-blood group antigens as candidates for direct modulation of the human microbiome in health and disease. A multi-locus genetic risk score study based on

2368-451: The body's own cells are called autoimmune diseases . Vaccines are examples of antigens in an immunogenic form, which are intentionally administered to a recipient to induce the memory function of the adaptive immune system towards antigens of the pathogen invading that recipient. The vaccine for seasonal influenza is a common example. Paul Ehrlich coined the term antibody ( German : Antikörper ) in his side-chain theory at

2432-431: The combinations obtained when one allele is taken from each parent; each has a 25% chance, but some occur more than once. The text above them summarizes the outcomes. Historically, ABO blood tests were used in paternity testing , but in 1957 only 50% of American men falsely accused were able to use them as evidence against paternity. Occasionally, the blood types of children are not consistent with expectations—for example,

2496-424: The destruction of the infected cell. Endogenous antigens are generated within normal cells as a result of normal cell metabolism , or because of viral or intracellular bacterial infection . The fragments are then presented on the cell surface in the complex with MHC class I molecules. If activated cytotoxic CD8 T cells recognize them, the T cells secrete various toxins that cause the lysis or apoptosis of

2560-428: The end of the 19th century. In 1899, Ladislas Deutsch (László Detre) named the hypothetical substances halfway between bacterial constituents and antibodies "antigenic or immunogenic substances" ( French : substances immunogènes ou antigènes ). He originally believed those substances to be precursors of antibodies, just as a zymogen is a precursor of an enzyme . But, by 1903, he understood that an antigen induces

2624-510: The fragments to T helper cells ( CD4 ) by the use of class II histocompatibility molecules on their surface. Some T cells are specific for the peptide:MHC complex. They become activated and start to secrete cytokines, substances that activate cytotoxic T lymphocytes (CTL), antibody-secreting B cells , macrophages and other particles. Some antigens start out as exogenous and later become endogenous (for example, intracellular viruses). Intracellular antigens can be returned to circulation upon

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2688-619: The immune system from pathogens carrying antigens from other hosts. Thus, individuals possessing rare types are better equipped to detect pathogens. The high within-population diversity observed in human populations would, then, be a consequence of natural selection on individuals. The carbohydrate molecules on the surfaces of red blood cells have roles in cell membrane integrity, cell adhesion , membrane transportation of molecules, and acting as receptors for extracellular ligands, and enzymes. ABO antigens are found having similar roles on epithelial cells as well as red blood cells. The ABO antigen

2752-482: The immune system so that each cell has a specificity for a single antigen. Upon exposure to an antigen, only the lymphocytes that recognize that antigen are activated and expanded, a process known as clonal selection . In most cases, antibodies are antigen-specific , meaning that an antibody can only react to and bind one specific antigen; in some instances, however, antibodies may cross-react to bind more than one antigen. The reaction between an antigen and an antibody

2816-435: The infected cell. In order to keep the cytotoxic cells from killing cells just for presenting self-proteins , the cytotoxic cells (self-reactive T cells) are deleted as a result of tolerance (negative selection). Endogenous antigens include xenogenic (heterologous), autologous and idiotypic or allogenic (homologous) antigens. Sometimes antigens are part of the host itself in an autoimmune disease . An autoantigen

2880-506: The journal Nature Biotechnology an inexpensive and efficient way to convert types A, B, and AB blood into type O. This is done by using glycosidase enzymes from specific bacteria to strip the blood group antigens from red blood cells . The removal of A and B antigens still does not address the problem of the Rh blood group antigen on the blood cells of Rh positive individuals, and so blood from Rh negative donors must be used. The modified blood

2944-628: The latter.) This classification was adopted by the National Research Council and became variously known as the National Research Council classification, the International classification, and most popularly the "new" Landsteiner classification. The new system was gradually accepted and by the early 1950s, it was universally followed. The first practical use of blood typing in transfusion was by an American physician Reuben Ottenberg in 1907. Large-scale application began during

3008-699: The molecular level, an antigen can be characterized by its ability to bind to an antibody's paratopes . Different antibodies have the potential to discriminate among specific epitopes present on the antigen surface. A hapten is a small molecule that can only induce an immune response when attached to a larger carrier molecule, such as a protein . Antigens can be proteins, polysaccharides, lipids , nucleic acids or other biomolecules. This includes parts (coats, capsules, cell walls, flagella, fimbriae, and toxins) of bacteria , viruses , and other microorganisms . Non-microbial non-self antigens can include pollen, egg white, and proteins from transplanted tissues and organs or on

3072-549: The mother and child do not usually cause hemolytic disease of the newborn (HDN) because antibodies to the ABO blood groups are usually of the IgM type, which do not cross the placenta. However, in an O-type mother, IgG ABO antibodies are produced and the baby can potentially develop ABO hemolytic disease of the newborn . In human cells, the ABO alleles and their encoded glycosyltransferases have been described in several oncologic conditions. Using anti-GTA/GTB monoclonal antibodies, it

3136-551: The occurrence was not affected by ADAMTS13 polymorphism, and the only significant genetic factor was the person's blood group. ABO(H) blood group antigens are also carried by other hemostatically relevant glycoproteins, such as platelet glycoprotein Ibα, which is a ligand for vWF on platelets. The significance of ABO(H) antigen expression on these other hemostatic glycoproteins is not fully defined, but may also be relevant for bleeding and thrombosis. ABO blood group incompatibilities between

3200-539: The pool of neoantigens. Tumor antigens are those antigens that are presented by MHC class I or MHC class II molecules on the surface of tumor cells . Antigens found only on such cells are called tumor-specific antigens (TSAs) and generally result from a tumor-specific mutation . More common are antigens that are presented by tumor cells and normal cells, called tumor-associated antigens (TAAs). Cytotoxic T lymphocytes that recognize these antigens may be able to destroy tumor cells. Tumor antigens can appear on

3264-494: The problem of an apparently genetically impossible blood group. Individuals with the rare Bombay phenotype (hh) produce antibodies against the A, B, and O groups and can only receive transfusions from other hh individuals. The table above summarizes the various blood groups that children may inherit from their parents. Genotypes are shown in the second column and in small print for the offspring: AO and AA both test as type A; BO and BB test as type B. The four possibilities represent

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3328-465: The production of immune bodies (antibodies) and wrote that the word antigen is a contraction of antisomatogen ( Immunkörperbildner ). The Oxford English Dictionary indicates that the logical construction should be "anti(body)-gen". The term originally referred to a substance that acts as an antibody generator. Antigen-presenting cells present antigens in the form of peptides on histocompatibility molecules . The T cells selectively recognize

3392-476: The protein-coding part of the genome (the exome ) and predict potential neoantigens. In mice models, for all novel protein sequences, potential MHC-binding peptides were predicted. The resulting set of potential neoantigens was used to assess T cell reactivity. Exome–based analyses were exploited in a clinical setting, to assess reactivity in patients treated by either tumor-infiltrating lymphocyte (TIL) cell therapy or checkpoint blockade. Neoantigen identification

3456-436: The quality of the T cell pool that is available for these antigens is not affected by central T cell tolerance. Technology to systematically analyze T cell reactivity against neoantigens became available only recently. Neoantigens can be directly detected and quantified. For virus-associated tumors, such as cervical cancer and a subset of head and neck cancers , epitopes derived from viral open reading frames contribute to

3520-466: The side-chain conformations of the antigen. It is measurable and need not be linear or of a rate-limited step or equation. Both T cells and B cells are cellular components of adaptive immunity . William Lorenzo Moss William Lorenzo Moss (23 August 1876 – August 12, 1957) was an American physician and professor of medicine. He developed the Moss System of blood groups in 1910 which

3584-454: The surface of the tumor in the form of, for example, a mutated receptor, in which case they are recognized by B cells . For human tumors without a viral etiology, novel peptides (neo-epitopes) are created by tumor-specific DNA alterations. A large fraction of human tumor mutations are effectively patient-specific. Therefore, neoantigens may also be based on individual tumor genomes. Deep-sequencing technologies can identify mutations within

3648-460: The surface of transfused blood cells. Antigens can be classified according to their source. Exogenous antigens are antigens that have entered the body from the outside, for example, by inhalation , ingestion or injection . The immune system's response to exogenous antigens is often subclinical. By endocytosis or phagocytosis , exogenous antigens are taken into the antigen-presenting cells (APCs) and processed into fragments. APCs then present

3712-418: The term 0 (null) for the group Landsteiner designated as C, and AB for the type discovered by Adriano sturli and Alfred von decastello ( https://www.rockefeller.edu/our-scientists/karl-landsteiner/2554-nobel-prize/ ). They were also the first to explain the genetic inheritance of the blood groups. Czech serologist Jan Janský independently introduced blood type classification in 1907 in a local journal. He used

3776-484: The α-D-N-galactosamine on the A glycoprotein to be able to elicit a cross-reaction. Anti-B antibodies are hypothesized to originate from antibodies produced against Gram-negative bacteria , such as E. coli , cross-reacting with the α-D-galactose on the B glycoprotein. However, it is more likely that the force driving evolution of allele diversity is simply negative frequency-dependent selection; cells with rare variants of membrane antigens are more easily distinguished by

3840-433: Was demonstrated that a loss of these enzymes was correlated to malignant bladder and oral epithelia. Furthermore, the expression of ABO blood group antigens in normal human tissues is dependent the type of differentiation of the epithelium. In most human carcinomas, including oral carcinoma, a significant event as part of the underlying mechanism is decreased expression of the A and B antigens. Several studies have observed that

3904-671: Was preferred in most European countries and some parts of US. To resolve the chaos, the American Association of Immunologists , the Society of American Bacteriologists , and the Association of Pathologists and Bacteriologists made a joint recommendation in 1921 that the Jansky classification be adopted based on priority. But it was not followed particularly where Moss's system had been used. In 1927, Landsteiner had moved to

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3968-404: Was successful for multiple experimental model systems and human malignancies. The false-negative rate of cancer exome sequencing is low—i.e.: the majority of neoantigens occur within exonic sequence with sufficient coverage. However, the vast majority of mutations within expressed genes do not produce neoantigens that are recognized by autologous T cells. As of 2015 mass spectrometry resolution

4032-524: Was the discovery of blood groups for which Landsteiner was awarded the Nobel Prize in Physiology or Medicine in 1930. In his paper, he referred to the specific blood group interactions as isoagglutination, and also introduced the concept of agglutinins (antibodies), which is the actual basis of antigen-antibody reaction in the ABO system. He asserted: [It] may be said that there exist at least two different types of agglutinins, one in A, another one in B, and both together in C. The red blood cells are inert to

4096-523: Was used to ensure safe blood transfusions before more detailed classifications based on refinements of Landsteiner 's work came into practice. Moss was born in Athens, Georgia and was educated at the University of Georgia . After receiving a bachelor's degree in 1897 in civil engineering before he joined Johns Hopkins University to study medicine and graduated MD in 1905. He worked as an instructor at

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