bluuebunny/crossref_metadata_2025_split huggingface dataset:
Random survival forests for dynamic predictions of a time-to-event outcome using a longitudinal biomarker
Authors: Pickett Kaci L , Suresh Krithika , Campbell Kristen R , Davis Scott , Juarez-Colunga Elizabeth 
Published: October 2021

AbstractBackgroundRisk prediction models for time-to-event outcomes play a vital role in personalized decision-making. A patient’s biomarker values, such as medical lab results, are often measured over time but traditional prediction models ignore their longitudinal nature, using only baseline information. Dynamic prediction incorporates longitudinal information to produce updated survival predictions during follow-up. Existing methods for dynamic prediction include joint modeling, which often suffers from computational complexity and poor performance under misspecification, and landmarking, which has a straightforward implementation but typically relies on a proportional hazards model. Random survival forests (RSF), a machine learning algorithm for time-to-event outcomes, can capture complex relationships between the predictors and survival without requiring prior specification and has been shown to have superior predictive performance.MethodsWe propose an alternative approach for dynamic prediction using random survival forests in a landmarking framework. With a simulation study, we compared the predictive performance of our proposed method with Cox landmarking and joint modeling in situations where the proportional hazards assumption does not hold and the longitudinal marker(s) have a complex relationship with the survival outcome. We illustrated the use of the RSF landmark approach in two clinical applications to assess the performance of various RSF model building decisions and to demonstrate its use in obtaining dynamic predictions.ResultsIn simulation studies, RSF landmarking outperformed joint modeling and Cox landmarking when a complex relationship between the survival and longitudinal marker processes was present. It was also useful in application when there were several predictors for which the clinical relevance was unknown and multiple longitudinal biomarkers were present. Individualized dynamic predictions can be obtained from this method and the variable importance metric is useful for examining the changing predictive power of variables over time. In addition, RSF landmarking is easily implementable in standard software and using suggested specifications requires less computation time than joint modeling.ConclusionsRSF landmarking is a nonparametric, machine learning alternative to current methods for obtaining dynamic predictions when there are complex or unknown relationships present. It requires little upfront decision-making and has comparable predictive performance and has preferable computational speed.
Statistical reanalysis of vascular event outcomes in primary and secondary vascular prevention trials
Authors: Woodhouse Lisa J. , Montgomery Alan A. , Mant Jonathan , Davis Barry R. , Algra Ale , Mas Jean-Louis , Staessen Jan A. , Thijs Lutgarde , Tonkin Andrew , Kirby Adrienne , Pocock Stuart J. , Chalmers John , Hankey Graeme J. , Spence J. David , Sandercock Peter , Diener Hans-Christoph , Uchiyama Shinichiro , Sprigg Nikola , Bath Philip M. 
Published: October 2021

Abstract
Background
Vascular prevention trials typically use dichotomous event outcomes although this may be inefficient statistically and gives no indication of event severity. We assessed whether ordinal outcomes would be more efficient and how to best analyse them.

Methods
Chief investigators of vascular prevention randomised controlled trials that showed evidence of either benefit or harm, or were included in a systematic review that overall showed benefit or harm, shared individual participant data from their trials. Ordered categorical versions of vascular event outcomes (such as stroke and myocardial infarction) were analysed using 15 statistical techniques and their results then ranked, with the result with the smallest p-value given the smallest rank. Friedman and Duncan’s multiple range tests were performed to assess differences between tests by comparing the average ranks for each statistical test.

Results
Data from 35 trials (254,223 participants) were shared with the collaboration. 13 trials had more than two treatment arms, resulting in 59 comparisons. Analysis approaches (Mann Whitney U, ordinal logistic regression, multiple regression, bootstrapping) that used ordinal outcome data had a smaller average rank and therefore appeared to be more efficient statistically than those that analysed the original binary outcomes.

Conclusions
Ordinal vascular outcome measures appear to be more efficient statistically than binary outcomes and provide information on the severity of event. We suggest a potential role for using ordinal outcomes in vascular prevention trials.
A novel weighting method to remove bias from within-subject exposure dependency in case-crossover studies
Authors: Kubota Kiyoshi , Kelly Thu-Lan , Sato Tsugumichi , Pratt Nicole , Roughead Elizabeth , Yamaguchi Takuhiro 
Published: October 2021

Abstract
Background
Case-crossover studies have been widely used in various fields including pharmacoepidemiology. Vines and Farrington indicated in 2001 that when within-subject exposure dependency exists, conditional logistic regression can be biased. However, this bias has not been well studied.

Methods
We have extended findings by Vines and Farrington to develop a weighting method for the case-crossover study which removes bias from within-subject exposure dependency. Our method calculates the exposure probability at the case period in the case-crossover study which is used to weight the likelihood formulae presented by Greenland in 1999. We simulated data for the population with a disease where most patients receive a cyclic treatment pattern with within-subject exposure dependency but no time trends while some patients stop and start treatment. Finally, the method was applied to real-world data from Japan to study the association between celecoxib and peripheral edema and to study the association between selective serotonin reuptake inhibitor (SSRI) and hip fracture in Australia.

Results
When the simulated rate ratio of the outcome was 4.0 in a case-crossover study with no time-varying confounder, the proposed weighting method and the Mantel-Haenszel odds ratio reproduced the true rate ratio. When a time-varying confounder existed, the Mantel-Haenszel method was biased but the weighting method was not. When more than one control period was used, standard conditional logistic regression was biased either with or without time-varying confounding and the bias increased (up to 8.7) when the study period was extended. In real-world analysis with a binary exposure variable in Japan and Australia, the point estimate of the odds ratio (around 2.5 for the association between celecoxib and peripheral edema and around 1.6 between SSRI and hip fracture) by our weighting method was equal to the Mantel-Haenszel odds ratio and stable compared with standard conditional logistic regression.

Conclusion
Case-crossover studies may be biased from within-subject exposure dependency, even without exposure time trends. This bias can be identified by comparing the odds ratio by the Mantel-Haenszel method and that by standard conditional logistic regression. We recommend using our proposed method which removes bias from within-subject exposure dependency and can account for time-varying confounders.
Analysis of COVID-19 data using neutrosophic Kruskal Wallis H test
Authors: Sherwani Rehan Ahmad Khan , Shakeel Huma , Awan Wajiha Batool , Faheem Maham , Aslam Muhammad 
Published: October 2021

AbstractBackgroundKruskal-Wallis H test from the bank of classical statistics tests is a well-known nonparametric alternative to a one-way analysis of variance. The test is extensively used in decision-making problems where one has to compare the equality of several means when the observations are in exact form. The test is helpless when the data is in an interval form and has some indeterminacy.MethodsThe interval-valued data often contain uncertainty and imprecision and often arise from situations that contain vagueness and ambiguity. In this research, a modified form of the Kruskal-Wallis H test has been proposed for indeterminacy data. A comprehensive theoretical methodology with an application and implementation of the test has been proposed in the research.ResultsThe proposed test is applied on a Covid-19 data set for application purposes. The study results suggested that the proposed modified Kruskal-Wallis H test is more suitable in interval-valued data situations. The application of this new neutrosophic Kruskal-Wallis test on the Covid-19 data set showed that the proposed test provides more relevant and adequate results. The data representing the daily ICU occupancy by the Covid-19 patients were recorded for both determinate and indeterminate parts. The existing nonparametric Kruskal-Wallis H test under Classical Statistics would have given misleading results. The proposed test showed that at a 1% level of significance, there is a statistically significant difference among the average daily ICU occupancy by corona-positive patients of different age groups.ConclusionsThe findings of the results suggested that our proposed modified form of the Kruskal-Wallis is appropriate in place of the classical form of the test in the presence of the neutrosophic environment.
Extended parallel process model (EPPM) in evaluating lung Cancer risk perception among older smokers
Authors: Zarghami Fatemeh , Allahverdipour Hamid , Jafarabadi Mohammad Asghari 
Published: October 2021

AbstractBackgroundThere is a lack of scientific literature on the application of fear appeals theories to evaluate lung cancer risk perception among smokers. The aim of the present study is to apply the Extended Parallel Process Model (EPPM) to discover the perception of the smokers about their lifetime risk of developing lung cancer (perceived susceptibility), their perception of lung cancer survival (perceived severity), response efficacy, self-efficacy, and readiness to quit.MethodsIn this cross-sectional study, 215 eligible smokers (aged 45 years and over who have smoked at least 1 pack per day in the last 5 years) were recruited. The data collection tool was designed using validate self-report questionnaires and it was contained items on the perceived risk of a smoker contracting lung cancer and perceived lung cancer survival rate. It also had questions to measure the main constructs of the EPPM and Readiness to quit (“Low_Readiness”, and “High_Readiness”). To test how the data support conceptual EPPM to data, Generalized Structural Equation Modeling (GSEM) was used.ResultsFindings showed a significant relationship between Perceived_Susceptibility and Perceived_Response Efficacy; (B = 1.16,P < 0.001); between Perceived_Susceptibility and Perceived_Self Efficacy, (B = -0.93, P < 0.001), Perceived_Severity, and Perceived_Response Efficacy (B = 1.07, P < 0.001). There was also a significant relationship between Perceived_Threat and Perceived_Response Efficacy; between Perceived_Threat and Perceived_Self Efficacy. The relationship between High_Readiness and Perceived_Self Efficacy, and between High_Readiness and Perceived_Severity also were significant. However, the relationships between High_Readiness and Perceived_Threat were not significant (P > 0.05).ConclusionPerceived_threat and Perceived_efficacy were important for smokers with low readiness to quit, while Perceived_efficacy was most important for smokers with high readiness to quit. These findings could be used in promoting lung cancer awareness and designing smoking cessation programs based on smokers’ stages of change.
Readability levels and thematic content analysis of online and printed lead poisoning informational materials
Authors: Okatch Harriet , Pitts Ebony , Ritchey Emily , Givler Kylie , Kuon Madeline 
Published: October 2021

AbstractBackgroundLead poisoning prevention efforts include preparing and disseminating informational materials such as brochures and pamphlets to increase awareness of lead poisoning, lead exposures and lead poisoning prevention. However, studies have demonstrated that patient education materials for diseases and health conditions are prepared at a reading level that is higher than the recommended 7th–8th grade reading level. This study, therefore, aims to assess the reading levels of lead poisoning informational materials.MethodsLead poisoning materials (N = 31) were accessed from three states; Michigan, New York and Pennsylvania. The readability levels of the materials were assessed using the Flesh Kincaid Grade Level readability test. The Kruskal-Wallis test was conducted to determine if the readability levels differed between the materials obtained from the different states. Thematic content analyses were carried out to assess the inclusion of four themes; definition of lead poisoning, risk factors and exposures, testing and referral and prevention covering 12 subtopics. The Wilcoxon rank sum test was used to examine if there was a difference in the number of subtopics by readability level (dichotomized to >8th grade and < 8th grade).ResultsThe median readability level of the informational materials was 6.7 (IQR: 5.1–8.1). However, there was variability in the readability levels of the materials (range 3.5 to 10.6); materials obtained from Michigan had the highest median reading level of 8.1 (IQR: 6.9–9.0) followed by Pennsylvania. Heterogeneity was observed in the content of the materials. Most of the materials (80%) from Michigan focused on water as a source of lead poisoning, whereas materials from New York and Pennsylvania focused on lead-based paint and other sources. The materials prepared at >8th grade reading level contained fewer topics than materials prepared at <8th grade reading level.ConclusionsWe find that the materials were often prepared at reading levels lower than the recommended 8th grade reading level. However, there is variability in the reading levels and in the content of the materials. While the materials met the general readability guidelines, they did not necessarily meet the needs of specific groups, especially groups at risk.
Curcumin upregulates transforming growth factor-β1, its receptors, and vascular endothelial growth factor expressions in an in vitro human gingival fibroblast wound healing model
Authors: Rujirachotiwat Auspreeya , Suttamanatwong Supaporn 
Published: October 2021

AbstractBackgroundCurcumin accelerates healing of oral wounds; however, the responsible mechanisms remain underexplored. Our hypothesis is curcumin regulates the expression of wound healing-related genes in human gingival fibroblasts (hGFs). This study investigated whether curcumin regulates transforming growth factor (TGF)-β1, type I TGF-β receptor (TGF-βRI), type II TGF-β receptor (TGF-βRII), and vascular endothelial growth factor (VEGF) expression in unwounded hGFs and an in vitro hGF wound healing model.MethodsThe cytotoxicity of curcumin was evaluated using the MTT assay. Unwounded hGFs were treated with non-cytotoxic concentrations of curcumin for 24 h. Gene expression was determined by quantitative polymerase chain reaction. Then, hGFs were treated with 1 µM curcumin in an in vitro wound healing model. PD98059 pretreatment was performed to determine whether extracellular signal-regulated kinase (ERK) signaling was required for regulation of gene expression by curcumin.ResultsCurcumin at 0.1–20 µM caused no significant change in cell viability. In unwounded hGFs, curcumin had no significant effect on TGF-β1, TGF-βRI, TGF-βRII, or VEGF expression. Conversely, curcumin significantly upregulated the expression of these genes in the in vitro wound healing model. PD98059 significantly attenuated the curcumin-stimulated TGF-βRI, TGF-βRII, and VEGF expression, whereas it had no effect on TGF-β1 expression.ConclusionsCurcumin upregulated TGF-β1, TGF-βRI, TGF-βRII, and VEGF expression in an in vitro hGF wound healing model. The ERK pathway is required for TGF-βRI, TGF-βRII, and VEGF induction by curcumin. Our findings support the development of curcumin as a therapeutic agent for gingival ulcers.
Interradicular distance and alveolar bone thickness for miniscrew insertion: a CBCT study of Persian adults with different sagittal skeletal patterns
Authors: Golshah Amin , Salahshour Mahya , Nikkerdar Nafiseh 
Published: October 2021

AbstractBackgroundThis study aimed to assess the interradicular distance and alveolar bone thickness of Persian adults with different sagittal skeletal patterns for miniscrew insertion using cone-beam computed tomography (CBCT).MethodsThis cross-sectional study was conducted on maxillary and mandibular CBCT scans of 60 patients (18–35 years) in three groups (n = 20) of class I, II and III sagittal skeletal pattern. Anatomical and skeletal parameters were measured at 2, 4 and 6 mm apical to the cementoenamel junction (CEJ) by one examiner. The intra- and inter-class correlation coefficients were calculated to assess the intra, and interobserver reliability. Data were analyzed by ANOVA and Tukey’s test (alpha = 0.05).ResultsThe intra- and interobserver reliability were > 0.9 for all parameters. The largest inter-radicular distance in the maxilla was between the central incisors (1–1) in classes I and III, and between premolars (4–5) in class II patients. The largest inter-radicular distance in the mandible was between molar teeth (6–7) in all three classes. The buccal cortical plate thickness was maximum at the site of mandibular first and second molars (6–7). The posterior maxilla and mandible showed the maximum thickness of cancellous bone and alveolar process. Wide variations were noted in this respect between class I, II and III patients.ConclusionsThe area with maximum inter-radicular distance and optimal alveolar bone thickness for miniscrew insertion varies in different individuals, depending on their sagittal skeletal pattern.
Women diagnosed with HIV and unknown HIV status perceived susceptibility to cervical cancer and perceived benefits of cervical cancer screening in Ghana: a cross-sectional study
Authors: Enyan Nancy Innocentia Ebu , Akaba Selorm , Amoo Sarah Ama 
Published: October 2021

Abstract
Background
Cervical cancer is an issue of global health concern, and it seems to be the next epidemic in Sub-Saharan Africa after Human Immunodeficiency Virus (HIV). This study compared the perceptions of susceptibility to cervical cancer and benefits of cervical cancer screening among women diagnosed and those with unknown HIV status and determined the association between socio-demographic factors and HIV status.

Methods
A cross-sectional study was conducted with 600 women diagnosed with HIV and 600 women with unknown HIV status in the Central Region of Ghana. Convenience sampling was used and a structured interview schedule was the main data collection instrument. Data were analysed using frequencies, percentages, chi-square test and independent samples t-test.

Results
A high proportion of women diagnosed with HIV 94.8% (n = 569) and those with unknown HIV status 93.5% (n = 561) agreed that “screening can find cervical changes”. Also, 58.0% (n = 348) of women diagnosed with HIV agreed that they have been in polygamous relationships so they may get cervical cancer. There was a statistically significant association between marital status (X2 = 167.071, p = 0.001), religion (X2 = 57.720, p = 0.001), level of education (X2 = 118.997, p = 0.001), employment status (X2 = 782.646, p = 0.001) and HIV status. A comparison of the mean difference for women diagnosed and those with unknown HIV status in relation to perceived benefits of cervical cancer screening showed a statistically significant difference (t = 7.418, df = 1198, p = 0.001). Nonetheless, there was no statistically significant difference in the means for women diagnosed and those with unknown HIV status regarding perceived susceptibility to cervical cancer (t = 0.935, df = 1198, p = 0.351).

Conclusions
Women with HIV perceived higher benefits of cervical cancer screening. Perception of susceptibility to cervical cancer by women with and those without HIV need to be addressed in efforts to improve their health. Furthermore, interventions for women with HIV should consider some important sociodemographic factors.
Association between dietary fat and fat subtypes with the risk of breast cancer in an Iranian population: a case-control study
Authors: Mozafarinia Maedeh , Sasanfar Bahareh , Toorang Fatemeh , Salehi-Abargouei Amin , Zendehdel Kazem 
Published: October 2021

Abstract
Aim
To examine the relationship between dietary fat intake and breast cancer (BC) development.

Method
This case-control study included 473 women with breast cancer (pathologically confirmed) and 501 healthy subjects matched by age and residency. Dietary intakes of different types and sources of fatty acids were assessed using a validated food frequency questionnaire. The association between dietary fats and odds of BC was assessed using a logistic regression model in crude and multivariable-adjusted models. P values below 0.05 were regarded as statistically significant.

Results
Participants’ age and body mass index were 44.0 ± 10.8 years and 28.4 ± 5.6 kg/m2, respectively. Individuals with the highest quartile of total fat intake and polyunsaturated fatty acid (PUFA) intake were 1.50 times more at risk to develop BC than others. A positive significant association was observed between animal fat (Q4 vs. Q1, OR = 1.89, 95 % CI = 0.93–3.81), saturated fatty acid (SFA) (Q4 vs. Q1, OR = 1.70, 95 % CI = 0.88–3.30), monounsaturated fatty acid (MUFA) (Q4 vs. Q1 OR = 1.85, 95 % CI = 0.95–3.61) and PUFA intake (Q4 vs. Q1, OR = 2.12, 95 % CI = 1.05–4.27) with BC risk in postmenopausal women. However, there was no association in premenopausal women.

Conclusions
Total dietary fat and its subtypes might increase the risk of BC, especially in postmenopausal women. This observational study confirms the role of dietary fat in breast cancer development. Intervention studies involving different estrogen receptor subgroups are needed.