bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety outcomes in patients with rheumatoid arthritis treated with abatacept: results from a multinational surveillance study across seven European registries
Authors: Dominique Alyssa , Hetland Merete Lund , Finckh Axel , Gottenberg Jacques-Eric , Iannone Florenzo , Caporali Roberto , Kou Tzuyung Douglas , Nordstrom Dan , Hernandez Maria Victoria , Sánchez-Piedra Carlos , Sánchez-Alonso Fernando , Pavelka Karel , Bond T. Christopher , Simon Teresa A. 
Published: December 2022

Abstract
Background
Patients with rheumatoid arthritis (RA) have an increased risk of infection and malignancy compared with the general population. Infection risk is increased further with the use of disease-modifying antirheumatic drugs (DMARDs), whereas evidence on whether the use of biologic DMARDs increases cancer risk remains equivocal. This single-arm, post-marketing study estimated the incidence of prespecified infection and malignancy outcomes in patients with RA treated with intravenous or subcutaneous abatacept.
Methods
Data were included from seven European RA quality registries: ATTRA (Anti-TNF Therapy in Rheumatoid Arthritis [Czech Republic]), DANBIO (Danish Rheumatologic Database), ROB-FIN (National Registry of Biological Treatment in Finland), ORA (Orencia and Rheumatoid Arthritis [France]), GISEA (Italian Group for the Study of Early Arthritis), BIOBADASER (Spanish Register of Adverse Events of Biological Therapies in Rheumatic Diseases), and the SCQM (Swiss Clinical Quality Management) system. Each registry is unique with respect to design, data collection, definition of study cohort, reporting, and validation of outcomes. In general, registries defined the index date as the first day of abatacept treatment and reported data for infections requiring hospitalization and overall malignancies; data for other infection and malignancy outcomes were not available for every cohort. Abatacept exposure was measured in patient-years (p-y). Incidence rates (IRs) were calculated as number of events per 1000 p-y of follow-up with 95% confidence intervals.
Results
Over 5000 patients with RA treated with abatacept were included. Most patients (78–85%) were female and the mean age range was 52–58 years. Baseline characteristics were largely consistent across registries. Among patients treated with abatacept, IRs for infections requiring hospitalization across the registries ranged from 4 to 100 events per 1000 p-y, while IRs for overall malignancy ranged from 3 to 19 per 1000 p-y.
Conclusions
Despite heterogeneity between registries in terms of design, data collection, and ascertainment of safety outcomes, as well as the possibility of under-reporting of adverse events in observational studies, the safety profile of abatacept reported here was largely consistent with previous findings in patients with RA treated with abatacept, with no new or increased risks of infection or malignancy.
Trial registration:
not applicable
A fast and high-order IMEX method for non-linear time-space-fractional reaction-diffusion equations
Authors: Kazmi Kamran 
Published: December 2022

Abstract
An efficient and high-order numerical method is presented for solving a time-space-fractional reaction-diffusion equation. Matrix transfer technique based on fourth order compact finite differences are first used to discretize the space-fractional Laplacian operator which results in a system with a linear stiff term. Then an implicit-explicit (IMEX) trapezoidal product-integration rule is implemented for time integration which treats the stiff linear term implicitly and non-linear non-stiff term explicitly. The stability and convergence of the method are analyzed. Due to the discontinuity of the solution derivative at t = 0, the numerical method is only 1+α order accurate in time where α is the order of the time-fractional derivative. Richardson extrapolation is introduced to obtain a modified version of the method which is second order accurate in time. A fast algorithm based on discrete sine transform is also implemented to reduce the cost of computing the discretized space-fractional Laplacian operator.
A prospective, multicenter, cohort study to evaluate the long-term quality of life and psychological factors among patients with breast cancer, 5-year follow-up: a study protocol
Authors: Lahiji Mahsa Raji , Sajadian Akram , Hashemi Elahe , Montazeri Ali , Anbiaee Robab , Omranipour Ramesh , Nafissi Nahid , Heydari Leila , Rasouli Mohsen , Kazemnejad Anoshirvan , Alaeddini Farshid 
Published: December 2022

Abstract
Background: Breast cancer is the most commonly occurring cancer among women worldwide. Quality of life and psychological status of patients with breast cancer could be affected after diagnosis, especially during treatment. The main objective of this study is investigation of long-term influence of breast cancer on quality of life’s dimensions and mental health status.
Methods: This is a multicenter, ongoing longitudinal prospective cohort study which administered in national institute for medical research development in May 2018 in Iran. 1250 patients with breast cancer who were completed their treatments, will be recruited from 5 referral medical centers located in Tehran, to be followed for 5 years. Questionnaires for evaluating the primary and secondary outcomes will be complete by trained investigators during face-to-face interviews with each participant in three phases: immediately after treatment, 1 year and 5 years later. Data will be collected on socio-demographic, quality of life, body image, hope, psychological problems such as anxiety, depression and mood, also sexual function and physical activity. Data will be analyzed in each phase and at the end of the project by SPSS version 22.
Discussion: It is the first nationwide, prospective, cohort study with large sample size, long-term follow-up and broad research aims which will evaluate quality of life-related factors in Iranian breast cancer population to justify the existing gap in literature.
Trial registration number: National Institute for Medical Research Development (NIMAD) (IR.NIMAD.REC.1397.322) July 1th, 2018.
Genome-wide association study identifies genes and networks that influence innate immune response in an age-specific manner in Drosophila melanogaster
Authors: Campbell Shonda , Gudino Isabella , Rhee Mary , Leips Jeff 
Published: December 2022

Abstract
Background
The innate immune response is an evolutionarily conserved process that is essential for survival in multicellular organisms. As individuals age, immune functions decline, a phenomenon known as immunosenescence, reducing one’s ability to fight infections. While immunosenescence is a universal feature of aging, the rate at which immune functions decline with age varies greatly among individuals and this variation has a genetic component. However, we have limited knowledge of the actual genes that contribute to this variation.
Methods
Here, we used 183 genetically distinct genotypes of the Drosophila Genetic Reference panel (DGRP) to assess their ability to clear an infection at one and five weeks of age. We then carried out a genome-wide association study (GWAS) to identify candidate genes that contribute to differences in immune responses among genotypes at each age.
Results
We found that, on average, the ability to clear infection declined by 70% with age. However, the effect of age on clearance ability varied significantly among genotypes. We identified a total of 242 single nucleotide polymorphisms (SNPs) and 107 candidate genes associated with variation in clearance ability. Polymorphisms in 48 genes were associated with clearance in 1 week old flies and fifty-nine genes were associated with clearance ability at 5 weeks of age. Only one gene, a G-coupled protein receptor, CG31760, was a candidate at both ages. Of the 107 candidate genes, 25 were mapped to genetic networks.
Conclusion
Our results identify candidate genes that could be targets for age-appropriate therapeutic treatments to maintain or restore immune function in the elderly.
Integration of bioinformatics and machine learning strategies identifies APM-related gene signatures to predict clinical outcomes and therapeutic responses for breast cancer patients
Authors: Shen Hong-yu , Xu Jia-lin , Zhu Zhen , Liang Ming-xing , Xu Di , Chen Wen-quan , Fang Zheng , Tang Jin-hai 
Published: December 2022

Abstract

Background: Tumor antigenicity and efficiency of antigen presentation jointly influence tumor immunogenicity, which largely determines the effectiveness of immune checkpoint blockade (ICB). However, the role of altered antigen processing and presentation machinery (APM) in breast cancer (BRCA) has not been fully elucidated.
Methods: A series of bioinformatic analyses and machine learning strategies were performed to construct APM-related gene signatures to guide personalized treatment for BRCA patients. A single-sample gene set enrichment analysis (ssGSEA) algorithm and weighted gene co-expression network analysis (WGCNA) were combined to screen for BRCA-specific APM-related genes. The non-negative matrix factorization (NMF) algorithm was used to divide the cohort into different clusters and the fgsea algorithm was applied to investigate the altered signaling pathways. Random survival forest (RSF) and the least absolute shrinkage and selection operator (Lasso) Cox regression analysis were combined to construct an APM-related risk score (APMrs) signature to predict overall survival. Furthermore, a nomogram and decision tree were generated to improve predictive accuracy and risk stratification for individual patients. Based on Tumor Immune Dysfunction and Exclusion (TIDE) method, random forest (RF) and Lasso logistic regression model were combined to establish an APM-related immunotherapeutic response score (APMis). Finally, immune infiltration, immunomodulators, mutational patterns, and potentially applicable drugs were comprehensively analyzed in different APM-related risk groups. Results: In this study, APMrs and APMis showed favorable performances in risk stratification and therapeutic prediction for BRCA patients. APMrs exhibited more powerful prognostic capacity and accurate survival prediction compared to conventional clinicopathological features. APMrs was closely associated with distinct mutational patterns, immune cell infiltration and immunomodulators expression. Furthermore, the two APM-related gene signatures were independently validated in external cohorts with prognosis or immunotherapeutic responses. Potential applicable drugs and targets were further mined in the APMrs-high group.
Conclusion: The APM-related gene signatures established in our study could improve the personalized assessment of survival risk and guide ICB decision-making for BRCA patients.
HNRNPA2B1 mediated MircoRNA-92a upregulation and section acts a promising non-invasive diagnostic biomarker in colorectal cancer
Authors: Li Yiling , Li Kexin , Lou Xiaoying , Wu Yue , Seery Samuel , Xu Danfei , Pei Yuqing , Qian Benheng , Wu Yuxin , Liang Shuang , Wu Kui , Cui Wei 
Published: December 2022

AbstractBackground MicroRNA-92a (miR-92a) may serve as a novel promising biomarker in multiple cancers including colorectal cancer (CRC). However, the diagnostic accuracy and the underlying molecular mechanism of miR-92a in CRC is poorly understood. Method Diagnostic studies were retrieved from PubMed, Embase, the Cochrane Library, and Web of Science, up until May 2022. Besides, an independent validation participants group (n = 144) was recruited for stool miR-92a test to prove the diagnosis efficiency in CRC. Then, totally studies were enrolled for meta-analysis using pooled sensitivity, specificity, and diagnostic odds ratios (DOR), summary receiver operating characteristic (SROC) curve and area under the curve (AUC) analysis. Next, GEO datasets, TCGA dataset and previous study data were used to explore the relationship between HRNPA2B1 and miR-92a. Finally, cell experiments demonstrated the regulatory effect of HRNPA2B1 on miR-92a in vitro. Results We first carried out meta-analysis and found that serum/plasma miR-92a yield better diagnostic efficacy when compared to stool samples and CRC tissues. And this finding was validated by our independent study through stool sample. Multiple bioinformatics assay indicated that miR-92a expression was positively correlated with heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) expression and closely related with the clinical characteristics of CRC. Experimental evidence shown that knockdown of HNRNPA2B1 could significantly decreased miR-92a expression and secretion in CRC cell lines. HNRNPA2B1 mediated miR-92a via with N6-methyladenosine (m6A) RNA modification validated by both bioinformatic analysis and vitro experiments. Conclusions These findings indicate that HNRNPA2B1-m6A RNA modification derived mircoRNA-92a upregulation and section from the local CRC acts a candidate non-invasive serum biomarker in colorectal cancer. Our study provides a novel insight into miR-92a mechanisms in relation to both expression and secretion for CRC diagnosis.
Mixed localized wave solutions of the (2+1)-dimensional Fokas-Lenells equation
Authors: Song Huijie , Zhao Qiulan , Li Xinyue 
Published: December 2022

Abstract
In this paper, we investigate the mixed localized wave solutions of the (2+1)-dimensional Fokas-Lenells equation. These localized wave solutions contain solitons, degenerate solitons, lumps and lump chains. Our focus is the mixed solutions including solitons and degenerate solitons, lumps and lump chains. The effective method we use to obtain the above solutions is generalized (n, M)-fold Darboux transformation. The characteristics and properties of these solutions are discussed analytically and graphically. Actually, these solutions can change the strength of the interactions by adjusting parameters, and preserve their own properties throughout the interaction process.
Carotid Atherosclerosis and its Correlation with ApoB/ApoA-I and Non-HDL-c/HDL-c Ratios among Adults with Type 2 Diabetes: A Cross-Sectional Study in Southwestern Uganda
Authors: Saasita Patrick Kambale , Kaddumukasa Mark , Najjuma Josephine Nambi , Mbalinda Scovia Nalugo , Kaddumukasa Martin , Lekuya Hervé Monka , Nakibuuka Jane , Burant Christopher J. , Moore Shirley , Blixen Carol , Katabira Elly T. , Sajatovic Martha , Malunde Frederick , Acan Moses , Muyingo Anthony 
Published: December 2022

Abstract
Background: Type 2 diabetes mellitus (T2DM) poses an increased risk for cardiovascular disease (CVD) through atherosclerosis. The apolipoprotein B (apoB)/apolipoprotein A-I (apoA-I) (ApoB/ApoA-I) ratio is a powerful predictor of atherosclerotic CVD and is associated with carotid atherosclerosis (CA) in T2DM; however, this association had never been studied in our setting. This study set out to determine the prevalence of CA and its correlation with ApoB/ApoA-I and non-high-density lipoprotein cholesterol (non-HDL-c)/high-density lipoprotein cholesterol (non-HDL-c/HDL-c) ratios among patients with T2DM in Southwestern Uganda.
Methods: A cross-sectional study conducted at Mbarara Regional Referral Hospital included 212 ambulatory patients with T2DM aged ≥40 years. Socio-demographic, clinical, and behavioral characteristics were determined. Fasting blood samples were collected for measuring serum glucose, Apo B, Apo A-I, and the routine lipid profile. The apoB/apoA-I ratio and the non-HDL-c/HDL-c ratio were calculated. Carotid intima-media thickness (CIMT) was measured bilaterally at three points by high-resolution B-mode ultrasound. A mean value of six measurements from the right and left carotid arteries was used as a measure of CIMT. Carotid atherosclerosis was defined as a mean CIMT≥1.0 mm. A stepwise multivariate regression analysis and Pearson’s correlation were used to assess the association and correlation of CIMT with clinical factors, apoB/apoA-I, and non-HDL/HDL-c ratios.
Results: The prevalence of CA was 35.9%. Age ≥55 years (OR 3.1; 95% CI:1.4 – 7.1; p<007) and age ≥ 65 years (OR 10.2; 95% CI: 3.5–29.5; p-< 0.001), coinfection with HIV (OR 3.8; 95% CI: 1.1–12.5; p-value = 0.030), high waist circumference (OR 2.7; 95% CI: 1.2 – 6.5; p-value = 0.022) and non-HDL-c/HDL-c ratio ≥ 4 (OR 3.0; 95% CI 1.0–8.5; p = 0.045) were associated with CA. The apoB/apoA-I ratio was elevated among T2DM patients with CA, but was not significantly associated with CA (OR 1.0; 95% CI: 0.4 – 2.5, p= 0.25). The optimal non-HDL-c/HDL-c ratio cutoff value for detecting CA was 3.39 (a sensitivity of 60.53% and a specificity of 54.41%).
Conclusion: There is a high prevalence of CA among patients with T2DM. The non-HDL-c/HDL-c ratio was significantly associated with high CIMT but not the apoB/apoA-I ratio.
Detectability analysis of very low frequency earthquakes: Methods and application in Nankai using F-net and DONET broadband seismometers
Authors: Takemura Shunsuke , Baba Satoru , Yabe Suguru , Yamashita Yusuke , Shiomi Katsuhiko , Matsuzawa Takanori 
Published: December 2022

Abstract
For a more quantitative discussion of slow earthquake activity, we evaluated the detectable limits of very low frequency earthquakes (VLFEs), which are seismic slow earthquakes observed in very low frequency (< 0.05 Hz) bands, in the Nankai subduction zone. We performed numerical simulations using a local three-dimensional model and used the observed noise level of permanent broadband seismometers. First, we investigated the effects of the source-time functions on the maximum amplitudes of the VLFE signals at a certain station. The maximum amplitudes of the VLFE signals were controlled by the VLFE moment rate. The detectable limit of VLFEs at each source location can be defined as the lowest moment rate of detectable VLFEs, which radiate signals larger than the noise levels of any component at ≥ 3 stations. For inland seismometers only, the detectable limits of VLFEs at deep (30–40 km) and shallow (≤ 10 km) depths were 1012.5–1012.8 and 1013.2 Nm/s, respectively. Due to the geometrical spreading of VLFE signals and large noise levels in horizontal components, offshore seismometers improved the detectability of shallow VLFEs in regions where seismometers were densely deployed. Based on our detectability and published catalogs, shallow slow earthquakes are less active south-southwest off the Kii Peninsula, where geodetic studies expect mechanical coupling.
A simple score for predicting cancer cachexia status in patients with Stage I–III colorectal cancer: Cancer Cachexia Score
Authors: Takano Yasuhiro , Kodera Keita , Tsukihara Shu , Takahashi Sumika , Yasunobu Kobayashi , Kanno Hironori , Ishiyama Satoshi , Saito Ryota , Hanyu Nobuyoshi , Eto Ken 
Published: December 2022

Abstract
Purpose: Cancer cachexia, a complex multifactorial syndrome associated with sarcopenia, negatively affects quality of life and survival in patients with several cancers. We aimed to develop a new score for cachexia assessment and evaluate its effectiveness in classification of patients undergoing radical resection for colorectal cancer.
Methods: This study included 396 patients who underwent radical resection for Stage I–III colorectal cancer. To develop the Cancer Cachexia Score (CCS), we analyzed predictive factors of cachexia status related to the development of sarcopenia and incorporated significant factors into the score. We then evaluated the relationship between CCS and overall survival after radical resection for colorectal cancer.
Results: As body mass index (P < 0.001), prognostic nutritional index (P = 0.005), and tumor volume (P < 0.001) were significantly associated with the development of sarcopenia, these factors were included in CCS. Using CCS, 221 (56 %), 98 (25 %), and 77 (19 %) patients were diagnosed with mild, moderate, and severe cancer cachexia, respectively. In multivariate analysis, severe CCS (P < 0.001), N stage 1–2 (P < 0.001), and occurrence of postoperative complications (P = 0.007) were independent predictors of disease-free survival. Age ≥ 65 years (P = 0.009), severe CCS (P < 0.001), and N stage 1–2 (P < 0.001) were independent predictors of overall survival.
Conclusions: CCS may be a strong predictor of poor survival in patients with colorectal cancer, suggesting the usefulness of CCS in classifying patients according to their cachexia status and predicting postoperative prognosis.
Effects of grazing on the ecosystems multifunctionality of montane meadow-grassland on the northern slope of the Tianshan Mountains, China
Authors: Jiang Kangwei , Zhang Qingqing , Wang Yafei , Li Hong , Yang Yongqiang , Reyimu Tursunnay 
Published: December 2022

Abstract
Ecosystem multifunctionality (EMF) plays an irreplaceable role in maintaining ecological balance and ensuring human survival and development. However, few studies have focused on the effects of different grazing intensities on EMF, and little is known about changes in the function of multiple ecosystems at different grazing intensities. The study investigated EMF of mountain meadow grasslands on the northern slopes of the Tianshan Mountains in China, by way of a plant community survey coupled with high-throughput sequencing technology. The study calculated the EMF using the mean value method and explore the effects of no grazing (CK), light grazing (LG), and heavy grazing (HG) on grassland EMF. Results showed that HG significantly improved moisture regulation (MR) function (p < 0.05), and decreased soil fertility (SF) (p > 0.05), soil carbon storage (SCS) (p > 0.05), nutrient conversion and cycling (NC) (p > 0.05), grassland productivity (GP) function (p < 0.05), and EMF (p < 0.05). The EMF index of the grassland ecosystem under grazing conditions ranged from 0.3328–0.6018. GP, SCS, and NC functions had the highest contribution to EMF under CK, LG, and HG conditions, respectively. Under grazing conditions, EMF showed a cooperative relationship with SF, SCS, and GP, and the correlation coefficient (r) was between 0.62–0.76 (p < 0.05). At the same time, EMF and grassland water MR showed a relationship of trade-offs (r = 0.68, p < 0.05). The results of structural equation models showed that grazing had a significant effect on EMF directly, and also indirectly through soil fungal diversity. Therefore, reasonable reduction of grazing intensity is the most effective management approach for maintaining ecosystem function. At the same time, grazing plays a key role in maintaining EMF by regulating both above- and below-ground ecosystem functions, primarily through soil fungal diversity. This study elucidates the response of mountain grassland EMF to grazing intensity and provides a theoretical basis for restoring degraded grassland and sustainable ecosystem development.
Asymptotic stability of two-dimensional Couette flow in a viscous fluid
Authors: Li Hui , Masmoudi Nader , Zhao Weiren 
Published: December 2022

Abstract
In this paper, we study the nonlinear asymptotic stability of Couette flow for the two-dimensional Navier-Stokes equation with small viscosity v > 0 in T×R. It's generally known that the nonlinear asymptotic stability of the Couette flow depends closely on the size and regularity of the initial perturbation, which yields the stability threshold problem. This work studies the relationship between the size and the regularity of the initial perturbation that makes the nonlinear asymptotic stability holds. More precisely, we proved that if the initial perturbation is in some Gevrey-1/s class with size εvβ where s ≥ 1-3β/2-3β and β∈[0,1/3], then the nonlinear asymptotic stability holds. We think this index is sharp.