Telehealth-Supported Physical Activity Among Veterans With a History of Lung Cancer: Protocol for a Single-Arm Feasibility Study

Abstract

Introduction

Lung cancer is among the top three most frequently diagnosed cancers, and the leading cause of cancer-related death among United States veterans. Improved screening and treatment for lung cancer has led to an increasing number of survivors, but many still face a persistent decline in physical function and overall quality of life. Exercise can improve outcomes, but most structured and supervised programs are delivered in hospital-based settings. Veterans often face substantial barriers to participation in these programs, including comorbid chronic illness, geographic isolation, and transportation challenges. Therefore, this study will examine the feasibility and acceptability of delivering a telehealth-supported home-based exercise intervention to improve physical activity and quality of life for veterans who are lung cancer survivors.

Methods

A protocol for a single-arm, nonrandomized, prospective feasibility pilot. Up to 15 veterans diagnosed with lung cancer will be recruited from the Veterans Affairs (VA) Boston Healthcare System for a three-month intervention. Participants will choose a single low-intensity telehealth exercise from the VA’s MOVE!^® Coach App and wear an activity tracker (Fitbit). Semi-structured qualitative interviews will be conducted at three points in the study. Participants will have the option to simultaneously participate in VA’s Whole Health coaching and will be asked to share their data via VA’s Share My Health Data App. Primary outcomes will measure feasibility, acceptability, and perceived appropriateness of the intervention. Secondary exploratory outcomes will examine changes in physical activity and health-related quality of life; while improvements are anticipated, this study is not powered to detect statistically significant differences. Descriptive statistics will be calculated. Qualitative interviews will be audio recorded and analyzed using directed content analysis methods. Ethical approval was obtained from VA Boston Institutional Review Board.

Conclusion

Telehealth-supported exercise represents a promising method for improving survivorship care for veterans with lung cancer and other diverse oncology populations.

Keywords

lung cancer cancer survivor telehealth physical activity exercise

Introduction

In the United States (U.S.), lung cancer is the leading cause of cancer-related deaths – and for U.S. military veterans, it ranks among the three most prevalent cancers diagnosed.^1-3 Compared with the general population, veterans are at increased risk of lung cancer due to military-specific factors, including historically higher rates of smoking,^4,5 and service-related environmental exposures (e.g., asbestos, burn pits, and chemical agents) that may contribute additional risk.^6,7 Within the U.S. Department of Veterans Affairs (VA), expanded lung cancer screening eligibility and uptake – together with advances in screening, early detection, and treatment over the past decade – have increased early-stage diagnosis and improved overall survival among veterans, contributing to a growing veteran survivorship population.^1,8-11 Despite these improvements, many lung cancer survivors (LCS) struggle with complex health challenges and high symptom burden (e.g., fatigue, dyspnea, insomnia, nausea, pain, depression) which has critically important adverse implications for health-related quality of life (HRQoL).^8,9,12-14 Prior research has found that regular exercise is an effective therapeutic strategy to improve HRQoL, muscle strength, and to reduce cancer-related fatigue.^15-21

Low-to-moderate intensity exercises are safe for cancer survivors,²² and emerging evidence also shows that engaging in physical activity lowers risk of cancer-specific mortality, underscoring the potential of exercise to improve survivorship outcomes.^8,23 Nationally recognized guidelines recommend that all cancer survivors engage in routine physical activity (e.g., at least 150 minutes of activity plus strength training per week).^22,24 However, physical activity engagement among LCS remains low despite national guidelines and growing evidence supporting physical activity in survivorship care, including its potential as a low-cost and accessible approach to improving symptom burden.^8,22,25-27 The factors related to low engagement are varied,²⁸ however, persistent barriers include geographic isolation, socioeconomic challenges, limited psychosocial support, and mobility constraints.^24,29-32 Telehealth-based exercise programs represent an emerging innovative and feasible approach to reducing sedentary behavior and improving HRQoL in cancer survivorship.^14,29 In this study, we define telehealth as the use of digital communication technologies, such as video or phone conference and mobile health (mHealth) tools (e.g., smartphone apps or wearables).³¹ Many cancer survivors have reported a preference for telehealth tools because they address access barriers, allow for individualized tailoring, and provide personalized feedback and flexibility that supports sustained engagement in physical activity.³³ Additionally, telehealth-supported, home-based exercise programs have demonstrated feasibility and benefit in several cancer populations; however, evidence among the veteran LCS population remains limited.³⁴ Veteran LCS frequently contend with complex physical and psychological comorbidities, including high rates of depression and PTSD, which may influence intervention engagement in exercise interventions.³⁵ Given the unique needs of the veteran LCS population and existing evidence gaps, investigating the feasibility and acceptability of telehealth-supported, home-based exercise programs is critically important.

The VA offers programs such as Gerofit, a supervised exercise program for veterans 65 and older, and MOVE!^®, a weight management program for overweight or obese patients that implements behavioral change strategies to promote and support lifestyle changes, which includes an emphasis on physical activity.^36-39 These programs were initially implemented only as facility-based interventions but have expanded over time to include telehealth approaches to improve access. While both Gerofit and MOVE!^® support physical activity, these VA programs were not designed with a focus on LCS. Furthermore, there remains a dearth of evidence that includes veterans who are LCS, thus limiting the understanding of the feasibility and implementation of telehealth-supported, home-based exercise interventions aimed at promoting sustained physical activity behavior change among veteran LCS.⁴⁰ Additionally, there’s no one exercise prescription for LCS, underscoring the need for a holistic, tailored exercise approach that honors survivors’ individual needs, energy levels, and life circumstances to support a sustainable physical activity routine.²⁴ Research has shown that among cancer survivors, perceived barriers – such as fatigue, limited motivation, and anxiety about exacerbating symptoms – often hinder the initiation of physical activity, highlighting the value of Whole Health coaching approaches.^41,42 Whole Health coaching – a VA system-wide, veteran-centered initiative – is a collaborative approach for health promotion that aids in facilitating health-related behavior change by utilizing a patient-engaged strategy that prioritizes patient-centered care, providing an opportunity to support a tailored, holistic exercise approach.⁴³ Thus, the goal of this study will be to examine the feasibility and acceptability of delivering a telehealth-supported, home-based exercise intervention that combines Whole Health coaching to improve physical activity and quality of life for veterans who are LCS.

Methods

Study Design and Setting

This study is a protocol for a single-arm, nonrandomized, prospective, feasibility pilot that will incorporate pre- and post-intervention assessments and qualitative interviews. In this study, T1 refers to the baseline assessment (month zero), T2 refers to the one-month assessment, and T3 refers to the final assessment at month three. An overview of the three-month pilot is illustrated in Figure 1. Study assessment time points one-month and three-month were based on previous telehealth research which have shown high rates of participant drop off in the early phase of those studies.^44,45 Therefore, the one-month check-in will help us gauge initial intervention engagement and implement strategies to retain participants and the three-month endpoint will allow participants enough time to integrate the digital health tool into their daily lives. This protocol strictly adheres to the reporting guidelines outlined in the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT).^46,47 This study will be conducted in accordance with the Helsinki Declaration of 1975, as revised in 2024.

Figure 1.

Overview of the 3-month pilot study

All study activities will take place at VA Boston Healthcare System, a network of healthcare facilities run by the U.S. Department of Veterans Affairs that provides medical and support services for veterans in eastern Massachusetts and the New England region. Ethical approval was given by the VA Boston Institutional Review Board (protocol number: 1857840-1), in accordance with VA guidelines. Written informed consent will be sought from all participants (Table 1).

Table 1.

Low-Intensity Exercises

Exercise type	Examples
Breathing exercises	Relaxation breathing
Aerobic exercises	Easy walking, relaxed biking
Strength training	Bodyweight exercises, resistance bands, light weights
Stretching and flexibility	Gentle yoga, Tai Chi, simple stretches

Study Participants

We will review the electronic health record prior to sending out recruitment letters to determine whether potential participants meet the inclusion criteria. Additionally, all enrolled participants will be offered the choice to participate virtually or in-person for all interviews.

Inclusion Criteria

During the three-month study period, we will identify veterans who (1) are aged 18 years or older, (2) have a diagnosis of lung cancer determined by the International Classification of Diseases, 10th Revision (ICD) codes (e.g., C34.0, C34.1, C34.2, C34.3, C34.4, C34.8, C34.9) – this will include those that have either completed treatment, are currently receiving treatment, or have declined treatment, (3) receive health care at VA Boston or have a VA Primary Care Provider, (4) are able to walk without assistance, (5) are fluent in English, and (6) own any device with internet access capability (e.g., smartphone, iPad, tablet, or computer). Given the high prevalence of service-related risk exposure and increased early detection of lung cancer, the VA serves a relatively younger lung cancer survivorship population than the general U.S. population. Therefore, including a broader range of veterans reflects the diversity among LCS receiving care in the VA. The sample will include veterans at varied points across the lung cancer survivorship continuum (e.g., post treatment and/or active treatment) and with differing levels of function and recovery.

Exclusion Criteria

We will exclude veterans who (1) have balance issues or weakness, (2) have a diagnosis of severe anemia (Hb <8 g/dL),⁴⁸ (3) have any known metastatic cancer, (4) lack the capacity to provide consent, (5) have experienced a psychiatric hospitalization during the past six months, as documented in their medical record, (6) have entered a drug or alcohol detoxification or rehabilitation program within the last six months prior to the study as documented in their medical record, (7) have attempted suicide within the previous year or have current or active suicidal ideation within the last 90 days as documented in the Columbia-Suicide Severity Rating Scale in their medical record. The above inclusion and exclusion criteria were based on previous studies involving physical activity among those with a diagnosis of lung cancer.^49-53

Recruitment, Screening & Consent

Potentially eligible participants will be identified using the electronic health record and via the VA Boston Cancer clinics. The study team will then screen eligible participants following the inclusion and exclusion criteria prior to inviting patients. Written informed consent will be obtained for all study participants, and they will be made aware of the voluntary nature of the study and that they may withdraw at any time. Additionally, participants will be given the option to participate in person or virtually.

Sample Size

This study is designed as a feasibility pilot, with a planned enrollment of 15 participants. Prior research suggests that for studies with continuous outcomes, sample sizes as small as 12 per group may be adequate.⁵⁴ Given that the primary goal is to assess feasibility, no formal statistical power calculations were conducted.

Intervention

Telehealth Exercise

Over the three-month pilot study, participants will be asked to engage in a low-intensity exercise at least 15-30 minutes/day, three times per week. Upon enrollment, participants will be asked to choose one of the offered exercises (Table 1) and will receive personalized text message prompts three times per week to perform the exercise of their choosing. Current literature suggests that exercise two to five times per week is acceptable across the lung cancer continuum (before, during, and post-treatment).²⁴ Low-intensity exercises were intentionally selected for our sample population because they can improve symptoms and health-related quality of life while supporting safe initiation of movement and adherence through a tolerable, progressive approach.^55,56.Prior research has shown that these specific low-intensity exercises are associated with improvements in cancer-related symptoms (e.g., fatigue, mental health, and sleep quality) and may promote adherence due to their simplicity and minimal equipment requirements.^57-60 Our study anticipates behavioral change that increases exercise capacity over time. Evidence suggests that gradual initiation of physical activity at manageable intensities – particularly among individuals with reduced baseline capacity – may promote physical activity engagement and support sustained behavior change in cancer survivors.^61,62 Participants will be given assistance on how to download, use, and choose a low-intensity exercise option from VA’s MOVE!^® Coach app. Designed for veterans and service members, MOVE!^® Coach is an evidence-based comprehensive lifestyle intervention combining dietary, physical activity, and behavioral strategies targeting clinically meaningful weight loss.^63,64 Key features include self-management modules, tracker functions, and supportive tools. The self-management modules provide education on weight management strategies through videos, worksheets, and games. Allowing veterans to select exercises they deem consistent with their functional and mobile capacity may enhance autonomy and exercise adherence.^65,66 In cancer survivorship populations, action planning approaches may reduce decisional barriers and anxiety, supporting the incorporation of physical activity into daily routines – an effect likely strengthened when individuals select activities they perceive as feasible.⁶² A tracker helps users keep a daily weight diary and track progress on healthy eating and physical activity. Notably for this study, which is focused on exercise rather than weight management, the app provides videos of exercises and stretching routines that participants can follow. Lastly, it allows the user to share their progress on social media and access additional resources. This free app is available for download on the Apple App Store and Google Play Store, and it can be used independently or in collaboration with a healthcare provider. The app allows exercise to be tailored to activities that the veteran prefers. Following choice selection of a low-intensity exercise, participants will be provided with a Fitbit. Fitbits are validated digital health devices that have been used in several studies.^67-69 Regardless of exercise selection, participation in Whole Health coaching to establish personal activity goals (e.g., step count and daily or weekly activity duration) will be promoted and encouraged.

Fitbit/Share My Health Data

Fitbit devices provide objective metrics to monitor physical activity, including calories burned, heart rate variability, sleep patterns, step count, and built-in GPS to track pace and distance without a phone. Fitbits will be paired with the VA Share My Health Data app to allow users to share information about their exercise with their VA care team and the research team. VA’s Share My Health Data app enables veterans to share Patient-Generated Health Data (PGHD) from wearable devices such as Fitbits and Apple Watches, Bluetooth devices like glucose or blood pressure monitors, and manually entered health measurements.⁷⁰ Users can use the app to view their health information and see charts and graphs of their data over time. Health information captured via the Share My Health Data app is automatically stored in the VA PGHD Database, with key metrics displayed in the electronic health record in a PGHD dashboard accessible to the VA care team.⁷¹

Whole Health Coaching

There’s no one exercise prescription for LCS, thus a holistic exercise approach is crucial to honor individual needs, energy levels, and life circumstances.²⁴ Studies have demonstrated the integral role health coaching plays in patients achieving behavioral changes such as exercise.^10,72-78 Whole Health coaching is an approach to healthcare that focuses on supporting a person’s overall well-being by prioritizing their values, needs, and goals, rather than just treating symptoms or managing disease.^41,76,79 The Whole Health model emphasizes identifying What Matters Most to the veteran, supported by a trained coach. This approach fosters an active, collaborative role in shared-decision making alongside their healthcare team.⁸⁰ Within the VA, Whole Health principles and shared decision-making have been integrated into lung cancer-related initiatives and have been associated with improved outcomes.^81-84 Whole Health coaching is a free, comprehensive service offered to veterans to help them achieve their personal health and well-being goals. The coaching will empower veterans to 1) connect with their purpose, values, and goals, 2) build a personalized plan designed to improve their health and well-being, and 3) take action on this plan. Group-based coaching will be offered during the same time of the study and involves one session per week over a 10-week time frame. The Coaching sessions will be taught by a certified Whole Health Coach. Participating in sessions will be optional, but it will be promoted and encouraged. Additionally, veterans will have the option to attend one or all sessions.

Messaging

Participant retention and intervention engagement is a major challenge in epidemiological and clinical trials deploying surveys or interventions with telehealth technologies.^85-87 Thus, over the three-month pilot, all participants will receive personalized text message prompts three times per week, tailored to their selected activity and individualized goals (e.g., step goal, activity type, and planned duration) to further support follow-through on planned exercise.

Outcomes and Measurements

Primary Outcome Measures

The primary outcome of this pilot study is the feasibility and acceptability of a telehealth-supported physical activity intervention. Feasibility will be assessed as recruitment rate (four persons/month), participant retention (≥80% at final timepoint), and data completion (≥80% completion of outcomes at final timepoint). Acceptability will be measured with the validated three-item Acceptability of Intervention Measure.⁸⁸ Additionally, baseline, one-month, and follow-up interviews will assess feasibility (practicality and barriers) and acceptability (perceived relevance, burden, and satisfaction).

Secondary Outcome Measures

The secondary outcomes are physical activity engagement and HRQoL, which will be assessed from T1 (baseline) to T3 (three-month follow-up). Physical activity engagement will be measured using the Past-Week Modifiable Activity Questionnaire (PWMAQ), a reliable and valid measure of leisure physical activity.⁸⁹ Additionally, wearable-derived metrics such as daily calories burned and heart rate variability will be used as objective indicators of physical activity engagement; calories burned reflect overall activity volume, while heart rate variability reflects autonomic response associated with activity, together serving as complementary measures of physical activity engagement relevant to feasibility assessment. HRQoL will be measured using the Functional Assessment of Cancer Therapy - General (FACT-G).⁹⁰ The FACT-G is a widely used measure for HRQoL across cancer types and contexts.⁹¹ These exploratory outcomes will provide opportunities to examine the intervention’s potential effectiveness in promoting physical activity behavior change and inform a future larger trial.

Procedures

T1, Baseline Interview

At enrollment, study team members will conduct semi-structured qualitative interviews. The interview guides will be based on the domains of the combined Capability, Opportunity, Motivation-Behavior (COM-B) and Theoretical Domains Frameworks.⁹² The central tenet of COM-B is that the three domains – capability (an individual’s capacity to engage in behavior modifications), opportunity (factors in the environment that influence individual behaviors), and motivation (willingness to change) – can be used to generate actions that positively impact interventions targeted at behavior change (e.g., physical activity).⁹³ The Theoretical Domains Framework elaborates on the COM-B domains by providing 14 specific domains to categorize factors that influence behavior. These domains include knowledge, skills, social/professional role and identity, beliefs about capabilities, optimism, beliefs about consequences, reinforcement, intentions, goals, memory, attention and decision processes, environmental context and resources, social influences, emotion, and behavioral regulation.^92,94 Using the combined frameworks helps inform and modify interventions by providing a more comprehensive understanding of the behavioral barriers and facilitators at play. The baseline interviews will capture demographic information of participants including recent life experiences, smoking status, physical activity behaviors, current exercise behaviors, lung cancer experience, facilitators and barriers to physical activity, and use of telehealth technology to support physical activity. As part of the baseline interview, participants will be asked to complete the physical activity engagement and HRQoL questionnaires FACT-G and PWMAQ. The REDCap platform, a secure web application for data capture, will be used to administer the questionnaires. During the baseline interview, participants will also be provided with an orientation on how to download and set up the three apps (VA Share My Health Data app, Fitbit, and VA MOVE!^® Coach) as well as the syncing of their Fitbit account to the Share My Health Data app. Following training, participants will be asked to use the MOVE!^® Coach app at least three times per week to support physical activity and to wear their Fitbit daily for the three-month period. The baseline interview will last about 90 minutes and will be audio recorded with supplementary notetaking, as necessary.

T2, One-Month Qualitative Interview

The one-month semi-structured interview will last up to 20 minutes. These brief interviews will be used to gather participants’ feedback on the acceptability, appropriateness, and practicality of the study. Additionally, they will be asked about their thoughts about continuing to exercise. The interviews will be audio recorded with supplementary notetaking, as necessary.

T3, Three-Month Follow-up Interview

The follow-up semi-structured interviews at the completion of the three-month study. Participants will be asked questions related to acceptability, appropriateness, practicality of the study, and if they attended Whole Health coaching. Participants will also be asked to complete the FACT-G and PWMAQ questionnaires. This interview will last up to 90 minutes and will be audio recorded with supplementary notetaking, as necessary.

Ethical Considerations and Approvals

Ethical approval was given by the VA Boston Institutional Review Board (protocol number: 1857840-1), in accordance with VA guidelines. Written informed consent will be sought from all participants. Participants will be compensated $25 US dollars (USD) for the initial interview, $25 USD for the one-month interview and $50 USD for the final interview. If they opt to participate in VA Boston’s Whole Health coaching group sessions, they will receive $10 USD for each session attended, for a total compensation of up to $200 USD. Study ID numbers will be assigned to participants to ensure confidentiality. Risks are minimal given the low impact of exercises planned, and measures to ensure data confidentiality.

Data Management and Monitoring

All study materials will be stored securely in VA-approved, password-protected servers and any paper documents in locked offices, only accessible to research staff. This includes data that is used only for recruitment and screening. The principal investigator will ensure that strict confidentiality measures are followed by trained research staff to safeguard all patient-related information.

Data Collection

Qualitative data will be collected from interviews and quantitative data will be collected from questionnaires and patient-generated health data collected from the VA Share My Health Data dashboard.

Data Analysis

Qualitative Analysis

We will take a combined approach to analysis. We will use a directed content analysis approach,⁹⁵ with predetermined codes based on the combined COM-B and Theoretical Domains Frameworks, followed by inductive coding to capture the accounts (experiences and views) of research participants. All interviews will be professionally transcribed verbatim. Interview transcripts will be uploaded into a qualitative data management program and analysis will begin with two researchers each reading three transcripts in their entirety to become familiar with the data. Following this, they will highlight all text tentatively related to the code for further discussion. Next, they will code all the highlighted passages using the predetermined codes. Any relevant text that cannot be categorized with the initial coding scheme will be given a new code. After the two researchers reach a consensus on the final coding framework, the remaining transcripts will be analyzed by one researcher, followed by discussions and consensus generation with the second researcher. Explanatory verbatim quotes will be selected that exemplify the themes. Disagreements or questions on these themes will be discussed in weekly team meetings and final decisions about appropriate categorizations and framing of information will be decided upon via consensus.

Quantitative Analysis

We will use descriptive statistics to summarize feasibility outcomes: the number of months each patient participated in the study, the number of patients that exercised at least three times per week, and the number of Whole Health coaching sessions attended. We will describe the patient characteristics (e.g., smoking status, age, and gender) descriptively. Summary statistics, including standard deviations and 95% confidence intervals, will be generated for continuous measures (e.g., questionnaire scores). We will also explore stratified analyses by key clinical characteristics as appropriate.

Discussion

This pilot is designed to evaluate the feasibility and acceptability of a tailored telehealth, home-based exercise intervention for veterans with a lung cancer diagnosis. Given the complex care needs that LCS often experience,^10,12,13 and the significant barriers many veterans face in accessing post-treatment support,^96,97 there is a clear need to address this critical gap and examine innovative, accessible models of care that can be scaled within integrated healthcare systems such as the VA. The anticipated results will identify barriers and facilitators that influence veterans’ intervention engagement in supportive care and physical activity engagement, including factors related to autonomy, action planning, and sustained adherence. Understanding these factors will inform the development of targeted implementation strategies and guide future research on integrating telehealth-based exercise interventions into survivorship care. The use of rapid qualitative analysis, coupled with patient-informed design, will enhance the intervention’s relevance and applicability for both veteran and broader oncology populations. These approaches are expected to improve acceptability, foster sustained physical activity engagement and intervention engagement, and increase the likelihood of successful uptake within integrated healthcare systems. The insights gained will serve as a foundation for designing a larger trial to evaluate both the effectiveness and scalability of this model of care.

Strengths and Limitations

A central strength of this pilot is its focus on feasibility and acceptability, which are essential precursors to a larger trial. By piloting a telehealth-supported, home-based exercise program in this veteran population, this study will contribute early evidence on the practicality of intervention delivery, recruitment, and adherence within a complex healthcare system. These methodological strengths will yield nuanced insights that may inform scalable approaches for future implementation efforts.

Several limitations are anticipated in this pilot study. As a small, single-arm feasibility trial, the sample size will be limited, reducing statistical power and restricting the generalizability of findings. Self-selection bias is also possible, as participants who volunteer for an exercise intervention may be more motivated or health conscious than the broader LCS population. Another anticipated challenge is variability in adherence to self-monitoring behaviors, particularly due to forgetfulness or competing demands. To mitigate this, tailored reminders will be delivered, with the timing adjusted to accommodate participants’ schedules – for example, sending prompts during non-working hours for those employed full-time. Although these strategies may reduce adherence barriers, they cannot fully eliminate them, and the results should be interpreted with these limitations in mind.

Conclusion

Adopting telehealth-supported, self-management programs represent a promising approach to fostering physical activity and promoting emotional well-being among veterans who are LCS. If shown to be feasible, this model may enhance survivorship care for veterans with lung cancer, as well as inform broader implementation strategies for supporting diverse oncology populations in unsupervised or home-based settings. This work aligns closely with VA priorities that emphasize healthcare innovation, patient-centered care, and enhanced cancer survivorship support for veterans.

Footnotes

Author Note

Statements contained in this article reflect the views of the authors and do not represent the official positions of the US Department of Veterans Affairs or other author affiliate organizations.

ORCID iDs

Sierra D. Ferris

Esther Boama-Nyarko

Renda Soylemez Wiener

Stephanie L. Shimada

Gemmae M. Fix

Marva V. Foster

Ethical Considerations

The study received research ethics approval from the VA Boston Institutional Review Board (1857840-1) in accordance with VA guidelines.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported with funding from the VA Office of Health Equity and support from Telehealth Research and Innovation for Veterans with Cancer (5P50CA271358).

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Data Availability Statement

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.*

Appendix

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