bluuebunny/crossref_metadata_2025 huggingface dataset:
When Biomass Electricity Demand Prompts Thinnings in Southern US Pine Plantations: A Forest Sector Greenhouse Gas Emissions Case Study
Authors: Buchholz Thomas , Gunn John S. , Sharma Benktesh
Published: May 2021

Increasing demand for woody biomass-derived electricity in the UK and elsewhere has resulted in a rapidly expanding wood pellet manufacturing industry in the southern US. Since this demand is driven by climate concerns and an objective to lower greenhouse gas (GHG) emissions from the electricity sector, it is crucial to understand the full carbon consequences of wood pellet sourcing, processing, and utilization. We performed a comparative carbon life cycle assessment (LCA) for pellets sourced from three mills in the southern US destined for electricity generation in the UK. The baseline assumptions included GHG emissions of the UK’s 2018 and 2025 target electricity grid mix and feedstock supplied primarily from non-industrial private forest (NIPF) pine plantations augmented with a fraction of sawmill residues. Based on regional expert input, we concluded that forest management practices on the NIPF pine plantations would include timely thinning harvest treatments in the presence of pellet demand. The LCA analysis included landscape carbon stock changes based on USDA Forest Service Forest Vegetation Simulator using current USDA Forest Service Forest Inventory and Analysis data as the starting condition of supply areas in Arkansas, Louisiana and Mississippi. We found that GHG emission parity (i.e., the time when accumulated carbon GHG emissions for the bioenergy scenario equal the baseline scenario) is more than 40 years for pellets produced at each individual pellet mill and for all three pellet mills combined when compared to either the UK’s 2018 electricity grid mix or the UK’s targeted electricity grid mix in 2025. The urgency to mitigate climate change with near-term actions as well as increasing uncertainty with longer-term simulations dictated a focus on the next four decades in the analysis. Even at 50% sawmill residues, GHG emission parity was not reached during the 40 years modeled. Results are most likely conservative since we assume a high share of sawmill residues (ranging from 20 to 50%) and did not include limited hardwood feedstocks as reported in the supply chain which are generally associated with delayed GHG emission parity because of lower growth rates.
Polygenic Risk for Insomnia in Adolescents of Diverse Ancestry
Authors: Ma Tengfei , Chen Honglei , Lu Qing , Tong Xiaoran
Published: May 2021

Background: Insomnia is a common mental disorder, affecting nearly one fifth of the pre-adult population in the United States. The recent, largest genome-wide association study (GWAS) conducted on the United Kingdom Biobank cohort identified hundreds of significant single-nucleotide polymorphism (SNP), allowing the epidemiologists to quantify individual genetic predisposition in the subsequent studies via the polygenic risk scoring technique. The nucleotide polymorphisms and risk scoring, while being able to generalize to other adult populations of European origin, are not yet tested on pediatric and adolescent populations of diverse racial-ethnic backgrounds, and our study intends to fill these gaps.

Materials and Methods: We took the summary of the same United Kingdom Biobank study and conducted a polygenic risk score (PRS) analysis on a multi-ethnicity, pre-adult population provided by the Adolescent Brain Cognitive Development (ABCD) Study.

Results: The PRSs according to the significant nucleotide polymorphisms found in white British adults is a strong predictor of insomnia in children of similar European background but lacks power in non-European groups.

Conclusions: Through polygenic risk scoring, the knowledge of insomnia genetics summarized from a white adult study population is transferable to a younger age group, which aids the search of actionable targets of early insomnia prevention. Yet population stratification may prevent the easy generalization across ethnic lines; therefore, it is necessary to conduct group specific studies to aid people of non-European genetic background.
Gene Environment Interactions in the Etiology of Neural Tube Defects
Authors: Finnell Richard H. , Caiaffa Carlo Donato , Kim Sung-Eun , Lei Yunping , Steele John , Cao Xuanye , Tukeman Gabriel , Lin Ying Linda , Cabrera Robert M. , Wlodarczyk Bogdan J.
Published: May 2021

Human structural congenital malformations are the leading cause of infant mortality in the United States. Estimates from the United States Center for Disease Control and Prevention (CDC) determine that close to 3% of all United States newborns present with birth defects; the worldwide estimate approaches 6% of infants presenting with congenital anomalies. The scientific community has recognized for decades that the majority of birth defects have undetermined etiologies, although we propose that environmental agents interacting with inherited susceptibility genes are the major contributing factors. Neural tube defects (NTDs) are among the most prevalent human birth defects and as such, these malformations will be the primary focus of this review. NTDs result from failures in embryonic central nervous system development and are classified by their anatomical locations. Defects in the posterior portion of the neural tube are referred to as meningomyeloceles (spina bifida), while the more anterior defects are differentiated as anencephaly, encephalocele, or iniencephaly. Craniorachischisis involves a failure of the neural folds to elevate and thus disrupt the entire length of the neural tube. Worldwide NTDs have a prevalence of approximately 18.6 per 10,000 live births. It is widely believed that genetic factors are responsible for some 70% of NTDs, while the intrauterine environment tips the balance toward neurulation failure in at risk individuals. Despite aggressive educational campaigns to inform the public about folic acid supplementation and the benefits of providing mandatory folic acid food fortification in the United States, NTDs still affect up to 2,300 United States births annually and some 166,000 spina bifida patients currently live in the United States, more than half of whom are now adults. Within the context of this review, we will consider the role of maternal nutritional status (deficiency states involving B vitamins and one carbon analytes) and the potential modifiers of NTD risk beyond folic acid. There are several well-established human teratogens that contribute to the population burden of NTDs, including: industrial waste and pollutants [e.g., arsenic, pesticides, and polycyclic aromatic hydrocarbons (PAHs)], pharmaceuticals (e.g., anti-epileptic medications), and maternal hyperthermia during the first trimester. Animal models for these teratogens are described with attention focused on valproic acid (VPA; Depakote). Genetic interrogation of model systems involving VPA will be used as a model approach to discerning susceptibility factors that define the gene-environment interactions contributing to the etiology of NTDs.
Comparative Analysis of the Circular Transcriptome in Muscle, Liver, and Testis in Three Livestock Species
Authors: Robic Annie , Cerutti Chloé , Kühn Christa , Faraut Thomas
Published: May 2021

Circular RNAs have been observed in a large number of species and tissues and are now recognized as a clear component of the transcriptome. Our study takes advantage of functional datasets produced within the FAANG consortium to investigate the pervasiveness of circular RNA transcription in farm animals. We describe here the circular transcriptional landscape in pig, sheep and bovine testicular, muscular and liver tissues using total 66 RNA-seq datasets. After an exhaustive detection of circular RNAs, we propose an annotation of exonic, intronic and sub-exonic circRNAs and comparative analyses of circRNA content to evaluate the variability between individuals, tissues and species. Despite technical bias due to the various origins of the datasets, we were able to characterize some features (i) (ruminant) liver contains more exonic circRNAs than muscle (ii) in testis, the number of exonic circRNAs seems associated with the sexual maturity of the animal. (iii) a particular class of circRNAs, sub-exonic circRNAs, are produced by a large variety of multi-exonic genes (protein-coding genes, long non-coding RNAs and pseudogenes) and mono-exonic genes (protein-coding genes from mitochondrial genome and small non-coding genes). Moreover, for multi-exonic genes there seems to be a relationship between the sub-exonic circRNAs transcription level and the linear transcription level. Finally, sub-exonic circRNAs produced by mono-exonic genes (mitochondrial protein-coding genes, ribozyme, and sno) exhibit a particular behavior. Caution has to be taken regarding the interpretation of the unannotated circRNA proportion in a given tissue/species: clusters of circRNAs without annotation were characterized in genomic regions with annotation and/or assembly problems of the respective animal genomes. This study highlights the importance of improving genome annotation to better consider candidate circRNAs and to better understand the circular transcriptome. Furthermore, it emphasizes the need for considering the relative “weight” of circRNAs/parent genes for comparative analyses of several circular transcriptomes. Although there are points of agreement in the circular transcriptome of the same tissue in two species, it will be not possible to do without the characterization of it in both species.
Immunomodulatory and Mechanistic Considerations of Hibiscus sabdariffa (HS) in Dysfunctional Immune Responses: A Systematic Review
Authors: Umeoguaju Francis U. , Ephraim-Emmanuel Benson C. , Uba Joy O. , Bekibele Grace E. , Chigozie Nwondah , Orisakwe Orish Ebere
Published: May 2021

Hibiscus sabdariffa calyx (HS) water decoction extract is a commonly consumed beverage with various pharmacological properties. This systematic review examines the possible effect of HS intake on immune mediators. The Scopus and PUBMED databases were searched for all human and animal studies that investigated the effect of HS administration on immune related biomarkers. For each of the immune biomarkers, the mean, standard deviation and number of subjects were extracted for both the HS treated and untreated group. These values were used in the computation of standardized mean difference (SMD). Statistical analysis and forest plot were done with R statistical software (version 3.6.1). Twenty seven (27) studies met the eligibility criteria. Twenty two (22) of the studies were used for the meta-analysis which included a total of 1211 subjects. The meta-analysis showed that HS administration significantly lowered the levels of TNF-α (n=10; pooled SMD: -1.55; 95% CI: -2.43, -0.67; P < 0.01), IL-6 (n=11; pooled SMD:-1.09; 95% CI: -1.77, -0.40; P < 0.01), IL-1β (n=7; pooled SMD:-0.62; 95% CI: -1.25, 0.00; P = 0.05), Edema formation (n=4; pooled SMD: -2.29; 95% CI: -4.47, -0.11; P = 0.04), Monocyte Chemoattractant Protein -1 (n=4; pooled SMD: -1.17; 95% CI: -1.78, -0.57; P < 0.01) and Angiotensin converting enzyme cascade (n=6; pooled SMD: -0.91; 95% CI: -1.57, -0.25; P < 0.01). The levels of IL-10 (n=4; pooled SMD: -0.38; 95% CI: -1.67, 0.91; P = 0.56), Interleukin 8 (n=2; pooled SMD:-0.12; 95% CI: -0.76, 0.51; P = 0.71), iNOS (n=2; pooled SMD:-0.69; 95% CI: -1.60, 0.23 P = 0.14) and C- Reactive Protein (n=4; pooled SMD: 0.05; 95% CI: -0.26, 0.36; P = 0.75), were not significantly changed by HS administration. Some of the results had high statistical heterogeneity. HS may be promising in the management of disorders involving hyperactive immune system or chronic inflammation.
Marginal Zone B Cells Assist With Neutrophil Accumulation to Fight Against Systemic Staphylococcus aureus Infection
Authors: Lo Li-Wen , Chang Chia-Wei , Chiang Ming-Feng , Lin I-Ying , Lin Kuo-I
Published: May 2021

In addition to regulating immune responses by producing antibodies that confer humoral immunity, B cells can also affect these responses by producing cytokines. How B cells participate in the clearance of pathogenic infectionsviafunctions other than the production of pathogen-specific antibodies is still largely unknown. Marginal zone (MZ) B cells can quickly respond to bacterial invasion by providing the initial round of antibodies. After a bloodborne bacterial infection, neutrophils promptly migrate to the MZ. However, the mechanisms regulating neutrophil accumulation in the MZ during the initial phase of infection also remain obscure. Here, we found that MZ B cell-deficient mice are more susceptible to systemicStaphylococcus aureus(S. aureus) infection compared with wildtype mice. The expression levels of interleukin (IL)-6 and CXCL1/CXCL2 in MZ B cells increased significantly in mice at 3–4 h after infection withS. aureus, then decreased at 24 h post-infection. After systemicS. aureusinfection, splenic neutrophils express increased CXCR2 levels. Our results from confocal microscopy imaging of thick-section staining demonstrate that neutrophils in wildtype mice form cell clusters and are in close contact with MZ B cells at 3 h post-infection. This neutrophil cluster formation shortly after infection was diminished in both MZ B cell-deficient mice and IL-6-deficient mice. Blocking the action of CXCL1/CXCL2 by injecting anti-CXCL1 and anti-CXCL2 antibodies 1 h beforeS. aureusinfection significantly suppressed the recruitment of neutrophils to the MZ at 3 h post-infection. Compared with peptidoglycan stimulation alone, peptidoglycan stimulation with neutrophil co-culture further enhanced MZ B-cell activation and differentiation. Using a Förster resonance energy transfer by fluorescence lifetime imaging (FLIM-FRET) analysis, we observed evidence of a direct interaction between neutrophils and MZ B cells after peptidoglycan stimulation. Furthermore, neutrophil depletion in mice resulted in a reduced production ofS. aureus-specific immunoglobulin (Ig)M at 24 h post-infection. Together, our results demonstrate that MZ B cells regulate the rapid neutrophil swarming into the spleen during the early phase of systemicS. aureusinfection. Interaction with neutrophils assists MZ B cells with their differentiation into IgM-secreting cells and contributes to the clearance of systemic bacterial infections.
Host Transcriptome and Microbiota Signatures Prior to Immunization Profile Vaccine Humoral Responsiveness
Authors: Gonçalves Elena , Guillén Yolanda , Lama Javier R. , Sanchez Jorge , Brander Christian , Paredes Roger , Combadière Behazine
Published: May 2021

The identification of new biomarkers is essential to predict responsiveness to vaccines. We investigated the whole-blood transcriptome and microbiome prior to immunization, in order to assess their involvement in induction of humoral responses two months later. We based our analyses on stool and skin microbiota, and blood transcriptome prior to immunization, in a randomized clinical study in which participants were vaccinated with the MVA-HIV clade B vaccine (MVA-B). We found that the levels of neutralizing antibody responses were correlated with abundance of Eubacterium in stool and Prevotella in skin. In addition, genus diversity and bacterial species abundance were also correlated with the expression of genes involved in B cell development prior to immunization and forecast strong responders to MVA-B. To our knowledge, this is the first study integrating host blood gene expression and microbiota that might open an avenue of research in this field and to optimize vaccination strategies and predict responsiveness to vaccines.
Immunological Responses to Envenomation
Authors: Ryan Rachael Y. M. , Seymour Jamie , Loukas Alex , Lopez J. Alejandro , Ikonomopoulou Maria P. , Miles John J.
Published: May 2021

Venoms are complex mixtures of toxic compounds delivered by bite or sting. In humans, the consequences of envenomation range from self-limiting to lethal. Critical host defence against envenomation comprises innate and adaptive immune strategies targeted towards venom detection, neutralisation, detoxification, and symptom resolution. In some instances, venoms mediate immune dysregulation that contributes to symptom severity. This review details the involvement of immune cell subtypes and mediators, particularly of the dermis, in host resistance and venom-induced immunopathology. We further discuss established venom-associated immunopathology, including allergy and systemic inflammation, and investigate Irukandji syndrome as a potential systemic inflammatory response. Finally, this review characterises venom-derived compounds as a source of immune modulating drugs for treatment of disease.
Effect of Epstein-Barr Virus DNA on the Incidence and Severity of Arthritis in a Rheumatoid Arthritis Mouse Model
Authors: Fadlallah Sukayna , Hussein Hadi , Jallad Mary-Ann , Shehab Marwa , Jurjus Abdo R. , Matar Ghassan M. , Rahal Elias A.
Published: May 2021

Objective

We recently demonstrated that EBV DNA is correlated with proinflammatory responses in mice and in rheumatoid arthritis (RA) patients; hence, we utilized an RA mouse model to examine whether EBV DNA enhances the risk and severity of arthritis and to assess its immunomodulatory effects.

Methods

C57BL/6J mice were treated with collagen (arthritis-inducing agent), EBV DNA 6 days before collagen, EBV DNA 15 days after collagen, Staphylococcus epidermidis DNA 6 days before collagen, EBV DNA alone, or water. Mice were then monitored for clinical signs and affected joints/footpads were histologically analysed. The relative concentration of IgG anti- chicken collagen antibodies and serum cytokine levels of IL-17A and IFNϒ were determined by ELISA. The number of cells co-expressing IL-17A and IFNϒ in joint histological sections was determined by immunofluorescence.

Results

The incidence of arthritis was significantly higher in mice that received EBV DNA prior to collagen compared to mice that only received collagen. Similarly, increased clinical scores, histological scores and paw thicknesses with a decreased gripping strength were observed in groups treated with EBV DNA and collagen. The relative concentration of IgG anti-chicken collagen antibodies was significantly increased in the group that received EBV DNA 6 days prior to collagen in comparison to the collagen receiving group. On the other hand, the highest number of cells co-expressing IFNϒ and IL-17A was observed in joints from mice that received both collagen and EBV DNA.

Conclusion

EBV DNA increases the incidence and severity of arthritis in a RA mouse model. Targeting mediators triggered by viral DNA may hence be a potential therapeutic avenue.
SARS-CoV-2 Infection and Guillain-Barré Syndrome: A Review on Potential Pathogenic Mechanisms
Authors: Shoraka Shahrzad , Ferreira Maria Lucia Brito , Mohebbi Seyed Reza , Ghaemi Amir
Published: May 2021

Since December 2019, the world has been facing an outbreak of a new disease called coronavirus disease 2019 (COVID-19). The COVID-19 pandemic is caused by a novel beta-coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 infection mainly affects the respiratory system. Recently, there have been some reports of extra-respiratory symptoms such as neurological manifestations in COVID-19. According to the increasing reports of Guillain-Barré syndrome following COVID-19, we mainly focused on SARS-CoV-2 infection and Guillain-Barré syndrome in this review. We tried to explain the possibility of a relationship between SARS-CoV-2 infection and Guillain-Barré syndrome and potential pathogenic mechanisms based on current and past knowledge.
The Role of Macrophages in the Pathogenesis of SARS-CoV-2-Associated Acute Respiratory Distress Syndrome
Authors: Kosyreva Anna , Dzhalilova Dzhuliia , Lokhonina Anastasia , Vishnyakova Polina , Fatkhudinov Timur
Published: May 2021

Macrophages are cells that mediate both innate and adaptive immunity reactions, playing a major role in both physiological and pathological processes. Systemic SARS-CoV-2-associated complications include acute respiratory distress syndrome (ARDS), disseminated intravascular coagulation syndrome, edema, and pneumonia. These are predominantly effects of massive macrophage activation that collectively can be defined as macrophage activation syndrome. In this review we focus on the role of macrophages in COVID-19, as pathogenesis of the new coronavirus infection, especially in cases complicated by ARDS, largely depends on macrophage phenotypes and functionalities. We describe participation of monocytes, monocyte-derived and resident lung macrophages in SARS-CoV-2-associated ARDS and discuss possible utility of cell therapies for its treatment, notably the use of reprogrammed macrophages with stable pro- or anti-inflammatory phenotypes.
Born With Bristles: New Insights on the Kölliker’s Organs of Octopus Skin
Authors: Villanueva Roger , Coll-Lladó Montserrat , Bonnaud-Ponticelli Laure , Carrasco Sergio A. , Escolar Oscar , Fernández-Álvarez Fernando Á. , Gleadall Ian G. , Nabhitabhata Jaruwat , Ortiz Nicolás , Rosas Carlos , Sánchez Pilar , Voight Janet R. , Swoger Jim
Published: May 2021

The entire skin surface of octopus embryos, hatchlings and juveniles bears scattered tufts of tiny chitinous setae within small pockets, from which they can be everted and retracted. Known as Kölliker’s organs (KO), they disappear before the subadult stage. The function of these structures during the early life of the octopus is unknown, despite having been first described nearly two centuries ago. To investigate these organs further, general trends in size of KO distribution and density were analyzed in hatchlings and juveniles of 17 octopod species from all oceans, representing holobenthic, holopelagic and meropelagic modes of life. The size of the KO is fairly constant across species, unrelated to mode of life or hatchling size. The density of KO is similar on ventral and dorsal body surfaces, but hatchlings of smaller size tend to have a higher density of KO on the aboral surface of the arms. Analysis of a series of post-hatchingOctopus vulgarisshows KO size to be constant throughout ontogeny; it is therefore a consistent structure during the octopus early life from planktonic hatchling to benthic juvenile. New KO are generated on the skin of the arm tips during the planktonic period and initial benthic lives of juveniles. Their density, on both the mantle and arms, gradually decreases as the octopus grows. In older benthic juveniles, the KO degrades, losing its setae and the base of its follicle becomes exposed as a nearly circular stump of muscle. It is estimated that fully everted KO increase the body surface area by around two-thirds compared to when the KO are retracted. This modular mechanism of body surface extension and roughness probably influences flow-related forces such as drag and propulsion of the moving surface of the young octopus while it is of small size with a relatively large surface area. In addition, the distribution of these organs on the aboral surface of the arms of the octopus and their birefringent properties suggest a role in camouflage. Further research is needed to test these hypotheses of KO function in live animals.
Understanding Persistent Non-compliance in a Remote, Large-Scale Marine Protected Area
Authors: Collins Claire , Nuno Ana , Broderick Annette , Curnick David J. , de Vos Asha , Franklin Thomas , Jacoby David M. P. , Mees Chris , Moir-Clark James , Pearce John , Letessier Tom B.
Published: May 2021

Area coverage of large-scale marine protected areas (MPAs) (LSMPAs, > 100,000 km2) is rapidly increasing globally. Their effectiveness largely depends on successful detection and management of non-compliance. However, for LSMPAs this can be difficult due to their large size, often remote locations and a lack of understanding of the social drivers of non-compliance. Taking a case-study approach, we review current knowledge of illegal fishing within the British Indian Ocean Territory (BIOT) LSMPA. Data stemming from enforcement reports (2010–20), and from fieldwork in fishing communities (2018–19) were combined to explore and characterise drivers of non-compliance. Enforcement data included vessel investigation reports (n = 188), transcripts of arrests (20) and catch seizures (58). Fieldwork data included fisher interviews (95) and focus groups (12), conducted in two communities in Sri Lanka previously associated with non-compliance in BIOT LSMPA. From 2010 to 2020, there were 126 vessels suspected of non-compliance, 76% of which were Sri Lankan. The majority of non-compliant vessels targeted sharks (97%), catching an estimated 14,340 individuals during the study period. Sri Lankan vessels were primarily registered to one district (77%) and 85% operated from just two ports within the fieldwork sites. Social Network Analysis (SNA) showed that 66% of non-compliant vessels were linked by social ties, including sharing crew members, compared with only 34% of compliant vessels. Thematic analysis of qualitative data suggested that perceptions of higher populations of sharks and social ties between vessels may both be important drivers. We discuss our findings within a global context to identify potential solutions for LSMPA management.
Coral Reef Restorations Can Be Optimized to Reduce Coastal Flooding Hazards
Authors: Roelvink Floortje E. , Storlazzi Curt D. , van Dongeren Ap R. , Pearson Stuart G.
Published: May 2021

Coral reefs are effective natural coastal flood barriers that protect adjacent communities. Coral degradation compromises the coastal protection value of reefs while also reducing their other ecosystem services, making them a target for restoration. Here we provide a physics-based evaluation of how coral restoration can reduce coastal flooding for various types of reefs. Wave-driven flooding reduction is greatest for broader, shallower restorations on the upper fore reef and between the middle of the reef flat and the shoreline than for deeper locations on the fore reef or at the reef crest. These results indicate that to increase the coastal hazard risk reduction potential of reef restoration, more physically robust species of coral need to be outplanted to shallower, more energetic locations than more fragile, faster-growing species primarily being grown in coral nurseries. The optimization and quantification of coral reef restoration efforts to reduce coastal flooding may open hazard risk reduction funding for conservation purposes.
Design and Performance Test of a Magnetic Rate Controlled Stage Damper
Authors: Yu Guo-Jun , Zhu Shao-Jie , Du Cheng-Bin , Wang Ling-Yun , Huang Jun-Chi
Published: May 2021

In order to control the vibration of civil building structures, a magnetic rate-controlled stage damper (MRCSD) is designed based on a magnetorheological shear thickening fluid (MR-STF). The key technology and performance test of the damper and the parameter identification of the mechanical model are studied. The experimental results show that the main cylinder filled with MR-STF combines the magnetorheological (MR) effect and the shear thickening effect, which has a strong impact on energy dissipation and vibration reduction. Therefore, the designed damper is superior to the traditional viscous damper. With the increase of magnetic field strength, the shear thickening effect of the MR fluid is inhibited and the MR effect is more obvious. The MRCSD can improve the performance of vibration isolation and vibration reduction by controlling damping. Under a different intensity of earthquake, the maximum output can reach 250.2 kN; the mechanical model of the MRCSD is established; and the design parameters of the damper are determined. The theoretical results obtained from the mechanical model of the MRCSD are consistent with the experimental results, which show that the parameter identification method is feasible and effective.
Risk of Systemic Lupus Erythematosus in Patients With Anti-phospholipid Syndrome: A Population-Based Study
Authors: Chen Hsin-Hua , Lin Ching-Heng , Chao Wen-Cheng
Published: May 2021

Objective: To investigate the association between anti-phospholipid syndrome (APS) and the risk of newly diagnosed systemic lupus erythematosus (SLE).

Methods: We used 2003–2013 data derived from Taiwan's National Health Insurance Research Database to conduct this nationwide, population-based. We identified AS patients newly diagnosed between 2005 to 2013 as the study group and applied age-sex matched (1:20) and propensity score-matched (PSM) (1:2) non-SLE individuals as controls. The association between APS and risk of incident SLE was determined by calculating hazard ratios (HRs) with 95% confidence intervals (CIs) using Cox proportional hazard regression analysis.

Results: We identified 1,245 patients with APS as well as 24,900 age- and sex-matched non-APS controls and 727 APS patients as well as 1,454 PSM non-APS controls. We found that the risk for incident SLE in the APS group was 80.70 times higher than the non-APS group, and the association remained robust after PSM (HR, 28.55; 95% CI, 11.49–70.91). The increased risk for SLE in patients with APS mainly existed within 5 years after the diagnosis of APS. The sensitivity analyses found that the risk for SLE in patients with APS was consistent excluding patients with ITP/AIHA and using distinct definitions of SLE.

Conclusion: The present population-based study revealed a robust association between SLE risk and recent APS and highlights the need for vigilance of SLE-associated symptoms in patients who had been diagnosed with APS.
Short-Term Outcomes and Predictors of Effectiveness of Tocilizumab in Systemic Juvenile Idiopathic Arthritis: A Prospective Cohort Study
Authors: Nada Doaa W. , Moghazy Abdelkawy , Allam Abdallah El-Sayed , Alunno Alessia , Ibrahim Amira M.
Published: May 2021

Background: Systemic Juvenile Idiopathic Arthritis (sJIA) is a unique category of juvenile arthritis in which interleukin 6 plays a major pathogenic role. This study aimed to describe the therapeutic short-term outcomes among patients with sJIA starting tocilizumab (TCZ) therapy and to identify possible predictors of treatment response.

Methods: We conducted a prospective observational study including 65 patients with sJIA meeting ILAR classification criteria with active disease despite conventional therapy that were treated by TCZ between August 2019 and October 2020 as the first-line biological therapy. Clinical and serological parameters were recorded at baseline and after 1 year of TCZ therapy.

Results: After 1 year, 25% of the patients achieved minimal disease activity and 35% achieved clinically inactive disease. A significant reduction of the 10-joint juvenile arthritis disease activity score and acute phase reactants was also observed. Patients with younger age (≤7 years), shorter disease duration (≤3 years), lower disease activity, and higher serum ferritin and systemic manifestations showed more favorable results.

Conclusion: Patients with sJIA showed favorable disease outcomes with TCZ treatment for 1 year, especially if the drugs were administered earlier in the disease course and in younger patients with a more pronounced inflammatory status. Our results may help to define the profile of patients with sJIA who are more likely to benefit from IL-6 blockade.
Biomarkers in Progressive Fibrosing Interstitial Lung Disease: Optimizing Diagnosis, Prognosis, and Treatment Response
Authors: Bowman Willis S. , Echt Gabrielle A. , Oldham Justin M.
Published: May 2021

Interstitial lung disease (ILD) comprises a heterogenous group of diffuse lung disorders that commonly result in irreversible pulmonary fibrosis. While idiopathic pulmonary fibrosis (IPF) is the prototypical progressive fibrosing ILD (PF-ILD), a high proportion of patients with other ILD subtypes develop a PF-ILD phenotype. Evidence exists for shared pathobiology leading to progressive fibrosis, suggesting that biomarkers of disease activity may prove informative across the wide spectrum of ILDs. Biomarker investigation to date has identified a number of molecular markers that predict relevant ILD endpoints, including disease presence, prognosis, and/or treatment response. In this review, we provide an overview of potentially informative biomarkers in patients with ILD, including those suggestive of a PF-ILD phenotype. We highlight the recent genomic, transcriptomic, and proteomic investigations that identified these biomarkers and discuss the body compartments in which they are found, including the peripheral blood, airway, and lung parenchyma. Finally, we identify critical gaps in knowledge within the field of ILD biomarker research and propose steps to advance the field toward biomarker implementation.
Bioleaching and Electrochemical Behavior of Chalcopyrite by a Mixed Culture at Low Temperature
Authors: Peng Tangjian , Liao Wanqing , Wang Jingshu , Miao Jie , Peng Yuping , Gu Guohua , Wu Xueling , Qiu Guanzhou , Zeng Weimin
Published: May 2021

Low-temperature biohydrometallurgy is implicated in metal recovery in alpine mining areas, but bioleaching using microbial consortia at temperatures <10°C was scarcely discussed. To this end, a mixed culture was used for chalcopyrite bioleaching at 6°C. The mixed culture resulted in a higher copper leaching rate than the pure culture of Acidithiobacillus ferrivorans strain YL15. High-throughput sequencing technology showed that Acidithiobacillus spp. and Sulfobacillus spp. were the mixed culture’s major lineages. Cyclic voltammograms, potentiodynamic polarization and electrochemical impedance spectroscopy unveiled that the mixed culture enhanced the dissolution reactions, decreased the corrosion potential and increased the corrosion current, and lowered the charge transfer resistance and passivation layer impedance of the chalcopyrite electrode compared with the pure culture. This study revealed the mechanisms via which the mixed culture promoted the chalcopyrite bioleaching.
Molecular Mechanics Study of Flow and Surface Influence in Ligand–Protein Association
Authors: Kaushik Shivansh , Chang Chia-en A.
Published: May 2021

Ligand–protein association is the first and critical step for many biological and chemical processes. This study investigated the molecular association processes under different environments. In biology, cells have different compartments where ligand–protein binding may occur on a membrane. In experiments involving ligand–protein binding, such as the surface plasmon resonance and continuous flow biosynthesis, a substrate flow and surface are required in experimental settings. As compared with a simple binding condition, which includes only the ligand, protein, and solvent, the association rate and processes may be affected by additional ligand transporting forces and other intermolecular interactions between the ligand and environmental objects. We evaluated these environmental factors by using a ligand xk263 binding to HIV protease (HIVp) with atomistic details. Using Brownian dynamics simulations, we modeled xk263 and HIVp association time and probability when a system has xk263 diffusion flux and a non-polar self-assembled monolayer surface. We also examined different protein orientations and accessible surfaces for xk263. To allow xk263 to access to the dimer interface of immobilized HIVp, we simulated the system by placing the protein 20Å above the surface because immobilizing HIVp on a surface prevented xk263 from contacting with the interface. The non-specific interactions increased the binding probability while the association time remained unchanged. When the xk263 diffusion flux increased, the effective xk263 concentration around HIVp, xk263–HIVp association time and binding probability decreased non-linearly regardless of interacting with the self-assembled monolayer surface or not. The work sheds light on the effects of the solvent flow and surface environment on ligand–protein associations and provides a perspective on experimental design.
Tracing Evolution Through Protein Structures: Nature Captured in a Few Thousand Folds
Authors: Bordin Nicola , Sillitoe Ian , Lees Jonathan G. , Orengo Christine
Published: May 2021

This article is dedicated to the memory of Cyrus Chothia, who was a leading light in the world of protein structure evolution. His elegant analyses of protein families and their mechanisms of structural and functional evolution provided important evolutionary and biological insights and firmly established the value of structural perspectives. He was a mentor and supervisor to many other leading scientists who continued his quest to characterise structure and function space. He was also a generous and supportive colleague to those applying different approaches. In this article we review some of his accomplishments and the history of protein structure classifications, particularly SCOP and CATH. We also highlight some of the evolutionary insights these two classifications have brought. Finally, we discuss how the expansion and integration of protein sequence data into these structural families helps reveal the dark matter of function space and can inform the emergence of novel functions in Metazoa. Since we cover 25 years of structural classification, it has not been feasible to review all structure based evolutionary studies and hence we focus mainly on those undertaken by the SCOP and CATH groups and their collaborators.
Brain SPECT as a Biomarker of Neurodegeneration in Dementia in the Era of Molecular Imaging: Still a Valid Option?
Authors: Ferrando Rodolfo , Damian Andres
Published: May 2021

Biomarkers are playing a progressively leading role in both clinical practice and scientific research in dementia. Although amyloid and tau biomarkers have gained ground in the clinical community in recent years, neurodegeneration biomarkers continue to play a key role due to their ability to identify different patterns of brain involvement that sign the transition between asymptomatic and symptomatic stages of the disease with high sensitivity and specificity. Both 18F-FDG positron emission tomography (PET) and perfusion single photon emission computed tomography (SPECT) have proved useful to reveal the functional alterations underlying various neurodegenerative diseases. Although the focus of nuclear neuroimaging has shifted to PET, the lower cost and wider availability of SPECT make it a still valid alternative for the study of patients with dementia. This review discusses the principles of both techniques, compares their diagnostic performance for the diagnosis of neurodegenerative diseases and highlights the role of SPECT to characterize patients from low- and middle-income countries, where special care of additional costs is particularly needed to meet the new recommendations for the diagnosis and characterization of patients with dementia.
Validation of Affect-tag Affective and Cognitive Indicators
Authors: Sparrow Laurent , Six Hugo , Varona Lauren , Janin Olivier
Published: May 2021

The Affect-tag solution measures physiological signals to deliver indicators derived from cognitive science. To provide the most accurate and effective results, a database of electrodermal activity (EDA) signals acquired using the Affect-tag A1 band was created. An experimental paradigm was designed to measure action-taking, autonomic regulation, cognitive load (CL), emotions, and stress, affects, and social stress. The Affect-tag emotional power (EP), emotional density (ED), and CL affective and cognitive indicators were refined based on the physiological responses of 48 participants during these tasks. Statistical significance was obtained for all indicators in tasks they were designed to measure, resulting in a total accuracy score of 89% for the combined indicators. Data obtained during this study will be further analyzed to define emotional and affective states.
Factors Affecting Gut Microbiome in Daily Diet
Authors: Su Qi , Liu Qin
Published: May 2021

There is a growing recognition that a good diet can help people maintain mental and physical health, while a bad one will cause the disorder of body function, and even lead to several diseases. A lot of attentions have been devoted to analyze every possible health-related factor in the daily diet, including food ingredients, additives, and cooking process. With the support of high-throughput sequencing technology, there is accumulating evidence gradually clarifying that most of these factors are mainly through the interactions with gut microbiome to trigger downstream effects. The gut microbiome may be able to act as a very sensitive mirror in response to human daily diet. A complex network of interactions among diet, gut microbiome, and health has been gradually depicted, but it is rarely discussed from a more comprehensive perspective. To this end, this review summarized the latest updates in diet-gut microbiome interactions, analyzed most identified factors involved in this process, showed the possibility of maintaining health or alleviating diseases by diet intervention, aiming to help people choose a suitable recipe more accurately.
Sex-Specific Metabolic Impairments in a Mouse Model of Disrupted Selenium Utilization
Authors: Kremer Penny M. , Torres Daniel J. , Hashimoto Ann C. , Berry Marla J.
Published: May 2021

The essential micronutrient selenium (Se) provides antioxidant defense and supports numerous biological functions. Obtained through dietary intake, Se is incorporated into selenoproteins via the amino acid, selenocysteine (Sec). Mice with genetic deletion of the Se carrier, selenoprotein P (SELENOP), and the Se recycling enzyme selenocysteine lyase (SCLY), suffer from sexually dimorphic neurological deficits and require Se supplementation for viability. These impairments are more pronounced in males and are exacerbated by dietary Se restriction. We report here that, by 10 weeks of age, female Selenop/Scly double knockout (DKO) mice supplemented with 1 mg/ml sodium selenite in drinking water develop signs of hyper-adiposity not seen in male DKO mice. Unexpectedly, this metabolic phenotype can be reversed by removing Se from the drinking water at post-natal day 22, just prior to puberty. Restricting access to Se at this age prevents excess body weight gain and restriction from either post-natal day 22 or 37 reduces gonadal fat deposits. These results provide new insight into the sex-dependent relationship between Se and metabolic homeostasis.
Case Report: Long-Term Survival of a Pediatric Patient With an Intra-Abdominal Undifferentiated Carcinoma of Unknown Primary
Authors: Stirnweiss Anja , Dholaria Hetal , Oommen Joyce , Hardy Kathy , Jevon Gareth , Beesley Alex H. , Kotecha Rishi S.
Published: May 2021

An 8-year and 10-month-old boy presented following 2 weeks of abdominal pain, vomiting, constipation, and rectal pain. A diffuse lower-abdominal mass was felt upon palpation, with radiological findings confirming the presence of a large, multilobulated intraperitoneal mass with mesenteric lymphadenopathy and hepatic metastatic disease. A biopsy of the mass revealed anatomical pathological findings consistent with a diagnosis of intra-abdominal undifferentiated carcinoma of unknown primary (CUP). The patient was treated with six cycles of carboplatin and gemcitabine prior to surgery. Following incomplete resection of the tumor, four further cycles were administered resulting in resolution of the pelvic mass, but progression in the right and left lobes of the liver. Therapy was accordingly adjusted, with administration of six cycles of ifosfamide and doxorubicin followed by 1 year of metronomic vinorelbine and cyclophosphamide maintenance therapy. The patient remains in remission 7 years from completion of therapy. Whole exome sequencing revealed missense mutations in the DNA-repair and chromatin-remodeling genes FANCM and SMARCD2, and a tumor-derived cell line revealed a complex karyotype suggesting chromosomal instability. CUP is an extremely rare diagnosis in the pediatric population, previously reported during adolescence. This report provides detailed characterization of CUP in a young child and in the absence of defined therapeutic guidelines for pediatric CUP, the successful treatment strategy described should be considered for similar cases.
Analysis of Autophagy-Related Signatures Identified Two Distinct Subtypes for Evaluating the Tumor Immune Microenvironment and Predicting Prognosis in Ovarian Cancer
Authors: Chen Xingyu , Lan Hua , He Dong , Wang Zhanwang , Xu Runshi , Yuan Jing , Xiao Mengqing , Zhang Yao , Gong Lian , Xiao Songshu , Cao Ke
Published: May 2021

Ovarian cancer (OC) is one of the most lethal gynecologic malignant tumors. The interaction between autophagy and the tumor immune microenvironment has clinical importance. Hence, it is necessary to explore reliable biomarkers associated with autophagy-related genes (ARGs) for risk stratification in OC. Here, we obtained ARGs from the MSigDB database and downloaded the expression profile of OC from TCGA database. The k-means unsupervised clustering method was used for clustering, and two subclasses of OC (cluster A and cluster B) were identified. SsGSEA method was used to quantify the levels of infiltration of 24 subtypes of immune cells. Metascape and GSEA were performed to reveal the differential gene enrichment in signaling pathways and cellular processes of the subtypes. We found that patients in cluster A were significantly associated with higher immune infiltration and immune-associated signaling pathways. Then, we established a risk model by LASSO Cox regression. ROC analysis and Kaplan-Meier analysis were applied for evaluating the efficiency of the risk signature, patients with low-risk got better outcomes than those with high-risk in overall survival. Finally, ULK2 and GABARAPL1 expression was further validated in clinical samples. In conclusion, Our study constructed an autophagy-related prognostic indicator, and identified two promising targets in OC.
MRI-Based Radiomics Models for Predicting Risk Classification of Gastrointestinal Stromal Tumors
Authors: Mao Haijia , Zhang Bingqian , Zou Mingyue , Huang Yanan , Yang Liming , Wang Cheng , Pang PeiPei , Zhao Zhenhua
Published: May 2021

Background

We conduct a study in developing and validating four MRI-based radiomics models to preoperatively predict the risk classification of gastrointestinal stromal tumors (GISTs).

Methods

Forty-one patients (low-risk = 17, intermediate-risk = 13, high-risk = 11) underwent MRI before surgery between September 2013 and March 2019 in this retrospective study. The Kruskal–Wallis test with Bonferonni correction and variance threshold was used to select appropriate features, and the Random Forest model (three classification model) was used to select features among the high-risk, intermediate-risk, and low-risk of GISTs. The predictive performance of the models built by the Random Forest was estimated by a 5-fold cross validation (5FCV). Their performance was estimated using the receiver operating characteristic (ROC) curve, summarized as the area under the ROC curve (AUC). Area under the curve (AUC), accuracy, sensitivity, and specificity for risk classification were reported. Linear discriminant analysis (LDA) was used to assess the discriminative ability of these radiomics models.

Results

The high-risk, intermediate-risk, and low-risk of GISTs were well classified by radiomics models, the micro-average of ROC curves was 0.85, 0.81, 0.87 and 0.94 for T1WI, T2WI, ADC and combined three MR sequences. And ROC curves achieved excellent AUCs for T1WI (0.85, 0.75 and 0.82), T2WI (0.69, 0.78 and 0.78), ADC (0.85, 0.77 and 0.80) and combined three MR sequences (0.96, 0.92, 0.81) for the diagnosis of high-risk, intermediate-risk, and low-risk of GISTs, respectively. In addition, LDA demonstrated the different risk of GISTs were correctly classified by radiomics analysis (61.0% for T1WI, 70.7% for T2WI, 83.3% for ADC, and 78.9% for the combined three MR sequences).

Conclusions

Radiomics models based on a single sequence and combined three MR sequences can be a noninvasive method to evaluate the risk classification of GISTs, which may help the treatment of GISTs patients in the future.