Miracle-dz/UniFAR-FTUs huggingface dataset:
Role for Maternal Asthma in Severe Human Metapneumovirus Lung Disease Susceptibility in Children

Abstract Background Severity of human metapneumovirus (hMPV) lower respiratory illness (LRTI) is considered similar to that observed for respiratory syncytial virus (RSV). However, differences in severity between these pathogens have been noted, suggesting the degree of illness may vary in different populations. Moreover, a potential association between hMPV and asthma also suggests that hMPV may preferentially affect asthmatic subjects. Methods In a population-based surveillance study in children aged <2 years admitted for severe LRTI in Argentina, nasopharyngeal aspirates were tested by RT-PCR for hMPV, RSV, influenza A, and human rhinovirus. Results Of 3947 children, 383 (10%) were infected with hMPV. The hospitalization rate for hMPV LRTI was 2.26 per 1000 children (95% confidence interval [CI], 2.04–2.49). Thirty-nine (10.2%) patients infected with hMPV experienced life-threatening disease (LTD; 0.23 per 1000 children; 95% CI, .16–.31/1000), and 2 died (mortality rate 0.024 per 1000; 95% CI, .003–.086). In hMPV-infected children birth to an asthmatic mother was an increased risk for LTD (odds ratio, 4.72; 95% CI, 1.39–16.01). We observed a specific interaction between maternal asthma and hMPV infection affecting risk for LTD. Conclusions Maternal asthma increases the risk for LTD in children <2 years old hospitalized for severe hMPV LRTI.
African climate response to orbital and glacial forcing in 140,000-y simulation with implications for early modern human environments

Significance A computer model calculates the changing climate/vegetation from 140,000 y ago to the present for Africa, Arabia, and the Mediterranean Basin. The results illustrate how and when changes in Earth’s orbit, greenhouse gases, and ice sheets change the climate. The model makes this long calculation using the full set of dynamic/thermodynamic equations with sufficient spatial resolution to calculate monsoon and storm track rainfall over this region. The results explain when and where the climate was wetter or drier and how the vegetation changed. The simulated environmental changes agree with observed paleoenvironmental data in most areas. The results will help assess whether and how climate, hydrology, and vegetation changes may have influenced human dispersal out of Africa. A climate/vegetation model simulates episodic wetter and drier periods at the 21,000-y precession period in eastern North Africa, the Arabian Peninsula, and the Levant over the past 140,000 y. Large orbitally forced wet/dry extremes occur during interglacial time, ∼130 to 80 ka, and conditions between these two extremes prevail during glacial time, ∼70 to 15 ka. Orbital precession causes high seasonality in Northern Hemisphere (NH) insolation at ∼125, 105, and 83 ka, with stronger and northward extended summer monsoon rains in North Africa and the Arabian Peninsula and increased winter rains in the Mediterranean Basin. The combined effects of these two seasonally distinct rainfall regimes increase vegetation and narrow the width of the Saharan–Arabian desert and semidesert zones. During the opposite phase of the precession cycle (∼115, 95, and 73 ka), NH seasonality is low, and decreased summer insolation and increased winter insolation cause monsoon and storm track rains to decrease and the width of the desert zone to increase. During glacial time (∼70 to 15 ka), forcing from large ice sheets and lowered greenhouse gas concentrations combine to increase winter Mediterranean storm track precipitation; the southward retreat of the northern limit of summer monsoon rains is relatively small, thereby limiting the expansion of deserts. The lowered greenhouse gas concentrations cause the near-equatorial zone to cool and reduce convection, causing drier climate with reduced forest cover. At most locations and times, the simulations agree with environmental observations. These changing regional patterns of climate/vegetation could have influenced the dispersal of early humans through expansions and contractions of well-watered corridors.
Patient functionality and walking speed after discharge from the intensive care unit

Objective To measure and compare the functionality of patients after discharge from the intensive care unit and at the time of hospital discharge. Methods Quantitative study of a prospective cohort performed between August of 2016 and December of 2017 at a university hospital. A 10-meter walk test was performed at 2 timepoints: after discharge from the intensive care unit and prior to hospital discharge. The data were analyzed using Student's t-test and Pearson or Spearman correlation. Statistical Package for Social Science (SPSS) version 21.0 was used for the analysis, and p ≤ 0.05 was adopted as the level of significance. Results Forty patients, with a mean age of 57.1 ± 12.2 years and with a predominance of males (60%), were evaluated. For the post-intensive care unit test, a mean speed of 0.48m/s was observed, and for the pre-hospital discharge test, there was an increase to 0.71m/s, evidencing functional evolution during the hospital stay (p < 0.001). Conclusion There was significant improvement in walking speed at the time of hospital discharge when compared to the walking speed at the time of intensive care unit discharge.
Nasal Microbiota Modifies the Effects of Particulate Air Pollution on Plasma Extracellular Vesicles

Air pollution exposure has been linked to modifications of both extracellular vesicle (EV) concentration and nasal microbiota structure (NMB), which might act as the respiratory health gatekeeper. This study aimed to assess whether an unbalanced NMB could modify the effect of particulate matter (PM) exposure on plasmatic EV levels. Due to two different NMB taxonomical profiles characterized by a widely different relative abundance of the Moraxella genus, the enrolled population was stratified into Mor− (balanced NMB) and Mor+ (unbalanced NMB) groups (Moraxella genus’s cut-off ≤25% and >25%, respectively). EV features were assessed by nanoparticle tracking analysis (NTA) and flow-cytometry (FC). Multivariable analyses were applied on EV outcomes to evaluate a possible association between PM10 and PM2.5 and plasmatic EV levels. The Mor− group revealed positive associations between PM levels and plasmatic CD105+ EVs (GMR = 4.39 p = 0.02) as for total EV count (GMR = 1.92 p = 0.02). Conversely, the Mor+ group showed a negative association between exposure and EV outcomes (CD66+ GMR = 0.004 p = 0.01; EpCAM+ GMR = 0.005 p = 0.01). Our findings provide an insight regarding how a balanced NMB may help to counteract PM exposure effects in terms of plasmatic EV concentration. Further research is necessary to understand the relationship between the host and the NMB to disentangle the mechanism exerted by inhaled pollutants in modulating EVs and NMB.
Prevalence and Interpersonal Correlates of Internet Gaming Disorders among Chinese Adolescents

This study investigated the prevalence and interpersonal correlates of Internet gaming disorders (IGD) among Chinese adolescents. A cross-sectional survey was conducted in two cities (Shanghai and Xi’an) in China. A total of 2666 (Meanage = 12.77 ± 0.75) year-one students from eight middle schools completed a self-reported questionnaire. It tested their levels of IGD, parental psychological control, negative interpersonal events (physical/verbal abuse by parents, verbal abuse by teachers, peer/online bullying), social support from parents/peers, and positive relationships with parents/peers. Results showed that 346 participants (13.0%) were classified as having IGD. Gender, city, single-parent family, family socio-economic status, and mother’s education level were significantly associated with the risk of IGD. Logistic regression analyses with and without controlling for the significant background variables showed that the studied interpersonal variables were significantly associated with IGD, respectively. Forward stepwise logistic regression showed that the significant correlates of IGD included parental psychological control, physical/verbal abuse by parents, verbal abuse by teachers, and peer/online bullying. Results highlight the importance of addressing interpersonal risk factors to reduce adolescent IGD. Limitations and implications of this study are discussed.
Chronic mirabegron treatment increases human brown fat, HDL cholesterol, and insulin sensitivity.

BACKGROUND Mirabegron is a β3-adrenergic receptor (β3-AR) agonist approved only for the treatment of overactive bladder. Encouraging preclinical results suggest that β3-AR agonists could also improve obesity-related metabolic disease by increasing brown adipose tissue (BAT) thermogenesis, white adipose tissue (WAT) lipolysis, and insulin sensitivity. METHODS We treated 14 healthy women of diverse ethnicity, 27.5 ± 1.1 y, BMI 25.4 ± 1.2 kg/m2, with 100 mg mirabegron (Myrbetriq extended-release tablet, Astellas Pharma) for four weeks, open-label. The primary endpoint was the change in BAT metabolic activity as measured by [18F]-2-fluoro-D-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT). Secondary endpoints included resting energy expenditure (REE), plasma metabolites, and glucose and insulin metabolism as assessed by frequently sampled intravenous glucose tolerance test. RESULTS Chronic mirabegron therapy increased BAT metabolic activity. Whole-body REE was higher, without changes in body weight or composition. Additionally, there were elevations in plasma levels of the beneficial lipoprotein biomarkers high-density lipoprotein (HDL) and ApoA1, as well as total bile acids. Adiponectin, a WAT-derived hormone that has anti-diabetic and anti-inflammatory capabilities, increased with acute treatment and was 35% higher at study completion. Finally, an intravenous glucose tolerance test demonstrated higher insulin sensitivity, glucose effectiveness, and insulin secretion. CONCLUSION These findings indicate that human BAT metabolic activity can be increased after chronic pharmacological stimulation with mirabegron and support the investigation of β3-AR agonists as a treatment for metabolic disease. TRIAL REGISTRATION Clinicaltrials.gov NCT03049462. FUNDING This work was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), DK075112, DK075116, DK071013, and DK071014.
Coordination of host and symbiont gene expression reveals a metabolic tug-of-war between aphids and Buchnera

Significance Symbioses between animals and microbes often involve host control of symbionts to harness a benefit. In aphids, Buchnera symbionts produce amino acids for their hosts, enabling these insects to survive solely on plant sap. Buchnera abundance varies among aphid lineages, suggesting that distinct host–symbiont relationships exist among host genotypes. We found that Buchnera gene expression varies among aphid lineages, indicating that Buchnera also contributes to the host–symbiont relationship. Aphids and Buchnera inversely up-regulate amino acid biosynthesis and cell-proliferation genes, and both aphid and Buchnera genes implicated in host–symbiont interactions were differentially expressed, indicating crosstalk. Overall, we demonstrated that Buchnera alters its gene expression in response to the host genetic background, and this likely affects host gene expression. Symbioses between animals and microbes are often described as mutualistic, but are subject to tradeoffs that may manifest as shifts in host and symbiont metabolism, cellular processes, or symbiont density. In pea aphids, the bacterial symbiont Buchnera is confined to specialized aphid cells called bacteriocytes, where it produces essential amino acids needed by hosts. This relationship is dynamic; Buchnera titer varies within individual aphids and among different clonal aphid lineages, and is affected by environmental and host genetic factors. We examined how host genotypic variation relates to host and symbiont function among seven aphid clones differing in Buchnera titer. We found that bacteriocyte gene expression varies among individual aphids and among aphid clones, and that Buchnera gene expression changes in response. By comparing hosts with low and high Buchnera titer, we found that aphids and Buchnera oppositely regulate genes underlying amino acid biosynthesis and cell growth. In high-titer hosts, both bacteriocytes and symbionts show elevated expression of genes underlying energy metabolism. Several eukaryotic cell signaling pathways are differentially expressed in bacteriocytes of low- versus high-titer hosts: Cell-growth pathways are up-regulated in low-titer genotypes, while membrane trafficking, lysosomal processes, and mechanistic target of rapamycin (mTOR) and cytokine pathways are up-regulated in high-titer genotypes. Specific Buchnera functions are up-regulated within different bacteriocyte environments, with genes underlying flagellar body secretion and flagellar assembly overexpressed in low- and high-titer hosts, respectively. Overall, our results reveal allowances and demands made by both host and symbiont engaged in a metabolic “tug-of-war. ”
Better stress coping associated with lower tau in amyloid-positive cognitively unimpaired older adults

Objective Research in animals has shown that chronic stress exacerbates tau pathology. In humans, psychological stress has been associated with higher risk of Alzheimer disease clinical syndrome. The objective of this cross-sectional study was to assess the hypothesis that stress coping ability (assessed via the Brief Resilience Scale [BRS]) is associated with tau burden and to evaluate whether these associations differed by sex and amyloid status (A+/A−) in cognitively unimpaired (CU) older adults. Methods We included 225 CU participants (mean age 70.4 ± 10.2 years, 48% female) enrolled in the population-based Mayo Clinic Study of Aging who completed the BRS and underwent amyloid-PET (Pittsburgh compound B–PET) and tau-PET (AV1451-PET). We fitted multiple regression and analysis of covariance models to assess the associations between BRS and tau-PET and the interaction with amyloid status and sex. We focused on entorhinal cortex (ERC) tau burden and also performed voxel-wise analyses. Age, sex, education, depression, and anxiety were considered as covariates. Results Higher stress coping ability was associated with lower tau burden in the medial temporal lobe (including ERC) and occipito-temporal and cuneal/precuneal cortices. The association was present in both A+ and A− but weaker in A− CU older adults. There was an interaction between amyloid status and stress coping ability that was restricted to the medial temporal lobe tau such that A+ CU older adults with lower stress coping abilities showed higher tau. There were no significant interactions between stress coping and sex. Conclusions A faster termination of the stress response (higher coping ability) may limit the negative effects of stress on tau deposition. Conversely, lower stress coping ability may be an early sign of accumulating tau pathology. Longitudinal studies are warranted to clarify whether stress mechanisms act to exacerbate tau pathology or tau influences stress-related brain mechanisms and lowers the ability to cope with stress.
CFTR dysregulation drives active selection of the gut microbiome

Patients with cystic fibrosis (CF) have altered fecal microbiomes compared to those of healthy controls. The magnitude of this dysbiosis correlates with measures of CF gastrointestinal (GI) disease, including GI inflammation and nutrient malabsorption. However, whether this dysbiosis is caused by mutations in the CFTR gene, the underlying defect in CF, or whether CF-associated dysbiosis augments GI disease was not clear. To test the relationships between CFTR dysfunction, microbes, and intestinal health, we established a germ-free (GF) CF mouse model and demonstrated that CFTR gene mutations are sufficient to alter the GI microbiome. Furthermore, flow cytometric analysis demonstrated that colonized CF mice have increased mesenteric lymph node and spleen TH17+ cells compared with non-CF mice, suggesting that CFTR defects alter adaptive immune responses. Our findings demonstrate that CFTR mutations modulate both the host adaptive immune response and the intestinal microbiome.
Effect of Cysteine on Methylglyoxal-Induced Renal Damage in Mesangial Cells

Methylglyoxal (MGO), a highly reactive dicarbonyl compound, is a key precursor of the formation of advanced glycation end products (AGEs). MGO and MGO-AGEs were reportedly increased in patients with diabetic dysfunction, including diabetic nephropathy. The activation of glyoxalase-I (GLO-I) increases MGO and MGO-AGE detoxification. MGO-mediated glucotoxicity can also be ameliorated by MGO scavengers such as N-acetylcysteine (NAC), aminoguanidine (AG), and metformin. In this study, we noted that l-cysteine demonstrated protective effects against MGO-induced glucotoxicity in renal mesangial cells. l-cysteine prevented MGO-induced apoptosis and necrosis, together with a reduction of reactive oxygen species (ROS) production in MES13 cells. Interestingly, l-cysteine significantly reduced MGO-AGE formation and also acted as an MGO-AGE crosslink breaker. Furthermore, l-cysteine treatment accelerated MGO catabolism to D-lactate via the upregulation of GLO-I. The reduction of AGE formation and induction of AGE breakdown, following l-cysteine treatment, further supports the potential use of l-cysteine as an alternative for the therapeutic control of MGO-induced renal complications in diabetes, especially against diabetic nephropathy.
Helminth Species and Infracommunities in Frogs Pelophylax ridibundus and P. esculentus (Amphibia: Ranidae) in Northern Ukraine

The study aims to characterise and compare the helminth assemblages and helminth infracommunities in the marsh frog, Pelophylax ridibundus and the edible frog, P. esculentus collected in the northern part of Ukraine. Occurrence and abundance of the helminths were analysed by calculating the prevalence, intensity, and mean abundance of infection; similarities between the infracommunities were estimated by the Bray–Curtis index and visualised using nMDS plots. Dissimilarities were estimated using the ANOSIM and SIMPER routines. In total, 27 helminth species were found in 143 frogs. Pelophylax ridibundus (n = 86) harboured 20 species of helminths, 24 species were found in P. esculentus (n = 57), and 17 species were shared by the two hosts. Oswaldocruzia bialata and larval Strigea sp. were absent in P. ridibundus, while they reached the prevalence of 30% and 10%, respectively, in P. esculentus. Cosmocerca ornata, Diplodiscus subclavatus, Opisthioglyphe ranae, and Codonocephalus urniger had significantly larger prevalence in P. ridibundus, whereas Haematoloechus asper was found to be more prevalent in P. esculentus. Acanthocephalus ranae, Icosiella neglecta, Haematoloechus variegatus, Pleurogenes claviger, Pleurogenoides medians, and Prosotocus confusus were equally common in both hosts. Helminth infracommunities in the two hosts had identical species richness (1–10 species, 4 on average); abundance was significantly higher in P. ridibundus. Helminth assemblages of the two hosts in northern Ukraine are rather similar; however, small but significant differences were found in their species composition, parameters of infection in some species, and structure of helminth infracommunities.
Plant diversity effect on water quality in wetlands: a meta-analysis based on experimental systems.

The ecological literature reports little empirical evidence from biodiversity - ecosystem functioning (BEF) experiments in wetland systems, even though wetlands are widely known for their water filtering capacity. Experiments comparing the effect of plant monocultures and mixtures on water quality to improve pollutant removal efficiency in treatment wetlands share the characteristics of classical BEF experiments, and so could provide insights for wetland management. To add to our understanding of BEF relationships in wetlands, we evaluated plant diversity effects on water purification through a meta-analysis of freshwater experimental wetlands comparing monocultures to mixtures. We found 28 studies that matched our criteria for BEF analysis, for a total of 561 diversity effects on pollutant removal. Overall, the meta-analysis shows no significant effect of plant richness on removal of total suspended solids, but a positive effect on chemical oxygen demand and total nitrogen removal, and a marginal effect on phosphorus removal. Thus, the results of this meta-analysis are consistent with reports of an overall positive biodiversity effect on ecosystem properties. An analysis of moderator variables shows that the experimental context (size of the experimental units, nutrient load, duration of the experiment) does not explain much of the residual variance. For pollutants that benefit from a positive plant richness effects on removal, mixtures do not perform better than the best monoculture. We found no evidence that plant richness effects are due to functional complementarity among species rather than to the presence of particularly efficient species. Complementarity effects may be less prevalent in highly productive, nutrient-rich wetlands, compared to nutrient-limited environments such as natural grasslands. Although findings must be confirmed by long-term field experiments under natural conditions, result from experimental wetland systems may contribute to a better understanding of biodiversity effect on ecosystem functions in wetlands, in addition to guide practices in natural wetland restoration and the use of constructed wetlands for water treatment.
Combined iDISCO and CUBIC tissue clearing and lightsheet microscopy for in toto analysis of the adult mouse ovary†

Abstract At any given time, the ovary contains a number of follicles in distinct growth stages, each with a set of identifying characteristics. Although follicle counting and staging using histological stains on paraffin-embedded ovary sections has been the gold standard in assessing ovarian health in fertility studies, the final counts rely on extrapolation factors that diverge greatly among studies. These methods also limit our ability to investigate spatial aspects of ovary organization. Recent advances in optical tissue clearing and lightsheet microscopy have permitted comprehensive analysis of intact tissues. In this study, we set out to determine the best clearing and imaging methods to generate 3D images of the complete adult mouse ovary that could be used for accurate assessments of ovarian follicles. We found that a combination of iDISCO and CUBIC was the best method to clear the immunostained ovary. Using lightsheet microscopy, we generated 3D images of the intact ovary and performed qualitative assessments of follicles at all stages of development. This study is an important step toward developing quantitative computational models that allow rapid and accurate assessments of growing and quiescent primordial follicles, and to investigate the integrity of extrinsic ovarian components including vascular and neuronal networks. Summary Sentence The combination of iDISCO and CUBIC tissue clearing methods allows in toto imaging of the ovarian follicle composition and extrinsic vascular and neuronal networks.