Abstract
Background
Patients with leukemia rely on social and family support. This study aimed to explore the knowledge, attitude, and practice (KAP) toward leukemia among family members of patients with leukemia and the general population in southeast China.
Methods
A cross-sectional study was conducted in September 2022 in southeast China (Anhui Province). The KAP scores and demographic data were assessed by questionnaire and analyzed by multivariable logistic regression and structural equation modeling.
Results
A total of 760 valid questionnaires were collected, including 117 (15.39%) answered by family members of patients with leukemia. The mean knowledge (8.30 ± 2.79 vs. 8.72 ± 2.56, P = 0.103), attitude (52.17 ± 5.52 vs. 52.27 ± 5.53, P = 0.862), and practice (8.06 ± 2.00 vs. 8.18 ± 2.05, P = 0.547) scores were comparable among family members and the general population. Higher knowledge scores [OR = 1.18 (1.10, 1.27), P < 0.001] and higher attitude scores [OR = 1.05 (1.02, 1.09), P = 0.002] were independently associated with better practice scores. Being a family member of a patient with leukemia had no significant effect on the KAP scores.
Conclusion
The participants demonstrated satisfactory knowledge, positive attitude, and appropriate practices toward leukemia, suggesting that access to information about leukemia to the general public might be sufficient in China. Health education might effectively improve knowledge, which could translate into improved attitude and practice.
Keywords: Hematologic diseases, Leukemia, Health knowledge, Attitudes, Practice, Surveys and questionnaires, Cross-sectional studies
1. Introduction
Leukemia is a progressive abnormal proliferation and expansion of leukemic cells generally classified by cell lineage (lymphocytic or myeloid) and stage (acute or chronic) [1]. In 2018, Leukemia was the 15th most commonly diagnosed cancer and the 11th leading cause of cancer mortality worldwide [2]. Acute myeloid leukemia (AML) is the most common form among adults, accounting for the highest annual mortality [2]. Globally, the incidence of leukemia is lower in females and Asian nationalities, including Japanese, Koreans, and Han Chinese [2,3]. Therefore, due to a lower exposure, China is one of the countries where leukemia diagnosis and treatment is probably less discussed in the general population.
Recent treatment options, such as targeted therapies and low-intensity regimens, led to complex decision making in leukemia management [2,4]. Moreover, hematopoietic cell transplantation (HCT), despite having the potential to re-establish normal hematopoietic and immune function, is mostly discussed through the risk of significant toxicities [5]. In this light, most patients and even healthcare providers still believe that the survival rates of patients with leukemia have not remarkably improved over the past few decades, which negatively impacts the decision-making ability and increases psychological distress for patients and their families [6]. Nation-wide educational programs and targeted educational interventions are needed to increase awareness about recent developments and effective therapy options among leukemia patients and their family members.
A knowledge, attitude, and practice (KAP) study is a tool that provides a practical guide for educational interventions and defining the target population [7]. Although KAP patterns, separately or together, were extensively explored for breast cancer [8,9] and cervical cancer [10], only a few KAP studies were conducted among patients with leukemia or healthcare providers. Most of those studies reported deficient knowledge and inadequate practices and emphasized the need to enhance care-seeking behaviors. In particular, Priya et al. [11] reported that mothers of children with leukemia had only about 50% knowledge regarding the treatment methods. A recent KAP study among adults with chronic myeloid leukemia in India reported that patient awareness about the disease was suboptimal, with nonadherence and treatment interruptions observed quite often [12]. A survey and focus groups of hematologists and oncologists discussed the knowledge gaps often affecting referral decision-making, including improper risk stratification and inappropriate use of chronologic age-based management [13]. To our knowledge, there is no recent study regarding the social attitude toward leukemia in the general population in China.
Therefore, this study aimed to explore the awareness of leukemia risks, screening options, and management in China in the general population and family members of patients with leukemia. The KAP scores and demographic data were assessed and analyzed to distinguish specific patterns and sub-populations that would need special approaches during future educational interventions. We hypothesized that the practice patterns would be affected by knowledge and attitude, while the role of family members would affect the knowledge and attitude of participants.
2. Materials and methods
2.1. Study design and participants
This cross-sectional study was conducted in Anhui Province in September 2022 and included family members of patients with leukemia and individuals from the general population. The inclusion criteria were 1) aged 16 years or older and 2) able to fully understand the questionnaire.
Both offline (paper) and online questionnaires were used in this study. The paper questionnaire was distributed to the family members of patients with leukemia during their visits to the consulting room. The online questionnaire was built using the Wenjuanxung platform. The link to the online questionnaire was shared with the general population via social media for recruitment. In the online questionnaires, the participants who responded “Yes” to the question “Do you have family members with leukemia?” were also considered family members of patients with leukemia. The study was approved by the Ethics Committee of Anhui Public Health Clinical Center (North District of the First Affiliated Hospital of Anhui Medical University), and verbal informed consent was obtained from the participants.
A total of 851 people participated in this study, and 760 valid questionnaires were collected (Cronbach's α = 0.847, KMO = 0.848). Most participants were of Chinese Han ethnicity (97.37%), from rural areas (71.05%), married (65.39%), and without a smoking history (85.66%). Among all questionnaires, 117 (15.39%) were answered by family members of patients with leukemia (Table 1).
Table 1.
General characteristics of patients.
| N (%) |
Knowledge |
Attitude |
Practice |
||||
|---|---|---|---|---|---|---|---|
| Mean ± SD | P | Mean ± SD | P | Mean ± SD | P | ||
| Age | <0.001 | 0.011 | 0.350 | ||||
| <30 | 294 (38.68) | 9.03 ± 2.63 | 52.52 ± 5.78 | 8.29 ± 1.91 | |||
| 31-40 | 248 (32.63) | 8.76 ± 2.37 | 52.75 ± 5.57 | 8.13 ± 2.08 | |||
| ≥41 | 218 (28.68) | 8.04 ± 2.70 | 51.32 ± 5.01 | 8.04 ± 2.17 | |||
| Gender | 0.689 | 0.405 | 0.645 | ||||
| Male | 401 (52.76) | 8.62 ± 2.73 | 52.09 ± 5.93 | 8.13 ± 2.04 | |||
| Female | 359 (47.24) | 8.70 ± 2.45 | 52.43 ± 5.03 | 8.20 ± 2.05 | |||
| Ethnicity | 0.035 | 0.203 | 0.527 | ||||
| Han | 740 (97.37) | 8.69 ± 2.59 | 52.29 ± 5.53 | 8.16 ± 2.06 | |||
| Others | 20 (2.63) | 7.45 ± 2.82 | 50.70 ± 5.22 | 8.45 ± 1.43 | |||
| Occupation | 0.954 | 0.969 | 0.739 | ||||
| Professional technical personnel | 189 (24.84) | 8.71 ± 2.53 | 52.31 ± 5.29 | 8.17 ± 2.00 | |||
| Office staff or related personnel | 175 (23.00) | 8.63 ± 2.67 | 52.17 ± 5.11 | 8.21 ± 2.03 | |||
| Others | 396 (52.11) | 8.65 ± 2.60 | 52.27 ± 5.82 | 8.06 ± 2.14 | |||
| Residence | 0.479 | 0.500 | 0.662 | ||||
| Urban | 220 (28.95) | 8.55 ± 2.58 | 52.04 ± 5.22 | 8.11 ± 1.96 | |||
| Others | 540 (71.05) | 8.70 ± 2.61 | 52.34 ± 5.64 | 8.19 ± 2.08 | |||
| Education | <0.001 | 0.467 | 0.231 | ||||
| Primary School or below | 71 (9.33) | 7.40 ± 2.43 | 51.43 ± 5.31 | 7.84 ± 2.15 | |||
| Secondary school/High School | 139 (18.27) | 9.13 ± 2.55 | 52.21 ± 5.33 | 8.17 ± 2.04 | |||
| College/University | 450 (59.13) | 8.69 ± 2.60 | 52.46 ± 5.46 | 8.27 ± 2.03 | |||
| Graduate or above | 101 (13.27) | 8.73 ± 2.55 | 51.94 ± 6.18 | 7.92 ± 2.04 | |||
| Monthly income | 0.500 | 0.167 | 0.260 | ||||
| <2000 | 84 (11.04) | 8.83 ± 2.51 | 51.51 ± 5.65 | 8.04 ± 2.04 | |||
| 2000-5000 | 204 (26.81) | 8.43 ± 2.68 | 51.93 ± 5.51 | 8.08 ± 2.07 | |||
| 5000-10000 | 226 (29.70) | 8.79 ± 2.56 | 52.99 ± 4.73 | 8.38 ± 1.88 | |||
| 10000-20000 | 147 (19.32) | 8.79 ± 2.72 | 52.13 ± 5.73 | 8.22 ± 2.06 | |||
| >20000 | 100 (13.14) | 8.49 ± 2.42 | 52.05 ± 6.63 | 7.87 ± 2.29 | |||
| Marital status | <0.001 | 0.091 | 0.182 | ||||
| Married | 497 (65.39) | 9.19 ± 2.47 | 52.01 ± 5.41 | 8.09 ± 2.13 | |||
| Unmarried | 263 (34.61) | 8.38 ± 2.62 | 52.72 ± 5.72 | 8.30 ± 1.86 | |||
| Smoking | 0.453 | 0.344 | 0.546 | ||||
| Yes | 109 (14.34) | 8.49 ± 2.67 | 51.79 ± 5.35 | 8.06 ± 2.12 | |||
| No | 651 (85.66) | 8.69 ± 2.59 | 52.33 ± 5.55 | 8.18 ± 2.03 | |||
| Medical insurance | 0.146 | 0.396 | 0.340 | ||||
| Social medical insurance | 656 (86.32) | 8.66 ± 2.56 | 52.18 ± 5.56 | 8.14 ± 2.08 | |||
| Commercial insurance | 74 (9.74) | 8.36 ± 2.78 | 53.07 ± 5.18 | 8.49 ± 1.74 | |||
| No insurance | 30 (3.95) | 9.47 ± 2.83 | 51.90 ± 5.63 | 8.00 ± 1.86 | |||
| Family member of a leukemia patient | 0.103 | 0.862 | 0.547 | ||||
| Yes | 117 (15.39) | 8.30 ± 2.79 | 52.17 ± 5.52 | 8.06 ± 2.00 | |||
| No | 643 (84.61) | 8.72 ± 2.56 | 52.27 ± 5.53 | 8.18 ± 2.05 | |||
3. Questionnaire
The questionnaire was designed according to previous KAP studies conducted in the general population [14,15]. After the initial design, some items were revised in line with the local policies; afterward, the questionnaire was revised based on the feedback from two experts in hematology to remove unclear or incorrect items. The final questionnaire was in Chinese and contained four dimensions: demographic characteristics (age, gender, residence, ethnicity, education, occupation, monthly income, marital status, underlying disease, smoking, and medical insurance), knowledge dimension, attitude dimension, and practice dimension. The knowledge dimension consisted of 12 questions, with 1 point for correct answers and 0 points for incorrect or unclear answers, with total scores ranging from 0 to 12. The attitude dimension consisted of 13 questions using a 5-point Likert scale ranging from “strongly agree” (5 points) to “strongly disagree” (1 point), with total scores ranging from 13 to 65. The practice dimension contained 10 questions, with 1 point for ‘Yes’ and 0 for “No”, with the total scores ranging from 0 to 10.
3.1. Statistical analysis
Questionnaires with inconsistent responses for the question of medical insurance type, a response time of <100 s, and 0 points in the knowledge section was considered invalid and excluded. Besides, only one copy of the questionnaire was retained for the questionnaires with all consistent responses.
Stata 17.0 (Stata Corp LLC, USA) was used for statistical analysis. The continuous data were expressed as means ± standard deviations (SD) and compared using one-way ANOVA. The categorical data were expressed as n (%) and compared using the chi-square test. Pearson's correlation was used to analyze the correlation among the knowledge, attitude, and practice scores. Multivariable logistic regression was used to explore the factors independently associated with the knowledge, attitude, and practice scores. The KAP scores of participants were converted to binary variables according to their median. It was first planned to include the variables with univariable P < 0.05 in the multivariable analyses, but for analysis for practice, no variables showed P < 0.05 in univariable analyses. Finally, all variables were included in the multivariable analysis for practice. Structural equation modeling (SEM) was used to analyze the relationship between factors influencing KAP scores according to the study hypothesis that (1) knowledge would impact attitude and practice; (2) attitude would impact practice; (3) the role of “family member” would affect both knowledge and attitude. Two-sided P < 0.05 was considered statistically significant.
4. Results
The mean knowledge (8.30 ± 2.79 vs. 8.72 ± 2.56, P = 0.103; total score: 12), attitude (52.17 ± 5.52 vs. 52.27 ± 5.53, P = 0.862; total score: 65), and practice (8.06 ± 2.00 vs. 8.18 ± 2.05, P = 0.547; total score: 10) scores were comparable between family members and the general population (Table 1).
In the knowledge dimension, most participants answered correctly on questions about the cause, type, and treatment for leukemia, with a correct rate of >90%; only half (49.34%) of the participants answered correctly that chronic leukemia occurs mainly in adults (Table S1).
In the attitude dimension, most participants agreed that they need to be screened for leukemia in the presence of symptoms such as anemia, bleeding, or recurrent infection. For the questions about the risk of leukemia, most respondents had either a positive or neutral view. In terms of social support, most participants agreed that leukemia patients should not be discriminated against, that there is a need to increase advocacy about leukemia, and that more psychological and financial support should be provided for patients with leukemia (Table S2).
In the practice dimension, most participants were aware that they needed to learn more about leukemia (84.74%) and seek prompt medical attention when symptoms appeared (94.34%). Most participants also indicated that they would be willing to participate in care activities for patients with leukemia or to befriend them (91.18%). The number of participants who were willing to register as members of the Bone Marrow Bank (66.32%) or willing to donate bone marrow (70.53%) was relatively high but lower in percentage compared with the previous items (Table S3).
Multivariable analysis showed that higher education was independently associated with better knowledge scores of the participants [OR = 2.97 (1.48, 5.97), P = 0.002]. Higher knowledge [OR = 1.33 (1.24, 1.42), P < 0.001] was independently associated with higher attitude scores of participants. Higher knowledge [OR = 1.18 (1.10, 1.27), P < 0.001] and attitude [OR = 1.05 (1.02, 1.09), P = 0.002] scores were independently associated with higher practice scores (Table 2).
Table 2.
Factors influencing knowledge, attitude, and practice scores of participants.
| Characteristic | OR (95% CI) | P |
|---|---|---|
| Knowledge | ||
| Age | ||
| <30 | Ref. | |
| 31–40 | 0.96 (0.61, 1.50) | 0.854 |
| ≥41 | 0.78 (0.48, 1.27) | 0.324 |
| Education | ||
| Primary School or below | Ref. | |
| Secondary school/High school | 2.97 (1.48, 5.97) | 0.002 |
| Junior college/University | 2.45 (1.30, 4.62) | 0.006 |
| Graduate or above | 2.79 (1.34, 5.81) | 0.006 |
| Marital status | ||
| Married | Ref. | |
| Unmarried | 1.36 (0.88, 2.09) | 0.169 |
| Medical Insurance | ||
| No insurance | Ref. | |
| Social medical insurance | 0.70 (0.32, 1.55) | 0.380 |
| Commercial insurance | 0.56 (0.22, 1.41) | 0.221 |
|
Attitude | ||
| Knowledge | 1.33 (1.24, 1.42) | <0.001 |
| Age | ||
| <30 | Ref. | |
| 31–40 | 1.12 (0.79, 1.60) | 0.530 |
| ≥41 | 0.78 (0.52, 1.18) | 0.241 |
| Education | ||
| Primary School or below | Ref. | |
| Secondary school/High school | 0.99 (0.53, 1.84) | 0.974 |
| Junior college/University | 1.32 (0.77, 2.28) | 0.311 |
| Graduate or above | 1.09 (0.56, 2.11) | 0.802 |
|
Practice | ||
| Knowledge | 1.18 (1.10, 1.27) | <0.001 |
| Attitude | 1.05 (1.02, 1.09) | 0.002 |
| Age | ||
| <30 | Ref. | |
| 31–40 | 0.92 (0.57, 1.49) | 0.742 |
| ≥41 | 1.32 (0.77, 2.26) | 0.307 |
| Gender | ||
| Male | Ref. | |
| Female | 1.16 (0.83, 1.63) | 0.379 |
| Ethnicity | ||
| Others | Ref. | |
| Chinese Han | 0.90 (0.34, 2.40) | 0.830 |
| Occupation | ||
| Others | Ref. | |
| Professional technical personnel | 1.19 (0.78, 1.81) | 0.429 |
| Office staff and related personnel | 0.94 (0.59, 1.51) | 0.811 |
| Residence | ||
| Others | Ref. | |
| City | 0.82 (0.53, 1.26) | 0.366 |
| Education | ||
| Primary School or below | Ref. | |
| Secondary school/High school | 1.37 (0.68, 2.78) | 0.379 |
| Junior college/University | 1.33 (0.65, 2.72) | 0.437 |
| Graduate or above | 0.83 (0.35, 1.98) | 0.678 |
| Monthly income | ||
| <2000 | Ref. | |
| 2000–5000 | 0.93 (0.51, 1.70) | 0.816 |
| 5000–10000 | 1.05 (0.57, 1.95) | 0.867 |
| 10000–20000 | 1.13 (0.58, 2.22) | 0.718 |
| >20000 | 1.01 (0.49, 2.08) | 0.972 |
| Marital status | ||
| Married | Ref. | |
| Unmarried | 1.18 (0.73, 1.89) | 0.495 |
| Smoking | ||
| No | Ref. | |
| Yes | 0.76 (0.46, 1.23) | 0.263 |
| Medical Insurance | ||
| No insurance | Ref. | |
| Social medical insurance | 1.48 (0.55, 3.98) | 0.438 |
| Commercial insurance | 1.32 (0.56, 3.12) | 0.521 |
| Family member of a leukemia patient | ||
| No | Ref. | |
| Yes | 0.69 (0.44, 1.09) | 0.111 |
The results of the SEM applied to the above factors are summarized in Fig. 1. Knowledge had the most significant direct impact on attitude [β = 0.88 (95% CI: 0.75, 1.02), P < 0.001] and practice [β = 0.14 (95% CI: 0.08, 0.20), P < 0.001], as well as possible indirect impact on practice through attitude [β = 0.07 (95% CI: 0.04, 0.10), P < 0.001]. Being a family member of a patient with leukemia had no significant effect on KAP, but negative trends were noted, namely a negative direct effect on knowledge [β = −0.43 (95% CI: −0.94, 0.08), P = 0.102] and indirect on attitude [β = −0.38 (95% CI: −0.83, 0.08), P = 0.105].
Fig. 1.
Results of structural equation modeling demonstrating the association between family connection with leukemia patients, knowledge, attitude, and practice. Knowledge had direct impact on attitude and practice, as well as indirect impact on practice through attitude.
5. Discussion
This study showed relatively good knowledge, positive attitude, and appropriate practice among the general population family members of patients with leukemia. The study hypothesis that the practice patterns would be mostly affected by knowledge and attitude was confirmed; however, it was not confirmed that the role of family members significantly affects the knowledge and attitude of the participants toward leukemia. To our knowledge, this is the first study to report and analyze KAP patterns toward leukemia in China. The results contribute to the ongoing discussion on educational interventions needed to improve the patient's engagement, prognostic awareness, and knowledge of leukemia progression signs.
The leukemia therapeutic landscape has been recently expanded from traditional cytotoxic chemotherapies to novel therapeutic agents that target receptor tyrosine kinase signaling, apoptosis, hedgehog pathway, and mitochondrial function, among others [4]. The questionnaires in this study were distributed among family members of patients with leukemia and the general population. The participants demonstrated satisfactory knowledge and positive attitude, with better scores than previously reported in the literature [11,12,16]. Notably, being a patient's family member was not associated with better knowledge scores in this study, suggesting that the knowledge of leukemia is already satisfactory in the general population. Still, the knowledge scores are not perfect, highlighting that some education remains to be done.
This study showed that higher knowledge scores were independently associated with higher attitude and practice scores, also supported by the SEM analysis. Therefore, improving the knowledge should also improve the attitude and practice toward leukemia. Educational interventions in the public might increase knowledge about the disease and decrease psychological distress in patients and their family members [6]. In this study, most participants expressed the need to learn more about leukemia to seek prompt medical attention when symptoms appear or to be able to understand doctor's decisions. It was demonstrated that multidisciplinary knowledge of doctors and nurses might improve shared decision-making and patient engagement in leukemia treatment [17]. Another way to increase education is via oncology clinical pharmacists, who are uniquely trained, equipped, and positioned to impact the KAP of clinicians and patients [18]. Reaching out to pharmacists may help manage the changing landscape of leukemia care and improve treatment outcomes [19]. Higher education was the only factor associated with higher knowledge scores, as previously noted [11]. It is supported by Svendsen et al. [20], who showed that a higher socioeconomic status, which includes education, is also associated with better health literacy. These results suggest that individuals with a lower socioeconomic status should be the first targets of educational education.
Previous studies reported that the general public's knowledge regarding bone marrow donation and willingness to donate bone marrow differ significantly from 15.1% to 6.4% in Greece [21] to 59% and 41.6% in Poland [22]. Although it is impossible to make a direct comparison among studies due to the differences in questionnaire contents and study population, this study found relatively good knowledge (72.17%) and a high number of participants who were willing to register as members of the Bone Marrow Bank or willing to donate their bone marrow (66.32%). Recent data from the Chinese Blood and Marrow Transplantation Registry Group partly confirms the results, reporting continued growth in transplant activity in China, with a rapid increase in HCT [23].
5.1. Limitations and future directions
The above results are limited by the conditions of this study. Firstly, it was conducted in a single center, with inherited limitations and biases. Secondly, answers in the practice part of the questionnaire do not always reflect the actual behaviors of the participants, as they might respond according to social expectations (i.e., the social desirability bias [24,25]). Although this study noted unexpected trends toward lower KAP in family members of patients with leukemia compared with the general population, which might be a sign of exhaustion, the differences were not statistically significant; it should be discussed further in future studies to plan focused interventions. Finally, some rare factors that influence practice, such as the type of family connection or other cancers in the family, might have been overlooked because the sample size in this study was balanced but still comparatively small. Studies that include a wider population and focus on rural areas might obtain more nuanced results and indicate other vulnerable groups in need of education/support.
6. Conclusions
Both the general population and family members of leukemia patients in China possess satisfactory knowledge, positive attitudes, and appropriate practices towards leukemia. This suggests that access to information about leukemia for the general public may be relatively adequate. However, it is important to note that there is room for improvement in their KAP scores.
These findings underscore the potential benefits of health education interventions in further enhancing overall understanding, attitudes, and behaviors related to leukemia. Targeted educational initiatives can play a crucial role in addressing existing knowledge gaps among the general population, while also contributing to positive shifts in the perspectives and behaviors of family members. By strategically addressing these knowledge disparities through educational campaigns, we have the opportunity to cultivate a more informed and supportive community, thereby creating a conducive environment for both leukemia patients and their families. Continuous efforts in education can serve as a cornerstone for building a stronger foundation of awareness and empathy in society.
Ethics approval and consent to participate
The research was carried out in accordance with the Declaration of Helsinki. The study has been ethically approved by the Ethics Committee of Anhui Public Health Clinical Center (North District of the First Affiliated Hospital of Anhui Medical University), the ethical number is PJ-YX2023-008, and verbal informed consent was obtained from the participants.
Consent for publication
Not applicable.
Data availability statement
All data generated or analyzed during this study are included in this article and supplementary materials. The raw data can be provided upon reasonable request to the corresponding author.
Funding
This work was supported by the Scientific Research Project of the Higher Education Department of Anhui Province (No. KJ2021A0333).
CRediT authorship contribution statement
Fengbo Jin: Writing – review & editing, Writing – original draft, Methodology, Data curation. Wanlu Tian: Writing – review & editing, Formal analysis, Conceptualization. Leiming Xia: Writing – review & editing, Writing – original draft, Methodology, Data curation. Mingzhen Yang: Writing – review & editing, Writing – original draft, Methodology, Data curation. Yingying Chen: Writing – review & editing, Formal analysis, Conceptualization. Jianjun Li: Writing – review & editing, Writing – original draft, Formal analysis, Data curation. Lixia Liu: Writing – review & editing, Writing – original draft, Formal analysis, Data curation.
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgments
Not applicable.
Footnotes
Supplementary data to this article can be found online at https://doi.org/10.1016/j.heliyon.2024.e26276.
Contributor Information
Leiming Xia, Email: 278461175@qq.com.
Mingzhen Yang, Email: yangmz89@163.com.
Appendix A. Supplementary data
The following are the supplementary data to this article:
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Data Availability Statement
All data generated or analyzed during this study are included in this article and supplementary materials. The raw data can be provided upon reasonable request to the corresponding author.