Miracle-dz/UniFAR-FTUs huggingface dataset:
Longitudinal Asthma Patterns in Italian Adult General Population Samples: Host and Environmental Risk Factors

Background: Asthma patterns are not well established in epidemiological studies. Aim: To assess asthma patterns and risk factors in an adult general population sample. Methods: In total, 452 individuals reporting asthma symptoms/diagnosis in previous surveys participated in the AGAVE survey (2011–2014). Latent transition analysis (LTA) was performed to detect baseline and 12-month follow-up asthma phenotypes and longitudinal patterns. Risk factors associated with longitudinal patterns were assessed through multinomial logistic regression. Results: LTA detected four longitudinal patterns: persistent asthma diagnosis with symptoms, 27.2%; persistent asthma diagnosis without symptoms, 4.6%; persistent asthma symptoms without diagnosis, 44.0%; and ex -asthma, 24.1%. The longitudinal patterns were differently associated with asthma comorbidities. Persistent asthma diagnosis with symptoms showed associations with passive smoke (OR 2.64, 95% CI 1.10–6.33) and traffic exposure (OR 1.86, 95% CI 1.02–3.38), while persistent asthma symptoms (without diagnosis) with passive smoke (OR 3.28, 95% CI 1.41–7.66) and active smoke (OR 6.24, 95% CI 2.68–14.51). Conclusions: LTA identified three cross-sectional phenotypes and their four longitudinal patterns in a real-life setting. The results highlight the necessity of a careful monitoring of exposure to active/passive smoke and vehicular traffic, possible determinants of occurrence of asthma symptoms (with or without diagnosis). Such information could help affected patients and physicians in prevention and management strategies.
Impact of Porcine Arterivirus, Influenza B, and Their Coinfection on Antiviral Response in the Porcine Lung

Interferon (IFN) cytokines induce an autonomous antiviral state in cells of the infected site to restrict virus spreading and critically regulate overall antiviral response. The antiviral state leads to host protection through expression of hundreds of IFN-stimulated genes that restrict viral infection through multiple mechanisms, for example, directly in viral genome degradation and indirectly through cellular metabolic inhibition. Young pigs were split into four treatment groups: control, porcine reproductive and respiratory syndrome virus (PRRSV, also known as porcine arterivirus) infected, influenza B virus (IBV) infected, and IBV/PRRSV coinfection. Lung tissue was collected at 3, 5, and 7 days post infection (dpi) for control, PRRSV and IBV/PRRSV coinfection, and at 3 and 5 dpi for IBV. Transcriptomic analysis, using usegalaxy.org tools, was performed against the S.scrofa 11.1 reference genome. Differentially expressed gene (DEG) analysis was carried out using DeSeq2 based on the model treatment + dpi + treatment:dpi + E. Downstream analysis examined the interaction of DEG at each dpi for over-enriched gene ontology (G.O.) terms and pathways. Comparisons of the infected groups vs. the controls yielded a total of (n = 1412) DEGs for the PRRSV group and (n = 1578) for the IBV/PRRSV group across all timepoints. The IBV group had (n = 64) total DEGs across 3 and 5 dpi. Expression data were considered statistically significant based on false discovery rate (FDR) ⫹ 0.1. Venn diagram comparisons of the DEGs across dpi showed that groups shared only 16 DEGs at 3 dpi, no DEGs were shared at 5 dpi, and for 7 dpi, only the PRRSV and IBV/PRRSV groups were compared and shared a total of 43 DEGs. Across the comparisons, differential expression was observed in antiviral genes such as IRF1, MX1, and OAS2. The IBV and IBV/PRRSV groups showed higher expression of antiviral genes at earlier dpi than the PRRSV group. Additionally, downregulated genes from the comparisons clustered around Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways effecting lung development and cellular integrity. Early expression of host IFN and antiviral genes may lead to viral RNA degradation, and assembly and transcription inhibition in the IBV infections. In comparison, expression of antiviral genes in the PRRSV group decreased across time. The decrease may explain why PRRSV infections persist, while IBV clears. Moreover, all infected groups showed prolonged upregulation in neutrophil degranulation pathway activity, possibly exacerbating symptomatic lung lesion pathology seen in these respiratory infections.
Effects of a Community-Based Pilot Intervention on Home Food Availability among U.S. Households

The purpose of this study was to assess the effects of a pilot community-based behavioral intervention on the home food environment in U.S. households. Parents (21 females, 2 males; age = 36 ± 5.5 years; 78% Hispanic) of elementary school-aged children attended a 10-week dietary improvement behavioral intervention targeting an increase in fruit and vegetable consumption and a reduction in sugar intake. Home food availability of fruit, vegetables, and sugar-laden foods and beverages were assessed before and after the intervention using a modified version of the Home Food Inventory. Relative to baseline, the intervention resulted in significant increases in fruit availability (7.7 ± 3.2 items vs. 9.4 ± 3.1 items; p = 0.004) and low sugar cereal (2.3 ± 1.4 types vs. 2.7 ± 1.4 types; p = 0.033). There was a significant reduction in sugar-sweetened beverage availability (3.2 ± 1.9 types vs. 1.7 ± 1.3 types; p = 0.004). There was a significant increase in the number of households with accessible ready-to-eat vegetables and fruit, and a significant reduction in available prepared desserts, and candy (p < 0.01). There were no significant changes in the availability of vegetables and sugar-laden cereals. The current intervention resulted in positive changes in the home food environment. Further research to confirm these results in a randomized controlled trial is warranted.
Creation and characterization of industrially applicable de novo lager yeast hybrids with a 1 unique genomic architecture 2 3

Creation and characterization of industrially applicable de novo lager yeast hybrids with a 1 unique genomic architecture 2 3 Zachari Turgeona#, Thomas Sierocinskia, Cedric A. Brimacombea, Yiqiong Jina, Brittany 4 Goldhawkea*, Jessica M. Swansona, John I. Husnika and Matthew S. Dahabieha+ 5 6 a Renaissance BioScience Corporation, 410-2389 Health Sciences Mall, Vancouver, BC, Canada 7 8 Running Head: Creation of Lager Strains with Unique Genomic Structure 9 10 # Address correspondence to Zachari Turgeon, zturgeon@renaissancebioscience.com 11 12 * Present address: Brittany Goldhawke, Barrelwise, 2366 Main Mall, Vancouver, BC, Canada 13 + Present address: Matthew S. Dahabieh, Terramera, 333 Seymour Street, Vancouver, BC, 14 Canada 15 16 17 18 19 20 21 22 AEM Accepted Manuscript Posted Online 13 November 2020 Appl Environ Microbiol doi:10.1128/AEM.02434-20 Copyright © 2020 Turgeon et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
Heterogeneous Trajectory Classes of Social Engagement and Sex Differences for Older Adults in China

This study aimed to identify the heterogeneous trajectory classes of social engagement among older adults in China and examine sex differences to determine how sociodemographic characteristics and health status impact these trajectory classes. A sample of 8117 participants aged ≥65 years from the Chinese Longitudinal Healthy Longevity Survey was included. Growth mixture modeling was conducted to estimate the trajectory classes of social engagement. Logistic regression was adopted to analyze the associations between individual characteristics and trajectory classes. Three trajectory classes of social engagement were identified: the high-decline (35.3%), medium-decline (57.6%), and low-increase (7.1%). Men were less likely to be in the medium-decline and low-increase classes than women. Older men benefited from economic factors more than women. Education exhibited a stronger protective effect on the high-decline class for older women. High physical functioning might enable older adults with the lowest initial level of social engagement to make efforts to engage in social activities, which was stronger for older men than women. For both men and women, a proper cognitive state and positive emotions were in favor of social engagement. These findings are valuable for achieving sex equity in social engagement development for healthy and active aging.
Phosphatidylinositol 4,5-bisphosphate is regenerated by speeding of the PI 4-kinase pathway during long PLC activation

Stimulation of muscarinic Gq-coupled receptors initially depletes phosphoinositide phosphatidylinositol 4,5-bisphosphate from the plasma membrane. Myeong et al. show that phosphoinositides subsequently regenerate during sustained receptor stimulation as a consequence of profound PI 4-kinase pathway acceleration and not desensitization of receptors.
Pornography Use in Adolescents and Its Clinical Implications

(1) Background: The Differential Susceptibility to Media Effects Model (DSMM) suggests that pornography use effects are conditional and they depend on dispositional, developmental, and social differential susceptibility variables. This framework also highlights that the differential susceptibility variables act as predictors of pornography use and as moderators of the effect of pornography on criterion variables. (2) Methods: By administering a survey to n = 1500 adolescents, we tested whether these assumptions were met. (3) Results: Pornography use was related to being male and older, having a bisexual or undefined sexual orientation, higher substance use, being non-Muslim, and reporting sexual interest and the use of the media to obtain sexual information. Structural Equation Modeling (SEM) showed that higher levels in the criterion variables were directly related to pornography use, older age, substance use, and being women. Some mediational links also emerged. Pornography use mediated between the age and criterion variables. Moreover, substance use mediated the association between age and gender with the criterion variables. (4) Conclusions: Our findings support the clinical applicability of the theoretical DSMM framework. Knowing adolescent pornography consumers’ profiles and the impact of pornography on this population would allow for the designing of more effective prevention and regulation proposals.
Glycinergic Inhibition Targets Specific Off Cone Bipolar Cells in Primate Retina

Abstract Adapting between scotopic and photopic illumination involves switching the routing of retinal signals between rod and cone-dominated circuits. In the daytime, cone signals pass through parallel On and Off cone bipolar cells (CBCs), that are sensitive to increments and decrements in luminance, respectively. At night, rod signals are routed into these cone-pathways via a key glycinergic interneuron, the AII amacrine cell (AII-AC). AII-ACs also provide On-pathway-driven crossover inhibition to Off-CBCs under photopic conditions. In primates, it is not known whether all Off-bipolar cell types receive functional inputs from AII-ACs. Here, we show that select Off-CBC types receive significantly higher levels of On-pathway-driven glycinergic input than others. The rise and decay kinetics of the glycinergic events are consistent with involvement of the α1 glycine receptor (GlyR) subunit, a result supported by a higher level of GLRA1 transcript in these cells. The Off-bipolar types that receive glycinergic input have sustained physiological properties and include the flat midget bipolar (FMB) cells, which provide excitatory input to the Off-midget ganglion cells (GCs; parvocellular pathway). Our results suggest that only a subset of Off-bipolar cells have the requisite receptors to respond to AII-AC input. Taken together with results in mouse retina, our findings suggest a conserved motif whereby signal output from AII-ACs is preferentially routed into sustained Off-bipolar signaling pathways.
Ellagitannin Monomers and Oligomers from Euphorbia prostrata AIT. and Oligomers from Loropetalum chinense OLIV.

Three new ellagitannins, prostratins A, B and C, along with eleven known polyphenols including three hydrolyzable tannin oligomers (rugosins D, E and G), have been isolated from the leaves of Euphorbia prostrata AIT. A hydrolyzable tannin trimer, prostatin B, and two dimers, rugosins D and E, were also obtained from the leaves of Loropetalum Chinense OLIV.
Sonoelastography to Assess Muscular Stiffness Among Older Adults and its Use for the Diagnosis of Sarcopenia: A Systematic Review

Abstract Changes in muscle stiffness have been reported with sarcopenia. Sonoelastography is an accessible and non-radiating imaging technique allowing quantification of elastic properties of tissue. We performed a systematic review of the literature to investigate whether sonoelastography can be a reliable method to assess sarcopenia in older patients. We searched Medline, Google Scholar, Scopus, SpringerLink and Science direct from January 1, 1990 to April 1, 2020. Three independent review authors assessed trial eligibility, extracted the data, and assessed risk of bias. We intended to learn which types of elastography have been tested, if such measures are repeatable, and if they have been compared to the currently accepted diagnostic method. Ten studies met the inclusion criteria. Most followed a cross-sectional design with young and older adult subgroups. The gastrocnemius, rectus femoris, and vastus intermedius appeared most frequently. Nine of the included studies used shear wave elastography and one-strain elastography. The passive elastic constant was significantly greater in sarcopenic versus healthy subjects after passive stretching (124.98 ± 60.82 vs. 46.35 ± 15.85, P = 0.004). However, even in non-sarcopenic patients, the age of the patient was responsible for about 45.5 % of the variance in SWV. Among ten included articles, four reported higher stiffness in the muscles of older adults, two reported lower stiffness, and four found no significant difference. Due to the substantial heterogenicity of actual data, we could not make any conclusions about the potential usefulness of elastography to assess sarcopenia. Further studies are needed, including a larger sample of older patients and using a standardized and reproducible protocol.
Design, Synthesis, and In Vitro/In Vivo Anti-Cancer Activities of Novel (20S)-10,11-Methylenedioxy-Camptothecin Heterocyclic Derivatives

A novel camptothecin analogue, (20S)-10,11-methylenedioxy-camptothecin (FL118), has been proven to show significant antitumor efficacy for a wide variety of solid tumors. However, the further development of FL118 is severely hindered due to its extremely poor water solubility and adverse side effects. Here, two series of novel 20-substituted (20S)-10,11-methylenedioxy-camptothecin coupled with 5-substituted uracils and other heterocyclic rings through glycine were synthesized. All the derivatives showed superior cytotoxic activities in vitro with IC50 values in the nanomolar range. Among them, 12e displayed higher cytotoxic activities in several cancer cell lines with better water solubility than FL118. Our results further showed that, like FL118, 12e inhibited cell proliferation resulting from cell cycle arrest and apoptosis by blocking the anti-apoptotic gene transcription of survivin, Mcl-1, Bcl-2, and XIAP in both A549 cells and NCI-H446 cells. Furthermore, 12e did not show any inhibitory activity on Topo I, which is involved in hematopoietic toxicity. In vivo, 12e showed similar antitumor efficacy to FL118 but lower toxicity. Our findings indicate that 12e is a promising therapeutic agent for cancer treatment, and the core structure of FL118 represents a promising platform to generate novel FL118-based antitumor drugs.
Cell Type-Specific Oxidative Stress Genomic Signatures in the Globus Pallidus of Dopamine-Depleted Mice

Neuron subtype dysfunction is a key contributor to neurologic disease circuits, but identifying associated gene regulatory pathways is complicated by the molecular complexity of the brain. For example, parvalbumin-expressing (PV+) neurons in the external globus pallidus (GPe) are critically involved in the motor deficits of dopamine-depleted mouse models of Parkinson's disease, where cell type-specific optogenetic stimulation of PV+ neurons over other neuron populations rescues locomotion. Despite the distinct roles these cell types play in the neural circuit, the molecular correlates remain unknown because of the difficulty of isolating rare neuron subtypes. To address this issue, we developed a new viral affinity purification strategy, Cre-Specific Nuclear Anchored Independent Labeling, to isolate Cre recombinase-expressing (Cre+) nuclei from the adult mouse brain. Applying this technology, we performed targeted assessments of the cell type-specific transcriptomic and epigenetic effects of dopamine depletion on PV+ and PV– cells within three brain regions of male and female mice: GPe, striatum, and cortex. We found GPe PV+ neuron-specific gene expression changes that suggested increased hypoxia-inducible factor 2α signaling. Consistent with transcriptomic data, regions of open chromatin affected by dopamine depletion within GPe PV+ neurons were enriched for hypoxia-inducible factor family binding motifs. The gene expression and epigenomic experiments performed on PV+ neurons isolated by Cre-Specific Nuclear Anchored Independent Labeling identified a transcriptional regulatory network mediated by the neuroprotective factor Hif2a as underlying neural circuit differences in response to dopamine depletion. SIGNIFICANCE STATEMENT Cre-Specific Nuclear Anchored Independent Labeling is an enhanced, virus-based approach to isolate nuclei of a specific cell type for transcriptome and epigenome interrogation that decreases dependency on transgenic animals. Applying this technology to GPe parvalbumin-expressing neurons in a mouse model of Parkinson's disease, we discovered evidence for an upregulation of the oxygen homeostasis maintaining pathway involving Hypoxia-inducible factor 2α. These results provide new insight into how neuron subtypes outside the substantia nigra pars compacta may be compensating at a molecular level for differences in the motor production neural circuit during the progression of Parkinson's disease. Furthermore, they emphasize the utility of cell type-specific technologies, such as Cre-Specific Nuclear Anchored Independent Labeling, for isolated assessment of specific neuron subtypes in complex systems.
Hypoglycemic Effect of Prolamin from Cooked Foxtail Millet (Setaria italic) on Streptozotocin-Induced Diabetic Mice

Millet proteins have been demonstrated to possess glucose-lowering and lipid metabolic disorder modulation functions against diabetes; however, the molecular mechanisms underlying their anti-diabetic effects remain unclear. The present study aimed to investigate the hypoglycemic effect of prolamin from cooked foxtail millet (PCFM) on type 2 diabetic mice, and explore the gut microbiota and serum metabolic profile changes that are associated with diabetes attenuation by PCFM. Our diabetes model was established using a high-fat diet combined with streptozotocin before PCFM or saline was daily administrated by gavage for 5 weeks. The results showed that PCFM ameliorated glucose metabolism disorders associated with type 2 diabetes. Furthermore, the effects of PCFM administration on gut microbiota and serum metabolome were investigated. 16S rRNA gene sequencing analysis indicated that PCFM alleviated diabetes-related gut microbiota dysbiosis in mice. Additionally, the serum metabolomics analysis revealed that the metabolite levels disturbed by diabetes were partly altered by PCFM. Notably, the decreased D-Glucose level caused by PCFM suggested that its anti-diabetic potential can be associated with the activation of glycolysis and the inhibition of gluconeogenesis, starch and sucrose metabolism and galactose metabolism. In addition, the increased serotonin level caused by PCFM may stimulate insulin secretion by pancreatic β-cells, which contributed to its hypoglycemic effect. Taken together, our research demonstrated that the modulation of gut microbiota composition and the serum metabolomics profile was associated with the anti-diabetic effect of PCFM.
Loose Fibrin Clot Structure and Increased Susceptibility to Lysis Characterize Patients with Central Acute Pulmonary Embolism: The Impact of Isolated Embolism

Abstract Background Prothrombotic fibrin clot properties are associated with higher early mortality risk in acute pulmonary embolism (PE) patients. It is unknown whether different types of PE are associated with particular clot characteristics. Methods We assessed 126 normotensive, noncancer acute PE patients (median age: 59 [48–70] years; 52.4% males), who were categorized into central versus peripheral PE with or without concomitant deep vein thrombosis (DVT). Plasma fibrin clot permeability (K s), clot lysis time (CLT), thrombin generation, platelet-derived markers, and fibrinolytic parameters were measured on admission. Plasma fibrin clot morphology was assessed by scanning electron microscopy (SEM). Results Patients with central PE (n = 76; 60.3%) compared with peripheral PE (n = 50; 39.7%) had 17.8% higher K s and 14.3% shortened CLT (both p < 0.01 after adjustment for potential confounders including fibrinogen), with no differences between segmental and subsegmental PE. SEM analysis demonstrated larger fibrin fiber diameter and pore size in central PE compared with peripheral PE (both p < 0.01). For isolated PE, there was 23.3% higher K s in central PE than in peripheral PE (n = 24; 19%) with no differences in other variables. Central PE combined with DVT (n = 45; 35.7%), as compared with central isolated PE (n = 31; 24.6%), was associated with shortened CLT (all p < 0.05). Conclusion Our findings suggest that looser fibrin networks composed of thicker fibers with increased susceptibility to lysis characterize patients with central PE, suggesting that fibrin clot phenotype affects the size of thrombi occluding the pulmonary arteries, highlighting the role of fibrin structures in thrombus formation and stability.