scholarly journals Complicated Relationship between Genetic Mutations and Phenotypic Characteristics in Transient and Permanent Congenital Hypothyroidism: Analysis of Pooled Literature Data

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Wei Long ◽  
Lingna Zhou ◽  
Ying Wang ◽  
Jiaxuan Liu ◽  
Huaiyan Wang ◽  
...  
Keyword(s):  
Congenital Hypothyroidism ◽  
Biological Function ◽  
Data Extraction ◽  
Genetic Mutations ◽  
Missense Mutations ◽  
Phenotypic Characteristics ◽  
Thyroid Morphology ◽  
The Relationship ◽  
Dual Site

Purpose. Mutations and phenotypic characteristics remain unclear in patients with congenital hypothyroidism (CH), and no study concerning whether the outcome of transient CH (TCH) or permanent CH (PCH) is determined by mutations has been reported. Methods. We searched the literature up to April 2019. Eligible studies and data extraction were performed. We estimated the relationship between mutations and phenotypic characteristics in pooled patients with CH. Results. Two hundred forty-one cases were pooled from 41 eligible studies. The thyroid morphology, classification of mutated genes, and types of mutations were different between 94 patients with TCH and 147 patients with PCH. Heterozygous missense mutations prevailed in PAX8, TSHR, FOXE1, and NKX2-5, and patients with these mutated genes had a higher risk of PCH (OR = 37.38, 95% CI 5.04–277.21, P<0.001). TCH and PCH have equal shares in patients with mutated DUOX2 or DUOXA2. Dual-site and multisite mutations were frequently detected in DUOX2. High phenotypic heterogeneity was observed in mutated DUOX2 even in the same mutations. However, there was no relationship found between mutations and transient or permanent outcome in patients with mutated DUOX2. Conclusion. Transient or permanent outcomes were influenced by the biological function of mutated genes instead of types of mutations among patients with CH. Patients whose mutations were related to thyroid dysgenesis (TD) were more likely to have PCH. The relationship between mutations and phenotypic characteristics is complicated, and phenotypic characteristics may be affected by mutations and other factors.

Double Genetic Mutations in PML-Rara Fusion Gene Confirmed in a Patient Showing Resistance to All-Trans Retinoic Acid and Arsenic-Trioxide Therapy.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1743-1743 ◽  
Author(s):  
Emi Goto ◽  
Akihiro Tomita ◽  
Akihide Atsumi ◽  
Hitoshi Kiyoi ◽  
Tomoki Naoe
Keyword(s):  
Drug Resistance ◽  
Retinoic Acid ◽  
Disease Progression ◽  
Research Funding ◽  
Fusion Gene ◽  
Leukemia Cells ◽  
Genetic Mutations ◽  
Missense Mutations ◽  
All Trans Retinoic Acid ◽  
The Relationship

Abstract Abstract 1743 Poster Board I-769 Background Molecular targeting drugs, all-trans retinoic acid (ATRA)and arsenic trioxide (ATO), have major advances in the treatment of acute promyelocytic leukemia (APL). However, resistance to these drugs has been also observed in clinical practice. ATRA acts as a ligand for retinoic acid receptor alpha (RAR) and restores the aberrant transcription repression by PML-RARA fusion protein in APL cells. Previous reports demonstrate that amino-acids substitution, resulting from genetic mutations, in ligand binding domain (LBD) of RARA region of PML-RARA were closely related to drug resistance to ATRA therapy. In contrast, for ATO therapy, the molecular mechanisms of the effectiveness and also the resistance are still unclear. Here we identified a PML-RARA that holds double genetic missense mutations in RARA and PML regions, respectively, from an APL patient, who showed clinically resistance to ATRA and ATO therapy. These mutations were observed as his disease progression, and we are interested in the relationship between these mutations with drug resistance to ATRA and/or ATO. Aims Analyses of the molecular and clinical significance of the double missense mutations of PML-RARA for disease progression and resistance to ATRA and ATO therapy. Results Eight APL patients were treated with ATO in Nagoya University Hospital, Japan, during ∼5 years from Apr. 1, 2000 to Dec. 31, 2004. One out of 8 patients showed clinically ATO resistance. The patient showing ATO resistance firstly diagnosed as APL (M3 variant) from cytogenetic and chromosomal analyses, and complete remission was obtained after combination chemotherapy with ATRA. Molecular CR was confirmed by RT-PCR analysis, but after 3 month from the induction therapy, ATRA-resistant relapse was observed. After treatment with ATO therapy, response was observed, but the effectiveness was gradually decreased, resulting finally into the resistance. The patient died of disease progression. During his 7 years clinical course, leukemia cells were harvested repeatedly from his bone marrow and peripheral blood. RT-PCR using the total RNA from his tumor cells followed by DNA sequencing was performed, with the result of PML-RARA fusion gene with the bcr3 breakpoint in the intron 3 of PML. When using the tumor cells that were harvested at his terminal stage, a missense point mutation in the LBD of the RARA region of PML-RARA was confirmed. Furthermore, missense point mutation in the PML-B2 domain was also confirmed in the same cDNA clones. Interestingly, these mutations were not observed in the leukemia cells obtained at the onset. These mutations were analyzed in each sample that was obtained as his disease progressed, and some correlation between disease progression and/or the drug resistance and the timing of appearance of these two mutations were suggested. These mutated fusion transcripts were cloned into expression vectors, and we are now analyzing the function relating to the drug resistance and disease progression. Conclusions Double genetic missense mutations in the RARA-LBD and PML-B2 of PML-RARA were confirmed in ATRA and ATO resistant patient. These genetic mutations were confirmed in the leukemia cells during his disease progression, and the relationship between those mutations and drug resistances were suggested from the clinical features. Mutations in the PML-B2 domain has not been reported previously, thus, it may be important to show whether this type of mutations are related to the drug resistance, especially to ATO therapy. Disclosures Kiyoi: Novartis Pharma Co. Ltd.: Research Funding; Kyowa Hakko Kirin Co. Ltd.: Consultancy. Naoe:Kyowa Hakko Kirin Co., Ltd. : Research Funding; Chugai Pharmaceutical Co.,Ltd.: Research Funding; Wyeth K.K.: Research Funding.

scholarly journals Screening and Functional Analysis of TPO Gene Mutations in a Cohort of Chinese Patients With Congenital Hypothyroidism

2021 ◽  
Vol 12 ◽  
Author(s):  
Huijjuan Wang ◽  
Wenxia Wang ◽  
Xi Chen ◽  
Hailong Shi ◽  
Yinmin Shi ◽  
...  
Keyword(s):  
Congenital Hypothyroidism ◽  
High Throughput Sequencing ◽  
Biological Function ◽  
Northwest China ◽  
Chinese Patients ◽  
Thyroid Peroxidase ◽  
Missense Mutations ◽  
Wild Type ◽  
Hormone Synthesis

BackgroundsAs a crucial enzyme in thyroid hormone synthesis, the genetic defective thyroid peroxidase (TPO) was one of the main genetic factors leading to congenital hypothyroidism (CH).MethodsMutations in the TPO gene were screened and identified in 219 patients with CH from northwest China by using high-throughput sequencing and bioinformatics analysis. The biological function of detected variants was studied by in vitro experiments and homology modeling.ResultsNineteen rare variants, including seven novel ones, were detected in 17 of 219 patients (7.8%). Most cases were detected with one single heterozygous variant, and only two patients were detected with multiple variants, i.e., compounds for (1) IVS7-1G&gt;A, p.Ala443Val, and p.Arg769Trp and (2) p.Asn592Ser and p.Asn798Lys. The biological function of the four missense mutations (i.e., p.Ala443Val, p.Arg769Trp, p.Asn592Ser, and p.Asn798Lys) they carried were further studied. Experimental data showed that these four mutations did not affect the protein expression level of the TPO gene but remarkably reduced the peroxidase activity toward guaiacol oxidation, retaining 8–32% of activity of the wild-type protein. The comparison of the predicted 3-D structures of wild-type and mutant TPO proteins showed that these four amino acid substitutions changed the non-covalent interactions of studied residues that might alter the structure and function of the TPO protein.ConclusionThis study was the first to analyze the TPO mutation spectrum of patients with CH in northwest China. Our data indicated that the TPO mutation was not a common reason to cause CH in China. The functional data may help to clarify the structure-function relationship of the TPO protein and provide further evidence for the elucidation of the genetic etiology of CH.

T Structured Semantic Weight Relationship Algorithm Combined with Decision Trees for Data Extraction

2019 ◽  
Vol 16 (2) ◽  
pp. 735-739 ◽  
Author(s):  
Saravana C. S. Kumar ◽  
P. Amudhavalli ◽  
R. Santhosh ◽  
C. Kalaiarasan
Keyword(s):  
Semantic Web ◽  
Decision Trees ◽  
Web Mining ◽  
Data Extraction ◽  
Cosine Similarity ◽  
Primary Input ◽  
New Approach ◽  
User Query ◽  
The Relationship

In Semantic Web Mining extracting the relevant data from web is the main objective. With the increase in the complexity of the data involved the focus is to achieve better accuracy by extracting the required information. In Semantic web mining the primary input is the user query but the accuracy is based on the domain classification of the data extracted. To achieve accuracy higher a new approach has been proposed where the algorithm same name as article titled maintains a Semantic structure combined with the decision trees. From the training set each word has been tokenized and the relationship between them has been established involving cosine similarity weight as well as to the possibility terms of the same word. Cosine Similarity is calculated not only between the words but also established between the group of the training sentences. The paper explains in detail regarding grouping of training sentences and establishing the weight between them using our proposed approach.

K-MEANS CLUSTERING ALGORITHM BASED CLASSIFICATION OF SOIL FERTILITY IN NORTH WEST NIGERIA

2020 ◽  
Vol 4 (2) ◽  
pp. 780-787
Author(s):  
Ibrahim Hassan Hayatu ◽  
Abdullahi Mohammed ◽  
Barroon Ahmad Isma’eel ◽  
Sahabi Yusuf Ali
Keyword(s):  
Soil Fertility ◽  
Crop Yield ◽  
Clustering Algorithm ◽  
Soil Samples ◽  
North West ◽  
R Programming ◽  
Available Information ◽  
Northwest Region ◽  
The Relationship

Soil fertility determines a plant's development process that guarantees food sufficiency and the security of lives and properties through bumper harvests. The fertility of soil varies according to regions, thereby determining the type of crops to be planted. However, there is no repository or any source of information about the fertility of the soil in any region in Nigeria especially the Northwest of the country. The only available information is soil samples with their attributes which gives little or no information to the average farmer. This has affected crop yield in all the regions, more particularly the Northwest region, thus resulting in lower food production.  Therefore, this study is aimed at classifying soil data based on their fertility in the Northwest region of Nigeria using R programming. Data were obtained from the department of soil science from Ahmadu Bello University, Zaria. The data contain 400 soil samples containing 13 attributes. The relationship between soil attributes was observed based on the data. K-means clustering algorithm was employed in analyzing soil fertility clusters. Four clusters were identified with cluster 1 having the highest fertility, followed by 2 and the fertility decreases with an increasing number of clusters. The identification of the most fertile clusters will guide farmers on where best to concentrate on when planting their crops in order to improve productivity and crop yield.

DONG SON BRONZE DRUM - THE WORK OF THE LAC VIET PEOPLE

2018 ◽  
Author(s):  
Nguyen Van Hao
Keyword(s):  
Classification Criteria ◽  
Way Of Life ◽  
Tribal Identity ◽  
The Relationship

Bronze drums are widely distributed, broader than the range of a nation. Therefore, the identification of each kind of drum is a basic subject, should be concerned. In determining the tribal identity of the drum, the classification of drum is the key stage, the relationship between the objective of the classification and classification criteria is the relation as shape and shadow, if there is no right criteria then the result of division will be difficult to reach the desired goal. Likewise, the criterion of the pattern on the bronze drum brought to the affirmation is the Dong Son bronze drum of the Lac Viet people. And the parallel is the affirmation of the culture, way of life, residence of the nation created the drum.

scholarly journals Pituitary MRI characteristics in 297 acromegaly patients based on T2-weighted sequences

2015 ◽  
Vol 22 (2) ◽  
pp. 169-177 ◽  
Author(s):  
Iulia Potorac ◽  
Patrick Petrossians ◽  
Adrian F Daly ◽  
Franck Schillo ◽  
Claude Ben Slama ◽  
...  
Keyword(s):  
Large Population ◽  
Optic Chiasm ◽  
Research Priority ◽  
Maximal Diameter ◽  
Magnetic Resonance Imaging Mri ◽  
Multimodal Management ◽  
Mri Characteristics ◽  
Weighted Sequences ◽  
The Relationship

Responses of GH-secreting adenomas to multimodal management of acromegaly vary widely between patients. Understanding the behavioral patterns of GH-secreting adenomas by identifying factors predictive of their evolution is a research priority. The aim of this study was to clarify the relationship between the T2-weighted adenoma signal on diagnostic magnetic resonance imaging (MRI) in acromegaly and clinical and biological features at diagnosis. An international, multicenter, retrospective analysis was performed using a large population of 297 acromegalic patients recently diagnosed with available diagnostic MRI evaluations. The study was conducted at ten endocrine tertiary referral centers. Clinical and biochemical characteristics, and MRI signal findings were evaluated. T2-hypointense adenomas represented 52.9% of the series, were smaller than their T2-hyperintense and isointense counterparts (P<0.0001), were associated with higher IGF1 levels (P=0.0001), invaded the cavernous sinus less frequently (P=0.0002), and rarely caused optic chiasm compression (P<0.0001). Acromegalic men tended to be younger at diagnosis than women (P=0.067) and presented higher IGF1 values (P=0.01). Although in total, adenomas had a predominantly inferior extension in 45.8% of cases, in men this was more frequent (P<0.0001), whereas in women optic chiasm compression of macroadenomas occurred more often (P=0.0067). Most adenomas (45.1%) measured between 11 and 20 mm in maximal diameter and bigger adenomas were diagnosed at younger ages (P=0.0001). The T2-weighted signal differentiates GH-secreting adenomas into subgroups with particular behaviors. This raises the question of whether the T2-weighted signal could represent a factor in the classification of acromegalic patients in future studies.

scholarly journals POS1456-HPR THE SERUM IRON LEVEL MIGHT BE USEFUL IN DETERMINING THE SEVERITY OF MALNUTRITION IN PATIENTS WITH RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1012.2-1012
Author(s):  
Y. Matsumoto ◽  
Y. Sugioka ◽  
M. Tada ◽  
T. Okano ◽  
K. Mamoto ◽  
...  
Keyword(s):  
Grip Strength ◽  
Serum Iron ◽  
Roc Analysis ◽  
Severe Malnutrition ◽  
Inflammatory Condition ◽  
Research Support ◽  
Chugai Pharmaceutical ◽  
The Relationship ◽  
Nutritional Indicator

Background:The Global Leadership Initiative on Malnutrition (GLIM) criteria, the first international criteria for diagnosis of malnutrition, was released in 2018 [1]. Patients with rheumatoid arthritis (RA) are thought to be prone to malnutrition due to decreased food intake and increased muscle catabolism caused by chronic inflammation or pain. However, there has been no report to assess the nutritional status of RA patients in accordance with the GLIM criteria. In addition, commonly used blood nutrient indicators such as albumin might not be appropriate as nutritional indicators for RA because these values are affected by inflammation.Objectives:This study aims to examine the rates of malnutrition in RA patients according to GLIM criteria, and the relationship between blood nutrient indicators and the severity of malnutrition.Methods:In this study, we conducted a cross-sectional survey of 135 female RA patients in 2020. According to the GLIM criteria, patients were considered to be malnourished if patients had one of the following phenotypic: (1) low body mass index, (2) non-volitional weight loss, (3) reduced muscle mass, and one of the following etiologic: (1) reduced food intake or assimilation, (2) disease burden/inflammatory condition. Reduced muscle mass was evaluated by measuring calf circumference, and inflammatory condition was evaluated by Disease Activity Score (DAS) 28. In accordance with the GLIM criteria, the severity of malnutrition was judged as three levels: no problem, moderate, and severe malnutrition. Albumin, transthyretin, transferrin, retinol binding protein, zinc, iron, ceruloplasmin, and total cholesterol were assessed as blood nutrition indicators. Also grip strength was assessed. We compared each nutritional indicator among the three groups according to the severity of malnutrition using age-adjusted analysis of covariance, and examined the relationship between each nutritional indicator and the severity of malnutrition using receiver operating characteristic (ROC) analysis.Results:In RA patients, 20% were classified as severe malnutrition, and 40% were moderate or more. Serum iron levels were significantly lower in the severe malnutrition group compared to the no problem group (p = 0.001). In ROC analysis, serum iron, zinc, albumin, and grip strength (area under curve; AUC; 0.680, 0.696, 0.636, 0.790, respectively) were significant parameters for classification of moderate and severe malnutrition. Serum iron and grip strength (AUC for respective parameters were 0.741, 0.747) were significant parameters for classification of severe malnutrition.Conclusion:Evaluation based on the GLIM criteria showed that about 40% of RA patients were under moderate or severe malnutrition. It was suggested that serum iron and grip strength might be useful to predict the severity of malnutrition.References:[1]Cederholm T, Jensen GL, Correia MITD, Gonzalez MC, Fukushima R, Higashiguchi T, et al. GLIM criteria for the diagnosis of malnutrition – A consensus report from the global clinical nutrition community. Clinical Nutrition 2019; 38: 1-9.Acknowledgements:We thank to Tomoko Nakatsuka, and the Center for Drug & Food Clinical Evaluation, Osaka City University Hospital, for management and collection of the study data. We also thank to study participants.Disclosure of Interests:Yoshinari Matsumoto Grant/research support from: Yamada Research Grant, Yuko Sugioka: None declared, Masahiro Tada: None declared, Tadasi Okano Speakers bureau: AbbVie, Asahikasei, Astellas Pharma Inc, Ayumi Pharmaceutical, Bristol-Myers Squibb, Chugai Pharmaceutical, Daiich Sankyo, Eisai, Janssen, Lilly, Mitsubishi Tanabe Pharma Corporation, Novartis Pharma, Ono Pharmaceutical, Pfizer, Sanofi, Takeda Pharmaceutical, Teijin Pharma and UCB, Grant/research support from: AbbVie, Eisai, Mitsubishi Tanabe Pharma Corporation and Nipponkayaku, Kenji Mamoto: None declared, Kentaro Inui Speakers bureau: Daiichi Sankyo Co. Ltd., Mitsubishi Tanabe Pharma, Janssen Pharmaceutical K.K., Astellas Pharma Inc., Takeda Pharmaceutical Co. Ltd., Ono Pharmaceutical Co. Ltd., Abbvie GK, Pfizer Inc., Eisai Co., Ltd., Chugai Pharmaceutical Co., Ltd, Grant/research support from: anssen Pharmaceutical K.K., Astellas Pharma Inc., Sanofi K.K., Abbvie GK, Takeda Pharmaceutical Co. Ltd., QOL RD Co. Ltd., Mitsubishi Tanabe Pharma, Ono Pharmaceutical Co. Ltd., Eisai Co., Ltd., Daiki Habu: None declared, Tatsuya Koike Speakers bureau: AbbVie, Astellas Pharma Inc, Bristol-Myers Squibb, Chugai Pharmaceutical, Eisai, Janssen, Lilly, Mitsubishi Tanabe Pharma Corporation, MSD, Ono Pharmaceutical, Pfizer, Roche, Takeda Pharmaceutical, Teijin Pharma, and UCB, Grant/research support from: AbbVie, Astellas Pharma Inc, Bristol-Myers Squibb, Chugai Pharmaceutical, Eisai, Janssen, Lilly, Mitsubishi Tanabe Pharma Corporation, MSD, Ono Pharmaceutical, Pfizer, Roche, Takeda Pharmaceutical, Teijin Pharma, and UCB

scholarly journals Formation of an Export-Oriented Agricultural Economy and Regional Open Innovations

2021 ◽  
Vol 7 (1) ◽  
pp. 32
Author(s):  
Victor L. Shabanov ◽  
Marianna Ya Vasilchenko ◽  
Elena A. Derunova ◽  
Andrey P. Potapov
Keyword(s):  
Agricultural Economy ◽  
Institutional Management ◽  
Agricultural Exports ◽  
Modeling Methodology ◽  
Fixed Assets ◽  
Analysis Application ◽  
The Impact ◽  
The Relationship

The aim of the work is to find relevant indicators for assessing the relationship between investments in fixed assets in agriculture, gross output of the industry, and agricultural exports using tools for modeling the impact of innovation and investment development on increasing production and export potential in the context of the formation of an export-oriented agricultural economy. The modeling methodology and the proposed estimating and forecasting tools for diagnosing and monitoring the state of sectoral and regional innovative agricultural systems are used to analyze the relationship between investments in fixed assets in agriculture, gross output of the industry, and agricultural exports based on the construction of the classification of Russian regions by factors that aggregate these features to diagnose incongruence problems and to improve institutional management in regional innovative export-oriented agrosystems. Based on the results of the factor analysis application, an underestimated role of indicators of investment in agriculture, the intensity and efficiency of agricultural production, were established. Based on the results of the cluster analysis, the established five groups of regions were identified, with significant differences in the level of investment in agriculture, the volume of production of the main types of agricultural products, and the export and exported food. The research results are of practical value for use in improving institutional management when planning reforms and transformations of regional innovative agrosystems.

A Functional Reading of the Epicurean Classification of Desires

Apeiron ◽  
2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Jan Maximilian Robitzsch
Keyword(s):  
Human Nature ◽  
Practical Significance ◽  
Textual Evidence ◽  
The Relationship

Abstract This paper examines the classification of desires that the Epicureans offer in their writings. It surveys the extant textual evidence for the classification and discusses the relationship between natural and necessary, natural and unnecessary, and unnatural and unnecessary desires. It argues that while the practical significance of the Epicurean classification is clear, which desires fall into which class is not. The paper suggests the reason for this may be that the Epicureans acknowledge some variability in their concept of human nature, arguing for a functional reading of the Epicurean classification of desires.

The International Classification of Functioning, Disability, and Health (ICF) as a community participation model for people with multiple sclerosis: A hierarchical regression analysis

2020 ◽  
Vol 26 (2) ◽  
pp. 55-72
Author(s):  
Joseph Pfaller ◽  
Fong Chan ◽  
Kanako Iwanaga ◽  
Jia-Rung Wu ◽  
Stuart Rumrill ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Regression Analysis ◽  
Community Participation ◽  
International Classification Of Functioning ◽  
Self Management ◽  
Hierarchical Regression ◽  
Personal Factors ◽  
Disability And Health ◽  
The Relationship

AbstractMultiple sclerosis (MS) is a central nervous system disorder that impacts more than 400,000 people in the U.S. The disease results in multiple functional impairments that are diverse and varied across individuals. Additonally, MS has a profound impact on community participation which, like other rehabilitation outcomes, cannot be explained on the basis of functional limitations alone. The purpose of this study was to develop and evaluate a model of community participation for people living with MS using the World Health Organization (WHO) International Classification of Functioning, Disability, and Health (ICF) framework. The model focused on the roles that personal factors have as predictors of community participation, while also serving as mediators and moderators for the relationship between activity limitation and participation. Results from the hierarchical regression analysis indicated that demographic characteristics (i.e. MS type), personal factors (i.e. core self-evaluations (CSE), MS self-management, resilience, and social skills), and activity limitations accounted for 64% of the variance in participation. Further, mediation analysis indicated that CSE mediated the relationship between activity limitation and community participation. Finally, moderation analysis indicated an interaction effect between educational attainment and MS self-management. Implications for future research in rehabilitation and clinical application are discussed.

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