Miracle-dz/UniFAR-FTUs huggingface dataset:
Trans-Cinnamaldehyde, Eugenol and Carvacrol Reduce Campylobacter jejuni Biofilms and Modulate Expression of Select Genes and Proteins

Campylobacter jejuni is the leading cause of human foodborne illness globally, and is strongly linked with the consumption of contaminated poultry products. Several studies have shown that C. jejuni can form sanitizer tolerant biofilm leading to product contamination, however, limited research has been conducted to develop effective control strategies against C. jejuni biofilms. This study investigated the efficacy of three generally recognized as safe status phytochemicals namely, trans-cinnamaldehyde (TC), eugenol (EG), or carvacrol (CR) in inhibiting C. jejuni biofilm formation and inactivating mature biofilm on common food contact surfaces at 20 and 37°C. In addition, the effect of phytochemicals on biofilm architecture and expression of genes and proteins essential for biofilm formation was evaluated. For the inhibition study, C. jejuni was allowed to form biofilms either in the presence or absence of sub-inhibitory concentrations of TC (0.75 mM), EG (0.61 mM), or CR (0.13 mM) for 48 h and the biofilm formation was quantified at 24-h interval. For the inactivation study, C. jejuni biofilms developed at 20 or 37°C for 48 h were exposed to the phytochemicals for 1, 5, or 10 min and surviving C. jejuni in the biofilm were enumerated. All phytochemicals reduced C. jejuni biofilm formation as well as inactivated mature biofilm on polystyrene and steel surface at both temperatures (P < 0.05). The highest dose of TC (75.64 mM), EG (60.9 mM) and CR (66.56 mM) inactivated (>7 log reduction) biofilm developed on steel (20°C) within 5 min. The genes encoding for motility systems (flaA, flaB, and flgA) were downregulated by all phytochemicals (P < 0.05). The expression of stress response (cosR, ahpC) and cell surface modifying genes (waaF) was reduced by EG. LC-MS/MS based proteomic analysis revealed that TC, EG, and CR significantly downregulated the expression of NapA protein required for oxidative stress response. The expression of chaperone protein DnaK and bacterioferritin required for biofilm formation was reduced by TC and CR. Scanning electron microscopy revealed disruption of biofilm architecture and loss of extracellular polymeric substances after treatment. Results suggest that TC, EG, and CR could be used as a natural disinfectant for controlling C. jejuni biofilms in processing areas.
A Microbiomic Analysis of a Pasture-Raised Broiler Flock Elucidates Foodborne Pathogen Ecology Along the Farm-To-Fork Continuum

While conventionally grown poultry continues to dominate the U. S. poultry industry, there is an increasing demand for locally-grown, “all natural” alternatives. The use of next generation sequencing allows for not only the gross (e.g., community structure) but also fine-scale (e.g., taxa abundances) examination of these complex microbial communities. This data provides a better understanding of how a pasture flock's microbiome changes throughout the production life cycle and how that change in microbial ecology changes foodborne pathogens in alternative poultry production systems. In order to understand this ecology better, pooled broiler samples were taken during the entire flock life cycle, from pre-hatch gastrointestinal samples (N = 12) to fecal samples from the brood (N = 5), and pasture (N = 10) periods. Additional samples were taken during processing, including skin and feather rinsates (N = 12), ceca (N = 12), and whole carcass rinses (N = 12), and finally whole carcasss rinsates of final products (N = 3). Genomic DNA was extracted, 16S rDNA microbiome sequencing was conducted (Illumina MiSeq), and microbiomes were analyzed and compared using QIIME 1.9. 1 to determine how microbiomes shifted throughout production continuum, as well as what environmental factors may be influencing these shifts. Significant microbiome shifts occurred during the life cycle of the pasture broiler flock, with the brood and pasture fecal samples and cecal samples being very distinct from the other pre-hatch, processing, and final product samples. Throughout these varied microbiomes, there was a stable core microbiome containing 13 taxa. Within this core microbiome, five taxa represented known foodborne pathogens (Salmonella, Campylobacter) or potential/emerging pathogens (Pseudomonas, Enterococcus, Acinetobacter) whose relative abundances varied throughout the farm-to-fork continuum, although all were more prevalent in the fecal samples. Additionally, of the 25 physiochemical and nutrient variables measured from the fecal samples, the carbon to nitrogen ratio was one of the most significant variables to warrant further investigations because it impacted both general fecal microbial ecology and Campylobacter and Enterococcus taxa within the core fecal microbiomes. These findings demonstrate the need for further longitudinal, farm-to-fork studies to understand the ecology of the microbial ecology of pasture production flocks to improve animal, environmental, and public health.
Patency of Branch Vessels After Pipeline Embolization: Comparison of Various Branches

Objective: Pipeline embolization devices (PEDs) are widely used to exclude intracranial aneurysms from their parent arteries. Side branches covered by PEDs, however, sometimes experience occlusion and related symptoms. Thus, predictors of branch occlusion and the patency and clinical outcomes of these branches are concerning. Methods: We conducted a retrospective review of consecutive patients who had been treated with PEDs in our institution during 2015–2018 to identify those in whom one or more branches were involved. Pretreatment and follow-up angiograms were assessed to determine patency of the involved branches. Demographic and clinical data, treatment strategies, and comorbidities were collected to investigate their relations with branch occlusion. Results: Altogether, 173 branches [24 (13.9%) occluded), 29 (16.8%) with diminished flow] in 126 patients were studied. Five patients (OphA involved) presented with blurred vision and 1 patient (ACA involved) presented with headache. None of the other patients had neurologic complications or clinical strokes related to branch occlusion. Multivariate analysis identified that small PED diameter [p = 0.003, odds ratio (OR) = 0.168], branches arising from the aneurysm (p = 0.004, OR = 6.614), and involvement of the anterior cerebral artery (ACA) (p < 0.001, OR = 25.656) significantly predicted branch occlusion. Conclusion: Branch occlusion rate after PED deployment was low and most occlusions was asymptomatic. Branches with rich collateral supply were more likely to occlude, especially the ACA. Smaller PED diameter, branches arising from the aneurysm, and ACA involvement were significant predictors of branch occlusion after PED treatment.
The Scales That Limit: The Physical Boundaries of Evolution

Organisms are subject to the laws of physics, so the process of evolution by genetic variation and natural selection is constrained by these fundamental laws. Classic and recent studies of the biophysical limits facing organisms have shown how fundamental physical constraints can be used to predict broad-scale relationships between body size and organismal biomechanics and physiology. These relationships often take the form of power laws across a wide range of body sizes for organisms sharing a common body plan. However, such biophysical perspectives have not been fully connected with the detailed dynamics of evolution by natural selection, nor with the variation between species around the central scaling relationships. Here we first discuss what a general biophysical theory of evolution would require and provide an abstracted framework for aspects of such a theory. We discuss how such a theory should eventually be capable of not only predicting scaling relationships, but also of identifying the types of tradeoffs shown by different species occupying a particular niche. We then discuss how one key higher-order requirement of a biophysical theory of evolution is the ability to predict asymptotic behavior and the limits of a particular body plan. We use several examples to illustrate how dominant physical constraints can be used to predict the minimum and maximum body sizes for a particular body plan, and we argue that prediction of these limits is essential for identifying the dominant physical constraints for a given category of organisms. Our framework proposes that a major portion of fitness should be the overlay of how all traits of a particular body plan interact with fundamental physical constraints. In our examples we investigate multiple physical limits on particular traits, and also how the interaction of a number of traits determines the size limits on entire body plans, such as those of vascular plants. We use bacteria as an example of the shifts in which traits are most limiting at various sizes. Finally, we address the effects of environmental conditions and ecological interactions in determining which of the physical constraints faced by organisms are most likely to affect their fitness.
Violence at School and the Well-Being of Teachers. The Importance of Positive Relationships

In the discipline of positive psychology, “well-being” is considered a fundamental aspect of “human flourishing. ” Inherent to this multidimensional model are emotional, psychological, and social forms of well-being, which can be grounded in positive relationships in the work environment. By adopting an interpretive framework that emphasizes these dynamics, researchers are able to focus on elements that actively help sustain the process of flourishing, rather than on negative environmental features that should be avoided if possible. Within this broader discussion, the specific question of teachers’ well-being is one that has global relevance and merits greater academic attention. After all, it has significant consequences for the educational environment and students’ ability to learn. The literature suggests that teachers are increasingly exposed to violence on the part of students and/or their parents. Inappropriate and/or aggressive behavior like this can reduce a teacher’s occupational well-being and make it more difficult to build positive relationships in the classroom. Ultimately, it is one of the most serious work-related stress factors affecting the profession today. Previous studies have attempted to characterize the contexts in which violence occurs, and its negative impact on both the individuals involved and the broader educational climate. Less attention has been devoted to the capacity of teachers to deal with violence and develop a more resilient mindset. The positive psychology perspective focuses on well-being as a multidimensional construct wherein psychosocial and physical comfort does not simply arise provided there is an absence of suffering and violence. Rather, according to this model, such experiences can be counteracted by a capacity to endure and build positive environments. With these considerations in mind, our study presents data gathered in primary and secondary schools in northern Italy. A total 475 teachers completed an online, self-report questionnaire. The results indicate that teachers can experience occupational well-being even if they are subjected to aggressive behaviors. Supportive leadership and good relationships with colleagues may be considered valuable resources for fostering well-being among teachers.
Is Innate Memory a Double-Edge Sword in Alzheimer's Disease? A Reappraisal of New Concepts and Old Data

An emergent concept in immunology suggests that innate immune system is capable to undergo non-specific long-term responses and to provide resistance by modifying the reactivity to sequential pathogen challenge. This phenomenon, named innate memory, involves epigenetic, and metabolic reprogramming of innate immune cells. Current literature shows that the innate memory process has a mainly beneficial role in host defense, but sometimes can exert detrimental effects, as common in many diseases. Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and dementia. Accumulating findings demonstrate that inflammation is involved in AD pathogenesis and progression and recent genetic and functional data confirm the driving role of the innate immune component in the disease. Furthermore, AD patients show high burden of the most relevant infectious agents and up-regulation of inflammatory features in their innate immune cells, including an activated, or “primed” status of myeloid phagocytic cells in both brain and periphery, resembling trained immunity conditions. Thus, it is conceivable that AD innate cells may be firstly involved in the attempt to resolve recurrent/persistent inflammation but then acquire a trained phenotype mostly unable to maintain the immune regulation, leaving uncontrolled or sometimes supporting the progression of neurodegeneration. The present review aims to summarize evidence evoking innate immune memory mechanisms in AD, and to interpret their potential role, either protective or harmful, in disease progression. A better understanding of such mechanisms will provide a fertile ground for development of novel diagnostic, and therapeutic pathways in AD cure.
Genetic Mapping and Prediction Analysis of FHB Resistance in a Hard Red Spring Wheat Breeding Population

Fusarium head blight (FHB) is one of the most destructive diseases in wheat worldwide. Breeding for FHB resistance is hampered by its complex genetic architecture, large genotype by environment interaction, and high cost of phenotype screening. Genomic selection (GS) is a powerful tool to enhance improvement of complex traits such as FHB resistance. The objectives of this study were to (1) investigate the genetic architecture of FHB resistance in a North Dakota State University (NDSU) hard red spring wheat breeding population, (2) test if the major QTL Fhb1 and Fhb5 play an important role in this breeding population; and (3) assess the potential of GS to enhance breeding efficiency of FHB resistance. A total of 439 elite spring wheat breeding lines from six breeding cycles were genotyped using genotyping-by-sequencing (GBS) and 102,147 SNP markers were obtained. Evaluation of FHB severity was conducted in 10 unbalanced field trials across multiple years and locations. One QTL for FHB resistance was identified and located on chromosome arm 1AL, explaining 5.3% of total phenotypic variation. The major type II resistance QTL Fhb1 only explained 3.1% of total phenotypic variation and the QTL Fhb5 was not significantly associated with FHB resistance in this breeding population. Our results suggest that integration of many genes with medium/minor effects in this breeding population should provide stable FHB resistance. Genomic prediction accuracies of 0.22–0.44 were obtained when predicting over breeding cycles in this study, indicating the potential of GS to enhance the improvement of FHB resistance.
The Verbal Interaction Social Threat Task: A New Paradigm Investigating the Effects of Social Rejection in Men and Women

In recent years, digital communication and social media have taken an indispensable role in human society. Social interactions are no longer bound to real-life encounters, but more often happen from behind a screen. Mimicking an online communication platform, we developed a new, fMRI compatible, social threat paradigm to investigate sex differences in reactions to social rejection. During the Verbal Interaction Social Threat Task (VISTTA), participants initiate 30 short conversations by selecting one of four predefined opening sentences. Two computerized interlocutors respond to the opening sentence mostly with negative comments and rejections toward the participant, which should induce social-evaluative threat. Physiological and subjective responses were measured, before, during, and after the VISTTA in 61 (29 male and 32 female) first year students who received either mostly negative (n = 31; threat group) or neutral comments (n = 30; control group). Two-level behavioral validation included social threat-induced mood changes in participants, and interlocutor evaluation. The latter consisted of multiple variables such as “willingness to cooperate” after every conversation, an overall fairness evaluation of interlocutors, and evaluations per reaction indicating how positive or negative it was received. We acquired additional physiological measures including cortisol assays via saliva samples, heart rate, and blood pressure. Confirming our hypotheses, peer rejection and exclusion during the VISTTA led to less willingness to cooperate and lower fairness evaluation of interlocutors. It also induced feelings of anger and surprise and lower happiness in the social-threat group. Women showed overall higher emotion ratings compared to men. Contrary to our a priori hypothesis, the VISTTA did not induce cortisol and heart rate increases. However, the stable cortisol response in women in the threat group does not follow the circadian decline and might reflect an endocrinological response. The decline in cortisol response in men in both the threat and control group could indicate faster habituation to the VISTTA. Taken together, these findings indicate effects of social-evaluative threat on a behavioral level, and more moderate effects on the emotional and physiological level. Sex differences in affective and cortisol responses may indicate that women are more susceptible for the social-evaluative threat than men. With a realistic implementation of verbal, interactive, and social components, the VISTTA is designed as an fMRI paradigm that can be applied to elucidate the neural representation of social-evaluative threat.
Insulin Sensitivity Is Not Decreased in Adult Patients With Hypopituitarism Without Growth Hormone Replacement

Decreased insulin sensitivity in patients with hypopituitarism without GH replacement (pHP-WGHR) remains conflicting in literature. It is known that these patients present a decrease in free fat mass and an increase in fat mass. Typically, these kinds of alterations in body composition are associated with a decrease in insulin sensitivity; however, there is no consensus if this association is found in pHP-WGHR. Thus, we investigated pHP-WGHR regarding insulin sensitivity by euglycemic hyperinsulinemic clamp, the gold standard method, and body composition. In a cross-sectional study, we evaluated 15 pHP-WGHR followed up in a Service of Neuroendocrinology and 15 individuals with normal pituitary function as a control group with similar age, gender and body mass index. Insulin sensitivity was evaluated by euglycemic hyperinsulinemic clamp and homeostatic model assessment insulin resistance (HOMA-IR). Kappa coefficient evaluated the agreement between these two methods. Percentage of fat mass, percentage of free fat mass, fat mass weight and free fat mass weight were assessed by electrical bioimpedance. The pHP-WGHR presented similar insulin sensitivity to control group by euglycemic hyperinsulinemic clamp, both by the M-value, (p = 0.0913) and by the area under the glucose infusion rate curve, (p = 0.0628). These patients showed lower levels of fasting glycemia (p = 0.0128), insulin (p = 0.0007), HOMA-IR (p = 0.009). HOMA-IR shows poor concordance with euglycemic hyperinsulinemic clamp (Kappa = 0.16) in pHP-WGHR, while in the control group the agreement was good (Kappa = 0.53). The pHP-WGHR presented higher values of percentage of fat mass (p = 0.0381) and lower values of percentage of free fat mass (p = 0.0464) and free fat mass weight (0.0421) than the control group. This study demonstrated that the insulin sensitivity evaluated by euglycemic hyperinsulinemic clamp in pHP-WGHR was similar to individuals with normal pituitary function, despite the pHP-WGHR presenting higher fat mass percentage. HOMA-IR was not a good method for assessing insulin sensitivity in pHP-WGHR.
Mutation-Derived Neoantigens for Cancer Immunotherapy

Mutation-derived neoantigens distinguish tumor from normal cells. T cells can sense the HLA-presented mutations, recognize tumor cells as non-self and destroy them. Therapeutically, immunotherapy antibodies can increase the virulence of the immune system by increasing T-cell cytotoxicity targeted toward neoantigens. Neoantigen vaccines act through antigen-presenting cells, such as dendritic cells, to activate patient-endogenous T cells that recognize vaccine-encoded mutations. Infusion of mutation-targeting T cells by adoptive cell therapy (ACT) directly increases the number and frequency of cytotoxic T cells recognizing and killing tumor cells. At the same time, publicly-funded consortia have profiled tumor genomes across many indications, identifying mutations in each tumor. For example, we find basal and HER2 positive tumors contain more mutated proteins and more TP53 mutations than luminal A/B breast tumors. HPV negative tumors have more mutated proteins than HPV positive head and neck tumors and in agreement with the hypothesis that HPV activity interferes with p53 activity, only 14% of the HPV positive mutations have TP53 mutations vs. 86% of the HPV negative tumors. Lung adenocarcinomas in smokers have over four times more mutated proteins relative to those in never smokers (median 248 vs. 61, respectively). With an eye toward immunotherapy applications, we review the spectrum of mutations in multiple indications, show variations in indication sub-types, and examine intra- and inter-indication prevalence of re-occurring mutation neoantigens that could be used for warehouse vaccines and ACT.
IL-36β Promotes CD8+ T Cell Activation and Antitumor Immune Responses by Activating mTORC1

Cytokine-amplified functional CD8+ T cells ensure effective eradication of tumors. Interleukin 36α (IL-36α), IL-36β, and IL-36γ share the same receptor complex, composed of the IL-36 receptor (IL-36R), and IL-1RAcP. Recently, we revealed that IL-36γ greatly promoted CD8+ T cell activation, contributing to antitumor immune responses. However, the underlying mechanism of IL-36-mediated CD8+ T cell activation remains understood. In the current study, we proved that IL-36β had the same effect on CD8+ T cell as IL-36γ, and uncovered that IL-36β significantly activated mammalian target of rapamycin complex 1 (mTORC1) of CD8+ T cells. When mTORC1 was inhibited by rapamycin, IL-36β-stimulated CD8+ T cell activation and expansion was drastically downregulated. Further, we elucidated that IL-36β-mediated mTORC1 activation was dependent on the pathway of phosphatidylinositol 3 kinase (PI3K)/Akt, IκB kinase (IKK) and myeloid differentiation factor 88 (MyD88). Inhibition of PI3K or IKK by inhibitor, or deficiency of MyD88, respectively, suppressed mTORC1 signal, causing arrest of CD8+ T cell activation. Additionally, it was validated that IL-36β significantly promoted mTORC1 activation and antitumor function of CD8+ tumor-infiltrating lymphocytes (TILs) in vivo, resulting in inhibition of tumor growth and prolongation of survival of tumor-bearing mice. Taken together, we substantiated that IL-36β could promote CD8+ T cell activation through activating mTORC1 dependent on PI3K/Akt, IKK and MyD88 pathways, leading to enhancement of antitumor immune responses, which laid the foundations for applying IL-36β into tumor immunotherapy.