Miracle-dz/UniFAR-FTUs huggingface dataset:
Pilot study of tolerability and safety of opioid receptor antagonists as novel therapies for chronic pain among persons living with HIV with past year heavy drinking: a randomized controlled trial

ABSTRACT Pain is common and associated with substance use among persons with HIV (PWH), yet limited management strategies exist. We assessed the feasibility, tolerability, and safety of low-dose naltrexone and standard dose nalmefene to treat chronic pain among PWH with past-year heavy alcohol use in a randomized, double-blinded, 2-arm study (planned enrollment 8 per arm). Participants were recruited in St. Petersburg, Russia between May and October 2018 and randomized to receive either nalmefene (16 mg) or low-dose naltrexone (4.5 mg) for 8 weeks. The primary outcome was tolerability of medication at eight weeks. Study visits included assessments of pain interference and severity, as well as cold-pressor testing. All participants in the nalmefene arm (N = 3) discontinued the study medication early due to side effects; nalmefene was subsequently deemed intolerable and this arm was terminated. The mean tolerability score at 8-weeks in the low-dose naltrexone arm was 90.7 (SD 22.44), median was 100 (IQR 95- 100), and median cold pain tolerance was approximately 10 s higher at the end of the 8 weeks. Low-dose naltrexone was well-tolerated, but nalmefene was not, in this sample. Further research is warranted to explore low-dose naltrexone’s potential efficacy as a non-addictive treatment for pain in this population. Clinical trial registration ClinicalTrials.gov identifier: NCT03278886.
High-resolution genome-wide association study pinpoints metal transporter and chelator genes involved in the genetic control of element levels in maize grain

Abstract Despite its importance to plant function and human health, the genetics underpinning element levels in maize grain remain largely unknown. Through a genome-wide association study in the maize Ames panel of nearly 2,000 inbred lines that was imputed with ∼7.7 million SNP markers, we investigated the genetic basis of natural variation for the concentration of 11 elements in grain. Novel associations were detected for the metal transporter genes rte2 (rotten ear2) and irt1 (iron-regulated transporter1) with boron and nickel, respectively. We also further resolved loci that were previously found to be associated with one or more of five elements (copper, iron, manganese, molybdenum, and/or zinc), with two metal chelator and five metal transporter candidate causal genes identified. The nas5 (nicotianamine synthase5) gene involved in the synthesis of nicotianamine, a metal chelator, was found associated with both zinc and iron and suggests a common genetic basis controlling the accumulation of these two metals in the grain. Furthermore, moderate predictive abilities were obtained for the 11 elemental grain phenotypes with two whole-genome prediction models: Bayesian Ridge Regression (0.33–0.51) and BayesB (0.33–0.53). Of the two models, BayesB, with its greater emphasis on large-effect loci, showed ∼4–10% higher predictive abilities for nickel, molybdenum, and copper. Altogether, our findings contribute to an improved genotype-phenotype map for grain element accumulation in maize.
Mowrah (Madhuca latifolia) seed saponin. Toxicological studies

Mowrah seed (Madhuca latifolia) meal contains high levels of saponin (7%) making it unsuitable for incorporation in animal feedstuff formulations. The saponin from mowrah seed meal was isolated and purified by paper chromatography. This was used for in vitro tests as well as pharmacological and acute toxicity studies for a better understanding of its properties and toxicity. The oral, intraperitoneal and intravenous LD50 of mowrah saponins in mice are 1 g, 15–20 mg and 15 mg/kg body weight respectively. Processing of the meal to remove or inactivate the saponin will be essential prior to its incorporation in animal feeds.
3D print material study to reproduce the function of pig heart tissue

BACKGROUND: Three-dimensional (3D) printing technology for heart simulation can be represented as complex anatomical structures, and objective information can be provided. OBJECTIVE: We studied 3D print material to find a material with the same elastic coefficient as pig elastic coefficient. METHODS: Pig heart sample, Agilus sample, Tango sample, TPU sample, and silicone sample were studied. The elastic coefficient of each specimen was measured using an elastic coefficient measuring instrument. The analysis was performed using the average value of ten specimens of the same size. We suggested an equation to find the elastic coefficient of material by the thickness using the elastic coefficient of Agilus, Tango, and silicone. RESULTS: The sample with similar elasticity to the pig sample did not show the same coefficient of elasticity at the same sample size. In Tango, the 0.5 mm high elastic force was about 3 times higher than the pig sample 7 mm elastic force. CONCLUSIONS: The study was conducted using 3D print material and silicone which can reproduce the elasticity of pig heart. However, no material is currently available to reproduce pig heart sample of the same size. However, if the heart is developed considering only elasticity, it can be sufficiently reproduced using the research results.
Conformational diversity defines substrate specificity of thymidylate/uridylate kinase from Candida albicans

Thymidylate kinase (TMK) from Candida albicans (CaTMK) contains a unique 15 residue insert, the CaLoop, that is not found on other TMKs. CaTMK is proficient at phosphorylating deoxyuridine monophosphate (dUMP), showing a rate 6‐fold higher than TMP. It has been shown that deletion of the CaLoop reduces the activity towards dUMP by 19‐fold, but has only a modest 4‐fold decrease in activity towards TMP. The molecular dynamics calculations presented here show that the increased activity towards dUMP is due to an increase in flexibility and correlated motions of the protein that allows the enzyme‐dUMP complex to more readily approach a catalytically competent state. Deletion of the CaLoop allows the dUMP‐enzyme complex to adopt catalytically non‐functional conformations. In contrast, TMP stabilizes the deletion such that it remains in a functional conformation that is similar to the conformation of the original enzyme.
Goat milk protein digestibility in relation to intestinal function

ABSTRACT Background Milk is an important high-quality animal protein source in low- and middle-income countries (LMICs). Although the true ileal digestibility and absorption of milk has been shown to be high in French adults, this may be lower in individuals from LMICs who are at risk of environmental enteropathy. Objective To determine the true ileal indispensable amino acid (IAA) digestibility of intrinsically labeled goat milk protein in South Indian women of reproductive age (WRA), using the dual-isotope tracer technique, and to measure intestinal absorption of amino acid and inert sugar in the same participants using L-allo-isoleucine and a dual-sugar assay. Methods Milk with 2H-labeled protein collected from a lactating goat fed intrinsically 2H-labeled fodder (maize and cowpea) was spray dried. Labeled milk protein was administered in a plateau feeding protocol to WRA with normal BMI, in whom urinary lactulose and mannitol recovery and the lactulose/mannitol ratio (LMR) were measured, to determine its true ileal IAA digestibility by the dual-isotope tracer technique with a reference U-13C–amino acid mixture. A phenylalanine absorption index was calculated from the plasma to meal ratio of 13C9 phenylalanine within the digestibility protocol. On a separate day, the allo-isoleucine absorption index was estimated from the ratio of plasma allo-isoleucine enrichments after oral 13C6-15N-L- and intravenous 2H10-L-allo-isoleucine administration. Results The means ± SDs of true ileal IAA digestibility of goat milk protein, lactulose and mannitol recovery, LMR, allo-isoleucine and phenylalanine absorption index were 94.0 ± 2.9%, 0.09 ± 0.03%, 7.9 ± 2.3%, 0.012 ± 0.004, 88.4 ± 3.8% and 24.5 ± 1.6%, respectively. The LMR correlated with the allo-isoleucine absorption index (rs = –0.93, P = 0.008). Conclusion The true ileal digestibility of goat milk protein in South Indian WRA with normal intestinal absorptive function and integrity was comparable to earlier estimates in healthy French adults.
IN-VITRO ANTIOXIDANT ACTIVITY OF A POLYHERBAL MENOPAUSAL FORMULATION: OVOUTOLINE TABLET

The polyherbal formulation, Ovoutoline tablet which has a combination of medicinal herbs such as Glycyrrhiza glabra, Saraca indica, Symplocos racemosa, Tinospora cordifolia, Asparagus racemosus, Valeriana walchii and Holarrhena antidysenterica was tested for its antioxidant activity and total phenolic content in vitro. This polyherbal formulation has been used for the treatment of postmenopausal symptoms, dysmenorrhea, menorrhagia and irregular menstruation. The in vitro scavenging activity of this formulation was tested by using DPPH (1,1 diphenyl-2-picrylhydrazyl), hydrogen peroxide and nitric oxide methods. All the experiments were performed in triplicate. The percentage inhibition IC50 values were found to be 49.72, 13.36 and 11.37 µg/ml for DPPH, hydrogen peroxide and nitric oxide respectively. The total phenolic content was found to be 97.11 µg of gallic acid equivalent per gram. The polyherbal formulation Ovoutoline tablet demonstrated significant antioxidant activity.
Simulating the Acquisition of Verb Inflection in Typically Developing Children and Children With Developmental Language Disorder in English and Spanish

Children with developmental language disorder (DLD) have significant deficits in language ability that cannot be attributed to neurological damage, hearing impairment, or intellectual disability. The symptoms displayed by children with DLD differ across languages. In English, DLD is often marked by severe difficulties acquiring verb inflection. Such difficulties are less apparent in languages with rich verb morphology like Spanish and Italian. Here we show how these differential profiles can be understood in terms of an interaction between properties of the input language, and the child's ability to learn predictive relations between linguistic elements that are separated within a sentence. We apply a simple associative learning model to sequential English and Spanish stimuli and show how the model's ability to associate cues occurring earlier in time with later outcomes affects the acquisition of verb inflection in English more than in Spanish. We relate this to the high frequency of the English bare form (which acts as a default) and the English process of question formation, which means that (unlike in Spanish) bare forms frequently occur in third-person singular contexts. Finally, we hypothesize that the pro-drop nature of Spanish makes it easier to associate person and number cues with the verb inflection than in English. Since the factors that conspire to make English verb inflection particularly challenging for learners with weak sequential learning abilities are much reduced or absent in Spanish, this provides an explanation for why learning Spanish verb inflection is relatively unaffected in children with DLD.
ALS2 regulates endosomal trafficking, postsynaptic development, and neuronal survival

Postsynaptic development requires the Frizzled nuclear import (FNI) pathway entailing the internalization and subsequent cleavage of Frizzled-2. Kim et al. show that Drosophila ALS2 regulates postsynaptic development by directing Frizzled-2 trafficking to late endosomes, where the Frizzled-2 C terminus is cleaved, and also promotes neuronal survival independently of the FNI pathway.
Preparation of high quality nanowires by tobacco mosaic virus templating of gold nanoparticles

A protocol for the preparation of stable suspensions of well-defined metallized tobacco mosaic virus (TMV) nanorods in high yields and with uniform coatings is reported. Inorganic growth on the virion surface was controlled by adding aliquots of gold precursor (HAuCl4) and reducing agent (NaBH4) incrementally over five addition–reduction cycles to produce hybrid anisotropic nanostructures consisting of densely packed gold nanoparticles. Several novel steps, including addition of ethanol after the first addition–reduction cycle and wrapping of the TMV/Au nanohybrids with poly-L-lysine, were introduced into the protocol to ensure high homogeneity and stability in the nanowire suspension. Control of the interparticle spacing in the metallized nanostructures was achieved by restricting the number of reaction cycles used to less than four iterations. The importance of bio-mediated reduction was probed using laser light scattering microscopy. The results indicated that short incubation times were consistent with increased nanoparticle monodispersity and high fidelity replication.
E‐cigarette users are associated with asthma disease: A meta‐analysis

At present, there are more than 300 million asthma patients in the world. Electronic cigarettes (e‐cigarettes) are considered as a new way of smoking and are loved by young people. The relationship between e‐cigarettes and asthma risk is still controversial. Therefore, we conducted a meta‐analysis to explore the relationship between e‐cigarettes and asthma.
nMAT3 is an essential maturase splicing factor required for holo-complex I biogenesis and embryo-development in Arabidopsis thaliana plants

Group II introns are large catalytic RNAs that are particularly prevalent in the organelles of terrestrial plants. In angiosperm mitochondria, group II introns reside in the coding-regions of many critical genes, and their excision is essential for respiratory-mediated functions. Canonical group II introns are self-splicing and mobile genetic elements, consisting of the catalytic intron-RNA and its cognate intron-encoded endonuclease factor (i.e. maturase, Pfam-PF01348). Plant organellar introns are extremely degenerate, and lack many regions that are critical for splicing, including their related maturase-ORFs. The high degeneracy of plant mitochondrial introns was accompanied during evolution by the acquisition of ‘host-acting’ protein cofactors. These include several nuclear encoded maturases (nMATs) and various other splicing-cofactors that belong to a diverse set of RNA-binding families, e.g. RNA helicases (Pfam-PF00910), Mitochondrial Transcription Termination Factors (mTERF, Pfam-PF02536), Plant Organelle RNA Recognition (PORR, Pfam-PF11955), and Pentatricopeptide repeat (PPR, Pfam-PF13812) proteins. Previously, we established the roles of MatR and three nuclear-maturases, nMAT1, nMAT2, and nMAT4, in the splicing of different subsets of mitochondrial introns in Arabidopsis. The function of nMAT3 (AT5G04050) was found to be essential during early embryogenesis. Using a modified embryo-rescue method, we show that nMAT3-knockout plants are strongly affected in the splicing of nad1 introns i1, i3 and i4 in Arabidopsis mitochondria. The embryo-defect phenotype is tightly associated with complex I biogenesis defects. Functional complementation of nMAT3 restored the splicing defects and altered embryogenesis phenotypes associated with the nmat3 mutant-line.
Use and Performance of the STOP-Bang Questionnaire for Obstructive Sleep Apnea Screening Across Geographic Regions

Key Points Question Is the STOP-Bang (snoring, tiredness, observed apnea, blood pressure, body mass index, age, neck size, gender) questionnaire a valid obstructive sleep apnea screening tool for patients referred to sleep clinics in different geographical populations? Findings This systematic review and meta-analysis of 47 studies including 26 547 individuals found that the STOP-Bang questionnaire has adequate sensitivity and diagnostic accuracy for detecting moderate to severe obstructive sleep apnea across geographic regions. Meaning These findings suggest that the STOP-Bang questionnaire can be used as a screening tool in different geographical regions for triaging patients suspected of having obstructive sleep apnea who are referred to sleep clinics.
Oral nutritional supplement use is weakly associated with increased subjective health-related quality of life in malnourished older adults: a multicentre randomised controlled trial

Abstract Malnutrition is common among older adults in health-care settings and is associated with decreased quality of life (QoL). The present study aimed to investigate the effect on health-related QoL (HRQoL) among older adults after 6 months of treatment with individual dietary advice (DA) and/or oral nutritional supplements (ONS), utilising 409 patients included in a multicentre randomised controlled trial of patients ≥ 65 years old, stratified according to nutrition status (malnourished/at risk of malnutrition), admitted to hospital in Sweden 2010–2014. Patients were randomised into four arms: DA, ONS, DA + ONS or routine care (control). The intervention started at discharge from hospital, with HRQoL measured using European QoL five-dimension, three-level (EQ-5D-3L) and European QoL-visual analogue scale (EQ-VAS) at baseline and at 6-month, 1-year and 3-year follow-ups. Data were analysed using the Kruskal–Wallis test and multiple linear regression. Overall, HRQoL increased from baseline to follow-ups, although the magnitude of change in EQ-5D-3L did not differ significantly between the four arms in any of the nutrition groups. However, a significant difference was observed for change in EQ-VAS from baseline to 6-month follow-up in the malnourished group, with mean changes of 22·4 and –3·4 points for the ONS and control groups, respectively (P = 0·009). In the multiple linear regression analyses, participants in the ONS arm had 27·5, 34·4 and 38·8 points larger increases in EQ-VAS from baseline to the 6-month (P = 0·011), 1-year (P = 0·007) and 3-year (P = 0·032), respectively, follow-ups than the control group. The use of ONS improved subjectively assessed HRQoL in these malnourished older adults.
Context counts: a qualitative study exploring the interplay between context and implementation success

Purpose Implementing change in healthcare is difficult to accomplish due to the unpredictability associated with challenging the status quo. Adapting the intervention/practice/program being implemented to better fit the complex context is an important aspect of implementation success. Despite the acknowledged influence of context, the concept continues to receive insufficient attention at the team-level within implementation research. Using two heterogeneous multidisciplinary healthcare teams as implementation case studies, this study evaluates the interplay between context and implementation and highlights the ways in which context influences the introduction of a collective leadership intervention in routine practice. Design/methodology/approach The multiple case study design adopted, employed a triangulation of qualitative research methods which involved observation (Case A = 16 h, Case B = 15 h) and interview data (Case A = 13 participants, Case B = 12 participants). Using an inductive approach, an in-depth thematic analysis of the data outlined the relationship between team-level contextual factors and implementation success. Findings Themes are presented under the headings: (1) adapting to the everyday realities, a key determinant for implementation success and (2) implementation stimulating change in context. The findings demonstrate a dynamic relationship between context and implementation. The challenges of engaging busy healthcare professionals emphasised that mapping the contextual complexity of a site and adapting implementation accordingly is essential to enhance the likelihood of successful implementation. However, implementation also altered the surrounding context, stimulating changes within both teams. Originality/value By exposing the reciprocal relationship between team-level contextual factors and implementation, this research supports the improved design of implementation strategies through better understanding the interplay and mutual evolution of evidence-based healthcare interventions within different contexts.
Pre-concentration of trace metals on centrifugal microfluidic discs with direct determination by laser ablation inductively coupled plasma mass spectrometry

Solid Phase Extraction (SPE) is commonly used for pre-concentration and matrix removal in trace metal determinations. We present a novel centrifugal microfluidic device for field sampling and on-site pre-concentration of water samples. Metal-8-hydroxyquinoline complexes are adsorbed onto miniature C18-bonded silica gel columns on centrifugal microfluidic discs. Laser Ablation (LA) is used to directly vaporize the analytes from the column, instead of eluting the pre-concentrated analytes for introduction in an Inductively Coupled Plasma Mass Spectrometer (ICP-MS) by conventional solution nebulization. Absolute detection limits ranging between 0.1 and 12 ng were obtained for Ni, Cu, V, Pb and Co in drinking water Certified Reference Materials (CRMs). These centrifugal devices require only 1–600 µL samples and necessitate no more than a simple motor to actuate fluid flow. The discs can be used to perform multiple extractions simultaneously as well as allowing the easy storage of samples before transport to the laboratory for LA-ICP-MS analysis.
Mapping the Soil Vulnerability Index across broad spatial extents to guide conservation efforts

THE NEED FOR TARGETED AGRICULTURAL CONSERVATION The 2008 Gulf of Mexico Hypoxia Action Plan was developed in response to national water quality impairments that were largely caused by agricultural land uses within and around the US Corn Belt (Alexander et al. 2008; Mississippi River Gulf of Mexico Watershed Nutrient Task Force 2008). The plan prompted states to create nutrient reduction strategies to achieve a 45% reduction in total nitrogen (N) and total phosphorus (P) loads into the Mississippi River, and thereby alleviate the hypoxic zone in the Gulf of Mexico (Mississippi River Gulf of Mexico Watershed Nutrient Task Force 2008). Similar to other state strategies, the Iowa Nutrient Reduction Strategy (INRS) promotes the widespread and voluntary adoption of best management practices (BMPs) to achieve nutrient reduction goals. The INRS establishes goals of 41% and 29% reductions in total N and total P, respectively, from nonpoint sources from a 1980 to 1996 baseline (Iowa Department of Agriculture and Land Stewardship et al. 2017). These goals are largely dependent on regional conservation funding and infrastructure to inform and incentivize BMP adoption at individual farm scales (Zimmerman et al. 2019a).
Theories of well-being and well-being policy: a view from methodology

ABSTRACT In the recent well-being literature, various theory-free accounts of well-being have been proposed to ground informative evaluations of policies’ welfare implications without relying on any specific theories of well-being. In this paper, I provide a methodological assessment of theory-free accounts and argue that, despite these accounts, grounding informative evaluations of policies’ welfare implications frequently requires policy makers to rely on specific theories of well-being. Policy makers should ground their evaluations of policies’ welfare implications on explicit specifications of what theories of well-being they rely on and should openly acknowledge the theory-dependent character of their evaluations rather than aiming to provide theory-free welfare evaluations.
The Helsinki approach to economic methodology, or, how to espouse the mainstream?

ABSTRACT This paper provides metaphilosophical reflections on economic methodology by way of discussing the ‘Helsinki approach’. This approach combines the study of the practice of economics with an endeavor to retain a normative perspective. It also explains that it is difficult to find explicit espousals of mainstream economics in the methodological literature not because nobody takes a mainstream view, but rather because expressing such a view is inconsistent with the prevalent metaphilosophical approach.