bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quality of a Supporting Mobile App for Rheumatic Patients: Patient-Based Assessment Using the User Version of the Mobile Application Scale (uMARS)
Authors: Lambrecht Antonia , Vuillerme Nicolas , Raab Christina , Simon David , Messner Eva-Maria , Hagen Melanie , Bayat Sara , Kleyer Arnd , Aubourg Timothée , Schett Georg , Hueber Axel , Knitza Johannes 
Published: July 2021

Introduction: Mobile applications promise to improve current health care. However, current mobile app quality ratings are mostly physician-based. The aim of this study was (1) to assess the quality of the self-management app Rheuma Auszeit using the validated uMARS (User Version of the Mobile App Rating Scale) app quality assessment tool and (2) to evaluate the association between uMARS scores and patients' characteristics.Materials and Methods: Consecutive patients with rheumatoid arthritis, psoriatic arthritis and spondyloarthritis were seen at the rheumatology clinic at university hospital Erlangen, Germany. They were asked to test Rheuma Auszeit, evaluate its quality using uMARS and complete a paper-based survey evaluating the individual preferences, attitudes and ehealth literacy. The association between uMARS scores and patients' characteristics was further explored.Results: Between December 2018 and January 2019, a total of 126 patients evaluated Rheuma Auszeit using uMARS and filled out the paper-based survey. The median uMARS score was 3.9, IQR 0.7. Functionality was the domain with the highest rating (median 4.8, IQR 0.8), followed by aesthetics (median 4.0, IQR 0.7), information (median 3.5, IQR 0.8), and engagement (median 3.2, IQR 1.0). Subjective quality was average (median 3.0, IQR 1.0). The lowest scoring individual item was customization with a median of 2.5/5. Lower functionality scores were reported among older female rheumatic patients (P &lt; 0.004). Older male rheumatic patients reported a higher subjective quality score (P &lt; 0.024). Perceived disease activity and disease duration did not significantly correlate with any uMARS subdomain scores. eHealth literacy significantly correlated with functionality uMARS subdomain ratings (Rho = 0.18; P &lt; 0.042). Preferred time of app usage significantly correlated with engagement (Rho = 0.20; P &lt; 0.024), functionality (Rho = 0.19; P &lt; 0.029), total uMARS score (Rho = 0.21; P &lt; 0.017) and subjective quality score (Rho = 0.21; P &lt; 0.017). The vast majority of rheumatic patients would consider recommending Rheuma Auszeit to other patients (117/126; 92.9%).Conclusion: Rheuma Auszeit was well-accepted by German patients suffering from rheumatoid arthritis, psoriatic arthritis and ankylosing spondyloarthritis. Lacking customization could lead to low app compliance and should be improved. Lower functionality scores among older female rheumatic patients highlight the need for patient education. The study underlines the potential and feasibility of therapeutic complementary digital solutions in rheumatology.
Generating Chromosome Geometries in a Minimal Cell From Cryo-Electron Tomograms and Chromosome Conformation Capture Maps
Authors: Gilbert Benjamin R. , Thornburg Zane R. , Lam Vinson , Rashid Fatema-Zahra M. , Glass John I. , Villa Elizabeth , Dame Remus T. , Luthey-Schulten Zaida 
Published: July 2021

JCVI-syn3A is a genetically minimal bacterial cell, consisting of 493 genes and only a single 543 kbp circular chromosome. Syn3A’s genome and physical size are approximately one-tenth those of the model bacterial organismEscherichia coli’s, and the corresponding reduction in complexity and scale provides a unique opportunity for whole-cell modeling. Previous work established genome-scale gene essentiality and proteomics data along with its essential metabolic network and a kinetic model of genetic information processing. In addition to that information, whole-cell, spatially-resolved kinetic models require cellular architecture, including spatial distributions of ribosomes and the circular chromosome’s configuration. We reconstruct cellular architectures of Syn3A cells at the single-cell level directly from cryo-electron tomograms, including the ribosome distributions. We present a method of generating self-avoiding circular chromosome configurations in a lattice model with a resolution of 11.8 bp per monomer on a 4 nm cubic lattice. Realizations of the chromosome configurations are constrained by the ribosomes and geometry reconstructed from the tomograms and include DNA loops suggested by experimental chromosome conformation capture (3C) maps. Using ensembles of simulated chromosome configurations we predict chromosome contact maps for Syn3A cells at resolutions of 250 bp and greater and compare them to the experimental maps. Additionally, the spatial distributions of ribosomes and the DNA-crowding resulting from the individual chromosome configurations can be used to identify macromolecular structures formed from ribosomes and DNA, such as polysomes and expressomes.
Development and Validation of the Prognostic Index Based on Inflammation-Related Gene Analysis in Idiopathic Pulmonary Fibrosis
Authors: Lu Yanjiao , Chen Jinkun , Tang Kun , Wang Shanshan , Tian Zhen , Wang Meijia , Zhao Jianping , Xie Jungang 
Published: July 2021

Background:Historically, idiopathic pulmonary fibrosis (IPF) was considered a chronic inflammation disorder, but this conception was reassessed in the past decades. Our understanding of the role of inflammation in IPF and its association with clinical significance remained incomplete.Methods:We downloaded mRNA expression data of peripheral blood mononuclear cells (PBMCs) from the Gene Expression Omnibus (GEO) repository. Inflammation-related genes (IRGs) expressed differently between IPF and control (CTRL) were determined. In this study, we systemically analyzed the expression of differently expressed IRGs by comprehensive bioinformatic analysis, and then investigated their potential prognostic values. The related prognostic gene expressions were verified in our cohort.Results:110 differently expressed IRGs were identified in this study, including 64 upregulated and 46 downregulated IRGs. Three IRGs (S100A12,CCR7, andTNFSF4) were identified as potential hub genes for prognosis. Those genes were subsequently subjected to the construction of the prognostic models. In the results, IPF patients categorized as high risk demonstrated a poor overall survival rate compared to patients categorized as low risk. Based on this prognostic model, the area under the curve (AUC) of the survival-dependent receiver operator characteristic (ROC) for 1-year, 2-year, and 3-year survival rates was 0.611, 0.695, and 0.681, respectively, in the GSE28042 cohort. These observations were validated in the GSE27957 cohort, confirming the good prognostic effect of this model. The expression of the three genes was validated in our cohort. We also conducted a nomogram based on the three IRGs’ mRNA for quantitative IPF prognosis.Conclusion:Three IRGs (S100A12,CCR7, andTNFSF4) were identified as potential markers for the prognosis of IPF.
Effectiveness, Healthcare Resource Utilization and Adherence to Subcutaneous Interferon Beta-1a According to Age in Patients With Multiple Sclerosis: A Cohort Study Using a US Claims Database
Authors: Allignol Arthur , Boutmy Emmanuelle , Sabidó Espin Meritxell , Marhardt Kurt , Vermersch Patrick 
Published: July 2021

Background: It is thought that older patients with multiple sclerosis (MS) may present with a different clinical disease phenotype, and therefore respond to subcutaneous interferon beta-1a (sc IFN β-1a) differently to younger patients. However, few real-world data are available concerning the effectiveness of sc IFN β-1a according to age. Using data from US claims databases, this cohort analysis aimed to determine the differences in relapse rates, healthcare utilization, treatment adherence, and discontinuation according to pre-defined age groups.Methods: Patient data were pooled from the IBM® MarketScan® Commercial Claims Database and Medicare Supplemental Database. Patients with a confirmed MS diagnosis who initiated treatment with sc IFN β-1a between July 01, 2010 and December 31, 2015, along with at least 6 months continuous enrolment in a healthcare plan, were followed from first prescription (index date) until date of discontinuation, treatment switch, or end of observation period (1 year after index date).Results: Of the 5,340 patients included in the analysis, there was a high proportion of patients free from relapse across all age groups (range: 94.1–95.4%), with a numerical decrease in the number of MRI performed by age (mean: 0.25, 18–30 years; 0.20, 31–40 years; 0.16, 41–50 years; 0.14, ≥51 years). Adherence (≥80%) was seen to increase with age (77.6%, 18–30 years; 79.6%, 31–40 years; 81.3%, 41–50 years; 84.0%, ≥51 years), at the same time as a non-significant decrease in discontinuation (incidence rate: 79.91, 73.01, 71.75, 68.71%).Conclusion: The effectiveness of sc IFN β-1a does not appear reduced as a consequence of age in this real-world setting. Older patients had lower discontinuation rates and reduced disease activity, reflected in lower relapse rates and fewer MRI scans compared with younger patients.
Sex Differences in Neurophysiological Changes Following Voluntary Exercise in Adolescent Rats
Authors: Ferguson Lindsay , Giza Christopher C. , Serpa Rebecka O. , Greco Tiffany , Robert Hannah , Folkerts Michael , Prins Mayumi L. 
Published: July 2021

Background: Adolescence is a period of time characterized by the onset of puberty and is marked by cognitive and social developments and gross physical changes that can play a role in athletic performance. Sex differences are present with differences in body size, height, physiology and behavior which contribute to differences in athletic performance as well. Pre-clinical studies representing this active group are lacking.Methods: Acute and chronic effects of exercise were evaluated. Male and female adolescent rats were given voluntary access to a running wheel for 10 consecutive days. Running behavior (males and females) and estrous cycling (females only) were analyzed daily. A second group was given 10 days of voluntary access to a running wheel, then rested for 10 days to determine the long-term effects of exercise on the adolescent brain. Brain and muscle tissue were harvested at 10 and 20 day time points to understand exercise-dependent changes in mitochondrial activity and neuroplasticity. Animal cohorts were carried out at two different sites: University of California Los Angeles and Pepperdine University.Results: On average, running distance, intensity of run, and length of running bout increased for both male and female rats across the 10 days measured. Females ran significantly further and for longer intervals compared to males. Cortical and muscle expression of PGC1α showed similar levels at 10 days regardless of sex and exercise. There was a significant increase in expression at 20 days in all groups correlating with body size (p's &lt; 0.05). Cortical and hippocampal levels of BDNF were similar across all groups, however, BDNF was significantly higher in exercised females at the acute compared to long-term time point.Discussion: Adolescent rats allowed 10 days of exercise show changes in physiologic function. There are sex differences in running behavior not impacted by sex hormones. These results are important to further our understanding of how exercise impacts the adolescent brain.
The Pathological Features of Common Hereditary Mitochondrial Dynamics Neuropathy
Authors: Wu Rui , Lv He , Wang Hui , Wang Zhaoxia , Yuan Yun 
Published: July 2021

ObjectivesMitofusin 2 and ganglioside-induced differentiation-associated protein 1 are two main mitochondrial dynamics-related proteins. Dysfunction of these two proteins leads to different subtypes of Charcot–Marie–Tooth disease type 2A (CMT2A) and CMT2K. This study aims to report the pathological difference between CMT2A and CMT2K in a large cohort.MethodsThirty patients with molecularly confirmed CMT2A and nine with CMT2K were identified by next-generation sequencing. Sural nerve biopsies were performed in 29 patients.ResultsThe patients with both diseases showed length-dependent neuropathy with distal weakness, sensory loss, and no deep tendon reflex. Optic neuropathy appeared in 3/30 (10%) patients with CMT2A. Tendon contracture appeared in 4/9 (50.0%) patients with CMT2K. Sural biopsy revealed the loss of both myelinated and unmyelinated nerve fibers. Closely packed, irregularly oriented neurofilaments were observed in axons of unmyelinated nerve fibers in both diseases. Another important finding was the ubiquitous presence of smaller, rounded, and fragmented mitochondria in CMT2A and elongated mitochondria in CMT2K in the myelinated and unmyelinated axons.ConclusionThis study confirmed large diversity in phenotypes between CMT2A and CMT2K. Mitochondrial dynamics-related variations can induce different mitochondrial morphological changes and neurofilament accumulation in axons.
A Novel Nomogram Based on Log Odds of Metastatic Lymph Nodes to Predict Overall Survival in Patients With Perihilar Cholangiocarcinoma After Surgery
Authors: Zou Wenbo , Zhu Chunyu , Wang Zizheng , Tan Xianglong , Li Chenggang , Zhao Zhiming , Hu Minggen , Liu Rong 
Published: July 2021

BackgroundVarious lymph node staging strategies were reported to be significantly correlated with perihilar cholangiocarcinoma(pCCA) prognosis. This study aimed to evaluate their predictive abilities and construct an optimal model predicting overall survival (OS).MethodsPatients with pCCA were collected as the training cohort from the Surveillance, Epidemiology, and End Results (SEER) database. Four models were constructed, involving four LNs staging strategies. The optimal model for predicting OS was evaluated by calculation of the concordance index (C-index) and Akaike information criterion (AIC), and validated by using the area under curve (AUC) and calibration curves. The clinical benefits of nomogram were evaluated by decision curve analysis (DCA). A Chinese cohort was collected to be an external validation cohort.ResultsThere were 319 patients and 109 patients in the SEER database and Chinese cohort respectively. We developed an optimal model involving age, T stage, tumor size, LODDS, which showed better predictive accuracy than others. The C-index of the nomogram was 0.695, the time-dependent AUC exceeded 0.7 within 36 months which was significantly higher than that of the American Joint Committee on Cancer (AJCC) stage. The calibration curves for survival probability showed the nomogram prediction had good uniformity of the practical survival. The DCA curves exhibited our nomogram with higher clinical utility compared with the AJCC stage and single LOODS.ConclusionsLODDS is a strong independent prognostic factor, and the nomogram has a great ability to predict OS, which helps assist clinicians to conduct personalized clinical practice.
Geometric and Dosimetric Changes in Tumor and Lung Tissue During Radiotherapy for Lung Cancer With Atelectasis
Authors: Chen Hua , Shao Yan , Gu Xiaohua , Zheng Zhijie , Wang Hao , Gu Hengle , Duan Yanhua , Feng Aihui , Huang Ying , Gan Wutian , Chen Chongyang , Xu Zhiyong 
Published: July 2021

Background and PurposeThis article retrospectively characterized the geometric and dosimetric changes in target and normal tissues during radiotherapy for lung cancer patients with atelectasis.Materials and MethodsA total of 270 cone beam computed tomography (CBCT) scans of 18 lung patients with atelectasis were collected. The degree and time of resolution or expansion of the atelectasis were recorded. The geometric, dosimetric, and biological changes in the target and lung tissue were also quantified.ResultsThere were two patients with expansion, four patients with complete regression, six patients with partial regression, and six patients with no change. The time of resolution or expansion varied. The tumor volume increased by 3.8% in the first seven fractions, then decreased from the 9th fraction, and by 33.4% at the last CBCT. In the LR direction, the average center of mass (COM), boundaries of the tumors gradually shifted mediastinally. In the AP direction, the COM of the tumors was shifted slightly in the posterior direction and then gradually shifted to the anterior direction; the boundaries of the tumors all moved mediastinally. In the SI direction, the COM of the tumors on the right side of the body was substantially shifted toward the head direction. The boundaries of the tumors varied greatly. D2, D98, Dmean, V95, V107, and TCP of the PTV were reduced during radiotherapy and were reduced to their lowest values during the last two fractions. The volume of the ipsilateral lung tended to increase gradually. The V5, V10, V20, V30, V40, and NTCP of the total lung gradually increased with the fraction.ConclusionsFor most patients, regression of the atelectasis occurred, and the volume of the ipsilateral lung tended to increase while the tumor volume decreased, and the COM and boundary of the tumors shifted toward mediastinum, which caused an insufficient dose to the target and an overdose to the lungs. Regression or expansion may occur for any fraction, and it is therefore recommended that CBCT be performed at least every other day.
Protein Tyrosine Kinase 7 Regulates EGFR/Akt Signaling Pathway and Correlates With Malignant Progression in Triple-Negative Breast Cancer
Authors: Cui Nai-Peng , Qiao Shu , Jiang Shan , Hu Jin-Lin , Wang Ting-Ting , Liu Wen-Wen , Qin Yan , Wang Ya-Nan , Zheng Li-Shuang , Zhang Jin-Chao , Ma Yong-Ping , Chen Bao-Ping , Shi Jian-Hong 
Published: July 2021

PurposeTriple-negative breast cancer (TNBC), the most aggressive subtype of breast cancer, is associated with high invasiveness, high metastatic occurrence and poor prognosis. Protein tyrosine kinase 7 (PTK7) plays an important role in multiple cancers. However, the role of PTK7 in TNBC has not been well addressed. This study was performed to evaluate the role of PTK7 in the progression of TNBC.MethodsCorrelation of PTK7 expression with clinicopathological parameters was assessed using tissue microarray immunohistochemistry (IHC) staining in 280 patients with breast cancer. PTK7 expression in TNBC (MDA-MB-468, MDA-MB-436 and MDA-MB-231) and non-TNBC (MCF7 and SK-BR-3) breast cancer cell lines were examined using immunoblotting assay. PTK7 correlated genes in invasive breast carcinoma were analyzed using cBioPortal breast cancer datasets including 1,904 patients. PTK7 overexpressed or knockdown TNBC cell lines (MDA-MB-468 and MDA-MB-436) were used to analyze the potential roles of PTK7 in TNBC metastasis and tumor progression. A TNBC tumor bearing mouse model was established to further analyze the role of PTK7 in TNBC tumorigenicity in vivo.ResultsPTK7 is highly expressed in breast cancer and correlates with worse prognosis and associates with tumor metastasis and progression in TNBC. Co-expression analysis and gain- or loss-of-function of PTK7 in TNBC cell lines revealed that PTK7 participates in EGFR/Akt signaling regulation and associated with extracellular matrix organization and migration genes in breast cancer, including COL1A1, FN1, WNT5B, MMP11, MMP14 and SDC1. Gain- or loss-of-function experiments of PTK7 suggested that PTK7 promotes proliferation and migration in TNBC cell lines. PTK7 knockdown MDA-MB-468 cell bearing mouse model further demonstrated that PTK7-deficiency inhibits TNBC tumor progression in vivo.ConclusionThis study identified PTK7 as a potential marker of worse prognosis in TNBC and revealed PTK7 promotes TNBC metastasis and progression via EGFR/Akt signaling pathway.
Prediction of EGFR Mutation Status Based on 18F-FDG PET/CT Imaging Using Deep Learning-Based Model in Lung Adenocarcinoma
Authors: Yin Guotao , Wang Ziyang , Song Yingchao , Li Xiaofeng , Chen Yiwen , Zhu Lei , Su Qian , Dai Dong , Xu Wengui 
Published: July 2021

ObjectiveThe purpose of this study was to develop a deep learning-based system to automatically predict epidermal growth factor receptor (EGFR) mutant lung adenocarcinoma in 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT).MethodsThree hundred and one lung adenocarcinoma patients with EGFR mutation status were enrolled in this study. Two deep learning models (SECT and SEPET) were developed with Squeeze-and-Excitation Residual Network (SE-ResNet) module for the prediction of EGFR mutation with CT and PET images, respectively. The deep learning models were trained with a training data set of 198 patients and tested with a testing data set of 103 patients. Stacked generalization was used to integrate the results of SECT and SEPET.ResultsThe AUCs of the SECT and SEPET were 0.72 (95% CI, 0.62–0.80) and 0.74 (95% CI, 0.65–0.82) in the testing data set, respectively. After integrating SECT and SEPET with stacked generalization, the AUC was further improved to 0.84 (95% CI, 0.75–0.90), significantly higher than SECT (p&lt;0.05).ConclusionThe stacking model based on 18F-FDG PET/CT images is capable to predict EGFR mutation status of patients with lung adenocarcinoma automatically and non-invasively. The proposed model in this study showed the potential to help clinicians identify suitable advanced patients with lung adenocarcinoma for EGFR‐targeted therapy.
Case Report: Successful Chimeric Antigen Receptor T Cell Therapy in Haploidentical-Allogeneic Stem Cell Transplant Patients With Post-Transplant Lymphoproliferative Disorder
Authors: Yan Nan , Wang Na , Zhang Peiling , Wang Gaoxiang , Mao Xia , Peng Dan , Kuang Dong , Chen Liting , Zhu Li , Zhou Jianfeng , Zhang Yicheng , Cao Yang 
Published: July 2021

BackgroundEpstein–Barr virus-associated post-transplant lymphoproliferative disorder (EBV-PTLD) is a potentially fatal complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Rituximab has been proven to dramatically improve the prognosis of patients with EBV reactivation and PTLD. However, reports on the curative management of refractory PTLD are scarce.Case PresentationIn this report, we describe the successful management of two patients with EBV-PTLD with chimeric antigen receptor T-cell (CAR-T) therapy.ConclusionThe present results demonstrated that patients with EBV-PTLD may benefit from CAR-T therapy and that the toxicity is manageable. Further studies are needed to verify these findings.