Miracle-dz/UniFAR-FTUs huggingface dataset:
MicroRNA124-IL6R Mediates the Effect of Nicotine in Inflammatory Bowel Disease by Shifting Th1/Th2 Balance Toward Th1

Epidemiological investigations have shown that smoking ameliorates ulcerative colitis (UC) but exacerbates Crohn's disease (CD), diseases that feature a Th2-mediated and Th1-mediated response, respectively. Cigarette extracts, especially nicotine, affect the Th1/Th2 balance. We previously reported that nicotine protects against mouse DSS colitis (similar to UC) by enhancing microRNA-124 (miR-124) expression. Intriguingly, elevation of miR-124 in CD is reported to aggravate the disease. Here we investigate the dual regulation of miR-124 in inflammatory bowel diseases (IBDs), which may explain the similar bidirectional regulation of tobacco. We found that overexpressed miR-124 protected against mouse DSS-induced colitis with a Th1 polarization in peripheral blood lymphocytes and colon tissues, which was also found in human peripheral blood lymphocytes. Conversely, miR-124 knockdown worsened DSS murine colitis with a Th2 polarization. Moreover, knockdown of miR-124 could eliminate the polarization toward Th1 after nicotine treatment, suggesting that miR-124 mediates the effect of nicotine on the Th1/Th2 balance. In addition, interference of IL-6R, which is a downstream target of miR-124, could remarkably weaken the Th1 polarization induced by miR-124. Taken together, these results suggest that nicotine shifts the balance of Th1/Th2 toward Th1 via a miR-124-mediated IL-6R pathway, which might explain its dual role in IBDs.
Plastidial and ER Triacylglycerol Biosynthesis in a Growth Phase-Dependent Manner in the Heterokont Nannochloropsis oceanica

Though microalgae have been considered the potential resource for lipid production, native strains are unable to meet the industrial demand. Here, we aim to uncover the complex molecular relationship between algal growth and lipid accumulation. Transcriptomic analysis revealed the crucial role of plastidial fatty acid and triacylglycerol (TAG) biosynthetic machinery in lipid overproduction. The expression of key fatty acid biosynthetic genes such as acetyl-CoA carboxylase (ACCase), malonyl CoA−acyl carrier protein transacylase (MCAT), 3-ketoacyl synthase (KAS), 3-ketoacyl-ACP reductase (KAR) increased during day 10–13 of cultivation, particularly plastidial TAG biosynthetic genes substantially increased. However, expression of genes involved in ER TAG biosynthesis increased only in the stationary phase, which implied the potential of plastidial TAG biosynthesis. This report provides a novel insight into the growth-phase dependent lipogenic orchestration, and also uncovers the signature genes and plastidial TAG biosynthesis that might be extrapolated for improving lipogenic traits of algae.
Pain and analgesia evaluated by the intraperitoneal bradykinin‐evoked pain method in man

Synthetic bradykinin WCM in;ected intraperitoneally to produce pain. The optimal individual dose of bradykinin was given every 15 minutes for 120 minutes after analgesic administration. experiments were performed double blind on groups of 16 sub;ects (4 per drug) in a random block design. The pain response WCM recorded by the sub;ect pressing one of four buttons on a pain signal box. Each button registered on a counter at a rate per second corresponding to the button number; the sum of the counts gave the weighted pain score (WPS). The latent period was recorded; it triggered a cutoff timer limiting pain responses to 4 minutes. To evaluate the effect of drugs, the WPS was expressed as a percentage of the individual control WPS and was compared by analysis of variance with the corresponding placebo or other data. Given orally, 650 mg. of aspirin, 20 mg. of dl‐amphetamine, and 100 mg. of meperidine were each analgesic, but half these doses had no such effect. The intraperitoneal in;ection of 20 to 40 mg. of Na‐CMpirin blocks the pain response to subsequent intraperitoneal in;ection of bradykinin, while the same dose given intravenously is ineffective. This suggests that aspirinanalgesia in man may be due to blockade of pain receptors at the periphery.
Crosstalk Between Gut Microbiota and Innate Immunity and Its Implication in Autoimmune Diseases

The emerging concept of microbiota contributing to local mucosal homeostasis has fueled investigation into its specific role in immunology. Gut microbiota is mostly responsible for maintaining the balance between host defense and immune tolerance. Dysbiosis of gut microbiota has been shown to be related to various alterations of the immune system. This review focuses on the reciprocal relationship between gut microbiota and innate immunity compartment, with emphasis on gut-associated lymphoid tissue, innate lymphoid cells, and phagocytes. From a clinical perspective, the review gives a possible explanation of how the “gut microbiota—innate immunity” axis might contribute to the pathogenesis of autoimmune diseases like rheumatoid arthritis, spondyloarthritis, and systemic lupus erythematosus.
Auto Micro Atomization Delivery of Human Epidermal Organoids Improves Therapeutic Effects for Skin Wound Healing

Severe skin wounds are often associated with large areas of damaged tissue, resulting in substantial loss of fluids containing electrolytes and proteins. The net result is a vulnerability clinically to skin infections. Therapies aiming to close these large openings are effective in reducing the complications of severe skin wounds. Recently, cell transplantation therapy showed the potential for rapid re-epithelialization of severe skin wounds. Here, we show the improved effects of cell transplantation therapy using a robust protocol of efficient expansion and delivery of epidermal cells for treatment of severe skin wounds. Human skin tissues were used to generate human epidermal organoids maintained under newly established culture conditions. The human epidermal organoids showed an improved capacity of passaging for at least 10 rounds, enabling organoids to expand to cell numbers required for clinical applications. A newly designed auto micro-atomization device (AMAD) was developed for delivery of human epidermal organoids onto the sites of severe skin wounds enhancing uniform and concentrated delivery of organoids, facilitating their engraftment and differentiation for skin reconstitution. With the optimal design and using pneumatic AMAD, both survival and functions of organoids were effectively protected during the spraying process. Cells in the sprayed human epidermal organoids participated in the regeneration of the epidermis at wound sites in a mouse model and accelerated wound healing significantly. The novel AMAD and out new protocol with enhanced effects with respect to both organoid expansion and efficient transplantation will be used for clincal treatments of complex, uneven, or large-area severe skin wounds.
The Critical Role of Bach2 in Shaping the Balance between CD4+ T Cell Subsets in Immune-Mediated Diseases

The transcription factor Bach2 which is predominantly expressed in B and T lymphocytes represses the expression of genes by forming heterodimers with small Maf and Batf proteins and binding to the corresponding sequence on the DNA. In this way, Bach2 serves as a highly conserved repressor which controls the terminal differentiation and maturation of both B and T lymphocytes. It is required for class switch recombination (CSR) and somatic hypermutation (SHM) of immunoglobulin genes in activated B cells, and its function in B cell differentiation has been well-described. Furthermore, emerging data show that Bach2 regulates transcriptional activity in T cells at super enhancers or regions of high transcriptional activity, thus stabilizing immunoregulatory capacity and maintaining T cell homeostasis. Bach2 is also critical for the formation and function of CD4+ T cell lineages (Th1, Th2, Th9, Th17, T follicular helper (Tfh), and regulatory T (Treg) cells). Genetic variations within Bach2 locus are associated with numerous immune-mediated diseases including multiple sclerosis (MS), rheumatoid arthritis (RA), chronic pancreatitis (CP), type 2 chronic airway inflammation, inflammatory bowel disease (IBD), and type 1 diabetes. Here, we reveal a critical role of Bach2 in regulating T cell biology and the correlation with these immune-mediated diseases.
Associations of Alpha and Beta Interhemispheric EEG Coherences with Indices of Attentional Control and Academic Performance

Introduction. Heretofore, research on optimizing academic performance has suffered from an inability to translate what is known about an individual's learning behaviors to how effectively they are able to use the critical nodes and hubs in their cerebral cortex for learning. A previous study from our laboratory suggests that lower theta-beta ratios (TBRs) measured by EEG may be associated with higher academic performance in a medical school curriculum. Methods In this study, we tested the hypothesis that TBR and academic performance may be correlated with EEG coherence, a measure of brain connectivity. We analyzed the interhemispheric coherences of the subjects involved in our prior study. TBR and coherence measurements were made at 19 scalp electrode recording sites and 171 electrode combinations with eyes open and closed (EO, EC). Control data were acquired during a session of acclimation to the research protocol 3 d before an initial examination in anatomy-physiology (control exam) and were repeated five weeks later, 3 d before a second exam covering different anatomy-physiology topics (comparison exam). Results Between the control and comparison exams, beta coherences increased significantly at the frontal pole, frontal, parietal, midtemporal, posterior temporal, and occipital recording sites under the EO condition and at the inferior frontal, central, midtemporal, and posterior temporal sites under the EC condition. Alpha coherences increased significantly at the same sites and under the same EO/EC conditions as found for the beta coherences. The beta coherences were negatively correlated with the TBR and were positively correlated with the comparison exam score at the midfrontal electrode site (F3-F4) but only under the EO condition. Beta and alpha coherences at the midfrontal, inferior frontal midtemporal, posterior temporal, and occipital sites were also negatively correlated with the average TBR under the EO condition. Conclusions Lower TBR, an indicator of attentional control, was associated with higher alpha and beta interhemispheric coherences measured with eyes open at sites overlying the frontal, temporal, and occipital cortices. Changes in EEG coherences and TBRs might be useful as neurophysiological measures of neuroplasticity and the efficacy of strategies for preventing academic underachievement and treatments for improving academic performance.
Non-viable chicken embryos: an overlooked niche harbouring a significant source of multidrug resistant bacteria in the poultry production

ABSTRACT Antimicrobial resistance (AMR) is a global issue, posing a grave threat to the public, animal, and environmental health. The AMR surveillance at the level of the hatchery is crucial to develop an AMR control strategy in the poultry industry. The objective of this study was to investigate the AMR profiles of bacteria isolated from yolk material of non-viable broiler chicken embryos at hatch from commercial hatcheries in western Canada. Antimicrobial susceptibility testing was done using the Kirby–Bauer disk diffusion method focusing on Escherichia coli (n = 170) and Enterococcus (n = 256) species, which are commonly used as indicators of AMR evolution. E. coli isolates were resistant to tetracycline, ampicillin, amoxycillin-clavulanic acid, triple sulpha, ceftiofur, gentamycin, and spectinomycin at the rate of 52.9%, 50.6%, 40.0% 31.8%, 29.4%, 29.4%, 21.8% respectively. Among those, 37.1% of E. coli were multidrug resistant. The descending order of antimicrobial resistance of E. faecalis was; tetracycline (61.9%), ceftiofur (46.2%), bacitracin (43.9%), erythromycin (31.4%) and tylosin (27.4%). Multidrug resistance was detected in 40.4% of E. faecalis isolates, and 85.7% of E. faecium isolates. To the best of our knowledge, this is the first report on AMR surveillance of non-viable chicken embryos. Overall, the present study revealed that non-viable chicken embryos, an overlooked niche for AMR surveillance, harbour multidrug-resistant E. coli, and enterococci that can be a substantial source of superbugs in the environment. Our data also highlight the urgency of including non-viable chicken embryos in AMR surveillance programme to understand AMR dissemination and its control.
Imaging spectrum of meningiomas: a review of uncommon imaging appearances and their histopathological and prognostic significance

Meningiomas are the most common primary non-glial intracranial neoplasms. In most cases, meningiomas have typical imaging appearances and locations, enabling a straightforward radiological diagnosis. However, a myriad of unusual appearances potentially complicate the imaging picture. Furthermore, certain imaging features can also predict the specific histopathological nature and WHO grade of the meningioma. ‘Typical’ meningiomas include meningothelial, fibrous, and transitional variants and have the characteristic imaging features described for meningiomas. Several ‘atypical’ variants exist, which, although less common, also generally have a less favourable prognosis and necessitate early diagnosis. In addition, meningiomas can occur in a variety of unusual intracranial and even extra-cranial locations and need to be distinguished from the more common tumours of these regions on imaging. Any associated oedema or haemorrhagic changes may alter the prognosis and have to be carefully assessed and reported. Cystic changes in meningiomas have been divided into five subtypes, and accurate characterisation is essential to predict the prognosis. An extensive review of the several possible variations in imaging appearances of meningiomas including the differential features of common and uncommon variants would facilitate informative radiological reporting of meningiomas. This would be expected to improve pre-operative planning prior to surgical biopsy and thereby improve disease prognosis and patient outcomes.
Prediction of Drug–Drug Interactions by Using Profile Fingerprint Vectors and Protein Similarities

Objectives Drug–drug interaction (DDI) is a vital problem that threatens people's health. However, the prediction of DDIs through in-vivo experiments is not only extremely costly but also difficult as many serious side effects are hard to detect in in-vivo and in-vitro settings. The aim of this study was to assess the effectiveness of similarity-based in-silico computational DDI prediction approaches and to provide a cost effective and scalable solution to predict potential DDIs. Methods In this study, widely known similarity-based computational DDI prediction methods were utilized to discover novel potential DDIs. More specifically, known interactions, drug targets, adverse effects, and protein similarities of drug pairs were used to construct drug fingerprints for the prediction of DDIs. Results Using the drug interaction profile, our approach achieved an area under the curve (AUC) of 0.975 in the prediction of a potential DDI. The drug adverse effect profile and protein profile similarity-based methods resulted in AUC values of 0.685 and 0.895, respectively, in the prediction of DDIs. Conclusions In this study, we developed a computational approach to the prediction of potential drug interactions. The performance of the similarity-based computational methods was comparatively evaluated using a comprehensive real-world DDI dataset. The evaluations showed that the drug interaction profile information is a better predictor of DDIs compared to drug adverse effects and protein similarities among DDI pairs.
Outcome of Critically Ill Patients With Influenza Infection: A Retrospective Study

Background: Influenza causes significant morbidity and mortality in adults, and numerous patients require intensive care unit (ICU) admission. Acute respiratory distress syndrome (ARDS) is clearly described in this context, but other clinical presentations exist that need to be assessed for incidence and outcome. The primary goal of this study was to describe the characteristics of patients admitted in ICU for influenza, their clinical presentation, and the 3-month mortality rate. The second objective was to search for 3-month mortality risk factors. Methods: This is a retrospective study including all patients admitted to 3 ICUs due to influenza-related disease between October 2013 and June 2016, which assesses the 3-month mortality rate. We compared clinical presentation, biological data, and outcome at 3 months between survivors and non-survivors. We created a predicting 3-month mortality model with Classification and Regression Tree analysis. Results: Sixty-nine patients were included, 50 patients (72.5%) for ARDS, 5 (7.2%) for myocarditis, and 14 (20.3%) for acute respiratory failure without ARDS criteria. Non-typed influenza A was found in 30 cases (43.5%), influenza A H1N1 in 18 (26.1%), H3N2 in 3 (4.3%), and influenza B in 18 cases (27.5%). The 3-month mortality rate was 29% (n = 20). Extracorporeal membrane oxygenation (ECMO) was implanted in 23 patients, without any significant increase in mortality (39% vs 24% without ECMO, P = .19). A creatinine serum superior to 96 μmol/L, an aspartate aminotransferase level superior to 68 UI/L, and a Pao2/Fio2 ration below 110 were associated with 3-month mortality in our predictive mortality model. Conclusion: Influenza in ICUs may have several clinical presentations. The mortality rate is high, but ECMO may be an effective rescue therapy.
A Novel Temporary Anchorage Device Aided Sectional Mechanics for Simultaneous Orthodontic Retraction and Intrusion

Closing spaces on light wires with inadequate knowledge and inappropriate mechanics can cause a “roller coaster” effect leading to an improper occlusion. Current knowledge of biomechanics, along with the incorporation of TADs, has made this process less challenging and more predictable. Resistance to sliding is considered the most prominent inhibitor of space closure in archwire-guided space closure or sliding mechanics, in turn delaying treatment duration considerably. In our case, resistance to sliding, primarily binding of the wire in the bracket slot, was nullified with the use of loop and sectional mechanics. This case report is aimed at showcasing the successful treatment of a young lady with a novel clinical setup to retract the canines into the premolar extraction space and simultaneously retract and intrude the anterior segment using sectional archwires and TADs in just under nine months. The current setup with sectional wires and TADs produced an uprighting, and an intrusive effect on the upper incisors during space closure. Additionally, the anchorage design avoided any significant change in the vertical dimension during sagittal correction of the Class II malocclusion. The occlusal plane remained almost stable with good amount of uprighting of the lower incisors following lower space closure too. The use of good biomechanical principles helped us achieve all the treatment goals and objectives in a very short period of time.
TOM1 confers resistance to the aminoglycoside hygromycin B in Saccharomyces cerevisiae

The ubiquitin ligase Tom1p contributes to regulated protein degradation, protein quantity control, and protein quality control in Saccharomyces cerevisiae. While GFP-tagged Tom1p is found in both the cytosol and nucleus, the majority of the protein is nuclear (Defenouillere et al. 2017). Among other substrates, Tom1p promotes the turnover of the DNA replication factor Cdc6p (Kim et al. 2012) and the ubiquitin ligase Dia2p (Kim and Koepp 2012) in a cell cycle-dependent manner. The enzyme also mediates the destruction of suprastoichiometric histone molecules (Singh et al. 2009) and ribosomal proteins (Sung et al. 2016). Further, Tom1p promotes the solubility of multiple aggregation-prone proteins (Theodoraki et al. 2012; Defenouillere et al. 2017). Knockout or knockdown of the mammalian homolog Huwe1 stabilizes excess ribosomal proteins (Sung et al. 2016), suggesting conservation of enzyme function.
Endoscopic laser surgery versus serial amnioreduction for severe twin-to-twin transfusion syndrome

BACKGROUND: Monochorionic twin pregnancies complicated by severe twin to twin transfusion syndrome at midgestation can be treated by either serial amnioreduction(removal of large volumes of amniotic fluid) or selective fetoscopic laser coagulation of the communicating vessels on the chorionic plate. We conducted a randomized trial to compare the efficacy and safety of these two treatments. METHODS: Pregnant women with severe twin to twin transfusion syndrome before 26 weeks of gestation were randomly assigned to laser therapy or amnioreduction. We assessed perinatal survival of at least one twin (a prespecified primary outcome),survival of at least one twin at six months of age, and survival without neurologic complications at six months of age on the basis of the number of pregnancies or the number of fetuses or infants, as appropriate. RESULTS:The study was concluded early, after 72 women had been assigned to the laser group and 70 to the amnioreduction group, because a planned interim analysis demonstrated a significant benefit in the laser group. As compared with the amnioreduction group, the laser group had a higher likelihood of the survival of at least one twin to 28 days of age (76 percent vs. 56 percent; relative risk of the death of both fetuses, 0.63; 95 percent confidence interval, 0.25to 0.93; P=0.009) and 6 months of age (P=0.002). Infants in the laser group also had a lower incidence of cystic periventricular leukomalacia (6 percent vs. 14 percent,P=0.02) and were more likely to be free of neurologic complications at six months of age (52 percent vs. 31 percent, P=0.003). CONCLUSIONS: Endoscopic laser coagulation of anastomoses is a more effective first linetreatment than serial amnioreduction for severe twin totwin transfusion syndrome diagnosed before 26 weeks of gestation.
Whole Genome Analysis Revealed the Genes Responsible for Citreoviridin Biosynthesis in Penicillium citreonigrum

Citreoviridin (CTV) is a mycotoxin that is produced by Aspergillus terreus, Eupenicillium ochrosalmoneum and Penicillium citreonigrum, and CTV has been detected in a wide range of cereal grains throughout the world. Furthermore, it is especially a serious problem in regions where rice is consumed as a staple food. Moreover, CTV is a well-known yellow rice toxin, and outbreaks of beriberi have occurred due to consumption of rice that is contaminated by CTV even in the recent years. Although CTV biosynthetic genes of A. terreus have been described, those of P. citreonigrum remain unclear, which is concerning since P. citreonigrum is the main cause of CTV contamination in rice. In the present study, we determined the draft genome of the P. citreonigrum strain IMI92228 and revealed the presence of all four genes that form a gene cluster and that are homologous to the CTV biosynthesis genes of A. terreus. The expression of these four homologous genes were highly correlated with CTV production, suggesting that they may play an important role in CTV biosynthesis in P. citreonigrum. We concluded that the gene cluster is a CTV biosynthesis cluster of P. citreonigrum. The findings will contribute to the understanding of the biosynthetic pathway of CTV and will ultimately lead to improvements in the CTV management of agricultural products.