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二、引言（Introduction） 问题： 背景部分丰富但略显冗长。 研究空白（gap）与研...

Creato il: 22 ottobre 2025

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Domanda

manuscript.docx

二、引言（Introduction）

问题：

背景部分丰富但略显冗长。

研究空白（gap）与研究目的的过渡不够凝练。

可补充“why BAR might outperform existing markers”的逻辑。

建议修改：

缩短对BUN和Albumin机制的重复描述（减少一段生理机制文字）。

用一段简洁句式指出研究意义，如：“However, no prior study has systematically evaluated BAR as a prognostic biomarker in cardiogenic shock, a population with distinct hemodynamic and metabolic features.”

在结尾用明确目标句收尾：“This study aimed to evaluate the prognostic value of BAR for short- and long-term mortality in CS using the MIMIC-IV database.”

三、方法（Methods）

问题：

方法部分内容详尽，但存在以下问题：

语言混杂（部分中文备注应完全英文化）。

多重插补次数不一致：正文提到 m=5，前文提及 m=20。

模型描述重复：Cox模型解释出现多次。

机器学习方法部分略显长，且混入Supplementary描述。

建议修改：

统一插补次数为 m=20（与补充材料一致）。

精简机器学习描述至主要算法和验证方法，详细参数保留在Supplement。

删除中文说明句（如“仅统计 ICU 入室 24h 内的已给药/处方”）。

在统计分析小节，明确软件环境（如R 4.3.1 + packages: survival, rms, xgboost）。

补充“Ethical approval and data access statement”一句，增强规范性。

四、结果（Results）

问题：

表格、图注非常详细，但以下细节需改进：

BAR分位点范围（T1/T2/T3）未在正文中首次说明。

Figure与Table编号需与正文一致（目前有混乱，如“Figure 5”、“Figure 6”无说明）。

建议在主文中添加HR per 5-unit increase的结果，增强临床可读性。

亚组结果的Pinteraction可汇总于补充表而非主文图。

建议修改：

在Results首段补充“BAR tertiles were defined by the 33rd and 67th percentiles (T1: ≤8; T2: 9–13; T3: ≥14, units mg·g⁻¹)”。

为Figure 5–6 添加简短说明（如机器学习PR和SHAP结果）。

检查所有Figure/Table编号是否一致。

考虑合并重复的统计检验说明。

五、讨论（Discussion）

问题：

思路清晰，但篇幅偏长，逻辑层次稍显密集。

临床意义阐述较好，但对新颖性与差异性阐释不足。

局限性部分已有深度，但统计方法改进（m=20、多变量验证等）应前置至结果补充说明。

建议修改：

第一段应概括主要结果（简要英文句式：“We found that higher BAR was independently associated with increased mortality across multiple time points…”）。

第二段加强机制解释与前人研究对比（引用2–3篇BAR与危重症相关文献，如Crit Care 2023; J Clin Med 2024）。

最后一段强化展望与临床应用场景，如“future studies should validate BAR cut-offs and explore its integration with dynamic risk scoring systems.”

🧾 六、结论（Conclusion）

建议修改为英文单段：

In patients with cardiogenic shock, an elevated blood urea nitrogen-to-albumin ratio on ICU admission independently predicts both short- and long-term mortality. BAR, as a simple and accessible biomarker, may complement conventional severity scores for early risk stratification. External validation and prospective studies are warranted to define clinical cut-offs and assess incremental prognostic value.

📚 七、参考文献与格式

问题与建议：

目前正文未出现引用（[1]、[2]形式缺失）。

需统一格式（参考目标期刊要求，如 Frontiers in Cardiovascular Medicine 或 Shock）。

中文补充材料引用需转为英文标题。

八、语言与风格（Language & Style）

建议：

语气正式学术，避免混入中文句。

检查缩写（如BAR、CRRT、IMV）首次出现时加括号。

检查数字格式（如 P<0.001 统一写法，不用 P < 0.001 与 P = 0.001 混用）。

将所有表题和图题改为英文完整句。
针对上述审稿意见，帮我进行修改

Pensiero

Adapting and refining

I’m working through crafting sections for the manuscript, ensuring a consistent style and format throughout. Incorporating accurate statistical analyses and calculations to support the findings.

Refining the manuscript

I’m gathering insights on Figures labeling, refining the Methods section, and emphasizing ethical approval and data access. Additionally, I’m thinking about generic references and citations to strengthen the review.

Calculating hazard ratios

I’m calculating five-unit hazard ratios (HRs) for Model 3 across different time frames, ensuring precise statistical analysis by applying logarithmic transformations and confidence intervals.

Gathering information

I’m collecting precise measurements and corrections, updating captions, addressing inconsistencies, and planning to enhance language for clarity and readability.

Identifying key studies
I’m gathering credible sources, focusing on three 2023 publications: Scientific Reports, BMC Anesthesiology, and Frontiers Endocrinology. Progress is steady towards a thorough selection.

Aligning key sources

I selected three key journals to align BAR usage in critical care: Sci Reports 2023, BMC Anesthesiology 2023, and IJMS 2023. Avoiding over-citation, I'll ensure citation and reference formatting align with the manuscript's content.

Clarifying tertile definitions

I worked through tertile cutpoints, aligning with the 33rd and 67th percentiles, to ensure clarity and consistency throughout the manuscript.

Ensuring consistent citations

I’m aligning all factual sources with "web.run" citations. Per-5-unit HR results are meticulously calculated and formatted to three decimal places for clarity.

Reasoned for 12m 51s

Risposta

下面给出可直接替换进稿件的英文修订文本（按审稿意见逐条落实），并附上需要在版式与引用上统一的“办理清单”。所有数值与模型设置均与您当前稿件一致，仅在措辞、结构和一致性上优化；个别新增句子给出合理引用建议与图表说明。文内涉及您稿件中数据与结果处已标注来源。(manuscript.docx)

2. Introduction（重写版）

Cardiogenic shock (CS) remains a major challenge in acute cardiovascular care, with persistently high mortality despite advances in pharmacologic therapy and mechanical circulatory support. There is a pressing need for simple, readily available biomarkers to aid early risk stratification at the bedside. The blood urea nitrogen‑to‑albumin ratio (BAR) has recently emerged as a composite indicator that integrates renal perfusion/neurohormonal stress (urea) and systemic inflammation/nutritional status (albumin), two pathophysiologic axes that are highly pertinent in shock states. Compared with single markers, BAR may better capture the combined burden of pre‑renal azotemia, catabolic drive, capillary leak, and hepatic synthetic down‑regulation, thereby offering additive prognostic information over conventional laboratory values and scores. Evidence from diverse critically ill populations supports the prognostic utility of BAR, including sepsis and surgical ICU cohorts, and albumin‑based indices in heart failure, but its performance in well‑defined CS populations has been underexplored. (Nature)

However, no prior study has systematically evaluated BAR as a prognostic biomarker in cardiogenic shock, a population with distinct hemodynamic and metabolic features. Contemporary CS reviews highlight the unmet need for pragmatic biomarkers that complement lactate and organ‑injury indices, underscoring the potential role of simple composite measures such as BAR. (SpringerOpen)

This study aimed to evaluate the prognostic value of BAR for short‑ and long‑term mortality in CS using the MIMIC‑IV database. (manuscript.docx)

改动说明：压缩了BUN/Albumin生理机制冗长描述；加入“why BAR might outperform existing markers”的逻辑；用两句英文分别完成“研究空白”和“研究目的”的承接。

3. Methods（精简与统一版）

Study Design and Data Source

We conducted a retrospective cohort study using MIMIC‑IV v3.1, a publicly available ICU database from Beth Israel Deaconess Medical Center (2008–2019). The database contains de‑identified data and is approved by the BIDMC IRB with a waiver of informed consent. The current analysis was conducted under certification number 13968729 and follows STROBE guidelines. (manuscript.docx)

Participants

Adults (≥18 years) with CS within 24 hours of ICU admission were identified by ICD‑9/10 codes. For patients with multiple ICU admissions, only the first ICU stay in the index hospitalization was included. Exclusion criteria were ICU length of stay <24 h and missing first‑day BUN, albumin, height, or weight. A total of 1,011 patients were included (Figure 1). (manuscript.docx)

Exposure

The index time was ICU admission. BAR was calculated as BUN (mg/dL) divided by albumin (g/dL) using the earliest measurement within the first 24 hours. BAR was modeled continuously (nonlinearity assessed) and categorically by tertiles. Units were harmonized a priori. (manuscript.docx)

Outcomes

The primary outcome was 30‑day all‑cause mortality. Secondary outcomes included 60‑, 120‑, and 365‑day mortality. Time zero was ICU admission; survivors were censored at last record. (manuscript.docx)

Covariates

Baseline covariates (first 24 h only) included demographics, illness‑severity scores (SOFA, SAPS II), comorbidities, vital signs, laboratory tests, and early ICU interventions (vasopressors, IMV, CRRT, antithrombotic and cardiovascular medications). Definitions, code lists, units, and plausibility ranges are provided in Supplementary Table S1. All Chinese remarks were removed. (manuscript.docx)

Data Pre‑processing and Missing Data

Variables with >20% missingness were excluded from primary multivariable models; variables with ≤20% missingness underwent multiple imputation by chained equations (m = 20; predictive mean matching for continuous, logistic for binary, polytomous for categorical). The imputation model included exposure, outcomes, and all baseline covariates; estimates were pooled using Rubin’s rules. Complete‑case analyses were performed as sensitivity tests. All preprocessing steps for machine‑learning analyses were performed within each resampling fold to prevent information leakage. (manuscript.docx)

Statistical Analysis

Continuous variables were summarized as median (IQR) and compared with Kruskal–Wallis; categorical variables as n (%) with χ²/Fisher tests. Time‑to‑event analyses used Kaplan–Meier/log‑rank and Cox models at 30, 60, 120, and 365 days. We specified three hierarchical models: (1) unadjusted; (2) +demographics; (3) fully adjusted for a priori clinical covariates measured within 24 h. Proportional‑hazards assumptions were checked via Schoenfeld residuals; nonlinearity was evaluated with restricted cubic splines. Prespecified subgroup/interaction and sensitivity analyses were conducted. Two‑sided α=0.05. (manuscript.docx)

Secondary (Exploratory) Machine‑Learning Analysis

As an internally validated exploratory analysis for 30‑day mortality, we trained gradient‑boosted trees (XGBoost), random forests, and regularized logistic regression on the same candidate features. Boruta was used for feature screening; hyperparameters were tuned via cross‑validated grid search. Model performance was summarized by precision–recall curves (average precision) and decision‑curve analysis; model explainability used SHAP. Detailed algorithms, tuning grids, and full results are reported in the Supplement. (manuscript.docx)

Software and Reproducibility

All analyses were performed in R 4.3.1 with packages including survival, rms, mice, xgboost, Boruta, pROC, and rmda. Code lists and analysis scripts are available upon reasonable request. (manuscript.docx)

Ethical Approval and Data Access Statement

Access to MIMIC‑IV requires completion of the PhysioNet credentialing process; all data are de‑identified. Institutional review approval for the MIMIC program was obtained by BIDMC, and the present analysis was performed under certification 13968729. (manuscript.docx)

改动说明：
• 将插补次数统一为 m=20；删除重复的Cox模型解释与中文备注；精简ML段落至算法与验证方法，其余移补充材料；补充软件环境与伦理合规一句。(manuscript.docx)

4. Results（关键增补与编号修正）

Add at the start of Results:
“BAR tertiles were defined by the 33rd and 67th percentiles of the cohort distribution (T1: ≤8; T2: 9–13; T3: ≥14; units mg·g⁻¹).” Please verify cut‑points against your analytic quantiles and update if needed. (manuscript.docx)

30‑day Mortality (Model 3, fully adjusted):

  • Per 1‑unit BAR increase: HR 1.026 (95% CI 1.011–1.041).
  • Per 5‑unit BAR increase (added for clinical readability): HR 1.137 (95% CI 1.056–1.223).
  • T3 vs T1: HR 1.80 (95% CI 1.26–2.58).
    Results were directionally consistent at 60, 120, and 365 days; the continuous effect per 5 units was 1.142 (95% CI 1.067–1.223) at 60/120 days and 1.137 (95% CI 1.067–1.217) at 365 days. (manuscript.docx)

Figure/Table numbering (harmonized across text):

  • Figure 1: Flowchart.
  • Figure 2: Kaplan–Meier curves by BAR tertile (30/60/120/365 d).
  • Figure 3: Restricted cubic spline (RCS) for BAR vs mortality (30/60/120/365 d).
  • Figure 4: Subgroup analyses for 30‑day mortality (note: move P<sub>interaction</sub> values to Supplementary Table Sx).
  • Figure 5 (new caption): Precision–recall curves for eight internally validated machine‑learning algorithms predicting 30‑day mortality; average precision (AP) reported for each model.
  • Figure 6 (new caption): Global SHAP summary plot for the best‑performing model, illustrating feature importance; BAR ranks among top contributors consistent with Cox model direction and magnitude.
  • Table 1: Baseline characteristics by BAR tertile（与注释一致）
  • Table 2: Cox models at all time points（新增每+5 unit栏，或在注释中说明等价换算）
    （请检查所有文中交叉引用与“Figure 5/6”处是否出现“无说明”的遗留。）(manuscript.docx)

改动说明：在首段定义BAR三分位范围；加入“per 5‑unit”HR；补充Figure 5–6简短说明；建议将P<sub>interaction</sub>整体汇总至补充表而非主文图。(manuscript.docx)

5. Discussion（重构与压缩版）

Principal findings. In a cohort of 1,011 CS patients from MIMIC‑IV, higher BAR measured within 24 hours of ICU admission was independently associated with increased short‑ and long‑term mortality. The association was approximately linear across the observed BAR range, robust to multivariable adjustment and sensitivity analyses, and consistent across prespecified subgroups. Machine‑learning models supported these findings by highlighting BAR among high‑impact predictors and demonstrating discrimination and net clinical benefit in decision‑curve analyses. (manuscript.docx)

Context and mechanisms. BAR integrates complementary biological domains—pre‑renal azotemia/neurohormonal activation (BUN) and inflammation‑nutrition axis (albumin)—that are particularly relevant in the low‑output, high‑sympathetic CS milieu. Prior studies in critically ill populations (e.g., sepsis, surgical ICU) and albumin‑based indices in cardiovascular disease have shown that BAR, or related albumin‑based ratios, predicts mortality beyond individual components, aligning with our results in CS. (Nature) Contemporary CS reviews emphasize the need for pragmatic, cost‑effective biomarkers to complement lactate and organ‑injury markers; our findings suggest BAR may fulfill part of this role. (SpringerOpen)

Clinical implications. Because BAR is simple, inexpensive, and available from routine labs on admission, it could complement severity scores (e.g., SOFA, SAPS II) to support early risk stratification and monitoring. The per‑5‑unit effect size (~14% relative increase in 30‑day risk) provides an intuitive increment for bedside interpretation and could be incorporated into dynamic risk scores. (manuscript.docx)

Limitations. This is a single‑center, retrospective analysis subject to residual confounding and potential misclassification based on ICD coding. Although we used MICE with m = 20 and restricted covariates to the first 24 h to limit immortal‑time bias, some variables had substantial missingness and BAR was assessed at a single time point, precluding trajectory analyses. The machine‑learning results were internally validated only; external validation and reclassification metrics (e.g., ΔC‑index, IDI/NRI) are needed. (manuscript.docx)

Future directions. Prospective, multicenter studies should validate BAR cut‑offs, test its incremental value over established risk scores, and evaluate whether serial BAR dynamics enhance prognostication or guide therapy in CS.

改动说明：开头用一句英文概括主要结果；第二段加强机制与前人研究对比并给出2–3条核心参考；末段突出应用前景与前瞻验证需求。(manuscript.docx)

6. Conclusion（按建议改写为英文单段）

In patients with cardiogenic shock, an elevated blood urea nitrogen‑to‑albumin ratio on ICU admission independently predicts both short‑ and long‑term mortality. BAR, as a simple and accessible biomarker, may complement conventional severity scores for early risk stratification. External validation and prospective studies are warranted to define clinical cut‑offs and assess incremental prognostic value. (manuscript.docx)

7. References & Formatting（执行要点）

  • 在正文中加入标准顺序编号引用（如 “[1]…[2]…”），并在参考文献表按目标期刊（Frontiers in Cardiovascular Medicine 或 Shock）要求统一格式。

  • 建议可选重点引用（可作为Discussion第二段的2–3条核心文献）：

    1. Wang Y, et al. Prognostic impact of blood urea nitrogen to albumin ratio on patients with sepsis: a retrospective cohort study. Sci Rep. 2023;13:10013.（BAR在脓毒症的预后价值） (Nature)
    2. Liu Y, et al. Relationship between BUN‑to‑albumin ratio and short‑term mortality among SICU patients. BMC Anesthesiol. 2023;23:…（SICU人群的BAR） (BioMed Central)
    3. Liu Y, et al. Prognostic value of albumin‑based indices (including BAR) for mortality after heart failure: a systematic review and meta‑analysis. BMC Cardiovasc Disord. 2024;24:…（心衰相关证据，含BAR） (BioMed Central)
    4. Review（用于背景/新颖性）：Biomarkers in cardiogenic shock: old pals, new friends. Ann Intensive Care. 2024;…（CS生物标志物综述） (SpringerOpen)

    以上为可选组合，正文中使用2–3条即可。请按期刊格式完善作者、卷页码等细目。

  • 中文补充材料标题与引用：将中文标题统一为英文标题；Supplementary的图表（e.g., Figures S1–S6, Tables S1–S6）用英文完整句式题目。

8. Language & Style（统一规范清单）

  • 全英文化：删除所有中文备注（例如“仅统计 ICU 入室 24h 内的已给药/处方”）。已在方法学段落改写。(manuscript.docx)
  • 缩写：首处给出全称+缩写（例如 blood urea nitrogen‑to‑albumin ratio [BAR]、continuous renal replacement therapy [CRRT]、invasive mechanical ventilation [IMV]）。
  • P值格式：统一为 P<0.001、P=0.001 等（不混用“P < 0.001”与“P=0.001”的空格风格）。
  • 单位与符号：BAR统一写作 mg·g⁻¹；指数与连字符用不间断连接（e.g., ICU‑admission）。
  • 图表题与图注：全部改为英文完整句；在正文首次引用处即说明BAR分位点定义；将所有Figure/Table编号与正文一一对应。
  • 统计学说明：在主文减少重复（例如Cox模型与分布检验只陈述一次），其余放入Supplement。
  • 表格：在Table 2中新增“HR per +5‑unit BAR”一列（或在表注中给出等价换算公式），提高临床可读性。
  • 机器学习：主文仅保留核心算法与验证方法；DCA/PR/SHAP的细节与完整曲线置于Supplement，主文对应Figure 5–6给出简明说明。

附：可直接粘贴到您对应章节的新增/替换句子

  • Results第一段（新增两句）
    “BAR tertiles were defined by the 33rd and 67th percentiles (T1: ≤8; T2: 9–13; T3: ≥14; units mg·g⁻¹). Across tertiles, 30‑day mortality increased stepwise (log‑rank P<0.001; Figure 2).” (manuscript.docx)

  • Results中“per‑5‑unit”效果量（新增）
    “In fully adjusted models, each 5‑unit increase in BAR was associated with a 13–14% relative increase in mortality risk: 30 days HR 1.137 (95% CI 1.056–1.223), 60/120 days HR 1.142 (95% CI 1.067–1.223), and 365 days HR 1.137 (95% CI 1.067–1.217).” (manuscript.docx)

  • Figures 5–6 图题（替换）
    Figure 5. Precision–recall curves and average precision for eight internally validated machine‑learning algorithms predicting 30‑day mortality.
    Figure 6. Global SHAP summary plot for the best‑performing model, showing feature contributions; BAR ranks among the top predictors.

变更对照（您可在稿件中按以下动作执行）

  1. Introduction：保留第一段前两句；合并生理机制为1段；加入“研究空白+目的”两句（已提供）。
  2. Methods：
    • 将“m=5”统一改为“m=20”，并确保Supplement一致；
    • 删除重复的Cox描述与中文句；
    • ML段落精简，详参Supplement；
    • 在统计分析末尾添加软件与版本；
    • 添加伦理与数据访问声明。(manuscript.docx)
  3. Results：
    • 首段补充BAR三分位定义与单位；
    • Table 2增加“per +5‑unit”列或在表注写明换算；
    • 将P<sub>interaction</sub>的汇总移至Supplement；
    • 核对并统一Figure/Table编号及在文内的首次说明。
  4. Discussion：按“主要结果—机制/对比—临床意义—局限—展望”结构重排，控制长度。
  5. Conclusion：替换为单段英文版（已提供）。
  6. References：在正文中插入编号引用；参考表按目标期刊模板统一；中文补充材料标题改英。

如需，我也可以在您确认三分位确切阈值后，生成一份已整合“per‑5‑unit”列并修正图表题/编号的干净版主文，以便直接提交。当前文本已与您提供的数据和模型严格对齐，关键效应量（例如30‑天每+5 unit HR≈1.137）来自您现有的完全校正模型结果。(manuscript.docx)

参考用于背景/对比的外部文献（可选加入）：

  • BAR与重症结局：Sci Rep 2023（脓毒症）、BMC Anesthesiol 2023（SICU）。(Nature)
  • 心血管领域的白蛋白基复合指标：BMC Cardiovasc Disord 2024（含BAR的荟萃分析）。(BioMed Central)
  • CS生物标志物综述（背景与新颖性定位）：Ann Intensive Care 2024；Eur J Heart Fail 2024。(SpringerOpen)

注：若您最终采用目标期刊为 Frontiers in Cardiovascular Medicine 或 Shock，请将参考文献样式改为其“Numerical Vancouver”或期刊指定风格（例如“doi与PMID是否必填”“作者>6人用et al.”等）。

Domanda

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这句话需要加上吗

Pensiero

Evaluating inclusion

I'm figuring out if a specific sentence should be added to the manuscript, considering journal norms, statistical justification, and potential issues like sample size justification or avoiding post-hoc power analysis.

Clarifying manuscript guidelines

I’m mapping out whether to include citations for citing manuscripts, focusing on STROBE guidelines without implying the necessity of a file cite in responses to specific image questions.

Refining the manuscript

I'm ensuring the manuscript includes a neutral statement about sample size in the Methods and framing "exploratory topic" in the Discussion Limitations, emphasizing adherence to STROBE guidelines.

Clarifying manuscript guidelines

I'm advising against including the sentence about not having a pre-specified analysis plan in the manuscript, as it contradicts the Methods section. I suggest placing the neutral statement about sample size in the Methods and framing "exploratory topic" in the Discussion Limitations.

Reasoned for 4m 2s

Risposta

结论：不建议把这句原样加入。
原因有三：

  1. 你在 Methods 里已写“prespecified/预设”的模型与亚组（hierarchical Cox、RCS、prespecified subgroups），如果再写“we did not develop a pre‑specified statistical analysis plan”会与现有表述相冲突，引出“数据驱动分析”的质疑。(manuscript.docx)
  2. STROBE 对回顾性研究并不要求必须有预注册或功效学计算，但要求说明样本量如何确定。直接承认“没有SAP和power”用语过于负面，容易被审稿人抓住。
  3. 对于数据库回顾性研究，更规范的做法是：说明样本量由可用病例决定、未做先验样本量估计，并强调报告效应量和95%CI（而非事后功效）。

建议替代写法（可直接粘贴）

Methods → Statistical analysis / Study size（首选）

Study size. All consecutive, eligible ICU admissions meeting the inclusion criteria were included; thus the study size was determined by data availability in MIMIC‑IV, and no a priori sample‑size calculation was performed. We focus on effect estimates with 95% confidence intervals to convey precision.

Discussion → Limitations（可选补充，强调探索性）

Given the retrospective, single‑center nature of this database study, analyses—particularly subgroup and machine‑learning findings—should be interpreted as exploratory and hypothesis‑generating.

若编辑明确要求披露“未预注册/未制定SAP”时，再采用更温和表述（放在 Limitations，而非 Methods）

This study was not preregistered and no formal statistical analysis plan was lodged in advance; however, the primary outcome (30‑day mortality), exposure (BAR), key covariates, and the modeling strategy (hierarchical Cox models with prespecified adjustments, spline assessment, and predefined subgroups) were determined before model fitting, with details provided in the Supplement.

放置位置与一致性检查

  • 把“Study size”一句放在 Methods 末段的统计学小节；保持与你已写的 R 版本与包列表同一小节风格。(manuscript.docx)
  • 在 Discussion–Limitations 中加入“exploratory/hypothesis‑generating”的温和说明即可，无需在 Methods 里写“did not develop a pre‑specified SAP”。
  • 避免与文中“prespecified models/subgroups”的措辞冲突；保持术语前后一致。(manuscript.docx)

如需，我可以把以上句子直接嵌入你稿件相应段落并检查前后措辞一致性。

Domanda

可是我进行分析时没有预设模型，机器学习只是印证bar的价值

Pensiero

Refining language

I'm editing methods section to avoid "prespecified" models, replacing with "planned" or "defined using clinical judgement" to ensure transparency and accuracy.

Crafting precise citations

I'm aligning with the file_search requirements for citations and ensuring statistical analysis and sample size references are accurately indicated with the special marker.

Refining clarity

I’m updating the manuscript to reflect the exploratory nature of the study, ensuring terms like "prespecified" are replaced with "predefined" or "planned," and providing recommended text adjustments.

Refining terminology

I’m updating the manuscript to reflect the study's exploratory nature, ensuring terms like "prespecified" are replaced with "exploratory" or "defined by quantiles," and addressing limitations and machine-learning disclaimers.

Reasoned for 11m 24s

Risposta

完全可以如实说明未预设模型；关键是怎么写，既透明又不自我“矮化”。下面给你一套可直接粘贴到稿件里的英文改写，同时把文中所有“prespecified”相关表述统一为“exploratory/报告用的调整集”。你当前稿件多处出现“prespecified subgroup/interaction”“three hierarchical models were prespecified”等措辞，和你现在的实际情况会产生矛盾，建议按下述文字替换。(manuscript.docx)

A. Methods 中的改写（直接替换/新增）

Statistical analysis（段首新增 3–4 句）

Analytic stance. This was an exploratory observational analysis. The study was not preregistered, and a formal statistical analysis plan was not lodged in advance. The cohort size was determined by the available cases in MIMIC‑IV; therefore no a priori sample‑size calculation was performed. We emphasize effect estimates with 95% confidence intervals rather than post‑hoc power calculations.

Modeling framework. We report results from three hierarchical adjustment sets to provide a transparent view of confounding control (unadjusted; +demographics; fully adjusted for clinically relevant covariates available within 24 h). These adjustment sets were determined during the analysis based on clinical reasoning, data availability, and model diagnostics, and are intended to standardize reporting rather than to reflect a preregistered plan.

Subgroups and sensitivity analyses. Subgroup and interaction analyses were exploratory and guided by clinical plausibility. Sensitivity analyses (alternative codings, complete‑case models, extreme‑value trimming) were likewise exploratory.

Machine‑learning analysis. The machine‑learning component (regularized logistic regression, random forest, gradient‑boosted trees) was designed solely as an internally validated robustness check to corroborate the association between BAR and mortality. It was not used for variable selection in the Cox models; details and tuning grids are provided in the Supplement.

Software. Analyses were performed in R 4.3.1 (packages: survival, rms, mice, xgboost, Boruta, pROC, rmda).

Missing data. Variables with ≤20% missingness were imputed with MICE (m = 20) and pooled via Rubin’s rules; variables with >20% missingness were excluded from the primary multivariable models and considered in sensitivity analyses.

Study size. All eligible ICU admissions were included; the sample size was therefore fixed by database availability.

(保留原有技术细节) Proportional‑hazards assumptions, restricted cubic splines, and model diagnostics按你原文写法继续，但删去“prespecified”的字样。

把文中这些字眼统一替换：

  • “prespecified tertiles” → “tertiles defined by the 33rd and 67th percentiles (…units mg·g⁻¹)”
  • “prespecified subgroup/interaction analyses” → “exploratory subgroup and interaction analyses”
  • “three hierarchical models were prespecified” → “we report three hierarchical adjustment sets” (manuscript.docx)

B. Discussion → Limitations 中新增 2–3 句（如实但不负面）

This study was not preregistered and the exact adjustment sets evolved during analysis; consequently, subgroup and machine‑learning findings should be regarded as exploratory and hypothesis‑generating. The cohort size was fixed by data availability, and we did not perform a priori sample‑size estimation; we therefore focus on effect estimates and 95% CIs to convey precision. External validation is needed to assess generalizability.

C. 给审稿人的“回复模板”句（Response to reviewers）

Comment: “Please clarify whether the models/subgroups were prespecified and why no statistical analysis plan or power calculation was provided.”
Response: We appreciate the comment. This work was conceived as an exploratory database study. The primary exposure (BAR) and mortality time points were defined at study outset; however, the exact adjustment sets and subgroup contrasts were not preregistered and were finalized during analysis to balance clinical plausibility, data availability, and model diagnostics. We have revised the Methods to remove “prespecified” language and to state explicitly that the machine‑learning component was used only as an internally validated robustness check rather than for model building. We also added a Study size statement explaining that the cohort size was determined by database availability and that we focus on effect sizes with 95% CIs rather than post‑hoc power. The revised text appears in Methods and Limitations.

D. 你稿件中需要同步的小改动清单

  1. 全文删除或替换“prespecified / prespecify”相关措辞为“exploratory/reporting adjustment sets”。(manuscript.docx)
  2. Methods 的 “缺失数据插补次数” 统一为 m = 20（Supplement 亦同步）。(manuscript.docx)
  3. 机器学习段首句加入“exploratory robustness check / not for variable selection”，并把详细参数留在补充材料。(manuscript.docx)
  4. 在 Results 首段保留你已写的主要效应量（含 per‑5‑unit HR），无需改动统计结论。(manuscript.docx)

一句话总结

你可以也应该如实说明“未预设模型、ML仅作印证”，但最好用上面这种中性、规范的写法：把“未预注册/未设SAP/样本量由数据库决定”放到 Methods 的“Analytic stance/Study size”与 Discussion 的“Limitations”，同时把正文里所有“prespecified”改成“exploratory/报告用的调整集”。这样既避免与现稿矛盾，又满足透明度和审稿规范要求。

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