Title: The incidence of chronic diarrhea decreases with increasing serum calcium levels: a cross-
sectional study based on NHANES 2005-2010
Version: 3 Date: 02 Oct 2023
Reviewer's report:
Dear Authors,
I appreciate your attention to my previous comments. I have further suggestions for your
consideration:
1. Title: It would be more accurate to use "cross-sectional study" instead of "survey" in the title,
as you did not directly conduct a survey.
2. Introduction:
a) In the statement, "Chronic diarrhea can be defined as 3 or more bowel movements or loose
stools over at least 4 weeks," could you please clarify whether you are referring to loose stools
per day? The frequency needs clarification.
b) In the statement, "Yu Peng[5] found that among patients under 60 years of age," consider
using "Yu et al." unless Yu Peng is the sole author.
c) For the statements, "...and elevate the electrolyte content in the intestinal lumen, leading to
diarrhea" and "a higher serum calcium level is significantly associated with decreased survival
in colorectal cancer," please provide the corresponding references.
3) Methods:
a) Please provide reference for Bristol stool scale in the statement, “The Bristol stool scale,
commonly used in research and clinical practice, was used to define chronic diarrhea”.
b) Covariates: The statement “Smoking status was categorized.” seems incomplete. Please
complete the sentence by adding the categories. For example, you may express it as "Smoking
status was categorized into two groups: individuals who smoked x cigarettes per year (referred
to as 'smokers') and those who did not smoke (referred to as 'nonsmokers')."
The categorization for smoking is not clear. How many cigarettes per year will categorize a
person as smoker? Do you have a clear threshold like you used for drinkers? If you prefer to
use the current category, please cite the source so that the readers can access it should they have
any questions.
c) Statistical Analysis: By the statement “and, Free Statistical software, version 1.7.1[13].”, are
you refereeing to R software? If so, please rephrase it because it seems that you are talking about
different software. Also, please check the citation 13 that you gave for R since it does not seem
correct.
4) Results: Consider revising the heading "As Serum Calcium Increased, the Risk of Diarrhea
Decreased" to something like "Association between serum calcium and diarrhea".
5) Discussion:
a) Ensure that paragraphs contain at least three sentences. Edit the first paragraph accordingly.
b) Define "simple nutritional calcium" within parentheses for clarity.
c) Introduce "Ca2+" earlier in the text if you plan to use it in the discussion; avoid introducing
new terms at this stage.
d) The following statements seem unrelated to your study: “In a retrospective cohort study
describing the relationship between serum calcium and inhospitable mortality in patients with
acute myocardial infarction (AMI), the authors found that both low and high serum calcium
levels were associated with AMI after correction for covariates. After adjusting the serum
calcium to 9.4 mg/dL (2.35 mmol/L), the risk of in-hospital mortality was reduced[16]. A cohort
study from China also found that lower serum calcium levels in non-diabetic patients increased
the risk of retinopathy[17]. A National Health and Nutrition Examination Survey (1999-2018)
study by Hou found an L-shaped association between serum calcium and all-cause mortality and
cardiovascular disease mortality in US adults.”
You can just say something like "In recent years, researchers have increasingly focused on serum
calcium-related studies. In particular, hypocalcemia was associated with a higher risk of all-
cause mortality and cardiovascular disease mortality (citations). However, to date, little attention
has been paid to the relationship between serum calcium and diarrhea."
e) This sentence does not conclude your argument, “Secondly, activation of intestinal CaSR
reduces overactive intestinal nerve activity and motility[19].” You need to conclude the process
by showing the relation of reduced diarrhea from reduced overactive intestinal nerve activity
and motility.
f) In this statement, “Finally, calcium-sensitive receptors can also reduce diarrhea by inhibiting
intestinal inflammation[24, 25].”, I believe, you are describing another process. If so, this is
not the 'final step'. Therefore, please remove 'finally'. You can write, "Alternatively, calcium-
sensitive receptors can reduce diarrhea by inhibiting intestinal inflammation (citations)".
g) Please elaborate the statement, “a sensitivity analysis was performed.”, to show why you
performed a sensitivity analysis.
h) In the statement, “First, causal deductions cannot be derived from cross-sectional studies.”,
please specify what kind of causal deductions cannot be derived from your study. You need to
complete your sentences for the readers to understand the whole picture.
i) Please remove ‘because’ from the statement, “Second, because the interview data in this study
were self-reported.”
j) Replace "conclusions" with "findings" in the sentence, "multicenter stochastic controlled trials
are needed to confirm our conclusions," as you have not yet presented your conclusions.
Overall comment on grammar: The manuscript still has several grammatical errors such as
spacing issues (e.g., Table1, Figure2, “returned to normal,and diarrhea ceased rapidly”), spelling
mistakes (e.g., Hance, cross-section analysis, biase), punctuation mark errors (e.g., in the
abstract conclusion, "incidence of diarrhea,  In the future..."), wrong sentences (e.g., “Household
income y was divided into...”, “with and without of diarrhea”, “we conducted out…”), singular/
plural issues (e.g., “a high serum calcium levels”). I’d suggest careful proofreading before
resubmitting.
Title: The incidence of chronic diarrhea decreases with increasing serum calcium levels: a cross-
sectional study based on NHANES 2005-2010
Version: 3 Date: 02 Oct 2023
Reviewer's report:
Dear Authors,
I appreciate your attention to my previous comments. I have further suggestions for your
consideration:
1. Title: It would be more accurate to use "cross-sectional study" instead of "survey" in the title,
as you did not directly conduct a survey.
2. Introduction:
a) In the statement, "Chronic diarrhea can be defined as 3 or more bowel movements or loose
stools over at least 4 weeks," could you please clarify whether you are referring to loose stools
per day? The frequency needs clarification.
b) In the statement, "Yu Peng[5] found that among patients under 60 years of age," consider
using "Yu et al." unless Yu Peng is the sole author.
c) For the statements, "...and elevate the electrolyte content in the intestinal lumen, leading to
diarrhea" and "a higher serum calcium level is significantly associated with decreased survival
in colorectal cancer," please provide the corresponding references.
3) Methods:
a) Please provide reference for Bristol stool scale in the statement, “The Bristol stool scale,
commonly used in research and clinical practice, was used to define chronic diarrhea”.
b) Covariates: The statement “Smoking status was categorized.” seems incomplete. Please
complete the sentence by adding the categories. For example, you may express it as "Smoking
status was categorized into two groups: individuals who smoked x cigarettes per year (referred
to as 'smokers') and those who did not smoke (referred to as 'nonsmokers')."
The categorization for smoking is not clear. How many cigarettes per year will categorize a
person as smoker? Do you have a clear threshold like you used for drinkers? If you prefer to
use the current category, please cite the source so that the readers can access it should they have
any questions.
c) Statistical Analysis: By the statement “and, Free Statistical software, version 1.7.1[13].”, are
you refereeing to R software? If so, please rephrase it because it seems that you are talking about
different software. Also, please check the citation 13 that you gave for R since it does not seem
correct.
4) Results: Consider revising the heading "As Serum Calcium Increased, the Risk of Diarrhea
Decreased" to something like "Association between serum calcium and diarrhea".
5) Discussion:
a) Ensure that paragraphs contain at least three sentences. Edit the first paragraph accordingly.
b) Define "simple nutritional calcium" within parentheses for clarity.
c) Introduce "Ca2+" earlier in the text if you plan to use it in the discussion; avoid introducing
new terms at this stage.
d) The following statements seem unrelated to your study: “In a retrospective cohort study
describing the relationship between serum calcium and inhospitable mortality in patients with
acute myocardial infarction (AMI), the authors found that both low and high serum calcium
levels were associated with AMI after correction for covariates. After adjusting the serum
calcium to 9.4 mg/dL (2.35 mmol/L), the risk of in-hospital mortality was reduced[16]. A cohort
study from China also found that lower serum calcium levels in non-diabetic patients increased
the risk of retinopathy[17]. A National Health and Nutrition Examination Survey (1999-2018)
study by Hou found an L-shaped association between serum calcium and all-cause mortality and
cardiovascular disease mortality in US adults.”
You can just say something like "In recent years, researchers have increasingly focused on serum
calcium-related studies. In particular, hypocalcemia was associated with a higher risk of all-
cause mortality and cardiovascular disease mortality (citations). However, to date, little attention
has been paid to the relationship between serum calcium and diarrhea."
e) This sentence does not conclude your argument, “Secondly, activation of intestinal CaSR
reduces overactive intestinal nerve activity and motility[19].” You need to conclude the process
by showing the relation of reduced diarrhea from reduced overactive intestinal nerve activity
and motility.
f) In this statement, “Finally, calcium-sensitive receptors can also reduce diarrhea by inhibiting
intestinal inflammation[24, 25].”, I believe, you are describing another process. If so, this is
not the 'final step'. Therefore, please remove 'finally'. You can write, "Alternatively, calcium-
sensitive receptors can reduce diarrhea by inhibiting intestinal inflammation (citations)".
g) Please elaborate the statement, “a sensitivity analysis was performed.”, to show why you
performed a sensitivity analysis.
h) In the statement, “First, causal deductions cannot be derived from cross-sectional studies.”,
please specify what kind of causal deductions cannot be derived from your study. You need to
complete your sentences for the readers to understand the whole picture.
i) Please remove ‘because’ from the statement, “Second, because the interview data in this study
were self-reported.”
j) Replace "conclusions" with "findings" in the sentence, "multicenter stochastic controlled trials
are needed to confirm our conclusions," as you have not yet presented your conclusions.
Overall comment on grammar: The manuscript still has several grammatical errors such as
spacing issues (e.g., Table1, Figure2, “returned to normal,and diarrhea ceased rapidly”), spelling
mistakes (e.g., Hance, cross-section analysis, biase), punctuation mark errors (e.g., in the
abstract conclusion, "incidence of diarrhea,  In the future..."), wrong sentences (e.g., “Household
income y was divided into...”, “with and without of diarrhea”, “we conducted out…”), singular/
plural issues (e.g., “a high serum calcium levels”). I’d suggest careful proofreading before
resubmitting.
Please review this paper.
user
Title: The incidence of chronic diarrhea decreases with increasing serum calcium levels: a cross-
sectional study based on NHANES 2005-2010
Version: 3 Date: 02 Oct 2023
Reviewer's report:
Dear Authors,
I appreciate your attention to my previous comments. I have further suggestions for your
consideration:
1. Title: It would be more accurate to use "cross-sectional study" instead of "survey" in the title,
as you did not directly conduct a survey.
2. Introduction:
a) In the statement, "Chronic diarrhea can be defined as 3 or more bowel movements or loose
stools over at least 4 weeks," could you please clarify whether you are referring to loose stools
per day? The frequency needs clarification.
b) In the statement, "Yu Peng[5] found that among patients under 60 years of age," consider
using "Yu et al." unless Yu Peng is the sole author.
c) For the statements, "...and elevate the electrolyte content in the intestinal lumen, leading to
diarrhea" and "a higher serum calcium level is significantly associated with decreased survival
in colorectal cancer," please provide the corresponding references.
3) Methods:
a) Please provide reference for Bristol stool scale in the statement, “The Bristol stool scale,
commonly used in research and clinical practice, was used to define chronic diarrhea”.
b) Covariates: The statement “Smoking status was categorized.” seems incomplete. Please
complete the sentence by adding the categories. For example, you may express it as "Smoking
status was categorized into two groups: individuals who smoked x cigarettes per year (referred
to as 'smokers') and those who did not smoke (referred to as 'nonsmokers')."
The categorization for smoking is not clear. How many cigarettes per year will categorize a
person as smoker? Do you have a clear threshold like you used for drinkers? If you prefer to
use the current category, please cite the source so that the readers can access it should they have
any questions.
c) Statistical Analysis: By the statement “and, Free Statistical software, version 1.7.1[13].”, are
you refereeing to R software? If so, please rephrase it because it seems that you are talking about
different software. Also, please check the citation 13 that you gave for R since it does not seem
correct.
4) Results: Consider revising the heading "As Serum Calcium Increased, the Risk of Diarrhea
Decreased" to something like "Association between serum calcium and diarrhea".
5) Discussion:
a) Ensure that paragraphs contain at least three sentences. Edit the first paragraph accordingly.
b) Define "simple nutritional calcium" within parentheses for clarity.
c) Introduce "Ca2+" earlier in the text if you plan to use it in the discussion; avoid introducing
new terms at this stage.
d) The following statements seem unrelated to your study: “In a retrospective cohort study
describing the relationship between serum calcium and inhospitable mortality in patients with
acute myocardial infarction (AMI), the authors found that both low and high serum calcium
levels were associated with AMI after correction for covariates. After adjusting the serum
calcium to 9.4 mg/dL (2.35 mmol/L), the risk of in-hospital mortality was reduced[16]. A cohort
study from China also found that lower serum calcium levels in non-diabetic patients increased
the risk of retinopathy[17]. A National Health and Nutrition Examination Survey (1999-2018)
study by Hou found an L-shaped association between serum calcium and all-cause mortality and
cardiovascular disease mortality in US adults.”
You can just say something like "In recent years, researchers have increasingly focused on serum
calcium-related studies. In particular, hypocalcemia was associated with a higher risk of all-
cause mortality and cardiovascular disease mortality (citations). However, to date, little attention
has been paid to the relationship between serum calcium and diarrhea."
e) This sentence does not conclude your argument, “Secondly, activation of intestinal CaSR
reduces overactive intestinal nerve activity and motility[19].” You need to conclude the process
by showing the relation of reduced diarrhea from reduced overactive intestinal nerve activity
and motility.
f) In this statement, “Finally, calcium-sensitive receptors can also reduce diarrhea by inhibiting
intestinal inflammation[24, 25].”, I believe, you are describing another process. If so, this is
not the 'final step'. Therefore, please remove 'finally'. You can write, "Alternatively, calcium-
sensitive receptors can reduce diarrhea by inhibiting intestinal inflammation (citations)".
g) Please elaborate the statement, “a sensitivity analysis was performed.”, to show why you
performed a sensitivity analysis.
h) In the statement, “First, causal deductions cannot be derived from cross-sectional studies.”,
please specify what kind of causal deductions cannot be derived from your study. You need to
complete your sentences for the readers to understand the whole picture.
i) Please remove ‘because’ from the statement, “Second, because the interview data in this study
were self-reported.”
j) Replace "conclusions" with "findings" in the sentence, "multicenter stochastic controlled trials
are needed to confirm our conclusions," as you have not yet presented your conclusions.
Overall comment on grammar: The manuscript still has several grammatical errors such as
spacing issues (e.g., Table1, Figure2, “returned to normal,and diarrhea ceased rapidly”), spelling
mistakes (e.g., Hance, cross-section analysis, biase), punctuation mark errors (e.g., in the
abstract conclusion, "incidence of diarrhea,  In the future..."), wrong sentences (e.g., “Household
income y was divided into...”, “with and without of diarrhea”, “we conducted out…”), singular/
plural issues (e.g., “a high serum calcium levels”). I’d suggest careful proofreading before
resubmitting.
assistant