Miracle-dz/UniFAR-FTUs huggingface dataset:
Environmental Parameters and Substrate Type Drive Microeukaryotic Community Structure During Short-Term Experimental Colonization in Subtropical Eutrophic Freshwaters

Microeukaryotes are key components of aquatic ecosystems and play crucial roles in aquatic food webs. However, influencing factors and potential assembly mechanisms for microeukaryotic community on biofilms are rarely studied. Here, those of microeukaryotic biofilms in subtropical eutrophic freshwaters were investigated for the first time based on 2,585 operational taxonomic units (OTUs) from 41 samples, across different environmental conditions and substrate types. Following conclusions were drawn: (1) Environmental parameters were more important than substrate types in structuring microeukaryotic community of biofilms in subtropical eutrophic freshwaters. (2) In the fluctuating river, there was a higher diversity of OTUs and less predictability of community composition than in the stable lake. Sessile species were more likely to be enriched on smooth surfaces of glass slides, while both free-swimming and attached organisms occurred within holes inside PFUs (polyurethane foam units). (3) Both species sorting and neutral process were mechanisms for assembly of microeukaryotic biofilms, but their importance varied depending on different habitats and substrates. (4) The effect of species sorting was slightly higher than the neutral process in river biofilms due to stronger environmental filtering. Species sorting was a stronger force structuring communities on glass slides than PFUs with more niche availability. Our study sheds light on assembly mechanisms for microeukaryotic community on different habitat and substrate types, showing that the resulting communities are determined by both sets of variables, in this case primarily habitat type. The balance of neutral process and species sorting differed between habitats, but the high alpha diversity of microeukaryotes in both led to similar sets of lifecycle traits being selected for in each case.
Scientist Online: Entomologists' Experiences Engaging With School Audiences Through Skype in the Classroom

Scientists often aim to inspire others who may not be as knowledgeable about specific scientific concepts to increase science interest and knowledge, mobilize communities for social and political change, and encourage the pursuit of STEM careers. Ideally, scientists would interact with public audiences face-to-face for rich dialogue and engagement at community venues such as libraries, churches, schools, and grocery stores. However, research shows the majority of Americans spend their time searching for scientific information on the web. As an alternative, some scientists have taken to participating in produced online video. Some online video platforms allow for synchronous dialogic engagement, such as Skype, for video-sharing. Skype in the Classroom is offered for school interactions with content experts through virtual field trips. The following study provides a practical overview of a specific program called “Scientist Online: The Science of Mosquitoes,” its application of Skype in the Classroom two-way video technology for fostering STEM dialogue, and a qualitative analysis of scientists' experiences and scientist-student interactions. The authors analyzed interviews with the participating scientists and call transcriptions of the scientist-student conversations with five schools and more than 100 students from Florida, Pennsylvania, Canada, and Pakistan. Skype in the Classroom served as an effective platform for scientists to engage with various school audiences, improving their confidence in science communication. The online synchronous format of Skype in the Classroom prompted scientists to prepare content and conduct background research of participants' locations in advance. Scientists recognized the importance of their roles as science communicators to dialogue about science in digestible terms, and Skype in the Classroom allowed them to balance their roles as researchers and contributors to public outreach. Recommendations are also discussed.
Single Cell Genomics Reveals Viruses Consumed by Marine Protists

The predominant model of the role of viruses in the marine trophic web is that of the “viral shunt,” where viral infection funnels a substantial fraction of the microbial primary and secondary production back to the pool of dissolved organic matter. Here, we analyzed the composition of non-eukaryotic DNA associated with individual cells of small, planktonic protists in the Gulf of Maine (GoM) and the Mediterranean Sea. We found viral DNA associated with a substantial fraction cells from the GoM (51%) and the Mediterranean Sea (35%). While Mediterranean SAGs contained a larger proportion of cells containing bacterial sequences (49%), a smaller fraction of cells contained bacterial sequences in the GoM (19%). In GoM cells, nearly identical bacteriophage and ssDNA virus sequences where found across diverse lineages of protists, suggesting many of these viruses are non-infective. The fraction of cells containing viral DNA varied among protistan lineages and reached 100% in Picozoa and Choanozoa. These two groups also contained significantly higher numbers of viral sequences than other identified taxa. We consider mechanisms that may explain the presence of viral DNA in protistan cells and conclude that protistan predation on free viral particles contributed to the observed patterns. These findings confirm prior experiments with protistan isolates and indicate that the viral shunt is complemented by a viral link in the marine microbial food web. This link may constitute a sink of viral particles in the ocean and has implications for the flow of carbon through the microbial food web.
2(5H)-Furanone Disrupts Bacterial Biofilm Formation and Indirectly Reduces the Settlement of Plantigrades of the Mussel Mytilus coruscus

Bacterial quorum sensing (QS) is a chemical communication that allows bacteria to coordinate their population and gene regulation in response to threshold concentrations of QS signals. Here, we study the effect of QS inhibitor 2(5H)-furanone (FUR) on the formation of Pseudoalteromonas marina ECSMB14103 biofilms and the effect of these biofilms on the settlement of plantigrades of the mussel Mytilus coruscus. FUR was added during biofilm formation of P. marina ECSMB14103 or in the settlement bioassay. FUR at 10–4 M added during biofilm formation significantly (p < 0.05) reduced the settlement of plantigrades, and it was associated with a significant (p < 0.05) reduction of bacterial density. The visualization of individual substances in biofilms shows that β-polysaccharides are the major components in the biofilm matrix. The decreased settlement rate may be attributed to the reduction of the biovolume of α-polysaccharides and β-polysaccharides in biofilms. The transcriptome of biofilms treated with 10–4 M FUR shows 61 genes are differentially expressed. Aspartate kinase and the flagellar assembly protein fliH gene are significantly affected after exposure to 10–4 M FUR (p < 0.05). They are involved in the synthesis of the bacterial cell wall and the mobility of bacteria, respectively. Exposure to 10–4 M FUR also significantly changes the carbapenem biosynthesis pathway, which is regulated by the QS system in bacteria (p < 0.05). These data suggest that FUR directly affects biofilm formation by altering extracellular polymeric substances (EPS) components and metabolic processes, which, in turn, indirectly reduce the settlement of plantigrades. The present study provides new insights into the molecular mechanisms of controlling biofouling.
Carotid Extra-Media Thickness in Children: Relationships With Cardiometabolic Risk Factors and Endothelial Function

Background: Emerging evidence suggests that structural adventitial modifications and perivascular adipose tissue (PAT) may have a role in early atherogenesis. In a cohort of children and adolescents, we explored (1) the association of carotid extra-media thickness (cEMT), an ultrasound measure whose main determinants are arterial adventitia and PAT, with obesity and its cardiometabolic complications; and (2) the interplay between cEMT and endothelial function. Methods: The study participants included 286 youths (age, 6–16 years; 154 boys, and 132 girls). Anthropometric and laboratory parameters, liver ultrasound, vascular structure measures [cEMT and carotid intima-media thickness (cIMT)], endothelial function [brachial artery flow-mediated dilation (FMD)] were obtained in all subjects. Non-alcoholic fatty liver disease (NAFLD) was diagnosed in the presence of hepatic fat on ultrasonography, in the absence of other causes of liver disease. Diagnosis of metabolic syndrome (MetS) was established on the basis of three or more of the following cardiovascular disease (CVD) risk variables: abdominal obesity, high triglycerides, low high-density lipoprotein cholesterol, elevated blood pressure (BP), and impaired fasting glucose. Results: cEMT demonstrated significant associations with body-mass index (BMI) and waist circumference (WC), BP, insulin resistance, NAFLD, and inflammation. No association was found between cEMT and lipid values, and between cEMT and MetS. A stepwise multivariate linear regression analysis indicated that WC (β coefficient, 0.35; P < 0.0001) was the only determinant of cEMT, independently of other major cardiometabolic risk factors. Further adjustment for cIMT did not significantly alter this association. FMD was correlated to age, Tanner stage, total and abdominal obesity, BP, NAFLD, and cEMT. The association between FMD and cEMT was independent of age, sex, Tanner stage, WC, and BMI (β coefficient, −0.14; P = 0.027). After controlling for CVD risk factors and basal brachial artery diameter, cEMT remained associated with FMD (β coefficient, −0.11; P = 0.049). Conclusions: In youths, cEMT is associated with abdominal fat, a well-established body fat depot with important implications for cardiovascular diseases. Furthermore, cEMT is related to FMD, suggesting that arterial adventitia and PAT may be involved in the early changes in endothelial function.
Hyper-Inflammatory Monocyte Activation Following Endotoxin Exposure in Food Allergic Infants

Several recent studies have reported a key role for innate cell hyper-responsiveness in food allergy. This has predominantly been observed in early life, with evidence that innate immune function may return to baseline if food allergy resolves in later childhood. Hallmarks of hyper-responsiveness include increased circulating frequency of monocytes and altered innate cell cytokine responses to in vitro exposure with bacterial endotoxin. These features mirror the defining signatures of trained innate immunity, seen in other complex diseases. In this study, detailed immune cell and cytokine profiling was performed on peripheral blood mononuclear cells at baseline from 27 1 year old infants in the HealthNuts cohort (n = 16 egg allergic and n = 11 non-allergic healthy controls) and following monocyte stimulation. We show that egg allergic infants have increased frequency of circulating monocytes, reduced numbers of regulatory CD4 T cells and increased monocyte: CD4 T cell ratios relative to healthy controls. Monocytes from both egg allergic and non-allergic infants responded to endotoxin stimulation with rapid cytokine production and downregulation of the surface receptor CD16, however monocytes from egg allergic infants were hyper-responsive, producing significantly more inflammatory cytokines (TNFα, IL-6, IL-1β, IL-8) and innate cell recruiting factors (MIP-1α) than healthy controls. This work indicates that monocytes of food allergic infants are programmed to a hyper-inflammatory phenotype and that the development of food allergy may be associated with trained immunity in early life.
Economic Evaluation of Interventions in Parkinson's Disease: A Systematic Literature Review

Parkinson's disease (PD) management comprises of drug treatments, surgery, and physical activity/occupational therapies to relieve PD's symptoms. The aim of this study is twofold; first, to appraise recent economic evaluation studies on PD management in order to update the existing knowledge; and second, to facilitate decision making on PD management by assessing the cost‐effectiveness of all types of PD interventions.
Oxidative DNA Damage Accelerates Skin Inflammation in Pristane-Induced Lupus Model

Systemic Lupus Erythematosus (SLE) is a chronic inflammatory autoimmune disease in which type I interferons (IFN) play a key role. The IFN response can be triggered when oxidized DNA engages the cytosolic DNA sensing platform cGAS-STING, but the repair mechanisms that modulate this process and govern disease progression are unclear. To gain insight into this biology, we interrogated the role of oxyguanine glycosylase 1 (OGG1), which repairs oxidized guanine 8-Oxo-2′-deoxyguanosine (8-OH-dG), in the pristane-induced mouse model of SLE. Ogg1−/− mice showed increased influx of Ly6Chi monocytes into the peritoneal cavity and enhanced IFN-driven gene expression in response to short-term exposure to pristane. Loss of Ogg1 was associated with increased auto-antibodies (anti-dsDNA and anti-RNP), higher total IgG, and expression of interferon stimulated genes (ISG) to longer exposure to pristane, accompanied by aggravated skin pathology such as hair loss, thicker epidermis, and increased deposition of IgG in skin lesions. Supporting a role for type I IFNs in this model, skin lesions of Ogg1−/− mice had significantly higher expression of type I IFN genes (Isg15, Irf9, and Ifnb). In keeping with loss of Ogg1 resulting in dysregulated IFN responses, enhanced basal and cGAMP-dependent Ifnb expression was observed in BMDMs from Ogg1−/− mice. Use of the STING inhibitor, H151, reduced both basal and cGAMP-driven increases, indicating that OGG1 regulates Ifnb expression through the cGAS-STING pathway. Finally, in support for a role for OGG1 in the pathology of cutaneous disease, reduced OGG1 expression in monocytes associated with skin involvement in SLE patients and the expression of OGG1 was significantly lower in lesional skin compared with non-lesional skin in patients with Discoid Lupus. Taken together, these data support an important role for OGG1 in protecting against IFN production and SLE skin disease.
A Potential Biomarker of Combination of Tumor Mutation Burden and Copy Number Alteration for Efficacy of Immunotherapy in KRAS-Mutant Advanced Lung Adenocarcinoma

Objectives The Kirsten Rat Sarcoma (KRAS) mutation is the commonest oncogenic drive mutation in lung adenocarcinoma (LUAD) and immunotherapy may be quite promising for KRAS-mutant LUAD. While the effects of tumor mutation burden (TMB) and copy number alteration (CNA) are poorly understood in this illness, our study aimed to explore the roles TMB and CNA play in the prediction of response to immune checkpoint inhibitor (ICI) therapy in advanced KRAS-mutant LUAD. Methods Mutation and clinical data were downloaded from cBioPortal. We evaluated KRAS mutation status and divided patients into different subgroups based on TMB and CNA cutoffs to investigate the predictive value of these biomarkers on ICI response. Results KRAS mutation with concurrent TP53 or STK11 mutations had higher TMB and CNA compared to KRAS mutation alone. The KRAS G12C and G > T mutation subgroups, with TP53 or STK11 co-mutation, also had higher TMB and CNA. We found that TMB and CNA were independently associated with progression-free survival (PFS) and durable clinical benefits (DCB); TMB was positively correlated with PFS (P = 0.0074) and DCB (P = 0.0008) while low CNA was associated with prolonged PFS (P = 0.0060) and DCB (P = 0.0018). However, TMB alone did not distinguish benefits among KRAS-mutant patients. Notably, when combining TMB and CNA, low TMB and high CNA revealed worse outcomes of ICI therapy (mPFS: 2.20m, P = 0.0023; proportion of DCB: 24%, P = 0.0001). Conclusion The combination of TMB and CNA provides more sensible and accurate prediction of ICI response than individual factors in KRAS-mutant LUAD. Moreover, low TMB and high CNA can be utilized as a potential biomarker to predict adverse outcome in KRAS-mutant LUAD.
Genomic Heritability and Genome-Wide Association Studies of Plasma Metabolites in Crossbred Beef Cattle

Metabolites, substrates or products of metabolic processes, are involved in many biological functions, such as energy metabolism, signaling, stimulatory and inhibitory effects on enzymes and immunological defense. Metabolomic phenotypes are influenced by combination of genetic and environmental effects allowing for metabolome-genome-wide association studies (mGWAS) as a powerful tool to investigate the relationship between these phenotypes and genetic variants. The objectives of this study were to estimate genomic heritability and perform mGWAS and in silico functional enrichment analyses for a set of plasma metabolites in Canadian crossbred beef cattle. Thirty-three plasma metabolites and 45,266 single nucleotide polymorphisms (SNPs) were available for 475 animals. Genomic heritability for all metabolites was estimated using genomic best linear unbiased prediction (GBLUP) including genomic breed composition as covariates in the model. A single-step GBLUP implemented in BLUPF90 programs was used to determine SNP P values and the proportion of genetic variance explained by SNP windows containing 10 consecutive SNPs. The top 10 SNP windows that explained the largest genetic variation for each metabolite were identified and mapped to detect corresponding candidate genes. Functional enrichment analyses were performed on metabolites and their candidate genes using the Ingenuity Pathway Analysis software. Eleven metabolites showed low to moderate heritability that ranged from 0.09 ± 0.15 to 0.36 ± 0.15, while heritability estimates for 22 metabolites were zero or negligible. This result indicates that while variations in 11 metabolites were due to genetic variants, the majority are largely influenced by environment. Three significant SNP associations were detected for betaine (rs109862186), L-alanine (rs81117935), and L-lactic acid (rs42009425) based on Bonferroni correction for multiple testing (family wise error rate <0.05). The SNP rs81117935 was found to be located within the Catenin Alpha 2 gene (CTNNA2) showing a possible association with the regulation of L-alanine concentration. Other candidate genes were identified based on additive genetic variance explained by SNP windows of 10 consecutive SNPs. The observed heritability estimates and the candidate genes and networks identified in this study will serve as baseline information for research into the utilization of plasma metabolites for genetic improvement of crossbred beef cattle.
Cellular Origins of the Lymphatic Endothelium: Implications for Cancer Lymphangiogenesis

The lymphatic system plays important roles in physiological and pathological conditions. During cancer progression in particular, lymphangiogenesis can exert both positive and negative effects. While the formation of tumor associated lymphatic vessels correlates with metastatic dissemination, increased severity and poor patient prognosis, the presence of functional lymphatics is regarded as beneficial for anti-tumor immunity and cancer immunotherapy delivery. Therefore, a profound understanding of the cellular origins of tumor lymphatics and the molecular mechanisms controlling their formation is required in order to improve current strategies to control malignant spread. Data accumulated over the last decades have led to a controversy regarding the cellular sources of tumor-associated lymphatic vessels and the putative contribution of non-endothelial cells to this process. Although it is widely accepted that lymphatic endothelial cells (LECs) arise mainly from pre-existing lymphatic vessels, additional contribution from bone marrow-derived cells, myeloid precursors and terminally differentiated macrophages, has also been claimed. Here, we review recent findings describing new origins of LECs during embryonic development and discuss their relevance to cancer lymphangiogenesis.
Nature-Assembled Structures for Delivery of Bioactive Compounds and Their Potential in Functional Foods

Consumers are demanding more natural, healthy, and high-quality products. The addition of health-promoting substances, such as bioactive compounds, to foods can boost their therapeutic effect. However, the incorporation of bioactive substances into food products involves several technological challenges. They may have low solubility in water or poor stability in the food environment and/or during digestion, resulting in a loss of their therapeutic properties. Over recent years, the encapsulation of bioactive compounds into laboratory-engineered colloidal structures has been successful in overcoming some of these hurdles. However, several nature-assembled colloidal structures could be employed for this purpose and may offer many advantages over laboratory-engineered colloidal structures. For example, the casein micelles and milk fat globules from milk and the oil bodies from seeds were designed by nature to deliver biological material or for storage purposes. These biological functional properties make them good candidates for the encapsulation of bioactive compounds to aid in their addition into foods. This review discusses the structure and biological function of different nature-assembled carriers, preparation/isolation methods, some of the advantages and challenges in their use as bioactive compound delivery systems, and their behavior during digestion.
Safety and tolerability results from a phase I study of MEDI4736, a human IgG1 anti-programmed cell death-ligand-1 (PD-L1) antibody, combined with gefitinib in patients (pts) with non-small-cell lung cancer (NSCLC).

3047 Background: MEDI4736 is a human IgG1 monoclonal antibody which blocks PD-L1 binding to PD-1 and CD-80 with high affinity and selectivity. A Phase I open-label multicenter study was initiated to evaluate MEDI4736 combined with the EGFR tyrosine kinase inhibitor (TKI) gefitinib in NSCLC (NCT02088112). Dose escalation phase data are reported. Methods: Key eligibility criteria included: locally advanced/metastatic NSCLC of any EGFR mutation status, relapsed/refractory/intolerant of standard treatment; ≤ 4 prior therapies. Cohort A received MEDI4736 3 mg/kg (starting dose) every 2 weeks plus gefitinib 250 mg once-daily (QD). If no dose-limiting toxicities were observed, Cohort B received MEDI4736 at a higher dose of 10 mg/kg every two weeks plus gefitinib 250 mg QD. Primary endpoint: safety/tolerability and recommended dose of the MEDI4736 plus gefitinib combination. Secondary endpoints included: tumor response (RECIST 1.1); pharmacokinetics (PK); immunogenicity. Results: Of 10 pts (Cohort A = 3; Cohort B.