bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of moderator by confounder interactions in the assessment of treatment effect modification: a simulation study
Authors: Marsden Antonia Mary , Dixon William G. , Dunn Graham , Emsley Richard 
Published: April 2022

Abstract
Background
When performed in an observational setting, treatment effect modification analyses should account for all confounding, where possible. Often, such studies only consider confounding between the exposure and outcome. However, there is scope for misspecification of the confounding adjustment when estimating moderation as the effects of the confounders may themselves be influenced by the moderator. The aim of this study was to investigate bias in estimates of treatment effect modification resulting from failure to account for an interaction between a binary moderator and a confounder on either treatment receipt or the outcome, and to assess the performance of different approaches to account for such interactions.

Methods
The theory behind the reason for bias and factors that impact the magnitude of bias is explained. Monte Carlo simulations were used to assess the performance of different propensity scores adjustment methods and regression adjustment where the adjustment 1) did not account for any moderator-confounder interactions, 2) included moderator-confounder interactions, and 3) was estimated separately in each moderator subgroup. A real-world observational dataset was used to demonstrate this issue.

Results
Regression adjustment and propensity score covariate adjustment were sensitive to the presence of moderator-confounder interactions on outcome, whilst propensity score weighting and matching were more sensitive to the presence of moderator-confounder interactions on treatment receipt. Including the relevant moderator-confounder interactions in the propensity score (for methods using this) or the outcome model (for regression adjustment) rectified this for all methods except propensity score covariate adjustment. For the latter, subgroup-specific propensity scores were required. Analysis of the real-world dataset showed that accounting for a moderator-confounder interaction can change the estimate of effect modification.

Conclusions
When estimating treatment effect modification whilst adjusting for confounders, moderator-confounder interactions on outcome or treatment receipt should be accounted for.
Methodology and experiences of rapid advice guideline development for children with COVID-19: responding to the COVID-19 outbreak quickly and efficiently
Authors: Zhou Qi , Li Qinyuan , Estill Janne , Wang Qi , Wang Zijun , Shi Qianling , Zhang Jingyi , Zhang Xiaobo , Mathew Joseph L. , Smyth Rosalind L. , Nurdiati Detty , Fu Zhou , Xu Hongmei , Zheng Xianlan , Zhao Xiaodong , Lu Quan , Liu Hui , Xun Yangqin , Li Weiguo , Yang Shu , Feng Xixi , Wang Mengshu , Lei Junqiang , Luo Xiaoping , Wu Liqun , Lu Xiaoxia , Lee Myeong Soo , Zhao Shunying , Chan Edwin Shih-Yen , Qian Yuan , Tu Wenwei , Dong Xiaoyan , Li Guobao , Zhao Ruiqiu , He Zhihui , Zhao Siya , Liu Xiao , Li Qiu , Yang Kehu , Luo Zhengxiu , Liu Enmei , Chen Yaolong 
Published: April 2022

Abstract
Background
Rapid Advice Guidelines (RAG) provide decision makers with guidance to respond to public health emergencies by developing evidence-based recommendations in a short period of time with a scientific and standardized approach. However, the experience from the development process of a RAG has so far not been systematically summarized. Therefore, our working group will take the experience of the development of the RAG for children with COVID-19 as an example to systematically explore the methodology, advantages, and challenges in the development of the RAG. We shall propose suggestions and reflections for future research, in order to provide a more detailed reference for future development of RAGs.

Result
The development of the RAG by a group of 67 researchers from 11 countries took 50 days from the official commencement of the work (January 28, 2020) to submission (March 17, 2020). A total of 21 meetings were held with a total duration of 48 h (average 2.3 h per meeting) and an average of 16.5 participants attending. Only two of the ten recommendations were fully supported by direct evidence for COVID-19, three recommendations were supported by indirect evidence only, and the proportion of COVID-19 studies among the body of evidence in the remaining five recommendations ranged between 10 and 83%. Six of the ten recommendations used COVID-19 preprints as evidence support, and up to 50% of the studies with direct evidence on COVID-19 were preprints.

Conclusions
In order to respond to public health emergencies, the development of RAG also requires a clear and transparent formulation process, usually using a large amount of indirect and non-peer-reviewed evidence to support the formation of recommendations. Strict following of the WHO RAG handbook does not only enhance the transparency and clarity of the guideline, but also can speed up the guideline development process, thereby saving time and labor costs.
KMSubtraction: reconstruction of unreported subgroup survival data utilizing published Kaplan-Meier survival curves
Authors: Zhao Joseph J. , Syn Nicholas L. , Tan Benjamin Kye Jyn , Yap Dominic Wei Ting , Teo Chong Boon , Chan Yiong Huak , Sundar Raghav 
Published: April 2022

Abstract
Background
Data from certain subgroups of clinical interest may not be presented in primary manuscripts or conference abstract presentations. In an effort to enable secondary data analyses, we propose a workflow to retrieve unreported subgroup survival data from published Kaplan-Meier (KM) plots.

Methods
We developed KMSubtraction, an R-package that retrieves patients from unreported subgroups by matching participants on KM plots of the overall cohort to participants on KM plots of a known subgroup with follow-up time. By excluding matched patients, the opposing unreported subgroup may be retrieved. Reproducibility and limits of error of the KMSubtraction workflow were assessed by comparing unmatched patients against the original survival data of subgroups from published datasets and simulations. Monte Carlo simulations were utilized to evaluate the limits of error of KMSubtraction.

Results
The validation exercise found no material systematic error and demonstrates the robustness of KMSubtraction in deriving unreported subgroup survival data. Limits of error were small and negligible on marginal Cox proportional hazard models comparing reconstructed and original survival data of unreported subgroups. Extensive Monte Carlo simulations demonstrate that datasets with high reported subgroup proportion (r = 0.467, p < 0.001), small dataset size (r = − 0.374, p < 0.001) and high proportion of missing data in the unreported subgroup (r = 0.553, p < 0.001) were associated with uncertainty are likely to yield high limits of error with KMSubtraction.

Conclusion
KMSubtraction demonstrates robustness in deriving survival data from unreported subgroups. The limits of error of KMSubtraction derived from converged Monte Carlo simulations may guide the interpretation of reconstructed survival data of unreported subgroups.
Moving towards a single-frame cell phone design in random digit dialing surveys: considerations from a French general population health survey
Authors: Soullier Noémie , Legleye Stéphane , Richard Jean-Baptiste 
Published: April 2022

AbstractBackgroundOver the last two decades, telephone surveys based on random digit dialing have developed considerably. At the same time, however, the proportion of the population with a cell phone has increased, whereas landline frame coverage has declined, thus raising the possibility of discontinuing landline phone surveys. This paper aims to assess the impact of using a single-frame (SF) cell phone design instead of a dual-frame (DF) design with landlines and cell phones in the context of repeated health surveillance surveys in the general population. We analyze data from a random digit dialing health survey of the French population and assess differences between the DF and the counterfactual SF design that excludes the landline phone sample from the DF design. We evaluate the quality of the two survey designs in terms of survey productivity, response rates, representativeness, balancing of external covariates, and prevalence estimates of key health behavior indicators.ResultsOur results show that a SF cell phone survey has several advantages over a combined DF landline and cell phone survey. Cell numbers require fewer call attempts to complete an interview, leading to a substantial reduction in the mean data collection duration and weight dispersion. The global representativeness of the SF design was slightly better than its DF counterpart, although the elderly were underrepresented. After calibration, differences in health behavior estimates were small for the seven health indicators analyzed.ConclusionsSwitching from a DF random telephone survey to a SF cell phone design has a number of practical advantages and would have a minimal impact on general population health surveys for monitoring health behavior at the population level. However, the different aspects of the survey quality had to be studied to make a decision. Further studies are needed to explore the scope of possibilities.
Bayesian variable selection and survival modeling: assessing the Most important comorbidities that impact lung and colorectal cancer survival in Spain
Authors: Rubio Francisco Javier , Alvares Danilo , Redondo-Sanchez Daniel , Marcos-Gragera Rafael , Sánchez María-José , Luque-Fernandez Miguel Angel 
Published: April 2022

AbstractCancer survival represents one of the main indicators of interest in cancer epidemiology. However, the survival of cancer patients can be affected by several factors, such as comorbidities, that may interact with the cancer biology. Moreover, it is interesting to understand how different cancer sites and tumour stages are affected by different comorbidities. Identifying the comorbidities that affect cancer survival is thus of interest as it can be used to identify factors driving the survival of cancer patients. This information can also be used to identify vulnerable groups of patients with comorbidities that may lead to worst prognosis of cancer. We address these questions and propose a principled selection and evaluation of the effect of comorbidities on the overall survival of cancer patients. In the first step, we apply a Bayesian variable selection method that can be used to identify the comorbidities that predict overall survival. In the second step, we build a general Bayesian survival model that accounts for time-varying effects. In the third step, we derive several posterior predictive measures to quantify the effect of individual comorbidities on the population overall survival. We present applications to data on lung and colorectal cancers from two Spanish population-based cancer registries. The proposed methodology is implemented with a combination of the R-packages and . We provide the code for reproducibility at https://github.com/migariane/BayesVarImpComorbiCancer.
Development and validation of a nomogram for prediction of cervical lymph node metastasis in middle and lower thoracic esophageal squamous cell carcinoma
Authors: Yan Zhaoyang , Xu Xinjian , Lu Juntao , You Yang , Xu Jinsheng , Xu Tongxin 
Published: April 2022

Abstract
Background
Estimates of cervical lymph node (LN) metastasis in patients with middle and lower thoracic esophageal squamous cell carcinoma (ESCC) are important. A nomogram is a useful tool for individualized prediction.

Methods
A total of 235 patients were enrolled in this study. Univariate and multivariate analyses were performed to screen for independent risk factors and construct a nomogram to predict the risk of cervical LN metastasis. The nomogram performance was assessed by discrimination, calibration, and clinical use.

Results
Totally, four independent predictors, including the maximum diameter of tumor, paraesophageal lymph node status, recurrent laryngeal nerve lymph node status, and the CT-reported cervical LN status, were enrolled in the nomogram. The AUC of the nomogram model in the training and validation dataset were 0.833 (95% CI 0.762–0.905), 0.808 (95% CI 0.696–0.920), respectively. The calibration curve demonstrated a strong consistency between nomogram and clinical findings in predicting cervical LN metastasis. Decision curve analysis demonstrated that the nomogram was clinically useful.

Conclusion
We developed a nomogram that could be conveniently used to predict the individualized risk of cervical LN metastasis in patients with middle and lower thoracic ESCC.
Whole blood GBP5 protein levels in patients with and without active tuberculosis
Authors: Yao Xiangyang , Liu Wei , Li Xiaofei , Deng Chenxi , Li Tingdong , Zhong Zhouyue , Chen Shuping , Ge Zhitan , Zhang Xuejie , Zhang Shiyin , Wang Yingbin , Liu Yongliang , Zheng Chao , Ge Shengxiang , Xia Ningshao 
Published: April 2022

Abstract
Background
The host blood transcriptional levels of several genes, such as guanylate binding protein 5 (GBP5), have been reported as potential biomarkers for active tuberculosis (aTB) diagnosis. The aim of this study was to investigate whole blood GBP5 protein levels in aTB and non-tuberculosis patients.

Methods
An in-house immunoassay for testing GBP5 protein levels in whole blood was developed, and suspected aTB patients were recruited. Whole blood samples were collected and tested at enrolment using interferon-gamma release assay (IGRA) and the GBP5 assay.

Results
A total of 470 participants were enrolled, and 232 and 238 patients were finally diagnosed with aTB and non-TB, respectively. The GBP5 protein levels of aTB patients were significantly higher than those of non-tuberculosis patients (p < 0.001), and the area under the ROC curve of the GBP5 assay for aTB diagnosis was 0.76. The reactivity of the GBP5 assay between pulmonary and extrapulmonary tuberculosis patients was comparable (p = 0.661). With the optimal cut-off value, the sensitivity and specificity of the GBP5 assay for diagnosing aTB were 78.02 and 66.81%, respectively, while those of IGRA were 77.59 and 76.47%. The combination of the GBP5 assay and IGRA results in 88.52% accuracy for diagnosing aTB in 63.83% of suspected patients with a positive predictive value of 89.57% and a negative predictive value of 87.59%.

Conclusions
Whole blood GBP5 protein is a valuable biomarker for diagnosing of aTB. This study provides an important idea for realizing the clinical application of whole blood transcriptomics findings by immunological methods.
Differential gene expression of 3D primary human airway cultures exposed to cigarette smoke and electronic nicotine delivery system (ENDS) preparations
Authors: Rayner Rachael E. , Makena Patrudu , Liu Gang , Prasad G. L. , Cormet-Boyaka Estelle 
Published: April 2022

AbstractBackgroundAcute exposure to cigarette smoke alters gene expression in several biological pathways such as apoptosis, immune response, tumorigenesis and stress response, among others. However, the effects of electronic nicotine delivery systems (ENDS) on early changes in gene expression is relatively unknown. The objective of this study was to evaluate the early toxicogenomic changes using a fully-differentiated primary normal human bronchial epithelial (NHBE) culture model after an acute exposure to cigarette and ENDS preparations.ResultsRNA sequencing and pathway enrichment analysis identified time and dose dependent changes in gene expression and several canonical pathways when exposed to cigarette preparations compared to vehicle control, including oxidative stress, xenobiotic metabolism, SPINK1 general cancer pathways and mucociliary clearance. No changes were observed with ENDS preparations containing up to 28 µg/mL nicotine. Full model hierarchical clustering revealed that ENDS preparations were similar to vehicle control.ConclusionThis study revealed that while an acute exposure to cigarette preparations significantly and differentially regulated many genes and canonical pathways, ENDS preparations containing the same concentration of nicotine had very little effect on gene expression in fully-differentiated primary NHBE cultures.
Low cholesterol is not associated with depression: data from the 2005-2018 National Health and Nutrition Examination Survey
Authors: Zhang Qun , Liu Ziping , Wang Qian , Li Xiaoqian 
Published: April 2022

Abstract
Background
Although high serum cholesterol is widely recognized as a major risk factor for heart disease, the health effects of low cholesterol are less clear. Several studies have found a correlation between low cholesterol and depression, but the results are inconsistent.

Methods
Data from the National Health and Nutrition Examination Survey (NHANES) 2005-2018 were utilized in this cross-sectional study. The analysis of the relationship between cholesterol and depression was performed at three levels: low total cholesterol, low high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol. The inclusion criteria were as follows: (1) people with low (<4.14 mmol/L) or normal (4.14-5.16 mmol/L) total cholesterol for Sample 1; people with low (<1 mmol/L) or normal (≥1 mmol/L) HDL cholesterol levels for Sample 2; and people with low (<1.8 mmol/L) or normal (1.8-3.4 mmol/L) LDL cholesterol levels for Sample 3; and (2) people who completed the Patient Health Questionnaire-9 depression scale. Age, sex, educational level, race, marital status, self-rated health, alcohol status, smoking status, body mass index (BMI), poverty income ratio, physical function, comorbidities, and prescription use were considered potential confounders. The missing data were handled by multiple imputations of chained equations. Logistic regression was used to assess the relationship between low cholesterol and depression.

Results
After controlling for potential confounding factors in the multivariate logistic regression, no association was observed between depression and low total cholesterol (OR=1.0, 95% CI: 0.9-1.2), low LDL cholesterol (OR=1.0, 95% CI: 0.8-1.4), or low HDL cholesterol (OR=0.9, 95% CI: 0.8-1.1). The results stratified by sex also showed no association between low total cholesterol, low LDL cholesterol, low HDL cholesterol and depression in either men or women.

Conclusion
This population-based study did not support the assumption that low cholesterol was related to a higher risk of depression. This information may contribute to the debate on how to manage people with low cholesterol in clinical practice.
In vitro evaluation of probiotic properties and antioxidant activities of Bifidobacterium strains from infant feces in the Uyghur population of northwestern China
Authors: Cai Jingjing , Bai Ji , Luo Baolong , Ni Yongqing , Tian Fengwei , Yan Wenli 
Published: April 2022

Abstract
Purpose
Bifidobacterium is an important probiotic used in food and medicine production. The probiotic properties of bifidobacteria are strain specific, so it is necessary to evaluate the probiotic properties of bifidobacteria isolated from specific populations, especially when developing products suitable for specific populations. The objective of this study was to evaluate the probiotic potential and safety of bifidobacteria isolated from healthy Uyghur infants from northwestern China.

Methods
In this study, antimicrobial activity, antibiotic sensitivity, hemolytic, acid and bile tolerance, hydrophobicity, co-aggregation, auto-aggregation, and antioxidant activity were evaluated.

Results
Based on antagonistic activity spectrum against seven intestinal pathogenic bacteria, 14 excellent strains were initially selected. Among 14 strains, four bifidobacteria strains (BF17-4, BF52-1, BF87-3, and BF88-5) were superior to strain Lactobacillus rhamnosus GG in cell surface hydrophobicity and auto-aggregation percentages and close to strain GG in co-aggregation with Escherichia coli EPEC O127: K63 (CICC 10411). The antioxidant activities of each of the 14 bifidobacteria strains varied with the cell components. Most of the strains were sensitive to all the antimicrobials tested, except kanamycin and amikacin.

Conclusion
BF17-4 and BF52-1 are good candidates for further in vivo studies and further used in functional foods.
Effects of straw and straw-derived biochar on bacterial diversity in soda saline-alkaline paddy soil
Authors: Li Hongyu , Xia Yuying , Zhang Gongliang , Zheng Guiping , Fan Mingyu , Zhao Haicheng 
Published: April 2022

Abstract
Purpose
In order to provide a scientific basis for the improvement of soda saline-alkaline paddy soil, the pot experiment was performed to explore the effects of rice straw and straw-derived biochar on the diversity of soil bacteria and community structure in soda saline-alkaline soil.

Methods
The experiment was four gradients of straw return (3 (RS1), 7.5 (RS2), 12 (RS3), and 16.5 (RS4) t/hm2) and four gradients of biochar return (3 (RB1), 7.5 (RB2), 12 (RB3), and 16.5 (RB4) t/hm2), using 0 t/hm2 as a control (CK). After 5 consecutive years of measuring straw returns, high-throughput sequencing was used to determine the relative abundance, alpha diversity, and changes in the community structure of soil bacteria.

Result
Our results demonstrated that straw return significantly increased the relative abundance of Bacteroidetes, Firmicutes, and Sphingomonas and significantly reduced the relative abundance of Acidobacteria, Actinobacteria, Gemmatimonadetes, Parcubacteria, Anaeromyxobacter, Pontibacter, uncultured_bacterium_f_Draconibacteriaceae, and Bryobacter. Straw-derived biochar return significantly increased the relative abundance of uncultured_bacterium_f_Draconibacteriaceae and significantly reduced the relative abundances of Actinobacteria, Gemmatimonadetes, Thiobacillus, and Anaeromyxobacter, indicating that both straw and its associated biochar return changed the relative abundance of the phyla and genera of some bacteria. Straw return affected bacteria phylum and genus more than straw-derived biochar. With the exception of the 16.5 t/hm2 straw return, which reduced bacterial richness, the treatments did not significantly impact alpha diversity. Compared with straw-derived biochar return, straw return significantly changed the bacterial community structure, and the higher the straw return, the higher the impact on the bacterial community structure. Redundancy analysis (RDA) demonstrated that there was a significant correlation between the physicochemical properties of the soil and the community structure of its bacteria. A Mantel test demonstrated that the content of available phosphorus, available potassium, and organic matter was all important environmental factors affecting community structure.

Conclusion
We speculate that straw return regulates the physicochemical properties of the soil, which affects the bacterial community structure.