Association between serum calcium and prognosis in patients with acute ischemic stroke in ICU: analysis of the MIMIC-IV database.

BACKGROUND: While serum Ca has proven to be a reliable predictor of mortality across various diseases, its connection with the clinical outcomes of ischemic stroke (IS) remains inconclusive. Our research aimed to explore the relationships between serum total Ca (tCa) and serum ionized Ca (iCa) and mortality among acute IS (AIS) patients. METHODS: We gathered data from 1773 AIS patients in the Medical Information Mart for Intensive Care Database IV, including baseline demographic data, comorbidities, vital signs, laboratory-based data, and scoring systems. Endpoints for the study encompassed 30-d, 90-d, and 365-d all-cause mortalities. Employing restricted cubic spline Cox regression, we explored potential nonlinear relationships between admission serum iCa and tCa levels and mortality. Participants were categorized into four groups based on serum iCa and tCa quartiles. Multivariable Cox regression analysis was then conducted to evaluate the independent association of iCa and tCa quartiles with all-cause mortality. RESULTS: The restricted cubic spline revealed a U-shaped association between iCa and 30-d and 90-d mortality (P<0.05), while the relationship between iCa and 365-d mortality was linear (P<0.05). After adjusting for confounders, multivariable Cox analysis demonstrated that the lowest serum iCa level quartile was independently associated with increased risks of 30-d, 90-d, and 365-d mortality. Similarly, the highest serum iCa level quartile was independently associated with increased risks of 30-d and 90-d mortality, but not 365-d mortality. Notably, serum tCa level showed no association with increased risks of 30-d, 90-d, and 365-d mortality. CONCLUSIONS: Our findings suggest that serum iCa, rather than tCa, is linked to ischemic stroke prognosis. Both high and low serum iCa levels are associated with poor short-term prognosis, while only low serum iCa is associated with poor long-term prognosis in AIS patients.

Impact of SARS-CoV-2 infection on patients with hematological malignancies: a retrospective study.

OBJECTIVES: This study aimed to evaluate the characteristics of patients with hematological malignancies (HM) and SARS-CoV-2 infection and analyze the risk factors of their severity and mortality. METHODS: A retrospective study including inpatients diagnosed HM and SARS-CoV-2 infection between December 2022 and February 2023 were conducted. Demographic information, medical history, comorbidities, diagnosis, treatment related information and outcomes were extracted from electronic medical database. The primary outcome of this study were the severity of SARS-CoV-2 infection and case-fatality rate. The clinical characteristic and outcomes of the patients were summarized and analyzed. RESULTS: A total of 74 patients with HM and SARS-CoV-2 infection were included. Out of the total cases, 85.1% (63) had a mild /moderate SARS-CoV-2 infection, and 14.9% (11) were severe/ critical infection cases. A total of 8 deaths occurred in all cases for a case-fatality rate of 10.8%. Multivariate analysis identified patients with acute myeloid leukemia (AML) (P = 0.043, OR:5.274, 95%CI:1.053-26.407), primary hematological disease in active state (P = 0.005, OR:13.905, 95%CI:2.180-88.704) were independent risk factors for the severity of SARS-CoV-2 infection and patients with AML had 11.145-fold higher risk of non-survival (P = 0.020, OR:11.145, 95%CI:1.460-85.103) in comparison to the patients with other types of HM. There were no significant differences in the severity and case-fatality rate (P > 0.05) between the patients receiving chemotherapy drugs administration waiting <14 days and ≥14 days after negative SARS-CoV-2 testing. CONCLUSION: The primary hematological disease in active state may be the main risk factor for negative outcome of the patents. Waiting 14 days for chemotherapy initiation after negative SARS-CoV-2 testing is unnecessary.

Nomogram model for predicting frailty of patients with hematologic malignancies - A cross-sectional survey.

Objective: This study aimed to develop and validate an assessment tool for predicting and mitigating the risk of frailty in patients diagnosed with hematologic malignancies. Methods: A total of 342 patients with hematologic malignancies participated in this study, providing data on various demographics, disease-related information, daily activities, nutritional status, psychological well-being, frailty assessments, and laboratory indicators. The participants were randomly divided into training and validation groups at a 7:3 ratio. We employed Lasso regression analysis and cross-validation techniques to identify predictive factors. Subsequently, a nomogram prediction model was developed using multivariable logistic regression analysis. Discrimination ability, accuracy, and clinical utility were assessed through receiver operating characteristic (ROC) curves, C-index, calibration curves, and decision curve analysis (DCA). Results: Seven predictors, namely disease duration of 6-12 months, disease duration exceeding 12 months, Charlson Comorbidity Index (CCI), prealbumin levels, hemoglobin levels, Generalized Anxiety Disorder-7 (GAD-7) scores, and Patient Health Questionnaire-9 (PHQ-9) scores, were identified as influential factors for frailty through Lasso regression analysis. The area under the ROC curve was 0.893 for the training set and 0.891 for the validation set. The Hosmer-Lemeshow goodness-of-fit test confirmed a good model fit. The C-index values for the training and validation sets were 0.889 and 0.811, respectively. The DCA curve illustrated a higher net benefit when using the nomogram prediction model within patients threshold probabilities ranging from 10% to 98%. Conclusions: This study has successfully developed and validated an effective nomogram model for predicting frailty in patients diagnosed with hematologic malignancies. The model incorporates disease duration (6-12 months and>12 months), CCI, prealbumin and hemoglobin levels, GAD-7, and PHQ-9 scores as predictive variables.

Risk factors for malnutrition in patients with nasopharyngeal carcinoma.

BACKGROUND: Malnutrition is a common complication in patients with nasopharyngeal carcinoma (NPC). However, there are few studies on risk factors for malnutrition in NPC patients. Our aims were to identify the risk factors for malnutrition in NPC patients. METHODS: NPC patients were recruited in this cross-sectional study, and they were divided into well-nourished and malnourished groups according to the Global Leadership Initiative on Malnutrition (GLIM). Potential risk factors were initially screened using univariate analysis (p < 0.1), and the selected ones were analyzed by logistic regression analysis (p < 0.05) to identify the risk factors for malnutrition in NPC patients. RESULTS: In total, 305 NPC patients meeting eligibility criteria were enrolled. Multivariate logistic regression analysis revealed that low body mass index (BMI) (OR = 0.596, 95% CI 0.520-0.683, p < 0.001), the high total radiation dose received (OR = 1.046, 95% CI 1.023-1.069, p < 0.001), appetite loss (OR = 2.839, 95% CI 1.269-6.353, p = 0.011), and low PA (OR = 0.993, 95% CI 0.988-0.998, p = 0.008) were risk factors for malnutrition in NPC patients. CONCLUSIONS: The low BMI, the high total radiation dose received, appetite loss, and low prealbumin were risk factors for malnutrition in NPC patients.

Resistance exercise promotes the resolution and recanalization of deep venous thrombosis in a mouse model via SIRT1 upregulation.

BACKGROUND: Early exercise for acute deep venous thrombosis (DVT) improves the patient's symptoms and does not increase the risk of pulmonary embolism. However, information about its effect on thrombus resolution is limited. The aim of this study was to investigate the role of resistance exercise (RE) in thrombus resolution and recanalization and determine its underlying mechanisms.  METHODS: Ninety-six C57BL/6 J mice were randomly divided into four groups: Control group (C, n = 24); DVT group (D, n = 24); RE + DVT group (ED, n = 24); and inhibitor + RE + DVT group (IED, n = 24). A DVT model was induced by stenosis of the inferior vena cava (IVC). After undergoing IVC ultrasound within 24 h post-operation to confirm DVT formation, mice without thrombosis were excluded. Other mice were sacrificed and specimens were obtained 14 or 28 days after operation. Thrombus-containing IVC was weighed, and the thrombus area and recanalization rate were calculated using HE staining. Masson's trichrome staining was used to analyze the collagen content. RT-PCR and ELISA were performed to examine IL-6, TNF-α, IL-10, and VEGF expression levels. SIRT1 expression was assessed using immunohistochemistry staining and RT-PCR. VEGF-A protein expression and CD-31-positive microvascular density (MVD) in the thrombus were observed using immunohistochemistry.  RESULTS: RE did not increase the incidence of pulmonary embolism. It reduced the weight and size of the thrombus and the collagen content. Conversely, it increased the recanalization rate. It also decreased the levels of the pro-inflammatory factors IL-6 and TNF-α and increased the expression levels of the anti-inflammatory factor IL-10. RE enhanced VEGF and SIRT1 expression levels and increased the MVD in the thrombosis area. After EX527 (SIRT1 inhibitor) was applied, the positive effects of exercise were suppressed. CONCLUSIONS: RE can inhibit inflammatory responses, reduce collagen deposition, and increase angiogenesis in DVT mice, thereby promoting thrombus resolution and recanalization. Its underlying mechanism may be associated with the upregulation of SIRT1 expression.

Prevalence and treatment of venous thromboembolism in patients with solid tumors.

Cancer-associated venous thromboembolism (VTE) has exhibited a rising incidence rate. Research focusing on cancer-associated VTE and current anticoagulation therapy strategies is limited. The present study aimed to investigate the prevalence, characteristics and anticoagulation therapy strategies of cancer-associated VTE. The study was performed on patients with major solid tumors who were admitted to The First Affiliated Hospital of Guangxi Medical University (Nanning, China) between January 2020 and December 2020. The medical records of the patients' demographic characteristics, disease and treatment were extracted from the medical record data system and reviewed. The prevalence of cancer-associated VTE was calculated, followed by statistical analysis. Patients who received anticoagulation therapy for cancer-associated VTE were followed up for 1 year. The characteristics and efficacy of anticoagulation therapy strategies were compared and analyzed. A total of 4,926 patients with major solid tumors (mean age, 55.86±11.97 years) were included in the analysis, of which 117 (2.4%; 117/4,926) were diagnosed with cancer-associated VTE. Patients with pancreatic cancer exhibited the highest prevalence of VTE (10.2%; 5/49), followed by patients with ovarian cancer (5.8%; 9/156) and lung cancer (3.3; 73/2,237). Multivariate analysis identified hypertension comorbidity [odds ratio (OR), 1.661; 95% CI, 1.031-2.674; P=0.037)] and cancer stage (OR, 1.266; 95% CI, 1.079-1.486; P=0.004) as independent risk factors for cancer-associated VTE. Deep vein thrombosis (DVT) of the lower extremity accounted for 62.0%; 62/100) of all DVTs. Moreover, pulmonary embolism (PE) with lower extremity DVT accounted for 53.5% (23/43) of all PE cases. The majority of cancer-associated VTE cases (63.2%; 74/117) developed 30 days before or after a cancer diagnosis. In addition, cancer-associated VTE was dominated by symptomatic VTE (59.8%; 70/117). Only 74.4% (87/117) of patients with VTE received anticoagulant treatment, with a median duration of 79 days. The most common anticoagulant treatment strategies were heparin during hospitalization and direct oral anticoagulants (rivaroxaban) after discharge. The anticoagulants associated with bleeding events were rivaroxaban (4.2%; 3/72) and enoxaparin (1.9%; 1/54). In total, 62.1% (36/58) of the patients received anticoagulant treatment for <90 days. In conclusion, the results indicated that the prevalence of cancer-associated VTE is common and exhibits numerous characteristics. Rivaroxaban has been widely used in cancer-associated VTE treatment. However, compliance with long-term anticoagulant treatment is not adequate at present, while the efficacy and safety of rivaroxaban must be evaluated to improve long-term medication monitoring and follow-up among patients with cancer-associated VTE.

How Can Nursing Teams Respond to Large-Scale COVID-19 Screening?

The COVID-19 virus has devastated lives and economies worldwide. The responses of nursing teams to large-scale COVID-19 screening have rarely been addressed or described. The aim of this study is to introduce an efficient response strategy for nurses in large-scale COVID-19 screening. A new COVID-19 case was confirmed on Jan 14, 2021 in Nanning, China. Immediately, a large-scale COVID-19 screening was launched and ran from Jan 14 to Jan 17, 2021. Our nurse team responding to the screening included three major components: (1) establishing a leadership group and a nucleic acid sampling emergency team; (2) defining, conducting, and evaluating nurse training; (3) implementing efficient sampling schemes (10 in 1 mixed sample technique). A total of 500 nurse volunteers were recruited and divided into three echelons. A total of 353 trained nurses were sent to 65 sampling stand stations. In cooperation with nurses from other health institutions, samples were collected from a total of 854,215 people in only 4 days for 2019-nCOV nucleic acid screening. The preparation and efficient response strategies used to conduct this screening may provide a baseline reference for future large-scale COVID-19 screening worldwide.

Q-15 Minutes Vital Sign Documentation Is a Poor Surrogate for Assessing Quality of Care After Acute Ischemic Stroke.

OBJECTIVE: Documenting vital signs and National Institutes of Health Stroke Scale (NIHSS) once every 15 minutes after intravenous thrombolytic therapy for acute ischemic stroke is often used as a metric to assess the quality of care. This study explores the association between "once every 15 minutes" documentation and stroke outcomes. METHODS: This is a retrospective study of the first 2 hours of vital signs and NIHSS documentation after thrombolytic stroke therapy. Sociodemographic and clinical data, including NIHSS, temperature, heart rate, systolic blood pressure, diastolic blood pressure, mean arterial blood pressure, and respiratory rate, were abstracted from the medical record. Missing documentation was examined for association with modified Rankin Scale (mRS) scores and neurologic changes. RESULT: Among 84 patients with a mean age of 68.8 years, there were 2276 documented assessments from an expected 3780. There were 104 clinically significant changes in 1 or more index variables. The most commonly missed documentation occurred during interventional radiology. After controlling for admission NIHSS, there was no significant relationship between the completeness of documentation and discharge mRS score (r2 = 0.047, P = .0561), nor between vital sign documentation and discharge mRS (r2 = 0.003, P = .6338). CONCLUSION: Frequency of documentation does not reflect the quality of care during the early phase of acute stroke treatment.

Resistance exercise affects catheter-related thrombosis in rats through miR-92a-3p, oxidative stress and the MAPK/NF-κB pathway.

BACKGROUND: MiR-92a-3p and oxidative stress are associated with catheter-related thrombosis (CRT). As a kind of physical intervention, resistance exercise can effectively promote blood circulation. In this study, we investigated the roles of miR-92a-3p, oxidative stress and the P38 mitogen-activated protein kinase/nuclear factor-κB (MAPK/NF-κB) pathway in CRT during resistance exercise. METHODS: The rat CRT model was used for resistance exercise intervention. Moreover, pathological changes from the right jugular vein to the right auricle were observed under an electron microscope. In addition, reactive oxygen species (ROS) production, malondialdehyde (MDA) activity and heme oxygenase (HO-1) level in rat serum were detected via ELISA. The expression levels of miR-92A-3p and HO-1 in the vascular tissues of the rats were determined via real-time quantitative PCR. Additionally, the expression levels of HO-1, NF-κB P65, p38MAPK and IκBa in the venous tissues of the rats were analysed by Western blot analysis. RESULTS: The pathological results showed that the thrombosis incidence rate in the CRT + RE group was lower than that in the CRT group. In the CRT group, the expression levels of ROS and MDA, which are markers related to oxidative stress in serum, significantly increased whilst the expression of HO-1 decreased. In the venous tissue, the expression of miR-92a-3p increased, the level of HO-1 decreased, the levels of p38MAPK and NF-κB p65 significantly increased but that of P-IκBa and IκBa significantly decreased. In the CRT + RE group, after administering the resistance exercise intervention, ROS production and MDA activity in serum significantly decreased, the expression level of HO-1 increased and the expression level of miR-92a-3p in the venous tissues significantly decreased and was negatively correlated with that of HO-1. The levels of p38MAPK and NF-κB p65 significantly decreased but that of P- IκBa and IκBa significantly increased. CONCLUSION: Resistance exercise intervention downregulated miR-92a-3p expression, repaired oxidative stress injury and prevented CRT formation.

Role of miR-92a-3p, oxidative stress, and p38MAPK/NF-κB pathway in rats with central venous catheter related thrombosis.

BACKGROUND: miR-92a-3p and oxidative stress are reportedly associated with venous thrombosis. However, the role of miR-92a-3p and oxidative stress in catheter-related thrombosis (CRT) remains ambiguous. Herein, we studied the roles of miR-92a-3p, oxidative stress, and p38-mitogen-activated protein kinase/nuclear factor kappa-B (MAPK/NF-κB) pathway in CRT. METHODS: Forty-five male rats were randomly and equally divided into control, sham operation, and CRT groups. The rats were sacrificed after 10 days. Reactive oxygen species (ROS), superoxide dismutase (SOD), and malondialdehyde (MDA) levels in the serum were determined by enzyme-linked immunosorbent assay (ELISA). The expression levels of miR-92a-3p, heme oxygenase-1 (HO-1), NF-κB p65, and p38 MAPK in the venous tissues were detected with quantitative polymerase chain reaction (qPCR) and Western blot. RESULTS: Thrombosis was observed only in the CRT group. Compared with the levels in the control and sham operation groups, ROS and MDA significantly increased in the CRT group, but SOD significantly decreased. qPCR and Western blot results showed that miR-92a-3p, HO-1, p38 MAPK, and NF-κB p65 expression was significantly upregulated in the venous tissues of the CRT group. Moreover, miR-92a-3p was positively correlated with HO-1, which was positively correlated with p38 MAPK and NF-κB p65. CONCLUSION: miR-92a-3p was correlated with oxidative stress in CRT. miR-92a-3p and oxidative stress contributed to endothelial dysfunction and simultaneously was associated with CRT.

An Infertile Man with Complementary Isochromosome of 46, XY, I(5)(P10),I(5)(Q10): A Case Report.

Chromosome aberration is associated with infertility and isochromosome is a rare chromosomal abnormality potentially associated with infertility or multiple miscarriages. Here we report a man of 29-yr-old diagnosed of infertility from China with rare isochromosome. Peripheral blood lymphocytes were obtained for chromosome G banding karyotyping. Hormones and other tests were performed. The semen analysis revealed Azoospermia. Complementary isochromosome of 46, XY, i(5)(p10),i(5)(q10) was identified. This is the first report of Complementary isochromosome of 46, XY, i(5)(p10),i(5)(q10).

Retrospective Analysis of Microbial Colonization Patterns in Central Venous Catheters, 2013-2017.

Objectives: This study was performed to provide epidemiological information on microbial colonization in central venous catheters (CVCs). Methods: CVCs submitted to Medical Microbiology Laboratory from January 1, 2013, through October 1, 2017, which met our criteria would be included for analysis. Quantitative culture was used for CVCs. The results of culture and related information on CVCs were collected and recorded in detail. The prevalence was calculated, and related factors were analyzed statistically. Results: A total of 2020 CVCs were submitted for culture and eligible for analysis. Positive microbial culture occurred in 379 catheters with 18.7% (379 of 2020) prevalence of colonization. There were 23 microbial genera and 45 organisms detected. Among the isolated organisms, there were 39 kinds of isolated bacteria and 6 kinds of isolated fungi. Acinetobacter (19.8%) predominated in total isolated microorganisms, followed by Staphylococcus epidermidis (11.3%) and Candida albicans (10.3%). There were no significant differences in isolated organisms and fungal species between different sexes (X 2 = 2.365, P = 0.50). Conversely, there were significant differences in isolated bacterial and fungal species between different wards and years (X 2 = 124.046, P = 0.000; X 2 = 77.064, P = 0.000). A total of 107 (5.3%, 107/2020) CVCs were associated with a diagnosis of central line-associated bloodstream infection (CLABSI). The most common organisms in causing CLABSI were Acinetobacter (23.4%), S. aureus (13.1%), and Candida albicans (12.1%). Conclusion: The prevalence of microbial colonization in CVCs is still significant and even has gradually changed over time. The study provides a new view of microbial colonization pattern in CVCs and a prevalence of CLABSI, which will facilitate catheter-related infection prevention and control in clinic.

Attitudes and knowledge of undergraduate nursing students about palliative care: An analysis of influencing factors.

BACKGROUND: With the growing aging population, continual increase of the number of the old, and increase of cancer survival rate, palliative care is being considered a global public health issue. As a core force for the sustainable development of the nursing field, undergraduate nursing students' knowledge about and attitudes toward palliative care will directly affect the quality of care for dying patients in the future. OBJECTIVE: To investigate undergraduate nursing students' knowledge about and attitudes toward palliative care and analyze their influencing factors. METHODS: This descriptive and cross-sectional survey was conducted in 2016. A total of 1200 Chinese undergraduate nursing students were randomly selected as the survey subjects using stratified sampling method. The revised palliative care quiz for nursing (PCQN) and a self-designed questionnaire were used to measure students' knowledge and attitudes. RESULTS: The mean score of the revised PCQN was 16.10 ±â€¯5.04. Only a few respondents (19.8%) expressed desire to work in palliative care in the future. The findings show that knowledge and school, grade, gender, birthplace, and religious beliefs have statistically significant impacts (P < 0.01). In addition, logistic regression analysis showed that talking about death and caring for dying family members can have a significant influence on students' attitudes (P < 0.05). CONCLUSION: At present, Chinese undergraduate nursing students' knowledge about palliative care is minimal with the majority holding negative attitudes. Thus, the development of an effective end-of-life care program for nursing students is critical.

Medical Adhesive-Related Skin Injury Prevalence at the Peripherally Inserted Central Catheter Insertion Site: A Cross-sectional, Multiple-Center Study.

PURPOSE: We examined prevalence and associated risk factors of medical adhesive-related skin injury (MARSI) at the peripherally inserted central catheter (PICC) insertion site in hospitalized oncology patients in Guangxi, China. DESIGN: A cross-sectional, multiple-center epidemiological study. SUBJECTS AND SETTING: The sample comprised 697 adult inpatients at 4 tertiary hospitals (3 general hospitals and 1 oncology hospital). The facilities are located in the western China. METHODS: Trained nurses examined and assessed all subjects' skin exposed to medical adhesive during PICC maintenance process followed by recording the morphological features of the skin lesions, complaints of the patients, and information of catheter maintenance. Data related to patient demographics, PICC insertion information, disease, and laboratory parameters were collected through the electronic medical record. The prevalence of MARSI was calculated statistically and risk factors were examined using a logistic regression model. RESULTS: A total of 697 patients (mean age, 48.86 years; range, 18-89 years) were enrolled. The prevalence of MARSI was 19.7% (137/697), including mechanical skin injury 5.0% (35/697), contact dermatitis 14.8% (103/697), folliculitis 1.0% (7/697), and moisture-associated skin damage 1.3% (9/697). There were significant differences in presence of MARSI and age, diagnoses, body mass index, smoking history, indwelling time of PICC, types of dressing, types of antiseptic, a history of MARSI, and skin allergies (P < .05). Multivariate analysis identified 50 years or older (odds ratio [OR], 2.202; 95% confidence interval [CI], 1.222-3.968; P = .009), a history of MARSI (OR, 14.834; 95% CI, 6.534-33.680; P = .000) as independent risk factors for MARSI. Additionally, type of transparent film dressing used was a risk factor for MARSI (OR, 3.292; 95% CI, 1.092-9.923; P = .034). CONCLUSION: The prevalence of MARSI is significant in hospitalized oncology patients in China. Our study provided new knowledge for the epidemiology of MARSI and identified high-risk population, which will guide clinical nursing practice and ensure patient safety.

Prevalence of medical adhesive-related skin injury at peripherally inserted central catheter insertion site in oncology patients.

INTRODUCTION: The aim of our study was to identify the prevalence and risk factors of medical adhesive-related skin injuries (MARSI) at peripherally inserted central catheters (PICC) insertion site in oncology patients. METHODS: A cross-sectional observational study lasting two weeks was carried out in four inpatient departments. Skin assessment data and photographs of skin were collected during PICC maintenance. Other related information came from medical records. The skin injuries were classified by dermatologists and PICC specialized nurses. MARSI prevalence was calculated and the associated factors were analyzed statistically. RESULTS: All 419 patients were included. The prevalence of total MARSI at PICC insertion site was 125, (29.83%), including mechanical skin injury (73, 17.42%), contact dermatitis (CD) (39, 9.31%), moisture-associated skin damage (11, 2.63%), folliculitis (2, 0.48%). Multivariate analysis identified two independent risk factors for MARSI including age ≥50 y (p = 0.031, odds ratio [OR] = 4.521, 95% confidence interval [CI] [1.389, 20.620]) and hematologic malignancies (p = 0.000, OR = 2.514, 95% CI [1.590,3.97]. Oxaliplatin and arsenic trioxide infusion through PICC, history of skin allergies was associated with CD, with p = 0.020, OR = 3.492, 95% CI (1.220, 9.990); p = 0.003, OR = 4.565, 95% CI (1.661,12.547); p = 0.000, OR = 12.333, 95% CI (3.669, 41.454), respectively. CONCLUSIONS: MARSI at PICC insertion site is a frequent event among oncology patients. Epidemiological data and independent risk factors are presented in our study, which provide a basis for future study in this area.