A careful, numerically reproducible NHANES analysis whose cohort and death counts match the public files exactly, but its central design claim of preregistration cannot be verified, and the abstract and conclusions lean on pointwise contrasts (men 1.17 at 2 eggs/day, 'incompatible above 1.6 eggs/day') after primary tests that are null after Holm adjustment and under non-proportional hazards.
Soundness
3/4
Presentation
3/4
Contribution
2/4
Confidence
4/5
✓ 12 confirmed✕ 5 discrepancy◐ 1 inconclusive○ 1 not checkable
Summary
The paper links one or two 24-hour dietary recalls from NHANES 1999–2018 (45,304 adults) to the 2019 public-use Linked Mortality File. It fits survey-weighted Cox models with a 3-knot restricted cubic spline of egg intake (eggs/day from MPED/FPED), separately in men and women, for all-cause mortality (all cycles) and cardiovascular mortality (1999–2014 only, because the public file does not identify stroke deaths after 2014). Six primary 2-df tests are Holm-adjusted; 25 sensitivity analyses, regression calibration and E-values follow.
Main claims: no primary test survives Holm adjustment (smallest Holm P 0.226). Men show a modest positive gradient (HR 1.17 at 2 eggs/day) that is confined to the first 10 years of follow-up and attenuated by dietary cholesterol. Women show a non-linear dip (HR 0.86 at 1 egg/day). CVD mortality shows no gradient but is imprecise. The evidence for a sex difference is weak (P=0.15; linear P=0.046). The paper also claims the analysis plan was frozen and time-stamped before mortality data were obtained, with 17 logged deviations.
According to the requester, the study was produced end to end by an AI system (IterSCI). Only the PDF was supplied. The plan, hash target, deviation log and code said to be 'released with this article' (Sec. 6.1) were not.
Strengths
Data provenance reproduces exactly from public NCHS files
Figure 1; Sec. 2.3, 3.1; Tables 3, 4
From the public DEMO, DR1TOT/DR2TOT files and the 2019 public-use LMF, applying the stated inclusion rules in order reproduces every Figure 1 count (101,316 → 55,081 → 48,740 → 48,657 → 45,304; 22,094 men / 23,210 women), 7,315 deaths (4,031/3,284), 431,164 person-years, 2,222 CVD deaths (1,228/994) and all 20 cycle-by-sex n in Table 3 exactly (checks 03, 07). The weighted crude rates in Table 4 (13.1 and 11.3 per 1,000 PY) are also reproduced (check 13). The analysis set is what the paper says it is.
Correct handling of the public-use cause-of-death limitation
Sec. 1 (p.2); Sec. 2.5; Figure 1 note
The paper restricts the primary CVD outcome to 1999–2014 because the 2015–2018 public LMF releases only heart disease and cancer. This is correct: cerebrovascular code 005 appears 519 times in 1999–2014 and 0 times in 2015–2018 (check 04). Heart-disease mortality over all cycles is added as S23. Sec. 1 notes that earlier subgroup analyses handled this inconsistently.
Transparent multiplicity control with the null result leading
Sec. 2.7, 3.2; Table 5; Abstract
Table 5 reports F, df, unadjusted and Holm-adjusted P for all six primary tests. All 12 P values follow from the reported F statistics, and the Holm step-down is correct (check 01). The abstract states the null Holm result before any point estimate.
Internally consistent spline results and interpretive aid
Tables 5, 6, 11, 15
In all four sex-by-outcome rows, the four Table 6 HRs are reproduced by a 2-parameter RCS with the stated knots (0, 0.17, 1.61). The covariance implied by the CIs gives Wald P close to Table 5, and the Table 11 thresholds are reproduced within rounding (check 02). The de-attenuated HRs in Table 15 equal HR^(1/λ) (check 10).
Candid sensitivity reporting, including unfavourable results
Sec. 2.8, 3.6, 3.8, 4.3; Tables 9, 10, 12–14
Twenty-five prespecified sensitivity analyses are tabulated for both sexes and both outcomes. They include results that weaken the men's gradient (S6 dietary cholesterol, S1 delayed entry) and the PH-violation follow-up for all four combinations (D17, Tables 9–10). The weaknesses section (Sec. 4.3) names small E-values, single-day recalls, λ≈0.3 and possible mediators in Model 3.
Causal language mostly well controlled
Title; Abstract; Sec. 2.7, 4.2, 4.4, 5, 7
The abstract, Sec. 3.7, 4.4, 5 and the plain-language summary repeatedly state that associations do not establish causation and that a CI including 1 is not evidence of safety ('No intake was shown to be safe'). Dietary cholesterol is explicitly treated as a mediator, so its attenuating effect is not read as confounding (Sec. 4.2). The title is neutral and matches the design.
Weaknesses
Preregistration and plan adherence cannot be verified
major · Abstract (Design); Sec. 2.2, 2.7, 2.9, 4.3, 6.1, 6.3, 7; Table 6
The abstract's Design line, Sec. 4.3 and the plain-language summary ('so that the results could not steer the analysis') rest on a plan frozen at 2026-11-09T10:55:03Z with a SHA-256 hash. However, Sec. 2.2 says only that the plan 'can be deposited' in a registry. The paper gives no registry ID, URL, DOI or repository, and none of the plan, the deviation log or the code was supplied (check 05). The time stamp is self-generated, and the PDF was created 4 h 37 min later on the same day. That leaves the authors' own statement as the only evidence that the plan came first, and that all 17 deviations (some substantive: D4 time-split PH test, D9 complete-case S24, D11, D16) preceded any association estimate. One concrete adherence lapse is visible: Sec. 2.7 prespecifies an HR at 1.5 eggs/day, but Table 6 omits it, which contradicts 'all prespecified estimates are reported' (Sec. 4.3, 6.3). The reconstructed values are men 1.12 (0.99–1.28) and women 0.89 (0.78–1.00) (check 02). Fix: deposit the frozen plan and deviation log with an independently verifiable time stamp (e.g. OSF registration or RFC 3161 token), report the 1.5 eggs/day contrast, and soften the design claims until then.
Abstract and conclusions emphasise pointwise contrasts after null primary tests
major · Abstract (Conclusions); Sec. 4.1, 4.4, 5, 7; Table 11
The primary test for men is H1m P=0.054 (Holm 0.269). Yet the abstract's conclusion that men eating about two or more eggs a day had 'modestly higher all-cause mortality', Sec. 5 and 4.1 ('intakes above about 1.6 eggs a day were incompatible with an unchanged hazard'), and the plain-language summary ('roughly 17% higher'; 'more than about one and a half eggs a day was linked to higher risk') all rest on pointwise 95% CIs along the spline. Sec. 2.7 defines that tool as a 'descriptive interpretive aid, not a hypothesis test'. Reading pointwise lower limits above 1 as incompatibility after a non-significant omnibus test undercuts the multiplicity framing the paper sets up. The message on 1 egg/day is also inconsistent. The abstract says 'No intake was shown to be safe', and the prespecified 10% margin cannot be excluded in men from 0.34 eggs/day (Table 11; men UCL at 1 egg/day 1.22). Sec. 4.4 and 5 nonetheless say one egg a day 'did not indicate a higher hazard … which accords with guidance'. Fix: lead with the null family-wise result, present pointwise contrasts as descriptive, and make Sec. 4.4/5 consistent with Table 11.
Non-proportional hazards make the averaged HRs hard to interpret, in both sexes
major · Sec. 3.6; Tables 9, 10; Abstract
Questions for the authors
Can you deposit the frozen plan (whose SHA-256 is given in Sec. 2.2) and the deviation log with an independently verifiable time stamp, and state when the 2019 LMF files were first downloaded by the pipeline?
Why is the prespecified HR at 1.5 eggs/day (Sec. 2.7) absent from Table 6, and were any other prespecified estimates omitted?
Which tests do P=0.43 and P=0.064 in Sec. 3.6 refer to, and what is the formal test of the ≤10 y vs >10 y difference in men?
In women, what is the 2-df P in Model 2b with and without prevalent CVD/cancer? That is, does the inverse association require adjustment for possible mediators?
How were the design df of 151/121 obtained, given that PSUs minus strata in the public DEMO files give 153/123?
Were the 99th percentiles in the text weighted and those in Table 3 unweighted (or vice versa)?
Verification
We ran 19 checks with scripts in work/verify/. Data provenance was checked hardest. Re-deriving the cohort from the public NHANES DEMO/dietary files and the 2019 public-use LMF reproduces every participant-flow count, death count, person-year total and cycle size exactly (checks 03, 04, 07), as well as the overall weighted crude rates (13). The hypothesis-test arithmetic (01), spline-HR internal consistency and interpretive-aid thresholds (02), linear-HR CIs (11), the sex-interaction test (12), regression calibration (10) and the agreement of abstract numbers with the tables (06) were all confirmed. Five minor discrepancies were found: design df 153/123 vs the stated 151/121 (03b); 99th percentiles in the text vs Table 3 (08); the E-value conversion label (09); two Sec. 3.6 P values that do not match their CIs (11); and a garbled reference [51] (15b). None changes a main result. The preregistration claim was not checkable because no plan, log or code was supplied and no registry entry exists (05). One citation claim about [2] was inconclusive (16b). Category-specific estimates and the Cox models themselves could not be refit, because MPED/FPED intake and the code were not available.
◐InconclusiveSection 1 (p.1, line 'associated with 8% higher all-cause mortality and 8% higher cardiovascular mortality [2]'; p.2 'stronger in women (P for interaction 0.001) [2]'); Section 4.2
[51] B. Rosner, D. Spiegelman, W. C. Willett. Correction of logistic regression relative risk estimates and confidence intervals for random within-person measurement error. American Journal of Epidemiology, 132(4):734-745, 1990.
Merges two papers by the same authors: the cited title is Am J Epidemiol 136(11):1400-1413 (1992, doi 10.1093/oxfordjournals.aje.a116453), while 132(4):734-745 (1990, doi 10.1093/oxfordjournals.aje.a115715) is '...for measurement error: the case of multiple covariates measured with error'. Both concern regression calibration, so support for the method is unaffected (work/verify/15b_ref51_rosner.log).
[2] V. W. Zhong et al. Associations of Dietary Cholesterol or Egg Consumption With Incident Cardiovascular Disease and Mortality. JAMA 321(11):1081, 2019.
Section 1 attributes '8% higher cardiovascular mortality' per half egg/day to [2], but its abstract reports incident CVD (fatal and nonfatal) with HR 1.06 (1.03-1.10); the 8% figure is for all-cause mortality. The claimed sex interaction (stronger in women, P=0.001) is not in the abstract and the full text was not openly available to verify (work/verify/16_cited_claims.log).
Suggestions
Register the frozen plan and deviation log in a public registry (or attach a trusted RFC 3161 time stamp), release the code, and cite the identifiers in Sec. 2.2 and 6.1.
Rewrite the abstract conclusions so the family-wise null result leads. Present the men's 2 eggs/day contrast and the 1.6 eggs/day threshold as descriptive pointwise findings, and align Sec. 4.4/5 on 1 egg/day with Table 11.
Report period-specific (≤10 y / >10 y) HRs for both sexes in the main results, with a formal test of their difference, and mention the women's time pattern in the abstract.
Report Model 2b alongside Model 3 for the women's primary test and discuss over-adjustment by BMI and cardiometabolic conditions.
Add the prespecified 1.5 eggs/day contrast to Table 6, and correct the Table 15 footnote, the Sec. 3.6 P values, the P99 values, the design df and the table cross-references.
Show intake distributions by database restricted to day-1 recalls, to separate the MPED/FPED change from the addition of a second recall.
Fix reference [51] and the attribution of cardiovascular mortality to [2]; fix the Table 2 layout and the table ordering.
Ethics and integrity
No ethical concern with the data: NHANES public-use files are anonymised and consented (Sec. 6.2). Integrity notes: per the requester, the manuscript was produced end to end by an AI system, and the only listed author is 'IterSCI'. No human is named as accountable for the analysis or for the transparency declaration in Sec. 6.3, which is a self-attestation. Sec. 6.1 states that the plan, log and code are 'released with this article', but none were provided and the paper contains no link. Venues would need a responsible human author and deposited materials. No instructions aimed at the reviewer were found in the paper or the requester's notes. We found no evidence of fabricated data: every count we could derive from the public files matched exactly.
Scope of this review
Only the PDF was supplied; no LaTeX source, analysis code, frozen plan or deviation log was supplied, so the preregistration and its 17 deviations could not be audited and no model could be refit. We rebuilt the analysis set from the public NHANES and 2019 LMF files and verified counts, deaths, person-years and overall weighted rates. Egg exposure (MPED/FPED), covariates, multiple imputation and the survey-weighted Cox models were not reconstructed, so category-specific rates and all HRs were checked only for internal consistency, not recomputed from data. The full text of reference [2] was not openly accessible.
Reference list is genuine and prior results are cited accurately
Sec. 1, 4.2; References [1]–[52]
All 52 references were checked and no fabricated entry was found. The load-bearing numbers from [23] (per-half-egg HR 1.13 men, 0.86 women, interaction P=0.01) and [3] (7% per half egg, P interaction 0.002) match the source papers (checks 15, 16).
For men's all-cause mortality the PH checks fail (Schoenfeld P<0.001; egg×log t P=0.007, Table 9). Table 10 gives 1.18 (1.02–1.36) for ≤10 y and 0.86 (0.68–1.09) for >10 y; an approximate Wald contrast gives z=2.24, P≈0.025, which the paper neither computes nor reports (checks 06, 11). Women show the mirror pattern (0.80 ≤10 y vs 1.01 >10 y), although their PH flag is not set. The headline whole-follow-up HRs (1.08, 1.17, 0.86) therefore average over a time-varying association. Together with attenuation under delayed entry, this points to reverse causation or a drift of exposure away from usual intake (Sec. 4.3). Fix: report period-specific HRs as co-primary descriptions, test the period difference formally, and state in the abstract that the women's dip is also confined to the first decade.
Women's inverse association depends on the adjustment set
minor · Sec. 2.6, 3.3, 4.3; Table 6; Table 12 (S25, S14a)
The women's HR at 1 egg/day is 0.91 (0.80–1.02) and 0.91 (0.81–1.03) in Models 1 and 2 (2-df P 0.230/0.246). It is 0.87 (0.77–0.98) in Model 2b (P 0.070) and 0.86 (0.76–0.97) in Model 3 (P 0.038, check 14). So the primary test falls below 0.05 only after adding BMI, diabetes, hypertension and hypercholesterolaemia, which Sec. 2.6 says 'may lie on a pathway from egg intake to death'. Sec. 4.3 says Model 2b 'gave similar estimates'; that holds for the HR but not for the test. Since the Holm result is null under every model, the main conclusion survives. Still, the abstract should not present 0.86 without this context. Fix: report the Model 2b P alongside Model 3 in the abstract or results, and discuss the over-adjustment risk.
Exposure discontinuity across MPED/FPED and one vs two recalls is asserted, not demonstrated
minor · Sec. 2.4, 3.1; Table 3; Table 12 (S3, S13)
Sec. 2.4 says MPED M_EGG and FPED PF_EGGS define the component identically and that no rescaling was applied. Yet Table 3 shows 38–42% zero intake and medians of 0.01–0.02 eggs/day in 1999–2002, against 12–18% and 0.13–0.25 later. Part of this reflects one vs two recalls, but the paper does not separate the two sources. S13 (FPED cycles only) changes the women's estimate to 0.81 (0.68–0.97). The 1999–2002 cycles also anchor the knot at 0. Fix: show day-1-only intake distributions by database, and justify (or test) the comparability of the two databases.
Limited independence from the prior NHANES analysis that motivated the sex hypothesis
minor · Sec. 1 (p.2), 2.2, 4.2
The sex hypothesis H3 is motivated by [23] (NHANES 1999–2014, per-half-egg HR 1.13 men vs 0.86 women, P=0.01). The 1999–2014 cycles supply 36,036 of the 45,304 participants (79.5%, check 03), largely the same people with longer follow-up. A plan frozen after [23] was published cannot protect against a hypothesis informed by overlapping data. 'Extends and partly replicates' (Sec. 1) should be qualified, and agreement with [23] (Sec. 4.2) should not be counted as replication.
Mislabelled or mismatched statistics
minor · Sec. 2.7, 3.1, 3.6, 4.1; Tables 3, 6, 8, 10, 11, 12, 15
(i) Sec. 3.6 reports P=0.43 next to the men's >10 y HR 0.86 (0.68–1.09), whose CI implies P≈0.21. It reports P=0.064 next to the stratified 1.10 (0.98–1.23), whose CI implies P≈0.10. These may be 2-df tests, but they are unlabelled (check 11). (ii) The Table 15 footnote says the E-values use a square-root HR conversion, but the men's 1.30 matches VanderWeele's (1−0.5^√HR)/(1−0.5^√(1/HR)) conversion (1.295), not √HR (1.241) (check 09). (iii) The 99th percentiles in Sec. 3.1, Sec. 2.7, the Table 6 note and Table 11 (3.59/2.81) differ from Table 3 (3.51/2.86) (check 08). (iv) Design df are 151/121, but PSUs minus strata in the public files give 153/123 (check 03b; negligible effect on P). (v) Sec. 4.1 and the Table 8 footnote point to Table 8/Table 6 for the linear egg×sex test, which is in Table 5. (vi) S3 lists 4,030 men's deaths vs 4,031 in the primary set, unexplained (check 07).
Speculative causal interpretation in the Discussion
minor · Sec. 4.2 (p.17), 4.4
Sec. 4.2 concludes from cross-population heterogeneity that 'the dietary context in which eggs are eaten may matter more than eggs themselves'. No analysis here examines dietary context or co-consumed foods (S7 only adds red/processed meat). Sec. 4.4 frames the 1 egg/day finding as according with guidance [1]. Both statements go beyond associational data that have E-values ≤1.60 (CI ≤1.21; check 09). Fix: present these as hypotheses for future work (as Sec. 4.5 partly does).
Citation inaccuracies
minor · Sec. 1 (pp.1–2); Reference [51], [2]
Reference [51] merges two Rosner–Spiegelman–Willett papers: the 1992 title with the 1990 volume/pages (check 15b). Sec. 1 attributes '8% higher cardiovascular mortality' per half egg to [2]. The abstract of [2] reports incident CVD, HR 1.06 (1.03–1.10), and the claimed sex interaction (P=0.001) could not be verified (check 16b). Neither affects the main results.
Presentation defects in tables
minor · Tables 2, 4, 7, 12–14 (pp.7–14); Sec. 3.1
Table 2 is split across pp.7–8, with the women's hypercholesterolaemia/CVD/cancer rows orphaned below Table 4. Table 14 is printed before Table 13, and Table 12 continues after Table 14 on p.14. Men's categorical HRs (Table 7: 0.87, 1.17, 1.06, 1.23) are non-monotone, yet the paper describes them only as a gradient. Sec. 3.1 summarises the men's crude rates as 'no monotonic pattern', although the weighted rates are 15.9/15.8 in the middle categories vs 12.1 at <0.15 (check 13).
All 12 reported values are attainable: e.g. men 1.08^(1/0.33)=1.263 (range 1.241-1.285) vs 1.27; 1.02->1.062 (1.045-1.079) vs 1.05; 1.16->1.568 (1.537-1.600) vs 1.55; women 0.96->0.869 vs 0.87; CVD women upper 1.17->1.752 (1.709-1.798) vs 1.71. Caveat (acknowledged in the footnote): CIs ignore uncertainty in lambda, and with lambda about 0.3 the correction multiplies log-HR by about 3, so the de-attenuated 1.27 in men is highly sensitive to the classical-error assumption.
HR^(1/lambda) applied to estimate and both CI limits, interval arithmetic over rounding of HR/limits (+-0.005) and lambda (+-0.005)
Linear HRs/CIs/P values are consistent (men 1.08 (1.02-1.16) P=0.017; women 0.96 (0.89-1.04) P=0.30; per half egg 1.04 (1.01-1.08)) and the Section 3.6 P values match their HRs (men >10 y 0.86 (0.68-1.09) 'P=0.43'; stratified 1.10 (0.98-1.23) 'P=0.064')
Linear results are consistent: men P=0.017 vs obtained 0.019 (rounding range 0.007-0.040; t151 0.020); women P=0.30 vs 0.304 (0.214-0.401); per half egg 1.04 (1.01, 1.08) = sqrt of per-egg values (1.039, 1.010, 1.077). Section 3.6 attaches P values to HRs they cannot belong to as Wald tests: men >10 y HR 0.86 (0.68, 1.09) implies P=0.210 (range 0.182-0.240), reported 'P=0.43'; stratified 1.10 (0.98, 1.23) implies P=0.100 (0.073-0.132), reported 'P=0.064'. They may be unlabelled 2-df overall spline tests, but the text does not say so; P=0.064 next to a CI that includes 1 by a wide margin overstates the stratified evidence (minor). Additionally the <=10 y vs >10 y contrast in men has z=2.24, P=0.025 (independence approximation), which is not reported or tested although the abstract states the gradient was 'confined to the first 10 years'.
SE from log-CI width/3.92, Wald z, two-sided P under N(0,1) and t(151), evaluated over all rounding combinations (+-0.005)
Linear egg-by-sex test P=0.046 (F 4.06; 1, 151 df) is consistent with the sex-specific linear HRs (Table 8: men 1.08 (1.01-1.15), women 0.97 (0.90-1.04))
Table 8 pooled-model HRs give z=2.17, F=4.70, P=0.032 under independence, rounding range 0.012-0.068; reported F 4.06, P=0.046 lies inside (and F(1,151)=4.06 gives P=0.0457). Using Table 6 sex-specific linear HRs gives P=0.024 (0.009-0.052), also compatible. The 'weak evidence' wording in the abstract is fair given that this is a secondary test and the primary 2-df test gave P=0.15. The Table 8 footnote 'Linear egg x sex P values are in Table 6' is wrong; the value is in Table 5 (see check 06).
z for ln(HRm/HRw) with CI-derived SEs, reference t(151), correlation between sex-specific estimates rho in {-0.2, 0, 0.2}, all rounding combinations (+-0.005)
Table 4 crude rates are internally coherent (weighted 13.1 and 11.3 per 1,000 PY) and show 'no monotonic pattern across intake categories in either sex'
Overall weighted rates reproduced from the public data: men all-cause 13.06 vs reported 13.1, women 11.29 vs 11.3, heart disease 3.31/2.71 vs 3.3/2.7, CVD 1999-2014 3.92/3.44 vs 3.9/3.4 (tolerance: 1-decimal rounding); CVD-set deaths 1,228/994 and PY 194,626/209,192 match exactly. Neither weighted nor unweighted rates are monotonic in any of the six rows, so the statement is literally correct; but in men the weighted all-cause rate is 15.9 and 15.8 in the 0.5-<1 and 1-<2 categories vs 12.1 at <0.15 (crude, not age-adjusted), which the summary 'no monotonic pattern' does not convey. The category-specific weighted rates themselves could not be recomputed because egg intake (FPED/MPED) was not downloaded.
Unweighted rates deaths/PY by category from the transcribed table; monotonicity of weighted and unweighted rates; overall weighted rates recomputed from the NHANES/LMF files in the reconstructed analysis set (n=45,304) with pooled day-1 weights as stated in Sec. 2.7 (WTDR4YR*2/10 for 1999-2002, WTDRD1/10 thereafter)
Women's all-cause association depends on the primary model: overall P 0.230/0.246 (Models 1/2) vs 0.070 (Model 2b, S25) vs 0.038 (Model 3); HR at 1 egg/day 0.91 in Models 1 and 2 vs 0.86 in Model 3 (Section 3.3)
Text statements match Table 6 exactly (women 0.91 (0.80, 1.02) M1, 0.91 (0.81, 1.03) M2, 0.86 (0.76, 0.97) M3; men linear 1.09 (1.03, 1.16) M1, 1.10 (1.04, 1.17) M2). Model choice moves the sexes in opposite directions. Women: 2-df P 0.230/0.246 (M1/M2), 0.070 in Model 2b (HR 0.87, 0.77-0.98; adds HEI-2015 without eggs and prevalent CVD/cancer, no BMI or cardiometabolic conditions), 0.038 in Model 3 (HR 0.86). So the shift of the women's HR away from 0.91 comes mainly with the diet-quality/prevalent-disease terms, while the 2-df test falls below 0.05 only once the possible mediators named in Sec. 2.6 are added. Men: 0.009/0.012/0.023 (M1/M2/M2b) vs 0.054 in M3. The null Holm-adjusted conclusion holds under every model (smallest Holm P 0.054, men in Model 1). The abstract reports only Model 3 HRs without noting this.
Tabulation of HR at 1 egg/day, 2-df P and linear HR across Models 1, 2, 2b, 3 and S10/S14a from the transcribed tables; text checked against table cells; Holm over the six primary tests with H1 P values taken from each model (H2/H3 unchanged)
Bibliography entries exist with the stated metadata, including the recent [13] Nutrients 2025, [21] NMCD 2025, [22] Sci Rep 2025, [27] Medicine 2026
34/52 references match Crossref automatically (title similarity >=0.85, year consistent), including [13] (2025), [21] (2025), [22] (2025) and [27] (2026), and the load-bearing [2], [3], [23], [52]. Of the 18 flagged: [10], [11], [12], [18], [25] differ only by online-first vs print year (e.g. [10] Crossref 2018, cited 2019 issue 58(2)); [4] exists (PubMed 33330926, Am J Clin Nutr 2021;113(4):948-959, as cited); [29], [32]-[36], [38], [41] are NCHS/USDA/NCI technical documents not indexed in Crossref; [43] Harrell RMS 2nd ed. 2015, [45] van Buuren JSS 45(3) 2011 and [49] Holm 1979 are standard and correctly cited (query hits were reviews/corrections). One garbled entry: [51] (see 15b). No fabricated reference found.
tools/check_refs.py (Crossref by DOI or bibliographic query; raw log work/verify/15_check_refs_tool.log, output work/refs_checked.json); title-similarity and year summary in 15_references.py; manual review of the 18 flagged entries; PubMed lookup for [4] (in 16_cited_claims.py)
Prior studies are cited accurately: [23] per-half-egg HR 1.13 in men and 0.86 in women, interaction P=0.01, no overall association; [3] 7% per half egg for all-cause and CVD mortality, stronger in men (P interaction 0.002); [2] 8% higher all-cause mortality per half egg
[23] (Xia et al., JAHA 2020): full text states 'a positive association was observed in men (HR, 1.13; 95% CI, 1.01-1.27), whereas an inverse association was found in women (HR, 0.86; 95% CI, 0.75-0.99; P=0.01 for interaction)', and the abstract reports no overall association (half egg HR 1.04, 0.96-1.13); matches. [3] (Zhuang et al., PLOS Med 2021): abstract HR per half egg 1.07 (1.06-1.08) all-cause and 1.07 (1.06-1.09) CVD; Table 4 men 1.08 (1.07-1.09) vs women 1.05 (1.04-1.07), P for interaction 0.002; matches. [2] (Zhong et al., JAMA 2019): abstract all-cause HR per half egg 1.08 (1.04-1.11); matches (other [2] statements: see 16b).
PubMed E-utilities: abstracts by DOI (PMIDs 32400247, 30874756, 33561122) and PMC open full texts (PMC7660855, PMC7872242); sentence and table extraction
Table 5 F, df and P values are mutually consistent and none of the six primary tests is below 0.05 after Holm adjustment
All 12 reported P values lie within the interval implied by F (e.g. H1m F=2.98 (2,151): P=0.054 obtained 0.0538; H1w 3.35: 0.038 vs 0.0377; H3a 1.92: 0.150 vs 0.1502; H4w 6.00 (1,151): 0.015 vs 0.0155; H3-linear 4.06: 0.046 vs 0.0457). Holm from rounded P: 0.270/0.228/1/1/0.600/1 vs reported 0.269/0.226/1.000/1.000/0.599/1.000 (differences <=0.002, consistent with use of unrounded P). Smallest Holm P 0.226, so the headline null result is arithmetically correct. Using df 153/123 (check 03b) changes P by <0.0002.
F survival function evaluated over the rounding interval F+-0.005 for all 12 rows; Holm step-down over the six primary P values
Table 6 Model 3 spline HRs are consistent with a 3-knot RCS (knots 0, 0.17, 1.61), with Table 5 P values and with the Table 11 interpretive-aid thresholds
In all four sex-outcome rows the four log HRs are reproduced by a 2-parameter RCS with residuals <=0.0032 (rounding tolerance 0.004-0.006); this also shows that the paper used the stated knots. Approximate Wald P: men all-cause 0.059 (reported 0.054; rounding range 0.052-0.067), women 0.041 (0.038), CVD men 0.806 (0.794), CVD women 0.771 (0.772); non-linearity women 0.018 (0.015), men 0.969 (0.976). Table 11: women CI below 1 for 0.02-1.46 (exact), UCL>1.10 from 2.14 (claimed 2.16); CVD UCL>1.10 from 0.26 men and 0.38 women (exact); men LCL>1 from 1.66 (claimed 1.62; rounding range 1.58-1.74) and UCL>1.10 from 0.36 (claimed 0.34; range 0.34-0.36). Reconstructed but unreported prespecified 1.5 eggs/day contrast: men 1.12 (0.99, 1.28), women 0.89 (0.78, 1.00). Tolerances: rounding of 2-d.p. HRs; thresholds within reconstruction range.
Least-squares fit of the two RCS coefficients to the four reported log HRs; covariance recovered from CI widths; approximate Wald tests; thresholds recomputed on the 0.02 grid; Monte Carlo over rounding of reported values
Participant flow (Figure 1), cycle sizes (Table 3 n), deaths, person-years and cause-specific death counts are derived from the public NHANES 1999-2018 files and 2019 public-use LMF as described
Every Figure 1 count reproduced exactly: 101,316 (49,893/51,423); 55,081 (26,473/28,608); 48,740 (23,508/25,232); 48,657 (23,473/25,184); 1,394 pregnant; 1,959 energy exclusions (1,379/580); 45,304 (22,094/23,210). Deaths 7,315 (4,031/3,284), PY 431,164 (207,698/223,465), 7 deaths in exam month (D3), unweighted median follow-up 9.17 y (claimed 9.2). CVD set 36,036 (17,635/18,401), CVD deaths 2,222 (1,228/994) using UCOD 001+005, heart-disease deaths 1,084/816, injury deaths 122/89, all 20 Table 3 cycle-by-sex n exact. Food-pattern-record criterion not applied (MPED/FPED not downloaded) but it excluded nobody beyond the other criteria given the exact match. Tolerance: exact integer match.
Downloaded DEMO, DRXTOT/DR1TOT, DR2TOT (10 cycles) and the 2019 public-use LMF from CDC; applied the stated rules in order (age>=20, DR1DRSTZ/DRDDRSTS=1 & WTDRD1>0, ELIGSTAT=1, RIDEXPRG=1, energy limits on mean of reliable recalls); counted MORTSTAT, UCOD_LEADING, PERMTH_EXM (death in exam month = 0.5 month)
Design degrees of freedom were 151 for the full frame and 121 for the 1999-2014 cycles
Obtained 153 (301 PSUs - 148 strata) for 1999-2018 and 123 for 1999-2014 in every variant (strata 1, 86, 90, 91, 92 have 3 PSUs), vs claimed 151 and 121. The difference of 2 df has negligible effect on F-test P values (see check 01) but indicates the stated df were not computed by the usual PSU-minus-strata rule or were adjusted without explanation.
#PSUs minus #strata (SDMVSTRA x SDMVPSU) computed from the public DEMO files for all records, dietary-weighted records, adults and the analysis set
In the 2019 public-use LMF, 2015-2018 cycles release only heart disease and malignant neoplasms as causes of death, so cerebrovascular deaths are not identifiable and the primary CVD outcome must be restricted to 1999-2014
For 2015-2016 and 2017-2018 only codes 001 (heart; 63 and 37 deaths), 002 (cancer; 67, 34) and 010 (all other; 146, 74) occur; code 005 (cerebrovascular) appears 519 times in 1999-2014 and 0 times in 2015-2018. The design choice is justified by the data. Death counts in the analysis set (7,315; CVD 2,222; heart 1,084/816; injury 122/89) reproduced exactly in check 03.
Tabulated UCOD_LEADING among deaths by cycle in the downloaded public-use LMF files
The analysis plan was frozen (2026-11-09T10:55:03Z, SHA-256 given) before any outcome data were obtained; the analysis adhered to it with 17 logged deviations
The hash is a well-formed 64-hex SHA-256 string, but there is nothing to hash it against: no plan, deviation log or code was supplied, the paper contains no URL, DOI, registry ID or repository link (0 matches; no PDF URI annotations), and Sec. 2.2 states the plan only can be deposited in a registry, i.e. it was not registered. The PDF was created 4 h 37 min after the stated freeze time (15:31:35 vs 10:55:03 UTC, same day), so the self-reported time stamp is the only evidence of temporal precedence. Adherence to the plan and the claim that all 17 deviations preceded any association estimate cannot be verified. Needed: the frozen plan file with an independently verifiable time stamp (registry deposit or trusted timestamp) and the deviation log.
Compared plan time stamp with the PDF CreationDate; checked hash format; searched text and PDF link annotations for any registry, repository or DOI; listed supplied materials
Abstract and Conclusions numbers match the tables; qualitative abstract statements are supported
All nine abstract numbers match the tables exactly (e.g. men 1.08 (0.96-1.22) and 1.17 (1.02-1.35), women 0.86 (0.76-0.97), CVD 0.99 (0.82-1.20)/0.96 (0.78-1.18), P=0.15 and 0.046, 7,315/2,222 deaths, 9.2 y). The 0.3 eggs/day statement summarises CVD thresholds 0.26 (men) and 0.38 (women) from Table 11. The difference between periods in men (1.18 vs 0.86) gives z=2.24, P approx 0.025 (independence approximation), which supports the confined-to-first-10-years description. Framing issues (not numeric errors): the abstract, Conclusions and plain-language summary ("roughly 17% higher") highlight pointwise contrasts after primary tests that were not significant (H1m P=0.054, Holm 0.269), and Sections 4.4 and 5 say one egg a day did not indicate higher hazard although the men upper limit at 1 egg/day (1.22) exceeds the prespecified 1.10 margin from 0.34 eggs/day (Table 11). Section 4.1 cites Table 8 for the linear test that is in Table 5.
Transcribed abstract values and table cells and compared them; computed a Wald z for the <=10 y vs >10 y difference in Table 10 from CI-derived SEs
Participant-flow subtractions, table sums and cross-table identities are internally consistent
All Figure 1 subtractions, Table 1/2 n and deaths (22,094/4,031; 23,210/3,284), Table 3 cycle sums (incl. 17,635/18,401 for 1999-2014 and 4,459/4,809 for 2015-2018), Table 4 deaths and PY by category for all three outcomes, Table 10 period splits (2,969+1,062=4,031 etc.) and the HR identities S17=Table 6, S22=Table 10 <=10 y, Table 15=Table 6 are exact; the PY total from rounded parts is 431,163 vs 431,164 (rounding). One unexplained difference: S3 (day-1 recall only, Table 12) lists 4,030 events in men vs 4,031 in the primary set while women (3,284) and CVD (1,228) are unchanged; re-applying the energy rule to day-1 energy would give 3,967/3,248, so the 1-death loss is not explained by the stated definition (minor).
Recomputed 60+ sums/differences and identities from transcribed counts; for S3, reconstructed the day-1-only set from the NHANES files
Weighted descriptive tables are internally coherent and the text intake summaries (mean 0.59/0.45, 99th percentiles 3.59/2.81, knots 0/0.17/1.61) agree with Table 3
Tables 1-2 are coherent: every 'All' value lies within its category range and all 96 percentage blocks sum to 100 +- 0.3. Means agree (0.59/0.45 in text, Tables 1-3). However the 99th percentiles differ: Sec. 3.1 'the 99th percentiles were 3.59 and 2.81 eggs/day' (also Sec. 2.7, Table 6 note, Table 11 range 0-3.59 / 0-2.81) vs Table 3 1999-2018 P99 3.51 (men) and 2.86 (women); differences 0.08 and 0.05, beyond rounding (tolerance 0.005). Possibly weighted vs unweighted percentiles, but the paper does not say. Since curve truncation and the 'extrapolation' label for 3 eggs/day in women rest on P99, this matters little for the conclusions (3 eggs/day exceeds both 2.81 and 2.86) (minor). Pooled median knot 0.17 is plausible (lies between sex medians 0.13 and 0.17).
Range check of each weighted 'All' column against its category values (78 rows), 96 percentage-block sums (tolerance 0.3 points), comparison of text values with the Table 3 1999-2018 rows (all transcriptions re-checked against paper.txt)
Table 15 E-values (1.30/1.00 men, 1.60/1.21 women, CVD 1.12/1.00 and 1.26/1.00) follow from the HRs at 1 egg/day using the square-root HR conversion when the outcome proportion exceeds 15%
Women all-cause (crude proportion 14.1%), CVD men (7.0%) and CVD women (5.4%) match the unconverted E-value: 1.60 obtained 1.598 (CI 1.21 vs 1.188-1.230), 1.12 vs 1.076-1.140, 1.26 vs 1.230-1.269 (tolerance: HR rounding +-0.005). Men all-cause (18.2% > 15%): reported 1.30 is NOT reproduced by the stated square-root conversion (1.241, range 1.232-1.250) nor by no conversion (1.374), but matches VanderWeele's 2017 common-outcome conversion (1.295, range 1.284-1.306). So the numbers are right under a different conversion than the footnote describes; this is a labelling error that does not affect conclusions (minor). All E-values are small (<=1.60, CI <=1.21), which supports the paper's own statement that moderate unmeasured confounding could explain the associations.
E-value = RR + sqrt(RR(RR-1)) under no conversion, sqrt(HR) and VanderWeele (2017) (1-0.5^sqrt(HR))/(1-0.5^sqrt(1/HR)) conversions, over HR +-0.005; crude outcome proportions from Tables 1-3 counts
Reference [51]: Rosner, Spiegelman, Willett, 'Correction of logistic regression relative risk estimates and confidence intervals for random within-person measurement error', Am J Epidemiol 132(4):734-745, 1990
The cited title belongs to Rosner et al. 1992, Am J Epidemiol 136(11):1400-1413 (doi 10.1093/oxfordjournals.aje.a116453), while volume 132(4):734-745, 1990 is a different paper by the same authors, '... for measurement error: the case of multiple covariates measured with error' (doi 10.1093/oxfordjournals.aje.a115715). The entry merges two papers. Both describe regression calibration, so the citation still supports the method (minor).
Crossref bibliographic queries restricted to Am J Epidemiol (ISSN 0002-9262)
[2] (six pooled US cohorts) found 8% higher cardiovascular mortality per half egg/day and a stronger association in women (P for interaction 0.001)
The abstract of [2] reports incident CVD (fatal and nonfatal), HR 1.06 (1.03-1.10) per half egg, not cardiovascular mortality of 8%; the sex interaction is not in the abstract, and the PMC record contains no body text (script output: 'contains body text: False'), so neither statement could be verified against the full text. If [2] reports only incident CVD, the Section 1 wording 'cardiovascular mortality' would misstate its outcome.
PubMed abstract of [2] (PMID 30874756); PMC record PMC6439941 checked for full body text