ResearchPad - organic-compounds https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Collagen methionine sulfoxide and glucuronidine/LW-1 are markers of coronary artery disease in long-term survivors with type 1 diabetes. The Dialong study]]> https://www.researchpad.co/article/elastic_article_13877 Type 1 diabetes is a risk factor for coronary heart disease. The underlying mechanism behind the accelerated atherosclerosis formation is not fully understood but may be related to the formation of oxidation products and advanced glycation end-products (AGEs). We aimed to examine the associations between the collagen oxidation product methionine sulfoxide; the collagen AGEs methylglyoxal hydroimidazolone (MG-H1), glucosepane, pentosidine, glucuronidine/LW-1; and serum receptors for AGE (RAGE) with measures of coronary artery disease in patients with long-term type 1 diabetes.MethodsIn this cross-sectional study, 99 participants with type 1 diabetes of ≥ 45-year duration and 63 controls without diabetes had either established coronary heart disease (CHD) or underwent Computed Tomography Coronary Angiography (CTCA) measuring total, calcified and soft/mixed plaque volume. Skin collagen methionine sulfoxide and AGEs were measured by liquid chromatography-mass spectrometry and serum sRAGE/esRAGE by ELISA.ResultsIn the diabetes group, low levels of methionine sulfoxide (adjusted for age, sex and mean HbA1c) were associated with normal coronary arteries, OR 0.48 (95% CI 0.27–0.88). Glucuronidine/LW-1 was associated with established CHD, OR 2.0 (1.16–3.49). MG-H1 and glucuronidine/LW-1 correlated with calcified plaque volume (r = 0.23–0.28, p<0.05), while pentosidine correlated with soft/mixed plaque volume (r = 0.29, p = 0.008), also in the adjusted analysis.ConclusionsLow levels of collagen-bound methionine sulfoxide were associated with normal coronary arteries while glucuronidine/LW-1 was positively associated with established CHD in long-term type 1 diabetes, suggesting a role for metabolic and oxidative stress in the formation of atherosclerosis in diabetes. ]]> <![CDATA[Improvement of steatotic rat liver function with a defatting cocktail during <i>ex situ</i> normothermic machine perfusion is not directly related to liver fat content]]> https://www.researchpad.co/article/elastic_article_13803 There is a significant organ shortage in the field of liver transplantation, partly due to a high discard rate of steatotic livers from donors. These organs are known to function poorly if transplanted but make up a significant portion of the available pool of donated livers. This study demonstrates the ability to improve the function of steatotic rat livers using a combination of ex situ machine perfusion and a “defatting” drug cocktail. After 6 hours of perfusion, defatted livers demonstrated lower perfusate lactate levels and improved bile quality as demonstrated by higher bile bicarbonate and lower bile lactate. Furthermore, defatting was associated with decreased gene expression of pro-inflammatory cytokines and increased expression of enzymes involved in mitochondrial fatty acid oxidation. Rehabilitation of marginal or discarded steatotic livers using machine perfusion and tailored drug therapy can significantly increase the supply of donor livers for transplantation.

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<![CDATA[Amino acids serve as an important energy source for adult flukes of <i>Clonorchis sinensis</i>]]> https://www.researchpad.co/article/elastic_article_13829 Clonorchiasis, closely related to cholangiocarcinoma and hepatocellular carcinoma, has led to a negative socioeconomic impact in global areas especially some Asian endemic regions. Owing to the emergence of drug resistance and hypersensitivity reactions after the massive and repeated use of praziquantel as well as the lack of effective vaccines, searching for new strategies that prevent and treat clonorchiasis has become an urgent matter. Clonorchis sinensis, the causative agent of clonorchiasis, long-term inhabits the microaerobic and limited-glucose environment of the bile ducts. Adequate nutrients are essential for adult flukes to resist the adverse condition and survive in the crowed habitat. Studies on energy metabolism of adult flukes are beneficial for further exploring host-parasite interactions and developing novel anti-parasitic drugs. Our results suggest that gluconeogenesis probably plays a vital role in energy metabolism of Clonorchis sinensis and exogenous amino acids might be an essential energy source for adult flukes to successfully survive in the host. Our foundational study opens a new avenue for explaining energy metabolism of Clonorchis sinensis and provides a valuable strategy that the gluconeogenesis pathway will be a potential and novel target for the prevention and treatment of clonorchiasis.

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<![CDATA[A modified arginine-depleting enzyme NEI-01 inhibits growth of pancreatic cancer cells]]> https://www.researchpad.co/article/elastic_article_11227 Arginine deprivation cancer therapy targets certain types of malignancies with positive result in many studies and clinical trials. NEI-01 was designed as a novel arginine-depleting enzyme comprising an albumin binding domain capable of binding to human serum albumin to lengthen its half-life. In the present work, NEI-01 is shown to bind to serum albumin from various species, including mice, rat and human. Single intraperitoneal administration of NEI-01 to mice reduced plasma arginine to undetectable level for at least 9 days. Treatment of NEI-01 specifically inhibited cell viability of MIA PaCa-2 and PANC-1 cancer cell lines, which were ASS1 negative. Using a human pancreatic mouse xenograft model, NEI-01 treatment significantly reduced tumor volume and weight. Our data provides proof of principle for a cancer treatment strategy using NEI-01.

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<![CDATA[Pooling individual participant data from randomized controlled trials: Exploring potential loss of information]]> https://www.researchpad.co/article/elastic_article_7838 Pooling individual participant data to enable pooled analyses is often complicated by diversity in variables across available datasets. Therefore, recoding original variables is often necessary to build a pooled dataset. We aimed to quantify how much information is lost in this process and to what extent this jeopardizes validity of analyses results.MethodsData were derived from a platform that was developed to pool data from three randomized controlled trials on the effect of treatment of cardiovascular risk factors on cognitive decline or dementia. We quantified loss of information using the R-squared of linear regression models with pooled variables as a function of their original variable(s). In case the R-squared was below 0.8, we additionally explored the potential impact of loss of information for future analyses. We did this second step by comparing whether the Beta coefficient of the predictor differed more than 10% when adding original or recoded variables as a confounder in a linear regression model. In a simulation we randomly sampled numbers, recoded those < = 1000 to 0 and those >1000 to 1 and varied the range of the continuous variable, the ratio of recoded zeroes to recoded ones, or both, and again extracted the R-squared from linear models to quantify information loss.ResultsThe R-squared was below 0.8 for 8 out of 91 recoded variables. In 4 cases this had a substantial impact on the regression models, particularly when a continuous variable was recoded into a discrete variable. Our simulation showed that the least information is lost when the ratio of recoded zeroes to ones is 1:1.ConclusionsLarge, pooled datasets provide great opportunities, justifying the efforts for data harmonization. Still, caution is warranted when using recoded variables which variance is explained limitedly by their original variables as this may jeopardize the validity of study results. ]]> <![CDATA[Juvenile hormone suppresses aggregation behavior through influencing antennal gene expression in locusts]]> https://www.researchpad.co/article/elastic_article_7742 A behavioral change from shy solitarious individuals to highly social gregarious individuals is critical to the formation of disastrous swarms of locusts. However, the underlying molecular mechanism of behavioral plasticity regulated by hormones is still largely unknown. Here, we investigated the effect of juvenile hormone (JH) on the behavioral transition in fourth-instar gregarious and solitarious locusts. We found that JH induced the behavioral shift of the gregarious locust from attraction to repulsion to the volatiles of gregarious locusts. The solitarious locust significantly decreased repulsion behavior after deprivation of JH by precocene or knockdown of JHAMT, a key enzyme to synthesize JH. JH application on gregarious locusts caused significant expression alteration of genes, especially the olfactory genes TO and CSP in the antennae. We further demonstrated that the JH signaling pathway suppressed aggregation behavior in gregarious locusts by increasing TO1 expression and decreasing CSP3 expression at the same time. Our results suggested that internal physiological factors can directly modulate periphery olfactory system to produce behavioral plasticity.

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<![CDATA[Nutritional and physicochemical characteristics of purple sweet corn juice before and after boiling]]> https://www.researchpad.co/article/elastic_article_7720 Sweet corn juice is becoming increasingly popular in China. In order to provide valuable health-related information to consumers, the nutritional and physicochemical characteristics of raw and boiled purple sweet corn juices were herein investigated. Sugars, antinutrients, total free phenols, anthocyanins, and antioxidant activity were analyzed by conventional chemical methods. The viscosity and stability of juices were determined by Ubbelohde viscosity meter and centrifugation, respectively. Boiling process could elevate viscosity, stability and sugar content, and reduce antinutrients, total free phenols, anthocyanins, and antioxidant activity in corn juice. In addition, short time boiling efficiently reduced the degradation of anthocyanins during subsequent refrigeration. The content of amino acids, vitamin B1/B2 and E were detected by High Performance Liquid Chromatography. Gas Chromatography Mass Spectrometry was used for the analysis of fatty acids and aroma compounds. Several aroma compounds not previously reported in corn were identified, including 1-heptanol, 2-methyl-2-butenal, (Z)-3-nonen-1-ol, 3-ethyl-2-methyl-1,3-hexadiene, and 2,4-bis(1,1-dimethylethyl)phenol. Interestingly, the boiling process had no apparent effect on the amino acids profile, but it caused a 45.8% loss of fatty acids in the juice by promoting the retention of fatty acids in the corn residue. These results provide detailed information that could be used for increasing consumers’ knowledge of sweet corn juice, further development of sweet corn juice by food producers, and maize breeding programs.

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<![CDATA[Digestibility of black soldier fly larvae (<i>Hermetia illucens</i>) fed to leopard geckos (<i>Eublepharis macularius</i>)]]> https://www.researchpad.co/article/elastic_article_7714 Black soldier fly (BSF) larvae have been marketed as an excellent choice for providing calcium to reptiles without the need of dusting or gut loading. However, previous studies have indicated that they have limited calcium digestibility and are deficient in fat soluble vitamins (A, D3, and E). In this feeding and digestibility trial, 24 adult male leopard geckos were fed one of three diets for 4 months: 1) whole, vitamin A gut loaded larvae; 2) needle pierced, vitamin A gut loaded larvae; or 3) whole, non-gut loaded larvae. Fecal output from the geckos was collected daily and apparent digestibility was calculated for dry matter, protein, fat, and minerals. There were no differences in digestibility coefficients among groups. Most nutrients were well digested by the leopard geckos when compared to previous studies, with the exception of calcium (digestibility co-efficient 43%), as the calcium-rich exoskeleton usually remained intact after passage through the GI tract. Biochemistry profiles revealed possible deficits occurring over time for calcium, sodium, and total protein. In regards to vitamin A digestibility, plasma and liver vitamin A concentrations were significantly higher in the supplemented groups (plasma- gut loaded groups: 33.38 ± 7.11 ng/ml, control group: 25.8 ± 6.72 ng/ml, t = 1.906, p = 0.04; liver- gut loaded groups: 28.67 ± 18.90 μg/g, control group: 14.13 ± 7.41 μg/g, t = 1.951, p = 0.03). While leopard geckos are able to digest most of the nutrients provided by BSF larvae, including those that have been gut loaded, more research needs to be performed to assess whether or not they provide adequate calcium in their non-supplemented form.

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<![CDATA[Multipurpose chemical liquid sensing applications by microwave approach]]> https://www.researchpad.co/article/elastic_article_7700 In this work, a novel sensor based on printed circuit board (PCB) microstrip rectangular patch antenna is proposed to detect different ratios of ethanol alcohol in wines and isopropyl alcohol in disinfectants. The proposed sensor was designed by finite integration technique (FIT) based high-frequency electromagnetic solver (CST) and was fabricated by Proto Mat E33 machine. To implement the numerical investigations, dielectric properties of the samples were first measured by a dielectric probe kit then uploaded into the simulation program. Results showed a linear shifting in the resonant frequency of the sensor when the dielectric constant of the samples were changed due to different concentrations of ethanol alcohol and isopropyl alcohol. A good agreement was observed between the calculated and measured results, emphasizing the usability of dielectric behavior as an input sensing agent. It was concluded that the proposed sensor is viable for multipurpose chemical sensing applications.

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<![CDATA[Abrogation of pathogenic attributes in drug resistant <i>Candida auris</i> strains by farnesol]]> https://www.researchpad.co/article/elastic_article_7651 Candida auris, a decade old Candida species, has been identified globally as a significant nosocomial multidrug resistant (MDR) pathogen responsible for causing invasive outbreaks. Biofilms and overexpression of efflux pumps such as Major Facilitator Superfamily and ATP Binding Cassette are known to cause multidrug resistance in Candida species, including C. auris. Therefore, targeting these factors may prove an effective approach to combat MDR in C. auris. In this study, 25 clinical isolates of C. auris from different hospitals of South Africa were used. All the isolates were found capable enough to form biofilms on 96-well flat bottom microtiter plate that was further confirmed by MTT reduction assay. In addition, these strains have active drug efflux mechanism which was supported by rhodamine-6-G extracellular efflux and intracellular accumulation assays. Antifungal susceptibility profile of all the isolates against commonly used drugs was determined following CLSI recommended guidelines. We further studied the role of farnesol, an endogenous quorum sensing molecule, in modulating development of biofilms and drug efflux in C. auris. The MIC for planktonic cells ranged from 62.5–125 mM, and for sessile cells was 125 mM (4h biofilm) and 500 mM (12h and 24h biofilm). Furthermore, farnesol (125 mM) also suppresses adherence and biofilm formation by C. auris. Farnesol inhibited biofilm formation, blocked efflux pumps and downregulated biofilm- and efflux pump- associated genes. Modulation of C. auris biofilm formation and efflux pump activity by farnesol represent a promising approach for controlling life threatening infections caused by this pathogen.

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<![CDATA[Aspirin-triggered resolvin D1 attenuates PDGF-induced vascular smooth muscle cell migration via the cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) pathway]]> https://www.researchpad.co/article/5989db50ab0ee8fa60bdc0e7

Background and objectives

Resolvin D1 (RvD1) is a specialized pro-resolving lipid mediator that has been previously shown to attenuate vascular smooth muscle cell (VSMC) migration, a key process in the development of intimal hyperplasia. We sought to investigate the role of the cAMP/PKA pathway in mediating the effects of the aspirin-triggered epimer 17R-RvD1 (AT-RvD1) on VSMC migration.

Methods

VSMCs were harvested from human saphenous veins. VSMCs were analyzed for intracellular cAMP levels and PKA activity after exposure to AT-RvD1. Platelet-derived growth factor (PDGF)-induced migration and cytoskeletal changes in VSMCs were observed through scratch, Transwell, and cell shape assays in the presence or absence of a PKA inhibitor (Rp-8-Br-cAMP). Further investigation of the pathways involved in AT-RvD1 signaling was performed by measuring Rac1 activity, vasodilator stimulated phosphoprotein (VASP) phosphorylation and paxillin translocation. Finally, we examined the role of RvD1 receptors (GPR32 and ALX/FPR2) in AT-RvD1 induced effects on VSMC migration and PKA activity.

Results

Treatment with AT-RvD1 induced a significant increase in cAMP levels and PKA activity in VSMCs at 5 minutes and 30 minutes, respectively. AT-RvD1 attenuated PDGF-induced VSMC migration and cytoskeletal rearrangements. These effects were attenuated by the PKA inhibitor Rp-8-Br-cAMP, suggesting cAMP/PKA involvement. Treatment of VSMC with AT-RvD1 inhibited PDGF-stimulated Rac1 activity, increased VASP phosphorylation, and attenuated paxillin localization to focal adhesions; these effects were negated by the addition of Rp-8-Br-cAMP. The effects of AT-RvD1 on VSMC migration and PKA activity were attenuated by blocking ALX/FPR2, suggesting an important role of this G-protein coupled receptor.

Conclusions

Our results suggest that AT-RvD1 attenuates PDGF-induced VSMC migration via ALX/FPR2 and cAMP/PKA. Interference with Rac1, VASP and paxillin function appear to mediate the downstream effects of AT-RvD1 on VSMC migration.

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<![CDATA[Chitosan-propolis nanoparticle formulation demonstrates anti-bacterial activity against Enterococcus faecalis biofilms]]> https://www.researchpad.co/article/5989db50ab0ee8fa60bdc122

Propolis obtained from bee hives is a natural substance with antimicrobial properties. It is limited by its insolubility in aqueous solutions; hence ethanol and ethyl acetate extracts of Malaysian propolis were prepared. Both the extracts displayed antimicrobial and anti-biofilm properties against Enterococcus faecalis, a common bacterium associated with hospital-acquired infections. High performance liquid chromatography (HPLC) analysis of propolis revealed the presence of flavonoids like kaempferol and pinocembrin. This study investigated the role of propolis developed into nanoparticles with chitosan for its antimicrobial and anti-biofilm properties against E. faecalis. Bacteria that grow in a slimy layer of biofilm are resistant to penetration by antibacterial agents. The use of nanoparticles in medicine has received attention recently due to better bioavailability, enhanced penetrative capacity and improved efficacy. A chitosan-propolis nanoformulation was chosen based on ideal physicochemical properties such as particle size, zeta potential, polydispersity index, encapsulation efficiency and the rate of release of the active ingredients. This formulation inhibited E. faecalis biofilm formation and reduced the number of bacteria in the biofilm by ~90% at 200 μg/ml concentration. When tested on pre-formed biofilms, the formulation reduced bacterial number in the biofilm by ~40% and ~75% at 200 and 300 μg/ml, respectively. The formulation not only reduced bacterial numbers, but also physically disrupted the biofilm structure as observed by scanning electron microscopy. Treatment of biofilms with chitosan-propolis nanoparticles altered the expression of biofilm-associated genes in E. faecalis. The results of this study revealed that chitosan-propolis nanoformulation can be deemed as a potential anti-biofilm agent in resisting infections involving biofilm formation like chronic wounds and surgical site infections.

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<![CDATA[Physicochemical and biological evaluation of JR-131 as a biosimilar to a long-acting erythropoiesis-stimulating agent darbepoetin alfa]]> https://www.researchpad.co/article/Na789b0ff-1b14-409c-afa6-0c7a70fc7c42

Renal anemia is predominantly caused by a relative deficiency in erythropoietin (EPO). Conventional treatment for renal anemia includes the use of recombinant human EPO (rhEPO) or a long-acting erythropoiesis-activating agent named darbepoetin alfa, which is a modified rhEPO with a carbohydrate chain structure that differs from native hEPO. We have developed a biosimilar to darbepoetin alfa designated JR-131. Here, we comprehensively compare the physicochemical and biological characteristics of JR-131 to darbepoetin alfa. JR-131 demonstrated similar protein structure to the originator, darbepoetin alfa, by peptide mapping and circular dichroism spectroscopy. Additionally, mass spectroscopic analyses and capillary zone electrophoresis revealed similar glycosylation patterns between the two products. Human bone marrow-derived erythroblasts differentiated and proliferated to form colonies with JR-131 to a similar degree as darbepoetin alfa. Finally, JR-131 stimulated erythropoiesis and improved anemia in rats similarly to darbepoetin alfa. Our data show the similarity in physicochemical and biological properties of JR-131 to those of darbepoetin alfa, and JR-131 therefore represents a biosimilar for use in the treatment of renal anemia.

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<![CDATA[Effectiveness of the Common Elements Treatment Approach (CETA) in reducing intimate partner violence and hazardous alcohol use in Zambia (VATU): A randomized controlled trial]]> https://www.researchpad.co/article/N3889b1ed-7187-41ba-b4d5-94f42ba3d649

Background

Both intimate partner violence (IPV) and alcohol misuse are highly prevalent, and partner alcohol misuse is a significant contributor to women’s risk for IPV. There are few evidence-based interventions to address these problems in low- and middle-income countries (LMICs). We evaluated the effectiveness of an evidence-based, multi-problem, flexible, transdiagnostic intervention, the Common Elements Treatment Approach (CETA) in reducing (a) women’s experience of IPV and (b) their male partner’s alcohol misuse among couples in urban Zambia.

Methods and findings

This was a single-blind, parallel-assignment randomized controlled trial in Lusaka, Zambia. Women who reported moderate or higher levels of IPV and their male partners with hazardous alcohol use were enrolled as a couple and randomized to CETA or treatment as usual plus safety checks (TAU-Plus). The primary outcome, IPV, was assessed by the Severity of Violence Against Women Scale (SVAWS) physical/sexual violence subscale, and the secondary outcome, male alcohol misuse, by the Alcohol Use Disorders Identification Test (AUDIT). Assessors were blinded. Analyses were intent-to-treat. Primary outcome assessments were planned at post-treatment, 12 months post-baseline, and 24 months post-baseline. Enrollment was conducted between May 23, 2016, and December 17, 2016. In total, 123 couples were randomized to CETA, 125 to TAU-Plus. The majority of female (66%) and a plurality of male (48%) participants were between 18 and 35 years of age. Mean reduction in IPV (via SVAWS subscale score) at 12 months post-baseline was statistically significantly greater among women who received CETA compared to women who received TAU-Plus (−8.2, 95% CI −14.9 to −1.5, p = 0.02, Cohen’s d effect size = 0.49). Similarly, mean reduction in AUDIT score at 12 months post-baseline was statistically significantly greater among men who received CETA compared to men who received TAU (−4.5, 95% CI −6.9 to −2.2, p < 0.001, Cohen’s d effect size = 0.43). The Data and Safety Monitoring Board recommended the trial be stopped early due to treatment effectiveness following the 12-month post-baseline assessment, and CETA was offered to control participants. Limitations of the trial included the lack of a true control condition (i.e., that received no intervention), self-reported outcomes that may be subject to social desirability bias, and low statistical power for secondary IPV outcomes.

Conclusions

Results showed that CETA was more effective than TAU-Plus in reducing IPV and hazardous alcohol use among high-risk couples in Zambia. Future research and programming should include tertiary prevention approaches to IPV, such as CETA, rather than offering only community mobilization and primary prevention.

Trial registration

The trial was registered on ClinicalTrials.gov (NCT02790827).

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<![CDATA[Uptake and speciation of zinc in edible plants grown in smelter contaminated soils]]> https://www.researchpad.co/article/N21b4cc8f-fdc5-4198-8cfa-2868c1971919

Heavy metal accumulation in edible plants grown in contaminated soils poses a major environmental risk to humans and grazing animals. This study focused on the concentration and speciation of Zn in different edible plants grown in soils contaminated with smelter wastes (Spelter, WV, USA) containing high levels of the metals Zn, Cu, Pb, Cd. Their accumulation was examined in different parts (roots, stem, and leaves) of plants and as a function of growth stage (dry seed, sprouting seed, cotyledon, and leaves) in the root vegetables radish, the leafy vegetable spinach and the legume clover. Although the accumulation of metals varied significantly with plant species, the average metal concentrations were [Zn] > [Pb] > [Cu] > [Cd]. Metal uptake studies were complemented with bulk and micro X-ray absorption spectroscopy (XAS) at Zn K-edge and micro X-ray fluorescence (μXRF) measurements to evaluate the speciation and distribution of Zn in these plant species. Dynamic interplay between the histidine and malate complexation of Zn was observed in all plant species. XRF mapping of spinach leaves at micron spatial resolution demonstrated the accumulation of Zn in vacuoles and leaf tips. Radish root showed accumulation of Zn in root hairs, likely as ZnS nanoparticles. At locations of high Zn concentration in spinach leaves, μXANES suggests Zn complexation with histidine, as opposed to malate in the bulk leaf. These findings shed new light on the dynamic nature of Zn speciation in plants.

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<![CDATA[Stepwise stroke recognition through clinical information, vital signs, and initial labs (CIVIL): Electronic health record-based observational cohort study]]> https://www.researchpad.co/article/N0f0adfcb-3c92-4db3-bdce-cd884fd183e7

Background

Stroke recognition systems have been developed to reduce time delays, however, a comprehensive triaging score identifying stroke subtypes is needed to guide appropriate management. We aimed to develop a prehospital scoring system for rapid stroke recognition and identify stroke subtype simultaneously.

Methods and findings

In prospective database of regional emergency and stroke center, Clinical Information, Vital signs, and Initial Labs (CIVIL) of 1,599 patients suspected of acute stroke was analyzed from an automatically-stored electronic health record. Final confirmation was performed with neuroimaging. Using multiple regression analyses, we determined independent predictors of tier 1 (true-stroke or not), tier 2 (hemorrhagic stroke or not), and tier 3 (emergent large vessel occlusion [ELVO] or not). The diagnostic performance of the stepwise CIVIL scoring system was investigated using internal validation. A new scoring system characterized by a stepwise clinical assessment has been developed in three tiers. Tier 1: Seven CIVIL-AS3A2P items (total score from –7 to +6) were deduced for true stroke as Age (≥ 60 years); Stroke risks without Seizure or psychiatric disease, extreme Sugar; “any Asymmetry”, “not Ambulating”; abnormal blood Pressure at a cut-off point ≥ 1 with diagnostic sensitivity of 82.1%, specificity of 56.4%. Tier 2: Four items for hemorrhagic stroke were identified as the CIVIL-MAPS indicating Mental change, Age below 60 years, high blood Pressure, no Stroke risks with cut-point ≥ 2 (sensitivity 47.5%, specificity 85.4%). Tier 3: For ELVO diagnosis: we applied with CIVIL-GFAST items (Gaze, Face, Arm, Speech) with cut-point ≥ 3 (sensitivity 66.5%, specificity 79.8%). The main limitation of this study is its retrospective nature and require a prospective validation of the CIVIL scoring system.

Conclusions

The CIVIL score is a comprehensive and versatile system that recognizes strokes and identifies the stroke subtype simultaneously.

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<![CDATA[Understanding ambivalence in help-seeking for suicidal people with comorbid depression and alcohol misuse]]> https://www.researchpad.co/article/N5bd48253-819c-499c-aeec-83c12fc90159

Help-seeking prior to a suicide attempt is poorly understood. Participants were recruited from a previous research trial who reported a history of suicidal behaviours upon follow-up. Qualitative interviews were conducted with six adults to understand their lived experience of a suicide attempt and the issues affecting help-seeking prior to that attempt. Participants described being aware of personal and professional supports available; however, were ambivalent about accessing them for multiple reasons. This paper employs an ecological systems framework to better understand the complex and multi-layered interpersonal, societal and cultural challenges to help-seeking that people with suicidal ideation can experience.

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<![CDATA[A compound attributes-based predictive model for drug induced liver injury in humans]]> https://www.researchpad.co/article/Ndeb57c49-a1cc-41d4-9618-08dc56c45dac

Drug induced liver injury (DILI) is one of the key safety concerns in drug development. To assess the likelihood of drug candidates with potential adverse reactions of liver, we propose a compound attributes-based approach to predicting hepatobiliary disorders that are routinely reported to US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). Specifically, we developed a support vector machine (SVM) model with recursive feature extraction, based on physicochemical and structural properties of compounds as model input. Cross validation demonstrates that the predictive model has a robust performance with averaged 70% of both sensitivity and specificity over 500 trials. An independent validation was performed on public benchmark drugs and the results suggest potential utility of our model for identifying safety alerts. This in silico approach, upon further validation, would ultimately be implemented, together with other in vitro safety assays, for screening compounds early in drug development.

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<![CDATA[Variation in plasma 25-hydroxyvitamin D2 and D3 in normal pregnancy with gestational age, sampling season, and complications: A longitudinal cohort study]]> https://www.researchpad.co/article/Ndf1a2733-e0b1-4fc7-90ad-b2bfa4368f5f

Introduction

Low levels of vitamin D in pregnancy have been associated with the risk of a variety of pregnancy outcomes. Few studies have investigated vitamin D concentrations throughout pregnancy in healthy women, and most guidelines recommend high vitamin D levels. In the present study, we investigated 25-hydroxyvitamin D concentrations in healthy Caucasian Danish women in relation to season, gestational age and possible vitamin D-linked complications.

Materials and methods

Eight hundred and one healthy Caucasian Danish women with an expected normal pregnancy were recruited among 2147 women attending first trimester screening. Seven blood samplings were planned throughout the pregnancy and delivery period. The 25-hydroxyvitamin D2 (25(OH)D2) and 25-hydroxyvitamin D3 (25(OH)D3) concentrations were measured by LC-MS/MS and total 25-hydroxyvitamin D (25(OH)D) were calculated.

Results

A total of 3304 samples from 694 women were available for 25(OH)D measurements. The mean (25th-75th percentiles) concentrations of 25(OH)D, 25(OH)D3, and 25(OH)D2 were 54.6 (38.8–68.6) nmol/L, 52.2 (36.4–66.4) nmol/L, and 2.4 (2.2–2.2) nmol/L, respectively. Season was the strongest predictor of 25(OH)D concentration, with the lowest values observed in winter and spring, where only 42% and 41% of samples, respectively, were above 50 nmol/L. Nearly all women had values below the suggested optimal level of 75 nmol/L, independent of season. 25(OH)D peaked at gestational weeks 21–34. Plasma 25(OH)D2 levels were low in all seasons. Women with complications during pregnancy had higher 25(OH)D (estimated difference 9.8 nmol/L, standard error 2.7, p<0.001) than did women without complications, and women giving birth vaginally had lower 25(OH)D than did those delivering via elective (10.0 nmol/L, standard error 2.1, p<0.001) or emergency cesarean section (6.8 nmol/L, standard error 2.2, p<0.001).

Conclusion

The 25(OH)D concentrations vary with both season and gestational age. Healthy women had lower 25(OH)D concentrations than recommended, without an association with an increased risk of pregnancy complications. Guidelines for vitamin D in pregnancy may require revision.

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<![CDATA[The effect of NaOH pretreatment on coal structure and biomethane production]]> https://www.researchpad.co/article/Nec5b1db1-34f5-4425-bec1-1f1e431a6eb6

Biogenic CBM is an important component of detected CBM, which is formed by coal biodegradation and can be regenerated by anaerobic microorganisms. One of the rate-limiting factors for microbial degradation is the bioavailability of coal molecules, especially for anthracite which is more condense and has higher aromaticity compared with low-rank coal. In this paper, NaOH solution with different concentrations and treating time was employed to pretreat anthracite from Qinshui Basin to alter the coal structure and facilitate the biodegradation. The results showed that the optimal pretreatment conditions were 1.5 M NaOH treating for 12 h, under which the biomethane production was increased by 17.65% compared with untreated coal. The results of FTIR and XRD showed that NaOH pretreatment mainly reduced the multi-substituted aromatics, increased the C-O in alcohols and aromatic ethers and the branching degree of aliphatic chain, and decreased the aromatic ring structure, resulting in the improvement of coal bioavailability and enhancement of biomethane yield. And some organics with potential to generate methane were released to filtrate as revealed by GC-MS. Our results suggested that NaOH was an effective solution for pretreating coal to enhance biogenic methane production, and anthracite after treating with NaOH could be the better substrate for methanogenesis.

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