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The Uptake of Apoptotic Cells Drives Coxiella burnetii Replication and Macrophage Polarization: A Model for Q Fever Endocarditis · 10.1371/journal.ppat.1000066

Name: Verified Rigor Record — The Uptake of Apoptotic Cells Drives Coxiella burnetii Replication and Macrophage Polarization: A Model for Q Fever Endocarditis · 10.1371/journal.ppat.1000066
Item: The Uptake of Apoptotic Cells Drives Coxiella burnetii Replication and Macrophage Polarization: A Model for Q Fever Endocarditis · 10.1371/journal.ppat.1000066
Rating: 79
Author: Αlpha¹

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Αlpha¹ Editorial

This rigor review was examined and confirmed by Αlpha¹ Editorial · July 6, 2026

Αlpha¹ Rigor Review

Rigor Reviewed

WARN

Warnings to address · Mixed Methods

Eight dimensions — click a segment for details

Critical

High-priority

Model-reported confidence: highReviewer agreement: moderateEngine: 7.6.0Source: full text

Not verified in this report

No reported statistical tests were found to recompute.
Declared data/code links were not checked for liveness or content.

This Αlpha¹ Rigor Review uses AI Rigor Reviewers trained on a curated corpus of high-fidelity and retracted papers, with expert supervision and curation. It can still make mistakes; verify each finding against the source before relying on it.

This paper presents a mechanistic study linking valvulopathy to altered macrophage polarization via apoptotic cell uptake, combining observational patient data with in vitro experiments. The scientific premise is well-supported and ethical approvals are adequately reported, but the study has notable reporting gaps including absent randomization/blinding details, missing effect sizes and confidence intervals, incomplete resource identification, and no data availability statement for non-microarray data.

This post-publication audit evaluated 8 dimensions with 3 independent reviewers and a copyedit pass. The statistics verification component could not recompute any tests because all p-values were reported as thresholds without test statistics or effect estimates with CIs. Citation checking found no retracted or unresolvable references. The reviewers substantially converged on most dimensions, with minor divergence on biological variables (reviewer 2/3 rated pass, reviewer 1 rated warn) and reporting transparency (reviewer 2 rated pass, reviewers 1/3 rated warn).

11 major claims checked against the paper's own evidence: all adequately supported.

Rigor

Eight Dimensions3 pass · 5 warn

11 major claims1 partial10 supported

The introduction cites extensive prior research on infective endocarditis, Q fever, apoptosis, and macrophage polarization. It acknowledges both strengths and weaknesses of prior work (e.g., mechanisms distinct from endothelial lesions are involved). The hypothesis follows logically from the cited evidence.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedINADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

The paper establishes a clear scientific premise linking valvulopathy, leukocyte apoptosis, and Q fever endocarditis, citing prior work and providing a logical rationale.

Evidence

direct quote[Introduction, paragraphs 1-3]

“In patients with acute Q fever and valve disease, chronic endocarditis will develop in 30% to 50% of cases.”

direct quote[Introduction, paragraph 4]

“It is tempting to speculate that leukocyte apoptosis induced by cardiac valvulopathy may impair the immune response to C. burnetii through the modulation of macrophage polarization induced by the binding of apoptotic cells.”

absence[Introduction]

Limitations of prior research are not explicitly discussed.

PASSReviewer 2· 90% conf

The scientific premise is well-established with extensive prior literature cited, a clear logical rationale linking valvulopathy, apoptosis, macrophage polarization, and Q fever endocarditis, and limitations of prior work are addressed.

Evidence

paraphrase[Introduction, paragraphs 1-3; references 1-22]

“The Introduction reviews clinical and mechanistic literature on infective endocarditis, Q fever, leukocyte apoptosis, and M1/M2 macrophage polarization, citing 22 references.”

direct quote[Introduction, final paragraph]

“The aim of this study was to determine the mechanisms by which valvulopathy creates favorable conditions for the establishment of Q fever endocarditis.”

direct quote[Discussion, paragraph 2]

“We hypothesized that the binding of apoptotic leukocytes to Mo and macrophages may be responsible for the immune impairment observed in Q fever endocarditis.”

PASSReviewer 3· 95% conf

The paper clearly establishes the scientific premise linking valvulopathy, leukocyte apoptosis, and Q fever endocarditis, citing relevant prior work and providing a logical rationale.

Evidence

direct quote[Introduction, paragraphs 1-6]

“Normal endocardium is resistant to colonization by bacteria unless it exhibits pre-existing lesions.”

direct quote[Introduction, final paragraph]

“We hypothesized that the binding of apoptotic leukocytes to Mo and macrophages may be responsible for the immune impairment observed in Q fever endocarditis.”

The human component is a cross-sectional comparison of patient groups with no randomization, blinding, or a priori sample size calculation. The in vitro experiments use isolated cells and include controls (e.g., necrotic cells), but randomization of samples and blinding of investigators are not mentioned. Replicate distinction is adequate: 'The results represent the mean±SEM of 5 experiments' for most assays. Inclusion/exclusion criteria for patients are implied (diagnosis-based) but not formally listed. Outlier handling is not discussed. Independent replication is not reported.

Sub-criteria

controlsADEQUATE

power analysisNOT REPORTED

blinding levelsNOT REPORTED

outlier handlingNOT REPORTED

randomization unitNOT REPORTED

inclusion exclusionINADEQUATE

randomization methodNOT REPORTED

replicate distinctionADEQUATE

independent replicationNOT REPORTED

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 80% conf

The in vitro experiments lack key design elements such as randomization, blinding, and power analysis, while the observational component is descriptive without pre-specified criteria.

Evidence

absence[Materials and Methods]

No randomization method is described for in vitro experiments.

absence[Materials and Methods]

Blinding is not mentioned.

direct quote[Results, paragraph 3]

“As a control, necrosis of lymphocytes was induced by a 95°C shock.”

WARNReviewer 2· 80% conf

The in vitro experimental design is generally sound (controls included, replication defined), but power analysis, randomization, and blinding are not reported, and outlier handling is not described.

Evidence

absence[Materials and Methods, entire section]

No randomization method, blinding, or power analysis described for in vitro experiments.

direct quote[Figure legends, e.g., Figure 3 legend]

“The results represent the mean±SEM of 5 experiments.”

paraphrase[Materials and Methods, 'C. burnetii infection' and 'Statistical analysis']

“Controls include unstimulated cells, necrotic lymphocytes, culture inserts, and anti-IL-10/TGF-β1 blocking antibodies.”

WARNReviewer 3· 85% conf

The human observational component lacks a pre-specified analysis plan and power analysis; the in vitro experiments are well-designed but lack explicit randomization and blinding.

Evidence

absence[Materials and Methods]

No randomization or blinding described for any component.

paraphrase[Materials and Methods, 'Patients']

“Nine patients with valvulopathy, 10 with acute Q fever, etc. were included based on epidemiological and clinical features, as previously described.”

direct quote[Results, 'Effect of apoptotic lymphocyte binding...']

“In contrast to AL binding, the binding of NL to Mo and MDM induced C. burnetii killing.”

For the human cohort, age and sex are provided for each of the five groups (controls, valvulopathy, acute Q fever, acute Q fever + valvulopathy, Q fever endocarditis). Sex is reported and both sexes are included, so sex_justified is not applicable. Species/strain/source criteria are applicable only to the C. burnetii culture, which is described as Nine Mile strain. Housing conditions are not applicable (human cells, no animal work). Demographics are adequately reported for the patient groups.

Sub-criteria

demographicsADEQUATE

sex reportedADEQUATE

sex justifiedN/A

age weight healthADEQUATE

housing conditionsN/A

species strain sourceADEQUATE

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 85% conf

Patient demographics are reported, but key biological variables for the in vitro experiments (e.g., age, sex, health status of cell donors) are not described.

Evidence

direct quote[Materials and Methods, Patients]

“Nine patients with valvulopathy (5 men and 4 women, mean age of 69.5 years), 10 with acute Q fever (3 men and 7 women, mean age of 46.3 years)...”

direct quote[Materials and Methods, Cell isolation and culture]

“PBMCs were isolated from leukopacks (Etablissement Français du Sang, Marseille, France)...”

direct quote[Materials and Methods, Bacteria]

“C. burnetii organisms (Nine Mile strain) were cultured as previously described.”

PASSReviewer 2· 85% conf

Biological variables are well-reported for the human subjects (sex, age, clinical groups) and for the in vitro cells (species, source, differentiation). Housing and animal variables are n/a as no live animals were used.

Evidence

direct quote[Materials and Methods, 'Patients' paragraph]

“Nine patients with valvulopathy (5 men and 4 women, mean age of 69.5 years), 10 with acute Q fever (3 men and 7 women, mean age of 46.3 years),...”

direct quote[Materials and Methods, 'Cell isolation and culture']

“PBMCs were isolated from leukopacks (Etablissement Français du Sang, Marseille, France)...”

paraphrase[Materials and Methods, 'Cell isolation and culture']

“Cells are human peripheral blood mononuclear cells from anonymous donors, differentiated into monocytes or MDM.”

PASSReviewer 3· 90% conf

Patient demographics (age, sex) are reported for all groups, and the in vitro work uses primary human cells from anonymous donor leukopacks.

Evidence

direct quote[Materials and Methods, 'Patients']

“Nine patients with valvulopathy (5 men and 4 women, mean age of 69.5 years), 10 with acute Q fever (3 men and 7 women, mean age of 46.3 years), 11 with acute Q fever and valvulopathy (6 men and 5 women, mean age of 51.3 years) and 11 with Q fever endocarditis (7 men and 4 women, mean age of 47.6) were included.”

direct quote[Materials and Methods, 'Bacteria']

“C. burnetii organisms (Nine Mile strain) were cultured as previously described.”

The paper states that informed written consent was obtained from each subject and the study was approved by the Ethics Committee of the Université de la Méditerranée. This covers both the observational and in vitro components (since cells were from human donors). Regulatory compliance is implied by the ethics committee approval.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

Ethical approval and informed consent are reported for the human observational component, and regulatory compliance is stated.

Evidence

direct quote[Materials and Methods, Patients]

“Informed and written consent was obtained from each subject and the study was approved by the Ethics Committee of the Université de la Méditerranée.”

PASSReviewer 2· 95% conf

Ethical approval and consent are reported adequately for the human subjects study; the in vitro component uses anonymous leukopacks from a blood bank, which typically does not require additional ethics review.

Evidence

direct quote[Materials and Methods, 'Patients' paragraph]

“Informed and written consent was obtained from each subject and the study was approved by the Ethics Committee of the Université de la Méditerranée.”

absence[Materials and Methods, 'Patients' paragraph]

No specific regulatory framework is named beyond a generic ethics approval.

PASSReviewer 3· 95% conf

The study reports ethical approval from a named committee and informed consent, meeting the criteria for human observational research.

Evidence

direct quote[Materials and Methods, 'Patients']

“Informed and written consent was obtained from each subject and the study was approved by the Ethics Committee of the Université de la Méditerranée.”

The paper identifies the C. burnetii strain (Nine Mile), culture media, and some kits (e.g., QIAamp Blood Mini Kit, LightCycler FastStart DNA SYBR green system). However, the antibodies used for flow cytometry (CD14-PE, MR-FITC) list vendors but not catalog numbers or clone information. The primers for qPCR are in the supplementary data but not shown in full in the main text. Software tools (e.g., WinMDI 2.8, Leica Confocal software) are named but versions are sometimes absent.

Sub-criteria

mycoplasma testingN/A

reagents identifiedADEQUATE

organisms identifiedADEQUATE

antibodies identifiedINADEQUATE

cell line authenticationN/A

software tools identifiedINADEQUATE

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 80% conf

Key resources are partially identified; antibodies and reagents are named but lack catalog numbers and RRIDs, and software versions are not fully reported.

Evidence

direct quote[Materials and Methods, C. burnetii intracellular trafficking]

“mouse anti-Lamp-1 (1:1,000 dilution, DHSB, Developmental Studies Hybridoma Bank) and rabbit anti-cathepsin D (1:1,000 dilution, a gift from S. Kornfeld...)”

direct quote[Materials and Methods, Circulating apoptosis markers]

“The percentage of CD3+ or CD14+ leukocytes with active caspases was determined using the Expo32 ADC and the WinMDI 2.8 software.”

direct quote[Materials and Methods, Bacteria]

“C. burnetii organisms (Nine Mile strain) were cultured as previously described.”

WARNReviewer 2· 80% conf

Key resources are partially identified: bacteria and primers are adequately described, but antibodies lack catalog numbers/RRIDs, and the cell line (L929) is identified without authentication or mycoplasma testing. Software versions are incomplete.

Evidence

direct quote[Materials and Methods, 'Flow cytometry' and 'Immunofluorescence']

“Mo and MDM were then incubated with 10 µl of CD14-PE (Beckman Coulter) and MR-FITC (BioLegend, San Diego, California, USA) Abs...”

direct quote[Materials and Methods, 'Bacteria']

“Dilacerated spleens of BALB/c mice infected with 10^8 C. burnetii organisms for 7 days were added to L929 cells.”

direct quote[Materials and Methods, 'Transcriptional profile']

“Datasets were analyzed with the GEArray Expression Analysis Suite software (SuperArray) and the TIGR's Multiexperiment Viewer.”

WARNReviewer 3· 85% conf

While cell sources, bacteria, and some reagents are identified, key resources such as antibodies used for flow cytometry lack vendor information and catalog numbers.

Evidence

direct quote[Materials and Methods, 'Flow cytometry']

“Mo and MDM were then incubated with 10 µl of CD14-PE (Beckman Coulter) and MR-FITC (BioLegend, San Diego, California, USA) Abs for 30 min at 4°C.”

direct quote[Materials and Methods, 'Flow cytometry' and 'Transcriptional profile']

“The percentage of CD3+ or CD14+ leukocytes with active caspases was determined using the Expo32 ADC and the WinMDI 2.8 software.”

The test is named (Mann-Whitney U test). Software is not identified for the primary analysis (no mention of a statistical package). Exact p-values are not reported; only thresholds (p<0.01, p<0.001) are given. Effect sizes and confidence intervals are not reported. Data presentation is adequate: individual data points are shown for the primary apoptosis measure, and bar graphs with SEM are used for in vitro experiments. Mathematical plausibility is not assessable from the summary data given.

Sub-criteria

tests namedADEQUATE

exact p valuesNOT REPORTED

effect sizes ciNOT REPORTED

data presentationADEQUATE

software identifiedNOT REPORTED

assumptions verifiedNOT REPORTED

mathematical plausibilityN/A

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 85% conf

Statistical tests are named, but assumptions are not verified, exact p-values are often not reported, and effect sizes with confidence intervals are absent.

Evidence

direct quote[Materials and Methods, Statistical analysis]

“Results are expressed as medians or means±SEM and compared with the non-parametric Mann-Whitney U test.”

direct quote[Results, paragraph 1]

“significantly (p<0.001) increased as compared to control subjects.”

absence[Results]

Effect sizes and confidence intervals are not reported.

WARNReviewer 2· 85% conf

Statistical tests are named (Mann-Whitney U, two-sided), exact p-values are reported, and data presentation includes individual values and SEM. However, test assumptions are not verified, software versions are missing, effect sizes and confidence intervals are not reported, and mathematical plausibility could not be fully verified due to lack of raw data.

Evidence

direct quote[Materials and Methods, 'Statistical analysis']

“Results are expressed as medians or means±SEM and compared with the non-parametric Mann-Whitney U test.”

direct quote[Results, multiple paragraphs, e.g., first paragraph]

“In patients with valvulopathy, acute Q fever and valvulopathy or Q fever endocarditis, circulating nucleosomes (...) and the percentage of active caspases in leukocytes (...) significantly (p<0.001) increased as compared to control subjects.”

absence[Results and figure legends, entire paper]

Effect sizes and confidence intervals are not reported.

WARNReviewer 3· 90% conf

The statistical analysis uses appropriate non-parametric tests but reporting is incomplete: p-values are given as thresholds rather than exact values, and effect sizes with confidence intervals are absent.

Evidence

direct quote[Materials and Methods, 'Statistical analysis']

“Results are expressed as medians or means±SEM and compared with the non-parametric Mann-Whitney U test.”

direct quote[Results, 'Circulating apoptosis markers...']

“In patients with valvulopathy, acute Q fever and valvulopathy or Q fever endocarditis, circulating nucleosomes and the percentage of active caspases in leukocytes significantly (p<0.001) increased as compared to control subjects.”

Microarray data are submitted to ArrayExpress with an accession number (E-MEXP-1289). However, no data availability statement is provided for other data (e.g., qPCR, flow cytometry). Custom code is not mentioned; analysis likely used commercial software. The data availability is partial.

Sub-criteria

code sharingNOT REPORTED

accession numbersADEQUATE

repository depositADEQUATE

data availability statementNOT REPORTED

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 90% conf

Microarray data are deposited in ArrayExpress, but no data availability statement for other data, and code is not shared.

Evidence

direct quote[Materials and Methods, Transcriptional profile of Mo and MDM]

“Data were submitted to the ArrayExpress database (MIAME Accession number E-MEXP-1289).”

absence[Materials and Methods]

No data availability statement for other data.

absence[Materials and Methods]

No code sharing mentioned.

WARNReviewer 2· 70% conf

Microarray data were deposited in ArrayExpress with an accession number, but a general data availability statement is missing for other data types (clinical data, flow cytometry, qPCR), and custom code was not shared.

Evidence

direct quote[Materials and Methods, 'Transcriptional profile of Mo and MDM']

“Data were submitted to the ArrayExpress database (MIAME Accession number E-MEXP-1289).”

absence[Materials and Methods and Discussion, entire paper]

No general data availability statement is provided.

absence[Materials and Methods, entire paper]

No code sharing is reported.

WARNReviewer 3· 85% conf

Microarray data are deposited in ArrayExpress with an accession number, but the statement is brief and no other data (qPCR, clinical) are deposited.

Evidence

direct quote[Materials and Methods, 'Transcriptional profile']

“Data were submitted to the ArrayExpress database (MIAME Accession number E-MEXP-1289).”

absence[Entire paper]

No data availability statement for other data types.

The methods section is detailed and would allow replication. Limitations are discussed in the Discussion section (e.g., the caveat about clinical relevance, the need for further studies). Conclusions are cautiously worded and generally proportional to the evidence. However, trial registration and reporting guidelines are not applicable (observational with no pre-registration). Funding and COI are reported. All outcomes described in the Methods appear to be reported, but no pre-specified analysis plan is stated.

Sub-criteria

funding coiADEQUATE

trial registrationN/A

reporting guidelineNOT REPORTED

methods completenessADEQUATE

all outcomes reportedINADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 85% conf

Methods are detailed, but no trial registration, reporting guideline, or pre-specified outcomes are mentioned; limitations are discussed, and conclusions are proportional.

Evidence

direct quote[Materials and Methods]

“PBMCs were isolated from leukopacks (Etablissement Français du Sang, Marseille, France) by Ficoll gradient (MSL, Eurobio) and suspended in RPMI 1640 containing 20 mM HEPES, 10% fetal calf serum (FCS), 2 mM L-glutamine, 100 U/ml penicillin and 100 µg/ml streptomycin (Invitrogen).”

direct quote[Discussion, paragraph 8]

“Our results give new comprehensive insights into the pathological processes resulting from valvulopathy that are associated with the high risk to develop rare and atypical IE.”

direct quote[Acknowledgments]

“The authors have declared that no competing interests exist. This work was supported by the «crédits ministériels du Programme Hospitalier de Recherche Clinique» (PHRC 2005)...”

PASSReviewer 2· 85% conf

Methods are sufficiently detailed for replication, limitations are discussed, conclusions are proportional, and funding/COI are stated. No trial registration or reporting guideline was required for this study type.

Evidence

paraphrase[Materials and Methods, entire section]

“All procedures for cell isolation, culture, infection, qPCR, confocal microscopy, flow cytometry, and microarray are described step-by-step.”

direct quote[Discussion, paragraph 3]

“The effect of AL was independent of the apoptosis-inducer agent since the replication of C. burnetii was increased in Mo and MDM that have bound apoptotic cells induced by either corticoids or staurosporine (data not shown).”

direct quote[End of text, before References]

“This work was supported by the «crédits ministériels du Programme Hospitalier de Recherche Clinique» (PHRC 2005) ... The authors have declared that no competing interests exist.”

WARNReviewer 3· 90% conf

Methods are largely complete and conclusions are proportional, but the study lacks trial registration, a reporting checklist, and explicit mention of all pre-specified outcomes.

Evidence

paraphrase[Materials and Methods]

“All experimental procedures—cell isolation, bacterial culture, infection, qPCR, immunofluorescence, flow cytometry—are described in enough detail to reproduce.”

direct quote[Discussion, final paragraphs]

“Our results give new comprehensive insights into the pathological processes resulting from valvulopathy that are associated with the high risk to develop rare and atypical IE.”

direct quote[Acknowledgments]

“This work was supported by the «crédits ministériels du Programme Hospitalier de Recherche Clinique» (PHRC 2005) ... The authors have declared that no competing interests exist.”

12 copyedit issues flagged: mostly grammar, consistency, punctuation.

Checked 62 references: 57 verified — 5 not checked.

Αlpha¹ Rigor Action ItemsFinal pass before journal submission

This published paper would benefit from corrections to reporting deficiencies: missing demographic data for cell donors, absent randomization/blinding documentation, lack of effect sizes and exact p-values, incomplete resource identification, and no data availability statement beyond microarray data. An informed reader should weigh these gaps when interpreting the robustness of the in vitro findings. A correction or erratum addressing the most consequential gaps—particularly the unspecified donor demographics and absence of blinding—would strengthen the paper's evidentiary value.

1.
HIGHdata code
Add a comprehensive Data Availability statement in the Materials and Methods section specifying that clinical, flow cytometry, qPCR, and microscopy data are available from the corresponding author upon reasonable request, and provide a mechanism for access.
Without a data availability statement, readers cannot verify or reanalyze the primary experimental data, which is a fundamental reporting requirement.
2.
HIGHrigor
Report the age, sex, and health status (if available) of cell donors for the in vitro experiments, or explicitly state that this information was not available from the blood bank.
Donor demographics can influence cellular responses and are essential for assessing the generalizability of in vitro findings.
3.
HIGHreporting
Describe the method of randomization for in vitro experiments (e.g., random assignment of cells to treatment groups) and state whether blinding was used for any experimental procedures (e.g., microscopy quantification).
Randomization and blinding reduce bias; their absence is a methodological concern that should be disclosed even if not performed.
4.
HIGHstatistics
Report exact p-values (e.g., p = 0.023) instead of thresholds (e.g., p < 0.05) for all statistical comparisons in the Results section.
Exact p-values allow readers to assess the precision of results and perform independent meta-analyses.
5.
HIGHstatistics
Include effect sizes (e.g., Cohen's d or rank-biserial correlation) and 95% confidence intervals for key comparisons in the Results section.
Effect sizes and confidence intervals convey the magnitude and precision of effects, which p-values alone do not provide.
6.
HIGHrigor
Provide catalog numbers, RRIDs, and lot numbers for all commercial antibodies (CD14-PE, MR-FITC, anti-Lamp-1, anti-cathepsin D, anti-IL-10, anti-TGF-β1) in the Materials and Methods section.
Complete antibody identification enables independent replication and verification of specificity.
7.
MEDIUMrigor
State authentication status (e.g., STR profiling) and mycoplasma testing results for the L929 cell line in the Materials and Methods section.
Uncertified cell lines risk cross-contamination or misidentification, which can invalidate results.
8.
MEDIUMreporting
Name the statistical software and version used for all analyses (e.g., GraphPad Prism, SPSS) in the Statistical analysis subsection.
Software version information is necessary for reproducibility of statistical computations.
9.
MEDIUMreporting
Add a statement on outlier handling criteria in the Statistical analysis section, specifying what thresholds were used and whether any data points were excluded.
Outlier handling decisions can substantially affect results and must be transparent.
10.
MEDIUMreporting
Mention adherence to a relevant reporting guideline (e.g., STROBE for the observational component) in the Materials and Methods section.
A reporting guideline ensures comprehensive disclosure of key study elements.
11.
LOWcopyedit
Revise the title for clarity: 'Apoptotic Cell Uptake Drives Coxiella burnetii Replication and Macrophage Polarization: A Model for Q Fever Endocarditis'.
The current title contains a redundant phrase that obscures the paper's focus.
12.
LOWcopyedit
Remove extra spaces before periods in the Introduction (e.g., 'valves .' → 'valves.') and fix subject-verb agreement in Figure 1 legend ('was' → 'were').
Minor typographical errors detract from manuscript professionalism.
13.
LOWreporting
Provide version numbers for all software tools (GEArray Analysis Suite, TIGR MeV, Leica Confocal software, Adobe Photoshop) in the Materials and Methods section.
Complete software versioning aids reproducibility.

Full text (53,310 chars)Analyzed: Jul 6, 2026

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