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Background
lung cancer, airway obstruction
LUNG CANCER, AIRWAY OBSTRUCTION
Acapella plus active cycle of breathing technique (ACBT), external diaphragm pacemaker (EDP) plus ACBT have been shown to facilitate the recovery of functional capacity and lung function in patients suffering from airway obstruction but the efficacy in perioperative patients with lung cancer has not been proven.
PMC10053339
Methods
lung cancer
LUNG CANCER
We conducted a three-arm, prospective, randomized, assessor-blinded, controlled trial in patients with lung cancer who underwent thoracoscopic lobectomy or segmentectomy in the department of thoracic surgery, China. Patients were randomly assigned (1:1:1) to receive Acapella plus ACBT, EDP plus ACBT, or ACBT group (con...
PMC10053339
Results
We recruited 363 participants over 17 months: 123 assigned to the Acapella plus ACBT group, 119 to the EDP plus ACBT group, and 121 to the ACBT group. Statistically significant differences were noted for functional capacity between the EDP plus ACBT and control groups at each follow-up time (1-week follow-up: differenc...
PMC10053339
Conclusion
lung cancer
LUNG CANCER
EDP plus ACBT and Acapella plus ACBT significantly improved functional capacity and lung function in perioperative patients with lung cancer, compared with single-model ACBT, and the effects of EDP plus ACBT were clearly superior to those of other programs.
PMC10053339
Trial registration
The study was registered in the clinical trial database (clinicaltrials.gov) on June 4, 2021 (No. NCT04914624).
PMC10053339
Supplementary Information
The online version contains supplementary material available at 10.1186/s12885-023-10750-4.
PMC10053339
Keywords
PMC10053339
Background
cancers, cancer, stroke, lung cancer, deaths
CANCERS, POSITIVE, CANCER, STROKE, LUNG CANCER
As a major public health issue worldwide, lung cancer is the second most commonly diagnosed cancer, accounting for approximately 11.7% of all diagnosed cancers, and is the predominant cause of cancer-induced mortality (approximately 1.8 million deaths) [The active cycle of breathing technique (ACBT) is an ACT that focu...
PMC10053339
Methods
PMC10053339
Study design and setting
lung cancer
LUNG CANCER
This randomised (1:1:1), assessor-blinded, controlled trial compared three parallel groups of patients with lung cancer who underwent surgical resection. This study was approved by the Ethics Committee of the hospital, under reference number B2020-173-01, and submitted to the clinical trial database (clinicaltrials.gov...
PMC10053339
Participants
lung cancer, non-small cell lung carcinoma, cognitive impairment
LUNG CANCER, THORACIC, NON-SMALL CELL LUNG CARCINOMA, MOTOR DISORDERS
The participants were patients with lung cancer admitted to the Department of Thoracic Surgery in China. Patients were included if they (1) were aged between 18 and 80 years, (2) were diagnosed with stage I to IIIA non-small cell lung carcinoma subtypes by pathological cytology, (3) were undergoing thoracoscopic lobect...
PMC10053339
Randomisation and blinding
Participants who satisfied the eligibility criteria were block randomised using SAS software (version 9.4; SAS Institute, Inc.) with a 1:1:1 allocation using random block sizes of 3 and 6. Patients were equally assigned to the Acapella plus ACBT, EDP plus ACBT, or ACBT group. Blinding of participants to the treatment a...
PMC10053339
Intervention
After enrolment, patients in all groups participated in a multidisciplinary conventional inpatient rehabilitation program on the day of admission and day before surgery, and the program was standardised using evidence from systematic reviews and mainly included exercise, education, nutritional, respiratory physiotherap...
PMC10053339
Control group
During the control period, participants underwent ACBT treatment, which was standardised using evidence from systematic reviews, comprising 3–5 breath controls, 3–4 thoracic expansion exercises, and 2–3 forced expiratory techniques [ CONSORT 2010 flow diagram for the trialNote:
PMC10053339
Intervention group
Participants in the Acapella plus ACBT intervention group received a five-session combined ACTs program targeted at facilitating airway clearance on the day of admission, day before surgery, and POD 1–3 in the ward. Initially, the participants were asked to maintain a semi-recumbent position with the abdomen relaxed in...
PMC10053339
Outcomes
lung cancer, cancer
LUNG CANCER, CANCER, SECONDARY
The primary outcome was functional capacity in patients with lung cancer, as measured by the 6-minute walk test (6MWT), 1 week preoperatively and 1 month postoperatively. The 6MWT is a standardised test used to predict the prognosis of functional capacity in adult and geriatric patients with cancer [The secondary outco...
PMC10053339
Statistical analysis
bleeding
SECONDARY, PATHOLOGY, BLEEDING
In this study, PASS 14 (PASS software, Kaysville, Utah, USA; All analyses were conducted in accordance with the intention-to-treat principle. Continuous variables are expressed as mean (SDs), and categorical variables as frequencies and percentages. Descriptive statistics were used for baseline characteristics and outc...
PMC10053339
Results
PMC10053339
Participant characteristic
lung cancer
LUNG CANCER
Between July 1, 2021, and November 31, 2022, 400 patients with lung cancer were enrolled in the study, and 35 were subsequently excluded because they did not meet the eligibility criteria. Therefore, 365 patients with lung cancer were randomised into groups. Two patients dropped out due to withdrawal of consent, result...
PMC10053339
Outcomes
bleeding
BLEEDING, PATHOLOGY
Table  Effects of the intervention on 6-minute walk test and lung function parametersǂ: Between-group difference for mean change, based on the linear mixed model, adjusted for baseline demographic and disease-related characteristics (i.e. age, sex, height, weight, education level, smoking amount, smoking years, patholo...
PMC10053339
Primary study endpoint
At the 1-week follow-up after surgery, the 6MWT of participants was significantly improved in the EDP plus ACBT (difference = 47.25 m; 95% CI, 31.56–62.93; (A) 6-minute walk test, (B) the predicted percentage of forced expiratory volume in the first secondData points indicate means and error bars represent 95% confide...
PMC10053339
Secondary study endpoint
lung cancer, Postoperative pulmonary complications, atelectasis, hypoxemia
LUNG CANCER, SECONDARY, ATELECTASIS, PULMONARY INFECTION
Compared with the control group, participants in the Acapella plus ACBT group had significantly improved FEV1% of predicted at the 1-week (difference = 13.35; 95% CI, 9.83–16.87; Among the remaining lung function parameters, between-group differences in the FVC% of predicted followed a similar pattern to FEV1% of predi...
PMC10053339
Discussion
lung cancer, pain, non-cystic fibrosis bronchiectasis, trauma
LUNG CANCER, NON-CYSTIC FIBROSIS BRONCHIECTASIS
To our knowledge, the present trial is the first to directly compare two combined ACT programs comprising Acapella plus ACBT and EDP plus ACBT, both with one another and with the single-model ACBT program. The results support the hypothesis that preparing perioperative patients for surgical resection of lung cancer wit...
PMC10053339
Limitations
BLIND
The main limitation of this study was the inability to blind the patients and therapists with regard to treatment allocation; therefore, potential performance bias might have been generated. Our study attempted to reduce the possibility of detection bias, including having assessors of outcomes blind to group allocation...
PMC10053339
Conclusions
lung cancer
LUNG CANCER
This study found that EDP plus ACBT and Acapella plus ACBT significantly improved functional capacity and lung function in perioperative patients with lung cancer, compared with single-model ACBT, and the effects of EDP plus ACBT were superior to those of Acapella plus ACBT. Thus, both combined ACT programs are effecti...
PMC10053339
Acknowledgements
We express our sincere appreciation to all patients, caregivers, and healthcare providers who participated in this study.
PMC10053339
Author Contribution
Chuanzhen Li
Jiudi Zhong, Hao Long, and Zhixing Guo conceived and drafted the protocol for this study and raised funds. Xiaoxue Chen, Chuanzhen Li, and Linjuan Zeng designed and performed experiments. Qinglin Wang, Tiehua Rong, and Peng Lin analysed the study data and prepared the figures. Xiaoxue Chen, Chuanzhen Li, and Linjuan Ze...
PMC10053339
Funding
-11
This project was supported by a grant from the Wu Jieping Medical Foundation, China (Grant/Award Number:320.6750.2020-15-11).
PMC10053339
Data Availability
The datasets used and/or analysed during the current study are available from the corresponding author on request.
PMC10053339
Declarations
The authors declare no competing interests.
PMC10053339
Ethics approval and consent to participate
ONCOLOGY
The study was approved by the Ethics Committee of the Oncology Center of Sun Yat-sen University on July 28, 2020 (B2020-173-01), and all methods were carried out in accordance with the Declaration of Helsinki. All patients participating in the study voluntarily signed the informed consent form in person.
PMC10053339
Consent for publication
Not applicable.
PMC10053339
Competing interests
All authors of this study stated that they had no conflict of interest.
PMC10053339
Abbreviations
Postoperative pulmonary complicationsAirway clearance techniquesActive cycle of breathing techniqueExternal diaphragm pacemakerForced expiratory volume in the first secondPostoperative days6-minute walk testPostoperative daysStandard deviationConfidence intervalLinear mixed model
PMC10053339
References
PMC10053339
Keywords
weight loss
To elucidate the role of neighborhood walkability and crime on weight loss, we examined data from older adults residing in Chicago who participated in a randomized controlled trial lifestyle intervention. Controlling for individual demographic characteristics and the intervention assignment, the neighborhood homicide r...
PMC10544679
Introduction
obesity, weight loss
OBESITY, DISEASE
The prevalence of adult obesity with Body Mass Index (BMI) greater than 30 is expected to reach nearly 50% of the United States (U.S.) population by 2030 (Centers for Disease Control and Prevention, Studies have documented the effect of neighborhood social conditions, including social support and cohesion, a sense of c...
PMC10544679
Methods
PMC10544679
Setting and data
This analysis utilized data from an RCT,
PMC10544679
Variables and statistical analysis
deaths, Ewing
Of the 185 original study participants, our analysis included 184 participants who resided within Cook County, Illinois. We geocoded participants’ residential addresses using ArcGIS and appended census tract numbers which were used to merge with the neighborhood variables.The outcome variable was weight change between ...
PMC10544679
Discussion
weight gain, weight loss
SAMPSON
Our findings showed that neighborhood crime measured by the homicide rate was significantly associated with less weight loss, controlling for all other variables including the intervention assignment. Participants who resided in neighborhoods at or above the 50th percentile of homicide rate actually gained weight betwe...
PMC10544679
Funding
Sage Kim was supported by NIMHD (R01MD014839); Lisa Tussing-Humphrys was supported by NIMHD (U54MD012523; Marian Fitzgibbon was supported by NHLBI (R01HL129153); Caryn Peterson was supported by NCI (U54CA202995; U54CA202997).
PMC10544679
Declarations
PMC10544679
Conflicts of interest/Competing interests
None.
PMC10544679
References
PMC10544679
Abstract
PMC10757118
Background
Approximately 40% of patients with hormone receptor (HR)‐positive and human epidermal growth factor receptor 2 (HER2)‐negative advanced breast cancer (ABC) exhibit PIK3CA mutations.
PMC10757118
Aims
This study aims to evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of HS‐10352, a selective PI3Kα inhibitor, in this patient population.
PMC10757118
Materials and Methods
toxicity
Conducted as a phase 1 dose‐escalation trial, HS‐10352 was administered orally once‐daily (QD) at dose levels of 2, 4, 6, and 8 mg. The primary endpoints were dose‐limiting toxicity (DLT) and the maximum tolerated dose (MTD). This study is registered at ClinicalTrials.gov (NCT04631835).
PMC10757118
Results
hyperglycemia, weight loss, mutated tumors, SD
HYPERGLYCEMIA, DISEASE, ADVERSE EVENTS
Between August 2020 and March 2022, a total of 18 female patients were enrolled. DLT, manifested as hyperglycemia, occurred in two patients in the 8 mg QD group, establishing an MTD of 6 mg QD. The most common treatment‐related adverse events were hyperglycemia (88.9%) and weight loss (61.3%). In the 6 mg QD group, fou...
PMC10757118
Discussion and Conclusion
cancer tumor, mutated tumors
PROLIFERATION, METASTATIC BREAST CANCER
HS‐10352 at 6 mg QD was well‐tolerated in patients with HR‐positive, HER2‐negative ABC, and showed preliminary antitumor activity in patients with PIK3CA mutated tumors. These findings support the further clinical development of HS‐10352.HS‐10352 is a novel selective PI3Kα inhibitor showing inhibitory effects on the pr...
PMC10757118
INTRODUCTION
breast cancer, cancer, Breast cancer, gastric cancer HGC‐27, human gastric cancer, deaths, tumors, weight loss
BREAST CANCER, PROLIFERATION, CANCER, BREAST CANCER, TUMOR GROWTH, TUMORS
Breast cancer is the most common cancer and the leading cause of cancer‐related deaths in females.HS‐10352 is a novel, highly selective PI3Kα inhibitor with an IC50 value of 0.34 nM. It exhibits far greater selectivity for PI3Kα over PI3Kβ, PI3Kδ, and PI3Kγ, with 321‐, 103‐, and 159‐fold higher selectivity, respectivel...
PMC10757118
METHODS
PMC10757118
Study design and patients
Tumors, diabetes symptoms, primary malignant tumors, diabetes
BRAIN METASTASES, DISEASES, SPINAL CORD COMPRESSION, TUMORS, CHRONIC PANCREATITIS, METASTASES, DIABETES
This was an open‐label, phase 1 dose‐escalation trial registered at Key inclusion criteria were as follows: (1) 18–75 years of age; (2) at least one measurable lesion according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1Key exclusion criteria were as follows: (1) previous treatment with PI3K, A...
PMC10757118
Procedure and assessments
Cancer
ADVERSE EVENT, DISEASE PROGRESSION, ADVERSE EVENTS, BLOOD, CANCER
This dose‐escalation trial employed a “Rolling 6” design,Blood samples were collected from each patient after a single dose of HS‐10352 on Day 1 of Cycle 0, followed by a 7‐day observation period. Repeated administration of the same dose commenced on Day 8, marking the beginning of Cycle 1. Each treatment cycle lasted ...
PMC10757118
E545D, Breast tumor
BREAST TUMOR, PIK3CA MUTATION
Breast tumor tissue samples were collected, and PIK3CA mutation status was determined by the central laboratory using the fluorescence quantitative PCR instrument (Cobas Z480) along with the PIK3CA Mutation Detection Kit (AmoyDx, Xiamen, China). This kit is specifically designed to detect the five hotspot PIK3CA mutati...
PMC10757118
Study endpoints
toxicity, SD
DISEASE
The primary endpoints were dose‐limiting toxicity (DLT) and MTD of HS‐10352. Secondary endpoints included safety, pharmacokinetics, objective response rate (ORR), disease control rate (DCR), duration of response (DoR), PFS, and overall survival (OS).DLT was defined as any grade ≥4 hematologic or grade ≥3 non‐hematologi...
PMC10757118
Statistical analysis
A “Rolling 6” design was adopted in this dose‐escalation study, with up to six evaluable patients enrolled in each dose group. The total number of participants was contingent on the number of dose‐escalation groups.Statistical analyses primarily utilized descriptive statistics. Continuous variables were presented as me...
PMC10757118
RESULTS
PMC10757118
Patient characteristics
ONCOLOGY
A total of 28 patients were screened for eligibility between August 2020 and March 2022. Of these, 18 female patients with HR‐positive, HER2‐negative ABC were enrolled and treated with HS‐10352 (Figure Study flowchart.Baseline patient characteristics.Abbreviations: BMI, body mass index; CDK, cyclin‐dependent kinase; EC...
PMC10757118
Safety
DLTs, TRAEs
HYPERGLYCEMIA
In the 8 mg QD group, two patients experienced DLTs of grade 3 hyperglycemia. No DLTs were reported in other dose groups, indicating an MTD of 6 mg QD. The incidence rates of AEs and grade ≥3 AEs were 100% and 27.8%, respectively. TRAEs occurred in all patients, regardless of the drug dose (Table TRAEs occurring in ≥10...
PMC10757118
Pharmacokinetics
Following a single‐dose oral administration of 2, 4, 6, or 8 mg in patients with ABC, HS‐10352 was rapidly absorbed. The median times to peak (Concentration–time curves in the 2, 4, 6, and 8 mg QD groups after single‐dose administration in Cycle 0 (A) and multiple‐dose administration in Cycle 2 (B).After multiple‐dose ...
PMC10757118
Efficacy
PD, tumor, tumors, mutated tumors
DISEASE, TUMORS, TUMOR
Five of the 18 patients had PR (4 and 1 in the 6 mg and 8 mg QD groups, respectively), with an ORR of 27.8% (95% CI, 9.7%–53.5%), a DCR of 55.6% (95% CI, 30.8%–78.5%) and a median PFS of 3.9 (95% CI, 2.0‐NA) months. In the 6 mg QD group, ORR and DCR were 66.7% (95% CI, 22.3%–95.7%) and 83.3% (95% CI, 35.9%–99.6%), resp...
PMC10757118
DISCUSSION
tumor, tumors
ONCOGENESIS, REGRESSION, TUMOR, TUMORS
The efficacy of PI3K inhibitors has been confirmed in randomized phase 3 trials.The safety profile of pan‐PI3K inhibitors has been a limiting factor for their use in clinical practice.HS‐10352 exhibited favorable pharmacokinetic characteristics. According to the concentration–time curves, an increase in dosage did not ...
PMC10757118
CONCLUSION
mutated tumors
HS‐10352, administered at 6 mg once‐daily, was well‐tolerated in patients with HR‐positive, HER2‐negative ABC and showed promising antitumor activity, particularly in individuals with PIK3CA mutated tumors. These findings lend support to the further clinical development of HS‐10352, including its potential use in combi...
PMC10757118
AUTHOR CONTRIBUTIONS
PMC10757118
CONFLICT OF INTEREST STATEMENT
All authors declare no financial or non‐financial conflicts of interests.
PMC10757118
ETHICS STATEMENT
The study protocol was registered at
PMC10757118
Supporting information
Click here for additional data file.
PMC10757118
ACKNOWLEDGMENTS
We thank all the patients who participated in the trial, their families, and the site staff at the three participating centers, without whom this study could not be completed. We also thank the study teams of Hansoh Pharmaceutical Group Co. Ltd., including Hong Xu, Yong Yang, Tianyu Sun, Huifeng Zhang, Min Zhang, Xiang...
PMC10757118
DATA AVAILABILITY STATEMENT
All data generated or analyzed in this study are included in the published article and its supplementary information files.
PMC10757118
REFERENCES
PMC10757118
Background
Trauma
This experimental study was performed to evaluate the role of blended learning for technical skill teaching on the European Trauma Course (ETC). While online modules are extensively used for theoretical teaching, their role in skills training remains less well explored. The ETC currently relies on the established 4-ste...
PMC10644658
Methods
SECONDARY
In a randomised, multi-centre trial, the conventional face-to-face 4-step technique for teaching a skill of medium complexity, the application of a pelvic binder, was compared with an innovative blended approach. It was hypothesised that the blended approach was non-inferior for skill performance measured after the tea...
PMC10644658
Results
Ninety participants, divided into 44 traditional and 46 blended method students, were analysed. Independent-samples t-test showed no significant difference in performance scores and non-inferiority of the blended approach with a half of one standard deviation margin. A statistically significant difference in mean reten...
PMC10644658
Supplementary Information
The online version contains supplementary material available at 10.1186/s13049-023-01127-4.
PMC10644658
Keywords
Open Access funding enabled and organized by Projekt DEAL.
PMC10644658
Background
Trauma
Drawing from the lessons of the Covid pandemic, the International Liaison Committee on Resuscitation (ILCOR) has advised that all life support courses, including the European Trauma Course (ETC), embrace blended learning methodologies to enhance the resilience of teaching and training [An experimental study was devised...
PMC10644658
Study methodology
trauma
Based on a post-positivist paradigm, this quantitative, experimental study compared two teaching techniques for their effectiveness. The hypotheses state that the blended approach will be non-inferior to the traditional approach in terms of skill performance, skill retention, student and teacher satisfaction and additi...
PMC10644658
Design
PMC10644658
Setting
The study occurred over five courses, each lasting 2.5 days. Pelvic binder teaching sessions took place on the first day, with 2 to 4 instructors teaching groups of 4 candidates. Sessions for control and research groups were conducted simultaneously in different rooms, and instructors taught the same session three time...
PMC10644658
Procedure for the control – and research group
Figure Study design. Two groups received skills training for pelvic binder application; a face-to-face 4-step approach for the control group and a blended modification for the research group. Both groups were assessed for their performance immediately after the teaching session and 2 days later (retention). Further out...
PMC10644658
Self-study for both groups
Candidates were expected to read the ETC course manual's pelvic binder instructions, before the course.
PMC10644658
Online module for research group
The research group received an additional online module two weeks before the course, including theoretical content, videos showing step 1 and 2, online activities for step 3, and self-assessment questions.All instructors received the online module, with the instructors for the control group instructed to teach the skil...
PMC10644658
Face-to-face teaching
trauma
Step 1 for both groups was a real-time demonstration of pelvic binder application during a simulated trauma scenario, aligning with the concept of contextual learning [Steps 2–4 for the control group involved a detailed explanation, followed by candidates guiding each other through the application with corrective feedb...
PMC10644658
Assessment
Trauma
After step 4, instructors assessed candidates' skill performance using a standardised checklist, which was based on the regular ETC criteria and the European Trauma Course Manual [
PMC10644658
Evaluation
After the teaching session, candidates were asked to rate their satisfaction with the teaching technique on a 5-point Likert scale, covering the aspects of explanation, feedback, practice time, and assessment objectivity (Additional file Instructors also rated their satisfaction on a 5-point scale, focusing on time for...
PMC10644658
Retention
All candidates completed a second performance assessment (retention assessment) on day three in a separate room with an assessor, a research assistant and a manikin.
PMC10644658
Data collection and analysis
Data collection was subjected to the European General Data Protection Regulation (2016). Data were analysed using SPSS Statistics version 29 (IBM). Descriptive statistics were given in terms of frequencies, means, medians, standard deviation, and range. Independent samples t-tests were used for performance and retentio...
PMC10644658
Results
PMC10644658
Participants
A total of 108 candidates were invited to take part in the study and all agreed to participate by signing informed consent. Four participants were lost to attrition because they did not attend the course. Two participants from the control group were excluded because they had viewed the online module which a fellow part...
PMC10644658
Performance score as outcome parameter
Both the control and research groups scored highly on the performance assessment, with mean scores of 17.07 (SD = 1.58) and 17.43 (SD = 0.98) respectively, out of a possible 18. An independent-samples t-test found no significant difference between the two groups (t (88) = −1.33,
PMC10644658
Retention score as outcome parameter
The retention assessment was done two days after the teaching session, with mean scores for the control group at 15.66 (SD = 1.86) and 17.02 (SD = 1.33) for the research group. The difference in mean retention scores was statistically significant in favour of the research group (Performance and Retention scores for eac...
PMC10644658
Satisfaction as outcome parameter
PMC10644658
Candidate satisfaction
The general satisfaction with the teaching session was measured on a scale of 1 (very satisfied) to 5 (very dissatisfied). Both groups reported 98% 'satisfied' or 'very satisfied', with a higher proportion of 'very satisfied' in the control group (77% vs. 59%). The Mann–Whitney U Test found no significant difference in...
PMC10644658
Instructor satisfaction
24 instructors participated in the study, with 12 teaching the control group and 12 the research group (four instructors' data were excluded due protocol violation).Instructor satisfaction was measured on a 5-point Likert scale. Overall, 96% of instructors were satisfied or very satisfied (Fig. Instructor satisfaction ...
PMC10644658
Teaching time as outcome parameter
The study included 24 teaching sessions, 12 using traditional teaching and 12 using a blended approach. The traditional teaching sessions took a mean time of 12.61min (SD = 2.80), ranging from 8 to 17 min. The blended approach sessions took a mean time of 6.76min (SD = 0.99), ranging from 5 to 8 min (Fig. Mean teaching...
PMC10644658
Discussion
The study confirmed that the blended teaching approach was non-inferior to the traditional method in skill performance, skill retention and satisfaction, whilst reducing face-to-face teaching time.
PMC10644658
Performance and retention scores
The results align with prior research showing no difference in performance scores when parts of the 4-step teaching technique are replaced by standardised videos [In this study, replacing teaching steps with best-practice videos and interactive exercises, led to equivalent performance and an even better retention in th...
PMC10644658
Candidate satisfaction with the teaching session
Both teaching sessions were well received by the candidates, as 98% of each group reported high satisfaction levels. It should be noted that the control group reported a higher proportion of candidates (77%) to be 'very satisfied' compared to the research group (59%). In contrast to the present study results, students ...
PMC10644658