Miracle-dz/UniFAR-FTUs huggingface dataset:
Beyond Just Bacteria: Functional Biomes in the Gut Ecosystem Including Virome, Mycobiome, Archaeome and Helminths

Gut microbiota refers to a complex network of microbes, which exerts a marked influence on the host’s health. It is composed of bacteria, fungi, viruses, and helminths. Bacteria, or collectively, the bacteriome, comprises a significant proportion of the well-characterized microbiome. However, the other communities referred to as ‘dark matter’ of microbiomes such as viruses (virome), fungi (mycobiome), archaea (archaeome), and helminths have not been completely elucidated. Development of new and improved metagenomics methods has allowed the identification of complete genomes from the genetic material in the human gut, opening new perspectives on the understanding of the gut microbiome composition, their importance, and potential clinical applications. Here, we review the recent evidence on the viruses, fungi, archaea, and helminths found in the mammalian gut, detailing their interactions with the resident bacterial microbiota and the host, to explore the potential impact of the microbiome on host’s health. The role of fecal virome transplantations, pre-, pro-, and syn-biotic interventions in modulating the microbiome and their related concerns are also discussed.
Teachers’ ambulatory heart rate variability as an outcome and moderating variable in the job demands-resources model

ABSTRACT Background and Objectives: According to the job demands-resources (JD-R) model, strain reactions are based on the level of job demands and moderating resources. The present study aims to contribute to psychophysiological research by integrating vagally mediated heart rate variability (HRV) into the JD-R framework. Design and Methods: Using a sample of school teachers, we conducted an ambulatory assessment study to investigate HRV as (1) a state outcome measure of job demands and resources and (2) a trait moderator in the relationship between job demands and emotional exhaustion. In total, 101 participants wore an electrocardiogram device on two school days and rated their level of job demands (emotional demands and time pressure), job resources (control and support), and exhaustion six times a day. Based on 669 measurements, multilevel models of the 5-minute state HRV measure and emotional exhaustion were built. Results: The results supported the health-impairing effects of job demands on emotional exhaustion but not state HRV. There was no evidence of the moderating effects of job resources. Notably, the 48-hour trait HRV measure significantly buffered the effect of emotional demands on exhaustion. Conclusions: These findings highlight the stress-buffering potential of trait HRV as theoretical research extension and practical intervention goal.
Polypseudorotaxanes of Pluronic® F127 with Combinations of α- and β-Cyclodextrins for Topical Formulation of Acyclovir

Acyclovir (ACV) is one of the most used antiviral drugs for the treatment of herpes simplex virus infections and other relevant mucosal infections caused by viruses. Nevertheless, the low water solubility of ACV limits both its bioavailability and antiviral performance. The combination of block copolymer micelles and cyclodextrins (CDs) may result in polypseudorotaxanes with tunable drug solubilizing and gelling properties. However, the simultaneous addition of various CDs has barely been investigated yet. The aim of this work was to design and characterize ternary combinations of Pluronic® F127 (PF127), αCD and βCD in terms of polypseudorotaxane formation, rheological behavior, and ACV solubilization ability and controlled release. The formation of polypseudorotaxanes between PF127 and the CDs was confirmed by FT-IR spectroscopy, X-ray diffraction, and NMR spectroscopy. The effects of αCD/βCD concentration range (0–7% w/w) on copolymer (6.5% w/w) gel features were evaluated at 20 and 37 °C by rheological studies, resulting in changes of the copolymer gelling properties. PF127 with αCD/βCD improved the solubilization of ACV, maintaining the biocompatibility (hen’s egg test on the chorio-allantoic membrane). In addition, the gels were able to sustain acyclovir delivery. The formulation prepared with similar proportions of αCD and βCD provided a slower and more constant release. The results obtained suggest that the combination of Pluronic with αCD/βCD mixtures can be a valuable approach to tune the rheological features and drug release profiles from these supramolecular gels.
Interleukin 34 Serves as a Novel Molecular Adjuvant against Nocardia Seriolae Infection in Largemouth Bass (Micropterus Salmoides)

DNA vaccines have been widely employed in controlling viral and bacterial infections in mammals and teleost fish. Co-injection of molecular adjuvants, including chemokines, cytokines, and immune co-stimulatory molecules, is one of the potential strategies used to improve DNA vaccine efficacy. In mammals and teleost fish, interleukin-34 (IL-34) had been described as a multifunctional cytokine and its immunological role had been confirmed; however, the adjuvant capacity of IL-34 remains to be elucidated. In this study, IL-34 was identified in largemouth bass. A recombinant plasmid of IL-34 (pcIL-34) was constructed and co-administered with a DNA vaccine encoding hypoxic response protein 1 (Hrp1; pcHrp1) to evaluate the adjuvant capacity of pcIL-34 against Nocardia seriolae infection. Our results indicated that pcIL-34 co-injected with pcHrp1 not only triggered innate immunity and a specific antibody response, but also enhanced the mRNA expression level of immune-related genes encoding for cytokines, chemokines, and humoral and cell-mediated immunity. Moreover, pcIL-34 enhanced the protection of pcHrp1 against N. seriolae challenge and conferred the relative percent survival of 82.14%. Collectively, IL-34 is a promising adjuvant in a DNA vaccine against nocardiosis in fish.
Interventions to Reduce the Risk of Cardiovascular Disease among Workers: A Systematic Review and Meta-Analysis

This study examined the effect of lifestyle interventions on cardiovascular disease risk factors among workers. The study comprised a systematic review and meta-analysis of controlled trials. Relevant controlled trials were searched, with selections based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Risk of bias was assessed using the Scottish Intercollegiate Guidelines Network (SIGN). Of 1174 identified publications, one low-quality study was excluded. Finally, 10 were analyzed. The effect sizes were analyzed for heterogeneity, and random effect models (Hedge’s g) were used. A subgroup analysis was performed on the follow-up point of intervention (≤ 12 months vs. > 12 months). Publication bias was also analyzed. Interventions were effective for systolic (g = 0.66, 95% CI: 0.27-1.60) and diastolic blood pressure (g = 0.63, 95% CI: 0.21–1.06), and BMI (g = 0.71, 95% CI: 0.15-1.11). Interventions were ineffective for weight (g = 0.18, 95% CI: −0.04, 0.40) and LDL-cholesterol (g = 0.46, 95% CI: −0.02, 0.93). There was high heterogeneity between studies (I2 =78.45 to I2 = 94.61). There was no statistically significant publication bias, except for systolic blood pressure. Interventions to reduce risk of cardiovascular disease risk might be effective in improving physical outcomes, but additional high-quality trials are needed in the future.
Lamin Mutations Cause Increased YAP Nuclear Entry in Muscle Stem Cells

Mutations in the LMNA gene, encoding the nuclear envelope A-type lamins, are responsible for muscular dystrophies, the most severe form being the LMNA-related congenital muscular dystrophy (L-CMD), with severe defects in myonucleus integrity. We previously reported that L-CMD mutations compromise the ability of muscle stem cells to modulate the yes-associated protein (YAP), a pivotal factor in mechanotransduction and myogenesis. Here, we investigated the intrinsic mechanisms by which lamins influence YAP subcellular distribution, by analyzing different conditions affecting the balance between nuclear import and export of YAP. In contrast to wild type (WT) cells, LMNADK32 mutations failed to exclude YAP from the nucleus and to inactivate its transcriptional activity at high cell density, despite activation of the Hippo pathway. Inhibiting nuclear pore import abolished YAP nuclear accumulation in confluent mutant cells, thus showing persistent nuclear import of YAP at cell confluence. YAP deregulation was also present in congenital myopathy related to nesprin-1 KASH mutation, but not in cells expressing the LMNAH222P mutation, the adult form of lamin-related muscle dystrophy with reduced nuclear deformability. In conclusion, our data showed that L-CMD mutations increased YAP nuclear localization via an increased nuclear import and implicated YAP as a pathogenic contributor in muscle dystrophies caused by nuclear envelop defects.
A Qualitative Evaluation of Patient Experiences With Group Medical and Individual Education Appointments for Type 2 Diabetes Management in Saskatchewan, Canada

Purpose The purpose of this study was to capture information on patient experiences and perspectives of group medical appointments (GMAs) and compare them to those attending individual appointments (IAs) with the diabetes education team (usual care) for managing type 2 diabetes. Methods Adults (N = 18; 61% male; 83% 50-70 years old ) with type 2 diabetes (or prediabetes) living in rural Saskatchewan were recruited to complete a semistructured interview on their experiences with GMAs or IAs. To be eligible to participate, individuals must have attended at least 2 GMAs or 2 IAs. Transcripts were coded and analyzed using content analysis. Results Overall, participants spoke highly of their respective appointment type. Results indicated that both appointment types positively influenced understanding of diabetes management, with the most notable difference being greater understanding of stress management in the GMAs. Participants identified several positive aspects of each appointment type, which included convenience, supportive and enjoyable, and informative for GMAs and time and tailored information for IAs. Participants provided some suggestions to improve diabetes related-care for their respective appointment type. Conclusions Participants of GMAs and IAs for type 2 diabetes each reported unique strengths to their respective care plan and reported benefiting from their care.
Genotyping by Sequencing Revealed QTL Hotspots for Trichome-Based Plant Defense in Gossypium hirsutum

Cotton possesses certain physical features, including leaf and stem trichomes that help plants deter damage caused by insect pests, and to some extent, from abiotic factors as well. Among those features, trichomes (pubescence) hold a special place as a first line of defense and a managemental tool against sucking insect pests of cotton. Different insect pests of cotton (whiteflies, aphids, jassids, and boll weevil) severely damage the yield and quality of the crop. Likewise, whiteflies, aphids, jassids, and other insect pests are considered as potential carriers for cotton leaf curl viruses and other diseases. Genotyping by sequencing (GBS) study was conducted to understand and explore the genomic regions governing hairy (Pubescence) leaves and stem phenotypes. A total of 224 individuals developed from an intraspecific cross (densely haired cotton (Liaoyang duomao mian) × hairless cotton (Zong 128)) and characterized phenotypically for leaf and stem pubescence in different environments. Here we identify and report significant QTLs (quantitative trait loci) associated with leaf and stem pubescence, and the response of plant under pest (aphid) infestation. Further, we identified putative genes colocalized on chromosome A06 governing mechanism for trichome development and host–pest interaction. Our study provides a comprehensive insight into genetic architecture that can be employed to improve molecular marker-assisted breeding programs aimed at developing biotic (insect pests) resilient cotton cultivars.
Serum Uric Acid Level as a Harbinger of Type 2 Diabetes: A Prospective Observation in Taiwan

Background: Current evidence suggests an association of uric acid with diabetes risk, but it is still unclear whether uric acid is merely a risk marker or an independent risk factor. We evaluate the impact of serum uric acid (SUA) levels on the future risk of developing type 2 diabetes, independent of other factors. Methods: A population-based cohort study was conducted among 4130 participants who were found to be free of type 2 diabetes at baseline recruitment in 2002. Baseline SUA measured in 2002 was longitudinally related to the incident type 2 diabetes that occurred during the follow-up period between 2002 and 2007. Hazard ratios (HRs) and 95% confidence intervals (CIs) derived from Cox proportional hazards models were used to quantify the association. Results: There was a graded increase in the incidence of type 2 diabetes among individuals with increasing levels of SUA. In the whole study cohort, compared to quartile 1, the multivariable-adjusted HRs (95% CIs) of type 2 diabetes in quartile 2, quartile 3, and quartile 4 were 1.69 (0.76–3.76), 1.86 (0.88–4.26), and 1.94 (1.05–4.05), respectively (P for trend = 0.004). This positive gradient for the risk of type 2 diabetes across quartiles of SUA was evident in both genders and across age groups. Conclusions: This study supports that high uric acid concentrations are associated with increased diabetes risk, independent of other known risk factors. These data expand on well-established associations between SUA level and metabolic syndrome, and extend the link to the future risk of type 2 diabetes.
Transporter–enzyme interplay and the hepatic drug clearance: what have we learned so far?

ABSTRACT Introduction: Transporters and enzymes play an important role in absorption, distribution, clearance and elimination of drugs. Areas covered: This review provides an overview of the extended clearance concept and usefulness of extended clearance classification system (ECCS) in early identification of predominant clearance mechanisms. Clinical studies demonstrating transporter–enzyme interplay, challenges in scaling clearance from in vitro systems, utility of animal models and modeling approaches for evaluating hepatic clearance and drug–drug interactions are reviewed. Expert opinion: Clinical evidence exists supporting organic anion transporting peptide (OATP)1B and drug metabolizing enzymes involvement in clearance of ECCS class 1B drugs. Emerging evidence point toward contribution of organic cation transporter (OCT)1 to hepatic uptake of cationic drugs. Although, limited clinical evidence is presented, preclinical studies and modeling suggests organic anion transporter (OAT)2–enzyme interplay in clearance of class 1A drugs. Data from in vitro assays and preclinical models coupled with physiologically based modeling approaches are key for understanding transporter–enzyme interplay, enabling prediction of pharmacokinetics, tissue exposure and drug interactions. Current methodologies incur limitations and emphasis should be placed on the development of physiologically relevant in vitro models and characterize in vivo animal models to inform mechanistic modeling and improve confidence in prospective predictions.
Computational modelling of social cognition and behaviour—a reinforcement learning primer

Abstract Social neuroscience aims to describe the neural systems that underpin social cognition and behaviour. Over the past decade, researchers have begun to combine computational models with neuroimaging to link social computations to the brain. Inspired by approaches from reinforcement learning theory, which describes how decisions are driven by the unexpectedness of outcomes, accounts of the neural basis of prosocial learning, observational learning, mentalizing and impression formation have been developed. Here we provide an introduction for researchers who wish to use these models in their studies. We consider both theoretical and practical issues related to their implementation, with a focus on specific examples from the field.
A Systematic Literature Review of E-Cigarette-Related Illness and Injury: Not Just for the Respirologist

Following the recent electronic cigarette (e-cigarette) illness outbreak, the current review aimed to collect all related clinical cases for study and analysis and provide a critical synopsis of the proposed injury mechanism. Adhering to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis) guidelines, e-cigarette-related clinical cases were identified via Google Scholar and PubMed databases. Additionally, references of published case reports and previous review papers were manually searched, revealing 159 publications presenting e-cigarette-related case reports and 19 reports by the Centers for Disease Control and Prevention. 238 individual cases were identified; 53% traumatic injuries due to e-cigarette explosion or self-combustion, 24% respiratory cases, and 12% poisonings. Additional cases pertained to oral, cardiovascular, immunologic, hematologic, allergic reactions, infant complications, and altered medication levels. Case reports were mainly published between 2016–2019 (78%). The oldest case, a lipoid pneumonia, was published in 2012. The current review showed that e-cigarette-related health effects extend beyond the acute lung injury syndrome, including traumatic, thermal injuries and acute intoxications. Physicians should be aware of the distinct clinical presentations and be trained to respond and treat effectively. Regulators and public health authorities should address the regulatory gap regarding electronic nicotine delivery systems (ENDS) and novel tobacco products.
Randomised Double-Blind Placebo-Controlled Trial of Inulin with Metronidazole in Non-Alcoholic Fatty Liver Disease (NAFLD)

Background: Non-alcoholic fatty liver disease (NAFLD) can be ameliorated by weight loss although difficult to maintain. Emerging evidence indicates that prebiotics and antibiotics improve NAFLD. Aim: To determine whether inulin supplementation after brief metronidazole therapy is effective in reducing alanine aminotransferase (ALT) and maintaining weight loss achieved through a very-low-calorie diet (VLCD) among people with NAFLD. Methods: Sixty-two people with NAFLD commenced 4-week VLCD using Optifast meal replacements (600 kcal/day). Sixty were then randomised into a 12-week double-blind, placebo-controlled, parallel three-arm trial: (1) 400 mg metronidazole twice daily in Week 1 then inulin 4 g twice daily OR (2) placebo twice daily in week one then inulin OR (3) placebo-placebo. Main outcomes were ALT and body weight at 12 weeks. Fecal microbiota changes were also evaluated. Results: Mean body mass index (BMI) and ALT reduced after VLCD by 2.4 kg/m2 and 11 U/L, respectively. ALT further decreased after metronidazole-inulin compared to after placebo-placebo (mean ALT change −19.6 vs. −0.2 U/L, respectively; p = 0.026); however, weight loss maintenance did not differ. VLCD treatment decreased the ratio of Firmicutes/Bacteroidetes (p = 0.002). Conclusion: Brief metronidazole followed by inulin supplementation can reduce ALT beyond that achieved after VLCD in patients with NAFLD.
Phenolic composition and antioxidant capacity of hawthorn (Crataegus oxyacantha L.) flowers and fruits grown in Algeria

Abstract Background To the best of our knowledge, up to now, there are no reports on the antioxidant activity of phenolic compounds of Crataegus oxyacantha flowers and fruits. Such detailed information is essential to advance the existing knowledge and to promote the use of this species growing in Africa. Therefore, the objective of this investigation was to analyze the content of phenolic compounds as well as the antioxidant activities of flowers and fruits of C. oxyacantha from Bejaia (Northeastern Algeria) by different analytical methods, and to determine the relationship between them. Methods Phenolic compounds and antioxidant activity of Algerian hawthorn flowers and fruits (C. oxyacantha L.) were studied. Total phenolics, flavonoids and flavonols were determined using colorimetric methods. The phenolic profile was analyzed by high-performance liquid chromatography with diode array detection, and the in vitro antioxidant activity was measured using scavenging assay (FRAP) and Fremy’s salt, using electronic paramagnetic resonance. Results Different classes of phenolic compounds were identified and quantified. Hawthorn flowers contained higher levels of hydroxycinnamic acids, vitexin derivatives and flavonols compared to fruits, while anthocyanins were present only in fruits. Significant correlations were found between phenolic content and antioxidant activity. The results also showed that although the phenolic content of the two parts was different, their antioxidant capacity was not statistically different. Conclusions The results of this study indicate that hawthorn flowers and fruits of C. oxyacantha may be considered as a natural source of bioactive compounds.
β3-Adrenoceptor redistribution impairs NO/cGMP/PDE2 signalling in failing cardiomyocytes

Cardiomyocyte β3-adrenoceptors (β3-ARs) coupled to soluble guanylyl cyclase (sGC)-dependent production of the second messenger 3’,5’-cyclic guanosine monophosphate (cGMP) have been shown to protect from heart failure. However, the exact localization of these receptors to fine membrane structures and subcellular compartmentation of β3-AR/cGMP signals underpinning this protection in health and disease remain elusive. Here, we used a Förster Resonance Energy Transfer (FRET)-based cGMP biosensor combined with scanning ion conductance microscopy (SICM) to show that functional β3-ARs are mostly confined to the T-tubules of healthy rat cardiomyocytes. Heart failure, induced via myocardial infarction, causes a decrease of the cGMP levels generated by these receptors and a change of subcellular cGMP compartmentation. Furthermore, attenuated cGMP signals led to impaired phosphodiesterase two dependent negative cGMP-to-cAMP cross-talk. In conclusion, topographic and functional reorganization of the β3-AR/cGMP signalosome happens in heart failure and should be considered when designing new therapies acting via this receptor.