Miracle-dz/UniFAR-FTUs huggingface dataset:
Energy balance climate models and the economics of climate change

Spatial energy balance models are used by climate scientists to help understand climate dynamics and to assist in construction of more complex general circulation models. In this paper we present the first, to our knowledge, coupled spatial energy balance and economic growth model. This leads to new insights regarding: (i) The contentious issue of whether a gradualist approach to mitigation, is preferable to an initially more aggressive approach, (ii) The effect of polar ice melting on optimal policy, (iii) Robustness of optimal climate policy to spatial damage uncertainty, and (iv) Economic justice considerations raised by variation in latitude specific damages. (JEL D62, Q54 )
Epigenetic signatures of methylated DNA cytosine in Alzheimer’s disease

The discovery of AD epigenetic signatures lays a molecular basis for new methods to detect early AD using patient blood cells. Alzheimer’s disease (AD), a progressive neurodegenerative disorder, is the most common untreatable form of dementia. Identifying molecular biomarkers that allow early detection remains a key challenge in the diagnosis, treatment, and prognostic evaluation of the disease. Here, we report a novel experimental and analytical model characterizing epigenetic alterations during AD onset and progression. We generated the first integrated base-resolution genome-wide maps of the distribution of 5-methyl-cytosine (5mC), 5-hydroxymethyl-cytosine (5hmC), and 5-formyl/carboxy-cytosine (5fC/caC) in normal and AD neurons. We identified 27 AD region–specific and 39 CpG site–specific epigenetic signatures that were independently validated across our familial and sporadic AD models, and in an independent clinical cohort. Thus, our work establishes a new model and strategy to study the epigenetic alterations underlying AD onset and progression and provides a set of highly reliable AD-specific epigenetic signatures that may have early diagnostic and prognostic implications.
Synchronous Germinal Center Onset Impacts the Efficiency of Antibody Responses

The germinal center reaction is an important target for modulating antibody responses. Antibody production from germinal centers is regulated by a negative feedback mechanism termed antibody feedback. By imposing antibody feedback, germinal centers can interact and regulate the output of other germinal centers. Using an agent-based model of the germinal center reaction, we studied the impact of antibody feedback on kinetics and efficiency of a germinal center. Our simulations predict that high feedback of antibodies from germinal centers reduces the production of plasma cells and subsequently the efficiency of the germinal center reaction by promoting earlier termination. Affinity maturation is only weakly improved by increased antibody feedback and ultimately interrupted because of premature termination of the reaction. The model predicts that the asynchronous onset and changes in number of germinal centers could alter the efficiency of antibody response due to changes in feedback by soluble antibodies. Consequently, late initialized germinal centers have a compromised output due to higher antibody feedback from the germinal centers formed earlier. The results demonstrate potential effects of germinal center intercommunication and highlight the importance of understanding germinal center interactions for optimizing the antibody response, in particular, in the elderly and in the context of vaccination.
Hexane Fraction of Turbo brunneus Inhibits Intermediates of RANK-RANKL Signaling Pathway and Prevent Ovariectomy Induced Bone Loss

Osteoporosis is a “silent disease” characterized by fragile and impaired bone quality. Bone fracture results in increased mortality and poor quality of life in aged people particularly in postmenopausal women. Bone is maintained through the delicate balance between osteoclast-mediated bone resorption and osteoblast-mediated bone formation. The imbalance is caused most often by overly active osteoclasts due to estrogen deficiency. Natural products have long been used to prevent and treat osteoporosis since they have fewer side effects. The marine environment is a potential source of biologically and structurally novel biomolecules with promising biological activities but is less explored for the treatment of bone-related diseases. The present study aims to evaluate the antiosteoporotic effect of Hexane fraction of Turbo brunneus methanolic extract (HxTME) and to investigate its role in RANK-RANKL signaling pathway using in vitro osteoclasts cultures and in vivo ovariectomized (OVX) Swiss mice model. The present study demonstrated that the HxTME significantly inhibited RANKL induced osteoclast differentiation and maturation in vitro. HxTME completely downregulated the mRNA expression of key transcription factors such as NFATc1, c-FOS, and osteoclasts related genes involved in osteoclastogenesis. In vivo studies also depicted the effectiveness of HxTME in ovariectomized mice by preserving bone microarchitecture, mineral content, and inhibiting bone loss in treated mice as analyzed by Histomorphometry, MicroCT, and Raman spectroscopy. Oral administration of HxTME fraction resulted in the decreased percentage of F4/80+, CD11b+, and CD4+ RANKL+ T cells in OVX mice whereas pro-osteoclastic cytokine, IL6 was markedly reduced upon treatment with HxTME. On stimulation with PMA/Io and PHA, a significant decrease in proliferative response in the splenocytes of HxTME treated OVX mice was observed. Fatty acid profiling revealed that HxTME is rich in ω3 and ω6 polyunsaturated fatty acids (PUFAs), which have high nutraceutical properties and are known to play important role in growth, development and maintenance of health. Therefore, HxTME may be a good source of nutraceutical in the treatment of bone-related diseases particularly in postmenopausal osteoporosis and may be pursued as a potential candidate for treatment and management of osteoporosis.
Treatment procedures and associated medical costs of methicillin-resistant Staphylococcus aureus infection in Japan: A retrospective analysis using a database of Japanese employment-based health insurance

Objectives: This study aimed to determine the patient characteristics, treatment procedures, and medical costs of methicillin-resistant Staphylococcus aureus infections in clinical practice in Japan. Methods: Using the MinaCare database of healthcare information covering nearly 3 million individuals, of which 90% were aged 20–59 years, we extracted and analyzed data of patients who were aged ⩾15 years and diagnosed with methicillin-resistant S. aureus during hospitalization between April 2010 and August 2015. Results: A total of 684 patients with methicillin-resistant S. aureus infection were listed in the database, of which 365 were eligible to be included in this study. Mean patient age was 52.9 years, and 31.5% of the patients were females. Methicillin-resistant S. aureus bacteremia was the most common methicillin-resistant S. aureus infection (32.9%) with a mean age of 48.5 years, followed by pneumonia (24.1%) with a mean age of 61.0 years and methicillin-resistant S. aureus surgical site infection (6.3%) with a mean age of 49.7 years. Vancomycin was the most frequently prescribed anti–methicillin-resistant S. aureus drug used as the first-line therapy (68.5%), followed by teicoplanin (14.2%), linezolid (7.9%), arbekacin (5.8%), and daptomycin (3.6%). The mortality rate was 11.0%, and the mean treatment duration was 13.3 days. The median total medical cost per patient was US$5083. The median treatment cost for methicillin-resistant S. aureus bacteremia was the highest among the methicillin-resistant S. aureus infections at US$9099, followed by methicillin-resistant S. aureus pneumonia at US$3676 and surgery site infections at US$2084. Conclusion: Although the proportion of patients with methicillin-resistant S. aureus is very small in the employment-based health insurance database, methicillin-resistant S. aureus bacteremia is the most common methicillin-resistant S. aureus infection in the working-age population and requires the highest medical cost. Methicillin-resistant S. aureus pneumonia is more common in the elderly and is a cause of high mortality.
Cj1388 Is a RidA Homolog and Is Required for Flagella Biosynthesis and/or Function in Campylobacter jejuni

Campylobacter jejuni is the leading bacterial cause of acute gastroenteritis worldwide and thus significant to public health. C. jejuni primarily lives in the gastrointestinal tracts of poultry and can contaminate meat during processing. Despite a small genome, the metabolic plasticity of C. jejuni allows proliferation in chicken ceca and mammalian host intestines, and survival in environments with a variety of temperatures, pH, osmotic conditions, and nutrient availabilities. The exact mechanism of C. jejuni infection is unknown, however, virulence requires motility. Our data suggest the C. jejuni RidA homolog, Cj1388, plays a role in flagellar biosynthesis, regulation, structure, and/or function and, as such is expected to influence virulence of the organism. Mutants lacking cj1388 have defects in motility, autoagglutination, and phage infectivity under the conditions tested. Comparison to the RidA paradigm from Salmonella enterica indicates the phenotypes of the C. jejuni cj1388 mutant are likely due to the inhibition of one or more pyridoxal 5′-phosphate-dependent enzymes by the reactive enamine 2-aminoacrylate.
Field Tests of Performance and Their Relationship to Age and Anthropometric Parameters in Adolescent Handball Players

Handball performance is influenced by age, anthropometric characteristics, technical skills, tactical understanding, and physical abilities. The aims of this study were (i) to determine differences in anthropometric characteristics and physical performance between adolescent handball players across age categories, and (ii) to determine which anthropometric and maturity variables have the greatest relative importance in fitness for this sport. Seventy-nine male handball players drawn from a team in the elite Tunisian Handball league [U18 (n = 10); U17 (n = 12); U16 (n = 17); U15 (n = 18); and U14 (n = 22)] volunteered for the investigation. Assessments included sprint performances; change in direction tests (T-half test and Illinois modified test); jumping tests (squat jump; counter movement jump; countermovement jump with aimed arms; five-jump test); medicine ball throwing; handgrip force; back extensor force and selected anthropometric measurements. The individual’s age category affected all measurements, with U17 and U18 players showing larger body measurements and significantly better absolute results on all physical tests than U14, U15 and U16 contestants. Scores for the majority of physical performance tests were closely inter-correlated. We conclude that U17 and U18 players show significantly better absolute results than the younger players on all physical tests. Multiple linear regressions, using block-wise entry, indicate that age is the strongest predictor of jump and sprint performances. Several anthropometric characteristics, including body mass, standing height and lower limb length were closely correlated with performance test scores, but after allowing for age only body mass added to the prediction of jumping ability.
Spatiotemporal Patterns of Small for Gestational Age and Low Birth Weight Births and Associations With Land Use and Socioeconomic Status

In addition to small for gestational age (SGA) and low birth weight at term (LBWT), critically ill cases of SGA/LBWT are significant events from outcomes and economic perspectives that require further understanding of risk factors. We aimed to assess the spatiotemporal distribution of locations where there were consistently higher numbers of critically ill SGA/LBWT (hot spots) in comparison with all SGA/LBWT and all births. We focused on Edmonton (2008-2010) and Calgary (2006-2010), Alberta, and used a geographical information system to apply emerging hot spot analysis, as a new approach for understanding SGA, LBWT, and the critically ill counterparts (ciSGA or ciLBWT). We also compared the resulting aggregated categorical patterns with proportions of land use and socioeconomic status (SES) using Spearman correlation and logistic regression. There was an overall increasing trend in all space-time clusters. Whole period emerging hot spot patterns among births and SGA generally coincided, but SGA with ciSGA and LBWT with ciLBWT did not. Regression coefficients were highest for low SES with SGA and LBWT, but not with ciSGA and ciLBWT. Open areas and industrial land use were most associated with ciLBWT but not with ciSGA, SGA, or LBWT. Differences in the space-time hot spot patterns and the associations with ciSGA and ciLBWT indicate further need to research the interplay of maternal and environmental influences. We demonstrated the novel application of emerging hot spot analysis for small newborns and spatially related them to the surrounding environment.
Individual Variability in Migration Timing Can Explain Long-Term, Population-Level Advances in a Songbird

Migratory animals may be particularly at-risk due to global climate change, as they must match their timing with asynchronous changes in suitable conditions across broad, spatiotemporal scales. It is unclear whether individual long-distance migratory songbirds can flexibly adjust their timing to varying inter-annual conditions. Longitudinal data for individuals sampled across migration are ideal for investigating phenotypic plasticity in migratory timing programs, but remain exceptionally rare. Using the largest, repeat-tracking data set available to date for a songbird (n=32, purple martin Progne subis), we investigated individual variability in migration timing across 7,000-14,000 kilometre migrations between North American breeding sites and South American overwintering sites. In contrast to previous studies of songbirds, we found broad, within-individual variability between years in the timing of spring departure (0-20d), spring crossing of the Gulf of Mexico (0-20d), and breeding site arrival (0-18d). Spring departure and arrival dates were consistent across years (depart r=0.61; arrive r=0.67), however the lower bounds of confidence intervals spanned 0.5 indicating that this finding should be cautiously interpreted until more data accumulates. Fall migration timing was more variable at the individual level (depart range= 0-19d; gulf crossing range range=1-15d; arrive range=0-24d). Fall arrival date was the least repeatable (r=0.002), perhaps due to timing of this leg being the least resource limited, as purple martins are not territorial in winter and join large communal roosts. High within-individual variability in the timing of this diurnal migrant may reflect the greater influence of environmental and social cues as compared to more solitary, nocturnally migrating songbirds. Further, large, within-individual variability in migration dates (0-24d) suggest that advances in spring arrival dates with climate change that have been reported for multiple songbird species (including purple martins) could potentially be explained by intra-individual flexibility in migration timing. However, whether phenotypic plasticity will be sufficient to keep up with the pace of climate change remains to be determined.
“That Robot Stared Back at Me!”: Demonstrating Perceptual Ability Is Key to Successful Human–Robot Interactions

Communication robots, such as robotic salespeople and guide robots, are increasingly becoming involved in various aspects of people's everyday lives. However, it is still unclear what types of robot behavior are most effective for such purposes. In this research, we focused on a robotic salesperson. We believe that people often ignore what such robots have to say owing to their weak social presence. Thus, these robots must behave in ways that attract attention encouraging people to nod or reply when the robots speak. In order to identify suitable behaviors, we conducted two experiments. First, we conducted a field experiment in a shop in a traditional Kyoto shopping street to observe customers' real-world interactions with a robotic salesperson. Here, we found that the first impression given by the robot had a crucial influence on its subsequent conversations with most customer groups and that it was important for the robot to indicate it could understand how much attention customers were paying to the robot in the early stages of its interactions if it was to persuade customers to respond to what it said. Although the field experiment enabled us to observe natural interactions, it also included many external factors. In order to validate some of our findings without the involving these factors, we further conducted a laboratory experiment to investigate whether having the robot look back at the participants when they looked at it increased their perception that the robot was aware of their actions. These results supported the findings of the field experiment. Thus, we can conclude that demonstrating that a robot can recognize and respond to human behavior is important if it is to engage with people and persuade them to nod and reply to its comments.
Oral microbiome and obesity in a large study of low-income and African-American populations

ABSTRACT Few studies have evaluated the relationship of oral microbiome with obesity. We investigated the oral microbiome among 647 obese and 969 non-obese individuals from the Southern Community Cohort Study, through 16S rRNA gene sequencing in mouth rinse samples. We first investigated 16 taxa in two probiotic genera, Bifidobacterium and Lactobacillus. Among them, eight showed nominal associations with obesity (P < 0.05). Especially, Bifidobacterium (odds ratio [OR] = 0.67, 95% confidence interval [CI]:0.54, 0.83) and Bifidobacterium longum (OR = 0.57, 95% CI: 0.45, 0.73) were significantly associated with decreased obesity prevalence with false-discovery rate (FDR)-corrected P of 0.01 and 5.41 × 10−4, respectively. Multiple other bacterial taxa were also significantly associated with obesity prevalence at FDR-corrected P < 0.05. Among them, five in Firmicutes and two respectively in Actinobacteria and Proteobacteria were significantly associated with increased obesity prevalence. Significant associations with decreased obesity prevalence were observed for two taxa respectively in Actinobacteria and Firmicutes. Most of these taxa were associated with body mass index at study enrollment and weight gain during adulthood. Also, most of these associations were observed in both European- and African-Americans. Our findings indicate that multiple oral bacterial taxa, including several probiotic taxa, were significantly associated with obesity.
Evaluation of cardiac hypertrophy in the setting of sudden cardiac death

Abstract Ventricular hypertrophy is a common pathological finding at autopsy that can act as a substrate for arrhythmogenesis. Pathologists grapple with the significance of ventricular hypertrophy when assessing the sudden and unexpected deaths of young people and what it could mean for surviving family members. The pathological spectrum of left ventricular hypertrophy (LVH) is reviewed herein. This article is oriented to the practicing autopsy pathologist to help make sense of various patterns of increased heart muscle, particularly those that are not clearly cardiomyopathic, yet present in the setting of sudden cardiac death. The article also reviews factors influencing arrhythmogenesis as well as genetic mutations most commonly associated with ventricular hypertrophy, especially those associated with hypertrophic cardiomyopathy (HCM).
The Virome of Cerebrospinal Fluid: Viruses Where We Once Thought There Were None

Traditionally, medicine has held that some human body sites are sterile and that the introduction of microbes to these sites results in infections. This paradigm shifted significantly with the discovery of the human microbiome and acceptance of these commensal microbes living across the body. However, the central nervous system (CNS) is still believed by many to be sterile in healthy people. Using culture-independent methods, we examined the virome of cerebrospinal fluid (CSF) from a cohort of mostly healthy human subjects. We identified a community of DNA viruses, most of which were identified as bacteriophages. Compared to other human specimen types, CSF viromes were not ecologically distinct. There was a high alpha diversity cluster that included feces, saliva, and urine, and a low alpha diversity cluster that included CSF, body fluids, plasma, and breast milk. The high diversity cluster included specimens known to have many bacteria, while other specimens traditionally assumed to be sterile formed the low diversity cluster. There was an abundance of viruses shared among CSF, breast milk, plasma, and body fluids, while each generally shared less with urine, feces, and saliva. These shared viruses ranged across different virus families, indicating that similarities between these viromes represent more than just a single shared virus family. By identifying a virome in the CSF of mostly healthy individuals, it is now less likely that any human body site is devoid of microbes, which further highlights the need to decipher the role that viral communities may play in human health.
NFAT1 Regulates Ly6Chi Monocyte Recruitment to the CNS and Plays an Essential Role in Resistance to Toxoplasma gondii Infection

Monocytes play key roles in the maintenance of homeostasis and in the control of the infection. Monocytes are recruited from the bone marrow to inflammatory sites and are essential for antimicrobial activity to limit tissue damage and promote adaptive T cell responses. Here, we investigated the role of Nuclear Factor of Activated T cells 1 (NFAT1) in the regulation of Ly6Chi inflammatory monocyte recruitment to the CNS upon T. gondii infection. We show that NFAT-1-deficient monocytes are unable to migrate to the CNS of T. gondii-infected mice. Moreover, NFAT1−/− mice are highly susceptible to chronic T. gondii infection due to a failure to control parasite replication in the CNS. The inhibition of Ly6Chi inflammatory monocyte recruitment to the CNS severely blocked CXCL10 production and consequently the migration of IFN-γ-producing CD4+ T cells. Moreover, the transfer of Ly6Chi monocytes to infected NFAT1−/− mice favored CD4+ T cell migration to the CNS and resulted in the inhibition of parasite replication and host defense. Together, these results demonstrated for the first time the contribution of NFAT1 to the regulation of Ly6Chi monocyte recruitment to the CNS and to resistance during chronic T. gondii infection.
Cardiogeneticsbank@UZA: A Collection of DNA, Tissues, and Cell Lines as a Translational Tool

Cardiogeneticsbank@UZA is an academic hospital integrated biobank that collects aortic tissue, blood, cell lines (fibroblasts, vascular smooth muscle cells, peripheral blood mononuclear cells, and induced pluripotent stem cells), and DNA from patients with cardiogenetic disorders, for both diagnostic and research purposes. We adhere to a quality management system and have established standard protocols for the sampling and processing of all cardiogenetic patient related materials. Cardiogeneticsbank@UZA is embedded in the Biobanking and Biomolecular Resources Research Infrastructure Belgium (BBMRI.be) and samples from this biobank are available for commercial and academic researchers, through an established access procedure. Currently, the extremely valuable cardiogenetics collection consists of more than 8,700 DNA samples, 380 tissue samples, and 500 cell lines of 7,578 patients, and is linked with extensive clinical data. Some interesting potential research applications are discussed.