scholarly journals Association Between Thyroid Hormones and Lipids Stratified by Race and Sex

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A283-A283
Author(s):  
Musa Shakoor ◽  
Zahid Ahmad
Keyword(s):  
Thyroid Hormones ◽  
Total Cholesterol ◽  
Correlation Coefficient ◽  
Thyroid Function ◽  
Black Males ◽  
Thyroid Dysfunction ◽  
Thyroid Function Tests ◽  
Free T4 ◽  
Black Females ◽  
The Relationship

Abstract It has been well-established that thyroid hormones play a role in cholesterol and lipoprotein metabolism. However, there is limited data assessing the variability in the association between thyroid hormones and lipids across sex and race. We hypothesized that thyroid dysfunction is associated with changes in lipids and lipoproteins with no substantial variability in this association between races and sex. The electronic medical record of a large county hospital in Dallas, TX was queried to obtain data on all patients who had lipid panels and thyroid function tests checked on the same day from 1/1/2013 to 1/1/2018. The results were stratified into hypothyroid (TSH greater than 4.5 mcIU/L and Free T4 less than 0.8 ng/dL), hyperthyroid (TSH less than 0.5 mcIU/L and Free T4 greater than 1.8 ng/dL) and normal (TSH between 0.5 and 4.5 mcIU/L, Free T4 between 0.8 and 1.8 ng/dL). Results consistent with subclinical thyroid disease were excluded from further analysis. There were 25,290 unique results for thyroid hormones and lipid panels checked on the same day. The results were further stratified by race and sex, and the relationship between thyroid function and lipids was assessed. The correlation coefficient (r) was compared between sexes within each race for the following variables: TSH vs HDL-C, TSH vs LDL-C, TSH vs Total Cholesterol, TSH vs triglycerides, FT4 vs HDL-C, FT4 vs LDL-C, FT4 vs Total Cholesterol, and FT4 vs triglycerides. Among black males with hypothyroidism, there was a notably stronger correlation when compared to black females in the relationship between TSH vs LDL-C, and TSH vs Total Cholesterol. Specifically, the correlation coefficient of TSH vs LDL-C among Black males with hypothyroidism was 0.582, compared to 0.133 among Black females with hypothyroidism (P=0.0053). Furthermore, the correlation coefficient of TSH vs Total Cholesterol among Black males was 0.567 compared to 0.184 among Black females (P=0.016). In contrast, no difference in any of the relationships between thyroid and lipids was demonstrated between sexes amongst Whites, Asians, and Hispanics. Overall, we found differences in Black patients compared to patients of other races with regards to the association between thyroid and lipids. Specifically, it was found that Black males with hypothyroidism had a stronger positive correlation in TSH vs LDL-C and TSH vs Total Cholesterol than Black females. This type of difference between sexes was not found amongst any other race. These findings suggest that thyroid dysfunction is associated with changes in lipids, and the way these changes manifest may vary depending on the race and sex. This further highlights the importance of checking lipid panels in patients with thyroid dysfunction. Further research is needed to more clearly characterize the variation that is seen in thyroid and lipid function amongst races.

Thyroid dysfunction in chronic schizophrenia in albania

2011 ◽  
Vol 26 (S2) ◽  
pp. 1515-1515 ◽  
Author(s):  
Y. Themeli ◽  
I. Aliko ◽  
A. Hashorva
Keyword(s):  
Thyroid Hormones ◽  
Thyroid Function ◽  
Thyroid Dysfunction ◽  
Chronic Schizophrenia ◽  
Hashimoto Thyroiditis ◽  
Diabetes Mellitus Type 1 ◽  
Thyroid Function Tests ◽  
Thyroid Antibodies ◽  
Normal Thyroid ◽  
Function Tests

BackgroundThyroid dysfunction is relatively common in patients with schizophrenia.This study seeks to determine the prevalence and pattern of thyroid dysfunction and thyroid antibodies presence in a group of adult psychiatric inpatients with chronic schizophrenia.MethodsThyroid function tests and thyroid antibodies measurement were performed on 88 patients hospitalized in Psichiatric Clinic of UHC “Mother Teresa” from december 2006 to december 2007.55 of them (62,5%) were females and 33 of them (37,5%) males. A median age of 43 years (range16 to 70 years) and a median duration of hospitalization of 10 years (range 1 to 30 years) was assessed.ResultsTAb were found in 22 patients (25%), of which 18 females and 4 males. 16% of them resulted with positive anticorps for Hashimoto Thyroiditis; 9% for Graves‘disease.According to thyroid function tests70% had normal test, 8% had elevated TSH: 3% of them with low thyroid hormones and 5% with normal thyroid hormones. 20% of cases had low TSH: 5% of them with high level of thyroid hormones, 15% with normal thyroid hormones. Hypothyroidism was more frequent in elderly patients ( > 60 years old), and in those treated with Risperidone. Most of cases (73%) with thyroid disorders resulted from endemic geographic areas. 37% of them mentioned familial history for thyroid pathology, and 23% for diabetes mellitus type 1.ConclusionThyroid abnormalities are common in patients with chronic schizophrenia.This fact call for caution in the use and interpretation of thyroid function tests in these patients.

scholarly journals Estimation of Tissue Hypothyroidism by a New Clinical Score: Evaluation of Patients with Various Grades of Hypothyroidism and Controls1

1997 ◽  
Vol 82 (3) ◽  
pp. 771-776 ◽  
Author(s):  
Henryk Zulewski ◽  
Beat Müller ◽  
Pascale Exer ◽  
André R. Miserez ◽  
Jean-Jacques Staub
Keyword(s):  
Relaxation Time ◽  
Thyroid Hormones ◽  
Total Cholesterol ◽  
Thyroid Function ◽  
Signs And Symptoms ◽  
Clinical Score ◽  
Overt Hypothyroidism ◽  
Free T4 ◽  
Low T3 ◽  
Hypothyroid Patients

Abstract The classical signs and symptoms of hypothyroidism were reevaluated in the light of the modern laboratory tests for thyroid function. We analyzed 332 female subjects: 50 overt hypothyroid patients, 93 with subclinical hypothyroidism (SCH), 67 hypothyroid patients treated with T4, and 189 euthyroid subjects. The clinical score was defined as the sum of the 2 best discriminating signs and symptoms. Beside TSH and thyroid hormones, we measured parameters known to reflect tissue manifestations of hypothyroidism, such as ankle reflex relaxation time and total cholesterol. Classical signs of hypothyroidism were present only in patients with severe overt hypothyroidism with low T3, but were rare or absent in patients with normal T3 but low free T4 or in patients with SCH (normal thyroid hormones but elevated basal TSH; mean scores, 7.8 ± 2.7 vs. 4.4 ± 2.2 vs. 3.4 ± 2.0; P < 0.001). Assessment of euthyroid subjects and T4-treated patients revealed very similar results (mean score, 1.6 ± 1.6 vs. 2.1 ± 1.5). In overt hypothyroid patients, the new score showed an excellent correlation with ankle reflex relaxation time and total cholesterol (r = 0.76 and r = 0.60; P < 0.0001), but no correlation with TSH (r = 0.01). The correlation with free T4 was r = −0.52 (P < 0.0004), and that with T3 was r = −0.56 (P < 0.0001). In SCH, the best correlation was found between the new score and free T4 (r =− 0.41; P < 0.0001) and TSH (r = 0.35; P < 0.0005). Evaluation of symptoms and signs of hypothyroidism with the new score in addition to thyroid function testing is very useful for the individual assessment of thyroid failure and the monitoring of treatment.

scholarly journals THYROID FUNCTION IN PREGNANCY: MATERNAL AND FETAL OUTCOMES WITH HYPOTHYROIDISM AND SUBCLINICAL THYROID DYSFUNCTION

2011 ◽  
Vol 22 (3) ◽  
pp. 169-187
Author(s):  
NEIL K VANES ◽  
JOHN H LAZARUS ◽  
SHIAO-Y CHAN
Keyword(s):  
Thyroid Hormones ◽  
Pregnant Women ◽  
Thyroid Function ◽  
Thyroid Dysfunction ◽  
Thyroid Disorders ◽  
Thyroid Function Tests ◽  
Fetal Outcomes ◽  
Function Tests ◽  
Maternal Wellbeing ◽  
In Pregnancy

Thyroid hormones are important in the development of the fetus and the placenta as well as in maintaining maternal wellbeing. Thyroid disorders are common in the population as a whole, particularly in women, and therefore are common during pregnancy and the puerperium. Biochemical derangement of thyroid function tests are present in approximately 2.5–5% of pregnant women.

scholarly journals Adherence to a Mediterranean Diet and Thyroid Function in Obesity: A Cross-Sectional Apulian Survey

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3173
Author(s):  
Roberta Zupo ◽  
Fabio Castellana ◽  
Francesco Panza ◽  
Luisa Lampignano ◽  
Isanna Murro ◽  
...  
Keyword(s):  
Thyroid Hormones ◽  
Mediterranean Diet ◽  
Thyroid Function ◽  
Serum Levels ◽  
Overweight And Obesity ◽  
Free T4 ◽  
Cross Sectional ◽  
Free T3 ◽  
Obese Subjects ◽  
The Relationship

Much research suggests that Mediterranean eating habits and lifestyle contribute to counteract the risk of chronic diseases while promoting longevity, but little information is available on the effects of the Mediterranean diet (Med-Diet) on thyroid function, particularly among overweight/obese subjects. Nevertheless, consistent data reported a slight increase in serum levels of the thyroid-stimulating hormone (TSH) and a higher rate of conversion of thyroxine (T4) to triiodothyronine (T3) in obesity. This cross-sectional study was aimed at investigating the relationship between adherence to the Med-Diet and circulating thyroid hormones in a cohort of overweight/obese subjects from Apulia (Southern Italy). Methods: We studied 324 consecutive outpatient subjects (228 women and 96 men, age range 14–72 years) taking no drug therapy and showing normal levels of thyroid hormones, but complicated by overweight and obesity (body mass index (BMI) ≥ 25 Kg/m2). The PREDIMED (PREvención con DIeta MEDiterránea) questionnaire was cross-sectionally administered to assess the adherence to the Med-Diet, and hormonal, metabolic, and routine laboratory parameters were collected. Results: Higher adherence to Med-Diet was found to be inversely related to free T3 (p < 0.01) and T4 (p < 0.01) serum levels. Considering each item in the PREDIMED questionnaire, people consuming at least four spoonfuls of extra-virgin olive oil (EVOO) per day, as well as those consuming at least two servings of vegetables per day, had lower free T3 levels (p 0.033 and p 0.021, respectively). Furthermore, consuming at least four spoonfuls of EVOO per day was found to be associated to lower free T4 serum concentrations (p 0.011). Multinomial logistic regression models, performed on tertiles of thyroid hormones to further investigate the relationship with Med-Diet, corroborated the significance only for free T4. Conclusion: Increased adherence to the Med-Diet was independently associated to a slightly reduced thyroid function, but still within the reference range for free T3 and T4 serum levels. This first finding in this field opens up a research line on any underlying biological interplay.

scholarly journals Glaucomatous Optic Nerve Changes and Thyroid Dysfunction in an Urban South Korean Population

2017 ◽  
Vol 2017 ◽  
pp. 1-9
Author(s):  
Yu Sam Won ◽  
Da Yeong Kim ◽  
Joon Mo Kim
Keyword(s):  
Optic Nerve ◽  
Thyroid Function ◽  
Univariate Analysis ◽  
Normal Subjects ◽  
Korean Population ◽  
Fundus Photography ◽  
Function Parameter ◽  
Thyroid Function Tests ◽  
Free T4 ◽  
The Relationship

Purpose.This study was performed to evaluate the relationship between intraocular pressure (IOP) and glaucomatous optic nerve change and thyroid factors in Korean population.Materials and Methods.The study included subjects who underwent health screening in Kangbuk Samsung Hospital. Detailed history taking and systemic and ocular examination including fundus photography were performed for all participants. All fundus photographs were divided into two groups based on disc and RNFL appearance: nonglaucoma and glaucoma group. Subjects were also divided into quartiles of each thyroid function parameter, and the relationship with IOP and glaucoma were analysed.Results.In univariate analysis, free T4, T3, and TSH in normal subjects and T3 in thyroid disease group were associated with the IOP. After adjusting for age and sex, the IOP tended to slightly decrease according to the level of the quartile of free T4 and T3 in normal subjects. In terms of glaucoma, on multivariate analysis, it did not show a significant correlation with any thyroid function tests.Conclusions.In normal subjects, the IOP tended to be decreased according to the level of free T4 and T3 but the amounts were clinically insignificant. Thyroid factors are not an independent risk factor for the development of glaucoma.

scholarly journals SAT-477 Melanoma Treated with Pembrolizumab Leading to Thyroiditis and Subsequent Hypothyroidism

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Heather Fishel
Keyword(s):  
Thyroid Function ◽  
T Cell Activation ◽  
Thyroid Dysfunction ◽  
Subsequent Development ◽  
Thyroid Function Tests ◽  
Free T4 ◽  
Specific Patient ◽  
Normal Thyroid ◽  
Free T3 ◽  
History Of

Abstract Background: Pembrolizumab (PD-1) is an immune checkpoint inhibitor used for treating melanoma and has been associated endocrine immune-related adverse events. Case Presentation: 76-year-old Caucasian male presented for evaluation of abnormal thyroid labs. Significant co-morbidities included recurrent melanoma, heart failure, atrial fibrillation, coronary artery disease, type 2 diabetes, hypertension. Patient’s melanoma was being treated with Pembrolizumab. Further history revealed no family/personal history of thyroid disease but a history of mouth cancer treated with radiation over 30 years ago. He denied any recent glucocorticoid or biotin use. Symptoms included worsening fatigue, weight loss, and diarrhea. He was afebrile and vitally stable. Physical exam was unremarkable. Prior to this year, patient had normal thyroid labs. Recent thyroid labs showed TSH of 0.01 uIU/mL (normal 0.34-4.94 uIU/mL), confirmed with repeat labs a week later (TSH: &lt; 0.01, Free T4: 2.23 ng/dL, normal Free T4: 0.7-1.48 ng/dL). There was a high suspicion that these labs were related to Pembrolizumab, but other etiologies were evaluated. Completed thyroid uptake and scan showed no evidence of increased activity (4-hour uptake: 1.6%, 24-hour update: 1.2%). Repeat thyroid labs indicated recovering thyroid function with a TSH: 0.14 uIU/mL, Free T4: 0.49 ng/dL, Free T3: 1.5 pg/mL (normal Free T3 2.3-4.2 pg/mL), TSI: 96% (normal &lt; 140%), TPO Ab: 111 IU/mL (normal TPO Ab &lt; 9 IU/mL). One month later thyroid tests resulted as TSH: 72.81 uIU/mL, Free T4: &lt; 0.40. He was started on levothyroxine, which was titrated over several weeks. Discussion: Pembrolizumab (PD-1) is an IgG4 programmed cell death 1-directed monoclonal antibody, whose mechanism of action is to inhibit cancer cells ability impede T-cell activation. However, because of this mechanism, some T-cells, will remain activated, leading to autoimmune diseases. PD-1 has been associated with thyroid dysfunction, with an incidence rate as high as 14-20%. The clinical presentation varies from isolated thyrotoxicosis to overt hypothyroidism. In our patient, he developed thyrotoxicosis with subsequent development of hypothyroidism. Generally, the timing of thyroid dysfunction after the initiation of PD-1 ranges from 3 to 40 weeks, with the median onset at week 6. Baseline TSH and free T4 should be obtained with rechecking of these labs monthly for the first 6 months. For patients who present with thyrotoxicosis, Grave’s disease should be ruled out, and initial treatment should include beta-blockers. Hypothyroidism should be treated with levothyroxine with titration to normal thyroid function tests. What remains to be determined is the mechanism in which PD-1 causes thyroid dysfunction and if specific patient characteristics, such as thyroid antibodies, can be used to risk stratify the likelihood of a patient developing thyroid dysfunction.

scholarly journals Thyroid Function Test in Patients with Chronic Kidney Disease

2021 ◽  
pp. 150-158
Author(s):  
V. Abhinaya ◽  
S. Magesh Kumar
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Thyroid Hormones ◽  
Thyroid Function ◽  
Thyroid Dysfunction ◽  
Thyroid Function Test ◽  
Free T4 ◽  
Cross Sectional ◽  
Male Predominance ◽  
Low T3

Background: Kidneys have a significant role in the metabolism, degradation and excretion of thyroid hormones. Both thyroid hormones and kidney functions have a multifaceted mutual interdependence. Objectives: To find out the possible association between the severity of chronic kidney disease and thyroid dysfunction; To estimate the correlation between thyroid dysfunction and various stages of chronic kidney disease. Materials and Methods: A prospective Cross-sectional study was done on 50 patients with Chronic kidney disease who were not on dialysis and fulfilled all the inclusion criteria at Saveetha medical college over a period of 6 months. Free T3, Free T4 and TSH levels were estimated for those patients. Results: Results of this study showed that majority of subjects included in our study were in the age group of 50-60 years with Male predominance. Out of 50 patients included in our study, 8 patients(16%) were found to hypothyroidism; 5 patients (10%) were having subclinical hypothyroidism; 20 patients (40%) were having low T3 syndrome and 17 patients (34%) were having normal functioning thyroid gland. Staging of CKD was done in relation to the glomerular filtration rate .Most of the patients(n=20) were in Stage 5 of Chronic kidney disease out of which 18 patients were having thyroid disorders. Conclusion: There is a positive correlation between the severity of CKD and thyroid dysfunction. Hence a routine thyroid function status should be evaluated in each and every patient of CKD to reduce the morbidity and mortality rate of CKD patients as well as reduce the social burden and health expenditure.

Study of Thyroid Function Tests in Cirrhosis of Liver And Correlation of Thyroid Function Tests Levels With Severity of Liver Dysfunction

2020 ◽  
Author(s):  
Mamatha B Patil
Keyword(s):  
Liver Cirrhosis ◽  
Liver Disease ◽  
Thyroid Hormones ◽  
Thyroid Function ◽  
Liver Dysfunction ◽  
Thyroid Dysfunction ◽  
Hepatic Function ◽  
Thyroid Function Tests ◽  
Function Tests ◽  
Cirrhosis Of Liver

Background: One of the leading causes of morbidity and mortality in the world is chronic liver diseases. Thyroid hormones regulate the basal metabolic rate of all cells, including hepatocytes, and thereby modulate hepatic function. The liver in turn metabolizes the thyroid hormones and regulates their systemic endocrine effects. Thyroid dysfunction may perturb liver function, liver disease modulates thyroid hormone metabolism, and a variety of systemic diseases affect both organs. Keeping in mind the above view we have done this study by highlighting the association between thyroid function tests with severity of liver dysfunction in cirrhosis of liver by using child Pugh scoring Methods: All patients aged 30-80 years with cirrhosis of liver who are attending Rajarajeshwari Medical College and Hospital. Detailed history, physical examination and drug history was taken as per pre-designed performa. Relevant investigations were done for assessing thyroid function and liver cirrhosis. Severity of liver dysfunction was graded by using Child Pugh Scoring Results: The prevalence of hypothyroidism among patients with liver cirrhosis was 64%. Majority of the cases had a high TSH and TSH levels were directly correlated severity of liver disease. Total T3 levels were low in majority of the cases and it was inversely correlated with severity of liver disease. FT3 was low in most of the cases with child B and child C score; it was inversely correlated with severity of liver disease. FT3 was found to be a more sensitive marker than total T3 for assessing severity of liver disease. Conclusion: Thyroid dysfunction is common in cirrhosis of liver hence thyroid function tests should be carried out in all cirrhotic patients to assess the severity and prognostication of such patients.

scholarly journals SAT-463 Thyrotoxicosis from Nivolumab in a Patient with Preexisting Graves’ Disease

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Preethi Polavarapu ◽  
Padmaja Akkireddy
Keyword(s):  
Adverse Events ◽  
Thyroid Function ◽  
Autoimmune Thyroiditis ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Thyroid Dysfunction ◽  
Checkpoint Inhibitors ◽  
Graves Disease ◽  
Thyroid Function Tests ◽  
Free T4

Abstract Introduction Thyroid dysfunction is one of the common immune-related adverse events associated with immune checkpoint inhibitors like Nivolumab. Thyroiditis or primary hypothyroidism is the most commonly reported presentation. Graves’ disease is less frequently reported. We report a case of preexisting Graves’ disease patient, on antithyroid meds who developed thyrotoxicosis followed by hypothyroidism after receiving Nivolumab therapy. Case 66 y/o female patient with newly diagnosed metastatic melanoma presented to us for evaluation of abnormal thyroid test after her second cycle of Nivolumab. She has a long-standing history of Graves’ disease and has been on methimazole since her diagnosis. Her baseline thyroid labs before the start of Nivolumab were within normal limits (on methimazole 2.5 mg daily). She presented with weight loss, palpitations, and tremors four weeks after the start of Nivolumab. On exam, she was tachycardic with tremors noted to outstretched hands and had diffusely enlarged thyroid. Repeat lab work done before her second cycle revealed suppressed TSH 0.02 (0.4-4.5 uIU/ml) with elevated free T4 and T3. Her TSI titers were elevated. Methimazole dose was increased to 10 mg daily, and follow up labs done in a month revealed TSH of 89 uIU/ml, Free T4 0.16 (0.76-1.8 ng/dl). Methimazole was completely stopped at this time. She continued to have elevated TSH despite being off of methimazole for more than a month, concerning for the development of hypothyroidism. She was started on levothyroxine, after which labs returned to normal. The patient continued on immunotherapy during this period. Discussion Immune checkpoint inhibitors have been increasingly used for cancer therapy. Endocrinopathies are the most common immune-related adverse events associated with the use of these agents, with thyroid dysfunction being more common. Our patient had well-controlled Graves’ disease and was on a stable dose of methimazole for years. She developed autoimmune thyroiditis four weeks after receiving immunotherapy and subsequently developed hypothyroidism. The literature search did not reveal cases of autoimmune thyroiditis in a patient with preexisting Graves’ disease. One study reported that the timeline for developing the thyrotoxic phase is five weeks, which is followed by the rapid development of either euthyroid or hypothyroid phase. Management during the thyrotoxic phase is usually beta-blockers. Current guidelines recommend checking thyroid function test before initiation of therapy and every two weeks after the diagnosis of thyrotoxicosis until they become euthyroid or hypothyroid. Our case illustrates that patients with preexisting Graves’ disease can develop thyroiditis after receiving immune checkpoint inhibitors, and hence, frequent monitoring with thyroid function tests is needed.

THYROID DYSFUNCTION IN PATIENTS WITH CHRONIC KIDNEY DISEASE: THE STATE OF THE PROBLEM AND THE WAYS OF SOLVING

2018 ◽  
Vol 22 (4) ◽  
pp. 40-49 ◽  
Author(s):  
A. R. Volkova ◽  
O. D. Dygun ◽  
B. G. Lukichev ◽  
S. V. Dora ◽  
O. V. Galkina
Keyword(s):  
Chronic Kidney Disease ◽  
Thyroid Gland ◽  
Kidney Disease ◽  
Thyroid Hormones ◽  
Thyroid Function ◽  
Thyroid Dysfunction ◽  
The Body ◽  
Type I ◽  
Low T3 ◽  
Iodine Excretion

Disturbance of the thyroid function is often detected in patients with different profiles. A special feature of patients with chronic kidney  disease is the higher incidence of various thyroid function  disturbances, especially hypothyroidism. It is known that in patients  with chronic kidney disease (CKD) iodine excretion from the body is  violated, since normally 90% of iodine is excreted in urine.  Accumulation of high concentrations of inorganic iodine leads to the  formation of the Wolf-Chaikoff effect: suppression of iodine  organization in the thyroid gland and disruption of the thyroid  hormones synthesis. Peripheral metabolism of thyroid hormones is  also disturbed, namely, deiodinase type I activity is suppressed and  peripheral conversion of T4 into T3 is inhibited (so-called low T3  syndrome). Therefore, patients with CKD are often diagnosed with  hypothyroidism, and the origin of hypothyroidism is not always  associated with the outcome of autoimmune thyroiditis. The article  presents an overview of a large number of population studies of  thyroid gland dysfunction in patients with CKD, as well as  experimental data specifying the pathogenetic mechanisms of  thyroid dysfunction in patients with CKD. Therapeutic tactics are still  not regulated. However, in a number of studies, replacement therapy with thyroid hormones in patients with CKD had some advantages.

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