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Implementation of a classification hierarchy for the GeneTests/GeneClinics genetic testing databases.

The combination of a) our changing understanding of genotypic and phenotypic classification of diseases and b) the rapid growth and expansion of the number of entries in two databases targeted toward clinicians resulted in the need to develop a flexible dynamic hierarchical classification system for genetic disorders. The two databases making use of this classification schemas are the GeneClinics (GC) database - www.geneclinics.org and the GeneTests (GT) database - www.genetests.org The GC and GT databases serve respsectively as the users manual and yellow pages of genetic testing. The GeneTests/GeneClinics (GT/GC) classification hierarchy is maintained as a simple set of parent/child relationships in a relational database. The hierarchy is generated in real time in response to a user request. It is not maintained as a set of members with relationships defined by characters that are parsed to determine the structure of the tree. The GT/GC classification hierarchy entries are handled as objects by the data maintenance and search tools and may have a number of attributes and associations that create a rich tool for defining and examining genetic disorders

Databases, Genetic↗

Building an asynchronous web-based tool for machine learning classification.

Various unsupervised and supervised learning methods including support vector machines, classification trees, linear discriminant analysis and nearest neighbor classifiers have been used to classify high-throughput gene expression data. Simpler and more widely accepted statistical tools have not yet been used for this purpose, hence proper comparisons between classification methods have not been conducted. We developed free software that implements logistic regression with stepwise variable selection as a quick and simple method for initial exploration of important genetic markers in disease classification. To implement the algorithm and allow our collaborators in remote locations to evaluate and compare its results against those of other methods, we developed a user-friendly asynchronous web-based application with a minimal amount of programming using free, downloadable software tools. With this program, we show that classification using logistic regression can perform as well as other more sophisticated algorithms, and it has the advantages of being easy to interpret and reproduce. By making the tool freely and easily available, we hope to promote the comparison of classification methods. In addition, we believe our web application can be used as a model for other bioinformatics laboratories that need to develop web-based analysis tools in a short amount of time and on a limited budget.

Algorithms↗

[Classifications and prognosis of hepatocellular carcinoma].

In this study are included 78 patients with hepatocellular carcinoma (HCC). In 22 the diagnosis is verified pathologically (obduction), while in the other patients the diagnosis is made by laparoscopy, laparoscopical ultrasonography and morphological verification (through FNAB cytology and/or histology). In 69.2% HCC is associated with cirrhosis. The prognosis of HCC associated with cirrhosis is evaluated through the classification of S. Chevret et all., and is compared to the Child-Pugh scoring system. 38.9% of patients in Chevret's class C score are in class B in the Child-Pugh score, while 25.9% of patients are in class C in both classifications, but Child-Pugh's class C patients are most often in B-C transition. It might be assumed that the prognosis of HCC depends more on the tumor prognosis than on the prognosis of the liver cirrhosis itself. Every classification which does not take in to account the liver function (like TNM system) and the whole characteristics of the tumor, would be incomplete, in some extent, in the prognosis of HCC with cirrhosis. In HCC without cirrhosis, the BCLC classification reflects both the liver function and the tumor characteristics. In BCLC class A patients hepatic resection or transplantation is recommended but hyperbilirubinemia and ascites, which might be seen in A3 and A4 classes contraindicate resection of the liver. All scoring systems define lower HCC stage than it is really found (personal and reference data), so there are no arguments to take classification scores as absolute treatment decision making rules.

Adult↗

Validation of Wagner's classification: a literature review.

To ensure high quality care, practitioners should base their practice on sound clinical evidence. Relying on quantitative measurements when evaluating this evidence demands measurement accuracy, reliability, and validity. Current diabetic foot ulcer classification systems include: Meggitt's, Wagner's, Knighton's, Pecoraro's, University of Texas San Antonio Diabetic Wound Classification, and Size (Area and Depth), Sepsis, Arteriopathy, and Denervation. Of these, the Wagner's classification system is the most widely used to describe the natural history of the dysvascular foot, even though evidence of its validity and reliability are lacking. A review of clinimetric properties and existing validation literature of the other diabetic classification systems suggest that the University of Texas San Antonio Diabetic Wound Classification and S(AD) SAD have the potential to fill the current void, once additional studies have been conducted.

Diabetic Foot↗

[Dynamic and flexible classification of transplant rejection].

Different classification systems of renal allograft rejection are in use. Although, significant progress has been made with the introduction of the widely recognized Banff classification scheme, major problems remain unsolved. Minimal diagnostic threshold levels for tubulo-interstitial rejection are lacking. "Hyperacute, acute and chronic rejection or allograft nephropathy" are ill defined entities and thereby hamper rather than promote the communication between clinicians and pathologists and prevent a better understanding of pathophysiological events. Here, we propose a classification system of renal allograft rejection which is primarily based on well characterized morphological changes. All anatomical compartments of the renal cortex i.e., the tubulo-interstitial compartment, arteries and glomeruli, can be affected by rejection individually or in combination. In the subgroups only morphological changes known to be induced by rejection are considered. Such a classification system has, in our opinion, several major advantages. Every group and subgroup can easily be amended by "qualifiers" providing additional immunohistochemical and molecular-biological information as they are known today or become available in the future. As knowledge expands, qualifiers may be added or removed without fundamentally changing the entire classification scheme--making the system flexible and dynamic.

Graft Rejection↗

[Classification of nucleotide sequences over their frequency dictionaries reveals a relation between the structure of sequences and taxonomy of their bearers].

Classification of 16S RNA sequences over their frequency dictionaries, both real ones, and transformed ones was studied. Two entities were considered to be close each other from the point of view of their structure, if their frequency dictionaries were close, in Eucledian metric. A transformation procedure of a frequency dictionary has been implemented that reveals the peculiarities of information structure of a nucleotide sequence. A comparative study of two classification developed over the real frequency dictionary vs. that one developed over the transformed frequency dictionary was carried out. The strong correlation is revealed between the classification and the taxonomy of 16S RNA bearer. For the classes isolated, the information valuable words were identified. These words are the main factors of a difference between the classes. The frequency dictionaries containing the words of the length 3 exhibit the best correlation between a class and a genus. A genus, as a rule, is included into the same class, and the exclusion are sporadic. A development of hierarchy classification over the transformed frequency dictionaries separated one or two taxonomy groups, as each stage of classification. The unexpectedly frequent, or contrary, unexpectedly rare occurred of words (of the length 3) in entities under consideration make the structure difference between the classes of the nucleotide sequences.

Bacteria↗

[New WHO classification of lymphoid neoplasms: understanding and consideration].

The latest version of new WHO classification of lymphoid neoplasms is a comprehensive and distinct opinion of lymphoid neoplasms, and maybe put an end to the controversy held in this field for a long time. The new classification defines the neoplasm categories according to the principle that the classification should be based on the real entities of diseases and should contain the morphology, immunophenotypes, genetic alterations and clinical features rather than simply emphasize the pure morphologic presentations. The new subtyping of lymphoid cancers provides a correct framework for malignant lymphoma, and also represents a new paradigm in disease classification. So far the accumulated experiences have demonstrated that the new classification is reproducible and practical. However, it remains to determine how the variants of lymphomas relate to their clinical prognostic factors, such as international prognostic index and individual difference, since the current treatment approach relays on the types of lymphomas. The diagnosis, treatment and researches of lymphomas in China are also discussed.

Humans↗

[TNM-classification of oral cavity neoplasms the value of clinically measurable factors (TN)].

Problems associated with the classification of cavum oris and labial carcinomata were discussed with particular reference to patients admitted to and treated in seven different clinical hospitals where identical methods of diagnosis and case history evaluation had been used. Using electronic data processing and biostatistical methods it was possible to study the effects of two clinically detectable factors (growth of primary tumor and degree of regional metastasizing) on both the prognosis and classification according to UICC rules. It was possible to show that a determination of the size of primary tumor (T) alone was not sufficient for three homogeneous, prognostically different collectives of tumors to be satisfactorily classified by the new UICC rules. It has been shown that a classification of three collectives of tumors (new classification according to UICC rules), especially as regards the proportion of N3 metastases within the collectives of tumors, was made possible. Therefore, it will be necessary to study the prognostic influences of additional clinically determinable factors with a view to arriving at a useful and practicable classification of oral cavity carcinomata.

Aged↗

Tumours in Iceland. 16. Malignant tumours of the stomach. Histological classification and description of epidemiological changes in a high-risk population during 30 years.

Iceland is one of the high-risk countries for stomach cancer. During the period 1955-84 the incidence declined from 76 to 28 per 10(5) p.a. for males and from 30 to 12 for females. Tissue material from the primary site in 978 males and 448 females was available for histological typing. By the WHO classification tubular carcinoma was most frequent in both sexes, 66% in males and 63% in females, and signet-ring carcinoma second, 13% in males and 16% in females. By the Laurén classification in males 78.1% were intestinal and 16.5% diffuse carcinomas, and in females 73.1% were intestinal and 20.7% diffuse carcinomas. The decline in stomach cancer in Icelanders has mostly affected the intestinal type of tumour (Laurén) and the tubular type of tumour (WHO). Diffuse type tumours (Laurén) have declined slightly. This supports the theory that intestinal carcinomas are more influenced by environmental and especially dietary factors, and that diffuse carcinomas are more influenced by other as yet unknown factors. For epidemiological studies both histological classifications have their value, the WHO especially in that it is based on standard histopathological criteria and the Laurén especially in that it only includes two tumour types. The WHO classification can roughly be transcribed to the Laurén classification as tubular, mucinous and papillary carcinomas fall into the group of intestinal tumours, and signet-ring and more than half of undifferentiated carcinomas into the group of diffuse tumours.

Adolescent↗

Performance curve classification of invalid responding on the Validity Indicator Profile.

The purpose of this article is to provide evidence for the validity of performance curve classification on the nonverbal subtest of the Validity Indicator Profile (VIP-NV). A four-fold classification scheme of performance on cognitive testing is proposed. This scheme combines effort and motivation to generate four response classifications: compliant, careless, irrelevant, and malingering. Data are presented across six studies from cognitive and personality testing for 737 male pretrial criminal defendants. Additionally, computer-generated VIP-NV performances were subjected to four levels of randomization to investigate VIP-NV carelessness indicators. The findings support the validity of the four-fold classification scheme and support the classification of response on the basis of motivation and effort.

Journal Article↗

Etiological classification of CNS malformations: integration of molecular genetic and morphological criteria.

Classification is a creative activity that helps us understand relationships. The traditional classifications of central nervous system malformations was based exclusively upon descriptive morphology, but these criteria must now be integrated with molecular genetic data to enable an etiological classification that also remains useful to the clinician, radiologist and pathologist, who rely upon imaging and tissue examination for diagnosis. Many cerebral malformations previously thought to be a single disorder are now known to be common end-results of several independent genetic mutations. Examples are holoprosencephaly and lissencephaly. Gradients of genetic expression along the axes of the neural tube, established at the time of gastrulation, may explain many varieties or anatomical and clinical manifestations of cerebral malformations, including the involvement of non-neural tissues such as in midfacial hypoplasia, that may be attributed to abnormal neural crest migration. Genes of cellular lineage and of symmetry may explain some hamartomatous malformations, such as tuberous sclerosis and hemimegalencephaly. Modern classification should be applicable to the entire CNS as well as regions; schemes that attempt to artificially isolate the cerebral cortex for a "regional classification" may be erroneous even though the genetic defect primarily affects cortical structures because genetic gradients in the neuraxis are excluded and some involve a more subtle but still important expression in subcortical structures.

Brain Diseases↗

[Diagnosis of gastric cancer on endobiopsies using the WHO classification].

Gastric cancer (GC), one of the most frequent malignancies can be early detected on endobiopsies. Our aim was to evaluate histologically the GC on endobiopsies, using WHO 2000 and Lauren classifications. The study included 2424 gastric endobiopsies, routine processed; sections stained with HE, Giemsa, PAS and AB. GC was diagnosed in 451 cases (19%), mostly in men (311 cases--69%). The highest incidence was in 60-69 year-old aged patients (34%). Using Lauren classification, 279 cases were included in diffuse type (62%), 167 intestinal-type (37%) and 5 (1%) mixed type. Each of these three types were also histologically analyzed considering the WHO classification. We pointed out that GC can be diagnosed histologically on endobiopsy specimens, although it is difficult to diagnose the GC--mixt type, due to reduced size of endobiopsies. Lauren classification (including the two major types: diffuse and intestinal) is very useful, especially if correlated with histological criteria of WHO classification.

Adenocarcinoma↗

[Clinical significance and relationship between traditional classification and Lavin-Osband criteria in Langerhans cell histiocytosis].

OBJECTIVE: To analyze the relationship between traditional classification and Lavin-Osband criteria on Langerhans cell histiocytosis (LCH) and to evaluate the importance of the criteria in clinical management and long-term prognosis of Lavin-Osband criteria. METHODS: From 1992 to 2003, 25 cases of LCH were studied. All cases were divided into four types by traditional classification and graded according to Lavin-Osband criteria simultaneously. All patients were analyzed with clinical manifestation, laboratory test, diagnoses, treatment and prognosis. The case numbers distributed in different Lavin-Osband criteria were summed up, and the advantage of the criteria was analyzed. RESULTS: The clinical manifestations according to the traditional classification (four types) overlapped mostly. The age of onset of the disease, the number of involved organs and the function of organs were all considered in the Lavin-Osband criteria, which also contained the characters of the traditional classification and could classify the cases into different severities. So Lavin-Osband criteria could predict the outcome of LCH. According to the traditional classification there were 10 cases with type I LCH, which was all graded to the criteria III and IV (100%), and there were 8 (80%) of criteria IV and none of criteria I and II. The situation was called "low type high criteria". There were 6 cases belong to LCH-II, of them 3 (50%) graded to the criteria III and 1 to the other criteria (17%), respectively. There were 4 cases with LCH-III, of them 3 (75%) graded to the criteria I and II, 1 (25%) to the criteria III and none to the criteria IV. There were 5 cases with LCH-IV, of them 4 (80%) graded to the criteria I and II, 1 (20%) to the criteria III and none to the criteria IV. This situation was called "high type low criteria". CONCLUSION: The Lavin-Osband criteria seemed to be simple, clear and easy to be handled and related to the severity of the disease, which will simplify the diagnoses, help the early-treatment and judge the prognosis.

Child, Preschool↗

[Classification of the orbital margin fractures].

OBJECTIVE: To study the classification of the orbital margin fractures. METHODS: There are 65 cases of the orbital margin fractures classified by Reduction-Orbital-Classification from January 1995 to December 1999 in Macau Conde de Sao Juanuario Hospital. RESULTS: The 65 cases are classified into six type: I Stable orbital fracture, II Orbital floor (blow-out) fracture, III Orbital-zygomatic fracture, IV Orbital-naso-maxillary fracture, V Comminuted fracture of the inferior orbital rim, VI Complex orbital fractures. CONCLUSION: The Reduction-Orbital-Classification are a complete, precise, practical, simple way for the orbital fractures; It not only presents the exist of the orbital margin fractures but also means the Classification for convenience of the treatment and treatment guiding the classification.

English Abstract↗

[A new system of diagnosis and classification--malignant lymphoma].

Malignant lymphoma is usually divided into Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) according to biological characteristics. Malignant lymphoma in Japan has such the characteristics as few incidence of HD, which is usually favorable in prognosis, and high incidence of NHLs, which have further distinctive features of less incidence of favorable follicular B cell lymphoma and of higher incidence of unfavorable diffuse T cell lymphoma including adult T cell leukemia/lymphoma (ATLL) in comparison with those in western countries. As a recent trend of progress in lymphoma diagnosis an introduction of immunological and molecular biological techniques has given an impact to the previous classification of malignant lymphoma based mainly on morphological criteria. Nowadays, the classification of pathologic type in HD seems to be settled in Rye classification. On the other hand in NHL the LSG classification has been well fixed in Japan and Working Formulation originated in USA has been well used internationally after a historical confusion. In this article a present state of working classification in malignant lymphoma is briefly described and discussed.

Hodgkin Disease↗

[Diagnosis of myeloid hematologic malignancies: contributions of the 2001 World Health Organization (WHO) classification].

Although the French-American-British (FAB) morphologic classification of myeloid malignancies has been accepted for many years, the important advances in cytogenetic, immunophenotype and genetic fields needed to be integrated in an updated approach using all the available informations. Thus, the World Health Organization (WHO) Classification of haematopoietic malignancies not only incorporates morphology, immunophenotype, cytogenetic and molecular features, but also ensures to be clinically useful. This collaborative project has begun in 1995 and has been published in 2001. The proposed WHO classification is less a disruption with regard to the FAB classification than an updated revision where morphology is always important. These review emphasises the modifications proposed in the new WHO classification concerning the myeloid disorders.

Acute Disease↗

[Idiopathic generalised epilepsy. The value of semiology and EEG scanning in its classification].

INTRODUCTION: The different syndromes included in the idiopathic generalized epilepsies present an important overlapping of their electroclinical characteristics. AIM: To compare the two actual classifications (International classification of epileptic syndromes: ILAE of 1989 and of 2001) in a sample of patients with idiopathic generalised epilepsy (IGE) and to evaluate which electro-clinical factors were more useful in order to classify a patient into a syndrome. PATIENTS AND METHODS: 70 patients (44 women/26 men). Neurological examination and neuro-radiological examination were normal in all cases. The EEG (standard or sleep deprived) showed generalised epileptiform discharges in all patients. Clinical findings included a median age of onset 12.3 years. Most frequent first type of seizure was tonic-clonic (71%). Seizures during awakening were the most frequent (37%) and lack of sleep was the most important precipitating factor (44.7%). Generalized epileptiform discharges were present in 62.9% of the basal sleep deprived EEG, on the other hand, only 22.3% of the basal standard EEG showed epileptiform discharges, p = 0.048. 28% of patients were unclassifiable according to the 1989 ILAE classification, 7% were unclassifiable according to the 2001 ILAE classification. EEG during intermittent photic stimulation (p = 0.007), at awakening (p = 0.015) and the timetable of the seizures (seizures generalised at awakening) (p = 0.053) differentiated between idiopathic generalised syndromes of adolescence. CONCLUSION: The 2001 ILAE classification is more useful in order to classify patients with IGE because includes patients previously considered unclassifiable in the syndrome of generalised epilepsy with different phenotypes.

Adult↗

[Recommendation for an expanded classification with operational diagnostic criteria for craniocerebral trauma].

Neither nationally nor internationally is there today agreement on a classification of head injuries. The traditional system using the terms commotio/concussion, contusion and compression, as well as more functionally oriented classifications are in-adequate for present-day purposes. Furthermore, there is no conformity in evaluating the severity and duration of the posttraumatic disturbances of consciousness. None of the classifications in use today includes information on important details such as the type of head injury (closed or open), possible complications or the findings of modern neurophysiological investigation and neuroimaging procedures. The requirements which a modern classification system must meet are specified and a classification of head injuries with operational diagnostic criteria is proposed, which is intended to satisfy both clinical and scientific requirements.

Brain Concussion↗