bluuebunny/crossref_metadata_2025 huggingface dataset:
Nanoparticulate RNA delivery systems in cancer
Authors: Sharma Ankur , Jha Niraj Kumar , Dahiya Kajal , Singh Vivek Kumar , Chaurasiya Kundan , Jha Aditya Narayan , Jha Saurabh Kumar , Mishra Prabhu Chandra , Dholpuria Sunny , Astya Rani , Nand Parma , Kumar Amit , Ruokolainen Janne , Kesari Kavindra Kumar
Published: July 2020

Background

Drug delivery system is a common practice in cancer treatment. RNA interference‐mediated post‐transcriptional gene silencing holds promise as an approach to knockdown in the expression of target genes responsible for cancer cell growth and metastasis. RNA interference (RNAi) can be achieved by delivering small interfering RNA (siRNA) and short hairpin RNA (shRNA) to target cells. Since neither interfering RNAs can be delivered in naked form due to poor stability, an efficient delivery system is required that protects, guides, and delivers the siRNA and shRNA to target cells as part of cancer therapy (chemotherapy).

Recent findings

In this review, a discussion is presented about the different types of drug delivery system used to deliver siRNA and shRNA, together with an overview of the potential benefits associated with this sophisticated biomolecular therapy. Improved understanding of the different approaches used in nanoparticle (NP) fabrication, along with an enhanced appreciation of the biochemical properties of siRNA/shRNA, will assist in developing improved drug delivery strategies in basic and clinical research.

Conclusion

These novel delivery techniques are able to solve the problems that form an inevitable part of delivering genes in more efficient manner and as part of more effective treatment protocols. The present review concludes that the nanoparticulate RNA delivery system has great possibility for cancer treatment along with several other proposed methods. Several NPs or nanocarriers are already in use, but the methods proposed here could fulfill the missing gap in cancer research. It is the future technology, which unravels the mystery of resolving genomic diseases that is, especially genomic instability and its signaling cascades.
The Effect of Heteroatom Doping on Nickel Cobalt Oxide Electrocatalysts for Oxygen Evolution and Reduction Reactions
Authors: Belkessam Celia , Bencherif Selma , Mechouet Mourad , Idiri Naima , Ghilane Jalal
Published: July 2020

The synthesis of nickel cobalt oxide materials and their electrocatalytic performance toward the oxygen reduction and evolution reactions are reported. Nickel cobalt oxides were synthesized in a sol‐gel process with different precursors, namely nitrate, sulfate, and chloride. Structural analyses show that the structures have mesoporous morphologies and indicate the formation of nickel cobalt oxide spinel structures with a size ranging from 35 to 65 nm. Furthermore, the physicochemical properties differ depending on the nature of the selected precursors, including the materials’ morphology and the chemical composition. Electrocatalytic investigations demonstrate that the catalytic activity toward the oxygen reduction reaction (ORR) could be modulated between two‐ and four‐electron pathways, depending on the precursors used. The Cl−NiCoO sample displays a selective two‐electron reduction of O2, with H2O2 production higher than 90 %. The sample prepared using sulfate displays the highest performance toward the oxygen evolution reaction (OER), with a low overpotential value (0.34 V) to drive a current density of 10 mA.cm−1. Overall, these results confirm that the chemical composition of the precursor used during the nanomaterials synthesis can be used to tune the electrocatalytic performances toward ORR and OER.
High‐Throughput Cellular RNA Sequencing (HiCAR‐Seq): Cost‐Effective, High‐Throughput 3′ mRNA‐Seq Method Enabling Individual Sample Quality Control
Authors: Veeranagouda Yaligara , Zachayus Jean‐Luc , Guillemot Jean‐Claude , Venier Olivier , Didier Michel
Published: July 2020

High‐throughput screening is one of the pillars of drug development. Unbiased transcriptome profiling is now widely used for a deeper understanding of a drug's mechanisms of action, off target effects, and cytotoxicity. Although currently available high‐throughput RNA‐Seq (HT RNA‐Seq) methods such as PLATE‐Seq, DRUG‐Seq, and BRB‐Seq serve these purposes, the inherent nature of these methods does not allow sample‐wise sequencing library quality control. Here, we describe an HTR method called High‐throughput CellulAr RNA Sequencing (HiCAR‐Seq). HiCAR‐Seq was optimized to work directly on cultured cells (as little as 1,000 cells) or 10 ng of total RNA. HiCAR‐Seq involves reverse transcription from cultured cells or total RNA using oligo‐dT primers followed by the PCR amplification of full‐length cDNAs using sample‐specific barcode primers in individual plate wells. Amplification of cDNA from every sample can be verified using Bioanalyzer. This step not only reveals cDNA amplification but also provides greater precision for pooling equal concentrations of cDNA from different samples. A single pooled cDNA library is made suitable for sequencing on Illumina sequencers using a tagmentation kit. Because HiCAR‐Seq targets a small region at the 3′ of the mRNAs, as little as 3 to 4 million reads/sample are enough to infer changes in gene expression in human or mouse cells. We believe that HiCAR‐Seq represents a robust and competitive addition to the existing set of transcriptome‐based high‐throughput screening methods. © 2020 Wiley Periodicals LLC.

Basic Protocol 1: cDNA synthesis and barcoding/enrichment PCR

Basic Protocol 2: Nextera tagmentation/amplification, quantification, and sequencing
Fine‐Tuning the Physicochemical and Electroluminescence Properties of Multiply‐Substituted Bipolar Carbazoles by Functional Group Juggling
Authors: Konidena Rajendra Kumar , Thomas K. R. Justin , Dubey Deepak Kumar , Sahoo Snehasis , Jou Jwo‐Huei
Published: July 2020

The nature of chromophores often plays a decisive role in imparting properties to functional materials. In this work, we demonstrate that the position of the chromophoric unit on the carbazole core is crucial to tune the photophysical and electroluminescence properties. A series of bipolar compounds featuring carbazole donor and cyano acceptor groups are used as model compounds to evaluate the proposed hypothesis. It is revealed that the conjugation connectivity and chromophore density significantly affects the functional properties of the dyes. A compound featuring carbazole on the C2 and C7 positions of a carbazole core displayed a more bathochromic absorption band than its structural isomer with carbazole on C1 and C8 positions. A major change in emission properties is achieved on changing the position of the carbazole and cyano units on carbazole nucleus. The emission spectra of the dyes are sensitive to solvent polarity and displayed positive solvatochromism attributable to the photoinduced charge transfer from the peripheral carbazole donor to the cyano acceptor. They are demonstrated as dopant emitters in solution‐processed multilayer organic light emitting devices and exhibited deep‐blue or sky‐blue emission with CIE coordinates varying in the range: 0.14≤x≤0.20, 0.07≤y≤0.16. A compound containing a carbazole donor on C3 and C6 and a cyano acceptor on C2 and C7 positions of the carbazole core exhibited the best performance in an OLED with a maximum external quantum efficiency of 3.4 %.
Antibacterial azole derivatives: Antibacterial activity, cytotoxicity, and in silico mechanistic studies
Authors: Sari Suat , Avci Ahmet , Koçak Ebru , Kart Didem , Sabuncuoğlu Suna , Doğan İnci Selin , Özdemir Zeynep , Bozbey İrem , Karakurt Arzu , Saraç Selma , Dalkara Sevim
Published: July 2020

Azole antifungal drugs are commonly used in antifungal chemotherapy. Antibacterial effects of some topical antifungals, such as miconazole and econazole, have lately been revealed, which suggests a promising venue in antimicrobial chemotherapy. In this study, we tested an in‐house azole collection with antifungal properties for their antibacterial activity to identify dual‐acting hits using the broth microdilution method. The in vitro screen yielded a number of potent derivatives against gram‐positive bacteria, Enterococcus faecalis and Staphylococcus aureus. Compound 73's minimum inhibitory concentration (MIC) value less than 1 μg/ml against S. aureus; however, none of the compounds showed noteworthy activity against methicillin‐resistant S. aureus (MRSA). All the active compounds were found safe at their MIC values against the healthy fibroblast cells in the in vitro cytotoxicity test. Molecular docking studies of the most active compounds using a set of docking programs with flavohemoglobin (flavoHb) structure, the proposed target of the azole antifungals with antibacterial activity, presented striking similarities regarding the binding modes and interactions between the tested compounds and the antifungal drugs with crystallographic data. In addition to being noncytotoxic, the library was predicted to be drug‐like and free of pan‐assay interference compounds (PAINS). As a result, the current study revealed several potential azole derivatives with both antifungal and antibacterial activities. Inhibition of bacterial flavoHb was suggested as a possible mechanism of action for the title compounds.
Notch and Bmp signaling pathways act coordinately during the formation of the proepicardium
Authors: Andrés‐Delgado Laura , Galardi‐Castilla María , Münch Juliane , Peralta Marina , Ernst Alexander , González‐Rosa Juan Manuel , Tessadori Federico , Santamaría Luis , Bakkers Jeroen , Vermot Julien , de la Pompa José Luis , Mercader Nadia
Published: July 2020

Background

The epicardium is the outer mesothelial layer of the heart. It encloses the myocardium and plays key roles in heart development and regeneration. It derives from the proepicardium (PE), cell clusters that appear in the dorsal pericardium (DP) close to the atrioventricular canal and the venous pole of the heart, and are released into the pericardial cavity. PE cells are advected around the beating heart until they attach to the myocardium. Bmp and Notch signaling influence PE formation, but it is unclear how both signaling pathways interact during this process in the zebrafish.

Results

Here, we show that the developing PE is influenced by Notch signaling derived from the endothelium. Overexpression of the intracellular receptor of notch in the endothelium enhances bmp expression, increases the number of pSmad1/5 positive cells in the DP and PE, and enhances PE formation. On the contrary, pharmacological inhibition of Notch1 impairs PE formation. bmp2b overexpression can rescue loss of PE formation in the presence of a Notch1 inhibitor, but Notch gain‐of‐function could not recover PE formation in the absence of Bmp signaling.

Conclusions

Endothelial Notch signaling activates bmp expression in the heart tube, which in turn induces PE cluster formation from the DP layer.
Soil biota increase the likelihood for coexistence among competing plant species
Authors: Stein Claudia , Mangan Scott A.
Published: July 2020

Theory predicts that stable species coexistence will occur when population growth rates of competitively dominant species are suppressed when at high conspecific density. Although there is now compelling evidence that plant communities exhibit negative density dependence, the relative importance of the underlying processes leading to these patterns is rarely tested. We coupled reciprocal greenhouse and field experiments with community dynamics modeling to untangle the relative importance of soil biota from competition as stabilizing forces to coexistence. We found that (1) plant–soil biotic interactions compared to competitive interactions were stronger stabilizing forces, (2) only the strength of plant–soil biotic interactions was dependent on plant evolutionary history, and (3) the variation in the strength of plant–soil biotic interactions was correlated with relative abundance patterns in an opposite way than was the variation in the strength of competitive interactions. Collectively, our results demonstrate the fundamental role soil biota have in maintaining plant community diversity.
The misuse of ratios in ecological stoichiometry
Authors: Isles Peter D. F.
Published: July 2020

Ecological stoichiometry is concerned with the ratios of different elements, particularly carbon, nitrogen, and phosphorus. Ratios by their nature do not respond symmetrically to changes in the numerator and denominator and do not follow normal distributions; however, researchers frequently fail to consider these properties in their analyses, which has biased reported results. Calculating means, variance, or linear slopes based on untransformed ratios results in biased results. I demonstrate the consequences of these errors for inferences from stoichiometric analyses using simple examples and several large monitoring data sets. I then review 100 studies in ecological stoichiometry and find that misuse of ratio data is common, with 93% of studies containing at least one error. These errors may be problematic, particularly in large‐scale meta‐analyses summarizing data over large ranges. Fortunately, most of these mistakes can be easily avoided by first log transforming elemental ratios. I therefore recommend that, to ensure robust and reproducible results, researchers in ecological stoichiometry should adopt a convention of presenting stoichiometric ratio data as the logarithm of molar ratios in the future. The widespread use of untransformed nitrogen to phosphorus ratio as an indicator of nutrient limitation has likely exaggerated the importance of phosphorus limitation, particularly in freshwater systems.
Early rehabilitation after stroke: relationship between the heart rate variability and functional outcome
Authors: Scherbakov Nadja , Barkhudaryan Anush , Ebner Nicole , von Haehling Stephan , Anker Stefan D. , Joebges Michael , Doehner Wolfram
Published: July 2020

Aims

Impaired autonomic nervous system regulation is frequently observed in patients with stroke. The aim of this prospective study was to evaluate the impact of cardiac autonomic tone on functional outcome after the early post‐stroke rehabilitation.

Methods and results

One hundred and three consecutive patients (67 ± 11 years, body mass index (BMI) 27.1 ± 5.4 kg/m2, 64% men) with ischaemic (84% of patients) and haemorrhagic stroke were studied. Depressed heart rate variability (HRV), as a surrogate marker of increased sympathetic tone, was defined by the standard deviation of NN intervals < 100 ms and HRV triangular index ≤ 20 assessed from a 24 h Holter electrocardiogram at admission to rehabilitation (23 ± 16 days after stroke). Twenty‐two per cent of patients had depressed HRV at baseline and were comparable with patients with normal HRV with regard to their functional [Barthel Index (BI), modified Rankin Scale (mRS), and Rivermead Motor Assessment (RMA)] and biochemical status. After a 4‐week follow‐up, 70% of patients with depressed HRV showed a cumulative functional disability, defined by mRS ≥ 4, BI ≤ 70, and RMA ≤ 5, in contrast to patients with normal HRV (35%, P = 0.003). Patients with depressed HRV showed a worse functional status by BI (−16%, P < 0.001), RMA (−12%, P < 0.05), and mRS (+16%, P < 0.01), compared with patients with normal HRV. Cumulative functional disability was associated with depressed HRV (odds ratio 4.25, 95% confidence interval 1.56–11.54, P < 0.005) after adjustment for age, sex, and body mass index (odds ratio 4.6, 95% confidence interval 1.42–14.97, P < 0.05).

Conclusions

The presence of autonomic cardiovascular dysregulation in patients with subacute stroke was associated with adverse functional outcome after the early post‐stroke rehabilitation.
Self‐compassion predicting pain, depression and anger in people suffering from chronic pain: A prospective study
Authors: Emmerich Anja Carina , Friehs Thilo , Crombez Geert , Glombiewski Julia Anna
Published: July 2020

Self‐compassion is associated with disability, pain‐related anxiety as well as depression and anger in patients with chronic pain. However, the unique value of self‐compassion versus other concepts such as psychological flexibility and self‐esteem is unknown. The present study therefore aimed to clarify these relationships. Individuals with chronic pain (NCP = 872) and without chronic pain (NNP = 356) took part in a longitudinal study. Participants completed self‐report instruments: Pain Disability Index (PDI), Pain Catastrophizing Scale (PCS), Pain Anxiety Symptom Scale (PASS‐20), Patient Health Questionnaire (PHQ‐9), State Trait Anger Expression Inventory (STAXI), Self‐Compassion Scale (SCS), Psychological Inflexibility in Pain Scale (PIPS) and Rosenberg Self‐Esteem Scale (RSES). Assessments were repeated after 8 weeks. We found differences in baseline levels of all relevant variables except for anger‐out and anger‐control between people with and without chronic pain. Subsequently, we computed a path model analysis regarding individuals suffering from chronic pain (NCP), addressing the predictive value of reduced uncompassionate self‐responding (RUS), compassionate self‐responding (CS), avoidance (PIPS), cognitive fusion (PIPS) and self‐esteem (RSES) regarding pain‐related (PDI, PCS, PASS) and emotional variables (PHQ‐9, STAXI). Avoidance predicted disability, catastrophizing, anxiety and depression. RUS predicted catastrophizing and pain‐related anxiety. Self‐esteem predicted depression. CS and cognitive fusion had no unique predictive value. The model explained 65.4%‐72.1% of the variance in pain‐related variables, 68.7% of the variance in depression and 38.7%‐60.7% in the variance of anger‐related variables. In conclusion, psychological flexibility, in terms of avoidance, seems to be more relevant for chronic pain than self‐compassion. Future research should focus on subgroups and tailored‐treatment approaches.

Significance

Applying a longitudinal design, this study examined the predictive value of self‐compassion regarding pain, depression and anger. The relevance of self‐compassion was compared to psychological flexibility and self‐esteem. We can conclude that psychological flexibility, in terms of avoidance behaviour, is the most relevant predictor concerning pain.
Reusable Immunosensor for Detection of C‐reactive Protein in Human Serum
Authors: Ribeiro Sandro H. D. , Alves Lívia M. , Flauzino José M. R. , Moço Anna C. R. , Segatto Mônica S. , Silva Jonathan P. , Borges Lizandra F. A. , Madurro João M. , Madurro Ana G. B.
Published: July 2020

This work describes the preparation of a reusable electrochemical immunosensor for detection of C‐reactive protein (CRP), based in modified carbon electrode with reduced graphene oxide and polytyramine as strategy for anchoring the anti‐CRP probe. This immunosensor was able to distinguish different concentrations of CRP target in human serum, by differential pulse voltammetry, showing a linear response from 1.09 to 100 μg L−1. The performance of the immunosensor allowed its application in four consecutive assays, without activity loss. Analyses by atomic force microscopy, scanning electron microscopy and electrochemical impedance spectroscopy corroborate with voltammetric analysis. The immunosensor showed selectivity, stability and reusability, being a promising platform for point‐of‐care quantification of CRP.
Radical Scavenging Activity of Antioxidants by Cyclic Voltammetry
Authors: Haque Md Azizul , Morozova Ksenia , Lawrence Nathan , Ferrentino Giovanna , Scampicchio Matteo
Published: July 2020

This work investigates the reactivity of individual antioxidants with the free radicals generated by 2,2′‐azobis(isobutironitrile) (AIBN). The consumption of antioxidants was followed by cyclic voltammetry. The fitting of such decay with a kinetic model yielded the rate constant
of radical formation and the rate constant
of radical inhibition exerted by each antioxidant. The antioxidant efficiency was defined as the ratio between
and
. The following ranking of antioxidants was obtained: α‐tocopherol≫catechin≫retinyl acetate≫hydroxytyrosol≫oleuropein≫caffeic acid. Overall, the approach shows the utility of cyclic voltammetry to investigate the kinetic rates at which antioxidants react with radicals.
Review: Dielectrophoresis in cell characterization
Authors: Henslee Erin A.
Published: July 2020

Many cellular functions are affected by and thus can be characterized by a cell's electrophysiology. This has also been found to correspond to other biophysical parameters such as cell morphology and mechanical properties. Dielectrophoresis (DEP) is an electrostatic technique which can be used to examine cellular biophysical parameters through the measuring of single or multiple cell response to electric field induced forces. This label‐free method offers many advantages in characterizing a cell population over conventional electrophysiology methods such as patch clamping; however, it has yet to see mainstream pharmacological application. Challenges such as the transdisciplinary nature of the field bridging engineering and the biological sciences, throughput, specificity as well as standardization are being addressed in current literature. This review focuses on the developments of DEP‐based cell electrophysiological characterization where determining cellular properties such as membrane conductance and capacitance, and cytoplasmic conductivity are the primary motivation. A brief theoretical review, techniques for obtaining these cell parameters, as well as the resulting cell parameters and their applications are included in this review. This review aims to further support the development of DEP‐based cell characterization as an important part of the future of DEP and electrophysiology research.
Frontal disconnection surgery for drug‐resistant epilepsy: Outcome in a series of 16 patients
Authors: Kamalboor Hamda , Alhindi Hindi , Alotaibi Faisal , Althubaiti Ibrahim , Alkhateeb Mashael
Published: July 2020

Objective

To evaluate the effectiveness of frontal disconnection surgery in seizure control and related consequences in a consecutive patient series.

Methods

We conducted a retrospective analysis of patients who underwent frontal disconnection surgery for drug‐resistant epilepsy (DRE). Baseline epilepsy characteristics, detailed presurgical evaluation including epileptogenic zone (EZ) localization, magnetic resonance imaging (MRI) detection of epileptogenic lesion, and pathological findings were reviewed. Patients were followed postoperatively for seizure outcome at 1 year.

Results

A total of 16 patients were identified (six children and 10 adults). Most patients had a childhood onset of DRE with a median duration of epilepsy of 6.5 years (interquartile range 3.5‐17.5 years) before surgery. In 10 (62.5%) patients, the EZ was localized to the frontal lobe, while in six patients, the EZ involved also adjacent lobes or consisted of multiple foci. In 10 (62.5%) patients, an epileptogenic lesion was detected on presurgical MRI, four of which (40%) had all MRI abnormalities confined to the frontal lobe. Two‐thirds of the patients (11/16; 68.8%) underwent isolated frontal disconnection procedure, while remaining patients had frontal disconnection combined with resection of an adjacent lobe. Of the 12 patients in whom biopsy was taken from the disconnected frontal lobe, six (50%) had pathology‐proven focal cortical dysplasia. We observed surgical‐related complications in three (18.8%) cases, neurological deficits in other three (18.8%) patients, and worsening cognitive abilities in one (6.3%) patient. Overall, eight (50%) patients became completely seizure‐free (ILAE 1) at one‐year follow‐up.

Significance

Frontal disconnection surgery for DRE can result in seizure freedom in certain patients, especially when the EZ is strictly limited to the ipsilateral frontal region, and the MRI shows an epileptogenic lesion that is purely frontal in location. Frontal lobe disconnection procedure is safe and has a limited complication rate. However, further studies with larger patient population will yield more significance.
Effects of Non-native Fish on Lacustrine Food Web Structure and Mercury Biomagnification along a Dissolved Organic Carbon Gradient
Authors: Barst Benjamin D. , Hudelson Karista , Lescord Gretchen L. , Santa-Rios Andrea , Basu Niladri , Crémazy Anne , Drevnick Paul E.
Published: July 2020

Although the introduction of non-native fish species has been shown to alter trophic ecology in aquatic ecosystems, there has been limited research on how invasive species alter methylmercury (MeHg) biomagnification in lacustrine food webs. We sampled surface water and biota from 8 lakes in Quebec, Canada, spanning a range of dissolved organic carbon (DOC) concentrations (2.9–8.4 mg/L); 4 lakes were inhabited by native brook trout (Salvelinus fontinalis), and the remaining lakes contained brook trout and a non-native fish, Allegheny pearl dace (Margariscus margarita). Periphyton, zooplankton, macroinvertebrates, and fish were analyzed for: 1) stable carbon (δ13C) and nitrogen (δ15N) isotope ratios to delineate food webs, and 2) total Hg (THg) or MeHg. Compared with the brook trout from reference lakes, fish from invaded lakes had higher length-standardized THg concentrations as well as a narrower dietary range and elevated trophic level, inferred from unadjusted δ13C and δ15N values, respectively. The rate of Hg biomagnification was similar across invaded and reference lakes, implying little effect of the invasive fish on the trophic transfer of MeHg. Despite differences in food web structure due to pearl dace invasion, DOC was the strongest predictor of brook trout THg levels for all lakes, suggesting that underlying environmental factors exerted a stronger influence on brook trout THg concentrations than the presence of a non-native forage fish. Environ Toxicol Chem 2020;39:2196–2207. © 2020 SETAC
Effect Modeling Quantifies the Difference Between the Toxicity of Average Pesticide Concentrations and Time-Variable Exposures from Water Quality Monitoring
Authors: Ashauer Roman , Kuhl Roland , Zimmer Elke , Junghans Marion
Published: July 2020

Synthetic chemicals are frequently detected in water bodies, and their concentrations vary over time. Water monitoring programs typically employ either a sequence of grab samples or continuous sampling, followed by chemical analysis. Continuous time-proportional sampling yields the time-weighted average concentration, which is taken as proxy for the real, time-variable exposure. However, we do not know how much the toxicity of the average concentration differs from the toxicity of the corresponding fluctuating exposure profile. We used toxicokinetic–toxicodynamic models (invertebrates, fish) and population growth models (algae, duckweed) to calculate the margin of safety in moving time windows across measured aquatic concentration time series (7 pesticides) in 5 streams. A longer sampling period (14 d) for time-proportional sampling leads to more deviations from the real chemical stress than shorter sampling durations (3 d). The associated error is a factor of 4 or less in the margin of safety value toward underestimating and an error of factor 9 toward overestimating chemical stress in the most toxic time windows. Under- and overestimations occur with approximate equal frequency and are very small compared with the overall variation, which ranged from 0.027 to 2.4 × 1010 (margin of safety values). We conclude that continuous, time-proportional sampling for a period of 3 and 14 d for acute and chronic assessment, respectively, yields sufficiently accurate average concentrations to assess ecotoxicological effects. Environ Toxicol Chem 2020;39:2158–2168. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Abstract

Real, time-variable exposure profiles can cause different effects than their corresponding time-weighted average concentration. When is the difference small enough for water quality assessment?
Provider responses to a global budgeting system: The case of drug expenditures in Taiwan hospitals
Authors: Chou Shin‐Yi , Dearden James A. , Deily Mary E. , Lien Hsien‐Ming
Published: July 2020

In July 2002, a global budgeting system was imposed on hospitals in Taiwan. This system set a fixed budget for all hospitals within a region but included special provisions that sheltered reimbursements for drug expenditures. We study the size and nature of changes in hospital physicians' use of drugs for outpatient care following this budgetary change and find that drug expenditures for outpatient care increased by 11.7%. Our results suggest that physicians began prescribing more expensive drugs, more drugs, and drugs for longer periods but that these different responses did not all occur at the same time. The overall response was strongest in for‐profit hospitals, but drug‐related decisions changed in all hospital types.
Current status of clinical pharmacy workforce, services and clinical pharmacist recruitment in Ho Chi Minh City, Vietnam
Authors: Nguyen‐Thi Hai‐Yen , Nguyen‐Ngoc Thuy‐Tram , Le Nha Hoang , Le Nghiem Quan , Le Nguyen Dang Tu
Published: July 2020

Objectives

Clinical pharmacy practices in Vietnam have not been well studied. We aimed to describe clinical pharmacy practices in terms of workforce, activities and the recruitment demand for clinical pharmacists (CPs) in hospitals.

Methods

A cross‐sectional survey was conducted, and 123 questionnaires were distributed to Heads/Deputy heads of Pharmacy department and Boards of directors in all of hospitals in Ho Chi Minh City, Vietnam between August 2018 and June 2019.

Results

There were 187 CPs in 79 participating hospitals, whereas the ratio of CPs per 100 patient beds was 0.67. The median number of CPs was 2 (1–4), with a significantly low median full time equivalent [0.4 (1, 2)]. The income of CPs was significantly low. Antibiotics were the most common medications that CPs discussed with physicians (93.06%). Interventions commonly performed by CPs were “Checking drug interactions” (77.78%), “Counseling physicians about the route of administration” (61.11%), “Checking drug allergies” (51.39%). The median number of CPs needed to recruit according to Heads/Deputy heads of Pharmacy Department and Boards of directors was 2 (1–3) and 2 (1–3.5), respectively.

Conclusion

The shortage of CPs, which was likely attributable to low income, might lead to numerous obstacles for delivering comprehensive healthcare services. Thus, the hospital recruitment strategies should focus on salary and benefits to attract more CPs, especially those with postgraduate degree.
Analysis of second law on Eyring‐Powell nanoliquid flow in a vertical microchannel considering magnetic field and convective boundary
Authors: Sindhu Sundar , Gireesha Bijjanal Jayanna
Published: July 2020

Studies related to enhancing heat transfer has attained much attention of researchers to avail optimized heat‐transfer devices. High viscous fluids are of great importance as they are widely used in petroleum products, organic chemistry, coating, printing, and so forth. In this study, heat transfer mechanism driven by Eyring‐Powell nanoliquid flow in a vertical microchannel is examined. Impact of considering buoyancy force, magnetic field, and convective boundary on the thermal system is demonstrated. The modeled nondimensional equations are computed by using the Runge‐Kutta‐Fehlberg method. The vital roles of thermophoresis and Brownian motion are discussed in detail. The significance of second law analysis for thermal systems is presented. The causes of irreversibilities in a microchannel due to Eyring‐Powell nanoliquid flow is also demonstrated in the current research study. The upshots of the current investigations are visualized through graphical elucidation. It is established that minimization of entropy generation can be achieved by enhancing the mechanism of thermophoresis. The convective boundary helps in transmitting heat from the thermal system to the ambience hence the lower thermal field is attained.
Beyond Thresholds: A Holistic Approach to Impact Assessment Is Needed to Enable Accurate Predictions of Environmental Risk from Oil Spills
Authors: Hook Sharon E
Published: July 2020

The risk assessment for the environmental impact of oil spills in Australia is often conducted in part using a combination of spill mapping and toxicological thresholds derived from laboratory studies. While this process is useful in planning operational responses, such as where to position equipment stockpiles and whether to disperse oil, and can be used to identify areas near the spill site where impacts are likely to occur, it cannot accurately predict the environmental consequences of an oil spill or the ecosystem recovery times. Evidence of this disconnect between model predictions and observed impacts is the lack of a profound effect of the Deepwater Horizon wellhead blowout on recruitment to fisheries in the northern Gulf of Mexico, contrary to the predictions made in the Natural Resources Damage Assessment and despite the occurrence of impacts of the spill on marine mammals, marshes, and deep water ecosystems. The incongruity between predictions made with the current approach using threshold monitoring and impacts measured in the field results from some of the assumptions included in the oil spill models. The incorrect assumptions include that toxicity is acute, results from dissolved phase exposure, and would be readily reversible. The toxicity tests from which threshold models are derived use members of the ecosystem that are easily studied in the lab but may not represent the ecosystem as a whole. The test species are typically highly abundant plankton or planktonic life stages, and they have life histories that account for rapid changes in environmental conditions. As a consequence, these organisms recover quickly from an oil spill. The interdependence of ecosystem components, including the reliance of organisms on their microbiomes, is often overlooked. Additional research to assess these data gaps conducted using economically and ecologically relevant species, especially in Australia and other understudied areas of the world, and the use of population dynamic models, will improve the accuracy of environmental risk assessment for oil spills. Integr Environ Assess Manag 2020;16:813–830. © 2020 SETAC
Macrofinancial linkages in Europe: Evidence from quantile local projections
Authors: Stolbov Mikhail , Shchepeleva Maria
Published: July 2020

The paper investigates macrofinancial linkages in the sample of 16 European economies over January 1997–December 2019 from a new twofold perspective. First, we put a particular emphasis on the role of news‐based sentiment measures in these relationships, that is, economic policy uncertainty and global geopolitical risk. Second, we pursue a hybrid econometric approach to capture a presumably nonlinear nature of these linkages by building on different quantiles of the data series and estimating impulse responses from smooth local projections (Barnichon and Brownlees, Review of Economics and Statistics, 101(3), 522–530, 2019). Our results legitimize such approach as the number of statistically significant impulse responses based on this approach is skewed towards upper (75th and 90th) quantiles. We find that global economic policy uncertainty index dampens the growth rates of industrial production in Austria, France, Italy, Luxembourg and Slovakia, which calls for specific measures to mitigate this adverse effect at the national level, for example, by curtailing yellow journalism, populist ideas and disbeliefs. However, there is only minor evidence for the relationship running between economic policy uncertainty and financial stress. Global geopolitical risk appears irrelevant in the country‐ and panel‐level analyses. Meanwhile, the VIX index performs a pervasive role in undermining industrial production and increasing economic policy uncertainty in Europe.
Solitary recurrence of prostate cancer surrounded by seminal vesicle/vas deferens‐like epithelium
Authors: Takamori Hajime , Kamba Tomomi , Sumiyoshi Shinji , Tsuzuki Toyonori , Kashima Soki , Yoshino Takayuki , Sano Takeshi , Goto Takayuki , Sawada Atsuro , Akamatsu Shusuke , Kobayashi Takashi , Yamasaki Toshinari , Mizowaki Takashi , Ogawa Osamu , Inoue Takahiro
Published: July 2020

Introduction

Clinical recurrence of prostate cancer after curative treatment with a limited number of metastases is often termed as oligorecurrence. We report a case of solitary recurrence of prostate cancer surrounded by epithelium of the seminal vesicle or vas deferens.

Case presentation

A 54‐year‐old man diagnosed with localized prostate cancer underwent radiation therapy. Six years later, imaging studies detected a solitary recurrence. We performed metastasectomy, and histopathological examination revealed the metastatic lesion surrounded by the epithelium of the seminal vesicle or vas deferens. Surgical resection achieved a complete biochemical response.

Conclusion

We presented with a case of prostate cancer metastasis surrounded by the epithelium of the seminal vesicle or vas deferens.
Outcomes of a practical approach for improving conversation skills in adults with autism
Authors: Custer Taylor N. , Stiehl Christie M. , Lerman Dorothea C.
Published: July 2020

Many individuals with autism spectrum disorder (ASD) have deficits in conversation skills that can interfere with the development of personal and professional relationships. Further research is needed on efficient interventions for targeting conversation skills in adults with ASD and for evaluating the social validity of the outcomes. In this study, 2 practitioners implemented a 4‐week training program for 5 adults with ASD that combined individualized computer‐based instruction (CBI) and practice with peers to promote the acquisition, maintenance, and generalization of conversation skills. Training was associated with improvements in 12 of 13 skills across participants. These findings, along with peer ratings of the participants' conversation skills, suggest that this model is a promising, socially valid approach for improving conversation skills in adults with ASD.
Cu2+ in liquid ammonia—The impact of solvent flexibility and electron correlation in ab initio quantum mechanical charge field molecular dynamics
Authors: Saputri Wahyu Dita , Pranowo Harno Dwi , Schuler Manuel J. , Hofer Thomas S.
Published: July 2020

The impact of solvent flexibility and electron correlation on the simulation results of Cu2+ in liquid ammonia has been investigated via an ab initio quantum mechanical charge field molecular dynamics (QMCF MD) simulation approach. To achieve this, three different simulation systems were considered in this study, namely Cu2+ in rigid and flexible ammonia at Hartree‐Fock (HF) level of theory, as well as resolution of identity second order Møller‐Plesset (MP2) perturbation theory in the rigid body case. In all cases, a stable octahedral [Cu(NH3)6]2+ complex subject to dynamic Jahn‐Teller distortions without the occurrence of ligand exchange was observed. The Cu2+ − NH3 distance in the first shell agrees well with the experimental and other theoretical data. In all three cases, the structural data shows that the rigid‐body ammonia model in conjunction with the HF level of theory provides accurate data for the first solvation shell, while at the same time, the computational demand and thus the achievable simulation time are much more beneficial. The vibrational analysis of the Cu2+ − NH3 interaction yields similar force constants in the three investigated systems indicating that there is no distinct difference on the dynamical properties of the first solvation shell. In addition to the QMCF MD simulations, a number of natural bond orbital (NBO) analyses were carried out, confirming the strong electrostatic character of the Cu2+ − NH3 interaction.
Free‐energy calculations of the host–guest association in grafted supramolecular assemblies
Authors: Garnier Ludovic , Bonal Christine , Malfreyt Patrice
Published: July 2020

Herein, we investigate the impact of grafting macrocyclic hosts with hydrophobic cavities onto a gold surface on the association with a guest molecule of particular importance to applications for molecular machines. We establish that the increase of the grafted alkyl chain length and number of anchor points strengthens the binding of the guest with the β‐cyclodextrin host. This is the opposite effect with the p‐sulfonatocalix[4]arene host for which the grafting considerably reduces the strength of the host–guest association. The structural and thermodynamic characterizations, carried out with free energy simulations, are combined to rationalize the differences in the association process in both heterogeneous and homogeneous conditions.
Elongation method with intermediate mechanical and electrostatic embedding for geometry optimizations of polymers
Authors: Mashkovtsev Denis , Mizukami Wataru , Korchowiec Jacek , Stachowicz‐Kuśnierz Anna , Aoki Yuriko
Published: July 2020

The elongation method with intermediate mechanical and electrostatic embedding (ELG‐IMEE) is proposed. The electrostatic embedding uses atomic charges generated by a charge sensitivity analysis (CSA) method and parameterized for three different population analyses, namely, the Merz–Singh–Kollman scheme, the charge model 5, and the atomic polar tensor. The obtained CSA models were tested on two model systems. Test calculations show that the electrostatic embedding provides several times of decrease in the difference of energies of testing and reference calculations in comparison with the conventional elongation approach (ELG). The mechanical embedding is implemented in a combination of the conventional elongation method and the ONIOM approach. Moreover, it was demonstrated that the geometry optimization with the ELG‐IMEE reduces the errors in the optimized structures by about one order in root‐mean‐square deviation, when compared to ELG.
Interatomic exchange‐correlation interaction energy from a measure of quantum theory of atoms in molecules topological bonding: A diatomic case
Authors: Anisimov Aleksei A. , Ananyev Ivan V.
Published: July 2020

The potential relations between the measure of topological interatomic bonding—integrals of electron density with respect to internuclear axis over the corresponding quantum theory of atoms in molecules (QTAIM)‐defined interatomic surface (IAS)—and interatomic exchange‐correlation contributions from the interacting quantum atoms approach are discussed. The quantum chemical computations of 38 equilibrium diatomic systems at different levels of theory (HF, MP2, MP4SDQ, and CCSD) are invoked to support abstract considerations. Parameters of excellent correlations between IAS integrals and interatomic exchange‐correlation energy are found by the optimization. The performance of these trends depends on the accuracy of the electronic correlation treatment. The resulting trends are a unique feature of equilibrium states, whereas more complicated dependencies are explored for several systems at non‐equilibrium conditions. The relations of established trends with other IAS‐based estimations of strength of bonding interactions between topological atoms and issues explored for multiatomic systems are briefly discussed.
The conditioned medium of human embryonic stem cell‐derived mesenchymal stem cells alleviates neurological deficits and improves synaptic recovery in experimental stroke
Authors: Asgari Taei Afsaneh , Dargahi Leila , Nasoohi Sanaz , Hassanzadeh Gholamreza , Kadivar Mehdi , Farahmandfar Maryam
Published: July 2020

The transplantation of mesenchymal stem cells (MSCs) is of main approaches in regenerative therapy for stroke. Due to the potential tumorigenicity and low survival rate of transplanted cells, focuses have been shifted from cell replacement to their paracrine effects. Therefore, stem cell‐conditioned medium (CM) therapy has emerged as an alternative candidate. Here, we investigated the effect of CM derived from human embryonic MSCs on experimental ischemic stroke. Wistar rats underwent ischemic stroke by the right middle cerebral artery occlusion (MCAO). CM was infused either one time (1 hr post‐MCAO) or three times (1, 24, and 48 hr post‐MCAO) through guide cannula into the left lateral ventricle. Neurological functions were evaluated using Bederson's test and modified Neurological Severity Score on Days 1, 3, and 7 following MCAO. Infarction volumes and cerebral edema were measured on Days 3 and 7. growth‐associated protein‐43, synaptophysin, cAMP response element‐binding protein, and phosphorylated‐cAMP response element‐binding protein levels were also assessed in peri‐ischemic cortical tissue on Day 7 postsurgery. Our results indicated that three times injections of CM could significantly reduce body weight loss, mortality rate, infarct volumes, cerebral edema, and improve neurological deficits in MCAO rats. Moreover, three injections of CM could restore decreased levels of synaptic markers in MCAO rats up to its normal levels observed in the sham group. Our data suggest that using the CM obtained from embryonic stem cells–MSCs could be a potent therapeutic approach to attenuate cerebral ischemia insults which may be partly mediated through modulation of synaptic plasticity.
The MTNR1A mRNA is stabilized by the cytoplasmic hnRNPL in renal tubular cells
Authors: Huang Yen‐Sung , Lu Kuo‐Cheng , Chao Hsu‐Wen , Chen Ann , Chao Tai‐Kuang , Guo Cheng‐Yi , Hsieh Hsin‐Yi , Shih Hsiu‐Ming , Sytwu Huey‐Kang , Wu Chia‐Chao
Published: July 2020

The downregulation of melatonin receptor 1A (MTNR1A) is associated with a range of pathological conditions, including membranous nephropathy. Knowledge of the mechanism underlying MTNR1A expression has been limited to the transcriptional regulation level. Here, RNA interference screening in human kidney cells revealed that heterogeneous nuclear ribonucleoprotein L (hnRNPL) upregulated MTNR1A RNA post‐transcriptionally. hnRNPL knockdown or overexpression led to increased or decreased levels of cyclic adenosine monophosphate‐responsive element‐binding protein phosphorylation, respectively. Molecular studies showed that cytoplasmic hnRNPL exerts a stabilizing effect on the MTNR1A transcript through CA‐repeat elements in its coding region. Further studies revealed that the interaction between hnRNPL and MTNR1A serves to protect MNTR1A RNA degradation by the exosome component 10 protein. MTNR1A, but not hnRNPL, displays a diurnal rhythm in mouse kidneys. Enhanced levels of MTNR1A recorded at midnight correlated with robust binding activity between cytoplasmic hnRNPL and the MTNR1A transcript. Both hnRNPL and MTNR1A were decreased in the cytoplasm of tubular epithelial cells from experimental membranous nephropathy kidneys, supporting their clinical relevance. Collectively, our data identified cytoplasmic hnRNPL as a novel player in the upregulation of MTNR1A expression in renal tubular epithelial cells, and as a potential therapeutic target.