Title: Exploring the association between life’s essential 8 and gallstone disease in the US adult
population: a population-based study utilizing NHANES data from 2017-2018
Version: 4 Date: 20 Oct 2024
Reviewer:  Amira A A Othman
Reviewer's report:
First of all
I want to congratulate the authors on their work. In this study, Xiao et al. aimed to assess the
prevalence of gallstone disease and associated factors, suggesting the potential of LE8 as a
predictor of gallstone risk.
Gallstone is the most common biliary pathology with a global incidence of 3-21.9%*. In Asia,
it is 4-15%**. In Africa, the prevalence is less than 5%***.  Most of the patients with gallstones
are asymptomatic and are diagnosed incidentally. Symptomatic patients classically present
with biliary colic, usually accompanied by nausea, vomiting, and diaphoresis. Laparoscopic
cholecystectomy is the gold standard treatment. However, about 5.2% of cases convert to open
cholecystectomy for better outcomes due to various reasons****
(*:doi.org/10.33545/surgery.2021.v5.i2e.697, **: doi: 10.5009/gnl.2012.6.2.172, *** doi:
10.29337/ijsp.143, **** DOI: 10.47009/jamp.2024.6.2.161).
The authors handled the reviewer comments satisfactorily, nevertheless, there is an observation
for which sufficient justification must be obtained.
In general:
1. The English writing level is shallow, and it is necessary to seek help from an English language
specialist to correct spelling and grammatical errors in the entire text.
2. I wonder, the study belongs to Chinese authors and depends upon a survey designed to assess
the health and nutritional status of adults and children in the United States. Shall they evaluate
the potential association between the prevalence of gallstone disease and associated factors in
Chinese people, so that science can be enriched with more surveys?
In Title:
3. gallstones disease should be gallstone disease.
In Abstract section
4. The background subsection:
-  Should be the shortest part of the abstract. It should briefly outline the following information:
What is already known about the subject, related to the paper in question. What is not known
about the subject and hence what the study intended to examine (or what the paper seeks to
present). Please reconstruct it properly.
5.  The type of study: a population-based study.
6. In method subsection:
- Nothing was mentioned about the participant's age, sex, ethnicity, etc.
- It would help if you described the aim of your statistical analysis. For example, Multivariate
linear regression models were used to examine the linear connection between the association
between life’s essential 8 and gallstones. Fitted smoothing curves and threshold effect analysis
were used to describe the nonlinear relationship, etc.
- A two-part linear regression model was also used to estimate threshold effects.
In the Introduction section:
7. Try to provide a summarized description of The National Health and Nutrition Examination
Survey (NHANES) in the background section. You may use the following:
“NHANES (www.cdc.gov/nchs/nhanes) is designed to assess the health and nutritional status
of adults and children in the United States. The survey is distinctive in that it incorporates
both physical examinations and interviews. Several cross-sectional, nationally representative
health examination surveys are part of the NHANES program. Questions about demographics,
health insurance status, dietary habits, acute and chronic medical issues, mental health, and
prescription drug use are all included in the health interview. Exam components can change
between survey cycles but typically include blood pressure, dental exams, vision, hearing,
dermatology, fitness, balance and strength testing, respiratory testing, taste and smell, and
body measurements (weight, height, skin folds, body composition scans). Hematology, organ
and endocrine function (e.g., thyroid, kidney), environmental exposure, dietary biomarkers,
metabolic and cardiovascular health, and infectious disease are a few examples of laboratory
components.”.
8. Gallstones are crystallized deposits in the gallbladder or within the biliary tree, composed of
cholesterol, bilirubin, and bile. Try to provide a better identification of gallstones and their types
accordingly. You may use the following:
“The primary ingredient in the most prevalent kind of gallstone is cholesterol. Hemoglobin
breaks down to form calcium bilirubinate, which is what causes black stones. Brown stones,
on the other hand, are made of a mixture of calcium substrates, such as calcium bilirubinate,
calcium phosphate or palmitate, cholesterol, and bile, and they develop in the context of
bacterial or parasite illness*. Those with diabetes and other metabolic disorders frequently
develop cholesterol stones. On the other hand, individuals who experience hemolysis or have an
inflammatory disease like Crohn's disease tend to get black stones, whereas people with biliary
strictures and infections from bacteria or parasites tend to get brown-pigmented stones**.
(*doi: 10.1111/eci.12935, **doi: 10.1016/j.ejphar.2021.174376 )
In the Methods section:
9. Please move the sentences defining the NHANES to the introduction section rather than the
methodology section.
10. The study utilized the 2017-2018 NHANES survey cycle, why did you choose the study
survey cycle? The survey includes study cycles from 2001 to 2020.
11. Please provide the participants' sociodemographic data.
12. How the sample size was calculated.
13. Inclusion and exclusion criteria must be provided.
14. How were patients with gallstone disease diagnosed?
15. Roughly one in five adults have gallbladder disease. Gallbladder problems such as gallstones
are less likely in children and teens but are becoming more common.
16. The studied parameters should include:
• Epidemiological data: age, gender, profession;
• Clinical data: presentation (asymptomatic, biliary colic, cholecystitis, common bile duct
lithiasis, angio-colitis, pancreatitis) consultation delay, duration of symptoms, sickle cell
disease, existence of metabolic risk factor (obesity, diabetes, dyslipidemia, hypertension),
alcohol and tobacco use, contraception, blood pressure, systolic pressure index, temperature,
heart rate, respiratory rate, weight, height, body mass index, waist circumference;
• Paraclinical data: hepatic test (SGOT, SGPT, prothrombin time), fasting blood glucose,
hemoglobin (anemia), hematocrit (hemoconcentration), white blood cell (leukocytosis),
creatinine level, imaging modality (ultrasonography, CT scan), location of the stone
(gallbladder, intrahepatic duct, common bile duct, pancreas);
• Therapeutic data: type of treatment (medical treatment, open surgery, laparoscopic surgery,
cholecystectomy, choledochotomy with extraction of stones); post-operative course (morbidity,
mortality, anatomopathological examination).
17. Statistical analysis:
- Why did not you choose mean ± standard error instead of mean ± standard deviation?
-   The Mann–Whitney U test is a nonparametric test and involves the summation of ranks. The
Mann–Whitney U test is applied to independent samples. T-test is used to compare the mean of a
continuous variable between a maximum of 2 groups. The Kruskal–Wallis test is a statistical test
used to compare two or more groups for a continuous or discrete variable. The Wilcoxon rank-
sum test is used to compare two independent samples, while the Wilcoxon signed-rank test is
used to compare two related samples, matched samples, or to conduct a paired difference test of
repeated measurements on a single sample to assess whether their population mean ranks differ.
Analysis of variance (ANOVA) is a statistical test used to assess the difference between the
means of more than two groups. How did you choose the proper test during your result analysis?
- In logistic regression analyses, is it multivariate or univariate? Please identify.
- “Three logistic regression models were employed to investigate the independent association
between life’s essential 8 and gallstones, with varying levels of adjustment for potential
confounders. Model 1 was unadjusted for covariates, while Model 2 included adjustments
for age, sex, and race. Model 3 was further adjusted for education, marital status, PIR, BMI,
alcohol intake, smoking status, physical activity, hypertension, diabetes, high cholesterol levels,
coronary heart disease, stroke, and cancer.” Could you please explain how covariates were
categorized?
- The generalized additive model and smoothed curve testing should be used to assess the
nonlinear relationship between circadian syndrome and gallstone disease.
- The analyses were performed with R (http://www.R-project.org, version X) and EmpowerStats
(http://www.empowerstats.com, version 4.2) or SPSS software.
In the Results section:
18. In all tables, please explain the abbreviations under tables.
19. You can title the statistical test column as “Test of significance” and use U= for the Mann–
Whitney U test, T= for the T-test, and #2 = for the Chi-square test, etc., Although the Chi-square
test was used to compare observed and expected results, nothing was mentioned in the statistical
analysis section.
20. What were the patients' complaints?
In the Discussion section:
21. The discussion section is one of the final parts of a research paper, in which an author
describes, analyzes, and interprets their findings. They explain the significance of those results
and tie everything back to the research question(s). In this manuscript, there is confusion
between what should be written in the introduction and discussion sections. Please reconstruct
the discussion section.
22. The discussion should explain how gallstones can be managed.
In the conclusion section:
23. The conclusion should restate your main points and provide closure. Please reconstruct.
Title: Exploring the association between life’s essential 8 and gallstone disease in the US adult
population: a population-based study utilizing NHANES data from 2017-2018
Version: 4 Date: 20 Oct 2024
Reviewer:  Amira A A Othman
Reviewer's report:
First of all
I want to congratulate the authors on their work. In this study, Xiao et al. aimed to assess the
prevalence of gallstone disease and associated factors, suggesting the potential of LE8 as a
predictor of gallstone risk.
Gallstone is the most common biliary pathology with a global incidence of 3-21.9%*. In Asia,
it is 4-15%**. In Africa, the prevalence is less than 5%***.  Most of the patients with gallstones
are asymptomatic and are diagnosed incidentally. Symptomatic patients classically present
with biliary colic, usually accompanied by nausea, vomiting, and diaphoresis. Laparoscopic
cholecystectomy is the gold standard treatment. However, about 5.2% of cases convert to open
cholecystectomy for better outcomes due to various reasons****
(*:doi.org/10.33545/surgery.2021.v5.i2e.697, **: doi: 10.5009/gnl.2012.6.2.172, *** doi:
10.29337/ijsp.143, **** DOI: 10.47009/jamp.2024.6.2.161).
The authors handled the reviewer comments satisfactorily, nevertheless, there is an observation
for which sufficient justification must be obtained.
In general:
1. The English writing level is shallow, and it is necessary to seek help from an English language
specialist to correct spelling and grammatical errors in the entire text.
2. I wonder, the study belongs to Chinese authors and depends upon a survey designed to assess
the health and nutritional status of adults and children in the United States. Shall they evaluate
the potential association between the prevalence of gallstone disease and associated factors in
Chinese people, so that science can be enriched with more surveys?
In Title:
3. gallstones disease should be gallstone disease.
In Abstract section
4. The background subsection:
-  Should be the shortest part of the abstract. It should briefly outline the following information:
What is already known about the subject, related to the paper in question. What is not known
about the subject and hence what the study intended to examine (or what the paper seeks to
present). Please reconstruct it properly.
5.  The type of study: a population-based study.
6. In method subsection:
- Nothing was mentioned about the participant's age, sex, ethnicity, etc.
- It would help if you described the aim of your statistical analysis. For example, Multivariate
linear regression models were used to examine the linear connection between the association
between life’s essential 8 and gallstones. Fitted smoothing curves and threshold effect analysis
were used to describe the nonlinear relationship, etc.
- A two-part linear regression model was also used to estimate threshold effects.
In the Introduction section:
7. Try to provide a summarized description of The National Health and Nutrition Examination
Survey (NHANES) in the background section. You may use the following:
“NHANES (www.cdc.gov/nchs/nhanes) is designed to assess the health and nutritional status
of adults and children in the United States. The survey is distinctive in that it incorporates
both physical examinations and interviews. Several cross-sectional, nationally representative
health examination surveys are part of the NHANES program. Questions about demographics,
health insurance status, dietary habits, acute and chronic medical issues, mental health, and
prescription drug use are all included in the health interview. Exam components can change
between survey cycles but typically include blood pressure, dental exams, vision, hearing,
dermatology, fitness, balance and strength testing, respiratory testing, taste and smell, and
body measurements (weight, height, skin folds, body composition scans). Hematology, organ
and endocrine function (e.g., thyroid, kidney), environmental exposure, dietary biomarkers,
metabolic and cardiovascular health, and infectious disease are a few examples of laboratory
components.”.
8. Gallstones are crystallized deposits in the gallbladder or within the biliary tree, composed of
cholesterol, bilirubin, and bile. Try to provide a better identification of gallstones and their types
accordingly. You may use the following:
“The primary ingredient in the most prevalent kind of gallstone is cholesterol. Hemoglobin
breaks down to form calcium bilirubinate, which is what causes black stones. Brown stones,
on the other hand, are made of a mixture of calcium substrates, such as calcium bilirubinate,
calcium phosphate or palmitate, cholesterol, and bile, and they develop in the context of
bacterial or parasite illness*. Those with diabetes and other metabolic disorders frequently
develop cholesterol stones. On the other hand, individuals who experience hemolysis or have an
inflammatory disease like Crohn's disease tend to get black stones, whereas people with biliary
strictures and infections from bacteria or parasites tend to get brown-pigmented stones**.
(*doi: 10.1111/eci.12935, **doi: 10.1016/j.ejphar.2021.174376 )
In the Methods section:
9. Please move the sentences defining the NHANES to the introduction section rather than the
methodology section.
10. The study utilized the 2017-2018 NHANES survey cycle, why did you choose the study
survey cycle? The survey includes study cycles from 2001 to 2020.
11. Please provide the participants' sociodemographic data.
12. How the sample size was calculated.
13. Inclusion and exclusion criteria must be provided.
14. How were patients with gallstone disease diagnosed?
15. Roughly one in five adults have gallbladder disease. Gallbladder problems such as gallstones
are less likely in children and teens but are becoming more common.
16. The studied parameters should include:
• Epidemiological data: age, gender, profession;
• Clinical data: presentation (asymptomatic, biliary colic, cholecystitis, common bile duct
lithiasis, angio-colitis, pancreatitis) consultation delay, duration of symptoms, sickle cell
disease, existence of metabolic risk factor (obesity, diabetes, dyslipidemia, hypertension),
alcohol and tobacco use, contraception, blood pressure, systolic pressure index, temperature,
heart rate, respiratory rate, weight, height, body mass index, waist circumference;
• Paraclinical data: hepatic test (SGOT, SGPT, prothrombin time), fasting blood glucose,
hemoglobin (anemia), hematocrit (hemoconcentration), white blood cell (leukocytosis),
creatinine level, imaging modality (ultrasonography, CT scan), location of the stone
(gallbladder, intrahepatic duct, common bile duct, pancreas);
• Therapeutic data: type of treatment (medical treatment, open surgery, laparoscopic surgery,
cholecystectomy, choledochotomy with extraction of stones); post-operative course (morbidity,
mortality, anatomopathological examination).
17. Statistical analysis:
- Why did not you choose mean ± standard error instead of mean ± standard deviation?
-   The Mann–Whitney U test is a nonparametric test and involves the summation of ranks. The
Mann–Whitney U test is applied to independent samples. T-test is used to compare the mean of a
continuous variable between a maximum of 2 groups. The Kruskal–Wallis test is a statistical test
used to compare two or more groups for a continuous or discrete variable. The Wilcoxon rank-
sum test is used to compare two independent samples, while the Wilcoxon signed-rank test is
used to compare two related samples, matched samples, or to conduct a paired difference test of
repeated measurements on a single sample to assess whether their population mean ranks differ.
Analysis of variance (ANOVA) is a statistical test used to assess the difference between the
means of more than two groups. How did you choose the proper test during your result analysis?
- In logistic regression analyses, is it multivariate or univariate? Please identify.
- “Three logistic regression models were employed to investigate the independent association
between life’s essential 8 and gallstones, with varying levels of adjustment for potential
confounders. Model 1 was unadjusted for covariates, while Model 2 included adjustments
for age, sex, and race. Model 3 was further adjusted for education, marital status, PIR, BMI,
alcohol intake, smoking status, physical activity, hypertension, diabetes, high cholesterol levels,
coronary heart disease, stroke, and cancer.” Could you please explain how covariates were
categorized?
- The generalized additive model and smoothed curve testing should be used to assess the
nonlinear relationship between circadian syndrome and gallstone disease.
- The analyses were performed with R (http://www.R-project.org, version X) and EmpowerStats
(http://www.empowerstats.com, version 4.2) or SPSS software.
In the Results section:
18. In all tables, please explain the abbreviations under tables.
19. You can title the statistical test column as “Test of significance” and use U= for the Mann–
Whitney U test, T= for the T-test, and #2 = for the Chi-square test, etc., Although the Chi-square
test was used to compare observed and expected results, nothing was mentioned in the statistical
analysis section.
20. What were the patients' complaints?
In the Discussion section:
21. The discussion section is one of the final parts of a research paper, in which an author
describes, analyzes, and interprets their findings. They explain the significance of those results
and tie everything back to the research question(s). In this manuscript, there is confusion
between what should be written in the introduction and discussion sections. Please reconstruct
the discussion section.
22. The discussion should explain how gallstones can be managed.
In the conclusion section:
23. The conclusion should restate your main points and provide closure. Please reconstruct.
Please review this paper.
user
Title: Exploring the association between life’s essential 8 and gallstone disease in the US adult
population: a population-based study utilizing NHANES data from 2017-2018
Version: 4 Date: 20 Oct 2024
Reviewer:  Amira A A Othman
Reviewer's report:
First of all
I want to congratulate the authors on their work. In this study, Xiao et al. aimed to assess the
prevalence of gallstone disease and associated factors, suggesting the potential of LE8 as a
predictor of gallstone risk.
Gallstone is the most common biliary pathology with a global incidence of 3-21.9%*. In Asia,
it is 4-15%**. In Africa, the prevalence is less than 5%***.  Most of the patients with gallstones
are asymptomatic and are diagnosed incidentally. Symptomatic patients classically present
with biliary colic, usually accompanied by nausea, vomiting, and diaphoresis. Laparoscopic
cholecystectomy is the gold standard treatment. However, about 5.2% of cases convert to open
cholecystectomy for better outcomes due to various reasons****
(*:doi.org/10.33545/surgery.2021.v5.i2e.697, **: doi: 10.5009/gnl.2012.6.2.172, *** doi:
10.29337/ijsp.143, **** DOI: 10.47009/jamp.2024.6.2.161).
The authors handled the reviewer comments satisfactorily, nevertheless, there is an observation
for which sufficient justification must be obtained.
In general:
1. The English writing level is shallow, and it is necessary to seek help from an English language
specialist to correct spelling and grammatical errors in the entire text.
2. I wonder, the study belongs to Chinese authors and depends upon a survey designed to assess
the health and nutritional status of adults and children in the United States. Shall they evaluate
the potential association between the prevalence of gallstone disease and associated factors in
Chinese people, so that science can be enriched with more surveys?
In Title:
3. gallstones disease should be gallstone disease.
In Abstract section
4. The background subsection:
-  Should be the shortest part of the abstract. It should briefly outline the following information:
What is already known about the subject, related to the paper in question. What is not known
about the subject and hence what the study intended to examine (or what the paper seeks to
present). Please reconstruct it properly.
5.  The type of study: a population-based study.
6. In method subsection:
- Nothing was mentioned about the participant's age, sex, ethnicity, etc.
- It would help if you described the aim of your statistical analysis. For example, Multivariate
linear regression models were used to examine the linear connection between the association
between life’s essential 8 and gallstones. Fitted smoothing curves and threshold effect analysis
were used to describe the nonlinear relationship, etc.
- A two-part linear regression model was also used to estimate threshold effects.
In the Introduction section:
7. Try to provide a summarized description of The National Health and Nutrition Examination
Survey (NHANES) in the background section. You may use the following:
“NHANES (www.cdc.gov/nchs/nhanes) is designed to assess the health and nutritional status
of adults and children in the United States. The survey is distinctive in that it incorporates
both physical examinations and interviews. Several cross-sectional, nationally representative
health examination surveys are part of the NHANES program. Questions about demographics,
health insurance status, dietary habits, acute and chronic medical issues, mental health, and
prescription drug use are all included in the health interview. Exam components can change
between survey cycles but typically include blood pressure, dental exams, vision, hearing,
dermatology, fitness, balance and strength testing, respiratory testing, taste and smell, and
body measurements (weight, height, skin folds, body composition scans). Hematology, organ
and endocrine function (e.g., thyroid, kidney), environmental exposure, dietary biomarkers,
metabolic and cardiovascular health, and infectious disease are a few examples of laboratory
components.”.
8. Gallstones are crystallized deposits in the gallbladder or within the biliary tree, composed of
cholesterol, bilirubin, and bile. Try to provide a better identification of gallstones and their types
accordingly. You may use the following:
“The primary ingredient in the most prevalent kind of gallstone is cholesterol. Hemoglobin
breaks down to form calcium bilirubinate, which is what causes black stones. Brown stones,
on the other hand, are made of a mixture of calcium substrates, such as calcium bilirubinate,
calcium phosphate or palmitate, cholesterol, and bile, and they develop in the context of
bacterial or parasite illness*. Those with diabetes and other metabolic disorders frequently
develop cholesterol stones. On the other hand, individuals who experience hemolysis or have an
inflammatory disease like Crohn's disease tend to get black stones, whereas people with biliary
strictures and infections from bacteria or parasites tend to get brown-pigmented stones**.
(*doi: 10.1111/eci.12935, **doi: 10.1016/j.ejphar.2021.174376 )
In the Methods section:
9. Please move the sentences defining the NHANES to the introduction section rather than the
methodology section.
10. The study utilized the 2017-2018 NHANES survey cycle, why did you choose the study
survey cycle? The survey includes study cycles from 2001 to 2020.
11. Please provide the participants' sociodemographic data.
12. How the sample size was calculated.
13. Inclusion and exclusion criteria must be provided.
14. How were patients with gallstone disease diagnosed?
15. Roughly one in five adults have gallbladder disease. Gallbladder problems such as gallstones
are less likely in children and teens but are becoming more common.
16. The studied parameters should include:
• Epidemiological data: age, gender, profession;
• Clinical data: presentation (asymptomatic, biliary colic, cholecystitis, common bile duct
lithiasis, angio-colitis, pancreatitis) consultation delay, duration of symptoms, sickle cell
disease, existence of metabolic risk factor (obesity, diabetes, dyslipidemia, hypertension),
alcohol and tobacco use, contraception, blood pressure, systolic pressure index, temperature,
heart rate, respiratory rate, weight, height, body mass index, waist circumference;
• Paraclinical data: hepatic test (SGOT, SGPT, prothrombin time), fasting blood glucose,
hemoglobin (anemia), hematocrit (hemoconcentration), white blood cell (leukocytosis),
creatinine level, imaging modality (ultrasonography, CT scan), location of the stone
(gallbladder, intrahepatic duct, common bile duct, pancreas);
• Therapeutic data: type of treatment (medical treatment, open surgery, laparoscopic surgery,
cholecystectomy, choledochotomy with extraction of stones); post-operative course (morbidity,
mortality, anatomopathological examination).
17. Statistical analysis:
- Why did not you choose mean ± standard error instead of mean ± standard deviation?
-   The Mann–Whitney U test is a nonparametric test and involves the summation of ranks. The
Mann–Whitney U test is applied to independent samples. T-test is used to compare the mean of a
continuous variable between a maximum of 2 groups. The Kruskal–Wallis test is a statistical test
used to compare two or more groups for a continuous or discrete variable. The Wilcoxon rank-
sum test is used to compare two independent samples, while the Wilcoxon signed-rank test is
used to compare two related samples, matched samples, or to conduct a paired difference test of
repeated measurements on a single sample to assess whether their population mean ranks differ.
Analysis of variance (ANOVA) is a statistical test used to assess the difference between the
means of more than two groups. How did you choose the proper test during your result analysis?
- In logistic regression analyses, is it multivariate or univariate? Please identify.
- “Three logistic regression models were employed to investigate the independent association
between life’s essential 8 and gallstones, with varying levels of adjustment for potential
confounders. Model 1 was unadjusted for covariates, while Model 2 included adjustments
for age, sex, and race. Model 3 was further adjusted for education, marital status, PIR, BMI,
alcohol intake, smoking status, physical activity, hypertension, diabetes, high cholesterol levels,
coronary heart disease, stroke, and cancer.” Could you please explain how covariates were
categorized?
- The generalized additive model and smoothed curve testing should be used to assess the
nonlinear relationship between circadian syndrome and gallstone disease.
- The analyses were performed with R (http://www.R-project.org, version X) and EmpowerStats
(http://www.empowerstats.com, version 4.2) or SPSS software.
In the Results section:
18. In all tables, please explain the abbreviations under tables.
19. You can title the statistical test column as “Test of significance” and use U= for the Mann–
Whitney U test, T= for the T-test, and #2 = for the Chi-square test, etc., Although the Chi-square
test was used to compare observed and expected results, nothing was mentioned in the statistical
analysis section.
20. What were the patients' complaints?
In the Discussion section:
21. The discussion section is one of the final parts of a research paper, in which an author
describes, analyzes, and interprets their findings. They explain the significance of those results
and tie everything back to the research question(s). In this manuscript, there is confusion
between what should be written in the introduction and discussion sections. Please reconstruct
the discussion section.
22. The discussion should explain how gallstones can be managed.
In the conclusion section:
23. The conclusion should restate your main points and provide closure. Please reconstruct.
assistant