bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vasoreactive phenotype in children with pulmonary arterial hypertension and syncope
Authors: Linder Alexandra N. , Hsia Jill , Krishnan Sheila V. , Rosenzweig Erika B. , Krishnan Usha S. 
Published: August 2022

BackgroundSyncope in Group 1 pulmonary arterial hypertension (PAH) is an independent predictor of poor prognosis in adults, but this is not well studied in children. We hypothesise that syncope in children with PAH often occurs in association with a reactive pulmonary vascular bed with sudden vasoconstriction in response to adverse stimuli. In the current study, we sought to determine the association of syncope with acute vasoresponsiveness and outcomes in children with Group 1 PAH.MethodsA retrospective chart review of children with PAH at a single pulmonary hypertension centre from 1 January 2005 to 31 October 2018 was performed. Data included demographics, symptoms, imaging, haemodynamics, and outcomes at baseline and follow-up.Results169 children had Group 1 PAH; 47 (28%) had syncope at presentation or follow-up. Children with significant shunts were excluded from the analysis. Children with syncope were older at diagnosis (7.5versus5.0 years; p=0.002) and had a higher incidence of chest pain (p=0.022) and fatigue (p=0.003). They had higher pulmonary vascular resistance at baseline (14.9versus9.1 WU·m2; p=0.01). More children with syncope were vasoresponders to inhaled nitric oxide (33%versus22%; p=0.08–NS). Children with syncope and acute vasoresponsiveness had the highest survival, and non-responders with syncope on medications had the worst long-term survival.ConclusionsChildren with syncope had higher rates of vasoreactivity compared to those without. This suggests that in some children with PAH, syncope may simply reflect acute pulmonary vasoconstriction to an adverse stimulus. Larger prospective studies are warranted to further assess syncope as a marker for a vasoreactive phenotype with implications for treatment and long-term outcomes.
Complete response to anti-interleukin-5 biologics in a real-life setting: results from the nationwide Danish Severe Asthma Register
Authors: Soendergaard Marianne Baastrup , Hansen Susanne , Bjerrum Anne-Sofie , Hilberg Ole , Lock-Johansson Sofie , Håkansson Kjell Erik Julius , Ingebrigtsen Truls Sylvan , Johnsen Claus Rikard , Rasmussen Linda Makowska , von Bülow Anna , Assing Karin Dahl , Schmid Johannes Martin , Ulrik Charlotte Suppli , Porsbjerg Celeste 
Published: August 2022

BackgroundPhase III regulatory trials show that anti-interleukin (IL)-5 biologics efficiently reduce exacerbations and the use of maintenance oral corticosteroids (mOCS) in patients with severe eosinophilic asthma. However, patients eligible for these trials differ significantly compared with real-life severe asthma populations. Therefore, our aim was to explore efficacy in a real-life setting. The Danish Severe Asthma Register (DSAR) is a complete, nationwide register that comprises all Danish patients on biological therapy for severe asthma.MethodsThis prospective study identified patients in the DSAR who were complete responders to anti-IL-5 biologics after 1 year of treatment. A complete response was defined as resolution of the parameter setting the indication,i.e.recurrent exacerbations and/or use of mOCS.ResultsA total of 289 out of 502 (58%) patients were complete responders to anti-IL-5 biologics after 12 months. Complete responders had greater improvements in forced expiratory volume in 1 s and Asthma Control Questionnaire (ACQ) score compared with noncomplete responders (Δ 210versus30 mL; p<0.0001 and Δ −1.04versus−0.68; p=0.016, respectively). A complete response was predicted by age at onset, less severe disease at baseline (i.e.no mOCS and lower ACQ score) and higher blood eosinophils.ConclusionsMore than half of Danish patients treated with anti-IL-5 biologics for severe asthma achieve a complete response to treatment, thereby becoming free from asthma exacerbations and the need for mOCS. Complete responders also achieved superior effects on lung function and symptoms compared with noncomplete responders.
Phase I studies of BI 1015550, a preferential phosphodiesterase 4B inhibitor, in healthy males and patients with idiopathic pulmonary fibrosis
Authors: Maher Toby M. , Schlecker Christina , Luedtke Doreen , Bossert Sebastian , Zoz Donald F. , Schultz Armin 
Published: August 2022

IntroductionBI 1015550 is a phosphodiesterase 4 (PDE4) inhibitor that has antifibrotic properties. Phase I and Ic studies were conducted to investigate the safety, tolerability and pharmacokinetics of BI 1015550 in healthy male subjects and patients with idiopathic pulmonary fibrosis (IPF).MethodsIn the phase I study, 42 subjects were partially randomised to receive placebo or BI 1015550 in single rising doses of 36 mg and 48 mg, or multiple rising doses of 6 mg and 12 mg twice daily over 14 days. In the phase Ic study, 15 patients with IPF were randomised to receive 18 mg BI 1015550 or placebo twice daily for up to 12 weeks. For both studies, the primary endpoint was the number of subjects with drug-related adverse events (AEs).ResultsIn the Phase I study, drug-related AEs were reported for 50.0% of healthy male subjects treated with a single dose of BI 1015550, compared with 16.7% receiving placebo. For those receiving multiple doses, drug-related AEs were reported for 37.5% of those treated with BI 1015550 and 12.5% receiving placebo. The most frequently reported AEs by organ class were nervous system disorders, which were largely driven by headache. In the Phase Ic study, drug-related AEs were reported in 90.0% of patients treated with BI 1015550, compared with 60.0% of those receiving placebo. The most frequent AEs by organ class were gastrointestinal AEs.ConclusionsBI 1015550 had an acceptable safety profile in healthy male subjects and male and female patients with IPF, supporting further development in larger trials.
A deep learning framework for identifying essential proteins based on multiple biological information
Authors: Yue Yi , Ye Chen , Peng Pei-Yun , Zhai Hui-Xin , Ahmad Iftikhar , Xia Chuan , Wu Yun-Zhi , Zhang You-Hua 
Published: August 2022

Abstract
Background
Essential Proteins are demonstrated to exert vital functions on cellular processes and are indispensable for the survival and reproduction of the organism. Traditional centrality methods perform poorly on complex protein–protein interaction (PPI) networks. Machine learning approaches based on high-throughput data lack the exploitation of the temporal and spatial dimensions of biological information.

Results
We put forward a deep learning framework to predict essential proteins by integrating features obtained from the PPI network, subcellular localization, and gene expression profiles. In our model, the node2vec method is applied to learn continuous feature representations for proteins in the PPI network, which capture the diversity of connectivity patterns in the network. The concept of depthwise separable convolution is employed on gene expression profiles to extract properties and observe the trends of gene expression over time under different experimental conditions. Subcellular localization information is mapped into a long one-dimensional vector to capture its characteristics. Additionally, we use a sampling method to mitigate the impact of imbalanced learning when training the model. With experiments carried out on the data of Saccharomyces cerevisiae, results show that our model outperforms traditional centrality methods and machine learning methods. Likewise, the comparative experiments have manifested that our process of various biological information is preferable.

Conclusions
Our proposed deep learning framework effectively identifies essential proteins by integrating multiple biological data, proving a broader selection of subcellular localization information significantly improves the results of prediction and depthwise separable convolution implemented on gene expression profiles enhances the performance.
Selecting implementation models, theories, and frameworks in which to integrate intersectional approaches
Authors: Presseau Justin , Kasperavicius Danielle , Rodrigues Isabel Braganca , Braimoh Jessica , Chambers Andrea , Etherington Cole , Giangregorio Lora , Gibbs Jenna C. , Giguere Anik , Graham Ian D. , Hankivsky Olena , Hoens Alison M. , Holroyd-Leduc Jayna , Kelly Christine , Moore Julia E. , Ponzano Matteo , Sharma Malika , Sibley Kathryn M. , Straus Sharon 
Published: August 2022

AbstractBackgroundModels, theories, and frameworks (MTFs) provide the foundation for a cumulative science of implementation, reflecting a shared, evolving understanding of various facets of implementation. One under-represented aspect in implementation MTFs is how intersecting social factors and systems of power and oppression can shape implementation. There is value in enhancing how MTFs in implementation research and practice account for these intersecting factors. Given the large number of MTFs, we sought to identify exemplar MTFs that represent key implementation phases within which to embed an intersectional perspective.MethodsWe used a five-step process to prioritize MTFs for enhancement with an intersectional lens. We mapped 160 MTFs to three previously prioritized phases of the Knowledge-to-Action (KTA) framework. Next, 17 implementation researchers/practitioners, MTF experts, and intersectionality experts agreed on criteria for prioritizing MTFs within each KTA phase. The experts used a modified Delphi process to agree on an exemplar MTF for each of the three prioritized KTA framework phases. Finally, we reached consensus on the final MTFs and contacted the original MTF developers to confirm MTF versions and explore additional insights.ResultsWe agreed on three criteria when prioritizing MTFs: acceptability (mean = 3.20, SD = 0.75), applicability (mean = 3.82, SD = 0.72), and usability (median = 4.00, mean = 3.89, SD = 0.31) of the MTF. The top-rated MTFs were the Iowa Model of Evidence-Based Practice to Promote Quality Care for the ‘Identify the problem’ phase (mean = 4.57, SD = 2.31), the Consolidated Framework for Implementation Research for the ‘Assess barriers/facilitators to knowledge use’ phase (mean = 5.79, SD = 1.12), and the Behaviour Change Wheel for the ‘Select, tailor, implement interventions’ phase (mean = 6.36, SD = 1.08).ConclusionsOur interdisciplinary team engaged in a rigorous process to reach consensus on MTFs reflecting specific phases of the implementation process and prioritized each to serve as an exemplar in which to embed intersectional approaches. The resulting MTFs correspond with specific phases of the KTA framework, which itself may be useful for those seeking particular MTFs for particular KTA phases. This approach also provides a template for how other implementation MTFs could be similarly considered in the future.Trial registrationOpen Science Framework Registration: osf.io/qgh64.
Developing an Unstructured Supplementary Service Data-based mobile phone app to provide adolescents with sexual reproductive health information: a human-centered design approach
Authors: Macharia Paul , Pérez-Navarro Antoni , Inwani Irene , Nduati Ruth , Carrion Carme 
Published: August 2022

Abstract
Background
Adolescent pregnancies and sexually-transmitted infections continue to impact 15 – 19-year-olds across the globe. The lack of sexual reproductive health information (SRH) in resource-limited settings due to cultural and societal attitudes towards adolescent SRH could be contributing to the negative outcomes. Innovative approaches, including mobile phone technologies, are needed to address the need for reliable adolescent SRH information.

Objective
The study aimed to co-design a Unstructured Supplementary Service Data (USSD) based mobile app prototype to provide confidential adolescent SRH information on-demand and evaluate the mobile app’s usability and user experience.

Methods
A human-centered design methodology was applied. This practice framework allowed the perspectives and feedback of adolescent users to be included in the iterative design process. To participate, an adolescent must have been 15 to 19 years old, resided in Kibra and would be able to access a mobile phone. Adolescents were enrolled for the alpha and field testing of the app prototype at different time-points. The Mobile Application Rating Scale (MARS) a multidimensional mobile phone evaluation tool was used to access the functionality, engagement, aesthetics and quality of information in the app. Responses from the MARS were reported as mean scores for each category and a mean of the aggregate scores making the app’s quality score. The MARS data was also evaluated as categorical data, A Chi square test of independence was carried out to show significance of any observed differences using cumulative and inverse cumulative distribution functions.

Results
During the usability test, 62/109 (54.9%) of the adolescents that were followed-up had used the app at least once, 30/62 (48.4%) of these were male participants and 32/62 (51.6%) female. On engagement, the app had a mean score of 4.3/5 (SD 0.44), 4.6/5 (SD 0.38) on functionality, 4.3/5 (SD 0.57) on aesthetics and 4.4/5 (SD 0.60) on the quality of information. The overall app quality mean score was 4.4/5 (SD 0.31). The app was described as ‘very interesting’ to use by 44/62 (70.9%) of the participants, 20/44 males and 24/44 females. The content was deemed to be either ‘perfectly’ or ‘well targeted’ on sexual reproductive health by 60/62 (96.7%) adolescents, and the app was rated ‘best app’ by 45/62 (72.6%) adolescents, 27/45 females and 18/45 males, with a p-value = 0.011.

Conclusions
Adolescents need on-demand, accurate and trusted SRH information. A mobile phone app is a feasible and acceptable way to deliver adolescent SRH information in resource-limited settings. The USSD mobile phone technology shows promise in the delivery of much needed adolescent SRH information on-demand..
A simple pooling method for variable selection in multiply imputed datasets outperformed complex methods
Authors: Panken A. M. , Heymans M. W. 
Published: August 2022

AbstractBackgroundFor the development of prognostic models, after multiple imputation, variable selection is advised to be applied from the pooled model. The aim of this study is to evaluate by using a simulation study and practical data example the performance of four different pooling methods for variable selection in multiple imputed datasets. These methods are the D1, D2, D3 and recently extended Median-P-Rule (MPR) for categorical, dichotomous, and continuous variables in logistic regression models.MethodsFour datasets (n = 200 andn = 500), with 9 variables and correlations of respectively 0.2 and 0.6 between these variables, were simulated. These datasets included 2 categorical and 2 continuous variables with 20% missing at random data. Multiple Imputation (m = 5) was applied, and the four methods were compared with selection from the full model (without missing data). The same analyzes were repeated in five multiply imputed real-world datasets (NHANES) (m = 5,p = 0.05,N = 250/300/400/500/1000).ResultsIn the simulated datasets, the differences between the pooling methods were most evident in the smaller datasets. The MPR performed equal to all other pooling methods for the selection frequency, as well as for the P-values of the continuous and dichotomous variables, however the MPR performed consistently better for pooling and selecting categorical variables in multiply imputed datasets and also regarding the stability of the selected prognostic models. Analyzes in the NHANES-dataset showed that all methods mostly selected the same models. Compared to each other however, the D2-method seemed to be the least sensitive and the MPR the most sensitive, most simple, and easy method to apply.ConclusionsConsidering that MPR is the most simple and easy pooling method to use for epidemiologists and applied researchers, we carefully recommend using the MPR-method to pool categorical variables with more than two levels after Multiple Imputation in combination with Backward Selection-procedures (BWS). Because MPR never performed worse than the other methods in continuous and dichotomous variables we also advice to use MPR in these types of variables.
Haemostatic profile of children with nephrotic syndrome attending University of Nigeria Teaching Hospital Ituku-Ozalla, Nigeria
Authors: Odimegwu Chioma L. , Ikefuna Anthony N. , Okafor Henrietta U. , Nwagha Theresa , Ubesie Agozie , Chinawa Josephat M. 
Published: August 2022

Abstract
Background
Haemostatic derangements are thought to be due to an imbalance between hepatic synthesis of pro-coagulants and urinary losses of anticoagulants.

Objectives
This study evaluated the coagulation profile of Nigerian children with nephrotic syndrome and examined the relationship between coagulation variables, disease state and steroid responsiveness.

Methods
A cross- sectional hospital based study on evaluation of coagulation profile of children with nephrotic syndrome compared with their age- and gender- matched controls.

Results
The median fibrinogen level in subjects and controls was the same (2.9 g/L). Sixteen of 46 (35%) children with nephrotic syndrome had hyperfibrinogenaemia. The median fibrinogen level of children in remission was 2.3 g/L and differed significantly when compared with those of children in relapse (p = 0.001). The median APTT of children with nephrotic syndrome was 45.0 s and differed significantly compared with those of controls (42.0 s) (p value = 0.02). The median prothrombin time in children with and without nephrotic syndrome were 12.0 and 13.0 s respectively, (p = 0.004). About 90% of children with nephrotic syndrome had INR within reference range. Thrombocytosis was found in 15% of children with nephrotic syndrome. The median platelet count in children with new disease was 432 × 103cells/mm3 and differed significantly when compared with those of controls (p = 0.01).
INR was significantly shorter in children with steroid resistant nephrotic syndrome (SRNS) (median 0.8 s; IQR 0.8 -0.9 s) compared with controls (median 1.0 s; IQR 1.0 -1.1 s) (p = 0.01). Steroid sensitivity was the strongest predictor of remission in children with nephrotic syndrome; steroid sensitive patients were 30 times more likely to be in remission than in relapse (OR 30.03; CI 2.01 – 448.04).

Conclusion
This study shows that the haemostatic derangements in childhood nephrotic involve mostly fibrinogen, APTT, PT, INR and platelet counts. Antithrombin levels are largely unaffected. Variations in fibrinogen, APTT, PT and INR values may be due to the heterogeneous nature of the disease.
Female breast cancer incidence predisposing risk factors identification using nationwide big data: a matched nested case-control study in Taiwan
Authors: Liu Ping-Hung , Wei James Cheng-Chung , Wang Yu-Hsun , Yeh Ming-Hsin 
Published: August 2022

Abstract
Background
Breast cancer is an umbrella term referring to a group of biologically and molecularly heterogeneous diseases originating from the breast. Globally, incidences of breast cancer has been increasing dramatically over the past decades. Analyses of multiple clinical “big data” can aid us in clarifying the means of preventing the disease. In addition, predisposing risk factors will be the most important issues if we can confirm their relevance. This study aims to provide an overview of the predisposing factors that contribute to a higher possibility of developing breast cancer and emphasize the signs that we ought to pay more attention to.

Methods
This is a matched nested case-control study. The cohort focused on identifying the eligible risk factors in breast cancer development by data screening (2000-2013) from the Taiwan National Health Insurance Research Database (NHIRD) under approved protocol. A total of 486,069 females were enrolled from a nationwide sampled database, and 3281 females was elligible as breast cancer cohort, 478,574 females who had never diagnosed with breast cancer from 2000 to 2013 were eligible as non-breast cancer controls, and matched to breast cancer cases according to age using a 1:6 ratio.

Results
We analyzed 3281 breast cancer cases and 19,686 non-breast cancer controls after an age-matched procedure. The significant predisposing factors associated with breast cancer development including obesity, hyperlipidemia, thyroid cancer and liver cancer. As for patients under the age of 55, gastric cancer does seem to have an impact on the development of breast cancer; compared with their counterparts over the age of 55, endometrial cancer appears to exhibit an evocative effect.

Conclusions
In this nationwide matched nested case-control study, we identified obesity, hyperlipidemia, previous cancers of the thyroid, stomach and liver as risk factors associated with breast cancer. However, the retrospective nature and limited case numbers of certain cancers still difficult to provide robust evidence. Further prospective studies are necessitated to corroborate this finding in order to nip the disease in the bud.

Trial registration
The studies involving human participants were reviewed and approved by the China Medical University Hospital [CMUH104-REC2-115(AR-4)].
Long-term air pollution levels modify the relationships between short-term exposure to meteorological factors, air pollution and the incidence of hand, foot and mouth disease in children: a DLNM-based multicity time series study in Sichuan Province, China
Authors: Luo Caiying , Qian Jian , Liu Yaqiong , Lv Qiang , Ma Yue , Yin Fei 
Published: August 2022

Abstract
Background
Epidemiological studies have investigated the short-term effects of meteorological factors and air pollution on the incidence of hand, foot, and mouth disease (HFMD). Several meteorological indicators, such as relative humidity and the diurnal temperature range (DTR), significantly modify the relationship between short-term exposure to temperature and HFMD incidence. However, it remains unclear whether (and how) long-term air pollution levels modify the short-term relationships of HFMD incidence with meteorological factors and air pollution.

Methods
We obtained daily data on meteorological factors, air pollutants, and HFMD counts in children from 21 prefecture-level cities in Sichuan Province in Southwest China from 2015 to 2017. First, we constructed a distributed lag nonlinear model (DLNM) at each prefecture-level site to evaluate the short-term impacts of meteorological variables and air pollutants on HFMD incidence. Then, we assessed the pooled effects of the exposures and incorporated long-term city-specific air pollutant indicators as meta-predictors to examine their potential modification effects by performing multivariate meta-regression models.

Results
We found that long-term SO2 and CO concentrations significantly modified the short-term relationships between climatic variables and HFMD incidence. Specifically, high concentrations of CO (P = 0.027) and SO2 (P = 0.039) reduced the risk of HFMD at low temperatures. The relationship between relative humidity and HFMD incidence was weakened at high SO2 concentrations (P = 0.024), especially when the relative humidity was below the median level. When the minimum relative humidity (32%) was compared to the median relative humidity (77%), the risk ratio (RR) was 0.77 (95% CI: 0.51–1.17) in the 90th percentile of SO2 (19.6 μg/m3) and 0.41 (95% CI: 0.27–0.64) in the 10th percentile of SO2 (10.6 μg/m3).

Conclusion
Our results indicated that long-term SO2 and CO levels modified the short-term associations between HFMD incidence in children and meteorological variables. These findings may inform health authorities to optimize targeted public health policies including reducing ambient air pollution and reinforcing self-protective actions to weaken the adverse health impacts of environmental factors on HFMD incidence.