Miracle-dz/UniFAR-FTUs huggingface dataset:
In silico identification of putative roles of food-derived xeno-mirs on diet-associated cancer

Abstract Aim: Dietary miRNAs in foods were recently suggested to be absorbed into the human circulation and engage in human gene regulation. This started a debate on their possible impacts on human diseases which need further investigation. In this study, we aimed to identify the putative functions and possible implications of selected Xeno-miRs in human diseases by using bioinformatic tools. Methods: Seventy-five human absorbable Xeno-miR candidates were selected from literature and narrowed down the list to miRNAs that share sequence homologies with human miRNAs. Sixteen distinct Xeno-miRs of animal species (cow, pig, chicken) were identified to have homologs in human and they were subsequently analyzed with target prediction, functional and pathway analysis tools. Results and Conclusion: Thirteen human genes were common targets of the miRNA sets grouped by species and shown evidence of associations with various cancer categories, specifically in large intestine adenocarcinoma by Ingenuity Pathway Analysis. miRNA functional enrichment analyses also highlighted the putative involvements of the dietary miRNAs in cancer pathways. Our effort provides “in silico” evidence for implications of animal-derived dietary miRNAs in cancer-associated pathways, and this shed on light the necessities of future translational research design to investigate the roles of dietary Xeno-miRs in cancer pathophysiology and nutrition-based interventions towards cancer management.
Effective Dosage of Oral Vancomycin in Treatment for Initial Episode of Clostridioides difficile Infection: A Systematic Review and Meta-Analysis

Background: Oral vancomycin is a first line treatment for an initial episode of Clostridioides difficile infection. However, the comparative efficacy of different dosing regimens is lacking evidence in the current literature. Methods: We searched PubMed, Embase, Cochrane Library, and ClinicalTrials.gov. from inception to May 2019. Only articles published in English are reviewed. This meta-analysis compares the effects of low dose oral vancomycin (<2 g per day) versus high dose vancomycin (2 g per day) for treatment of initial Clostridioides difficile infection. Results: One randomized controlled trial and two retrospective cohort studies are included. A total of 137 patients are identified, 53 of which were treated with low dose oral vancomycin (39%) and 84 with high dose oral vancomycin (61%). There is no significant reduction in recurrence rates with high dose vancomycin compared to low dose vancomycin for treating initial episodes of non-fulminant Clostridioides difficile infection ((odds ratio (OR) 2.058, 95%, confidence interval (CI): 0.653 to 6.489). Conclusions: Based on limited data in the literature, low dose vancomycin is no different than high dose vancomycin for treatment of an initial episode of Clostridioides difficile infection in terms of recurrence rate. Additional large clinical trials comparing the different dosages of vancomycin in initial Clostridioides difficile infection are warranted.
Evaluation of Switchgrass Genotypes for Cold-Tolerant Seed Germination from Native Populations in the Northeast USA

The focus of this research was to evaluate genotypes for cold-tolerant germination from wild switchgrass (Panicum virgatum L.) populations collected in the Northeast USA. Switchgrass nurseries were established in 2008 and 2009 with seed collected from native stands of switchgrass in the Northeast USA between 1991 and 2008. Switchgrass seed harvested from individual genotypes was evaluated for cold-tolerant germination in a series of laboratory experiments. Germination assays of seed of 13 switchgrass genotypes harvested in the fall of 2016 are the primary focus of this reported research. The selected genotypes were evaluated for cold-tolerant seed germination in three experiments, during the spring of 2017, fall of 2017 and spring of 2018, (with and without stratification) using a 10/15 °C regime with a 12 h photoperiod. Germination tests showed that several genotypes had significantly higher percentage germination as well as faster germination rates expressed as T50 (number of days required to reach 50% maximum germination) when compared to Cave-in-Rock, a moderately sensitive cold-tolerant commercial cultivar established in the original switchgrass nursery as a control. A final germination test was conducted to compare seed from the original population (no selection cycle 0), with one of the top performing cold-tolerant germination genotypes, and a commercial cultivar, ‘Espresso’, developed for low seed dormancy and low temperature germination. In this test, the selected genotype had significantly higher percentage germination in the stratified treatment and was not significantly different than Espresso in the non-stratified test. These data indicate successful selection for cold-tolerant germination in switchgrass genotypes from native germplasm collected in the Northeast USA.
Protein Expression Profiling Identifies Key Proteins and Pathways Involved in Growth Inhibitory Effects Exerted by Guggulsterone in Human Colorectal Cancer Cells

Colorectal cancer (CRC) is a leading killer cancer worldwide and one of the most common malignancies with increasing incidences of mortality. Guggulsterone (GS) is a plant sterol used for treatment of various ailments such as obesity, hyperlipidemia, diabetes, and arthritis. In the current study, anti-cancer effects of GS in human colorectal cancer cell line HCT 116 was tested, potential targets identified using mass spectrometry-based label-free shotgun proteomics approach and key pathways validated by proteome profiler antibody arrays. Comprehensive proteomic profiling identified 14 proteins as significantly dysregulated. Proteins involved in cell proliferation/migration, tumorigenesis, cell growth, metabolism, and DNA replication were downregulated while the protein with functional role in exocytosis/tumor suppression was found to be upregulated. Our study evidenced that GS treatment altered expression of Bcl-2 mediated the mitochondrial release of cytochrome c which triggered the formation of apoptosome as well as activation of caspase-3/7 leading to death of HCT 116 cells via intrinsic apoptosis pathway. GS treatment also induced expression of p53 protein while p21 expression was unaltered with no cell cycle arrest. In addition, GS was found to inhibit NF-kB signaling in colon cancer cells by quelling the expression of its regulated gene products Bcl-2, cIAP-1, and survivin.
Objective and Subjective Effects of a Passive Exoskeleton on Overhead Work

Overhead work is a frequent cause of shoulder work-related musculoskeletal disorders. Exoskeletons offering arm support have the potential to reduce shoulder strain, without requiring large scale reorganization of the workspace. Assessment of such systems however requires to take multiple factors into consideration. This paper presents a thorough in-lab assessment of PAEXO, a novel passive exoskeleton for arm support during overhead work. A list of evaluation criteria and associated performance metrics is proposed to cover both objective and subjective effects of the exoskeleton, on the user and on the task being performed. These metrics are measured during a lab study, where 12 participants perform an overhead pointing task with and without the exoskeleton, while their physical, physiological and psychological states are monitored. Results show that using PAEXO reduces shoulder physical strain as well as global physiological strain, without increasing low back strain nor degrading balance. These positive effects are achieved without degrading task performance. Importantly, participants’ opinions of PAEXO are positive, in agreement with the objective measures. Thus, PAEXO seems a promising solution to help prevent shoulder injuries and diseases among overhead workers, without negatively impacting productivity.
Laxative use does not preclude diagnosis or reduce disease severity in Clostridiodes difficile infection.

BACKGROUND To optimize utility of laboratory testing for Clostridiodes difficile infection (CDI), the 2017 Infectious Diseases Society of America-Society for Healthcare Epidemiology of America (IDSA-SHEA) clinical practice guidelines recommend excluding patients from stool testing for C. difficile if they have received laxatives within the preceding 48 hours. Sparse data support this recommendation. METHODS Patients with new-onset diarrhea (≥3 bowel movements in any 24 hour period in the 48 hours before stool collection) and a positive stool C. difficile nucleic acid amplification test (NAAT) were enrolled. Laxative use within 48 hours prior to stool testing, severity of illness (defined by four distinct scoring methods), and clinical outcomes were recorded. RESULTS 209 patients with CDI were studied, 65 of whom had received laxatives. There were no significant differences in the proportion of patients meeting severe CDI criteria by four severity scoring methods, in patients receiving versus not receiving laxatives (66.2% vs 56.3%, respectively, p = 0.224) by IDSA-SHEA, the primary scoring system. Similar rates of serious outcomes attributable to CDI, including death, ICU admission, and colectomy, were observed in the laxative and no laxative groups. CONCLUSION Our study found similar rates of severe CDI and serious CDI-attributable clinical outcomes in CDI-diagnosed patients who did or did not receive laxatives. Precluding recent laxative users from CDI testing, as proposed by the IDSA-SHEA guideline, carries a potential for harm due to delayed diagnosis and treatment.
When to start and when to stop: Effects of climate on breeding in a multi‐brooded songbird

Climate warming has been shown to affect the timing of the onset of breeding of many bird species across the world. However, for multi‐brooded species, climate may also affect the timing of the end of the breeding season, and hence also its duration, and these effects may have consequences for fitness. We used 28 years of field data to investigate the links between climate, timing of breeding, and breeding success in a cooperatively breeding passerine, the superb fairy‐wren (Malurus cyaneus). This multi‐brooded species from southeastern Australia has a long breeding season and high variation in phenology between individuals. By applying a “sliding window” approach, we found that higher minimum temperatures in early spring resulted in an earlier start and a longer duration of breeding, whereas less rainfall and more heatwaves (days > 29°C) in late summer resulted in an earlier end and a shorter duration of breeding. Using a hurdle model analysis, we found that earlier start dates did not predict whether or not females produced any young in a season. However, for successful females who produced at least one young, earlier start dates were associated with higher numbers of young produced in a season. Earlier end dates were associated with a higher probability of producing at least one young, presumably because unsuccessful females kept trying when others had ceased. Despite larger scale trends in climate, climate variables in the windows relevant to this species’ phenology did not change across years, and there were no temporal trends in phenology during our study period. Our results illustrate a scenario in which higher temperatures advanced both start and end dates of individuals’ breeding seasons, but did not generate an overall temporal shift in breeding times. They also suggest that the complexity of selection pressures on breeding phenology in multi‐brooded species may have been underestimated.
Cloning and heterologous expression of the β-galactosidase gene from Bifidobacterium longum RD47 in B. bifidum BGN4.

The gene encoding β-galactosidase was cloned from Bifidobacterium longum RD47 with combinations of several bifidobacterial promoters and expressed in B. bifidum BGN4. Among the recombinant bifidobacteria, BGN4+G1 showed the highest β-galactosidase level, for which the hydrolytic activity was continuously 2.5 to 4.2 times higher than that of BGN4 and 4.3 to 9.6 times higher than that of RD47. The β-galactosidase activity of BGN4+G1 was exceedingly superior to that of any of the other 35 lactic acid bacteria. When commercial whole milk and BGN4+G1 were reacted, BGN4+G1 removed almost 50% of lactose in the milk already at 63 h and finally 61% at 93 h. This figure is about twice the lactose removal rate of conventional fermented milk. In the case of the reaction of commercial whole milk and crude enzyme extract from BGN4+G1, the β-galactosidase of BGN4+G1 eliminated 51% of the lactose in milk in 2 h. Incidentally, a comparison was done for the strength and characteristics between the strong bifidobacterial promoters shown by previous studies.
Mechanisms and functional impact of Group I metabotropic glutamate receptor modulation of excitability in mouse MNTB neurons

We examined effects of Group I metabotropic glutamate receptors on the excitability of mouse medial nucleus of the trapezoid body (MNTB) neurons. The selective agonist, S‐3,5‐dihydroxyphenylglycine (DHPG), evoked a dose‐dependent depolarization of the resting potential, increased membrane resistance, increased sag depolarization, and promoted rebound action potential firing. Under voltage‐clamp, DHPG evoked an inward current, referred to as IDHPG, which was developmentally stable through postnatal day P56. IDHPG had low temperature dependence in the range 25–34°C, consistent with a channel mechanism. However, the I‐V relationship took the form of an inverted U that did not reverse at the calculated Nernst potential for K+ or Cl−. Thus, it is likely that more than one ion type contributes to IDHPG and the mix may be voltage dependent. IDHPG was resistant to the Na+ channel blockers tetrodotoxin and amiloride, and to inhibitors of iGluR (CNQX and MK801). IDHPG was inhibited 21% by Ba2+ (500 μM), 60% by ZD7288 (100 μM) and 73% when the two antagonists were applied together, suggesting that KIR channels and HCN channels contribute to the current. Voltage clamp measurements of IH indicated a small (6%) increase in Gmax by DHPG with no change in the voltage dependence. DHPG reduced action potential rheobase and reduced the number of post‐synaptic AP failures during high frequency stimulation of the calyx of Held. Thus, activation of post‐synaptic Group I mGlu receptors modifies the excitability of MNTB neurons and contributes to the reliability of high frequency firing in this auditory relay nucleus.
Four Different Carotid Atherosclerotic Behaviors Based on Luminal Stenosis and Plaque Characteristics in Symptomatic Patients: An in Vivo Study

Correct stratification of ischemic stroke risk allows for the proper treatment of carotid atherosclerotic disease. We seek to differentiate plaque types based on stenosis level and plaque morphology. The Chinese Atherosclerosis Risk Evaluation (CARE–II) study is a cross-sectional, observational, multicenter study to assess carotid atherosclerotic plaques in symptomatic subjects using vessel wall magnetic resonance imaging. Plaque morphology and presence of plaque components were reviewed using multi-contrast magnetic resonance imaging. The carotid arteries were divided into four groups based on stenosis level and plaque components. Out of 1072 ischemic stroke subjects, 452 ipsilateral side carotid arteries were included. Significant stenosis (SS) (≥50% stenosis) with high-risk plaque (HRP) features was present in 37 arteries (8.2%), SS(+)/HRP(−) in 29 arteries (6.4%), SS(−)/HRP(+) in 57 arteries (12.6%), and SS(−)/HRP(−) in 329 arteries (72.8%). The prevalence of SS(−)/HRP(+) arteries in this cohort was substantial and had greater wall thickness than the SS(+)/HRP(−) group. These arteries may be misclassified for carotid revascularization by current guidelines based on the degree of luminal stenosis only. These findings have implications for further studies to assess stroke risk using vessel wall imaging.
Memristive Characteristic of an Amorphous Ga-Sn-O Thin-Film Device with Double Layers of Different Oxygen Density

We have found a memristive characteristic of an amorphous Ga-Sn-O (α-GTO) thin-film device with double layers of different oxygen density. The double layers are deposited using radio frequency (RF) magnetron sputtering, whose gas for the lower layer contains less oxygen, whereas that for the upper layer contains more oxygen, and it is assumed that the former contains more oxygen vacancies, whereas the latter contains fewer vacancies. The characteristic is explained by drift of oxygen and is stable without forming operation because additional structures such as filament are unnecessary. The fabrication is easy because the double layers are successively deposited simply by changing the oxygen ratio in the chamber.
Increasing Level of Interleukin-1β in Epicardial Adipose Tissue Is Associated with Persistent Atrial Fibrillation.

Epicardial adipose tissue (EAT) is associated with the pathogenesis of atrial fibrillation (AF). The role of local inflammation in persistent AF is unclear. The purpose of this study was to assess the relationship between regional interleukin-1β (IL-1β) and persistent AF. Thirty-seven persistent AF patients underwent coronary artery bypass grafting surgery were enrolled. Patients without a history of AF (n = 37), but received the same surgery matched by age, gender, and body mass index, were enrolled in the control group. EAT thickness was measured by echocardiography. We obtained blood and EAT samples at open-heart surgery. In each patient, serum and EAT levels of IL-1β and adiponectin were measured. The EAT thickness in patients with persistent AF was significantly greater than that in the control group (5.6 ± 1.1 versus 5.0 ± 1.3 mm, P = 0.02). The mRNA level of IL-1β was higher in persistent AF group than the control group (4.94 ± 1.69 versus 2.93 ± 0.91, P < 0.01). Adiponectin expression decreased in persistent AF patients (7.04 ± 2.21 versus 8.63 ± 2.95, P = 0.01). There were no significant differences in plasma levels of IL-1β and adiponectin between the 2 groups. Multiple logistic regression analysis showed that IL-1β was an independent risk factor of persistent AF. These findings suggested that regional IL-1β in EAT was an independent risk factor of persistent AF, which may promote the persistence of AF.
Renal Reabsorption of Folates: Pharmacological and Toxicological Snapshots

Folates are water-soluble B9 vitamins that serve as one-carbon donors in the de novo synthesis of thymidylate and purines, and in the conversion of homocysteine to methionine. Due to their key roles in nucleic acid synthesis and in DNA methylation, inhibiting the folate pathway is still one of the most efficient approaches for the treatment of several tumors. Methotrexate and pemetrexed are the most prescribed antifolates and are mainly used in the treatment of acute myeloid leukemia, osteosarcoma, and lung cancers. Normal levels of folates in the blood are maintained not only by proper dietary intake and intestinal absorption, but also by an efficient renal reabsorption that seems to be primarily mediated by the glycosylphosphatidylinositol- (GPI) anchored protein folate receptor α (FRα), which is highly expressed at the brush-border membrane of proximal tubule cells. Folate deficiency due to malnutrition, impaired intestinal absorption or increased urinary elimination is associated with severe hematological and neurological deficits. This review describes the role of the kidneys in folate homeostasis, the molecular basis of folate handling by the kidneys, and the use of high dose folic acid as a model of acute kidney injury. Finally, we provide an overview on the development of folate-based compounds and their possible therapeutic potential and toxicological ramifications.
Migration Properties Distinguish Tumor Cells of Classical Hodgkin Lymphoma from Anaplastic Large Cell Lymphoma Cells

Anaplastic large cell lymphoma (ALCL) and classical Hodgkin lymphoma (cHL) are lymphomas that contain CD30-expressing tumor cells and have numerous pathological similarities. Whereas ALCL is usually diagnosed at an advanced stage, cHL more frequently presents with localized disease. The aim of the present study was to elucidate the mechanisms underlying the different clinical presentation of ALCL and cHL. Chemokine and chemokine receptor expression were similar in primary ALCL and cHL cases apart from the known overexpression of the chemokines CCL17 and CCL22 in the Hodgkin and Reed-Sternberg (HRS) cells of cHL. Consistent with the overexpression of these chemokines, primary cHL cases encountered a significantly denser T cell microenvironment than ALCL. Additionally to differences in the interaction with their microenvironment, cHL cell lines presented a lower and less efficient intrinsic cell motility than ALCL cell lines, as assessed by time-lapse microscopy in a collagen gel and transwell migration assays. We thus propose that the combination of impaired basal cell motility and differences in the interaction with the microenvironment hamper the dissemination of HRS cells in cHL when compared with the tumor cells of ALCL.
A Multifunctional Therapy Approach for Cancer: Targeting Raf1- Mediated Inhibition of Cell Motility, Growth, and Interaction with the Microenvironment

Prostate cancer cells move from their primary site of origin, interact with a distant microenvironment, grow, and thereby cause death. It had heretofore not been possible to selectively inhibit cancer cell motility. Our group has recently shown that inhibition of intracellular activation of Raf1 with the small-molecule therapeutic KBU2046 permits, for the first time, selective inhibition of cell motility. We hypothesized that simultaneous disruption of multiple distinct functions that drive progression of prostate cancer to induce death would result in advanced disease control. Using a murine orthotopic implantation model of human prostate cancer metastasis, we demonstrate that combined treatment with KBU2046 and docetaxel retains docetaxel's antitumor action, but provides improved inhibition of metastasis, compared with monotherapy. KBU2046 does not interfere with hormone therapy, inclusive of enzalutamide-mediated inhibition of androgen receptor (AR) function and cell growth inhibition, and inclusive of the ability of castration to inhibit LNCaP-AR cell outgrowth in mice. Cell movement is necessary for osteoclast-mediated bone degradation. KBU2046 inhibits Raf1 and its downstream activation of MEK1/2 and ERK1/2 in osteoclasts, inhibiting cytoskeleton rearrangement, resorptive cavity formation, and bone destruction in vitro, with improved effects observed when the bone microenvironment is chemically modified by pretreatment with zoledronic acid. Using a murine cardiac injection model of human prostate cancer bone destruction quantified by CT, KBU2046 plus zoledronic exhibit improved inhibitory efficacy, compared with monotherapy. The combined disruption of pathways that drive cell movement, interaction with bone, and growth constitutes a multifunctional targeting strategy that provides advanced disease control.