Review for 10.1186/s12876-024-03504-4 (2024)

Title: Association between circadian syndrome and gallstones: a cross-sectional study of
NHANES 2017–2020
Version: 3 Date: 12 Sep 2024
Reviewer:  Amira A A Othman
Reviewer's report:
First of all
I want to congratulate the authors on their work. In this study, Liang et al used data from the
2017–2020 National Health and Nutrition Examination Survey (NHANES) for Americans, this
research aims to investigate the potential association between circadian syndrome and the risk
of gallstones in adult US citizens.
The circadian rhythms ‘Body Clock’ is the major regulator of almost every aspect of human
health and metabolism through controlling body functions, and synchronizing peripheral clocks
in almost all cells in the body, including the body's key tissues such as the heart, liver,
muscle and adipose tissue.* The circadian system is affected by environmental signals such as
light, temperature, changes in nutritional intake, and others.** Disruptions to natural circadian
rhythms can have negative consequences on our metabolic health, leading to an increased risk
of inflammatory, cardiovascular, neurological, and malignant diseases.***
(*: doi: 10.1111/joim.12924, ** doi: 10.1016/j.neuroscience.2014.01.043: ***:doi:10.1016/
j.pharep.2016.04.007)
The authors tried to contribute to this field of research with new findings, 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. Abbreviations must be fully written at their first appearance (PIR, etc.)
In Title:
3. The authors may consider indicating the locality at which the National Health and Nutrition
Examination Survey (NHANES) was performed.
I suggest “Association between circadian syndrome and gallstones in US adult: a cross-sectional
study of NHANES 2017–2020”
In Abstract section
4. “The relationship between circadian syndrome and gallstones is poorly understood.”? Please
give more explanation in the introduction section.
5. “We aim to investigate whether the circadian syndrome is associated with gallstones in
a nationally representative sample of the population.” Please use “….. in a population-based
study” instead.
6. In method: please use “Using data from the National Health and Nutrition Examination
Survey (NHANES) database spanning from 2017 to 2020, a cross-sectional study included 2924
participants was performed to assess the relationship …….”.
7. 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 CircS and
gallstones incidence. Fitted smoothing curves and threshold effect analysis were used to describe
the nonlinear relationship.
8. A two-part linear regression model was also used to estimate threshold effects (the 2nd aim
of the study.
9. Nothing was mentioned about the participant’s age.
In the Introduction section:
10. 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.”.
11. Authors must give an account of Gallstones, one of the most prevalent digestive system
disorders in the world, the symptoms if present, the risk factors, the affection % in the American
population, etc.
(https://doi.org/10.3389/fnut.2024.1428488 ).
12.  Authors must give an account of the circadian rhythm (circadian cycle; a natural oscillation)
before discussing its disturbance (Circadian syndrome).
13. Please focus on the relationship between circadian rhythm and gallstones more than its
relationship with cardiovascular disorders.
14. “To the best of our understanding, few studies have been few studies that have reported
association between CircS and the occurrence of gallstones.” Please mention them as citations.
In the Methods section:
15. Please move the sentences defining the NHANES to the introduction section rather than the
methodology section.
16. The information on gallstones is based on the question “Has a doctor or other health
professional ever told you that had gallstones ". It does not give any information on the type
of Gallstones. Depending on the etiology, gallstones have different compositions. The three
most common types are cholesterol gallstones, black pigment gallstones, and brown pigment
gallstones.
17. Where is the Patient Health Questionnaire-9 (PHQ-9)?
18. What was the source of the covariate data?
19. Statistical analysis:
- Continuous variables were presented as mean (SE): I guess it is mean ± standard error (mean
± SE).
- Why did you choose mean ± standard error rather than mean ± standard deviation?
-  The Mann–Whitney U test / Wilcoxon rank-sum test: both are nonparametric and involve
the summation of ranks. The Mann–Whitney U test is applied to independent samples. The
Wilcoxon signed-rank test is applied to matched or dependent samples. T-test is used to compare
the mean of a continuous variable between a maximum of 2 groups. Why did you choose the
Wilcoxon rank-sum test?
- In logistic regression analyses, is it multivariate or univariate? Please identify.
- “Three logistic regression models were employed to investigate the independent relationship
between circadian syndrome 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? Why such diseases were excluded (hypertension, diabetes, high cholesterol levels,
coronary heart disease, stroke, and cancer)?
- 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 4.3.2) and
EmpowerStats
(http://www.empowerstats.com, version 4.2).
In the Results section:
20. In Tables: 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.
21. Subgroup analyses must be performed to evaluate the effect of circadian syndrome on
gallstones and their stability in different populations. Subgroup analyses based on differences
in diagnostic components were performed to elaborate correlations. The results were presented
in forest plots using odds ratios (ORs) and 95% confidence intervals (CIs).
22. Log2 logarithmic transformation shall be analyzed.
23. Future article readers may not know whether the above-mentioned variables were originally
collected as continuous data during data collection by NHANES, or whether the data were
originally categorized in the current study. In addition, in case there is a methodology article
published by NHANES or by other authors that specifically describes the variables, the authors
of the current study may consider citing that paper in the methodology section where the authors
of the current study mentioned the NHANES website.
24. The marital status category should be categorized into cohabitation (married/living with a
partner) and solitude (widowed/divorced/separated/unmarried).”
In the Discussion section:
25. 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 section and the discussion section. Please reconstruct
the discussion section.
26. I would suggest a language check throughout the entire manuscript. There are typos and
minor grammar mistakes.
27. The bias associated with using a self-reported outcome variable was not mentioned by the
authors. Since the majority of gallstones are clinically silent, it is possible to incorrectly diagnose
someone as having or not having gallstones. Results could get skewed as a result.
In the conclusion section:
28. The conclusion should restate your main points and provide closure.
- a notable association: a positive or negative correlation, be precise.
- For example:
“In US adults, Circs was significantly associated with the risk of gallstones, particularly in
35-49-year-old non-Hispanic female participants with ………. These findings provide new
insights into GSD management, but more prospective studies are warranted to confirm these
relationships.”
Thanks