Miracle-dz/UniFAR-FTUs huggingface dataset:
Epigenetic reprogramming of DCCs into dormancy suppresses metastasis via restored TGFβ–SMAD4 signaling

Disseminated cancer cells (DCCs) identified in secondary organs, sometimes before the primary tumor becomes detectable and treated, can remain dormant for years to decades before manifesting. Microenvironmental and epigenetic mechanisms may control the onset and escape from dormancy, and here we reveal how a combination of the DNA methylation inhibitor 5-azacytidine (AZA) and retinoic acid receptor ligands all-trans retinoic acid (atRA), orchestrate a novel program of stable dormancy. Treatment of HNSCC tumor cells with AZA+atRA induced a SMAD2/3/4 dependent regulation of downstream transcriptional program that restored the anti-proliferative function of TGFβ signaling. Significantly, AZA+atRA or AZA+AM80, an RARα specific agonist, strongly suppresses lung metastasis formation. The metastatic suppression occurs via the induction and maintenance of phenotypically homogenous dormant SMAD4+/NR2F1+ non-proliferative DCCs. These findings suggest that strategies that maintain or induce dormancy programs may be a viable alternative strategy to improve patient outcomes by preventing or significantly delaying metastasis development.
Visuo-vestibular gaze control – conserved subcortical processing

Gaze stabilization compensates for movements of the head or external environment to minimize image blurring, which is critical for visually-guided behaviors. Multisensory information is used to stabilize the visual scene on the retina via the vestibulo-ocular (VOR) and optokinetic (OKR) reflexes. While the organization of neuronal circuits underlying VOR is well described across vertebrates, less is known about the contribution and evolutionary origin of the OKR circuits. Moreover, the integration of these two sensory modalities is still poorly understood. Here, we developed a novel experimental model, the isolated lamprey eye-brain-labyrinth preparation, to analyze the neuronal pathways underlying visuo-vestibular integration which allowed electrophysiological recordings while applying vestibular stimulation using a moving platform, coordinated with visual stimulation via two screens. We show that lampreys exhibit robust visuo-vestibular integration, with optokinetic information processed in the pretectum and integrated with vestibular inputs at several subcortical levels. The enhanced eye movement response to multimodal stimulation favored the vestibular response at increased velocities. The optokinetic signals can be downregulated from tectum. Additionally, saccades are present in the form of nystagmus. The lamprey represents the oldest living group of vertebrates, thus all basic components of the visuo-vestibular control of gaze were present already at the dawn of vertebrate evolution.
Adaptation de la faune souterraine aux basses températures : mécanismes et enjeux écologiques

De par leur structure, les ecosystemes souterrains presentent des variations thermiques extremement faibles (± 1°C sur l'annee). De ce fait, les animaux hypoges devraient presenter des caracteristiques de stenothermes (faible tolerance aux variations thermiques), puisqu'ils ne subissent aucune variation de la temperature durant leur cycle de vie. Pourtant, plusieurs biospeologistes ont constate que le crustace aquatique souterrain Niphargus rhenorhodanensis pouvait supporter des temperatures negatives. Afin de determiner l'echelle thermobiologique de N. rhenorhodanensis ainsi que les mecanismes adaptatifs lui permettant de tolerer les basses temperatures, nous avons compare ses reponses a celles d'un autre amphipode souterrain (N. virei), ainsi qu'a celles d'un crustace morphologiquement proche vivant dans les cours d'eau epige (Gammarus fossarum). N. rhenorhodanensis montre des temps de survies a -2°C significativement superieurs a ceux des deux autres organismes. Les mesures de performance (metabolisme, activite locomotrice, ventilation) en fonction de la temperature (sur une gamme allant de -2°C a 28°C) demontrent que N. rhenorhodanensis presente les caracteristiques d'un organisme eurytherme : il maximise sa performance sur large plage de temperature. Enfin, lors d'une exposition au froid, N. rhenorhodanensis accumule des substances cryoprotectrices dans ses tissus (trehalose, acides amines libres), diminue sa teneur en eau libre (eau corporelle disponible pour la congelation), et tolere la congelation lorsqu'elle est initie par contact avec la glace. A l'inverse, chez les deux autres organismes, la congelation est mortelle, les teneurs en substances cryoprotectrices n'augmentent que tres peu et l'eau libre ne varie pas. Avec l'appui de recents travaux phylogeographiques, nous emettons l'hypothese que la presence de telles adaptations chez N. rhenorhodanensis serait liee a son histoire de vie durant les dernieres eres glaciaires.
Extraction of Vehicle CAN Bus Data for Roadway Condition Monitoring

Obtaining timely information across the state roadway network is important for monitoring the condition of the roads and operating characteristics of traffic. One of the most significant challenges in winter roadway maintenance is identifying emerging or deteriorating conditions before significant crashes occur. For instance, almost all modern vehicles have accelerometers, anti-lock brake (ABS) and traction control systems. This data can be read from the Controller Area Network (CAN) of the vehicle, and combined with GPS coordinates and cellular connectivity, can provide valuable on-the-ground sampling of vehicle dynamics at the onset of a storm. We are rapidly entering an era where this vehicle data can provide an agency with opportunities to more effectively manage their systems than traditional procedures that rely on fixed infrastructure sensors and telephone reports. This data could also reduce the density of roadway weather information systems (RWIS), similar to how probe vehicle data has reduced the need for micro loop or side fire sensors for collecting traffic speeds.
High common childhood illnesses while treatment seeking behavior of mothers’/care givers’ was low at rural northwest Ethiopia

Background: In most developing countries, childhood illness and deaths are among the most challenging health issues. Most of these deaths were due to preventable causes including acute respiratory infections (ARI), diarrhea, and febrile illnesses. Thus, identification of determinants of childhood illness would help to guide strategic planning and prioritize interventions.Method: Community based cross-sectional study was conducted. A two-stage cluster sampling technique was used to select households and mothers/caregivers. A total of 2,158 mothers with at least one under-five child were included. Mothers were interviewed at their homes using structured questionnaire. Adjusted Odds Ratio with a 95% Confidence Interval and P-value <0.05 in the multivariable model were reported to show the significance and direction of association.Result: The overall prevalence of childhood illnesses was 16.5% (95% CI: 15.0, 18.2). Of all, 6.5% (95% CI: 5.5, 6.72), 7.5% (95% CI: 6.5, 8.76), and 12.0% (95% CI: 10.66, 13.40) had diarrhea, ARI, and fever, respectively. The treatment-seeking behavior of mothers/care-givers for any of the childhood illness was 22.7% (18.72, 27.42). The odds of childhood illness was higher among mothers’ age 15-19 years (AOR=2.87-; 95% CI: 1.33, 6.13), employed mothers’ (AOR=2.28; 95%CI: 1.84, 4.39), living far away from nearest health center (AOR=1.02; 95%CI: 1.01, 1.03), two under-five children (AOR=1.33;95%CI: 1.029,1.74) and three or more children in the house (AOR=2.70; 95%CI: 1.12, 6.53). About 22.8% (95% CI: 18.7, 27.4) of mothers/caregivers sought health care. Mothers’ occupation (AOR= 4.08 (95% CI: 1.35, 12.39) was the only independent predictor of treatment-seeking behavior.Conclusion: In this study, common childhood illnesses remain high while the treatment-seeking behavior of the mothers’/caregivers’ was low. Mothers’ age, occupation, distance from the nearest health center, and two or more children in the house were independent factors of childhood illness. Being a skilled/semi-skilled mothers was significantly associated with health-seeking behavior of mothers/caregivers. Thus, involving women in skilled/semi-skilled occupations would help in decreasing childhood illness and enhance health-seeking behaviors for their under-five children. Besides, providing access to health care facilities in their nearby area would be essential in reducing childhood illness.
14-3-3 Proteins Are Involved in BR-Induced Ray Petal Elongation in Gerbera hybrida

14-3-3 proteins play a major role in the regulation of primary metabolism, protein transport, ion channel activity, signal transduction and biotic/abiotic stress responses. However, their involvement in petal growth and development is largely unknown. Here, we identified and characterized the expression patterns of seven genes of the 14-3-3 family in gerbera. While none of the genes showed any tissue or developmental specificity of spatiotemporal expression, all seven predicted proteins have the nine α-helices typical of 14-3-3 proteins. Following treatment with brassinolide, an endogenous brassinosteroid, the Gh14-3-3 genes displayed various response patterns; for example, Gh14-3-3b and Gh14-3-3f reached their highest expression level at early (2 h) and late (24 h) timepoints, respectively. Further study revealed that overexpression of Gh14-3-3b or Gh14-3-3f promoted cell elongation, leading to an increase in ray petal length. By contrast, silencing of Gh14-3-3b or Gh14-3-3f inhibited petal elongation, which was eliminated partly by brassinolide. Correspondingly, the expression of petal elongation-related and brassinosteroid signaling-related genes was modified in transgenic petals. Taken together, our research suggests that Gh14-3-3b and Gh14-3-3f are positive regulators of brassinosteroid-induced ray petal elongation and thus provides novel insights into the molecular mechanism of petal growth and development.
Validation of New Methods of Using Simulated Whole-Body Movements as Implicit Indicators of Sound and Odor Preferences

Would you get close to a stinky perfume bottle or to a loudspeaker producing noise? In this paper, we present two procedures that allowed us to assess the ability of auditory and olfactory cues to elicit automatic approach/avoidance reactions toward their sources. The procedures resulted from an adaptation of the Visual Approach/Avoidance by the Self Task (VAAST; Rougier et al., 2018), a task having the peculiarity of simulating approach/avoidance reactions by using visual feedback coming from the whole-body movements. In the auditory VAAST (Experiment 1), participants were instructed to move forward or backward from a loudspeaker that produced spoken words differentiated by their level of distortion and thus by their hedonic value. In the olfactory VAAST (Experiment 2), participants were asked to move forward or backward from a perfume bottle that delivered pleasant and unpleasant odors. We expected, consistent with the approach/avoidance compatibility effect, shorter latencies for approaching positive stimuli and avoiding negative stimuli. In both experiments, we found an effect of the quality of the emotional stimulus on forward actions of participants, with undistorted words and pleasant odors inducing faster forward movements compared with that for distorted words and unpleasant odors. Notably, our results further suggest that the VAAST can successfully be used with implicit instructions, i.e., without requiring participants to explicitly process the valence of the emotional stimulus (in Experiment 1) or even the emotional stimulus itself (in Experiment 2). The sensitivity of our procedures is analyzed and its potential in cross-modal and (contextualized) consumer research discussed.
Fibroblast Growth Factor 23 and Left Ventricular Hypertrophy in Chronic Kidney Disease—A Pediatric Perspective

Cardiovascular diseases (CVD) are a hallmark in pediatric patients with chronic kidney disease (CKD) contributing to an enhanced risk of all-cause and CV morbidity and mortality in these patients. The bone-derived phosphaturic hormone fibroblast growth factor (FGF) 23 progressively rises with declining kidney function to maintain phosphate homeostasis, with up to 1,000-fold increase in patients with kidney failure requiring dialysis. FGF23 is associated with the development of left ventricular hypertrophy (LVH) and thereby accounts to be a CVD risk factor in CKD. Experimentally, FGF23 directly induces hypertrophic growth of cardiac myocytes in vitro and LVH in vivo. Further, clinical studies in adult CKD have observed cardiotoxicity associated with FGF23. Data regarding prevalence and determinants of FGF23 excess in children with CKD are limited. This review summarizes current data and discusses whether FGF23 may be a key driver of LVH in pediatric CKD.
Hanseniaspora vineae and the Concept of Friendly Yeasts to Increase Autochthonous Wine Flavor Diversity

In this perspective, we will explain the concept of “friendly” yeasts for developing wine starters that do not suppress desirable native microbial flora at the initial steps of fermentation, as what usually happens with Saccharomyces strains. Some non-Saccharomyces strains might allow the development of yeast consortia with the native terroir microflora of grapes and its region. The positive contribution of non-Saccharomyces yeasts was underestimated for decades. Avoiding them as spoilage strains and off-flavor producers was the main objective in winemaking. It is understandable, as in our experience after more than 30 years of wine yeast selection, it was shown that no more than 10% of the isolated native strains were positive contributors of superior flavors. Some species that systematically gave desirable flavors during these screening processes were Hanseniaspora vineae and Metschnikowia fructicola. In contrast to the latter, H. vineae is an active fermentative species, and this fact helped to build an improved juice ecosystem, avoiding contaminations of aerobic bacteria and yeasts. Furthermore, this species has a complementary secondary metabolism with S. cerevisiae, increasing flavor complexity with benzenoid and phenylpropanoid synthetic pathways practically inexistent in conventional yeast starters. How does H. vineae share the fermentation niche with other yeast strains? It might be due to the friendly conditions it creates, such as ideal low temperatures and low nitrogen demand during fermentation, reduced synthesis of medium-chain fatty acids, and a rich acetylation capacity of aromatic higher alcohols, well-known inhibitors of many yeasts. We will discuss here how inoculation of H. vineae strains can give the winemaker an opportunity to develop ideal conditions for flavor expression of the microbial terroir without the risk of undesirable strains that can result from spontaneous yeast fermentations.
A Systematic Review of Flurbiprofen 8.75 mg Dose and Risk of Haemorrhagic Events

Oral non-steroidal anti-inflammatory drugs (NSAIDs) are known to be associated with an increased risk of bleeding. The NSAID, flurbiprofen, in the form of 8.75 mg lozenge or oromucosal spray is indicated for the symptomatic relief of sore throat. Despite the low dose as compared to alternative flurbiprofen preparations, concerns have been raised regarding its safety in terms of haemorrhagic events. This systematic review was conducted to identify existing evidence on the risk of haemorrhagic events with flurbiprofen 8.75 mg dose (any formulation), particularly where this may be due to potential interactions with other medicinal products. The systematic review examined studies reporting haemorrhagic events in patients receiving flurbiprofen 8.75 mg dose. Six individual electronic databases were searched up to 28th April 2020. Records were initially screened for relevance followed by further review of potentially eligible studies. Data extraction was performed for eligible studies and risk of bias in studies was assessed. The search strategy identified 1093 individual records. Of these, 1038 records were excluded after initial review; the majority of these records related to flurbiprofen in alternative formulations with alternative doses (e.g., eye drops, skin patches, oral tablets) thus were not considered relevant for further review. The 55 remaining records related to flurbiprofen 8.75 mg dose (any formulation) or flurbiprofen lozenge/oromucosal spray where the dose was not specified. After further review, 52 of these records were not considered eligible. Thus, only three records were included in this systematic review. The three studies reported a total of five haemorrhagic events in patients taking flurbiprofen 8.75 mg lozenge; the corresponding risk in each of the studies was 8.33, 1.98 and 1.96%. Where possible, comparison of flurbiprofen 8.75 mg lozenge to placebo produced risk ratios of 0.96 (95% CI 0.07, 13.25) and 2.00 (95% CI 0.10, 118.0). This systematic review found limited evidence on the risk of haemorrhagic events with flurbiprofen when used at a dose of 8.75 mg. Counts were low across all studies and results comparing flurbiprofen and placebo treatment arms were non-significant. However, scarcity of studies and low certainty of evidence for the outcome of haemorrhagic events limits the conclusions of this systematic review.
Anthropometric Measures and Incident Diabetic Nephropathy in Participants With Type 2 Diabetes Mellitus

Background The prevalence of diabetes is on the rise globally coupled with its associated complications, such as diabetic nephropathy (DN). Obesity has been identified as a risk factor for the development of DN but it is still unclear which obesity index is the best predictor of incident DN. Methods Data from the participants with type 2 diabetes mellitus (T2DM) in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study were used to examine the sex-specific association between waist circumference (WC), waist-to-height ratio (WHtR), and body mass index (BMI) with incident DN risk. Results Among the 8,887 participants with T2DM (5,489 men and 3,398 women), 5,296 participants (3,345 men and 1,951 women) developed the DN composite outcome during a follow-up period of 24302 person-years. Among men, null associations were observed between all anthropometric measures with incident DN in the multivariate analysis although the 3rd quartile of WHtR showed marginally significant results (P = 0.052). However, among women, both central and general obesity measures were associated with increased risks of incident DN. Compared with participants in the WC <88 cm category, the fully adjusted HR and 95% CI for those in the ≥88 cm of WC was 1.35 (95% CI 1.15-1.57). Compared with the lowest quartile, the fully adjusted HRs and 95% CIs for the 2nd to the 4th quartile of WHtR were 1.09 (95% CI 0.96-1.25), 1.12 (95% CI 0.98-1.28), and 1.14 (95% CI 1.00-1.30) respectively; also, compared with the normal BMI category, the fully adjusted HRs and 95% CIs for class I – class III obese were 1.36 (95% CI 1.10 – 1.67), 1.43 (95% CI 1.16 – 1.78) and 1.32 (95% CI 1.05 – 1.66) respectively. Conclusions Among participants with T2DM, higher levels of both central and general obesity indexes were associated with DN risk among women but not in men. Women with T2DM should maintain a healthy weight targeted at reducing both central and general obesity to enhance nephroprotection. Trial registration: ClinicalTrials.gov. , no. NCT00000620.
Expression Profiling of microRNA From Peripheral Blood of Dairy Cows in Response to Staphylococcus aureus-Infected Mastitis

As the main pathogen causing dairy cow mastitis, Staphylococcus aureus can cause subclinical mastitis, which is difficult to be diagnosed. It seriously affects milk quality and the economic benefits of the dairy industry. Therefore, it is very necessary to find biomarkers for early diagnosis of S. aureus-infected mastitis in peripheral blood of dairy cows. In this study, S. aureus was used to infect the mammary gland tissues of dairy cows, and a mastitis model was successfully constructed. The RNAseq technology was used to determine the expression profiles of microRNA (miRNA) from peripheral blood of dairy cows infected with S. aureus at 0, 1, 3, 5, and 7 days. A total of 288 differentially expressed miRNAs (DIE-miRNAs) were found, of which 108 were known miRNAs and 180 were novel predicted miRNAs. Bioinformatics analysis results showed that the above DIE-miRNAs might be involved in 10 immune system-related signaling pathways (i.e., chemokine signaling pathway, leukocyte transendothelial migration, natural killer cell-mediated cytotoxicity, toll-like receptor signaling pathway, Jak-STAT signaling pathway, MAPK signaling pathway, Wnt signaling pathway, cell adhesion molecules, cytokine-cytokine receptor interaction, and ECM-receptor interaction), thus regulating the process of S. aureus mastitis. It was also found that the expression variation of up-regulated expression of miR-320a, miR-19a, and miR-19b as well as down-regulated expression of miR-143, miR-205, and miR-24 reached a significant level on the 5th and 7th day of infection, suggesting that they might play an important biological role in mastitis and provide a direction for the research and development of molecular therapy technology for mastitis. However, at different times after S. aureus infection, miR-1301 was significantly up-regulated in peripheral blood. miR-2284r was significantly down-regulated, suggesting that these two miRNAs might be the new blood biomarkers for S. aureus-infected dairy cow mastitis. The above results laid a new foundation for the research and development of molecular diagnosis and biological therapy technology for S. aureus-infected mastitis in dairy cow.
COSMO-Onset: A Neurally-Inspired Computational Model of Spoken Word Recognition, Combining Top-Down Prediction and Bottom-Up Detection of Syllabic Onsets

Recent neurocognitive models commonly consider speech perception as a hierarchy of processes, each corresponding to specific temporal scales of collective oscillatory processes in the cortex: 30–80 Hz gamma oscillations in charge of phonetic analysis, 4–9 Hz theta oscillations in charge of syllabic segmentation, 1–2 Hz delta oscillations processing prosodic/syntactic units and the 15–20 Hz beta channel possibly involved in top-down predictions. Several recent neuro-computational models thus feature theta oscillations, driven by the speech acoustic envelope, to achieve syllabic parsing before lexical access. However, it is unlikely that such syllabic parsing, performed in a purely bottom-up manner from envelope variations, would be totally efficient in all situations, especially in adverse sensory conditions. We present a new probabilistic model of spoken word recognition, called COSMO-Onset, in which syllabic parsing relies on fusion between top-down, lexical prediction of onset events and bottom-up onset detection from the acoustic envelope. We report preliminary simulations, analyzing how the model performs syllabic parsing and phone, syllable and word recognition. We show that, while purely bottom-up onset detection is sufficient for word recognition in nominal conditions, top-down prediction of syllabic onset events allows overcoming challenging adverse conditions, such as when the acoustic envelope is degraded, leading either to spurious or missing onset events in the sensory signal. This provides a proposal for a possible computational functional role of top-down, predictive processes during speech recognition, consistent with recent models of neuronal oscillatory processes.