bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient characteristics, biomarkers and exacerbation risk in severe, uncontrolled asthma
Authors: Kraft Monica , Brusselle Guy , FitzGerald J. Mark , Pavord Ian D. , Keith Matthew , Fagerås Malin , Garcia Gil Esther , Hirsch Ian , Goldman Mitchell , Colice Gene 
Published: June 2021

BackgroundGreater precision in asthma exacerbation risk prediction may improve outcomes. We sought to identify clinical characteristics and biomarkers associated with elevated exacerbation risk in patients with severe, uncontrolled asthma.MethodsData were pooled from seven similarly designed phase II and III randomised controlled clinical trials of biologic therapies for the treatment of severe, uncontrolled asthma that enrolled comparable patient populations. Annualised asthma exacerbation rates (AAERs) for patients randomised to placebo were assessed by baseline clinical characteristics, and by biomarker concentrations at baseline and over the study duration.ResultsThe AAER for the 2016 patients in the combined placebo group was 0.91 (95% CI 0.84‒0.98). Baseline characteristics associated with greater AAER were frequent or severe exacerbations within the prior 12 months, nasal polyposis, maintenance oral corticosteroid use, Asian race and Asian or Western European region. AAER increased with baseline blood eosinophil counts and exhaled nitric oxide fraction (FENO) concentration, with the greatest AAER occurring for patients with eosinophils ≥300 cells·μL−1andFENO≥50 ppb. No relationship was observed between baseline serum IgE concentration and AAER. Combining type 2 inflammation criteria for eosinophils andFENOhad greater prognostic value than either biomarker alone. Persistent eosinophil andFENOelevations throughout the study period were associated with greater AAER.ConclusionsExacerbation history, maintenance corticosteroid use, nasal polyposis, Asian race, geographic region, and elevations in blood eosinophil counts andFENOconcentrations (particularly when combined and/or persistently achieving type 2 inflammation criteria) were associated with increased exacerbation risk in patients with severe, uncontrolled asthma.
Deep Spatiotemporal Convolutional-Neural-Network-Based Remaining Useful Life Estimation of Bearings
Authors: Wang Xu , Wang Tianyang , Ming Anbo , Han Qinkai , Chu Fulei , Zhang Wei , Li Aihua 
Published: June 2021

AbstractThe remaining useful life (RUL) estimation of bearings is critical for ensuring the reliability of mechanical systems. Owing to the rapid development of deep learning methods, a multitude of data-driven RUL estimation approaches have been proposed recently. However, the following problems remain in existing methods: 1) Most network models use raw data or statistical features as input, which renders it difficult to extract complex fault-related information hidden in signals; 2) for current observations, the dependence between current states is emphasized, but their complex dependence on previous states is often disregarded; 3) the output of neural networks is directly used as the estimated RUL in most studies, resulting in extremely volatile prediction results that lack robustness. Hence, a novel prognostics approach is proposed based on a time–frequency representation (TFR) subsequence, three-dimensional convolutional neural network (3DCNN), and Gaussian process regression (GPR). The approach primarily comprises two aspects: construction of a health indicator (HI) using the TFR-subsequence–3DCNN model, and RUL estimation based on the GPR model. The raw signals of the bearings are converted into TFR-subsequences by continuous wavelet transform and a dislocated overlapping strategy. Subsequently, the 3DCNN is applied to extract the hidden spatiotemporal features from the TFR-subsequences and construct HIs. Finally, the RUL of the bearings is estimated using the GPR model, which can also define the probability distribution of the potential function and prediction confidence. Experiments on the PRONOSTIA platform demonstrate the superiority of the proposed TFR-subsequence–3DCNN–GPR approach. The use of degradation-related spatiotemporal features in signals is proposed herein to achieve a highly accurate bearing RUL prediction with uncertainty quantification.
PPalign: optimal alignment of Potts models representing proteins with direct coupling information
Authors: Talibart Hugo , Coste François 
Published: June 2021

Abstract
Background
To assign structural and functional annotations to the ever increasing amount of sequenced proteins, the main approach relies on sequence-based homology search methods, e.g. BLAST or the current state-of-the-art methods based on profile Hidden Markov Models, which rely on significant alignments of query sequences to annotated proteins or protein families. While powerful, these approaches do not take coevolution between residues into account. Taking advantage of recent advances in the field of contact prediction, we propose here to represent proteins by Potts models, which model direct couplings between positions in addition to positional composition, and to compare proteins by aligning these models. Due to non-local dependencies, the problem of aligning Potts models is hard and remains the main computational bottleneck for their use.

Methods
We introduce here an Integer Linear Programming formulation of the problem and PPalign, a program based on this formulation, to compute the optimal pairwise alignment of Potts models representing proteins in tractable time. The approach is assessed with respect to a non-redundant set of reference pairwise sequence alignments from SISYPHUS benchmark which have lowest sequence identity (between $$3\%$$

3
%

and $$20\%$$

20
%

) and enable to build reliable Potts models for each sequence to be aligned. This experimentation confirms that Potts models can be aligned in reasonable time ($$1'37''$$

1
′

37

′
′

in average on these alignments). The contribution of couplings is evaluated in comparison with HHalign and independent-site PPalign. Although Potts models were not fully optimized for alignment purposes and simple gap scores were used, PPalign yields a better mean $$F_1$$

F
1

score and finds significantly better alignments than HHalign and PPalign without couplings in some cases.

Conclusions
These results show that pairwise couplings from protein Potts models can be used to improve the alignment of remotely related protein sequences in tractable time. Our experimentation suggests yet that new research on the inference of Potts models is now needed to make them more comparable and suitable for homology search. We think that PPalign’s guaranteed optimality will be a powerful asset to perform unbiased investigations in this direction.
Mapping methylation quantitative trait loci in cardiac tissues nominates risk loci and biological pathways in congenital heart disease
Authors: Li Ming , Lyu Chen , Huang Manyan , Do Catherine , Tycko Benjamin , Lupo Philip J. , MacLeod Stewart L. , Randolph Christopher E. , Liu Nianjun , Witte John S. , Hobbs Charlotte A. 
Published: June 2021

Abstract
Background
Most congenital heart defects (CHDs) result from complex interactions among genetic susceptibilities, epigenetic modifications, and maternal environmental exposures. Characterizing the complex relationship between genetic, epigenetic, and transcriptomic variation will enhance our understanding of pathogenesis in this important type of congenital disorder. We investigated cis-acting effects of genetic single nucleotide polymorphisms (SNPs) on local DNA methylation patterns within 83 cardiac tissue samples and prioritized their contributions to CHD risk by leveraging results of CHD genome-wide association studies (GWAS) and their effects on cardiac gene expression.

Results
We identified 13,901 potential methylation quantitative trait loci (mQTLs) with a false discovery threshold of 5%. Further co-localization analyses and Mendelian randomization indicated that genetic variants near the HLA-DRB6 gene on chromosome 6 may contribute to CHD risk by regulating the methylation status of nearby CpG sites. Additional SNPs in genomic regions on chromosome 10 (TNKS2-AS1 gene) and chromosome 14 (LINC01629 gene) may simultaneously influence epigenetic and transcriptomic variations within cardiac tissues.

Conclusions
Our results support the hypothesis that genetic variants may influence the risk of CHDs through regulating the changes of DNA methylation and gene expression. Our results can serve as an important source of information that can be integrated with other genetic studies of heart diseases, especially CHDs.
Internal validation and comparison of the prognostic performance of models based on six emergency scoring systems to predict in-hospital mortality in the emergency department
Authors: Rahmatinejad Zahra , Tohidinezhad Fariba , Rahmatinejad Fatemeh , Eslami Saeid , Pourmand Ali , Abu-Hanna Ameen , Reihani Hamidreza 
Published: June 2021

Abstract
Background
Medical scoring systems are potentially useful to make optimal use of available resources. A variety of models have been developed for illness measurement and stratification of patients in Emergency Departments (EDs). This study was aimed to compare the predictive performance of the following six scoring systems: Simple Clinical Score (SCS), Worthing physiological Score (WPS), Rapid Acute Physiology Score (RAPS), Rapid Emergency Medicine Score (REMS), Modified Early Warning Score (MEWS), and Routine Laboratory Data (RLD) to predict in-hospital mortality.

Methods
A prospective single-center observational study was conducted from March 2016 to March 2017 in Edalatian ED in Emam Reza Hospital, located in the northeast of Iran. All variables needed to calculate the models were recorded at the time of admission and logistic regression was used to develop the models’ prediction probabilities. The Area Under the Curve for Receiver Operating Characteristic (AUC-ROC) and Precision-Recall curves (AUC-PR), Brier Score (BS), and calibration plots were used to assess the models’ performance. Internal validation was obtained by 1000 bootstrap samples. Pairwise comparison of AUC-ROC was based on the DeLong test.

Results
A total of 2205 patients participated in this study with a mean age of 61.8 ± 18.5 years. About 19% of the patients died in the hospital. Approximately 53% of the participants were male. The discrimination ability of SCS, WPS, RAPS, REMS, MEWS, and RLD methods were 0.714, 0.727, 0.661, 0.678, 0.698, and 0.656, respectively. Additionally, the AUC-PR of SCS, WPS, RAPS, REMS, EWS, and RLD were 0.39, 0.42, 0.35, 0.34, 0.36, and 0.33 respectively. Moreover, BS was 0.1459 for SCS, 0.1713 for WPS, 0.0908 for RAPS, 0.1044 for REMS, 0.1158 for MEWS, and 0.073 for RLD. Results of pairwise comparison which was performed for all models revealed that there was no significant difference between the SCS and WPS. The calibration plots demonstrated a relatively good concordance between the actual and predicted probability of non-survival for the SCS and WPS models.

Conclusion
Both SCS and WPS demonstrated fair discrimination and good calibration, which were superior to the other models. Further recalibration is however still required to improve the predictive performance of all available models and their use in clinical practice is still unwarranted.
Subjective and objective health predicting mortality and institutionalization: an 18-year population-based follow-up study among community-dwelling Finnish older adults
Authors: Viljanen Anna , Salminen Marika , Irjala Kerttu , Heikkilä Elisa , Isoaho Raimo , Kivelä Sirkka-Liisa , Korhonen Päivi , Vahlberg Tero , Viitanen Matti , Wuorela Maarit , Löppönen Minna , Viikari Laura 
Published: June 2021

Abstract
Background
Objective health measures, such as registered illnesses or frailty, predict mortality and institutionalization in older adults. Also, self-reported assessment of health by simple self-rated health (SRH) has been shown to predict mortality and institutionalization. The aim of this study was to assess the association of objective and subjective health with mortality and institutionalization in Finnish community-dwelling older adults.

Methods
In this prospective study with 10- and 18-year follow-ups, objective health was measured by registered illnesses and subjective health was evaluated by simple SRH, self-reported walking ability (400 m) and self-reported satisfaction in life. The participants were categorized into four groups according to their objective and subjective health: 1. subjectively and objectively healthy, 2. subjectively healthy and objectively unhealthy, 3. subjectively unhealthy and objectively healthy and 4. subjectively and objectively unhealthy. Cox regression model was used in the analyses. Death was used as a competing factor in the institutionalization analyses.

Results
The mean age of the participants (n = 1259) was 73.5 years (range 64.0–100.0). During the 10- and 18-year follow-ups, 466 (37%) and 877 (70%) died, respectively. In the institutionalization analyses (n = 1106), 162 (15%) and 328 (30%) participants were institutionalized during the 10- and 18-year follow-ups, respectively. In both follow-ups, being subjectively and objectively unhealthy, compared to being subjectively and objectively healthy, was significantly associated with a higher risk of institutionalization in unadjusted models and with death both in unadjusted and adjusted models.

Conclusions
The categorization of objective and subjective health into four health groups was good at predicting the risk of death during 10- and 18-year follow-ups, and seemed to also predict the risk of institutionalization in the unadjusted models during both follow-ups. Poor subjective health had an additive effect on poor objective health in predicting mortality and could therefore be used as part of an older individual’s health evaluation when screening for future adverse outcomes.
Topical estrogen, testosterone, and vaginal dilator in the prevention of vaginal stenosis after radiotherapy in women with cervical cancer: a randomized clinical trial
Authors: Martins Jumara , Vaz Ana Francisca , Grion Regina Celia , Costa-Paiva Lúcia , Baccaro Luiz Francisco 
Published: June 2021

Abstract
Background
We aimed to evaluate the effects of different therapeutic options to prevent the evolution of vaginal stenosis after pelvic radiotherapy in women with cervical cancer.

Methods
open-label randomized clinical trial of 195 women, stage I-IIIB, aged 18–75 years, using topical estrogen (66), topical testosterone (34), water-based intimate lubricant gel (66), and vaginal dilators (29) to assess the incidence and severity of vaginal stenosis after radiotherapy at UNICAMP-Brazil, from January/2013 to May/2018. The main outcome measure was vaginal stenosis assessed using the Common Terminology Criteria for Adverse Events (CTCAE) scale and percental changes in vaginal volume. The women were evaluated at four different times: shortly after the end of radiotherapy, and four, eight, and 12 months after the beginning of the intervention. Statistical analysis was carried out using Symmetry test, Kruskal-Wallis test and multiple regression.

Results
the mean age of women was 46.78 (±13.01) years, 61,03% were premenopausal and 73,84% had stage IIB-IIIB tumors. The mean reduction in vaginal volume in the total group was 25.47%, with similar worsening in the four treatment groups with no statistical difference throughout the intervention period. There was worsening of vaginal stenosis evaluated by CTCAE scale after 1 year in all groups (p < 0.01), except for the users of vaginal dilator (p = 0.37).

Conclusions
there was a reduction in vaginal volume in all treatment groups analyzed, with no significant difference between them. However, women who used vaginal dilators had a lower frequency and severity of vaginal stenosis assessed by the CTCAE scale after one year of treatment.

Trial registration
Brazilian Registry of Clinical Trials, RBR-23w5fv. Registered 10 January 2017 - Retrospectively registered.
Identification of prognostic markers for hepatocellular carcinoma based on the epithelial-mesenchymal transition-related gene BIRC5
Authors: Xu Rongzhong , Lin Liubing , Zhang Bo , Wang Jian , Zhao Fanchen , Liu Xiaolin , Li Yiping , Li Yan 
Published: June 2021

Abstract
Background
The baculoviral IAP repeat containing 5 (BIRC5) related to epithelial-mesenchymal transition (EMT) plays a crucial role in the pathogenesis of hepatocellular carcinoma (HCC). However, it remains unclear whether BIRC5-related genes can be used as prognostic markers of HCC.

Methods
Kaplan-Meier (K-M) survival curve was used to assess the Overall Survival (OS) of high- and low-expression group divided by the median of BIRC5 expression. The differentially expressed genes (DEGs) between the two groups were screened using the limma package, and performed the functional enrichment analysis by the clusterProfiler package. WGCNA was used to analyze the relationship of the module and the clinical traits. The risk signature was constructed by univariate and multivariate Cox regression analyses and the enrichment analysis of genes in the risk signature was performed by the Intelligent pathway analysis (IPA). The immunophenoscore (IPS) and the tumor immune dysfunction and exclusion (TIDE) were used to estimate the clinical significance of the risk groups.

Results
BIRC5 was high-expressed in HCC samples and associated with a poor prognosis (p-value < 0.0001). WGCNA screened 180 module genes which were overlapped with the 241 DEGs, ultimately getting 33 candidate genes. After the Cox regression analyses, CENPA, CDCA8, EZH2, KIF20A, KPNA2, CCNB1, KIF18B and MCM4 were preserved and used to construct risk signature, followed by calculating the risk score. The patients in high-risk groups stratified by median of the risk score were associated with a poor prognosis. The risk score had high accuracy [the area under the curve (AUC) > 0.72] and was closely associated with clinicopathological characteristics of HCC patients. IPA suggested that the 8 genes were enriched in Cancer and Immunological disease related pathways. IPS and TIDE score indicated that the genes in low-risk group could cause an immune response, and patients in the low-risk group may be more sensitive to the immune checkpoint blockade (ICB) therapy.

Conclusion
The risk score constructed by the 8 genes could not only predict the clinical outcome but also distinguish the cohort of ICB therapy in HCC, which exerted a vital value in treatment and prognosis of HCC.
High-level psychotropic polypharmacy: a retrospective comparison of children in foster care to their peers on Medicaid
Authors: Davis Deborah Winders , Lohr W. David , Feygin Yana , Creel Liza , Jawad Kahir , Jones V. Faye , Williams P. Gail , Le Jennifer , Trace Marie , Pasquenza Natalie 
Published: June 2021

Abstract
Background
The use of antipsychotic medication and psychotropic polypharmacy has increased in the United States over the last two decades especially for children from low-income families and those in foster care. Although attention has been paid to providing greater insight, prescribing patterns remain concerning since there is a lack of evidence related to safety and efficacy. High-level psychotropic polypharmacy has not been described. We aim to compare the use of HLPP for children receiving Medicaid services and those in foster care and identify factors associated with the duration of use of high-level psychotropic polypharmacy. Additionally, we will examine the frequency of laboratory metabolic screening and emergency department, inpatient, and outpatient visits.

Methods
A cross-sectional, secondary analysis of statewide data describes trends in high-level psychotropic polypharmacy from 2012 to 2017 and the prevalence and predictors of high-level psychotropic polypharmacy duration and resource use in 2017 for all children on Medicaid and those in foster care. High-level psychotropic polypharmacy included concurrent use, at least four classes of medications including an antipsychotic, and at least 30 days duration.

Results
High-level psychotropic polypharmacy increased from 2012 to 2014 for both groups but stabilized in 2015–2016. Children in foster care showed a slight increase compared to their peers in 2017. There was no association between duration and demographic characteristics or foster care status. Diagnoses predicted duration. Neither group received metabolic monitoring at an acceptable rate.

Conclusions
Concerning patterns of high-level psychotropic polypharmacy and metabolic monitoring were identified. Cautious use of high-level psychotropic polypharmacy and greater oversight to ensure that these children are receiving comprehensive services like behavioral health, primary care, and primary prevention.
Guidelines on analgosedation, monitoring, and recovery time for flexible bronchoscopy: a systematic review
Authors: Strohleit Daniel , Galetin Thomas , Kosse Nils , Lopez-Pastorini Alberto , Stoelben Erich 
Published: June 2021

Abstract
Background
Patients undergoing bronchoscopy in spontaneous breathing are prone to hypoxaemia and hypercapnia. Sedation, airway obstruction, and lung diseases impair respiration and gas exchange. The restitution of normal respiration takes place in the recovery room. Nonetheless, there is no evidence on the necessary observation time. We systematically reviewed current guidelines on bronchoscopy regarding sedation, monitoring and recovery.

Methods
This review was registered at the PROSPERO database (CRD42020197476). MEDLINE and awmf.org were double-searched for official guidelines, recommendation or consensus statements on bronchoscopy from 2010 to 2020. The PICO-process focussed on adults (Patients), bronchoscopy with maintained spontaneous breathing (Interventions), and recommendations regarding the intra- and postprocedural monitoring and sedation (O). The guideline quality was graded. A catalogue of 54 questions was answered. Strength of recommendation and evidence levels were recorded for each recommendation.

Results
Six guidelines on general bronchoscopy and three expert statements on special bronchoscopic procedures were identified. Four guidelines were evidence-based. Most guidelines recommend sedation to improve the patient’s tolerance. Midazolam combined with an opioid is preferred. The standard monitoring consists of non-invasive blood pressure, and pulse oximetry, furthermore electrocardiogram in cardiac patients. Only one guideline discusses hypercapnia and capnometry, but without consensus. Two guidelines discuss a recovery time of two hours, but a recommendation was not given because of lack of evidence.

Conclusion
Evidence for most issues is low to moderate. Lung-diseased patients are not represented by current guidelines. Capnometry and recovery time lack evidence. More primary research in these fields is needed so that future guidelines may address these issues, too.