Abstract
The metabolic syndrome (MS) is a cluster of conditions that occur. togehther, increase risk of heart disease, storke, type 2 diabetes mellitus and hypertension as a possible outcome. The previous research has shown a link between hearing loss and being overweight, diabetic, or suffering from heart disease. However, research on the possible link between hearing loss and metabolic syndrome is limited. Hearing loss due to metabolic syndrome was evaluated in the present investigation. Two hundred individuals with metabolic syndrome were included. All the patients were evaluated on three types of audiometry (pure tone, impedence, and DPOAE).Anthropometric data, blood pressure, blood sugar, and lipid profiles, were all collected from each patient. We also asked about their smoking and drinking habits in the past. SPSS v. 22.0 was used to conduct the statistical analysis. Overall, SNHL affected 58.5% of patients. Patients having moderate hearing loss were the largest demographic group (40%), followed by those with mild hearing loss (15% ). Severe hearing loss only occurred in 3.5% of patients. Hearing loss was shown to be more prevalent in patients with more than three components of metabolic syndrome. Significant associations were found between hearing impairment and metabolic risk factors as waist circumference, fasting blood sugar, serum high-density lipoprotein, serum triglycerides, and systolic and diastolic blood pressure. Hearing loss was only marginally connected to smoking and excessive drinking.
Keywords: Metabolic syndrome, Sensorineural hearing loss, Blood pressure, Obesity, BMI, Waist circumference, HDL, Triglycerides, Dyslipidemia, Smoking, Alcohol
Introduction
Multiple sclerosis has been linked to many different diseases. These include coronary insufficiency, sleep apnea, type 2 diabetes mellitus, cancer, polycystic ovary syndrome, fatty liver, abnormal cholesterol levels, high blood pressure, atherosclerosis, transient ischemic attack, stroke, and myocardial infarction. Patients with metabolic syndrome often have insulin resistance, which disrupts glucose metabolism and lessens the body’s ability to produce energy through glycolysis. However, due to its extensive information processing, the auditory system has a high energy need. Thus, energy is obtained by non-conventional metabolic routes such lipid peroxidation and protein oxidation. This results in the production of many free radicals along with ROS (Reactive Oxygen species). The results of this process in the inner ear is impaired auditory perception. Impaired insulin signalling in the tissue is another consequence of insulin resistance. Impaired glucose uptake, endothelial dysfunction, poor angiogenesis, metabolic rigidity, vascular stiffness, and atherosclerosis all arise from impaired insulin metabolic signalling. Hearing loss occurs when blood supply to the cochlea is interrupted, resulting in ischemia events that cause hair cell apoptosis or necrosis [1, 2].
Definition of Metabolic Syndrome
“The World Health Organization (WHO) defines metabolic syndrome as the presence of two or more of the following features: impaired glucose tolerance (IGT), diabetes mellitus (DM), and/or insulin resistance.
Raised arterial pressure, i.e., 140/90 mm of Hg.
Raised plasma triglyceride (150 mg/dl) and/or low HDL-C (< 35 mg/dl in men and < 39 mg/dl in women).
Central, i.e., waist/hip ratio (WHR) > 0.9 in men and > 0.85 in women and/or body mass index (BMI) > 30 kg/m2.
Microalbuminuria, i.e., urinary albumin excretion rate ≥ 20µgm/minute or albumin/creatine ratio30µgm/mg [5].
NCEP ATP-III is the most widely used of these scenarios. The following criteria were used in this definition to diagnose metabolic syndrome:
Abdominal obesity: WC (waist circumference) 102 cm (> 40 inch) in men and 88 cm (> 35 inch) in women.
Hypertriglyceridemia (TGs): 150 mg/dl (1.695mmol/l).
Low HDL-C: <40 mg/dl in men and < 50 mg/dl in women.
High blood pressure (BP): >130/85 mm Hg.
High fasting glucose: >100 mg/dl.”
To diagnose Metabolic Syndrome, 3 (or more than 3) out of these 5 should be fulfilled. [3].
There is paucity of data on co-relation between MS and SNHL. Although not much studies have been done on the association between MS and SNHL, but the few studies that have been done which show positive co-relation between MS and SNHL. Here, we tried to determine how often sensorineural hearing loss is amongst 200 people with metabolic syndrome. This study was conducted on 200 subjects at the outpatient department (OPD) of Otorhinolaryngology at Rajindra hospital, Government Medical college, Patiala.
Aims and Objectives
To address relation between sensorineural hearing loss and metabolic syndrome.
To analysis the prevalence of hearing loss in patients with metabolic syndrome.
To examine the relation between metabolic syndrome and hearing loss.
Materials and Methods
Study design and population-Cases with metabolic syndrome with an established diagnosis were chosen for this research. All patients provided their written informed consent .detailed medical history regarding duration and medication of diseases (hypertension, diabetes mellitus, dyslipidemia) was taken. Personal history about smoking, alcohol or any other addiction, demographic data and socioeconomic background were noted. Also, complete ENT history was taken along with clinical examination of ear, nose and throat was done. General physical examination of the patient included height and weight of the patient (BMI was calculated) along with blood pressure checkup (in sitting down position after calming down the patient for 10 min). Patients underwent biochemical investigations that included serum triglycerides level, blood glucose levels, as well as serum high density lipoproteins level.
Inclusion Criteria
Patients who qualify 3 or more than 3 criteria of NCEP-ATP III Protocol for diagnosing metabolic syndrome.
Age less than 55 years.
Willingness to participate in study.
Patient of both sexes.
Exclusion Criteria
Causes of permanent hearing loss include loud noise exposure at work, a family history of deafness, traumatic brain injury, and congenital causes of sensorineural hearing loss.
Patients taking ototoxic drug (e.g. aminoglycosides).
Patients unwilling or unable to comply with study proceedings.
Age more than 55 years.
Audiological Examination
PTA (Pure tone audiometry), impedance audiometry (tympanometry), and OAE (otoacoustic emission) testing were all part of the comprehensive audiological evaluation. In the soundproofed outpatient clinic of the ENT Department at Rajindra Hospital in Patiala, the audiological evaluation was done. The hearing thresholds were measured using an ALPS Advanced digital audiometer AD2100, which is available commercially and can measure both speech frequencies and higher frequencies.
Tympanometry was performed using the commercially available AT235INTERACOUSTICS device. Tympanometry was performed utilizing 226 Hz probe tone and a pressure range of + 200 to -300da Pa. The MAICO DIAGNOSTICS ERO-SCAN (Item No.8,106,838) was used to measure otoacoustic emissions.
Statistical Analysis
SPSS software, version 22.0 (Chicago, Illinois, USA), has been utilized for statistical analysis. To be statistically significant, a p value needed to be less than 0.05, while a p value < 0.01 was regarded as very significant. Spearman’s r, a measure of correlation, was determined.
Observations and Results
Two hundred people in total participated in the research. The patients’ average age was 43.4 ± 7.13 years. Nearly half of the patients were between the ages of 41 and 50. There were 129 (64.50%) male and 71 (35.50%) female. 1.8: 1 was the ratio between male and female.
The baseline biochemical investigations were done and 155 (77.50%) patients had abnormal HBA1C levels, 200(100%) patients had abnormal FBS levels. 140 (70%) patients had abnormal Serum Triglycerides levels and 68 (34%) patients had decreased HDL levels. Out of 200, 184(92%) patients had Hypertension. Majority of patients (n = 124; 62%) had abdominal obesity.
The mean HbA1C level was 7.59 ± 0.52, fasting blood sugar was 145.18 ± 25.02 mg/dL. The Mean serum triglyceride was 163.72 ± 20.88 mg/dl, and serum HDL was 45.72 ± 10.12 mg/dL. majority of patients (n = 173; 86.50%) were obese (BMI ≥ 25), followed by patients with normal weight (n = 14; 7%), overweight patients (n = 12; 6%), and underweight patients (n = 1; 0.50%).The mean waist circumference of patients was 98.65 ± 7.31 cm (with a range from 84 to 110 cm). The mean SBP of patients was 147.85 ± 14.44 mm Hg (having range of 102-180 mm Hg), while mean DBP was 94.03 ± 8.10 mm Hg (having range of 68-124 mm Hg). There were 200 patients, and 55 (27.50%) had a history of alcohol use, whereas 40 (20%) had a smoking history. 7% of patients (14) had a history of alcohol and tobacco use.
Out of the total 200 subjects, 117 patients (58.5%) had hearing loss, and 84 patients (42%) did not have hearing loss. Only 58 patients (29%) had tinnitus. 83 patients (41.50%) received the “Pass” result on OAE screening, while 117 patients (58.50%) received the “Refer” result Out of total 200 patients, 83 patients had PTA ≤ 25 dB (Normal hearing), 80 patients had PTA 26–40 dB (Mild SNHL), 30 patients had PTA 41–55 dB (Moderate SNHL), and 7 patients had PTA 71–90 dB (Severe SNHL). The mean PTA was 32.02 ± 12.12 db. The current research demonstrated that individuals with higher metabolic syndrome components (for example 4 or 5) were more likely to have hearing loss (like 3). Hearing impairment was significantly associated with increased waist circumference, lower HDL, higher triglycerides, higher fasting glucose, and higher blood pressure (Tables 1 and 2). Hearing loss was only marginally connected to smoking and excessive drinking (Fig. 1, 2, 3 and 4).
Table 1.
Correlation of Sensori-neural hearing loss variables with different components of Metabolic syndrome
| Spearman’s correlation coefficient (r value) | Sensori-neural hearing loss | |
|---|---|---|
| Diabetes mellitus (FBS) | r* | 0.714 (High +) |
| p value# | 0.001 | |
| Serum triglycerides | r* | 0.533 (Mod. +) |
| p value# | 0.001 | |
| Serum HDL | r* | − 0.456 (Mod. -) |
| p value# | 0.001 | |
| Obesity (Waist Circumference) | r* | 0.302 (Low +) |
| p value# | 0.001 | |
| DBP | r* | 0.707 (High +) |
| p value# | 0.001 | |
| SBP | r* | 0.594 (Mod. +) |
| p value# | 0.001 | |
Table 2.
Correlation of hearing loss variables with different components of Metabolic Syndrome
| Spearman’s correlation coefficient (r value) | Hearing loss | PTA right ear | PTA left ear | OAE | |
|---|---|---|---|---|---|
| Diabetes Mellitus | r* | 0.714 (High +) | 0.581 (Mod. +) | 0.526 (Mod. +) | 0.700 (High +) |
| p value# | 0.001 | 0.001 | 0.001 | 0.001 | |
| Serum Triglycerides | r* | 0.533 (Mod. +) | 0.560 (Mod. +) | 0.492 (Mod. +) | 0.530 (Mod. +) |
| p value# | 0.001 | 0.001 | 0.001 | 0.001 | |
| Serum HDL | r* | − 0.456 (Mod. -) | − 0.404 (Mod. -) | − 0.371 (Low -) | − 0.455 (Mod. -) |
| p value# | 0.001 | 0.001 | 0.001 | 0.001 | |
| Obesity(Waist Circumference) | r* | 0.302 (Low +) | 0.309 (Low +) | 0.259 (Low +) | 0.303 (Low +) |
| p value# | 0.001 | 0.001 | 0.001 | 0.001 | |
| DBP | r* | 0.707 (High +) | 0.568 (Mod. +) | 0.578 (Mod. +) | 0.701 (High +) |
| p value# | 0.001 | 0.001 | 0.001 | 0.001 | |
| SBP | r* | 0.594 (Mod. +) | 0.454 (Mod. +) | 0.433 (Mod. +) | 0.591 (Mod. +) |
| p value# | 0.001 | 0.001 | 0.001 | 0.001 | |
| H/o alcohol | r* | 0.138 (V.low +) | 0.135 (V.low +) | 0.079 (V.low +) | 0.155 (V.low +) |
| p value# | 0.051 | 0.057 | 0.266 | 0.028 | |
| H/o smoking | r* | 0.071 (V.low +) | 0.106 (V.low +) | 0.125 (V.low +) | 0.066 (V.low +) |
| p value# | 0.318 | 0.137 | 0.079 | 0.353 | |
| > 3 components of metabolic Syndrome | r* | 0.490 (Mod. +) | 0.582 (Mod. +) | 0.479 (Mod. +) | 0.484 (Mod. +) |
| p value# | 0.001 | 0.001 | 0.001 | 0.001 | |
Fig. 1.
: Gender distribution
Fig. 2.
: Abdominal Obesity
Fig. 3.
PTA findings
Fig. 4.
OAE findings
Discussion
The metabolic syndrome is defined as a group of symptoms and conditions, which raises one’s chances of experiencing cardiovascular issues. Impaired glucose tolerance/diabetes mellitus, hypertension, and altered lipid profiles are all part of this syndrome. Each component of metabolic syndrome has been connected to hearing loss.
Cochlear ischemia and peripheral vascular disease have been linked to stria vascularis damage, which in turn causes hearing loss and metabolic syndrome, indicating a connection between the two conditions. Disruptions in the ion transport system, including the Na+/K + pump and gap junctions, seem to be the source of significant decreases in endocochlear potential and the concomitant morphological aberrations in the fine structure of the stria vascularis. [4] The link between high blood sugar and hearing loss might be due to a number of factors in the body. Pathogenic alterations in the microvasculature and sensory nerves were seen in diabetic complications as retinopathy, peripheral neuropathy along with nephropathy. [16] Capillaries, which include sensory neurons in the inner ear, may be affected by these degenerative alterations. The brains of those who died of hyperglycemia and diabetes showed demyelination of the eighth cranial nerve. This nerve transports auditory information from the cochlea to the brainstem. [17, 18] Cochlear-specific pathologic alterations include increased outer hair cell loss and thicker vessel walls in the lower basal turn. Narrowing of internal auditory artery along with other vascular alterations were also mentioned [19]. High plasma glucose is linked to elevated oxidative stress, which may play a role in the pathogenesis of noise-induced hearing loss [20] [21].
Effect of Diabetes Mellitus on Hearing
Retina, peripheral artery, kidney, and peripheral nerve problems are microvascular and neuropathic consequences of diabetes mellitus. Sensorineural hearing loss might be the result of damage to the vascular or neuronal system of the inner ear brought on by pathologic changes associated with diabetes mellitus. [5] Oxidative stress, hyperglycemia, as well as endothelial dysfunction caused by diabetes mellitus all contribute to cellular damage. Stria vascularis atrophy and vascular basement membrane thickening are additional complications of diabetes mellitus. The consequence of this is a disruption in the formation of endocochlear potentials and the processing of auditory signals by hair cells. [6] A Spearman’s r value of + 0.714 indicates a positive relation between sensorineural hearing loss and diabetes mellitus in this research of 200 individuals with metabolic syndrome (High).
Effect of Dyslipidemia on Hearing
In contrast to LDL-C, which facilitates atherosclerosis by transporting cholesterol, TG, phospholipids, and other fat molecules, HDL-C carries excess cholesterol and so prevents atherosclerosis. Hearing loss may occur when abnormalities in the cochlear vasculature, caused on by atherosclerosis, damage the hair cells of the inner ear. [7] Statistically, there was a connection between abnormal Serum triglycerides and abnormal Serum HDL levels and Sensorineural hearing loss (p value 0.001 for both). There was a moderately positive (+ 0.533) connection between TGs and SNHL, but a moderately negative (− 0.533) one between TGs and HDL (− 0.456).
Effect of Obesity on Hearing
Obesity-related atherosclerosis causes the internal auditory arteries to stiffen and constrict, reducing blood flow to the cochlea and raising the risk of stria vascularis, cell death, and hearing loss. [8] Obesity-related atherosclerosis causes capillary constriction, which is thought to induce mortality through ischemia damage, oxidative stress, as well as the formation of ROS in the cochlea and spiral ganglia [9]. A statistically significant (p < 0.001) correlation has been found between obesity (measured by waist circumference) and sensorineural hearing loss (r = + 0.302). (low).
Effect of Hypertension on Hearing
An increase in hypertension increases the risk of inner ear hemorrhage, which in turn increases the risk of gradual or abrupt SNHL, and a decrease in capillary blood flow may increase the risk of hearing impairment due to a shortage of oxygen. Hearing loss may result from hypertension-related arteriosclerotic abnormalities in the inner ear, which decrease elasticity of blood vessels, narrow inner ear blood vessels, and decrease blood flow. [10] Both systolic as well as diastolic blood pressure have been moderately and highly correlated with sensorineural hearing loss (p < 0.001 for both) as measured by the Spearman Correlation Coefficient (r value).
Effect of Smoking and Alcohol Intake on Hearing
Smoking-related increases in inflammatory markers and reactive oxygen species in the bloodstream, as well as atherosclerotic alterations, may cause nerve degeneration and injury to the cochlea [11, 12]. The increased risk of exposure from diabetes means that the link between hearing loss and smoking is stronger in this population. Carbon monoxide causes hearing loss by hypoxic stress on hair cells, whereas nicotine causes hearing loss through direct ototoxic effects on hair cell activity and neurotransmission of auditory stimuli.[13, 14]. Acute alcohol use may momentarily disrupt auditory processing and alter auditory thresholds, while chronic alcohol consumption was connected to permanent hearing loss. [15] There was a history of alcohol use in 55 patients (27.50%) and smoking in 40 individuals (20%). 7% of patients (14) had a history of alcohol and tobacco use. However, the link between smoking and health outcomes was minimal (r value 0.071 and p-value 0.318) as well as drinking (r = 0.128, p = 0.051) with auditory dysfunction.
Conclusion
Hearing loss was shown to be more common among individuals with a larger number of metabolic syndrome components (such as 4 or 5), as shown in the current research (like 3). A substantial correlation has been found between waist size and hearing loss, serum triglycerides, serum HDL, fasting blood sugar, as well as systolic and diastolic blood pressure. Smoking along with alcohol usage were weakly related to hearing loss.
Limitation
The present study’s Limitation is small sample size with limited duration of study. In Future larger-scale prospective randomized trials over to larger geographical locations will facilitate more reliable investigation and greatly substantiate the conclusions of this study.
Acknowledgements
The authors did not receive support from any organization for submitted work.
Author Contributions
All authors were equally involved in data collection, conception, analysis, drafting, design and approval of final manuscript.
Funding
None.
Data Availability
Research data are not shared.
Declarations
Conflict of interest
The authors declare no conflict of interest.
Ethical Approval
The study protocol was approved by the Institutional Review Board for Ethical Clearance of Government Medical College and Rajindra Hospital.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
- 1.Le T, Keithley EM. Effects of antioxidants on the aging inner ear. Hear Res. 2007;226:194–202. doi: 10.1016/j.heares.2006.04.003. [DOI] [PubMed] [Google Scholar]
- 2.Aroor AR, McKarns S, Demarco VG, Jia G, Sowers JR. Maladaptive immune and inflammatory pathways lead to cardiovascular insulin resistance. Metabolism. 2013;62:1543–1552. doi: 10.1016/j.metabol.2013.07.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.NCEP expert panel in (2001) Detection, evaluation and treatment of high blood pressure in adults executive summary of the third report of the national cholesterol education Programme (NCEP) expert panel on detection, evaluation and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA 285:2486–2497 [DOI] [PubMed]
- 4.Ramos A, Lorenzo AI, Ferrán S, Manrique M Metabolic risk factors. GAES Medica. Available at: https://www.gaesmedica.com/es-es/fragility-and-presbycusis/predisposing-factors-linked-to-presbycusis-and-balance-disorders/metabolic-risk-factors
- 5.Bainbridge KE, Hoffman HJ, Cowie CC. Diabetes and hearing impairment in the United States: audiometric evidence from the National health and nutrition examination survey, 1999 to 2004. Ann Intern Med. 2008;149(1):1–0. doi: 10.7326/0003-4819-149-1-200807010-00231. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Akinpelu OV, Ibrahim F, Waissbluth S, Daniel SJ. Histopathologic changes in the cochlea associated with diabetes mellitus–A review. Otol Neurotol. 2014;35(5):764–774. doi: 10.1097/MAO.0000000000000293. [DOI] [PubMed] [Google Scholar]
- 7.Evans MB, Tonini R, Shope CD, Oghalai JS, Jerger JF, Insull W, Jr, Brownell WE. Dyslipidemia and auditory function. Otol Neurotol. 2006;27(5):609–614. doi: 10.1097/01.mao.0000226286.19295.34. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Sun YS, Fang WH, Kao TW, Yang HF, Peng TC, Wu LW, et al. Components of metabolic syndrome as risk factors for hearing threshold shifts. PLoS ONE. 2015;10(8):e0134388. doi: 10.1371/journal.pone.0134388. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Curhan SG, Eavey R, Wang M, Stampfer MJ, Curhan GC. Body mass index, waist circumference, physical activity, and risk of hearing loss in women. Am J Med. 2013;126(12):1142. doi: 10.1016/j.amjmed.2013.04.026. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Agarwal S, Mishra A, Jagade M, Kasbekar V, Nagle SK. Effects of hypertension on hearing. Indian J Otolaryngol Head Neck Surg. 2013;65(Suppl 3):614–618. doi: 10.1007/s12070-013-0630-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Durante AS, Pucci B, Gudayol N, et al. Tobacco exposure during childhood: effect on cochlear physiology. Int J Environ Res Public Health. 2013;10:5257–5265. doi: 10.3390/ijerph10115257. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Durazzo TC, Mattsson N, Weiner MW. For the ADNI. Smoking and increased Alzheimer’s disease risk: a review of potential mechanisms. Alzheimers Dement. 2014;10:S122–S145. doi: 10.1016/j.jalz.2014.04.009. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Agrawal Y, Platz EA, Niparko JK. Risk factors for hearing loss in US adults: data from the National health and nutrition examination survey, 1999 to 2002. Otol Neurotol. 2009;30(2):139–145. doi: 10.1097/MAO.0b013e318192483c. [DOI] [PubMed] [Google Scholar]
- 14.Curhan SG, Eavey Wang R, Stampfer M, Curhan MJGC. Occupational noise, smoking, and a high body mass index are risk factors for age-related hearing impairment and moderate alcohol consumption is protective: a European population-based multicenter study. J Assoc Res Otolaryngol. 2008;9(3):264–276. doi: 10.1007/s10162-008-0123-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Curhan SG, Eavey R, Wang M, Stampfer MJ, Curhan GC. Prospective study of alcohol consumption and self-reported hearing loss in women. Alcohol. 2015;49(1):71–77. doi: 10.1016/j.alcohol.2014.10.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Friedman SA, Schulman RH, Weiss S. Hearing and diabetic neuropathy. Arch Intern Med. 1975;135(4):573–576. doi: 10.1001/archinte.1975.00330040085014. [DOI] [PubMed] [Google Scholar]
- 17.Jorgensen MB. The inner ear in diabetes mellitus. Histological studies. Arch Otolaryngol. 1961;74:373–381. doi: 10.1001/archotol.1961.00740030382003. [DOI] [PubMed] [Google Scholar]
- 18.Makishima K, Tanaka K. Pathological changes of the inner ear and central auditory pathway in diabetics. Ann Otol Rhinol Laryngol. 1971;80(2):218–228. doi: 10.1177/000348947108000208. [DOI] [PubMed] [Google Scholar]
- 19.Fukushima H, Cureoglu S, Schachern PA, et al. Cochlear changes in patients with type 1 diabetes mellitus. Otolaryngol Head Neck Surg. 2005;133(1):100–106. doi: 10.1016/j.otohns.2005.02.004. [DOI] [PubMed] [Google Scholar]
- 20.Makishima K. Arteriolar sclerosis as a cause of presbycusis. Otolaryngology. 1978;86(2):ORL322–ORL326. doi: 10.1177/019459987808600225. [DOI] [PubMed] [Google Scholar]
- 21.Daiber A, Kröller-Schön S, Oelze M, Hahad O, Li H, Schulz R, et al. Oxidative stress and inflammation contribute to traffic noise-induced vascular and cerebral dysfunction via uncoupling of nitric oxide synthases. Redox Biol. 2020;34:101506. doi: 10.1016/j.redox.2020.101506. [DOI] [PMC free article] [PubMed] [Google Scholar]
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Data Availability Statement
Research data are not shared.