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. 2023 Jun 20;23(7):549–557. doi: 10.1111/ggi.14629

Effects of the salivary gland massage program in older type 2 diabetes patients on the salivary flow rate, xerostomia, swallowing and oral hygiene: A randomized controlled trial

Supanee Jeamanukulkit 1, Tippanart Vichayanrat 2,, Patcharaphol Samnieng 3
PMCID: PMC11503633  PMID: 37337980

Abstract

Aim

To evaluate the effect of a salivary gland massage program to improve salivary flow, swallowing, and oral hygiene in older type 2 diabetes patients.

Methods

This randomized control trial consisted of 73 older diabetes patients with a low salivary flow; 39 and 34 in intervention and control groups, respectively. The intervention group received a salivary gland massage from a trained dental nurse, whereas the control group received a dental education. The salivary flow rates were collected using spit methods at baseline, 1‐month and 3‐month follow up. All participants were examined for the objective and subjective symptoms of xerostomia, the Simplified Debris Index and the Repetitive Saliva Swallowing Test.

Results

After 3 months, the resting (0.32 vs 0.14 mL/min, P < 0.001) and stimulating salivary flow (3.66 vs 2.83 mL/min, P = 0.025) in the intervention group was significantly higher than the control group. The objective symptoms in the intervention group were significantly lower than the control group after 3 months (1.41 vs 2.26, P = 0.001). The participants who were able to swallow least three times in the Repetitive Saliva Swallowing Test in the intervention group increased by 35.89% after 3 months, whereas the control group increased by 8.82%. Oral hygiene was improved in both groups, but the changes in the intervention were significantly greater than in the control group.

Conclusions

The 3‐month salivary glands massage program increases the salivary flow rate, and affects swallowing, objective dry mouth symptoms and oral hygiene in older patients with type 2 diabetes. Geriatr Gerontol Int 2023; 23: 549–557.

Keywords: diabetes, oral hygiene, salivary flow, salivary gland massage, xerostomia


Effects of salivary gland massage in older type 2 diabetes patients on salivary flow rate, xerostomia, swallowing, and oral hygiene.

graphic file with name GGI-23-549-g001.jpg

Introduction

Diabetes mellitus (DM) is a global epidemic, and affect patients' quality of life due to its complications and lifestyle modification. 1 In 2021, diabetes prevalence was 10.5% (536.6 million people), and is projected to rise to 12.2% (783.2 million) in 2045. 2 The increase in diabetes is expected to occur the most in middle‐income countries and be the highest among those aged 75–79 years. 2

Major oral problems of diabetes patients include mouth dryness or xerostomia, 3 , 4 often associated with a burning sensation, ulcers, candidiasis, cheilitis, lichen planus, salivary gland swelling, delayed wound healing, increased severity of infection, periodontal diseases and increased the risk of dental caries. 4 Although xerostomia is the subjective symptom of mouth dryness, hyposalivation is the objective reduction of salivary flow defined when an unstimulated saliva flow rate is <0.1 mL/min. 3 The systematic review showed that xerostomia and hyposalivation are more frequent among DM patients than non‐DM patients. 3 However, no significant difference was observed in the salivary flow rate between type 1 and type 2 diabetes patients. 5 Hyperglycemia in DM patients results in polyuria and osmotic diuresis, causing dehydration, which relates to a reduced salivary flow. 6 In addition, some antidiabetic drugs inhibit glucose reabsorption in the kidneys, and glycosuria leads to oral dryness. 6 , 7 , 8

Various methods for dry mouth treatment and symptom management include salivary stimulants, topical agents, saliva substitutes and systemic sialogogues. 9 , 10 Nevertheless, studies of salivary gland massage were scarce. Two studies in Japan showed that the oral function promotion program, including facial and tongue exercise, and salivary gland massage, increased salivary flow rate in independent older persons. 11 , 12 A simple oral exercise carried out in Korea, which included mastication, salivation and swallowing exercises, showed that the 2‐min twice‐daily oral exercise could improve the unstimulated saliva and swallowing immediately and 1 week after the program. 13 Recently, the supportive program for patients with head and neck cancer radiation, including oral hygiene instruction, facial and tongue massage, and salivary gland massage, resulted in greater relief of xerostomia at 3 months post‐radiotherapy, and better recovery of the salivary flow rate at 12‐month post‐radiotherapy. 14

Although the various oral health programs to reduce xerostomia reported improving salivary secretion among older persons, no intervention was exclusively on salivary gland massage. 15 In addition, the salivary gland massage intervention specifically for diabetes patients has not been evaluated. Thus, the present study aimed to evaluate the effects of the salivary gland massage program among Thai older persons with type 2 diabetes. We hypothesized that the salivary gland massage program taught by the dental nurse could improve the salivary flow rate, dry mouth symptoms, oral hygiene and swallowing among older diabetes patients after 3 months.

Methods

The present study was approved by the ethical committee of the Faculty of Dentistry/Faculty of Pharmacy, Mahidol University, Institutional Review Board (No.MU‐DT/PY‐IRB 2020/081.2212). All participants had the process explained to them and voluntarily agreed to participate in this study. Before data collection, written informed consent was obtained from all participants. This study was registered with the Thai Clinical Trial Registry (Registration TCTR ID: TCTR20210507003).

Study population and samples

The present study included older patients aged ≥60 years who received diabetes medication at the Health Promotion Hospital in Wangchan district, Rayong province, Thailand. The sample size was calculated by two independent samples from the previous study. 11 The sample size required in each group was 34 and increased by 10% for loss of follow up in each group, and overall was 74 participants. Inclusion criteria were DM patients aged ≥60 years with resting saliva <0.3 mL/min. Patients with hypotension, renal disease, thyroid disease, smoking history and anemia were excluded, because certain health conditions can affect the study results.

Random allocation and concealment

A trained dentist screened and examined the oral cavity for objective symptoms of xerostomia and collected saliva from the patients. The rest of the questionnaire was collected if the resting salivary flow rate was <0.3 mL/min. Then, the eligible patient was sent to the dental nurse in another room for random assignment to intervention or control groups by taking the sealed envelope number. However, if the dental nurse noticed that the patients came together, they would be assigned to the same group. Thus, throughout the study, the examiner was blinded to the patient's group, whereas the patients were unaware of the group assigned.

Intervention procedures

The trained dental nurse taught the patients in the intervention group to massage the salivary glands at baseline, 1 month and 3 months. The dental nurse invited the patient to sit on the chair in a comfortable position. The dental nurse used the poster and showed the patients how to massage three salivary glands, including the parotid gland, submandibular gland and sublingual gland, and instructed the patient to massage three times before meals every day.

The instruction of salivary gland massage in the present study followed the guideline from the Mahidol Geriatric Dental Clinic, Faculty of Dentistry. For the parotid gland, the patient used four fingers (index, middle, ring and little fingers) to massage in front of the ears on both sides 10 times. Then, the patient used the left and right thumbs to massage the submandibular gland under the chin on both sides 10 times. Finally, for the sublingual gland, the patient used the thumbs to massage underneath the jawline, pressing under the ears toward the chin on both sides (see Appendix A; Salivary Gland Massage Poster). Patients were instructed to carry out this massage on both sides for approximately 2 min three times daily. This technique is slightly different from the Sjögren's Foundation, Patient Education Sheet 16 in that our method uses four fingers instead of two fingers for parotid gland massage, and different from the previous study that used the palm to massage the parotid gland. 17

To evaluate the patient's practice, the dental nurse put the cotton roll on the floor of the mouth and checked the wetness of the cotton roll after salivary gland massage. The dental nurse also gave the patient a 4‐month follow‐up calendar to check the frequency of the patient's actual salivary massage (Appendix B; Calendar For Checking and Recalling). The dental nurse telephoned the patient once a week to encourage daily massages.

For the control group, the dental nurse provided general dental education regarding tooth wear, tooth loss, dental caries and gingivitis using the education poster (Appendix C; Oral Health Education Poster). Both groups were taught again at 1 and 3 months, the same as the first time, and the patients were encouraged to keep following the instructions.

Outcome measures

The questionnaire for collecting the participant's information had six parts, as follows.

Part 1: General information

General information, including sex, age, fasting blood sugar, glycated hemoglobin, systemic diseases and medication, was collected by interviewing the patients and obtained from the hospital chart record.

Part 2: Objective symptoms of xerostomia (10 items)

A 10‐point clinical oral dryness score based on Osailan et al. was used. 18 A trained dentist examined the oral cavity and checked if the following conditions were present: mouth mirror sticks to the buccal mucosa, tongue, saliva frothy, no saliva pooling on the floor of the mouth, tongue shows loss of papillae, altered (smooth) gingival architecture, glassy appearance to the oral mucosa, cervical caries on more than two teeth, tongue highly fissured and debris on the palate.

Part 3: Subjective symptoms of xerostomia (4 items)

The four specific questions were used to evaluate oral dryness, which responded to saliva secretion from the study by Fox et al. 19 The trained dentist asked the patients to indicate “Yes” or “No” whether the following conditions were present: (i) “Does the amount of saliva in your mouth seem to be too little?”; (ii) “Do you have any difficulty swallowing?”; (iii) “Does your mouth feel dry when eating a meal?”; and (iv) “Do you sip liquids to aid in swallowing dry food?”.

Part 4: Repetitive saliva swallowing test

The repetitive saliva swallowing test (RSST) was measured by asking the patient to swallow saliva as many times as possible for 30 s, while deglutition was counted through palpation of the larynx. 20 The swallowing times were recorded as 0 (cannot swallow), one or two times, or three times or more. Less than three swallowing times was indicated as difficulty swallowing. 20 , 21

Part 5: Salivary flow rate

The salivary flow rate was collected in the morning, and the patients were asked to abstain from food and water, and not brush their teeth at least 2 h before salivary collection. The patient's posture during the salivary collection procedure was to sit on a chair and tilt the head slightly forward. The resting salivary flow rate was collected by having the patients spit the whole secreted saliva directly into a sterile tube for 5 min. 22 A stimulated salivary flow rate was collected by having a patient spit into a tube while chewing a piece of sterile paraffin for 5 min. 22 The resting and stimulated salivary flow rates were recorded in milliliters (mL) from the scale of the sterile tube.

Part 6: Simplified Debris Index

Debris was determined by examining six surfaces of six teeth, including four posterior teeth of the four quadrants of the upper and lower jaws, and two anterior teeth based on the Greene and Vermilion method. 23

After 1 month and 3 months, the patients were measured for salivary flow rate, RSST and the Simplified Debris Index (DI‐S) again. At 3 months, the patients were asked about the subjective and objective symptoms of xerostomia.

Statistical analysis

The data were statistically analyzed by using spss software, version 22 (IBM Corporation, Armonk, NY, USA). The Mann–Whitney U‐test, χ2‐test and Wilcoxon signed‐rank test were used as appropriate. The significance level was set at P < 0.05. In addition, the questionnaires were tested for internal consistency reliability using Cronbach's alpha coefficient. Cronbach's alphas for the subjective symptom scale items were 0.709, which was considered reliable.

Results

Characteristics of the samples

Table 1 shows the characteristics of the samples in the present study. A total of 73 participants were included, 39 in the intervention group and 34 in the control group. Most participants, both in the intervention and control groups, were in the 65–74 years age group. The mean ages of the intervention and control groups were 68.13 ± 6.19 years and 69.91 ± 7.48 years, respectively. The majority of participants had primary school education, and had a monthly income of <10 000 Baht. All sociodemographic data in both groups were not significantly different. The mean fasting blood sugar and glycated hemoglobin levels were not significantly different between the intervention and control groups at baseline and after the intervention.

Table 1.

Sociodemographics, fasting blood sugar and glycated hemoglobin between the intervention and control groups

Intervention (n = 39) Control (n = 34) P‐value
n % n %
Sex
Female 29 74.4 26 76.5 0.835
Male 10 25.6 8 23.5
Age group
60–64 years 13 33.3 9 26.5 0.216
65–74 years 21 53.8 15 44.1
≥75 years 5 12.8 10 29.4
Education
No education 5 12.8 3 8.8 0.596
Primary school 34 87.2 31 91.2
Income (monthly)
<10 000 Baht 28 71.8 20 58.8 0.244
≥10 000 Baht 11 28.2 14 41.2
No. medications 0.536
0–3 6 15.4 3 8.8
4–6 26 66.7 22 64.7
≥ 7 7 17.9 9 26.5
Denture wearer 0.686
Yes 27 69.2 25 73.5
No 12 30.8 9 26.5
FBS Mean SD Mean SD
Pre‐test 147.74 35.71 150.15 53.74 0.588
Post‐test 147.03 47.49 162.32 39.59 0.177
HbA1C Mean SD Mean SD
Pre‐test 7.02 1.10 7.42 1.67 0.517
Post‐test 6.92 1.09 7.49 1.42

0.085

Statistical analysis used was χ2‐test.

Statistical analysis used was Mann–Whitney U‐test.

FBS, fasting blood glucose; HbA1C, glycated hemoglobin.

Salivary flow rate

Table 2 shows the resting and stimulating salivary flow between the intervention and control groups. After 1 month, the intervention group had a higher resting salivary flow rate than the control groups (0.25 vs 0.12, P < 0.001, effect size = 0.44). After 3 months, the resting salivary flow rate in the intervention group was significantly higher than the control group (0.32 vs 0.14, P < 0.001, effect size = 0.56). Although there was a significant difference between resting saliva at baseline, after 1 month and after 3 month follow up in both groups, the change difference in the intervention group was significantly greater than in the control group (0.019 vs 0.04, P < 0.001, effect size = 0.52).

Table 2.

Resting and stimulating salivary flow (mL/min) between the intervention and control groups at baseline, 1 month and 3 months

Resting saliva Stimulating saliva
Mean (SD) P‐value Mean (SD) P‐value
Intervention (n = 39) Control (n = 34) Intervention (n = 39) Control (n = 34)
Baseline 0.13(0.12) 0.11 (0.10) 0.608 2.14(1.17) 2.36 (1.14) 0.496
1 month 0.25(0.16) 0.12 (0.11) <0.001 3.21(1.43) 2.30 (1.10) 0.008
3 months 0.32(0.16) 0.14 (0.12) <0.001 3.66(1.62) 2.83 (1.43) 0.025
P‐value <0.001 0.015 <0.001 <0.001
Mean difference
1 month–baseline 0.12(0.11) 0.01 (0.09) <0.001 1.06(1.05) 0.06 (0.34) <0.001
P‐value § <0.001 0.669 <0.001 0.317
3 months–1 month 0.07(0.12) 0.03 (0.07) 0.235 0.46(0.84) 0.53 (0.73) 0.267
P‐value § 0.001 0.019 0.003 <0.001
3 month–baseline 0.19(0.15) 0.04 (0.10) <0.001 1.52(1.25) 0.47 (0.83) <0.001
P‐value § <0.001 0.058 <0.001 0.005

Statistical analysis used was the Mann–Whitney U‐test.

Statistical analysis used was the Friedman test.

§

Statistical analysis used was the Wilcoxon signed‐rank test.

After 1 month, the intervention group had a stimulating salivary flow rate significantly higher than the control groups (3.21 vs 2.30, P = 0.008, effect size = 0.31). After 3 months, the stimulating salivary flow rate of the intervention group was significantly higher than the control group (3.66 vs 2.83, P < 0.025, effect size = 0.26). Although there was a significant difference between stimulating saliva at baseline, after 1 month and after 3‐month follow up in both groups, the change difference in the intervention group was significantly higher than in the control group (1.52 vs 0.47, P < 0.001, effect size = 0.44).

Subjective and objective symptoms of xerostomia

Table 3 shows subjective and objective symptom scores. After 3 months, the subjective scores decreased in both groups and were significantly different between the two groups (0.56 vs 2.91, P < 0.001, effect size = 0.84). The subjective symptoms between baseline and after 3‐month follow up were significantly different in the intervention group (P < 0.001), but not in the control group (P = 0.334).

Table 3.

Subjective and objective symptoms of xerostomia between the intervention and control groups at baseline and after 3 months

Yes n (%) P‐value
Intervention (n = 39) Control (n = 34)
Subjective symptoms (baseline)
Q.1 Does the saliva in your mouth seem to be too little? 28 (71.8) 29 (85.3) 0.164
Q.2 Do you have any difficulty swallowing? 30 (76.9) 28 (82.4) 0.567
Q.3 Does your mouth feel dry when eating a meal? 27 (69.2) 24 (70.6) 0.900
Q 4. Do you sip liquids to aid in swallowing dry food? 28 (71.8) 25 (73.5) 0.868
Subjective symptoms (3 months)
Q.1 Does the saliva in your mouth seem to be too little? 8 (20.5) 24 (70.6) <0.001
Q.2 Do you have any difficulty swallowing? 11 (28.2) 23 (67.6) 0.001
Q.3 Does your mouth feel dry when eating a meal? 1 (2.6) 29 (85.3) <0.001
Q 4. Do you sip liquids to aid in swallowing dry food? 2 (5.1) 23 (67.6) <0.001
Mean scores (SD) P‐value
Subjective symptoms (0–4)
Baseline 2.90 (1.33) 3.12 (1.20) 0.530
3 months 0.56 (0.72) 2.91 (0.79) <0.001
Difference 3 months‐baseline 2.33 (1.54) 0.21 (1.49) <0.001
P‐value <0.001 0.334
Objective symptoms (0–10)
Baseline 2.31 (1.03) 2.44 (1.19) 0.729
3 months 1.41 (0.97) 2.26 (1.02) 0.001
Difference 3 months‐baseline 0.90 (1.12) 0.18 (0.90) 0.002
P‐value § <0.001 0.291

Statistical analysis used was the χ2‐test.

Statistical analysis used was the Mann–Whitney U‐test.

§

Statistical analysis used was the Wilcoxon signed‐rank test.

After a 3‐month follow up, the objective scores decreased in both groups, but were significantly different between the two groups (1.41 vs 2.26, P = 0.001, effect size = 0.38). The objective symptoms between baseline and after 3‐month follow up were significantly different in the intervention group (P < 0.001), but not in the control group (P = 0.291).

RSST

Table 4 shows the number of RSST and percentage changes. For the intervention group, the number of patients who had three or more times swallowing increased from 19 to 33 patients (35.89% of increasing) after 1 month, whereas the control group increased by 5.89%. After 3 months, the number of participants who had normal swallowing (≥3 times) in the intervention group had a 41.01% increase from baseline, significantly higher than the control group (8.82%; P < 0.01).

Table 4.

The repetitive salivary swallowing test of the control and experimental groups for baseline, 1 month, and 3 months

RSST (swallowing times) Intervention Control P‐value
0 1–2 ≥3 Percentage change 0 1–2 ≥3 Percentage change
Baseline 2 18 19 3 13 18
1 month 0 6 33 35.89 3 11 20 5.89 0.010
3 months 0 2 37 41.01 3 10 21 8.82 0.010

RSST, repetitive salivary swallowing test.

DI‐S

Table 5 shows the mean score of the DI‐S between the control and intervention groups. The DI‐S in the intervention group was significantly lower than the control group at 1 month (0.47 vs 0.82, P = 0.005, effect size = 0.13) and 3 months (0.54 vs 1.16, P < 0.001, effect size = 0.14). Friedman's test showed a significant difference between DI‐S at baseline, after 1 month and after 3 months in both the intervention and control groups (P < 0.001). However, the changes in DI‐S in the intervention group 3 months from baseline were significantly higher than in the control group (1.51 vs 0.82, P = 0.001).

Table 5.

The mean score of the Simplified Debris Index for the intervention and control groups at baseline, after 1 month and after 3 months

DI‐S Mean (SD) P‐value
Intervention Control
(n = 39) (n = 34)
Baseline 2.05 (0.48) 1.98 (0.43) 0.611
1 month 0.47 (0.55) 0.82 (0.77) 0.005
3 months 0.54 (0.53) 1.16 (0.73) <0.001
P‐value <0.001 <0.001
Mean difference
Baseline–1 month 1.58 (0.83) 1.16 (0.88) 0.033
P‐value § <0.001 <0.001
1 month–3 months 0.07 (0.76) 0.34 (0.94) 0.123
P‐value § 0.244 0.253
Baseline–3 months 1.51 (0.66) 0.82 (0.89) 0.001
P‐value § <0.001 <0.001

Statistical analysis used was the Mann–Whitney U‐Test.

Statistical analysis used was the Friedman test.

§

Statistical analysis used was the Wilcoxon signed‐rank test.

DI‐S, Simplified Debris Index.

Discussion

The present study showed that regular self‐stimulating salivary massage is practical and effective in improving salivary flow, oral hygiene and difficulty swallowing among older diabetes patients. Our results corresponded with the previous study by Ohara et al., which provided group oral hygiene instruction, facial and tongue muscle exercise, and salivary gland massage every 2 weeks for 3 months, and showed improved resting salivary flow rate and swallowing. 11 Another study showed that group sessions for 2 h, a total of six sessions in 3 months, including facial muscle and tongue exercises, and salivary gland massages, could improve the salivary flow rate among older persons in Tokyo. 12 In addition to the increased saliva flow from the measurements, the present study showed that the symptoms of dry mouth and the signs of saliva insufficiency from the patient's oral examination were also improved by salivary gland massage. As xerostomia causes discomfort in the oral cavity, and is associated with swallowing disorders, eating disorders and worsening of oral symptoms, the present study suggests that the improvement of dry mouth symptoms among diabetes patients could be minimized by salivary gland massage, which will lead to improving the patient's overall oral health and quality of life.

As saliva is important in providing oral lubrication that links to the sensory input to the oral cavity and impacts swallow initiation, 24 several studies reported the correlation between hyposalivation and swallowing problems. 25 , 26 Previous interventions to improve dry mouth and increase salivary flow rate, including the oral function program 11 , 13 and saliva substitutes, 27 also reported improved swallowing, similar to the present study. Although the salivary flow rate increases, the reflex swallowing might be initiated when the salivary film reaches a critical thickness or when saliva travels over receptors in a specific location. 28 Thus, it could explain the increased swallowing frequency after improving saliva volume and flow rate.

The findings showed that debris scores were significantly improved in both groups, but the intervention group was significantly better than the control group. The oral health education in the control group also affected and motivated patients to improve their oral hygiene at recall visits. Although the participants in the intervention group received instruction to massage the salivary gland, they did not receive general oral health education directly. Thus, the results showed that the increasing salivary flow rate affected oral self‐cleansing. The findings corresponded with a previous study that the effects of saliva substitutes also reduced the dental plaque index in patients with type 2 diabetes. 29 Besides oral hygiene, reduced saliva secretion also increases the risk of dental caries and periodontal disease. 30

Regarding the duration and simplicity of the massage, the findings showed that teaching older patients to massage the three salivary glands by a dental nurse using a poster was easy to follow and effective in improving the salivary flow rate in 1 month. In terms of applying the results to older adults or diabetic clinics, the nurse or hospital staff might teach salivary gland massage techniques to improve salivary flow, swallowing and oral hygiene.

However, there were some limitations in the present study. As our study was carried out for a limited time, in the long term, the patient might not be able to massage continuously and lack the motivation to continue stimulating the salivary glands. We did not investigate whether the rate of saliva flow remains after the salivary gland stimulation is stopped, which should be further studied. Another limitation was that the massage skills of patients might vary, and the quality of the massage was unable to be determined for each patient. Although we included the checking calendar and emphasized that patients carried out salivary gland massage 2 min and three times daily, and it showed that >90% of the patients complied with study protocol, the patients might not maintain the same quality of massage every time. Besides the frequency, the future study should include the performance record reporting the duration and number of times patients massage each position. In addition, an automatic massage machine might be developed to aid this method and assure the consistent procedure if followed in salivary gland massage for older persons.

This research showed that the salivary gland massage program could increase the salivary flow rate in older type 2 diabetes patients. Subjective and objective symptoms of mouth dryness improved significantly in the intervention group. Swallowing was significantly better in the intervention group at 1 month and 3 months. Debris scores were significantly improved in both groups, but the intervention group was significantly better than the control group.

Disclosure statement

The author declare no conflict of interest.

Acknowledgements

This study was funded by the Ministry of Public Health, Thailand. The authors express gratitude to the staff, dental nurse and participants at Health Promotion Hospital in Wang Chan district for their kind participation throughout this research.

APPENDIX A. SALIVARY GLAND MASSAGE POSTER

APPENDIX A.

APPENDIX B. CALENDAR FOR CHECKING AND RECALLING

APPENDIX B.

APPENDIX C. ORAL HEALTH EDUCATION POSTER

APPENDIX C.

Jeamanukulkit S, Vichayanrat T, Samnieng P. Effects of the salivary gland massage program in older type 2 diabetes patients on the salivary flow rate, xerostomia, swallowing and oral hygiene: A randomized controlled trial. Geriatr. Gerontol. Int. 2023;23:549–557. 10.1111/ggi.14629

Data availability statement

Data available on request from the authors

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

Data available on request from the authors


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