Miracle-dz/UniFAR-FTUs huggingface dataset:
A long-term open-label safety study of galcanezumab in Japanese patients with migraine

ABSTRACT Background Because of the burden of migraine in Japan, there is a need for safe and effective preventive treatments. This study assessed the long-term safety and tolerability of galcanezumab in Japanese patients with episodic (EM) or chronic (CM) migraine. Research design and methods In this 12-month open-label study, adult patients with EM who previously completed a 6-month, double-blind, placebo-controlled trial were newly randomized to either galcanezumab dose from placebo or continued their assigned galcanezumab doses (all: 120 mg, n = 120; 240 mg, n = 126). Newly enrolled patients with CM were randomized to 120-mg (n = 32) or 240-mg (n = 33) galcanezumab. The primary outcome was long-term safety and tolerability. Results The incidence of TEAEs was similar between treatment groups. Nasopharyngitis was the most common TEAE, followed by injection site reactions. The discontinuation rate was low (EM = 9.3%; CM = 15.4%) and no deaths were reported. Patients with EM who received galcanezumab in the placebo-controlled trial had sustained efficacy. Both doses reduced the number of migraine headache days in patients with CM. Conclusions Long-term treatment with 120-mg or 240-mg galcanezumab was safe and effective in Japanese patients with EM or CM. Trial registration https://clinicaltrials.gov, identifier: NCT02959190.
SubLocEP: a novel ensemble predictor of subcellular localization of eukaryotic mRNA based on machine learning

MOTIVATION mRNA location corresponds to the location of protein translation and contributes to precise spatial and temporal management of the protein function. However, current assignment of subcellular localization of eukaryotic mRNA reveals important limitations: (1) turning multiple classifications into multiple dichotomies makes the training process tedious; (2) the majority of the models trained by classical algorithm are based on the extraction of single sequence information; (3) the existing state-of-the-art models have not reached an ideal level in terms of prediction and generalization ability. To achieve better assignment of subcellular localization of eukaryotic mRNA, a better and more comprehensive model must be developed. RESULTS In this paper, SubLocEP is proposed as a two-layer integrated prediction model for accurate prediction of the location of sequence samples. Unlike the existing models based on limited features, SubLocEP comprehensively considers additional feature attributes and is combined with LightGBM to generated single feature classifiers. The initial integration model (single-layer model) is generated according to the categories of a feature. Subsequently, two single-layer integration models are weighted (sequence-based: physicochemical properties = 3:2) to produce the final two-layer model. The performance of SubLocEP on independent datasets is sufficient to indicate that SubLocEP is an accurate and stable prediction model with strong generalization ability. Additionally, an online tool has been developed that contains experimental data and can maximize the user convenience for estimation of subcellular localization of eukaryotic mRNA.
Preserving prospective memory in daily life: A systematic review and meta-analysis of mnemonic strategy, cognitive training, external memory aid, and combination interventions.

OBJECTIVE To preserve or improve independent functioning in older adults and those with neurocognitive impairments, researchers and clinicians need to address prospective memory deficits. To be effective, prospective memory interventions must restore (or circumvent) the underlying attention and memory mechanisms that are impaired by aging, brain injury, and neurodegeneration. We evaluated two decades of prospective memory interventions for efficacy, time/resource costs, and ecological validity. METHOD We systematically reviewed 73 prospective memory intervention studies of middle- to older-aged healthy adults and clinical groups (N = 3,749). We also rated the ecological validity of each study's prospective memory assessment/task using a newly developed scale. When possible (72% of studies), we estimated effect sizes using random-effects models and Hedges' g. RESULTS We identified four categories of prospective memory interventions, including mnemonic strategy, cognitive training, external memory aid, and combination interventions. Mnemonic strategy (g = .450) and cognitive training (g = .538) interventions demonstrated efficacy. Combination interventions showed mixed results (g = .254), underscoring that "more is not always better. " External memory aids demonstrated very positive outcomes (g = .805), though often with small-sample, case-series designs. Prospective memory assessments had high ecological validity in external memory aid studies (84%), but not in mnemonic strategy (14%), cognitive training (20%), or combination intervention (50%) studies, p < . 001, ηp2 = . 33. CONCLUSIONS Everyday prospective memory can be meaningfully improved, perhaps particularly with external memory aids, but larger trials are required to optimize treatments, increase adherence, and broaden implementation in daily life. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
Plant Response to Fish Farming Wastes in Volcanic Soils

Agricultural use of aquaculture wastes appears to be a sound ecological and economical means to improve soil fertility and to decrease the potential for adverse water quality impacts in South Argentina. A 3-mo greenhouse experiment with ryegrass (Lolium perenne L.) was conducted to determine plant availability of N and P from aquaculture wastes and compare results with previous laboratory incubations. Treatments included: (i) wastes taken from sediments under cages in a 3-yr-old fish farm (EA) applied at 40 and 80 Mg ha -1 ; (ii) wastes taken from sediments under cages in an 8-yr-old farm (LM), applied at 10 and 20 Mg ha -1 ; (iii) the lowest waste rates amended with 50 kg ha -1 synthetic N; (iv) four synthetic fertilizer treatments including a single N rate of 80 kg N ha -1 and four P levels of 30, 40, 60, and 80 kg P ha -1 , and (v) a no-fertilizer control. Although total N and P were higher in LM than in EA, and N mineralization rates in lab incubations were similar (13%), ryegrass yields and N uptake were much higher in EA than in LM. When mineralized N was estimated as the difference between added N and total N uptake, values were 50 to 63% for EA and 5 to 14% for LM. Ryegrass yields were approximately as follows: EA > FI > LM > Control. Synthetic fertilizer treatments showed the lowest values of P utilization efficiency, residual Olsen-P in soil and plant P uptake in biomass, and the highest P retention in soils. The lowest waste rates with addition of N produced comparable ryegrass yields with the highest rates. Results emphasize: (i) the need to include living plants in mineralization potential evaluations to avoid significant errors in nutrient cycling models, and (ii) the importance of organic amendments in ameliorating plant P availability in high P-fixing volcanic soils.
Integrative analysis of miRNA–mRNA network in high altitude retinopathy by bioinformatics analysis

Abstract High-altitude retinopathy (HAR) is an ocular manifestation of acute oxygen deficiency at high altitudes. Although the pathophysiology of HAR has been revealed by many studies in recent years, the molecular mechanism is not yet clear. Our study aimed to systematically identify the genes and microRNA (miRNA) and explore the potential biomarkers associated with HAR by integrated bioinformatics analysis. The mRNA and miRNA expression profiles were obtained from the Gene Expression Omnibus database. We performed Gene Ontology functional annotations and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Potential target gene analysis and miRNA–mRNA network analysis were also conducted. Quantitative RT-PCR (qRT-PCR) was used to validate the results of the bioinformatics analysis. Through a series of bioinformatics analyses and experiments, we selected 16 differentially expressed miRNAs (DE-miRNAs) and 157 differentially expressed genes related to acute mountain sickness (AMS) and constructed a miRNA–mRNA network containing 240 relationship pairs. The hub genes were filtered from the protein-protein interaction network: IL7R, FOS, IL10, FCGR2A, DDX3X, CDK1, BCL11B and HNRNPH1, which were all down-regulated in the AMS group. Then, nine up-regulated DE-miRNAs and eight hub genes were verified by qRT-PCR in our hypoxia-induced HAR cell model. The expression of miR-3177-3p, miR-369-3p, miR-603, miR-495, miR-4791, miR-424-5p, FOS, IL10 and IL7R was consistent with our bioinformatics results. In conclusion, FOS, IL10, IL-7R and 7 DE-miRNAs may participate in the development of HAR. Our findings will contribute to the identification of biomarkers and promote the effective prevention and treatment of HAR in the future.
Topiramate, acupuncture, and BoNT‐A for chronic migraine: a network meta‐analysis

Botulinum neurotoxin A (BoNT‐A) was the primary choice for preventive treatment of chronic migraine. Topiramate and acupuncture showed promising effect for chronic migraine, but their effectiveness relative to BoNT‐A was rarely studied. We aimed to perform a network meta‐analysis to compare the effectiveness and acceptability between topiramate, acupuncture, and BoNT‐A.
Evaluating bedaquiline as a treatment option for multidrug-resistant tuberculosis

ABSTRACT Introduction: Despite efforts to the contrary, tuberculosis remains one of the leading causes of death in the world. The appearance of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis has increased the need for new therapeutic options against these strains. Areas covered: This review covers the in vitro susceptibility, pharmacokinetics, and pharmacodynamics of bedaquiline, a new drug shown to be active against M. tuberculosis-resistant strains. The authors further review clinical data concerning its use against MDR and XDR strains, discussing recent clinical guidelines from different international societies. Expert opinion: Available data demonstrate the usefulness of bedaquiline against resistant M. tuberculosis. Despite the difficulty in analyzing multidrug therapies, the use of bedaquiline in MDR and XDR tuberculosis increases success rates, allowing shortened treatments and lower drug use than previously recommended regimens. Moreover, the fact that MDR and XDR strains are common in many places creates a need to include this drug in the currently available protocols. It is essential to overcome the substantial barriers that some countries encounter in obtaining bedaquiline, as doing so will make therapeutic regimens including this drug available for all patients.
Proteomic analysis from skin swabs reveals a new set of proteins identifying skin impairment in atopic dermatitis

Atopic Dermatitis (AD) is a common inflammatory skin disease characterized by skin and systemic inflammation, and barrier dysfunction. Herein, we investigate the proteomic profile of AD skin barrier to identify a unique signature with an easy‐performed sampling approach. We enrolled 8 moderate‐to‐severe AD patients and 8 age‐ and gender‐matched healthy controls. Swabs were obtained from non‐lesional skin of retroauricular area and antecubital fold. Peptide mixtures obtained through protein precipitation and in‐solution digestion were analysed using NanoLC‐MS/MS. Label‐free quantification and statistical analysis were conducted in MaxQuant and Perseus. Bioinformatics analysis was performed using Gene Ontology and STRING. We identified 908 proteins and 35 differentially expressed proteins were selected (fold change 2, FDR < 0.05). Particularly, AD skin showed downregulation of skin hydration factors, structural and epidermal proteins, abnormalities in protease‐proteasome complex and lipid metabolism profile. Imbalance of antioxidant and inflammatory processes, along with TDRD15 upregulation was also observed. Our result showed partial overlap with skin biopsy/tape‐strips studies, showing the reliability of our sampling approach which could be an easier method of detection of hallmark barrier proteins in AD. Furthermore, we displayed a new differentially expressed set of proteins, not yet explored in AD which can have a potential role in AD pathomechanisms.
Hydromethanolic root and aerial part extracts from Echium arenarium Guss suppress proliferation and induce apoptosis of multiple myeloma cells through mitochondrial pathway

Echium arenarium Guss is a Mediterranean plant traditionally used in healing skin wound and it was reported exhibiting potent antioxidant, antibacterial, and antiparasitic activities. However, antitumoral activities of this plant have not yet been explored. Here we investigated for the first time, root (EARE) and aerial part (EAAPE) extracts of E. arenarium Guss to examine cytotoxicity and apoptosis activation pathway on U266 human multiple myeloma (MM) cell line. We demonstrated that EARE and EAAPE decreased U266 cell viability in a dose dependent manner. Based on 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay, EARE was significantly two times more efficient (IC50 value 41 μg/ml) than EAAPE (IC50 value 82 μg/ml) considering 48 h of treatment. Furthermore, after 24 h of exposure to 100 μg/ml of EARE or EAAPE, cell cycle showed remarkable increase in sub‐G1 population and a decrease of U266 cells proportion in G1 phase. In addition, EARE increased cell percentage in S phase. Moreover, analysis revealed that EAAPE or EARE induced apoptosis of U266 cells after 24 h of treatment. Interestingly, depolarization of mitochondrial membrane potential and activation of caspase 3/7 were demonstrated in treated U266 cells. Phytochemical analysis of E. arenarium extracts showed that EARE exhibited the highest content of total phenolic content. Interestingly, six phenolic compounds were identified. Myricitrin was the major compound in EARE, followed by luteolin 7‐O‐glucoside, resorcinol, polydatin, Trans‐hydroxycinnamic acid, and hyperoside. These findings proved that an intrinsic mitochondria‐mediated apoptosis pathway probably mediated the apoptotic effects of E. arenarium Guss extracts on U266 cells, and this will suggest several action plans to treat MM.
GERMANIUM SOLVENT EXTRACTION FROM SULFURIC ACID SOLUTIONS (AND CO-EXTRACTION OF GERMANIUM AND GALLIUM)

Abstract The U.S. Bureau of Mines investigated solvent extraction methods for recovering germanium from sulfuric acid leach filtrates. A new organic extractant system was developed which synergistically and selectively recovered germanium from these solutions. A continuous solvent extraction circuit was operated for over 150 hr, extracting over 90% of the germanium from 0.30 g/L Ge filtrates containing 40 to 60 g/L free acid. Over 90% of the loaded germanium was stripped from the organic phase with water at 75 °C. A section on germanium and gallium co-extraction is also presented.
SUMOylation of α-tubulin is a novel modification regulating microtubule dynamics

Abstract Microtubules (MTs) are regulated by a number of known posttranslational modifications (PTMs) on α/β-tubulin to fulfill diverse cellular functions. Here, we showed that SUMOylation is a novel PTM on α-tubulin in vivo and in vitro. The SUMOylation on α-tubulin mainly occurred at Lys 96 (K96), K166, and K304 of soluble α-tubulin and could be removed by small ubiquitin-related modifier (SUMO)-specific peptidase 1. In vitro experiments showed that tubulin SUMOylation could reduce interprotofilament interaction, promote MT catastrophe, and impede MT polymerization. In cells, mutation of the SUMOylation sites on α-tubulin reduced catastrophe frequency and increased the proportion of polymerized α-tubulin, while upregulation of SUMOylation with fusion of SUMO1 reduced α-tubulin assembly into MTs. Additionally, overexpression of SUMOylation-deficient α-tubulin attenuated the neurite extension in Neuro-2a cells. Thus, SUMOylation on α-tubulin represents a new player in the regulation of MT properties.
Stock price reaction to cash dividend announcements in Vietnam

Mar. 31, 2017 This study attempts to investigate the stock price reaction to dividend announcements using data of Vietnamese listed firms on Hochiminh Stock Exchange (HOSE). Standard event study methodology has been employed on a sample of 198 cash dividend announcements made in 2011. The results show that stock prices react significantly and positively to the announcements of cash dividends, including both dividend increasing and dividend decreasing events. It is also plausible that cumulative abnormal returns exhibit an increasing trend before announcement yet a decreasing trend after announcement dates. More specifically, we find positively significant cumulative abnormal returns of around 1.03% on announcement dates; other larger windows also demonstrate positive abnormal returns of around 1.3%. In addition, cash dividends have different effects on share prices of firms from different industries. These results support the signaling hypothesis and are also consistent with prior findings of empirical research done on more developed markets, i.e. the US and the UK.
Estrogens in Swiss rivers and effluents: Sampling matters

Estrogenic activity of treated sewage effluents and receiving waters surfaced as an issue of general concern some 15 years ago. Since then, a large number of studies investigated the distribution and nature of the estrogenic substances in various aquatic ecosystems. Within NRP50, a five-year Swiss research programme on endocrine disruptors, four field studies were performed to characterize the presence of environmental estrogens in rivers and effluents. The estrogenic activity was quantified with a biological assay - the yeast estrogen screen. An overview of the sampling approaches and results of the various studies is presented here. In a first study, using grab sampling, it appeared that estrogenic activity in river water was highly variable. Average estrogenicity values did not correlate with sewage treatment works and/or river characteristics, e.g. effluent dilution factor. However, variability was not 'random' but clearly associated with river size, and possibly its discharge. A second study specifically addressed this issue of variability of estrogenicity. The study was conducted at a single effluent source and its receiving river. Variability of estrogenicity in the grab samples was again large but again not 'random'; some of the variability was explained by the time over which the effluent resided in the treatment process. In a third study it was explored if passive sampling would be a better way to assess average estrogenicity. Indeed, passive samplers identified sources of estrogens, and passive sampling data correlated well with both repeated grab sampling and bioaccumulation data. Subsequently, passive samplers were deployed across Switzerland in a fourth study. It involved 22 effluent discharges and the associated rivers. Data analysis of the last study is still ongoing, preliminary observations are discussed here. Although a lot could be learned from repeated grab sampling campaigns, it emerged that passive sampling is a very effective and appropriate technique to assess: i) effluent treatment efficiency, and ii) the chemical load of river water. For these reasons it is a valuable monitoring tool for water quality criteria assessments as well as for studies that aim to link exposure and effect. The passive samplers that are currently available not only target estrogenic substances, but many other polar organic compounds of concern, such as antibiotics (see NRP49), other pharmaceuticals and biocides.
SPECTROPHOTOMETRIC DETERMINATION OF RUTHENIUM

Conditions for the spectrophotometric determination of ruthenium as perruthenate have been established. Stable solutions of perruthenate are obtained only when the tetroxide is distilled into dilute sodium hydroxide (1M) containing hypochlorite. At higher hydroxide concentrations (6M) perruthenate is reduced rapidly by water to ruthenate even in the presence of hypochlorite. From 200 to 400 gamma of ruthenium can be determined to an accuracy of +2% at the 95% confldence level. An improved procedure for the distillation of ruthenium tetroxide which is particularly rapid and clean uses a slurry of sodium bismuthate in dilute sulfuric acid as the oxidant. (auth)
Surface sites on spinel-type and corundum-type metal oxide powders

The surface sites on isostructural metal oxides containing Al{sup 3+}, Fe{sup 3+}, and Cr{sup 3+} have been investigated by IR spectroscopy. The IR spectra of surface hydroxy groups and of pyridine coordinated on Lewis acidic surface cationic sites on the defective spinel-type sesquioxides {gamma}-Al{sub 2}O{sub 3}, {theta}-Al{sub 2}O{sub 3}, and {gamma}-Fe{sub 2}O{sub 3}, on the spinels MgAl{sub 2}O{sub 4}, MgFe{sub 2}O{sub 4}, MgCr{sub 2}O{sub 4}, ZnAl{sub 2}O{sub 4}, ZnFe{sub 2}O{sub 4}, and ZnCr{sub 2}O{sub 4}, as well as on the corundum-type sesquioxides {alpha}-Al{sub 2}O{sub 3}, {alpha}-Fe{sub 2}O{sub 3}, and {alpha}-Cr{sub 2}O{sub 3}, have been compared. Some Co{sup 2+} and Ni{sup 2+} spinel-type compounds have also been considered. An extension of the criteria previously proposed for the identification of the surface sites on aluminum-based materials to ferrites and chromites is suggested. The OH stretchings of surface hydroxy groups are indicative of the nature and the coordination of the cations to which they are bonded. Pyridine species bonded to tetrahedrally- and octahedrally-coordinated trivalent cations are well distinguishable on aluminates, while the distiction is more difficult for ferrites. 41 refs., 9 figs., 3 tabs.
Modeling of the oxidation of n-octane and n-decane using an automatic generation of mechanisms

Detailed modeling of the oxidation of n-octane and n-decane in the gas phase was performed by using mechanisms written by means of a software recently developed in our laboratory. This computer-aided design of mechanisms permits the automatic generation of detailed oxidation and combustion kinetic models in the case of paraffins and isoparaffins [1]. For n-octane, the predictions of the model were compared with experimental results obtained by Dryer and Brezinsky by means of a turbulent plug flow reactor (1080 K, 1 atm) [2]. The experimental study of Bales–Gueret et al., performed in a perfectly stirred reactor (922–1033 K, 1 atm) [3], was used as a basis of comparison for the modeling of the oxidation of n-decane. Considering that no fitting of any kinetic parameter was done, the agreement between the computed and the experimental values is satisfactory both for conversions and for the distribution of the products formed. This modeling has required improvement in the generation of the secondary reactions of alkenes, which are the main primary products obtained during the oxidation of these two alkanes in the range of temperature studied and for which reaction paths are detailed. © 1998 John Wiley & Sons, Inc. Int J Chem Kinet 30: 949–959, 1998
Infrared Resonant Desorption of H 2 O from Ice Multilayers

The resonant desorption of H2O from ice multilayers was studied using a train of picosecond pulses from an infrared free electron laser. The infrared light was used to excite the O−H stretching vibration in H2O in the ice multilayers and to cause H2O resonant desorption. The H2O resonant desorption spectrum was measured at infrared wavelengths between λ = 2.8 μm and λ = 3.4 μm. The peak H2O desorption yield occurred at λ = 3.0 μm. The H2O resonant desorption spectrum was substantially enhanced relative to the infrared absorption spectrum of ice at infrared wavelengths shorter than λ ∼ 3.1 μm. This enhancement was attributed to the melting of the ice film prior to H2O desorption and the temperature-dependent absorption coefficient of the O−H stretching vibration. The H2O desorption yields from 1 and 5 μm thick films were also measured at λ = 2.94 μm and λ = 3.09 μm for successive infrared pulses and versus pulse energy. The results were consistent with the melting of the ice film and the expected optical p.