bluuebunny/crossref_metadata_2025 huggingface dataset:
Deixis In Jakarta Post Article
Authors: Adi Mohammad Sofyan , Rahmat Muhamad Bagus Iqbal
Published: August 2021

The design of this research was descriptive qualitative research that aimed at describing, interpreting and explaining deixis in the newspaper article. The main instrument in this study the researcher himself in doing his analysis supported by using the documentary technique. The data that had been collected were analyzed by the researcher himself. After analyzing the data, then the researcher drew the conclusion about the types and the function of deixis in the sentences of the newspaper articles. Based on the discussion findings,  there were four types of deixis found in The Jakarta Post article, namely 19 person deixis, 29 spatial deixes , 59 time deixis, 55 discourse deixis. From the analysis, the most types of deixis found in Jakarta Post articles time deixis. Thus, it can be said that The Jakarta Post tends to use time deixis as the dominant type compound than another.
Metabolic Benefit of Bulls Being Fed Moringa Leaves Twigs and Branches as a Major Concentrate Ingredient
Authors: Sultana Nasrin , Das Nani Gopal , Kabir Md Ahsanul , Deb Gautam Kumar , Islam Md Tarequl
Published: August 2021

The study was conducted to investigate nutrient metabolism and semen quality of bulls fed with moringa (Moringa oleifera) leaves, twigs, and branches as a major concentrate ingredient. Twenty-one Red Chittagong bulls of about 204 (±50) kg initial live weight (LW) were randomly divided into three equal LW groups. They were fed maize silage as a basal feedstuff for 65 days with the supplementation of concentrate mixtures at 1% of LW, consisting of either 0, 25, or 50% moringa mash on a fresh basis. Moringa mash was a sun-dried ground preparation of leaves, twigs, and branches of moringa. The results indicated that different levels of moringa in concentrate mixtures (0, 25, and 50%) did not change daily DM intake, digestibility, and LW gain of bulls (p > 0.05). However, increasing dietary moringa (up to 203 g/kg DM) significantly decreased production cost of methane (CH4) (methane emission [kg/kg gain] = 1.6422—[0.0059 × moringa intake, g/kg DM], n = 12, R2 = 0.384, P = 0.032) in a similar metabolizable energy intake level (0.21 ± 0.01 MJ/kg LW). Also, higher dietary moringa significantly reduced urinary nitrogen loss (urinary nitrogen [% digested nitrogen] = 43.0 – 0.069 × moringa intake [g/kg DM]; R2 = 0.3712, P = 0.034). Thus, increasing moringa by 1 g/kg DM decreased CH4 emission by 6 g/kg gain and absorbed nitrogen loss by 0.069 %. Also, progressive motility of sperm increased significantly (33.0, 51.0, and 60.1%, respectively; p = 0.03) in bulls fed with concentrate mixtures containing moringa at 0, 25, or 50%. It may be concluded that feeding moringa mash at 203 g/kg DM may decrease energy loss as methane and urinary nitrogen loss without impacting the production of beef cattle. Feeding moringa mash to beef cattle may abate dietary energy and nitrogen loss and consequently decrease the environmental pollution.
Effects of Prosthetic Socket Design on Residual Femur Motion Using Dynamic Stereo X-Ray - A Preliminary Analysis
Authors: Maikos Jason T. , Chomack John M. , Loan J. Peter , Bradley Kathryn M. , D’Andrea Susan E.
Published: August 2021

Individuals with transfemoral amputation experience relative motion between their residual limb and prosthetic socket, which can cause inefficient dynamic load transmission and secondary comorbidities that limit mobility. Accurately measuring the relative position and orientation of the residual limb relative to the prosthetic socket during dynamic activities can provide great insight into the complex mechanics of the socket/limb interface. Five participants with transfemoral amputation were recruited for this study. All participants had a well-fitting, ischial containment socket and were also fit with a compression/release stabilization socket. Participants underwent an 8-wk, randomized crossover trial to compare differences between socket types. Dynamic stereo x-ray was used to quantify three-dimensional residual bone kinematics relative to the prosthetic socket during treadmill walking at self-selected speed. Comfort, satisfaction, and utility were also assessed. There were no significant differences in relative femur kinematics between socket types in the three rotational degrees of freedom, as well as anterior-posterior and medial-lateral translation (p > 0.05). The ischial containment socket demonstrated significantly less proximal-distal translation (pistoning) of the femur compared to the compression/release stabilization socket during the gait cycle (p < 0.05), suggesting that the compression/release stabilization socket provided less control of the residual femur during distal translation. No significant differences in comfort and utility were found between socket types (p > 0.05). The quantitative, dynamic analytical tools used in the study were sensitive to distinguish differences in three-dimensional residual femur motion between two socket types, which can serve as a platform for future comparative effectiveness studies of socket technology.
Potential Strategies to Improve the Effectiveness of Drug Therapy by Changing Factors Related to Tumor Microenvironment
Authors: Cao Dehong , Naiyila Xiaokaiti , Li Jinze , Huang Yin , Chen Zeyu , Chen Bo , Li Jin , Guo Jianbing , Dong Qiang , Ai Jianzhong , Yang Lu , Liu Liangren , Wei Qiang
Published: August 2021

A tumor microenvironment (TME) is composed of various cell types and extracellular components. It contains tumor cells and is nourished by a network of blood vessels. The TME not only plays a significant role in the occurrence, development, and metastasis of tumors but also has a far-reaching impact on the effect of therapeutics. Continuous interaction between tumor cells and the environment, which is mediated by their environment, may lead to drug resistance. In this review, we focus on the key cellular components of the TME and the potential strategies to improve the effectiveness of drug therapy by changing their related factors.
Iron Deficiency: A New Target for Patients With Heart Failure
Authors: Rizzo Caterina , Carbonara Rosa , Ruggieri Roberta , Passantino Andrea , Scrutinio Domenico
Published: August 2021

Iron deficiency (ID) is one of the most frequent comorbidities in patients with heart failure (HF). ID is estimated to be present in up to 50% of outpatients and is a strong independent predictor of HF outcomes. ID has been shown to reduce quality of life, exercise capacity and survival, in both the presence and absence of anemia. The most recent 2016 guidelines recommend starting replacement treatment at ferritin cutoff value <100 mcg/l or between 100 and 299 mcg/l when the transferrin saturation is <20%. Beyond its effect on hemoglobin, iron plays an important role in oxygen transport and in the metabolism of cardiac and skeletal muscles. Mitochondria are the most important sites of iron utilization and energy production. These factors clearly have roles in the diminished exercise capacity in HF. Oral iron administration is usually the first route used for iron repletion in patients. However, the data from the IRONOUT HF study do not support the use of oral iron supplementation in patients with HF and a reduced ejection fraction, because this treatment does not affect peak VO2 (the primary endpoint of the study) or increase serum ferritin levels. The FAIR-HF and CONFIRM-HF studies have shown improvements in symptoms, quality of life and functional capacity in patients with stable, symptomatic, iron-deficient HF after the administration of intravenous iron (i.e., FCM). Moreover, they have shown a decreased risk of first hospitalization for worsening of HF, as later confirmed in a subsequent meta-analysis. In addition, the EFFECT-HF study has shown an improvement in peak oxygen consumption at CPET (a parameter generally considered the gold standard of exercise capacity and a predictor of outcome in HF) in patients randomized to receive ferric carboxymaltose. Finally, the AFFIRM AHF trial evaluating the effects of FCM administration on the outcomes of patients hospitalized for acute HF has found significantly fewer hospital readmissions due to HF among patients treated with FCM rather than placebo.
ANTASed – An Updated Sediment Model for Antarctica
Authors: Baranov A. , Morelli A. , Chuvaev A.
Published: August 2021

We compile existing seismic, gravity, radar and magnetic data, together with the subglacial bedrock relief from the BEDMACHINE project, to build the most detailed sediment model for Antarctica. We interpolate these data according to a tectonic map of Antarctica using a statistical kriging method. Our results reveal significant sediment accumulation in Antarctica with several types of sedimentary basins: parts of the Beacon Supergroup and more recent rifting basins. The basement relief closely resembles major geological and tectonic structures. The thickness of sediments has significant variations around the continent, and depends on the degree of crustal extension. West Antarctica has wide sedimentary basins: the Ross basin (thickness 2–6 km), the Filchner-Ronne basin (2–12 km) with continuations into East Antarctica, the Bentley Subglacial Trench and the Byrd basin (2–4 km). The deepest Filchner-Ronne basin has a complex structure with multi-layered sediments. East Antarctica is characterized by vast sedimentary basins such as the Pensacola-Pole (1–2 km), Coats Land (1–3 km), Dronning Maud Land (1–2 km), Vostok (2–7 km), Aurora (1–3 km), Astrolabe (2–4 km), Adventure (2–4 km), and Wilkes (1–4 km) basins, along with narrow deep rifts filled by sediments: JutulStraumen (1–2 km), Lambert (2–5 km), Scott, Denman, Vanderford and Totten (2–4 km) rifts. The average thickness of sediments for the whole continent is about 0.77 km. The new model, ANTASed, represents a significant improvement over CRUST 1.0 for Antarctica, and reveals new sedimentary basins. Differences between ANTASed and CRUST 1.0 reach +12/−3 km.
Economic Evaluation of Combined Heat and Power Integrated With Food Waste-Based Ethanol Production
Authors: Shafinas Muhammad Noor Intan , Rosentrater Kurt A.
Published: August 2021

The concern of food waste (FW) impact on the environment, societies, and economies, has triggered many researchers to find alternative ways to utilize these materials. FW can be high in glucose and other sugars (depending upon the food used) and has the potential to be converted into value-added products such as ethanol. Ethanol is an organic material that has a high demand from different industries for products such as fuel, beverages, pharmaceuticals, and other industrial applications. FW fermentation to produce ethanol may be a promising method, and might results in positive impacts on economies. However, it is a challenge for the product price to compete with that of corn ethanol due to low yield and the inconsistency of FW composition. Thus, to increase the profitability, a conventional fermentation plant integrated with a combined heat and power (CHP) system might be a great combination, and was analyzed in this study. Solid waste stream from the process can be converted into energy and could reduce the utility cost. Therefore, the main focus of this study is to evaluate the economic impact of this integrated system by estimating the minimum selling price (MSP) using techno-economic analysis (TEA) and compare to conventional plants without CHP. Results from this analysis showed that the MSE value for this integrated system was $1.88 per gallon ($0.50 per liter). This study suggests that an integrated system with CHP was found to be more economical and attractive to be implemented on a commercial scale.
Conducting Research in a Post-normal Paradigm: Practical Guidance for Applying Co-production of Knowledge
Authors: Nogueira Leticia Antunes , Bjørkan Maiken , Dale Brigt
Published: August 2021

Meaningful engagement between scientists and stakeholders has been extensively promoted as a tool for increasing public participation in science, as well as for increasing the relevance and impact of scientific research. Yet, co-production of knowledge entails practical challenges, since participants with diverse worldviews, expertise and interests are expected to collaborate. These obstacles have not received enough attention, as current debate has focused more on the merits and principles of this approach. We address this gap by reflecting upon our experiences with both practical and methodological challenges stemming from research projects based on co-production of knowledge, thereby exposing what we see as common but under-discussed obstacles, as well as guidance for tackling them. We highlight the role of social scientists in the process not merely as facilitators but also as agents that promote critical reflection and safeguard the salience, credibility, and legitimacy of both the process and its outputs.
Nitrogen Deposition Effects on Soil Properties, Microbial Abundance, and Litter Decomposition Across Three Shrublands Ecosystems From the Mediterranean Basin
Authors: Lo Cascio Mauro , Morillas Lourdes , Ochoa-Hueso Raúl , Delgado-Baquerizo Manuel , Munzi Silvana , Roales Javier , Spano Donatella , Cruz Cristina , Gallardo Antonio , Manrique Esteban , Pérez-Corona María Esther , Dias Teresa , Sirca Costantino , Mereu Simone
Published: August 2021

Atmospheric nitrogen (N) inputs in the Mediterranean Basin are projected to increase due to fossil fuel combustion, fertilizer use, and the exacerbation of agricultural production processes. Although increasing N deposition is recognized as a major threat to ecosystem functioning, little is known about how local environmental conditions modulate ecosystem function response to N addition, particularly in the context of Mediterranean-Basin ecosystems. Here, we assess how N addition affects important ecosystem properties associated with litter decomposition, soil physical-chemical properties, soil extracellular enzymatic activity and microbial abundance across three long-term N addition experimental sites in the Mediterranean Basin. Sites were located in El Regajal (Madrid, Spain), Capo Caccia (Alghero, Italy), and Arrábida (Lisbon, Portugal) and are all representative of Mediterranean shrublands. No common pattern for litter decomposition process or other studied variables emerged among the control plots of the studied sites. Nitrogen supply only affected soil pH, a major driver of decomposition, in two out of three experimental sites. Moreover, when we explored the role of N addition and soil pH in controlling litter decay, we found that the effects of these factors were site-dependent. Our results point out to local ecosystem features modulating N addition effects in controlling litter decomposition rates in Mediterranean ecosystems, suggesting that the responses of soil functioning to N deposition are site-dependent. These findings provide further knowledge to understand contrasting ecosystem responses to N additions based on a single field experiments.
Threadfin Porgy (Evynnis Cardinalis) Haplotype Pattern and Genetic Structure in Beibu Gulf, South China Sea
Authors: Xu Lei , Wang Xuehui , Wang Lianggen , Ning Jiajia , Li Yafang , Huang Delian , Liu Shuangshuang , Du Feiyan
Published: August 2021

Threadfin porgy (Evynnis cardinalis) is one of the important commercial fishing targets of bottom trawl fishery in the northern South China Sea. It is mainly threatened by overexploitation and listed as endangered species in the IUCN Red List. To investigate the demographic history and genetic structure of E. cardinalis population, partial sequences of the mitochondrial cytochrome c oxidase subunit I (COI) gene were obtained from 162 individuals collected from Beibu Gulf, South China Sea. In total, 44 different haplotypes were identified, and the dominant haplotype was found in all sampling sites. Across the dataset, nucleotide diversity was low, whereas haplotype diversity was high. Low pairwise comparisons of ΦST and high gene flow among sampling sites revealed a genetically homogeneous population structure in Beibu Gulf, indicating a single panmictic stock of E. cardinalis in this area. The star-like haplotype network, unimodal mismatch distribution, and significantly negative Tajima’s D and Fu’s Fs values indicated recent population demographic expansion of E. cardinalis. The mismatch distribution and Bayesian skyline plot results indicated that E. cardinalis from Beibu Gulf might have experienced colonization and demographic expansion due to sea level fluctuations during the late Pleistocene.
Genetics, Epigenetics, and Gender Impact in Axial-Spondyloarthritis Susceptibility: An Update on Genetic Polymorphisms and Their Sex Related Associations
Authors: Chimenti Maria Sole , Perricone Carlo , D’Antonio Arianna , Ferraioli Mario , Conigliaro Paola , Triggianese Paola , Ciccacci Cinzia , Borgiani Paola , Perricone Roberto
Published: August 2021

Spondyloarthritis (SpA) is a group of chronic inflammatory rheumatic disease that can be divided into predominantly axial or predominantly peripheral involvement, with or without associated psoriasis, inflammatory bowel disease or previous infection. Axial SpA (axSpA) encompasses ankylosing spondylitis (AS) with radiological sacroiliitis, and a type without radiographic sacroiliitis, called “non-radiographic axial SpA” (nr-axSpA). Males and females show large differences in their susceptibility to SpA, such as distinctions in clinical patterns, phenotypes and in therapeutical response, particularly to TNF inhibitors (TNFi). Several studies indicate that AS women have doubled risk to failure TNFi compared with males. This diversity in drugs’ efficacy among women and men may be caused by differences in the balance of sex hormones and in gene-specific expression likely triggered by X-chromosome instability and gene-specific epigenetic modifications. Evidence reported that polymorphisms in microRNAs on X- and other chromosomes, such as miR-146a, miR-155, miR-125a-5p, miR-151a-3p and miR-22-3p, miR-199a-5p could be involved in the different clinical presentation of SpA, as well as disease activity. In addition, association with non−response to TNFi treatment and presence of IRAK3 and CHUCK genes in SpA patients was recently detected. Finally, polymorphisms in genes involved in IL-23/IL-17 pathway, such as in drug pharmacodynamics and pharmacokinetics may have a role in response to TNFi, IL17i, and IL23i. A major understanding of genomic variability could help in the development of new therapeutic targets or in taking advantages of different mechanisms of action of biological drugs. Moving from the multifactorial etiology of disease, the present review aims at evaluating genetic and epigenetic factors and their relationship with sex and bDMARDs response, helping to investigate the different expression among males and females of genes on X- and other chromosomes, as well as mi-RNA, to highlight relationships between sex and occurrence of specific phenotypes and symptoms of the disease. Moreover, the role of the epigenetic modification in relation to immune-regulatory mechanisms will be evaluated.
Immune Privilege of Heart Valves
Authors: Hill Morgan Ashley , Kwon Jennie H. , Gerry Brielle , Hardy William A. , Walkowiak Olivia Agata , Kavarana Minoo N. , Nadig Satish N. , Rajab T. Konrad
Published: August 2021

Immune privilege is an evolutionary adaptation that protects vital tissues with limited regenerative capacity from collateral damage by the immune response. Classical examples include the anterior chamber of the eye and the brain. More recently, the placenta, testes and articular cartilage were found to have similar immune privilege. What all of these tissues have in common is their vital function for evolutionary fitness and a limited regenerative capacity. Immune privilege is clinically relevant, because corneal transplantation and meniscal transplantation do not require immunosuppression. The heart valves also serve a vital function and have limited regenerative capacity after damage. Moreover, experimental and clinical evidence from heart valve transplantation suggests that the heart valves are spared from alloimmune injury. Here we review this evidence and propose the concept of heart valves as immune privileged sites. This concept has important clinical implications for heart valve transplantation.
Hemoglobin Extracted From Perinereis aibuhitensis Acts as a Cell Culture Medium Supplement to Reduce Apoptosis
Authors: Huo Qianyu , Liu Jing , Cheng You , Cao Bin , Lei Ming , Liu Yunde
Published: August 2021

The environmental oxygen concentration is a crucial factor affecting cell proliferation. Owing to the reversible binding property of hemoglobin to oxygen, it can be utilized to regulate the oxygen concentrationin vitro, and its ability to reduce apoptosis can be evaluated. In this study, a process comprising isolation, purification, and extraction was used to obtain hemoglobin fromPerinereis aibuhitensis, a polychaete invertebrate. Extracts were separated and characterized using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Extract component identity was confirmed by matrix-assisted laser desorption time-of-flight mass spectrometry analysis, with the molecular weight determined as 412,216.6875 Da. The oxygen carrying capacity ofP. aibuhitensishemoglobin was comparable with that of human hemoglobin.P. aibuhitensishemoglobin remarkably downregulated the apoptosis rate. Reactive oxygen species (ROS) assays confirmed the reduction in ROS production, enabling a better elucidation of the mechanism underlying the decrease in apoptosis. These results suggested thatP. aibuhitensishemoglobin is a natural oxygen carrier, that, owing to its low-cost and accessibility, can be considered a candidate for culture medium supplement to reduce the apoptosis rate.
Phytoplankton Increase Along the Kuroshio Due to the Large Meander
Authors: Lizarbe Barreto Daniel Andres , Chevarria Saravia Ricardo , Nagai Takeyoshi , Hirata Takafumi
Published: August 2021

The Kuroshio Large Meander (LM) is known to be highly aperiodic and can last from 1 to 10 years. Since a stationary cold core formed between the Kuroshio and the southern coast of Japan off Enshu-Nada and approaching warm saltier water on the eastern side of the LM changes the local environment drastically, many commercially valuable fish species distribute differently from the non-LM period, impacting local fisheries. Despite this importance of the LM, the influences of the LM on the low trophic levels such as phytoplankton and zooplankton have still been unclear. In this study, satellite daily sea surface chlorophyll data are analyzed in relation to the LM. The results show positive anomalies of the chlorophyll-a concentration along the Kuroshio path during the LM periods, 2004–2005 and 2017–2019, from the upstream off Shikoku to the downstream (140°E). These positive anomalies are started by the triggering meander generated off south of Kyushu, which then slowly propagates to the downstream LM region in both the LM periods. Even though the detailed patterns along the Kuroshio region in the two LM periods were different, similar formations of the positive anomalies on the western side of the LM with shallower mixed layer depth are observed. Furthermore, we found clear relationships between the minimum distance from several stations along the coast to the Kuroshio axis and the mean chlorophyll-a anomaly, with significant correlations with the distance from different stations.
Case Report: Near-Fatal Intestinal Hemorrhage and Acute Acalculous Cholecystitis due to Vi-Negative and Fluoroquinolone-Insensitive Salmonella enterica Serovar Typhi Infection: A Rare Entity
Authors: Gong Yuehua , Li Jianlin , Zhu Dongnan , Wang Songsong , Xu Yingchun , Li Yan , Wang Yanqing , Song Yan , Liu Wenjuan , Tian Yunlong
Published: August 2021

Typhoid fever is usually a mild clinical disease. Typhoid fever with massive intestinal hemorrhage is rare in the antibiotic era. Acute acalculous cholecystitis (AAC) is also rare in adults. Here, we describe the first adult case of typhoid fever with both complications due to Vi-negative and fluoroquinolone-insensitive Salmonella enterica serovar Typhi (S. Typhi) infection. We aim to alert physicians to this rare condition.
Active Surveillance, Drug Resistance, and Genotypic Profiling of Staphylococcus aureus Among School-Age Children in China
Authors: Liang Bingshao , Liang Xiaoyun , Gao Fei , Long Yan , Mai Jialiang , Ai Xiaolan , Wang Jielin , Gao Xiurong , Xiong Zhile , Liang Zhuwei , Zhang Chao , Gong Sitang , Zhou Zhenwen
Published: August 2021

Methicillin-susceptible (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) nasal colonization predisposes individuals for endogenous infections and is a major threat to children. Recently, oxacillin/cefoxitin-susceptible mecA-positive S. aureus (OS-MRSA) has been reported worldwide. Herein, a prospective, cross-sectional study was conducted across five schools, representing three educational stages, in Guangzhou, China. Nasal swabs from 2,375 students were cultured for S. aureus and all isolates were subjected to antibiotic susceptibility testing phenotypically and confirmed by femB and mecA genetic detection; all the isolates were classified as MSSA, MRSA, or OS-MRSA. All strains were also analyzed by multi-locus sequence typing. Among the 2,375 swabs, S. aureus was detected in 744 children (31.3%, 95% CI: 25.9–36.7%), of whom 72 had MRSA (3.0%, 95% CI: 0.6–5.4%) and 4 had OS-MRSA (0.2%, 95% CI: 0.1–0.3%), of which an oxacillin- and cefoxitin-susceptible MRSA strain was identified. The prevalence of S. aureus and MRSA was higher in younger children. The highest percentage of drug resistance of the S. aureus isolates (n = 744) was to penicillin (85.5%), followed by erythromycin (43.3%) and clidamycin (41.0%). The most prevalent sequence types (STs) were ST30, ST45, and ST188 in MSSA, accounting for 38.7% of the total isolates, whereas ST45, ST59, and ST338 accounted for 74.6% of the MRSA isolates and ST338 accounted for 50.0% of the OS-MRSA isolates. The MRSA and OS-MRSA isolates (n = 76) were grouped into three clades and one singleton, with clonal complex (CC) 45 as the most predominant linkage. The top nine multi-locus sequence typing-based CCs (CC30, CC45, CC5, CC1, CC15, CC944, CC398, CC59, CC7) represented 86.7% of all S. aureus isolates. All CC30 isolates were resistant to erythromycin and clidamycin, and almost all these isolates were also resistant to penicillin (99.2%). The CC45 and CC59 isolates exhibited high resistance rates to oxacillin at 31.5 and 59.0%, respectively. This study provides updated data valuable for designing effective control strategies to mitigate the burden of disease and to improve the adequacy of empirical antimicrobial treatments for potentially harmful infections.
MicroRNAs as Biomarkers for the Diagnosis of Ankylosing Spondylitis: A Systematic Review and Meta-Analysis
Authors: Li Jiangbi , Xie Xiaoping , Liu Weibing , Gu Feng , Zhang Ke , Su Zilong , Wen Qiangqiang , Sui Zhenjiang , Zhou Pengcheng , Yu Tiecheng
Published: August 2021

Background: Abnormal expression levels of microRNAs (miRNAs) were observed in ankylosing spondylitis (AS) in recent articles, suggesting that miRNAs may be used as biomarkers for AS diagnoses. In this paper, we conducted a meta-analysis to identify the overall diagnostic accuracy of miRNA biomarkers in AS patients.

Methods: An extensive search was undertaken in PubMed, Embase, Cochrane databases, and Wan Fang database up to 30 December 2020 using the following key words: (“microRNAs” or “microRNA” or “miRNA” or “miR” or “RNA, Micro” or “Primary MicroRNA”) and (“Spondylitis Ankylosing” or “Spondyloarthritis Ankylopoietica” or “Ankylosing Spondylarthritis” or “Ankylosing Spondylarthritides” or “Spondylarthritides Ankylosing” or “Ankylosing Spondylitis”) and (“blood” or “serum” or “plasma”). Statistical evaluation of dysregulated miRNAs using the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the area under the curve (AUC).

Results: Twenty-nine articles reporting on the miRNAs of AS were included. A total of 42 miRNAs were observed to be up-regulated and 45 miRNAs were down-regulated in the AS cases compared with the controls. Besides, 29 studies from nine articles were included in our meta-analysis. The pooled sensitivity, specificity, PLR, NLR, DOR, and AUC were 0. 76 (95% CI, 0.70–0.81), 0.80 (95% CI, 0.74–0.85), 3.75 (95% CI, 2.82–5.01), 0.30 (95% CI, 0.24–0.39), 12.32 (95% CI, 7.65–19.83), 0.85 (95% CI, 0.81–0.88), respectively, suggesting a good diagnostic accuracy of miRNAs for AS.

Conclusions: Circulating miRNAs are deregulated in AS patients. miRNAs may be used as a relatively non-invasive biomarkers for the detection of AS.
Nailfold Capillaroscopy Abnormalities Correlate With Disease Activity in Adult Dermatomyositis
Authors: Johnson Dylan , van Eeden Charmaine , Moazab Naima , Redmond Desiree , Phan Cecile , Keeling Stephanie , Gniadecki Robert , Cohen Tervaert Jan Willem , Osman Mohammed
Published: August 2021

Objectives:The aim of this study was to determine the relationship between disease activity in adult patients with dermatomyositis (DM) and other biomarkers of disease activity such as C-reactive protein creatinine kinase and nailfold video capillaroscopy (NVC).

Methods:We performed a prospective single center study of 15 adult patients with DM. Study participants underwent two assessments at least 9 months apart including clinical, laboratory and NVC evaluations. Patients received immunosuppressive medications for their dermatomyositis, and ongoing disease activity was measured by the Myositis Intention to Treat Index (MITAX). NVC evaluation included assessment of capillary density, capillary apical diameter (mm), and the number of microhemorrhages per digit.

Results:Microvascular abnormalities were present in most DM patients. Of these, capillary density (4.71 vs. 6.84,p= 0.006) and mean apical diameter (56.09 vs. 27.79 μm,p= 0.003) significantly improved over the study period in concordance with improving disease control (MITAX 8.53 vs. 2.64,p= 0.002). Longitudinal analysis demonstrated that capillary density was independently associated with MITAX (β = −1.49 [CI −2.49, −0.33],p= 0.013), but not other parameters such as C-reactive protein and creatinine kinase.

Conclusions:Nailfold capillary density is a dynamic marker of global disease activity in adult DM. NVC may be utilized as a non-invasive point-of-care tool to monitor disease activity and inform treatment decisions in patients with DM.
Development and Validation of Nomograms to Predict Operative Link for Gastritis Assessment Any-Stage and Stages III–IV in the Chinese High-Risk Gastric Cancer Population
Authors: Wang Song , Ye Fei , Sheng Yuan , Yu Wenyong , Liu Yingling , Liu Dehua , Zhang Kaiguang
Published: August 2021

Purpose: It is very essential to diagnose gastric atrophy in the area with high prevalence of gastric cancer. Operative link for gastritis assessment (OLGA) was developed to detect the severity of gastric atrophy. The aim of this study was to develop and validate nomograms for predicting OLGA any-stage and stages III–IV in the Chinese high-risk gastric cancer population.

Methods: We retrospectively analyzed 7,945 participants obtained by a multicenter cross-sectional study. We randomly selected 55% individuals (4,370 participants, training cohort) to analyze and generate the prediction models and validated the models on the remaining individuals (3,575 participants, validation cohort). A multivariate logistic regression model was used to select variables in the training cohort. The corresponding nomograms were developed to predict OLGA any-stage and stages III–IV, respectively. The area under the receiver operating characteristic curves and the GiViTI calibration belts were used to estimate the discrimination and calibration of the prediction models.

Results: There were 1,226 (28.05%) participants in the training sample and 970 (27.13%) in the validation sample who were diagnosed with gastric atrophy. The nomogram predicting OLGA any-stage had an area under the curve (AUC) of 0.610 for the training sample and 0.615 for the validation sample, with favorable calibrations in the overall population. Similarly, the nomogram predicting OLGA stages III–IV had an AUC of 0.702 and 0.714 for the training and validation samples, respectively, with favorable calibrations in the overall population.

Conclusions: The prediction model can early identify the occurrence of gastric atrophy and the severity stage of gastric atrophy to some extent.
Clandestinovirus: A Giant Virus With Chromatin Proteins and a Potential to Manipulate the Cell Cycle of Its Host Vermamoeba vermiformis
Authors: Rolland Clara , Andreani Julien , Sahmi-Bounsiar Dehia , Krupovic Mart , La Scola Bernard , Levasseur Anthony
Published: August 2021

For several decades, the vast world of DNA viruses has been expanding constantly. Various discoveries in this field have broadened our knowledge and revealed that DNA viruses encode many functional features, which were once thought to be exclusive to cellular life. Here, we report the isolation of a giant virus named “clandestinovirus,” grown on the amoebal host Vermamoeba vermiformis. This virus was discovered in a mixed co-culture associated with another giant virus, Faustovirus ST1. Clandestinovirus possesses a linear dsDNA genome of 581,987 base pairs containing 617 genes. Phylogenetically, clandestinovirus is most closely related to Acanthamoeba castellanii medusavirus and was considered a member of the proposed Medusaviridae family. However, clandestinovirus genome is 65% larger than that of medusavirus, emphasizing the considerable genome size variation within this virus family. Functional annotation of the clandestinovirus genes suggests that the virus encodes four core histones. Furthermore, clandestinovirus appears to orchestrate the cell cycle and mitochondrial activities of the infected host by virtue of encoding a panel of protein kinases and phosphatases, and a suite of functionally diverse mitochondrial protein homologs, respectively. Collectively, these observations illuminate a strategy employed by clandestinovirus to optimize the intracellular environment for efficient virus propagation.
Simulating PIP2-Induced Gating Transitions in Kir6.2 Channels
Authors: Bründl Michael , Pellikan Sarala , Stary-Weinzinger Anna
Published: August 2021

ATP-sensitive potassium (KATP) channels consist of an inwardly rectifying K+channel (Kir6.2) pore, to which four ATP-sensitive sulfonylurea receptor (SUR) domains are attached, thereby coupling K+permeation directly to the metabolic state of the cell. Dysfunction is linked to neonatal diabetes and other diseases. K+flux through these channels is controlled by conformational changes in the helix bundle region, which acts as a physical barrier for K+permeation. In addition, the G-loop, located in the cytoplasmic domain, and the selectivity filter might contribute to gating, as suggested by different disease-causing mutations. Gating of Kir channels is regulated by different ligands, like Gβγ, H+, Na+, adenosine nucleotides, and the signaling lipid phosphatidyl-inositol 4,5-bisphosphate (PIP2), which is an essential activator for all eukaryotic Kir family members. Although molecular determinants of PIP2activation of KATPchannels have been investigated in functional studies, structural information of the binding site is still lacking as PIP2could not be resolved in Kir6.2 cryo-EM structures. In this study, we used Molecular Dynamics (MD) simulations to examine the dynamics of residues associated with gating in Kir6.2. By combining this structural information with functional data, we investigated the mechanism underlying Kir6.2 channel regulation by PIP2.
Versatile Surface Electrodes for Combined Electrophysiology and Two-Photon Imaging of the Mouse Central Nervous System
Authors: Schweigmann Michael , Caudal Laura C. , Stopper Gebhard , Scheller Anja , Koch Klaus P. , Kirchhoff Frank
Published: August 2021

Understanding and modulating CNS function in physiological as well as pathophysiological contexts remains a significant ambition in research and clinical applications. The investigation of the multifaceted CNS cell types including their interactions and contributions to neural function requires a combination of the state-of-the-art in vivo electrophysiology and imaging techniques. We developed a novel type of liquid crystal polymer (LCP) surface micro-electrode manufactured in three customized designs with up to 16 channels for recording and stimulation of brain activity. All designs include spare central spaces for simultaneous 2P-imaging. Nanoporous platinum-plated contact sites ensure a low impedance and high current transfer. The epidural implantation of the LCP micro-electrodes could be combined with standard cranial window surgery. The epidurally positioned electrodes did not only display long-term biocompatibility, but we also observed an additional stabilization of the underlying CNS tissue. We demonstrate the electrode’s versatility in combination with in vivo 2P-imaging by monitoring anesthesia-awake cycles of transgenic mice with GCaMP3 expression in neurons or astrocytes. Cortical stimulation and simultaneous 2P Ca2+ imaging in neurons or astrocytes highlighted the astrocytes’ integrative character in neuronal activity processing. Furthermore, we confirmed that spontaneous astroglial Ca2+ signals are dampened under anesthesia, while evoked signals in neurons and astrocytes showed stronger dependency on stimulation intensity rather than on various levels of anesthesia. Finally, we show that the electrodes provide recordings of the electrocorticogram (ECoG) with a high signal-to noise ratio and spatial signal differences which help to decipher brain activity states during experimental procedures. Summarizing, the novel LCP surface micro-electrode is a versatile, convenient, and reliable tool to investigate brain function in vivo.
Why Me? To Be an Ultra-Responder to Antiplatelet Therapy: A Case Report
Authors: Rosafio Francesca , Bigliardi Guido , Lelli Nicoletta , Vandelli Laura , Naldi Federica , Ciolli Ludovico , Meletti Stefano , Zini Andrea
Published: August 2021

Background: Platelet function testing is a valid tool to investigate the clinical response to antiplatelet therapy in different clinical settings; in particular, it might supply helpful information in patients with cerebrovascular disease. Oral antiplatelet treatment, such as Aspirin (ASA) and Clopidogrel, is the gold standard in secondary stroke prevention of non-cardiogenic ischemic stroke; conversely, its application as a primary prevention therapy is not routinely recommended in patients with vascular risk factors. Multiple electrode platelet aggregometry (MEA) impedance aggregometer is a validated device to test platelet inhibition induced by ASA or Clopidogrel.

Case Report: We report the case of a 78-year-old patient without relevant clinical history, taking ASA as primary prevention strategy, who was admitted for sudden onset of dysarthria and left facial hyposthenia during physical effort. Brain CT revealed two small subcortical bilateral spontaneous intracranial hemorrhages. Platelet aggregometry with MEA performed upon admission revealed a very strong platelet inhibition induced by ASA (result of the ASPI Test was 5 U, consistent with an ultra-responsiveness to ASA, and the cutoff value of correct responsiveness is <40 U). MRI at longitudinal follow-up revealed the presence of two small cavernous angioma underlying hemorrhagic spots.

Conclusion: The evaluation of platelet reactivity in stroke patients undergoing antiplatelet therapies, not commonly performed in clinical practice, could be useful to optimize prevention strategies; the verification of the biological effectiveness of ASA or Clopidogrel could be a valid tool in the definition of each patient's risk profile, particularly in patients with cerebrovascular disease known to be at increased risk for both hemorrhagic and thrombotic complications.
Certain Associations Between Iron Biomarkers and Total and γ' Fibrinogen and Plasma Clot Properties Are Mediated by Fibrinogen Genotypes
Authors: Rautenbach Petro H. , Nienaber-Rousseau Cornelie , de Lange-Loots Zelda , Pieters Marlien
Published: August 2021

Introduction: Evidence for the relationship between body iron and cardiovascular disease (CVD) is inconsistent and mechanisms involved remain poorly understood. Therefore, we first investigated whether there are linear or non-linear relationships between iron status and total and γ' fibrinogen as well as plasma fibrin clot properties and, second, determined whether there are interactions with iron biomarkers and fibrinogen and FXIII single nucleotide polymorphisms (SNPs) in relation to fibrinogen concentration and functionality.

Methods: In this cross-sectional analysis of 2,010 apparently healthy Black South Africans we quantified total and γ' fibrinogen, serum iron, ferritin and transferrin using standardized methods and calculated transferrin saturation (TS). Clot architecture and lysis were explored with a global analytical turbidity assay. The SNPs were determined through an Illumina BeadXpress® platform.

Results: Total, but not %γ', fibrinogen negatively correlated with serum iron concentrations, although both decreased over iron tertiles. %γ' fibrinogen correlated negatively with transferrin and decreased over the transferrin tertiles. A weak negative association between total fibrinogen and TS was detected with fibrinogen decreasing over the TS tertiles and categories based on TS. Lag time correlated positively with transferrin and increased over transferrin tertiles, when adjusting for fibrinogen. Before adjusting for fibrinogen, lag time was shorter in those with adequate iron status based on TS than other iron subcategories. Clot lysis time (CLT) negatively correlated with ferritin and was longer in the first than in the third ferritin tertile. Among iron status categories based on ferritin, only CLT differed and was longer in those with adequate iron than with iron-overload. CLT negatively correlated with TS, albeit weakly, shortened over the TS tertiles and was shorter in those with adequate iron based on TS categories. Interactions were observed between FGB SNPs and some of the markers of iron status investigated, in relation to the clot properties with the most prominent associations detected in homozygous carriers of the variant alleles for whom increased iron status was more beneficial than for those harboring the wild-type alleles. Iron modulated the influence of the SNPs so that for the majority iron was beneficial in respect of clot properties, but even more so for a minority group harboring specific variant alleles.

Conclusion: This is the first large-scale epidemiological study to relate fibrinogen concentration and functionality to markers of iron status and to take genetic factors into consideration. We have detected a relationship between iron biomarkers and fibrinogen as well as clot characteristics that are influenced by the genetic make-up of an individual.
The Emerging Landscapes of Long Noncoding RNA in Thyroid Carcinoma: Biological Functions and Clinical Significance
Authors: Zhu Jian , Liu Changrui , Wang Dan , Cao Xianjiao , Wang Shuai , Liu Yixin , Wang Jun , Li Peifeng , He Qingqing
Published: August 2021

Thyroid carcinoma (TC) is one of the most prevalent primary endocrine tumors, and its incidence is steadily and gradually increasing worldwide. Accumulating evidence has revealed the critical functions of long noncoding RNAs (lncRNAs) in the tumorigenesis and development of TC. Many TC-associated lncRNAs have been documented to be implicated in TC malignant behaviors, including abnormal cell proliferation, enhanced stem cell properties and aggressiveness, and resistance to therapeutics, through interaction with proteins, DNA, or RNA or encoding small peptides. Therefore, further elucidating the lncRNA dysregulation sheds additional insights into TC tumorigenesis and progression and opens new avenues for the early diagnosis and clinical therapy of TC. In this review, we summarize the abnormal expression of lncRNA in TC and the fundamental characteristics in TC tumorigenesis and development. Additionally, we introduce the potential prognostic and therapeutic significance of lncRNAs in TC.
Fetal Brain Biometric Measurements on 3D Super-Resolution Reconstructed T2-Weighted MRI: An Intra- and Inter-observer Agreement Study
Authors: Khawam Marie , de Dumast Priscille , Deman Pierre , Kebiri Hamza , Yu Thomas , Tourbier Sébastien , Lajous Hélène , Hagmann Patric , Maeder Philippe , Thiran Jean-Philippe , Meuli Reto , Dunet Vincent , Bach Cuadra Meritxell , Koob Mériam
Published: August 2021

We present the comparison of two-dimensional (2D) fetal brain biometry on magnetic resonance (MR) images using orthogonal 2D T2-weighted sequences (T2WSs) vs. one 3D super-resolution (SR) reconstructed volume and evaluation of the level of confidence and concordance between an experienced pediatric radiologist (obs1) and a junior radiologist (obs2). Twenty-five normal fetal brain MRI scans (18–34 weeks of gestation) including orthogonal 3-mm-thick T2WSs were analyzed retrospectively. One 3D SR volume was reconstructed per subject based on multiple series of T2WSs. The two observers performed 11 2D biometric measurements (specifying their level of confidence) on T2WS and SR volumes. Measurements were compared using the paired Wilcoxon rank sum test between observers for each dataset (T2WS and SR) and between T2WS and SR for each observer. Bland–Altman plots were used to assess the agreement between each pair of measurements. Measurements were made with low confidence in three subjects by obs1 and in 11 subjects by obs2 (mostly concerning the length of the corpus callosum on T2WS). Inter-rater intra-dataset comparisons showed no significant difference (p > 0.05), except for brain axial biparietal diameter (BIP) on T2WS and for brain and skull coronal BIP and coronal transverse cerebellar diameter (DTC) on SR. None of them remained significant after correction for multiple comparisons. Inter-dataset intra-rater comparisons showed statistical differences in brain axial and coronal BIP for both observers, skull coronal BIP for obs1, and axial and coronal DTC for obs2. After correction for multiple comparisons, only axial brain BIP remained significantly different, but differences were small (2.95 ± 1.73 mm). SR allows similar fetal brain biometry as compared to using the conventional T2WS while improving the level of confidence in the measurements and using a single reconstructed volume.