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"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



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On Aug 2018




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Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
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Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
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In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Original article / research
Year : 2024 | Month : July | Volume : 18 | Issue : 7 | Page : QC01 - QC04 Full Version

Serum Copeptin as a Biomarker of Polycystic Ovarian Syndrome and its Correlation with Metabolic Syndrome Components: A Cross-sectional Analytical Study


Published: July 1, 2024 | DOI: https://doi.org/10.7860/JCDR/2024/69942.19604
Jyotsna Mirabel Coelho, Prema D’Cunha, AR Shivshankara

1. Assistant Professor, Department of Obstetrics and Gynaecology, Father Muller Medical College, Mangalore, Karnataka, India. 2. Professor, Department of Obstetrics and Gynaecology, Father Muller Medical College, Mangalore, Karnataka, India. 3. Professor, Department of Biochemistry, Father Muller Medical College, Mangalore, Karnataka, India.

Correspondence Address :
Prema D’Cunha,
Professor, Department of Obstetrics and Gynaecology, Father Muller Medical College, Mangalore-575002, Karnataka, India.
E-mail: prema_dcunha@fathermuller.in

Abstract

Introduction: Approximately 5 to 10% of women of reproductive age suffer from the prevalent endocrine illness known as Polycystic Ovarian Syndrome (PCOS). Copeptin, irrespective of age and weight, has been found to have significant associations with cardiometabolic parameters. Studies on the diagnostic and prognostic significance of copeptin and its correlation with components of metabolic syndrome in PCOS are scarce, particularly in the Indian context.

Aim: To assess the utility of copeptin as a diagnostic marker of PCOS and to evaluate the correlation of serum copeptin levels with metabolic syndrome components in women with PCOS.

Materials and Methods: This cross-sectional analytical study was conducted at Father Muller Medical College Hospital, Mangalore, Karnataka, India, from June 2022 to September 2023. A total of 60 subjects with PCOS were selected through convenient sampling and divided into two groups: Group 1-subjects with PCOS having metabolic syndrome, and Group 2-subjects with PCOS but not having metabolic syndrome. Blood samples for serum copeptin were taken under aseptic precautions, and levels were analysed using a commercially available Enzyme-Linked Immunosorbent Assay (ELISA) kit (Biovendor, USA) following the manufacturers’ instructions. The copeptin ELISA kit had an assay range of 0-100 pmol/L and results were expressed in ng/mL. Serum insulin levels were measured using specific Electro-chemiluminescence immunoassays. Levels of total cholesterol, High-Density Lipoprotein Cholesterol (HDL-C), and Triglycerides (TG) were determined with enzymatic colorimetric assays by spectrophotometry. Low-Density Lipoprotein Cholesterol (LDL-C) was calculated using the Friedewald formula. Insulin resistance was calculated using the Homeostasis Model Assessment Insulin Resistance Index (HOMA-IR). Statistical analysis was done by using descriptive statistics. A comparison was done by student’s unpaired t-test. The chi-square test and Pearson correlation test were used for categorical data. The Statistical Package for Social Sciences (SPSS) version 24.0 was used for analysis.

Results: The mean age of the study participants was 24.24±4.721 years, ranging from 15 to 43 years. The mean age of patients with metabolic syndrome was 23.96±6.3 years, while those without metabolic syndrome was 24.40±3.52 years. The mean Body Mass Index (BMI) was 31.17±5.38 in those with metabolic syndrome and 23.2±4.7 in those without (p=0.0001). The Waist-to-Hip Ratio (WHR) of Group 1 was significantly higher than Group 2 (p=0.001). The two groups did not differ significantly with regard to serum copeptin level, i.e., 7.386±4.58 in Group 1 and 8.66±6.03 in Group 2 (p=0.736). Serum copeptin levels showed a significant correlation with fasting serum insulin (0.006) and Homeostatic Model Assessment - Insulin Resistance (HOMA-IR) (0.012).

Conclusion: Serum copeptin cannot be used as an independent marker for the diagnosis of metabolic syndrome in PCOS patients but may indicate other prognostic factors.

Keywords

Copeptin, Metabolic syndrome, Polycystic ovarian syndrome

Increased plasma concentrations of Arginine Vasopressin (AVP) have been linked to the development of type 2 diabetes, metabolic syndrome, chronic renal, and cardiovascular illnesses, according to recent research (1). However, AVP’s short half-life of 16 to 20 minutes in plasma, small size, and poor stability, which make direct measurement challenging, limit its therapeutic utility as a biomarker (2). Copeptin, the stable and physiologically inactive C-terminal portion of pro-vasopressin, is co-secreted in equimolar levels with AVP, making it a suitable and practical surrogate marker for AVP in clinical settings (3). The range of copeptin plasma concentration in healthy adults is 1 to 13.8 pmol/L, with an average of 4.2 pmol/L (4). There is notable variation in the concentration of copeptin across genders, with lower values in females (5),(6).

The role of the AVP system in controlling human metabolic homeostasis has received more attention recently. Numerous elements of the metabolic syndrome, including dyslipidemia, insulin resistance, glucose intolerance, hyper-insulinemia, hypertension, and abdominal obesity, have been linked to high levels of circulating plasma copeptin (7). Enhorning S et al., showed a strong link between elevated copeptin and a higher frequency of Non-Alcoholic Fatty Liver Disease (NAFLD) in a population-based study with mixed ethnicities. Copeptin also showed a negative correlation with HDL and a positive correlation with raised HbA1c, insulin, BMI, HOMA-IR, and waist circumference (8).

There is a link between copeptin and the probability of elevated HOMA-IR ≥2.5, according to a case-control research involving PCOS women (9). Patients with PCOS, particularly those who are obese, have been found to have elevated serum copeptin levels and a favourable association between serum copeptin concentrations and cardiometabolic markers such as total testosterone, HOMA-IR, WHR, BMI, and hirsutism score. This suggests that copeptin may be helpful in identifying future cardiovascular risk in PCOS patients (9).

Copeptin, like AVP and neurophysin II, is generated from the precursor pre-vasopressin. Copeptin is thought to be an accurate and feasible clinical surrogate for AVP in disorders involving the homeostasis of bodily fluids (10). It has been found that there is a strong positive correlation between copeptin and AVP levels in both healthy individuals and patients with different cardiovascular illnesses (11).

Studies on the diagnostic and prognostic significance of copeptin and its correlation with components of the metabolic syndrome in PCOS are scarce, particularly in the Indian context. In the present study, the authors aimed to assess the utility of copeptin as a diagnostic marker of PCOS and the correlation of serum copeptin levels with metabolic syndrome components in women with PCOS.

Material and Methods

This was an observational study conducted at Father Muller Medical College Hospital, Mangalore, Karnataka, India, from June 2022 to September 2023. The research was approved by the Institutional Ethics Committee (FMMCIEC/CCM/513/2022). Voluntary informed consent was obtained from all participants. A total of 60 subjects with PCOS were selected via convenient sampling after calculating the sample size using the following formula: N=Sα2 s2/d2, where Sα=1.96 at a 95% confidence level, and s=standard deviation, and d=relative precision=10% of the mean Dehydroepiandrosterone (DHEAS) level (μg/dL).

Sample size calculation: For DHEAS, d=10% of 275.65, and S=15.45. With a 95% confidence level and 90% power, the sample sise was calculated as 60. DHEAS was chosen instead of copeptin level as the two groups were divided based on the presence or absence of metabolic syndrome in the patients with PCOS.

Inclusion criteria: Patients diagnosed with PCOS as per Rotterdam’s criteria (presence of any two of the following: clinical or biochemical hyperandrogenism, clinical evidence of oligo-anovulation, Polycystic appearing-ovarian morphology on ultrasound, and belonging to the age group of 19-40 years were included in the study and allocating to two groups (12).

Group-1 included 30 individuals with PCOS and metabolic syndrome, while Group-2 included subjects with PCOS but without metabolic syndrome.

Exclusion criteria: Individuals with a history of chronic smoking and systemic illnesses such as diabetes mellitus, hyperprolactinemia, congenital adrenal hyperplasia, androgen-secreting tumours, thyroid disorders, Cushing syndrome, infectious diseases, hypertension, and hepatic or renal dysfunction were excluded from the study. Patients with a history of usage of medications like oral contraceptive agents, anti-lipidemic drugs, hypertensive medications, and insulin-sensitising drugs within three months before enrollment were also excluded.

Metabolic syndrome criteria were based on the International Diabetes Federation (IDF) criteria (13): abdominal obesity (>88 cm in women), raised concentration of Triglycerides (TGs) (≥150 mg/dL), reduced concentration of High Density Lipoprotein (HDL) cholesterol (<40 mg/dL (1.03 mmol/L) in women or raised blood pressure (systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥85 mmHg), and high fasting plasma glucose concentration (≥100 mg/dL).

Method of data collection and analysis: Subjects diagnosed with PCOS as per the Rotterdam criteria, who visited the outpatient department of Obstetrics and Gynaecology, were enrolled in the study after obtaining consent. Height and weight were measured with subjects wearing light clothing without shoes. BMI was calculated by dividing weight by the square of height (kg/m2). Waist circumference was measured at the narrowest level between the costal margin and iliac crest, and hip circumference was measured at the widest level over the buttocks with the subjects standing, after which the Waist-to-Hip Ratio (WHR) was calculated. Blood pressure was measured in the right arm with the subject in a sitting position.

A blood sample for serum Copeptin was taken under aseptic precautions; fasting blood samples (2 mL) were collected into tubes containing Ethylene Diamine Tetra-Acetic Acid (EDTA). The blood sample was centrifuged at 1600 × g for 15 minutes, plasma was separated, and stored at -80°C until the assessment of copeptin. Copeptin levels in the serum samples were analysed using a commercially available ELISA kit (Biovendor, USA) following the manufacturer’s instructions. The assay range of the copeptin ELISA kit was 0-100 pmol/L and the results were expressed in ng/mL.

Biochemical evaluation: After overnight fasting, venous blood samples were obtained for fasting plasma glucose levels (using the glucose oxidase/peroxidase method). Serum insulin was measured using specific Electro-chemiluminiscence immunoassays.

Levels of total cholesterol, High Density Lipoprotein-Cholesterol (HDL-C), and TG were determined using enzymatic colorimetric assays by spectrophotometry. LDL-C was calculated using the Friedewald formula. Insulin resistance was calculated using the HOMA-IR formula, which is calculated as fasting plasma glucose (mmol/L)×fasting serum insulin (mU/mL)/22.5. The cut-off value for HOMA-IR was set at 2.7 (12).

Statistical Analysis

This was done by using descriptive statistics. Comparisons were made using either the Student’s unpaired t-test or Pearson correlation test as per the normality of the data. The Chi-square test was utilised for qualitative data. The statistical package SPSS version 24.0 was used for the analysis. A p-value of <0.05 was considered significant.

Results

Out of the total 60 study participants, one did not return with the requested laboratory investigations; asked for, hence data from only 59 participants were included. Among the 59 study participants, 22 (37.2%) had metabolic syndrome. The mean age of the study participants was 24.24±4.721 years, ranging between 15 to 43 years. The mean age of patients with metabolic syndrome was 23.96±6.3 years, while those without it was 24.40±3.52 years. The mean BMI was 31.17±5.38 in those with metabolic syndrome and 23.2±4.7 in those without it (p=0.0001).

Among the study participants, 22 had metabolic syndrome, while 37 did not meet the criteria for metabolic syndrome. Of the participants with metabolic syndrome, two had normal weight, 10 were overweight, six had Grade-I obesity, and four had Grade-II obesity. Among those without metabolic syndrome, five were underweight, 17 had normal weight, 11 were overweight, and four had Grade-I obesity.

The mean Copeptin value was 7.38±4.58 (ng/mL) in patients with metabolic syndrome and 8.66±6.03 (ng/mL) in patients without metabolic syndrome (Table/Fig 1).

Serum copeptin levels showed a significant correlation with fasting serum insulin (p=0.006) and HOMA-IR (p=0.012) (Table/Fig 2).

There was a significant negative moderate correlation between serum copeptin and serum insulin levels, and between serum copeptin and HOMA-IR (Table/Fig 3),(Table/Fig 4). The accuracy, sensitivity, and specificity of copeptin as a biomarker for PCOS were low and not significant (Table/Fig 5),(Table/Fig 6).

Discussion

In the present study, the authors observed that 37.2% of the subjects with PCOS had metabolic syndrome. There was a significant correlation between serum copeptin levels and serum insulin and insulin resistance among PCOS patients with metabolic syndrome. The accuracy, sensitivity, and specificity of copeptin as a biomarker for PCOS were found to be low and not significant.

In a research done by Aly AE et al., it was found that in PCOS women with positive insulin resistance (>2.5), plasma copeptin levels were significantly higher compared to healthy controls and PCOS women with insulin resistance <2.5 (11). The authors suggested that copeptin could be a useful marker of insulin resistance among PCOS patients. They also found that serum copeptin levels were significantly higher in the obese PCOS group compared to non-obese individuals and healthy controls and proved that plasma copeptin cut-off value for detecting insulin resistance in PCOS with 88% sensitivity and 36% specificity, with an AUC of 0.88 (13), which is not in agreement with the present study.

In the present study, when comparing serum copeptin levels in patients with metabolic syndrome and those without, the authors concluded that serum copeptin values were not statistically significant. Widecka J et al., in their case-control study involving 150 PCOS women, concluded that copeptin is associated with insulin resistance in PCOS patients, but due to low sensitivity, it cannot be considered as a marker of insulin resistance (14). Similarly, a study by Saleem U et al., revealed a cross-sectional association between plasma copeptin and measures of insulin resistance and metabolic syndrome (15).

The present study showed copeptin levels were not significantly raised in patients with metabolic syndrome. Therefore, copeptin cannot serve as an independent marker for metabolic syndrome in patients with PCOS. Overall, it is evident from the study that circulating copeptin levels serve as a biomarker of insulin resistance and metabolic derangements in patients with PCOS (16).

Limitation(s)

Some of the limitations in the present study include the lack of a control group, the inability to establish the temporal changes in plasma copeptin and its relationship with pre-existing metabolic risk factors or the development of future complications. Additionally, the authors did not measure psychosocial stress in participants or their plasma cortisol levels, which is the final mediator of a perturbed HPA axis.

Furthermore, the authors reported insulin resistance based on HOMA-IR values. Although the gold standard for establishing insulin resistance is the Euglycaemic-hyperinsulinemic clamp, this elaborate procedure is not suitable as a screening method.

Conclusion

The serum copeptin cannot be used as an independent marker for the diagnosis of metabolic syndrome in PCOS patients, as copeptin measurements in plasma have very low sensitivity. However, due to the limited availability of studies on serum copeptin in PCOS patients in the Indian context, further research in a larger cohort is warranted.

References

1.
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DOI and Others

DOI: 10.7860/JCDR/2024/69942.19604

Date of Submission: Feb 05, 2024
Date of Peer Review: Mar 15, 2024
Date of Acceptance: Apr 17, 2024
Date of Publishing: Jul 01, 2024

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. NA

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Feb 06, 2024
• Manual Googling: Mar 19, 2024
• iThenticate Software: Apr 16, 2024 (16%)

ETYMOLOGY: Author Origin

EMENDATIONS: 7

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