bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association Between Inflammatory Cytokines and Immune-Checkpoint Molecule in Rheumatoid Arthritis
Authors: Matsumoto Haruki , Fujita Yuya , Asano Tomoyuki , Matsuoka Naoki , Temmoku Jumpei , Sato Shuzo , Yashiro-Furuya Makiko , Yokose Kohei , Yoshida Shuhei , Suzuki Eiji , Yago Toru , Watanabe Hiroshi , Kawakami Atsushi , Migita Kiyoshi 
Published: June 2021

Abstract
BackgroundRheumatoid arthritis (RA) is a heterogeneous inflammatory disease. Both anti-citrullinated peptide antibodies (ACPA) and inflammatory cytokines play an important role in the development of RA. The aim of this study was to investigate the association between inflammatory cytokines and co-inhibitory checkpoint molecules in patients with RA.MethodsOne hundred and thirty-two Japanese patients with established RA were enrolled. Serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF- α) were determined by ELISA. Patients were stratified into two groups based on ACPA titers: low-medium ACPA (ACPA <200 U/mL) and high ACPA (ACPA ≥200 U/mL). Serum levels of cytokines or co-inhibitory checkpoint molecules were compared according to the status of ACPA titers and joint progression stage.ResultsBaseline serum levels of TNF-α and IL-6 were significantly elevated in RA patients; however, the two cytokines showed no correlation with each other. Serum levels of IL-6 or TNF-α showed a significant correlation with DAS28-CRP, independent of ACPA status. Although serum levels of soluble T-cell immunoglobulin and mucin-domain containing-3 (sTIM-3) were elevated in RA patients, significant correlation of sTIM-3 with IL-6 or TNF-α was only observed in RA patients with low-medium levels of ACPA titers (<200 U/mL). Serum levels of IL-6 and TNF-α were significantly correlated with elevated levels of galectin-9 (Gal-9) independent of ACPA status. Whereas, a significant correlation between IL-6 and Gal-9 was observed only in RA patients without advanced joint damage (Stage I). Conversely, significant correlation between TNF-α and Gal-9 was observed only in RA patients with advanced joint damage (Stage II–IV).ConclusionsRA patients may be differentiated based on the interplay between serum cytokines and co-inhibitory molecules. RA patients with minimal joint damage (Stage I) appear to show positive correlation between Gal-9 and IL-6. Conversely, RA patients with advanced joint damage (Stage II–IV) appear to show positive correlation between Gal-9 and TNF-α. Serum levels of cytokines and immune-checkpoint molecules may be useful markers for predicting the immune phenotype and further personalized treatment of RA.
The Dynamics of Frailty Development and Progression in Older Adults in England (2006 – 2017): A Retrospective Cohort Profile
Authors: Fogg Carole , Fraser Simon DS , Roderick Paul , Lusignan Simon , Clegg Andrew , Brailsford Sally , Barkham Abigail , Patel Harnish P , Windle Vivienne , Harris Scott , Zhu Shihua , England Tracey , Evenden Dave , Lambert Francesca , Walsh Bronagh 
Published: June 2021

Abstract
Background: Frailty is a common condition in older adults and has a major impact on patient outcomes and service use. Information on the prevalence in middle-aged adults and the patterns of progression of frailty at an individual and population level is scarce. To address this, a cohort was defined from a large primary care database in England to describe the epidemiology of frailty and understand the dynamics of frailty within individuals and across the population. This article describes the structure of the dataset, cohort characteristics and planned analyses.Methods: Retrospective cohort study using electronic health records. Participants were aged ≥50 years registered in practices contributing to the Oxford Royal College of General Practitioners Research and Surveillance Centre between 2006 to 2017. Data include GP practice details, patient sociodemographic and clinical characteristics, twice-yearly electronic Frailty Index (eFI), deaths, medication use and primary and secondary care health service use. GP and patient characteristics at cohort entry are described. Planned analyses include frailty incidence, prevalence and transitions between frailty categories, predictors of transitions and trajectories, and relationships between frailty, service use and outcomes. Techniques including regression, multistate models and cost analyses will be used. Results: The cohort includes 2,177,656 patients, contributing 15,552,946 person-years, registered at 419 primary care practices in England. The mean age was 61 years, 52.1% of the cohort was female, and 77.6% lived in urban environments. Frailty increased with age, affecting 10% of adults aged 50-64 and 43.7% of adults aged ≥65. The prevalence of long-term conditions and specific frailty deficits increased with age, as did the eFI and the severity of frailty categories. Conclusion: A comprehensive understanding of frailty dynamics will inform predictions of current and future care needs to facilitate timely planning of appropriate interventions, service configurations and workforce requirements. Analysis of this large, nationally representative cohort including participants aged ≥50 will capture earlier transitions to frailty and enable a detailed understanding of progression and impact. These results will inform novel simulation models which predict future health and service needs of older people living with frailty. Study registration: registered on www.clinicaltrials.gov October 25th 2019, NCT04139278.
The Influence of Mass Media on Italian Web Users During COVID-19: An Infodemiological Analysis
Authors: Rovetta Alessandro , Castaldo Lucia 
Published: June 2021

Abstract
Alongside the COVID-19 pandemic, the world has had to face a growing infodemic, which has caused severe damage to economic and health systems and has often compromised the effectiveness of infection containment regulations. Although this has spread mainly through social media, there are numerous occasions in which the mass media have shared dangerous information, giving resonance to statements without a scientific basis. For these reasons, infoveillance and infodemiology methods are increasingly exploited to monitor online information traffic. The same tools have also been used to make epidemiological predictions. Among these, Google Trends - a service by GoogleTM that quantifies the web interest of users in the form of relative search volume - has often been adopted by the scientific community. In this regard, the purpose of this paper is to use Google Trends to estimate the impact of Italian mass media on users' web searches in order to understand the role of press and television channels in both the infodemic and the interest of Italian netizens on COVID-19. In conclusion, our results suggest that the Italian mass media have played a decisive role both in the spread of the infodemic and in addressing netizens' web interest, thus favoring the adoption of terms unsuitable for identifying the novel coronavirus (COVID- 19 disease). Therefore, it is highly advisable that the directors of news channels and newspapers be more cautious and government dissemination agencies exert more control over such news.
Climatic control on the location of the Southern Andes volcanic arc
Authors: Muller Veleda Paiva , Sternai Pietro , Sue Christian 
Published: June 2021

Abstract
Volcanic arcs at convergent plate margins are primary surface expressions of plate tectonics. Although climate affects many of the manifestations of plate tectonics via erosion, the upwelling of magmas and location of volcanic arcs are considered insensitive to climate. In the Southern Andes, subduction of the Nazca oceanic plate below the South American continent generates the Southern Andes Volcanic zone. Orographic interactions with Pacific westerlies lead to high precipitation and erosion on the western slopes of the belt between 42-46°S. At these latitudes, the topographic water divide and the volcanic arc are respectively farther and closer to the subduction trench than at lower latitudes, despite a constant subduction dip angle along strike. Here, we use thermomechanical numerical modeling to investigate how magma upwelling is affected by topographic changes due to orography. We show that a leeward topographic shift may entail a windward asymmetry of crustal structures accommodating the magma upwelling, consistent with the observed trench-ward migration of the Southern Andes Volcanic Zone. A climatic control on the location of volcanic arcs via orography and erosion is thus revealed.
Microbial Dehydration of 2-Methylisoborneol in Forest Soil
Authors: Drummond Laura , von Wallbrunn Christian , Buchhaupt Markus 
Published: June 2021

Abstract
Microorganisms use a complex array of chemical compounds to interact with their surroundings. They produce and process different molecules in response to changes in the environment or in their metabolism. One of the most well known volatile organic compounds produced by microorganisms is the C11-terpenoid 2-methylisoborneol (2-MIB), which has received attention because of the off-flavor it confers to fresh and reservoir water as well as to cultured fish. Cleaning water supplies of the off-flavor 2-MIB has been of interest for the scientific community for years, with the use of techniques that are either expensive e.g. activated carbon, or create toxic byproducts e.g. ozonation. In the present study, soil samples from nature were collected from a forest and the volatile organic compounds produced by microbes were extracted and analyzed with focus on non-canonical terpenoid structures. HS-SPME-GC/MS analysis of soil samples revealed 1-methylcamphene, 2-methylenebornane and 2-methylisoborneol as C11-terpenoids. Due to the high 1-MC/2-MIB ratio compared to previous reports, it was hypothesized that microbial degradation of 2-MIB was in place. Addition of synthetic 2-MIB to biologically active soil revealed complete dehydration of the pollutant to 2-MB, 1-MC and 2-methyl-2-bornene (2-M2B). The results suggest the potential of using respective natural microorganisms for biodegradation of 2-MIB, with applications in water treatment, fishery and soil ecology.
An Integrative Prognostic and Immune Analysis of PTPRD in Pan-Cancer
Authors: Ou Chunpei , Peng Qin , Zeng Changchun 
Published: June 2021

Abstract
Background: PTPRD plays an indispensable role in the occurrence of multiple tumors. However, pan-cancer analysis is unavailable. The purpose of this research was to investigate the relationship between PTPRD and immunity and describe its prognostic landscape across various tumors. Methods: We explored expression profile, survival analysis, and genomic alterations of PTPRD based on the TIMER, GEPIA, UALCAN, PrognoScan, and cBioPortal database. The frequency of PTPRD mutation and its correlation with response to immunotherapy were evaluated using the cBioPortal database. The relationship between PTPRD and immune-cell infiltration was analyzed by the TIMER and TISIDB databases. A protein interaction network was constructed by the STRING database. GO and KEGG enrichment analysis was executed by the Metascape database.Results: A significant correlation between PTPRD expression and prognosis was found in various cancers. Aberrant PRPRD expression was closely related to immune infiltration. Importantly, the patients who harbored PTPRD mutation and received immune checkpoint inhibitors had worse overall survival, especially in non-small cell lung cancer and melanoma, and had a higher TMB score. Moreover, PTPRD mutation was involved in numerous biological processes, including immunological signaling pathways. Additionally, a PTPRD protein interaction network was constructed, and genes that interacted with PTPRD were identified. Functional enrichment analysis demonstrated that a variety of GO biological processes and KEGG pathways of PTPRD were primarily involved in the therapeutic mechanisms. Conclusions: These results revealed that PRPRD might function as a biomarker for prognosis and immune infiltration in cancers, throwing new light on cancer therapeutics.
Accelerated Discovery of the Polymer Matrix for Cartilage Repair Through Machine Learning Algorithms
Authors: Mairpady A. , Mourad Abdel-Hamid I. , Mozumder A S Mohammad Sayem 
Published: June 2021

Abstract
Cartilage repair is one of the most challenging tasks for the orthopedic surgeons and researchers. The primary challenge lies on the fact that the development of the extracellular matrixes requires specialized cells known as chondrocytes which are sparse in numbers. Chondrocytes’ minimal self-renewal capacity makes it further troublesome and expensive to repair the cartilages. In designing successful substitutes for the cartilages, the selection of materials used for the scaffold fabrication plays the central role among several other important factors in order to ensure the success of the survival and proliferation of any biomaterial substitutes. Since last few decades, polymer and polymers' combination have been extensively used to fabricate such scaffolds and have shown promising results in terms of mechanical integrity and biocompatibility. In an empirical approach, the selection of the most appropriate polymer(s) for cartilage repair is an expensive and time-consuming affair, as traditionally, it requires numerous trials. Moreover, it is humanly impossible to go through the huge library of literature available on the potential polymer(s) and to correlate their physical, mechanical and biological properties that might be suitable for cartilage tissue engineering. With the advancement of machine learning, material design may experience a significant reduction in experimental time and cost. The objective of this study is to implement an inverse design approach to select the best polymer(s) or composites for cartilage repair by using the machine learning algorithms, such as random forest regression (i.e., regression trees) and the multinomial logistic regression. In these algorithms, the mechanical properties of the polymers, which are similar to the cartilages, are considered as the input and the polymer(s)/composites are the predicted output. According to the random forest regression and multinomial logistic regression, the polymer(s)/composites (i.e., the output) having the closest characteristics of the articular cartilages were found to be a composite of polycaprolactone and poly(bisphenol A carbonate) and a blend of polyethylene/polyethylene-graft-poly(maleic anhydride), respectively. These composites exhibit similar biomechanical properties of the natural cartilages and initiate only minimal immune responses in the body environment.
Women’s Empowerment and Community Norms Association on Women’s Access to Health Facility Delivery in Ethiopia. A Multilevel Analysis.
Authors: Bekele Daniel 
Published: June 2021

Abstract
Background Health-care facility delivery was the most critical in ensuring the provision of high-quality care and a distribution location that was ready in the case of an emergency for reproductive women. However, maternal mortality remains high in African nations, and the majority of women were still giving birth at home. This study was aimed to determine whether women's empowerment and community norms, plus other proximate factors, are related to the health facility delivery utilization of women in Ethiopia. Methods The data for this study was taken from the Performance Monitoring for Action (PMA) in Ethiopia of the 2019 cross-sectional survey. A weighted sample of 4864 women with at least one birth history, clustered within 264 clusters was used for this study. The impact of women's empowerment, cultural norms, and other proximate factors on the use of health facility deliveries among reproductive-age women across clusters in Ethiopia was studied using a two-level multilevel logistic regression. Results In Ethiopia, around 51 % of women were delivered their most recent child at the health facility. The use of a health facility delivery was more common among empowered women and those living in where the most people encourage a health facility delivery. Older women were less likely to deliver at a health facility and women from the highest wealth quantile more likely to have a facility delivery. Those women with higher education and living in an urban area were more likely to have a health facility delivery. Women’s chances of giving birth in health facilities vary significantly across the 264 clusters of Ethiopia ( σ_uo^2 =2.49,p.value<0.001). Conclusions This study emphasizes the importance of women's empowerment and cultural norms in enhancing maternal health outcomes of women in Ethiopia. It is more important than ever that the government and development agency should invest more in women's empowerment and raising community consciousness about the benefits of using health facility delivery as part of a strategic intervention to improve maternal health outcomes.
Cost-utility of Two Minimally-invasive Surgical Techniques for Operable Oropharyngeal Cancer: Transoral Robotic Surgery Versus Transoral Laser Microsurgery
Authors: Parimbelli Enea , Soldati Federico , Duchoud Lorry , de Almeida John , Broglie Martina , Quaglini Silvana , Simon Christian , Armas Gian Luca 
Published: June 2021

Abstract
Background:In the past few decades, a re-evaluation of treatment paradigms of head and neck cancers with a desire to spare patients the treatment-related toxicities of open surgery, has led to the development of new minimally invasive surgical techniques to improve outcomes. Besides Transoral Laser Microsurgery (TLM), a new robotic surgical technique namely Transoral Robotic Surgery (TORS) emerged for the first time as one of the two most prominent and widely used minimally invasive surgical approaches particularly for the treatment of oropharyngeal cancer, a sub-entity of head and neck cancers. Recent population-level data suggest equivalent tumor control, but different total costs, and need for adjuvant chemoradiation. A comparative analysis of these two techniques is therefore warranted from the cost-utility (C/U) point of view.Methods:Decision-analytical model for comparing TORS and TLM from the cost-utility (C/U) point of view.Results: In the base case analysis TLM dominates TORS. This advantage remains robust, even if the costs for TORS reduce by up to 25%. TORS begins to dominate TLM, if less than 59,7% patients require adjuvant treatment, whereby in an interval between 55%-62% cost effectiveness of TORS is sensitive to the prescription of adjuvant CRT. Exceeding 29% of TLM patients requiring a revision of surgical margins renders TORS more cost-effective.Conclusion: Non-robotic endoscopic surgery (TLM) is more cost-effective than robotic endoscopic surgery (TORS) for the treatment of oropharyngeal cancers. However, this advantage is sensitive to various parameters, i.e.to the number of re-operations and adjuvant treatment.
Edaphic Factors as Agents of Genetic Diversity and Adaptation of Native Plant Species of Harsh Environments in the Brazilian Savanna
Authors: Andrade Leide Rovênia Miranda , Aquino Fabiana Góis , Echevarria Guillaume , Oliveira Jamile S. , Pereira Cícero D. , Malaquias Juaci V. , Souza Karina Santos , Montargès-Pelletier Emmanuelle , Faleiro Fábio Gelape , Júnior Fábio Bueno Reis , Miranda Zenilton Gayoso , Sano Edson Eyji 
Published: June 2021

Abstract
Purposes To analyze the main edaphic factors that differentiate ultramafic from typical Cerrado environments and act as agents of the development of biochemical and morphological mechanisms of species adaptation to these harsh environments; and to determine the genetic diversity of three Cerrado’s shrubland native species (Justicia lanstyakii, Euploca salicoides, and Oxalis hirsutissima). Methods We conducted chemical analysis of metal contents in soils, as well as on elemental composition, and analysis of DNA extracted from leaf tissues of the three species found in both environments. In leaves of E. salicoides grown in both environments we evaluated the changes in the levels of non-structural carbohydrates (NSC), and total proteins. Results The accessions obtained in ultramafic soils were closer with each other, indicating genetic similarity and major differences in relation to the accessions collected in the Cerrado area. These differentiations probably are related with higher adaptation to soils rich in metals, mainly Ni in ultramafic, and Al in the Cerrado environments. The highest levels of NSC were observed in plants grown in ultramafic soils, including raffinose, which is related to responses to metal detoxification and drought. The allocation of Ni in the trichomes, which does not affect important processes of plant metabolism, is another mechanism developed by E. salicoides to overcome the hyperaccumulation of Ni in their tissues. Conclusions These findings can help select seed collection sites representative of the genetic diversity of native plant species for restoring degraded areas or for phytoremediation of metals.
Identification of a Novel Missense Mutation in the Fibroblast Growth Factor 5 Gene Associated with Longhair in the Maine Coon Cat
Authors: Shaffer Lisa G , Shaffer Griffin D , Ballif Blake C , Meurs Kathryn , Flores-Smith Helen 
Published: June 2021

Abstract
Hair length can be a highly variable trait within the Felis catus species, varying between and within different cat breeds. Previous research has demonstrated this variability is due to recessive mutations within the fibroblast growth factor 5 (FGF5) gene. Following a clinical genetic screen, four long-haired Maine Coons were identified that had only one copy of a known FGF5 mutation. We performed DNA sequencing on two of the Maine Coons and identified a missense mutation in FGF5 c.G>A625 p.A193T (Mutation 5, M5). Genetic screening via restriction digest was then performed on an additional 275 cats of various breeds, revealing two more Maine Coons heterozygous for M5 and a previously known mutation. No additional cases were identified after in silico analysis of 68 whole genome cat sequences from various breeds, demonstrating that this novel mutation is most likely a breed-specific variant for the Maine Coon, contributing to the longhair phenotype in about 3% of cats.