Miracle-dz/UniFAR-FTUs huggingface dataset:
Sweet pepper and its principle constituent capsiate: functional properties and health benefits

Abstract Capsiate is a non-pungent analogue of capsaicin. It belongs to the family of capsinoids which are esters of vanillyl alcohol with fatty acids while capsaicin belongs to the family of capsaicinoids that are amides of vanillylamine with a variety of branched-chain fatty acids. While capsaicin is extensively reported for plethora of pharmacological actions, capsiate remains much less explored. Extracted from various species of Capsicum plant, the molecule has also been chemically synthesized via a number of synthetic and enzymatic routes. Based on its action on transient receptor potential vanilloid subfamily member 1 receptors, recent research has focused on its potential roles in treatment of obesity, metabolic disorders, cancer, cardiovascular disorders and gastro-intestinal disorders. Its toxicity profile has been reported to be much safe. The molecule, however, faces the challenge of low aqueous solubility and stability. It has been commercialized for its use as a weight loss supplement. However, the therapeutic potential of the compound which is much beyond boosting metabolism remains unexplored hitherto. This comprehensive review summarizes the studies demonstrating the therapeutic potential of capsiate in various pathological conditions. Discussed also are potential future directions for formulation strategies to develop efficient, safe and cost-effective dosage forms of capsiate to explore its role in various disease conditions. The databases investigated include Cochrane library, Medline, Embase, Pubmed and in-house databases. The search terms were “capsiate,” “capsinoids,” “thermogenesis,” and their combinations. The articles were screened for relevance by going through their abstract. All the articles pertaining to physicochemical, physiological, pharmacological and therapeutic effects of capsiate have been included in the manuscript.
Epitranscriptomic regulation of insecticide resistance

A cytochrome P450 that confers insecticide resistance in whitefly is regulated by an epitranscriptomic mechanism. N6-methyladenosine (m6A) is the most prevalent messenger RNA modification in eukaryotes and an important posttranscriptional regulator of gene expression. However, the biological roles of m6A in most insects remain largely unknown. Here, we show that m6A regulates a cytochrome P450 gene (CYP4C64) in the global whitefly pest, Bemisia tabaci, leading to insecticide resistance. Investigation of the regulation of CYP4C64, which confers resistance to the insecticide thiamethoxam, revealed a mutation in the 5′ untranslated region of this gene in resistant B. tabaci strains that introduces a predicted m6A site. We provide several lines of evidence that mRNA methylation of the adenine at this position, in combination with modified expression of m6A writers, acts to increase expression of CYP4C64 and resistance. Collectively, these results provide an example of the epitranscriptomic regulation of the xenobiotic response in insects and implicate the m6A regulatory axis in the development of insecticide resistance.
Genetic Analysis of Sirtuin Deacetylases in Hyphal Growth of Candida albicans

Candida albicans is one of the most common causes of hospital-acquired systemic fungal infections in the United States. It can switch between ovoid yeast and elongated hyphal growth forms in response to environmental cues. ABSTRACT Candida albicans is a major human fungal pathogen that encounters varied host environments during infection. In response to environmental cues, C. albicans switches between ovoid yeast and elongated hyphal growth forms, and this morphological plasticity contributes to virulence. Environmental changes that alter the cell’s metabolic state could be sensed by sirtuins, which are NAD+-dependent deacetylases. Here, we studied the roles of three sirtuin deacetylases—Sir2, Hst1, and Hst2—in the hyphal growth of C. albicans. We made single, double, and triple sirtuin knockout strains and tested their ability to switch from yeast to hyphae. We found that true hypha formation was significantly reduced by the deletion of SIR2 but not HST1 or HST2. Moreover, the expression of hypha-specific genes HWP1, ALS3, and ECE1 decreased in the sir2Δ/Δ mutant compared to the wild type. This regulation of hypha formation was likely dependent on the deacetylase activity of Sir2, as a similar defect in hypha formation was observed when an asparagine known to be required for deacetylation was mutated. Finally, we found that Sir2 and Hst1 were localized to the nucleus, with Sir2 specifically focused in the nucleolus. This nuclear localization suggests a role for Sir2 and Hst1 in regulating gene expression. In contrast, Hst2 was localized to the cytoplasm. In conclusion, our results suggest that Sir2 plays a critical and nonredundant role in hyphal growth of C. albicans. IMPORTANCE Candida albicans is one of the most common causes of hospital-acquired systemic fungal infections in the United States. It can switch between ovoid yeast and elongated hyphal growth forms in response to environmental cues. This morphological transition is essential for its survival in the host. Thus, identifying regulators involved in this process can lead to new therapies. In this study, we examined the contribution of three regulators called sirtuins (Sir2, Hst1, and Hst2) to the yeast-to-hypha transition of C. albicans. We found that loss of Sir2 but not Hst1 or Hst2 hampered hypha formation. Moreover, the defect was caused by the loss of the catalytic activity of Sir2. Our study may lay the groundwork for discovering novel targets for antifungal therapies.
Liposuction treatment improves disease‐specific quality of life in lipoedema patients

This study examined the disease‐specific quality of life (QoL) in lipoedema patients undergoing treatment for the condition with liposuction. We conducted a retrospective analysis of all patients (n = 69) who underwent liposuction for treatment of lipoedema between 2004 and 2019, and gathered data on patient age, body mass index, the number of liposuction sessions, and the amount of fat removed per side. The study also prospectively evaluated the QoL in 20 lipoedema patients before and after liposuction using the Freiburg Life Quality Assessment for lymphatic diseases questionnaire. The mean age was 50.6 ± 12.8 years, and the average number of liposuction sessions performed was 2.9 ± 1.9, with a mean volume of 1868 ± 885.5 mL of fat removed per side. Before treatment with liposuction, disease‐specific QoL in patients with lipoedema was low on every single subscale as well as on the global score and showed a significant improvement in all aspects after liposuction. There was a significant correlation between a higher number of liposuction treatment sessions and general health status in lipoedema patients (P = .007). Liposuction greatly improves the QoL in lipoedema patients. A higher number of liposuction treatment sessions seem to have a positive effect on general health status in these patients.
Theory of Mind in Offending: A Systematic Review

Theory of mind (ToM) impairment is associated with poor social functioning in some psychological disorders (e.g., autism and schizophrenia). ToM deficits have also been linked with offending behavior in the theoretical literature. However, no review has examined the empirical evidence for such a link. We carried out a systematic review to provide a critical overview of studies involving ToM ability in offenders. We included studies published in English that used an instrument to measure at least one aspect of ToM. Twenty-eight eligible studies were identified and coded. Our findings reveal a generally mixed literature. Taking study quality into account, our findings suggest that offenders and nonoffenders do not differ in their first-order ToM. For second-order ToM, findings are mixed, even when only the highest quality studies are examined. Studies exploring advanced ToM showed mixed results overall, though the highest quality research appeared to indicate that offenders have impairments in advanced ToM which means that they may have difficulty understanding various mental states such as pretense, white lies, irony, double bluffs, and sarcasm. We suggest that well-controlled future studies, which also measure other facets of ToM (e.g., distinguishing between cognitive and affective ToM or examining ToM content), are needed to fully understand the role of ToM in offending.
Occurrence and accuracy of a register-based diagnosis of pediatric bipolar disorder: A nationwide cohort study

Objective: To investigate the accuracy of a diagnosis of pediatric bipolar disorder in the Danish National Register compared to the patient charts. Second, we reported on the occurrence of a diagnosis of pediatric bipolar disorder during the study period. Methods: All persons appearing in the Danish nationwide registers between 1995 and 2014 with an incident ICD-10 diagnosis of single hypomanic/manic episode or a diagnosis of bipolar disorder (summarized as bipolar disorder [BD]) before turning 18 years were identified (n = 521) and a random sample (n = 131) hereof was selected for chart review. Each chart was reviewed by two independent Schedules for Clinical Assessment in Neuropsychiatry (SCAN) certified raters to assess whether symptoms documented in the chart were consistent with a formal diagnosis of BD according to the ICD-10 criteria or not. Results: The formal diagnostic criteria for BD according to the ICD-10 were fulfilled in 48 charts (45.3%, 95% CI: [36.1%, 54.8%]) out of 106 reviewable charts, age at index = 16.4 ± 1.6 (range = 9.1–18.3) years. Cohen’s Kappa ranged from 94.4% to 100%. The estimate of a lifetime prevalence up till the current age for bipolar disorder for those of aged 5–18 years, was 0.019% in 2014. Conclusion: Less than half of the register-based pediatric BD diagnoses were confirmed by chart review, which was lower than expected. The occurrence of a register diagnosis of pediatric BD was relatively low.
No effect of very brief exposure to masked food pictures on fear of food in anorexia nervosa.

OBJECTIVE Very brief exposure to masked images of spider stimuli can facilitate approach behaviour towards spiders in fearful subjects. We hypothesized that a similar effect might occur for fear of food in patients with anorexia nervosa (AN), possibly offering a new treatment approach, with advantages over other methods of food exposure. METHODS Patients with AN (n = 60) were randomly assigned to one of three experimental conditions and received a single session of exposure to either masked and very briefly presented food images, clearly visible food images, or masked non-food images (i.e. household items). Effects of the three exposure conditions on fear of food and food avoidance were examined. RESULTS Contrary to our expectations, very brief food cue exposure was not superior to the control conditions regarding fear of food and approach behaviour towards food immediately after the intervention and body mass index four weeks later. CONCLUSION This finding suggests important differences between fear of food in AN and specific phobias such as fear of spiders. The absence of an effect reveals limitations of the very brief exposure method, which might be better suited for evolutionarily relevant threat stimuli.
Secondary attack rates from asymptomatic and symptomatic influenza virus shedders in hospitals: Results from the TransFLUas influenza transmission study

Abstract Objective: Nosocomial transmission of influenza is a major concern for infection control. We aimed to dissect transmission dynamics of influenza, including asymptomatic transmission events, in acute care. Design: Prospective surveillance study during 2 influenza seasons. Setting: Tertiary-care hospital. Participants: Volunteer sample of inpatients on medical wards and healthcare workers (HCWs). Methods: Participants provided daily illness diaries and nasal swabs for influenza A and B detection and whole-genome sequencing for phylogenetic analyses. Contacts between study participants were tracked. Secondary influenza attack rates were calculated based on spatial and temporal proximity and phylogenetic evidence for transmission. Results: In total, 152 HCWs and 542 inpatients were included; 16 HCWs (10.5%) and 19 inpatients (3.5%) tested positive for influenza on 109 study days. Study participants had symptoms of disease on most of the days they tested positive for influenza (83.1% and 91.9% for HCWs and inpatients, respectively). Also, 11(15.5%) of 71 influenza-positive swabs among HCWs and 3 (7.9%) of 38 influenza-positive swabs among inpatients were collected on days without symptoms; 2 (12.5%) of 16 HCWs and 2 (10.5%) of 19 inpatients remained fully asymptomatic. The secondary attack rate was low: we recorded 1 transmission event over 159 contact days (0.6%) that originated from a symptomatic case. No transmission event occurred in 61 monitored days of contacts with asymptomatic influenza-positive individuals. Conclusions: Influenza in acute care is common, and individuals regularly shed influenza virus without harboring symptoms. Nevertheless, both symptomatic and asymptomatic transmission events proved rare. We suggest that healthcare-associated influenza prevention strategies that are based on preseason vaccination and barrier precautions for symptomatic individuals seem to be effective.
Liquid–liquid phase separation of Tau by self and complex coacervation

The liquid–liquid phase separation (LLPS) of Tau has been postulated to play a role in modulating the aggregation property of Tau, a process known to be critically associated with the pathology of a broad range of neurodegenerative diseases including Alzheimer's Disease. Tau can undergo LLPS by homotypic interaction through self‐coacervation (SC) or by heterotypic association through complex‐coacervation (CC) between Tau and binding partners such as RNA. What is unclear is in what way the formation mechanisms for self and complex coacervation of Tau are similar or different, and the addition of a binding partner to Tau alters the properties of LLPS and Tau. A combination of in vitro experimental and computational study reveals that the primary driving force for both Tau CC and SC is electrostatic interactions between Tau‐RNA or Tau‐Tau macromolecules. The liquid condensates formed by the complex coacervation of Tau and RNA have distinctly higher micro‐viscosity and greater thermal stability than that formed by the SC of Tau. Our study shows that subtle changes in solution conditions, including molecular crowding and the presence of binding partners, can lead to the formation of different types of Tau condensates with distinct micro‐viscosity that can coexist as persistent and immiscible entities in solution. We speculate that the formation, rheological properties and stability of Tau droplets can be readily tuned by cellular factors, and that liquid condensation of Tau can alter the conformational equilibrium of Tau.
Integrated support vector machine and pharmacophore based virtual screening driven identification of thiophene carboxamide scaffold containing compound as potential PARP1 inhibitor

Abstract Poly (ADP-ribose) polymerase-1 (PARP1) inhibition strategy for cancer treatment is gaining advantage particularly in patients having a mutation in BRCA1/BRCA2 gene. To date, four drugs have obtained FDA approval and some inhibitors are in clinical trials. To identify more potent PARP1 inhibitors extensive research is going on to enrich the library of PARP1 inhibitors with compounds belonging to different classes. We employed an integrated virtual screening approach to identify potential PARP1 inhibitors. The sequential support vector machine (SVM) and pharmacophore model based virtual screening was carried out on the Maybridge library. The obtained hits were docked in the binding site of the PARP1 catalytic domain and nine drug-like compounds showing good ADME properties and form critical molecular interactions with the binding site residues were considered for the in vitro PARP1 inhibition assay. MD simulations were performed to decipher the stability of the PARP1-ligand complexes. Hydrogen bond interactions were also probed for their stability during MD simulations. We have identified three compounds (BTB02767, GK01172, and KM09200) showing 50% inhibition of PARP1 enzyme activity at 25 μM. BTB02767 and KM09200 have phthalazinone scaffold, while GK01172 bears a thiophene carboxamide scaffold, which could be a new chemotype of PARP1 inhibitors. In conclusion, GK01172 may serve as an important compound for further development of PARP1 inhibitors containing thiophene carboxamide scaffold. Communicated by Ramaswamy H. Sarma
Couples’ decision-making on post-partum family planning and antenatal counselling in Uganda: A qualitative study

Background Although health workers have been trained to provide post-partum family planning (PPFP), uptake remains low in Uganda. An important reason is that women want the agreement of their partner, who is often absent at the time of delivery. In order to address this, we aimed to understand the views of couples and explore barriers and facilitators to implementation of antenatal couples’ counselling on PPFP in Uganda. Methods We conducted individual interviews with a purposive sample of 12 postpartum and 3 antenatal couples; and 34 focus groups with a total of 323 participants (68 adolescent women, 83 women aged 20–49, 79 men, 93 health workers) in four contrasting communities (urban and rural) in South-West and Central Uganda. These were recorded, transcribed, translated, and analysed thematically. Results Although most participants felt that it is important for partners to discuss family planning, half of the couples were unaware of each other’s views on contraception. Most had similar views on motivation to use family planning but not on preferred contraceptive methods. Most liked the idea of antenatal couples’ counselling on PPFP. The main barrier was the reluctance of men to attend antenatal clinics (ANC) in health facilities. Respondents felt that Village Health Teams (VHTs) could provide initial counselling on PPFP in couples’ homes (with telephone support from health workers, if needed) and encourage men to attend ANC. Suggested facilitators for men to attend ANC included health workers being more welcoming, holding ANC clinics at weekends and “outreach” clinics (in rural villages far from health facilities). Conclusion Antenatal couples’ counselling has the potential to facilitate agreement PPFP, but some men are reluctant to attend antenatal clinics. Counselling at home by VHTs as well as simple changes to the organisation of antenatal clinics, could make it possible to deliver antenatal couples’ counselling on PPFP.
The compounding effect of having HIV and a disability on child mortality among mothers in South Africa

Background Previous research on the association between maternal HIV status and child mortality in sub–Saharan Africa was published between 2005–2011. Findings from these studies showed a higher child mortality risk among children born to HIV–positive mothers. While the population of women with disabilities is growing in developing countries, we found no research that examined the association between maternal disability in HIV–positive mothers, and child mortality in sub–Saharan Africa. This study examined the potential compounding effect of maternal disability and HIV status on child mortality in South Africa. Methods We analyzed data for women age 15–49 years from South Africa, using the nationally representative 2016 South Africa Demographic and Health Survey. We estimated unadjusted and adjusted risk ratios of child mortality indicators by maternal disability and maternal HIV using modified Poisson regressions. Results Children born to disabled mothers compared to their peers born to non-disabled mothers were at a higher risk for neonatal mortality (RR = 1.80, 95% CI:1.31–2.49), infant mortality (RR = 1.69, 95% CI:1.19–2.41), and under-five mortality (RR = 1.78, 95% CI:1.05–3.01). The joint risk of maternal disability and HIV-positive status on the selected child mortality indicators is compounded such that it is more than the sum of the risks from maternal disability or maternal HIV-positive status alone (RR = 3.97 vs. joint RR = 3.67 for neonatal mortality; RR = 3.57 vs. joint RR = 3.25 for infant mortality; RR = 6.44 vs. joint RR = 3.75 for under-five mortality). Conclusions The findings suggest that children born to HIV-positive women with disabilities are at an exceptionally high risk of premature mortality. Established inequalities faced by women with disabilities may account for this increased risk. Given that maternal HIV and disability amplify each other’s impact on child mortality, addressing disabled women’s HIV-related needs and understanding the pathways and mechanisms contributing to these disparities is crucial.
Contrasting demographic histories revealed in two invasive populations of the dry rot fungus Serpula lacrymans

Globalization and international trade have impacted organisms around the world leading to a considerable number of species establishing in new geographic areas. Many organisms have taken advantage of human‐made environments, including buildings. One such species is the dry rot fungus Serpula lacrymans, which is the most aggressive wood‐decay fungus in indoor environments in temperate regions. Using population genomic analyses of 36 full genome sequenced isolates, we demonstrated that European and Japanese isolates are highly divergent and the populations split 3000–19,000 generations ago, probably predating human influence. Approximately 250 generations ago, the European population went through a tight bottleneck, probably corresponding to the fungus colonization of the built environment in Europe. The demographic history of these populations, probably lead to low adaptive potential. Only two loci under selection were identified using a Fst outlier approach, and selective sweep analyses identified three loci with extended haplotype homozygosity. The selective sweep analyses found signals in genes possibly related to decay of various substrates in Japan and in genes involved DNA replication and protein modification in Europe. Our results suggest that the dry rot fungus independently established in indoor environments in Europe and Japan and that invasive species can potentially establish large populations in new habitats based on a few colonizing individuals.
MoiRNAiFold: a novel tool for complex in silico RNA design

Abstract Novel tools for in silico design of RNA constructs such as riboregulators are required in order to reduce time and cost to production for the development of diagnostic and therapeutic advances. Here, we present MoiRNAiFold, a versatile and user-friendly tool for de novo synthetic RNA design. MoiRNAiFold is based on Constraint Programming and it includes novel variable types, heuristics and restart strategies for Large Neighborhood Search. Moreover, this software can handle dozens of design constraints and quality measures and improves features for RNA regulation control of gene expression, such as Translation Efficiency calculation. We demonstrate that MoiRNAiFold outperforms any previous software in benchmarking structural RNA puzzles from EteRNA. Importantly, with regard to biologically relevant RNA designs, we focus on RNA riboregulators, demonstrating that the designed RNA sequences are functional both in vitro and in vivo. Overall, we have generated a powerful tool for de novo complex RNA design that we make freely available as a web server (https://moiraibiodesign.com/design/).