Miracle-dz/UniFAR-FTUs huggingface dataset:
Updating Phospholipase A2 Biology

The phospholipase A2 (PLA2) superfamily contains more than 50 enzymes in mammals that are subdivided into several distinct families on a structural and biochemical basis. In principle, PLA2 has the capacity to hydrolyze the sn-2 position of glycerophospholipids to release fatty acids and lysophospholipids, yet several enzymes in this superfamily catalyze other reactions rather than or in addition to the PLA2 reaction. PLA2 enzymes play crucial roles in not only the production of lipid mediators, but also membrane remodeling, bioenergetics, and body surface barrier, thereby participating in a number of biological events. Accordingly, disturbance of PLA2-regulated lipid metabolism is often associated with various diseases. This review updates the current state of understanding of the classification, enzymatic properties, and biological functions of various enzymes belonging to the PLA2 superfamily, focusing particularly on the novel roles of PLA2s in vivo.
Effects of equine-assisted therapy on the functionality of individuals with disabilities: systematic review and meta-analysis

ABSTRACT Purpose Evaluate the effects of Equine-Assisted Therapy (EAT) on the functioning of individuals with different health conditions through a systematic review and meta-analysis of randomized clinical trials (RCT). Methods This review was registered in the International Prospective Register of Systematic Reviews (CRD42018100035) and followed the Preferred Reporting Items for Systematic Review and Meta-analyses recommendations. RCT were searched in eight different databases, using relevant keywords until July 7, 2020. Two independent reviewers performed selection of articles and data extraction that were synthesized and analyzed according to the International Classification of Functioning, Disability and Health. Methodological quality and evidence of the effects were established through the PEDro score and GRADE. For meta-analysis we used random effects method, pooled-effect results, and mean difference with 95% confidence interval. Results Among 713 selected articles, 23 were included in the review. There is evidence of positive effects of the EAT on: exercise tolerance (p = .004) and quality of life (p < .0001), with high confidence in those effects; mobility (p = .002) and interpersonal interactions and relationships (p < .0001), with moderate confidence in those effects. Conclusion There are significant positive effects of the EAT on exercise tolerance, mobility, interpersonal interactions and relationships and quality of life of people with disabilities.
Spatial Changes in Microbial Communities along Different Functional Zones of a Free-Water Surface Wetland

Constructed wetlands (CWs) are complicated ecosystems that include vegetation, sediments, and the associated microbiome mediating numerous processes in wastewater treatment. CWs have various functional zones where contrasting biochemical processes occur. Since these zones are characterized by different particle-size composition, physicochemical conditions, and vegetation, one can expect the presence of distinct microbiomes across different CW zones. Here, we investigated spatial changes in microbiomes along different functional zones of a free-water surface wetland located in Moscow, Russia. The microbiome structure was analyzed using Illumina MiSeq amplicon sequencing. We also determined particle diameter and surface area of sediments, as well as chemical composition of organic pollutants in different CW zones. Specific organic particle aggregates similar to activated sludge flocs were identified in the sediments. The highest accumulation of hydrocarbons was found in the zones with predominant sedimentation of fine fractions. Phytofilters had the highest rate of organic pollutants decomposition and predominance of Smithella, Ignavibacterium, and Methanothrix. The sedimentation tank had lower microbial diversity, and higher relative abundances of Parcubacteria, Proteiniclasticum, and Macellibacteroides, as well as higher predicted abundances of genes related to methanogenesis and methanotrophy. Thus, spatial changes in microbiomes of constructed wetlands can be associated with different types of wastewater treatment processes.
Identification and Tracking of Antiviral Drug Combinations

Combination therapies have become a standard for the treatment for HIV and hepatitis C virus (HCV) infections. They are advantageous over monotherapies due to better efficacy, reduced toxicity, as well as the ability to prevent the development of resistant viral strains and to treat viral co-infections. Here, we identify new synergistic combinations against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), echovirus 1 (EV1), hepatitis C virus (HCV) and human immunodeficiency virus 1 (HIV-1) in vitro. We observed synergistic activity of nelfinavir with convalescent serum and with purified neutralizing antibody 23G7 against SARS-CoV-2 in human lung epithelial Calu-3 cells. We also demonstrated synergistic activity of nelfinavir with EIDD-2801 or remdesivir in Calu-3 cells. In addition, we showed synergistic activity of vemurafenib with emetine, homoharringtonine, anisomycin, or cycloheximide against EV1 infection in human lung epithelial A549 cells. We also found that combinations of sofosbuvir with brequinar or niclosamide are synergistic against HCV infection in hepatocyte-derived Huh-7.5 cells, and that combinations of monensin with lamivudine or tenofovir are synergistic against HIV-1 infection in human cervical TZM-bl cells. These results indicate that synergy is achieved when a virus-directed antiviral is combined with another virus- or host-directed agent. Finally, we present an online resource that summarizes novel and known antiviral drug combinations and their developmental status.
A biogeography of the mesopelagic community

There are a large number of research vessels and fishing vessels equipped with echosounders plying the world ocean, making continual observations of the ocean interior. Developing data collation programmes (e.g. Integrated Marine Observing System) and automated, repeatable analyses techniques enable the upper c. 1,200 meters of the world ocean to be sampled routinely, and for their characteristic deep scattering layers (DSLs) to be compared. Deep scattering layers are comprised of zooplankton (e.g. euphausiids) and fish, particularly myctophids or lantern fish, and comprise the majority of sub-surface biomass. Here we present, by the analysis of a global acoustic dataset, a mesopelagic biogeography of the sea. This was accomplished by (i) the collation and processing of a global active acoustic dataset, (ii) the development of a standardised and automated method of sound scattering layer (SSL) extraction and description, (iii) the derivation of the environmental drivers of DSL depth and biomass, (iv) the definition of a mesopelagic biogeography based on the drivers of DSL metrics and (v) the prediction, using output from the NEMO-MEDUSA-2.0 coupled model, of how the metrics and biogeography may change by 2100. Key findings include, the development of the Sound Scattering Layer Extraction Method (SSLEM) the inference that primary production, water temperature and wind stress are key drivers in DSL depth and biomass and that mesopelagic fish biomass may increase by 2100. Such an increase is a result of increased trophic efficiency from the shallowing of DSLs and rising water temperatures, suggesting, that as the climate warms the ocean is becoming more efficient. The biophysical relationships and biogeography derived here, serve to improve our understanding of mesopelagic mid-trophic level dynamics in open-ocean ecosystems. This will aid both fisheries and conservation management, which now adopt more holistic approaches when monitoring and evaluating ecosystem health and stability.
Differential demographic filtering by surface fires: How fuel type and fuel load affect sapling mortality of an obligate seeder savanna tree

We studied the effects of fuel type, fuel load and their associated flammability attributes on growth and survival of Callitris intratropica saplings. Callitris intratropica is a fire‐sensitive conifer that is widespread across northern Australia, but its range is contracting because of frequent and intense fires. A small‐scale field experiment was used to compare the effect of three fuel types (grass, eucalypt litter and C. intratropica litter), and a mix of grass and eucalypt litter by varying fuel loads within their naturally occurring bounds, and measuring multiple flammability attributes. Fuel type had the strongest influence on flammability attributes and hence sapling survival. Grass burnt rapidly, producing high temperatures, while duration of flaming was longer for eucalypt litter. Grass–eucalypt litter mixtures had flammability attributes more like grass, while C. intratropica litter was difficult to burn. Fuel load had a secondary effect, with strong interactions between fuel type and load. Differences in sapling survival could be attributed to temperatures at 5 cm height; there was no additional effect of fuel type or canopy temperature. Sapling size variables were also important, and strongly correlated with bark thickness, so we could not identify the protective mechanism. Synthesis. Mortality of Callitris intratropica saplings was consistent with damage to the lower stem, because of the direct relationship with temperatures at 5 cm height. Our results demonstrate the existence of a grass–fire cycle in C. intratropica stands, whereby hot fires damage the stands and allow grass to invade, increasing the stand ignitability and combustibility and promoting further fires. Interrupting this cycle by reducing grass fuel loads and hence the frequency of hot fires should therefore be a management priority to safeguard C. intratropica populations. Our findings also highlight that, under a common climate, vegetation type can shape fire regimes, because fuel type strongly influences flammability attributes, which in turn act as a powerful filter of plant populations.
The Course of Cognitive Performance during Inpatient Treatment in Patients with Alcohol Use Disorder with No, Mild or Major Neurocognitive Disorders

Abstract Aims In patients with a history of chronic alcohol abuse, neurocognitive disorders (NCD) are not uncommon. The current study aimed to explore the course of cognitive performance, as measured by the Montreal Cognitive Assessment (MoCA), and everyday cognitive functioning, as measured by the Patient Competency Rating Scale (PCRS), in a large group of patients with alcohol use disorder (AUD) admitted to the Center of Excellence for Korsakov and Alcohol-related Cognitive Impairments. Methods A multiple time-series design was used, in which the MoCA was administered at three time points of assessment, and the PCRS was completed by both the patient and a clinician at two time points, all during clinical treatment. Results A total of 524 patients were included, 71 of whom were diagnosed with AUD only, 284 with AUD and mild NCD (ARCI) and 169 with AUD, major NCD and fulfilling criteria for Korsakoff’s syndrome (KS). Conclusions Cognitive performance improved for all three groups during treatment, sustained abstinence and recovery from AUD. A low memory performance on the MoCA without improvement over time was predictive for KS, while improvement on this domain did not differentiate between AUD and ARCI. Changes in overall cognitive performance and orientation in patients with KS were positively related to changes in everyday cognitive functioning.
CT imaging features of the normal parathyroid gland in the dog

Zusammenfassung Gegenstand und Ziel Ziel dieser prospektiven Pilotstudie war zu beurteilen, ob die physiologische Glandula parathyroidea beim Hund computertomografisch dargestellt werden kann, und eine Beschreibung ihres CT-Erscheinungsbildes zu geben. Material und Methoden In die Studie wurden 25 Hunde aufgenommen, bei denen aufgrund von Erkrankungen im Halsbereich ohne Bezug zu Schild- oder Nebenschilddrüse ein CT-Scan erfolgte. Einschlusskriterium waren unauffällige Befunde bei der allgemeinen klinischen Untersuchung und der Blutuntersuchung (Blutbild und blutchemische Analyse). CT-Bilder vor und nach Kontrastmittelapplikation (30–45 Sekunden nach der Kontrastmittelinjektion, frühe venöse Phase) wurden mit einem 16-Schichten-Spiral-CT unter Verwendung eines Field of View von 18 cm, einer Schichtdicke von 1 mm und einer Matrix von 512 × 512 angefertigt. Zwei Radiologen begutachteten die CT-Aufnahmen unabhängig voneinander. Die Sichtbarkeit der Parathyreoidea wurde erfasst und die Interobserver-Reliabilität ermittelt. Bei den darstellbaren Nebenschilddrüsen wurden folgende Parameter bestimmt: Größe, Dichte (in Hounsfield Units [HU], vor und nach Kontrastmittelgabe), Dichte der Schilddrüse, Abgrenzung (exzellent, mäßig, schlecht). Ergebnisse Nur 20 bzw. 25 Nebenschilddrüsen waren durch die beiden Untersucher erkennbar. Die Anzahl differierte zwischen Nativaufnahmen und Bildern nach Kontrastmittelgabe nicht. Die Interobserver-Reliabilität hinsichtlich der Erkennbarkeit war moderat (κ = 0,40). Für Länge, Breite und Höhe der Nebenschilddrüsen (Mittelwert ± Standardabweichung) ergaben sich 4,2 × 2,5 × 2,9 mm ± 1,3 × 0,8 × 1,0 mm. Die Dichte betrug 39,7 ± 20,6 HU vor und 103,1 ± 47,1 HU nach Kontrastmittelgabe. Damit stellten sich die Nebenschilddrüsen im Vergleich zur Schilddrüse (vor und nach Kontrastmittelgabe 166,7 ± 34,3 HU bzw. 234,0 ± 60,1 HU) hypoattenuierend dar. Schlussfolgerung Diese Studie liefert die erste Beschreibung des CT-Erscheinungsbilds der angenommen physiologischen Nebenschilddrüse beim Hund. Die Sichtbarkeit des Organs war jedoch schlecht. Klinische Relevanz Trotz der schlechten Visualisierung der Nebenschilddrüse im CT ist sie gelegentlich wahrnehmbar. Die ermittelten Dimensionen waren teilweise größer als bisher für sonografische Darstellung beschrieben, ohne dass die untersuchten Hunde erkennbare Symptome eines Hyperparathyreodismus aufwiesen. Eine computertomografisch sichtbare Nebenschilddrüse impliziert daher möglicherweise nicht unbedingt eine Erkrankung. Weitere Studien dazu sind notwendig.
The impact of bariatric surgery on in-patient clinical outcomes among patients with autoimmune hepatitis

Abstract Autoimmune hepatitis (AIH) is a form of liver inflammation in which immune cells target hepatocytes, inducing chronic inflammatory states. Bariatric surgery (BS) was shown to reduce inflammation in severely obese patients. We hypothesize that obese patients with AIH and BS have lower prevalence of liver-related complications and in-patient mortality compared to those without BS. The National Inpatient Sample from 2007 to 2013 was queried for hospitalizations of adults over 18 years of age with a diagnosis of AIH. Of those, hospitalizations with BS were selected as cases and those with morbid obesity as controls. Case-control 1:2 matching was done based on sex, age, race, and comorbidities. Primary outcomes were prevalence of liver-related complications and in-patient mortality. Independent risk factors of in-patient clinical outcomes were identified using multivariate regression analysis. From 137,834 hospitalizations with a diagnosis of AIH, 688 with BS were selected as cases, and 1295 were matched as controls. The prevalence of ascites was higher in the BS group compared to the control (odds ratio 1.73, 95% confidence interval (CI) 1.27–2.36). The prevalence of cirrhosis (36.8% vs 33.2%), portal hypertension (7.4% vs 10.0%), hepatic encephalopathy (10.6% vs 8.7%), and varices and variceal bleeding (3.9% vs 5.5%) was not statistically different from case controls, (P > .05). BS was an independent risk factor for ascites (adjusted odds ratio (aOR) 1.87; 95% CI 1.36–2.56) and hepatic encephalopathy (aOR 1.42; 95% CI 1.03–1.97) but was an independent protective factor against in-patient mortality (aOR 0.21, 95% CI 0.08–0.55) once adjusted for age, sex, race, and comorbidities.
Resistance/fitness trade-off is a barrier to the evolution of MarR inactivation mutants in Escherichia coli

Abstract Background Mutations that inactivate MarR reduce susceptibility to ciprofloxacin and competitive growth fitness in Escherichia coli. Both phenotypes are caused by overexpression of the MarA regulon, which includes the AcrAB-TolC drug efflux pump. Objectives We asked whether compensatory evolution could reduce the fitness cost of MarR-inactivating mutations without affecting resistance to ciprofloxacin. Methods The cost of overexpressing the AcrAB-TolC efflux pump was measured independently of MarA overexpression. Experimental evolution of MarR-inactive strains was used to select mutants with increased fitness. The acquired mutations were identified and their effects on drug susceptibility were measured. Results Overexpression of the AcrAB-TolC efflux pump was found not to contribute to the fitness cost of MarA regulon overexpression. Fitness-compensatory mutations were selected in marA and lon. The mutations reduced the level of MarA protein thus reducing expression of the MarA regulon. They restored growth fitness but also reduced resistance to ciprofloxacin. Conclusions The fitness cost caused by overexpression of the MarA regulon has multiple contributing factors. Experimental evolution did not identify any single pump-independent cost factor. Instead, efficient fitness compensation occurred only by mechanisms that reduce MarA concentration, which simultaneously reduce the drug resistance phenotype. This resistance/fitness trade-off is a barrier to the successful spread of MarR inactivation mutations in clinical isolates where growth fitness is essential.
A GAL80 collection to nullify transgenes in Drosophila olfactory sensory neurons

Fruit flies recognize hundreds of ecologically relevant odors and respond appropriately to them. The noise, redundancy and interconnectedness of the olfactory machinery complicate efforts to pinpoint the functional contributions of any component neuron or receptor to behavior. Some contributions can only be elucidated in flies that carry multiple mutations and transgenes, but the production of such flies is currently labor-intensive and time-consuming. Here, we describe a set of transgenic flies that express the Saccharomyces cerevisiae GAL80 in specific olfactory sensory neurons (OrX-GAL80s). The GAL80s effectively and specifically subtract the activities of GAL4-driven transgenes that impart anatomical, behavioral, and physiological phenotypes. OrX-GAL80s can allow researchers to efficiently activate only one or a few types of functional neurons in an otherwise nonfunctional olfactory background. Such experiments will improve our understanding of the mechanistic connections between odorant inputs and behavioral outputs at the resolution of only a few functional neurons.
Formulation of directly compressible tablets from Psidium guajava, Mangifera indica, and Moringa oleifera using the Quality-by-Design (QbD) Approach

Quality-by-Design (QbD) is a concept which aims to provide a systematic approach to product development based on sound science and quality risk management. In this study QbD approach was applied to obtain optimized formulations of directly compressible tablets of Psidium guajava, Mangifera indica, and Moringa oleifera ethanolic leaf extracts. To do this, risk assessment as part of QbD was conducted to identify the critical quality attributes (CQAs) from the quality target products’ profile (QTPPs). A 3-level factorial design was used which generated nine formulation trials, and statistical treatment and interpretation of the formulation data utilizing Design Expert® 10 were the basis of the selection of the optimized formulation. All excipients used were found compatible in the formulations based on compatibility and stability studies. Most of the formulations met the acceptance criteria for different quality control parameters. There was also no significant change in the alpha-glucosidase inhibition activity between the positive control, crude extracts, and the formulated herbal tablets (p > 0.05). Optimum formulations of the ethanolic leaf extracts were obtained. The data gathered may be used to design new formulation for scale-up production.
A comparative study of trabecular bone micro-structural measurements using different CT modalities

Osteoporosis, characterized by reduced bone mineral density and micro-architectural degeneration, significantly enhances fracture-risk. There are several viable methods for trabecular bone micro-imaging, which widely vary in terms of technology, reconstruction principle, spatial resolution, and acquisition time. We have performed an excised cadaveric bone specimen study to evaluate different computed tomography (CT)-imaging modalities for trabecular bone micro-structural analysis. Excised cadaveric bone specimens from the distal radius were scanned using micro-CT and four in vivo CT imaging modalities: high-resolution peripheral quantitative computed tomography (HR-pQCT), dental cone beam CT (CBCT), whole-body multi-row detector CT (MDCT), and extremity CBCT. A new algorithm was developed to optimize soft thresholding parameters for individual in vivo CT modalities for computing quantitative bone volume fraction maps. Finally, agreement of trabecular bone micro-structural measures, derived from different in vivo CT imaging, with reference measures from micro-CT imaging was examined. Observed values of most trabecular measures, including trabecular bone volume, network area, transverse and plate-rod micro-structure, thickness, and spacing, for in vivo CT modalities were higher than their micro-CT-based reference values. In general, HR-pQCT-based trabecular bone measures were closer to their reference values as compared to other in vivo CT modalities. Despite large differences in observed values of measures among modalities, high linear correlation (r ε [0.94 0.99]) was found between micro-CT and in vivo CT-derived measures of trabecular bone volume, transverse and plate micro-structural volume, and network area. All HR-pQCT-derived trabecular measures, except the erosion index, showed high correlation (r ε [0.91 0.99]). The plate-width measure showed a higher correlation (r ε [0.72 0.91]) among in vivo and micro-CT modalities than its counterpart binary plate-rod characterization-based measure erosion index (r ε [0.65 0.81]). Although a strong correlation was observed between micro-structural measures from in vivo and micro-CT imaging, large shifts in their values for in vivo modalities warrant proper scanner calibration prior to adopting in multi-site and longitudinal studies.