bluuebunny/crossref_metadata_2025_split huggingface dataset:
Performance of a diagnostic algorithm for fibrotic hypersensitivity pneumonitis. A case–control study
Authors: Guler Sabina A. , Wohlfarth Eva , Berezowska Sabina , Geiser Thomas K. , Ebner Lukas , Funke-Chambour Manuela 
Published: April 2021

Abstract
Background
The differential diagnosis fibrotic hypersensitivity pneumonitis (HP) versus idiopathic pulmonary fibrosis (IPF) is important but challenging. Recent diagnostic guidelines for HP emphasize including multidisciplinary discussion (MDD) in the diagnostic process, however MDD is not comprehensively available.
We aimed to establish the diagnostic accuracy and prognostic validity of a previously proposed HP diagnostic algorithm that foregoes MDD.

Methods
We tested the algorithm in patients with an MDD diagnosis of fibrotic HP or IPF (case control study) and determined diagnostic test performances for diagnostic confidences of ≥ 90% and ≥ 70%. Prognostic validity was established using Cox proportional hazards models.

Results
Thirty-one patients with fibrotic HP and 50 IPF patients were included. The algorithm-derived ≥ 90% confidence level for HP had high specificity (0.94, 95% confidence interval [CI] 0.83–0.99), but low sensitivity (0.35 [95%CI 0.19–0.55], J-index 0.29). Test performance was improved for the ≥ 70% confidence level (J-index 0.64) with a specificity of 0.90 (95%CI 0.78–0.97), and a sensitivity of 0.74 (95%CI 0.55–0.88). MDD fibrotic HP diagnosis was strongly associated with lower risk of death (adjusted hazard ratio [HR] 0.10 [0.01–0.92], p = 0.04), whereas the algorithm-derived ≥ 70% and ≥ 90% confidence diagnoses were not significantly associated with survival (adjusted HR 0.37 [0.07–1.80], p = 0.22, and adjusted HR 0.41 [0.05–3.25], p = 0.39, respectively).

Conclusion
The algorithm-derived ≥ 70% diagnostic confidence had satisfactory test performance for MDD-HP diagnosis, with insufficient sensitivity for ≥ 90% confidence. The lowest risk of death in the MDD-derived HP diagnosis validates the reference standard and suggests that a diagnostic algorithm not including MDD, might not replace the latter.
DNA hypermethylation contributes to colorectal cancer metastasis by regulating the binding of CEBPB and TFCP2 to the CPEB1 promoter
Authors: Shao Keke , Pu Weilin , Zhang Jianfeng , Guo Shicheng , Qian Fei , Glurich Ingrid , Jin Qing , Ma Yanyun , Ju Shaoqing , Zhang Zhao , Ding Weifeng 
Published: April 2021

Abstract
Background
Aberrant DNA methylation has been firmly established as a factor contributing to the pathogenesis of colorectal cancer (CRC) via its capacity to silence tumour suppressor genes. However, the methylation status of multiple tumour suppressor genes and their roles in promoting CRC metastasis are not well characterised.

Methods
We explored the methylation and expression profiles of CPEB1 (the gene encoding cytoplasmic polyadenylation element-binding protein 1), a candidate CRC tumour suppressor gene, using The Cancer Genome Atlas (TCGA) database and validated these results in both CRC cell lines and cells from Han Chinese CRC patients (n = 104). The functional role of CPEB1 in CRC was examined in experiments performed in vitro and in vivo. A candidate transcription factor capable of regulating CPEB1 expression was predicted in silico and validated by luciferase reporter, DNA pull-down, and electrophoretic mobility shift assays.

Results
Hypermethylation and decreased expression of CPEB1 in CRC tumour tissues were revealed by TCGA database. We also identified a significant inverse correlation (Pearson’s R = − 0.43, P < 0.001) between promoter methylation and CPEB1 expression. We validated these results in CRC samples and two CRC cell lines. We also demonstrated that up-regulation of CPEB1 resulted in significantly decreased tumour growth, migration, invasion, and tumorigenicity and promoted tumour cell apoptosis both in vitro and in vivo. We identified the transcription factors CCAAT enhancer-binding protein beta (CEBPB) and transcription factor CP2 (TFCP2) as critical regulators of CPEB1 expression. Hypermethylation of the CPEB1 promoter resulted in a simultaneous increase in the capacity for TFCP2 binding and a decreased likelihood of CEBPB binding, both of which led to diminished expression of CPEB1.

Conclusions
Our results identified a novel tumour-suppressive role of CPEB1 in CRC and found that hypermethylation of the CPEB1 promoter may lead to diminished expression due to decreased chromatin accessibility and transcription factor binding. Collectively, these results suggest a potential role for CPEB1 in the diagnosis and treatment of CRC.
Remote monitoring technologies in Alzheimer’s disease: design of the RADAR-AD study
Authors:   the RADAR-AD Consortium, Muurling Marijn , de Boer Casper , Kozak Rouba , Religa Dorota , Koychev Ivan , Verheij Herman , Nies Vera J. M. , Duyndam Alexander , Sood Meemansa , Fröhlich Holger , Hannesdottir Kristin , Erdemli Gul , Lucivero Federica , Lancaster Claire , Hinds Chris , Stravopoulos Thanos G. , Nikolopoulos Spiros , Kompatsiaris Ioannis , Manyakov Nikolay V. , Owens Andrew P. , Narayan Vaibhav A. , Aarsland Dag , Visser Pieter Jelle 
Published: April 2021

Abstract
Background
Functional decline in Alzheimer’s disease (AD) is typically measured using single-time point subjective rating scales, which rely on direct observation or (caregiver) recall. Remote monitoring technologies (RMTs), such as smartphone applications, wearables, and home-based sensors, can change these periodic subjective assessments to more frequent, or even continuous, objective monitoring. The aim of the RADAR-AD study is to assess the accuracy and validity of RMTs in measuring functional decline in a real-world environment across preclinical-to-moderate stages of AD compared to standard clinical rating scales.

Methods
This study includes three tiers. For the main study, we will include participants (n = 220) with preclinical AD, prodromal AD, mild-to-moderate AD, and healthy controls, classified by MMSE and CDR score, from clinical sites equally distributed over 13 European countries. Participants will undergo extensive neuropsychological testing and physical examination. The RMT assessments, performed over an 8-week period, include walk tests, financial management tasks, an augmented reality game, two activity trackers, and two smartphone applications installed on the participants’ phone. In the first sub-study, fixed sensors will be installed in the homes of a representative sub-sample of 40 participants. In the second sub-study, 10 participants will stay in a smart home for 1 week.
The primary outcome of this study is the difference in functional domain profiles assessed using RMTs between the four study groups. The four participant groups will be compared for each RMT outcome measure separately. Each RMT outcome will be compared to a standard clinical test which measures the same functional or cognitive domain. Finally, multivariate prediction models will be developed. Data collection and privacy are important aspects of the project, which will be managed using the RADAR-base data platform running on specifically designed biomedical research computing infrastructure.

Results
First results are expected to be disseminated in 2022.

Conclusion
Our study is well placed to evaluate the clinical utility of RMT assessments. Leveraging modern-day technology may deliver new and improved methods for accurately monitoring functional decline in all stages of AD. It is greatly anticipated that these methods could lead to objective and real-life functional endpoints with increased sensitivity to pharmacological agent signal detection.
Physiological relevance of post-translational regulation of the spindle assembly checkpoint protein BubR1
Authors: Bloom Celia R. , North Brian J. 
Published: April 2021

AbstractBubR1 is an essential component of the spindle assembly checkpoint (SAC) during mitosis where it functions to prevent anaphase onset to ensure proper chromosome alignment and kinetochore-microtubule attachment. Loss or mutation of BubR1 results in aneuploidy that precedes various potential pathologies, including cancer and mosaic variegated aneuploidy (MVA). BubR1 is also progressively downregulated with age and has been shown to be directly involved in the aging process through suppression of cellular senescence. Post-translational modifications, including but not limited to phosphorylation, acetylation, and ubiquitination, play a critical role in the temporal and spatial regulation of BubR1 function. In this review, we discuss the currently characterized post-translational modifications to BubR1, the enzymes involved, and the biological consequences to BubR1 functionality and implications in diseases associated with BubR1. Understanding the molecular mechanisms promoting these modifications and their roles in regulating BubR1 is important for our current understanding and future studies of BubR1 in maintaining genomic integrity as well as in aging and cancer.
MSE minimized joint transmission in coordinated multipoint systems with sparse feedback and constrained backhaul requirements
Authors: Nezafati Mohammad Bagher , Taki Mehrdad , Svensson Tommy 
Published: April 2021

AbstractIn a joint transmission coordinated multipoint (JT-CoMP) system, a shared spectrum is utilized by all neighbor cells. In the downlink, a group of base stations (BSs) coordinately transmit the users’ data to avoid serious interference at the users in the boundary of the cells, thus substantially improving area fairness. However, this comes at the cost of high feedback and backhaul load; In a frequency division duplex system, all users at the cell boundaries have to collect and send feedback of the downlink channel state information (CSI). In centralized JT-CoMP, although with capabilities for perfect coordination, a central coordination node have to send the computed precoding weights and corresponding data to all cells which can overwhelm the backhaul resources. In this paper, we design a JT-CoMP scheme, by which the sum of the mean square error (MSE) at the boundary users is minimized, while feedback and backhaul loads are constrained and the load is balanced between BSs. Our design is based on the singular value decomposition of CSI matrix and optimization of a binary link selection matrix to provide sparse feedback—constrained backhaul link. For comparison, we adopt the previously presented schemes for feedback and backhaul reduction in the physical layer. Extensive numerical evaluations show that the proposed scheme can reduce the MSE with at least$$25\%$$25%, compared to the adopted and existing schemes.
On new generalized unified bounds via generalized exponentially harmonically s-convex functions on fractal sets
Authors: Chu Yu-Ming , Rashid Saima , Abdeljawad Thabet , Khalid Aasma , Kalsoom Humaira 
Published: April 2021

AbstractThe visual beauty reflects the practicability and superiority of design dependent on the fractal theory. Based on the applicability in practice, it shows that it is the completely feasible, self-comparability and multifaceted nature of fractal sets that made it an appealing field of research. There is a strong correlation between fractal sets and convexity due to its intriguing nature in the mathematical sciences. This paper investigates the notions of generalized exponentially harmonically ($GEH$
G
E
H
) convex and $GEH$
G
E
H
s-convex functions on a real linear fractal sets $\mathbb{R}^{\alpha }$

R
α

($0<\alpha \leq 1$
0
<
α
≤
1
). Based on these novel ideas, we derive the generalized Hermite–Hadamard inequality, generalized Fejér–Hermite–Hadamard type inequality and Pachpatte type inequalities for $GEH$
G
E
H
s-convex functions. Taking into account the local fractal identity; we establish a certain generalized Hermite–Hadamard type inequalities for local differentiable $GEH$
G
E
H
s-convex functions. Meanwhile, another auxiliary result is employed to obtain the generalized Ostrowski type inequalities for the proposed techniques. Several special cases of the proposed concept are presented in the light of generalized exponentially harmonically convex, generalized harmonically convex and generalized harmonically s-convex. Meanwhile, an illustrative example and some novel applications in generalized special means are obtained to ensure the correctness of the present results. This novel strategy captures several existing results in the corresponding literature. Finally, we suppose that the consequences of this paper can stimulate those who are interested in fractal analysis.
Determinants of under-five mortality in the high mortality regions of Ethiopia: mixed-effect logistic regression analysis
Authors: Worku Misganaw Gebrie , Teshale Achamyeleh Birhanu , Tesema Getayeneh Antehunegn 
Published: April 2021

AbstractBackgroundEven though the global under-five mortality rate substantially decreased over time, Sub-Saharan African (SSA) countries including Ethiopia continue to share the huge burden of under-five mortality. Ethiopia showed a substantial reduction in under-five mortality over time but the rate of reduction has varied across regions. Therefore, this study aimed to investigate determinants of under-five mortality in the high mortality regions of Ethiopia.MethodsA secondary data analysis was done based on the 2016 Ethiopian Demographic and Health Survey (EDHS) data. A total weighted sample of 3446 live births were included for this study. For the determinants of under-five mortality, mixed-effect logistic regression was fitted. The Intra-Class Correlation Coefficient (ICC), and Median Odds Ratio (MOR) were done to assess the presence of a significant clustering effect. The standard binary logistic regression and the mixed-effect logistic regression model were fitted and deviance (−2LL) was used for model comparison as the models were nested models. Variables with ap-value less than 0.2 in the bi-variable mixed-effect binary logistic regression analysis were considered for the multivariable analysis. In the multivariable mixed-effect logistic regression analysis, the Adjusted Odds Ratio (AOR) with the 95% Confidence Interval (CI) were reported to declare the statistical significance and strength of association of under-five mortality and the determinant factors.ResultsOverall, the under-five mortality rate in the high mortality regions of Ethiopia was 74 per 1000 live births and it was highest among twin births (262 per 1000 live births). In the multivariable mixed-effect logistic regression analysis, being having 6 and above births (AOR = 3.66, 95% CI: 1.55, 8.67), preceding birth interval of 2–3 years (AOR = 0.57, 95% CI: 0.41, 0.81) and above 3 years (AOR = 0.35, 95% CI: 0.22, 0.55), being twin (AOR = 5.12, 95% CI: 2.28, 11.46), and being having antenatal care (ANC) visit during pregnancy (AOR = 0.27, 95% CI: 0.16, 0.45) were significant determinants of under-five mortality.ConclusionIn this study, under-five mortality rate was highest in high mortality regions of Ethiopia. Parity, ANC visit, preceding birth interval, and multiple births were significant predictors of under-five mortality. Therefore, public health interventions that increase maternal health service utilization such as ANC and family planning service utilization to increase birth interval are needed to reduce under-five mortality among these regions of Ethiopia.
Risk factors for surgery-related muscle quantity and muscle quality loss and their impact on outcome
Authors: van Wijk Laura , van Duinhoven Stijn , Liem Mike S. L. , Bouman Donald E. , Viddeleer Alain R. , Klaase Joost M. 
Published: April 2021

Abstract
Background
Surgery-related loss of muscle quantity negatively affects postoperative outcomes. However, changes of muscle quality have not been fully investigated. A perioperative intervention targeting identified risk factors could improve postoperative outcome. This study investigated risk factors for surgery-related loss of muscle quantity and quality and outcomes after liver resection for colorectal liver metastasis (CRLM).

Methods
Data of patients diagnosed with CRLM who underwent liver resection between 2006 and 2016 were analysed. Muscle quantity (psoas muscle index [PMI]), and muscle quality, (average muscle radiation attenuation [AMA] of the psoas), were measured using computed tomography. Changes in PMI and AMA of psoas after surgery were assessed.

Results
A total of 128 patients were analysed; 67 (52%) had surgery-related loss of muscle quantity and 83 (65%) muscle quality loss. Chronic obstructive pulmonary disease (COPD) (P = 0.045) and diabetes (P = 0.003) were risk factors for surgery-related loss of muscle quantity. A higher age (P = 0.002), open resection (P = 0.003) and longer operation time (P = 0.033) were associated with muscle quality loss. Overall survival was lower in patients with both muscle quantity and quality loss compared to other categories (P = 0.049). The rate of postoperative complications was significantly higher in the group with surgery-related loss of muscle quality.

Conclusions
Risk factors for surgery-related muscle loss were identified. Overall survival was lowest in patients with both muscle quantity and quality loss. Complication rate was higher in patients with surgery-related loss of muscle quality.
Key Chagas disease missing knowledge among at-risk population in Spain affecting diagnosis and treatment
Authors: Romay-Barja María , Iglesias-Rus Laura , Boquete Teresa , Benito Agustín , Blasco-Hernández Teresa 
Published: April 2021

Abstract
Background
Chagas disease is endemic in Latin America and, over the last few decades, due to population movements, the disease has spread to other continents. Early diagnosis and treatment are critical in terms of improving outcomes for those living with Chagas disease. However, poor knowledge and awareness is one of barriers that affects access to Chagas disease diagnosis and treatment for the population at risk. Information regarding immigrants’ knowledge concerning Chagas disease control and prevention is insufficient in non-endemic countries and, therefore, this study sought to assess Chagas disease knowledge and awareness within the Bolivian community residing in Madrid.

Methods
This cross-sectional study was carried out in March–August 2017. A total of 376 Bolivians answered a structured questionnaire. A knowledge index was created based on respondents’ knowledge about transmission, symptoms, diagnosis, and place to seek treatment. Multivariate logistic regressions analyses were performed to assess the factors associated with respondents’ knowledge of Chagas disease.

Results
A total 159 (42.4%) of Bolivians interviewed about their knowledge of Chagas disease were men and 217 (57.6%) were women. Vinchuca was mentioned as mode of transmission by 71% of the Bolivians surveyed, while only 9% mentioned vertical transmission. Almost half of the Bolivians did not know any symptom of Chagas disease and only 47% knew that a specific blood test is necessary for diagnosis. Most of Bolivians were aware of the severity of Chagas disease, but 45% of Bolivians said that there is no cure for Chagas and 96% did not know any treatment. Based on the index of knowledge generated, only 34% of Bolivians had a good knowledge about Chagas disease transmission, symptoms, diagnosis and treatment. According to the multiple logistic regression analysis, knowledge regarding Chagas disease, diagnosis and treatment was significantly higher amongst older Bolivians who had secondary education at least, as well as amongst those who had already been tested for Chagas disease.

Conclusions
This study found that most of the Bolivian population living in Spain had poor knowledge about Chagas disease transmission, symptoms, diagnostic methods and treatment. A poor understanding of the disease transmission and management is one of the most important barriers when it comes to searching for early diagnosis and appropriate care.
Happiness in marginalized populations: a community–based study in South Central Iran
Authors: Kazemi Maryam , Honarvar Behnam , Heydari S. Taghi , Joulaei Hassan , Haghighi Mohammad Reza Rahmanian , Lankarani Kamran Bagheri 
Published: April 2021

AbstractBackgroundHappiness has multiple levels and determinants in different communities, cultures, and social groups. The current study aimed to investigate happiness and its main determinants in slums in south central Iran.MethodsThis community-based, cross-sectional study was conducted with the participation of adults at least 18 years of age living in the biggest slum area in Shiraz, south central Iran. To determine levels of happiness, participants were asked to complete the Persian version of the GHQ28 questionnaire and a checklist based on the 2017 World Happiness Report. Data was analyzed using SPSS software version 19. Ap-value less than 0.05 was considered significant.ResultsThe mean age of the participants was 42.06 ± 16.34 years. Overall, 542 participants (45 %) were females, 257 (21.3 %) were illiterate, 678 (56.3 %) were married, and 495 (41.1 %) were unemployed and lived with their household. The happiness score, according to the Cantril ladder score, was 6.41 ± 2 (out of a total score of 10). Happiness was not correlated with gender (p = 0.37) or immigration (p = 0.06). Lower levels of happiness were seen in older adults (r=− 0.12,p < 0.001), illiterates (p = 0.03), the unemployed (p < 0.001), and people separated from their spouses (p < 0.001). Job satisfaction (p < 0.001, r = 0.47), total general health (p < 0.001, r=-0.36) and hope (p < 0.001, r = 0.41) were significantly correlated with happiness. Social support (< 0.001) and sufficient income and satisfaction (p < 0.001) were related with a higher score of happiness.ConclusionsMarital status, smoking, employment and job satisfaction, social support and trust, feelings of insecurity in the neighborhood, hope for the future, facing violence, and income satisfaction were the main determinants of happiness in the Sang Siah slum area.
Combined epigenetic/genetic study identified an ALS age of onset modifier
Authors: Zhang Ming , Xi Zhengrui , Saez-Atienzar Sara , Chia Ruth , Moreno Danielle , Sato Christine , Montazer Haghighi Mahdi , Traynor Bryan J. , Zinman Lorne , Rogaeva Ekaterina 
Published: April 2021

AbstractAge at onset of amyotrophic lateral sclerosis (ALS) is highly variable (eg, 27–74 years in carriers of the G4C2-expansion in C9orf72). It might be influenced by environmental and genetic factors via the modulation of DNA methylation (DNAm) at CpG-sites. Hence, we combined an epigenetic and genetic approach to test the hypothesis that some common single nucleotide polymorphisms (SNPs) at CpG-sites (CpG-SNPs) could modify ALS age of onset. Our genome-wide DNAm analysis suggested three CpG-SNPs whose DNAm levels are significantly associated with age of onset in 249 ALS patients (q < 0.05). Next, genetic analysis validated the association of rs4970944 with age of onset in the discovery (n = 469; P = 0.025) and replication (n = 4160; P = 0.007) ALS cohorts. A meta-analysis of the cohorts combined showed that the median onset in AA-carriers is two years later than in GG-carriers (n = 4629; P = 0.0012). A similar association was observed with its tagging SNPs, implicating a 16 Kb region at the 1q21.3 locus as a modifier of ALS age of onset. Notably, rs4970944 genotypes are also associated with age of onset in C9orf72-carriers (n = 333; P = 0.025), suggesting that each A-allele delays onset by 1.6 years. Analysis of Genotype-Tissue Expression data revealed that the protective A-allele is linked with the reduced expression of CTSS in cerebellum (P = 0.00018), which is a critical brain region in the distributed neural circuits subserving motor control. CTSS encodes cathepsin S protein playing a key role in antigen presentation. In conclusion, we identified a 16 Kb locus tagged by rs4970944 as a modifier of ALS age of onset. Our findings support the role of antigen presenting processes in modulating age of onset of ALS and suggest potential drug targets (eg, CTSS). Future replication studies are encouraged to validate the link between the locus tagged by rs4970944 and age of onset in independent ALS cohorts, including different ethnic groups.