bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tracing the Anharmonicity and Superionic Phase Transition of Hydrous FeO2H
Authors: Hu Qingyang , Tang Mingxue 
Published: June 2022

The weak x-ray scattering of hydrogen (H) has brought major challenges to the characterization of superionic transitions in high-pressure ice, hydrides, and hydroxides. Combining first-principles molecular dynamics and simulated nuclear magnetic resonance (NMR) spectroscopy, we investigated the behavior of the hydroxyl bonding and structural transitions in the hydrous FeO2H between 300 and 2750 K and up to 130 GPa. Evidence show that an intermediate plastic state with regional H diffusion and anharmonic O-H vibration exists in between the ordinary solid and the superionic phase. The intermediate state features asymmetric hydrogen bonds and anharmonic vibrations, which are readily distinguished from the high-temperature superionic phase. Our work shows NMR is a more sensitive probe to detect H diffusion in superionic solids even in the extreme conditions of Earth’s deep interiors.
A Sparse Mixture-of-Experts Model With Screening of Genetic Associations to Guide Disease Subtyping
Authors: Courbariaux Marie , De Santiago Kylliann , Dalmasso Cyril , Danjou Fabrice , Bekadar Samir , Corvol Jean-Christophe , Martinez Maria , Szafranski Marie , Ambroise Christophe 
Published: June 2022

Motivation: Identifying new genetic associations in non-Mendelian complex diseases is an increasingly difficult challenge. These diseases sometimes appear to have a significant component of heritability requiring explanation, and this missing heritability may be due to the existence of subtypes involving different genetic factors. Taking genetic information into account in clinical trials might potentially have a role in guiding the process of subtyping a complex disease. Most methods dealing with multiple sources of information rely on data transformation, and in disease subtyping, the two main strategies used are 1) the clustering of clinical data followed by posterior genetic analysis and 2) the concomitant clustering of clinical and genetic variables. Both of these strategies have limitations that we propose to address.Contribution: This work proposes an original method for disease subtyping on the basis of both longitudinal clinical variables and high-dimensional genetic markers via a sparse mixture-of-regressions model. The added value of our approach lies in its interpretability in relation to two aspects. First, our model links both clinical and genetic data with regard to their initial nature (i.e., without transformation) and does not require post-processing where the original information is accessed a second time to interpret the subtypes. Second, it can address large-scale problems because of a variable selection step that is used to discard genetic variables that may not be relevant for subtyping.Results: The proposed method was validated on simulations. A dataset from a cohort of Parkinson’s disease patients was also analyzed. Several subtypes of the disease and genetic variants that potentially have a role in this typology were identified.Software availability: The R code for the proposed method, named DiSuGen, and a tutorial are available for download (see the references).
Rare Variants in Novel Candidate Genes Associated With Nonsyndromic Patent Ductus Arteriosus Identified With Whole-Exome Sequencing
Authors: Gao Ying , Wu Dan , Chen Bo , Chen Yinghui , Zhang Qi , Zhao Pengjun 
Published: June 2022

Background: Patent ductus arteriosus (PDA) is one of the most common congenital heart defects causing pulmonary hypertension, infective endocarditis, and even death. The important role of genetics in determining spontaneous ductal closure has been well-established. However, as many of the identified variants are rare, thorough identification of the associated genetic factors is necessary to further explore the genetic etiology of PDA.Methods: We performed whole-exome sequencing (WES) on 39 isolated nonsyndromic PDA patients and 100 healthy controls. Rare variants and novel genes were identified through bioinformatic filtering strategies. The expression patterns of candidate genes were explored in human embryo heart samples.Results: Eighteen rare damaging variants of six novel PDA-associated genes (SOX8, NES, CDH2, ANK3, EIF4G1, and HIPK1) were newly identified, which were highly expressed in human embryo hearts.Conclusions: WES is an efficient diagnostic tool for exploring the genetic pathogenesis of PDA. These findings contribute new insights into the molecular basis of PDA and may inform further studies on genetic risk factors for congenital heart defects.
Bioinformatics-Led Discovery of Osteoarthritis Biomarkers and Inflammatory Infiltrates
Authors: Hu Xinyue , Ni Songjia , Zhao Kai , Qian Jing , Duan Yang 
Published: June 2022

The molecular mechanisms of osteoarthritis, the most common chronic disease, remain unexplained. This study aimed to use bioinformatic methods to identify the key biomarkers and immune infiltration in osteoarthritis. Gene expression profiles (GSE55235, GSE55457, GSE77298, and GSE82107) were selected from the Gene Expression Omnibus database. A protein-protein interaction network was created, and functional enrichment analysis and genomic enrichment analysis were performed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) databases. Immune cell infiltration between osteoarthritic tissues and control tissues was analyzed using the CIBERSORT method. Identify immune patterns using the ConsensusClusterPlus package in R software using a consistent clustering approach. Molecular biological investigations were performed to discover the important genes in cartilage cells. A total of 105 differentially expressed genes were identified. Differentially expressed genes were enriched in immunological response, chemokine-mediated signaling pathway, and inflammatory response revealed by the analysis of GO and KEGG databases. Two distinct immune patterns (ClusterA and ClusterB) were identified using the ConsensusClusterPlus. Cluster A patients had significantly lower resting dendritic cells, M2 macrophages, resting mast cells, activated natural killer cells and regulatory T cells than Cluster B patients. The expression levels of TCA1, TLR7, MMP9, CXCL10, CXCL13, HLA-DRA, and ADIPOQSPP1 were significantly higher in the IL-1β-induced group than in the osteoarthritis group in an in vitro qPCR experiment. Explaining the differences in immune infiltration between osteoarthritic tissues and normal tissues will contribute to the understanding of the development of osteoarthritis.
Availability of the Yellow Fever Vaccine in Primary Health Care Services in Brazil
Authors: Hermsdorf Marina Oliveira , da Silva Tércia Moreira Ribeiro , Lachtim Sheila Aparecida Ferreira , Matozinhos Fernanda Penido , Beinner Mark Anthony , Vieira Ed Wilson Rodrigues 
Published: June 2022

ObjectivesTo analyze the availability of the Yellow Fever (YF) vaccine at Primary Health Care (PHC) services located in areas with vaccine recommendation in Brazil between two different periods.MethodsSecondary data from the Program for Improving Access and Quality in PHC, with 13,666 services in 2013-14, and 19,125 in 2017-18, were used. A structured questionnaire was used for the data collection. Pearson’s chi-square and thematic cartographic maps were used to analyze the frequency of the YF vaccine, and Poisson regression with robust variances was used to analyze the associated factors.ResultsThe overall frequency of PHC facilities with YF vaccine always available increased from 87.0% (CI 95%; 86.4-87.5) in 2013-14 to 89.7% (CI 95%; 89.2-90.1) in 2017-18. Facilities located in the South, Southeast, Midwest and Northern regions and in non-state capitals, as well as centers that had adequate facilities for vaccination actions, as well as an adey -50quate cold chain network, showed a greater prevalence of YF vaccine always available.ConclusionThe frequency of a steady supply of YF vaccine available at PHC facilities, located in Areas with Routine Vaccination Recommendations, increased between 2013-14 and 2017-18. Geographical and structural characteristics related to vaccine actions at PHC facilities influenced access. The effective supply chain networks for the YF vaccine, together with adequate services at PHC facilities are essential to ensuring that the YF vaccine is always available.
Diagnostic Accuracy of Liquid Biomarkers in Airway Diseases: Toward Point-of-Care Applications
Authors: Landry Vivianne , Coburn Patrick , Kost Karen , Liu Xinyu , Li-Jessen Nicole Y. K. 
Published: June 2022

BackgroundLiquid biomarkers have shown increasing utility in the clinical management of airway diseases. Salivary and blood samples are particularly amenable to point-of-care (POC) testing due to simple specimen collection and processing. However, very few POC tests have successfully progressed to clinical application due to the uncertainty and unpredictability surrounding their diagnostic accuracy.ObjectiveTo review liquid biomarkers of airway diseases with well-established diagnostic accuracies and discuss their prospects for future POC applications.MethodologyA literature review of publications indexed in Medline or Embase was performed to evaluate the diagnostic accuracy of liquid biomarkers for chronic obstructive pulmonary disease (COPD), asthma, laryngopharyngeal reflux (LPR), and COVID-19.ResultsOf 3,628 studies, 71 fulfilled the inclusion criteria. Sputum and blood eosinophils were the most frequently investigated biomarkers for the management of asthma and COPD. Salivary pepsin was the only biomarker with a well-documented accuracy for the diagnosis of LPR. Inflammatory blood biomarkers (e.g., CRP, D-dimers, ferritin) were found to be useful to predict the severity, complications, and mortality related to COVID-19 infection.ConclusionMultiple liquid biomarkers have well-established diagnostic accuracies and are thus amenable to POC testing in clinical settings.
Application of Internet of Medical/Health Things to Decentralized Clinical Trials: Development Status and Regulatory Considerations
Authors: Sato Takahiro , Ishimaru Hikaru , Takata Takuya , Sasaki Hajime , Shikano Mayumi 
Published: June 2022

BackgroundThe need for a new style of clinical trials, called decentralized clinical trials (DCTs), has been increasing as they do not depend on physical visits to clinical sites. DCTs are expected to provide a new opportunity to patients who cannot participate in a clinical trial due to geographical and time limitations. For the adoption of DCTs, it is essential that medical devices with Internet of Medical Things (IoMT) and Internet of Health Things (IoHT) based technologies are developed and commercially adopted. In this study, we aimed to identify the regulatory considerations when IoMT/IoHT-based technologies are used in DCTs or products developed using DCTs.MethodTo understand the study and development field of IoMT/IoHT comprehensively and panoramically, relevant papers published in Web of Science were searched online. Subsequently, a citation network was obtained and characterized as a cluster using a text mining method to identify IoMT/IoHT-based technologies expected to be utilized in DCTs or products developed using DCTs.Result and DiscussionUpon analysis of the top 15 clusters and subsequent 51 sub-clusters, we identified the therapeutic areas (psychology, neurology) and IoMT/IoHT-based technologies (telemedicine, remote monitoring, and virtual reality) that are expected to be used in DCTs. We also identified several considerations based on the current regulatory guidance.ConclusionIoMT/IoHT-based technologies that are expected to be used or products developed using DCTs and key considerations made when they are used in DCTs were identified. The considerations could encourage conducting DCTs using IoMT/IoHT-based technologies.
Metformin Induces PRODH/POX-Dependent Apoptosis in Breast Cancer Cells
Authors: Huynh Thi Yen Ly , Oscilowska Ilona , Szoka Lukasz , Piktel Ewelina , Baszanowska Weronika , Bielawska Katarzyna , Bucki Robert , Miltyk Wojciech , Palka Jerzy 
Published: June 2022

Although the antineoplastic activity of metformin (MET) is well established, the underlying mechanism of the activity is not understood. Since MET activates AMP kinase (AMPK) and proline dehydrogenase/proline oxidase (PRODH/POX) is stimulated by AMPK ligands (implicated in the regulation of cancer cell survival/apoptosis), the effect of MET on PRODH/POX-dependent apoptosis in wild-type MCF-7 cells (MCF-7WT) and POX knockdown MCF-7 cells (MCF-7crPOX cells) was studied. PRODH/POX catalyzes proline degradation generating ROS-induced apoptosis or autophagy. Availability of proline for PRODH/POX functions is regulated by the activity of prolidase (enzyme releasing proline from imidodipeptides), collagen biosynthesis (process consuming proline), and metabolism of proline, ornithine, and glutamic acid. We have found that MET is cytotoxic for MCF-7 cells (IC50∼17 mM), and to the lower extent for MCF-7crPOX cells (IC50∼28 mM). In MCF-7WT cells, the effect was accompanied by the inhibition of DNA biosynthesis, collagen biosynthesis, stimulation of ROS formation, AMPKα phosphorylation, and expression of prolidase, p53, caspase 8, caspase 9, and cleaved PARP. In MET-treated MCF-7crPOX cells, the processes were less affected than in MCF-7WT cells and the expression of caspase 9 was decreased, while cleaved caspase 8 and cleaved PARP were not detected. The effects were accompanied by an increase in the prolidase activity and proline concentration. The mechanism for MET-induced apoptosis involves the up-regulation of prolidase activity and a decrease in collagen biosynthesis contributing to an increase in the concentration of substrate (proline) for PRODH/POX-dependent ROS formation and activation of caspases −9 and −8. The data suggest that PRODH/POX participates in the MET-induced intrinsic and extrinsic apoptosis in MCF-7 cells.
Gray Matter Volume Abnormality in Chronic Pain Patients With Depressive Symptoms: A Systemic Review and Meta-Analysis of Voxel-Based Morphometry Studies
Authors: Ma Teng , Ji Yuan-Yuan , Yan Lin-Feng , Lin Jia-Ji , Li Ze-Yang , Wang Wen , Li Jin-Lian , Cui Guang-Bin 
Published: June 2022

BackgroundGray matter volume (GMV) alteration in specific brain regions has been widely regarded as one of the most important neuroplasticity features in chronic pain patients with depressive symptoms (CP-D). However, the consistent and significant results were still lacking. Thus, further exploration was suggested to be performed.ObjectivesThis study aimed to comprehensively collect the voxel-based morphometry (VBM) studies on GMV alteration between CP-D and healthy controls (HCs). And a systemic review and meta-analysis were made to explore the characteristic brain regions in chronic pain and depression comorbidity.MethodsSearch of PubMed, MEDLINE, Web of Science, and Cochrane Library databases updated to July 13, 2021. The altered GMV between CP-D and HCs in VBM studies was included in this meta-analysis. In total, 18 studies (20 datasets) and 1320 participants (520 patients and 800 HCs) were included. The significant coordinate information (x, y, z) reported in standard space and the effect size (t-value or z-score) were extracted and analyzed by anisotropic effect size-signed differential mapping (AES-SDM) 5.15 software.ResultsAccording to the main analysis results, CP-D showed significant and consistent increased GMV in the left hippocampus (HIP. L) and decreased GMV in the medial part of the left superior frontal gyrus (SFG. L, BA 10) compared to HCs. Subgroup analysis showed significant decreased GMV in the medial orbital part of SFG.R (BA 10) in neuropathic pain, as well as significant increased GMV in the right parahippocampal gyrus (PHG.R, BA 35), left hippocampus (HIP.L, BA 20), and right middle frontal gyrus (MFG.R) in musculoskeletal pain. Furthermore, meta-regression showed a positive relationship between the decreased GMV in the medial part of SFG.L and the percentage of female patients.ConclusionGMV abnormality in specific brain areas (e.g., HIP.L and SFG) was robust and reproducible, which could be significantly involved in this comorbidity disease. The findings in this study may be a valuable reference for future research.Systematic Review Registration[www.crd.york.ac.uk/prospero/].
Discrete Wavelet Transform Analysis of the Electroretinogram in Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder
Authors: Constable Paul A. , Marmolejo-Ramos Fernando , Gauthier Mercedes , Lee Irene O. , Skuse David H. , Thompson Dorothy A. 
Published: June 2022

BackgroundTo evaluate the electroretinogram waveform in autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) using a discrete wavelet transform (DWT) approach.MethodsA total of 55 ASD, 15 ADHD and 156 control individuals took part in this study. Full field light-adapted electroretinograms (ERGs) were recorded using a Troland protocol, accounting for pupil size, with five flash strengths ranging from –0.12 to 1.20 log photopic cd.s.m–2. A DWT analysis was performed using the Haar wavelet on the waveforms to examine the energy within the time windows of the a- and b-waves and the oscillatory potentials (OPs) which yielded six DWT coefficients related to these parameters. The central frequency bands were from 20–160 Hz relating to the a-wave, b-wave and OPs represented by the coefficients: a20, a40, b20, b40, op80, and op160, respectively. In addition, the b-wave amplitude and percentage energy contribution of the OPs (%OPs) in the total ERG broadband energy was evaluated.ResultsThere were significant group differences (p &lt; 0.001) in the coefficients corresponding to energies in the b-wave (b20, b40) and OPs (op80 and op160) as well as the b-wave amplitude. Notable differences between the ADHD and control groups were found in the b20 and b40 coefficients. In contrast, the greatest differences between the ASD and control group were found in the op80 and op160 coefficients. The b-wave amplitude showed both ASD and ADHD significant group differences from the control participants, for flash strengths greater than 0.4 log photopic cd.s.m–2 (p &lt; 0.001).ConclusionThis methodological approach may provide insights about neuronal activity in studies investigating group differences where retinal signaling may be altered through neurodevelopment or neurodegenerative conditions. However, further work will be required to determine if retinal signal analysis can offer a classification model for neurodevelopmental conditions in which there is a co-occurrence such as ASD and ADHD.
The Use of Bioelectrical Impedance Analysis Measures for Predicting Clinical Outcomes in Critically Ill Children
Authors: Xiong Zi-Hong , Zheng Xue-Mei , Zhang Guo-Ying , Wu Meng-Jun , Qu Yi 
Published: June 2022

BackgroundThe study aimed to investigate the association of bioelectrical impedance analysis (BIA) for predicting clinical outcomes in critically ill children.MethodsThis single-center prospective observational study included patients admitted to a mixed Pediatric Intensive Care Unit (PICU). All patients underwent anthropometric measurement and BIA measurements in the first 24 h of admission. The patients were classified into different groups based on body mass index (BMI) for age. Electronic hospital medical records were reviewed to collect clinical data for each patient. All the obtained data were analyzed by the statistical methods.ResultsThere were 231 patients enrolled in our study, of which 31.6% were diagnosed with malnutrition. The phase angle (PhA) of 90-day survivors was significantly higher than that of the non-survivors (4.3° ± 1.1°vs. 3.1° ± 0.9°, P = 0.02). The age-adjusted Spearman partial correlation analysis showed a weak negative correlation between PhA and duration of medical ventilation (rs = -0.42, P &lt; 0.05). Furthermore, length of stay in PICU has a very weak correlation with ECW/TBW (rs = 0.29, P &lt; 0.05), and a negative correlation with protein (rs = -0.27, P &lt; 0.05). Multivariate analysis found that PhA was a significant predictor associated with the 90-day mortality when it was adjusted for PRISM III score (adjusted OR = 1.51, CI: 1.10–2.07, p = 0.01). The area under the ROC (AUROC) of PhA for predicting 90-day mortality was 0.69 (95% CI: 0.53–0.85, p &lt; 0.05), and the cutoff value of PhA was 3.0°, with a sensitivity and specificity of 83 and 53%, respectively.ConclusionBIA-derived PhA was found to be an independent predictor of 90-day mortality among critically ill children. A low PhA was associated with a prolonged duration of medical ventilation.
A Novel Combined Nomogram Model for Predicting the Pathological Complete Response to Neoadjuvant Chemotherapy in Invasive Breast Carcinoma of No Specific Type: Real-World Study
Authors: Zhu Xuelin , Shen Jing , Zhang Huanlei , Wang Xiulin , Zhang Huihui , Yu Jing , Zhang Qing , Song Dongdong , Guo Liping , Zhang Dianlong , Zhu Ruiping , Wu Jianlin 
Published: June 2022

ObjectiveTo explore the value of a predictive model combining the multiparametric magnetic resonance imaging (mpMRI) radiomics score (RAD-score), clinicopathologic features, and morphologic features for the pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in invasive breast carcinoma of no specific type (IBC-NST).MethodsWe enrolled, retrospectively and consecutively, 206 women with IBC-NST who underwent surgery after NAC and obtained pathological results from August 2018 to October 2021. Four RAD-scores were constructed for predicting the pCR based on fat-suppression T2-weighted imaging (FS-T2WI), diffusion-weighted imaging (DWI), contrast-enhanced T1-weighted imaging (T1WI+C) and their combination, which was called mpMRI. The best RAD-score was combined with clinicopathologic and morphologic features to establish a nomogram model through binary logistic regression. The predictive performance of the nomogram was evaluated using the area under receiver operator characteristic (ROC) curve (AUC) and calibration curve. The clinical net benefit of the model was evaluated using decision curve analysis (DCA).ResultsThe mpMRI RAD-score had the highest diagnostic performance, with AUC of 0.848 among the four RAD-scores. T stage, human epidermal growth factor receptor-2 (HER2) status, RAD-score, and roundness were independent factors for predicting the pCR (P &lt; 0.05 for all). The combined nomogram model based on these factors achieved AUCs of 0.930 and 0.895 in the training cohort and validation cohort, respectively, higher than other models (P &lt; 0.05 for all). The calibration curve showed that the predicted probabilities of the nomogram were in good agreement with the actual probabilities, and DCA indicated that it provided more net benefit than the treat-none or treat-all scheme by decision curve analysis in both training and validation datasets.ConclusionThe combined nomogram model based on the mpMRI RAD-score combined with clinicopathologic and morphologic features may improve the predictive performance for the pCR of NAC in patients with IBC-NST.