bluuebunny/crossref_metadata_2025 huggingface dataset:
High‐throughput Preparation of DNA, RNA, and Protein from Cryopreserved Human iPSCs for Multi‐omics Analysis
Authors: Zhang Jeffrey X. , Lau Edward , Paik David T. , Zhuge Yan , Wu Joseph C.
Published: June 2020

We describe the procedure to isolate genomic DNA, RNA, and protein directly from cryopreserved induced pluripotent stem cell (iPSC) vials using commercially available solid‐phase extraction kits, and we report the relationship between macromolecule yields and experimental and storage factors. Sufficient quantities of DNA, RNA, and protein are recoverable from as low as 1 million cryopreserved cells across 728 distinct iPSC lines suitable for whole‐genome sequencing, RNA sequencing, and mass spectrometry experiments. Nucleic acids extracted from iPSC stocks cryopreserved up to 4 years maintain sufficient quantity and integrity for downstream analysis with minimal genomic DNA fragmentation. An expected positive correlation exists between cell count and DNA or RNA yield, with comparable yields recovered between cells across different cryostorage timespans. This article provides an effective way to simultaneously isolate iPSC biomolecules for multi‐omics investigations. © 2020 Wiley Periodicals LLC.

Basic Protocol 1: QIAshredder and AllPrep DNA/RNA/protein mini kit extraction and subsequent DNA quantification and quality analysis

Basic Protocol 2: Broad‐range RNA quantification and quality assay using QuBit 4 Fluorometer and associated kits
DNA Fiber Assay for the Analysis of DNA Replication Progression in Human Pluripotent Stem Cells
Authors: Halliwell Jason A. , Gravells Polly , Bryant Helen E.
Published: June 2020

Human pluripotent stem cells (PSC) acquire recurrent chromosomal instabilities during prolonged in vitro culture that threaten to preclude their use in cell‐based regenerative medicine. The rapid proliferation of pluripotent cells leads to constitutive replication stress, hindering the progression of DNA replication forks and in some cases leading to replication‐fork collapse. Failure to overcome replication stress can result in incomplete genome duplication, which, if left to persist into the subsequent mitosis, can result in structural and numerical chromosomal instability.

We have recently applied the DNA fiber assay to the study of replication stress in human PSC and found that, in comparison to somatic cells states, these cells display features of DNA replication stress that include slower replication fork speeds, evidence of stalled forks, and replication initiation from dormant replication origins. These findings have expanded on previous work demonstrating that extensive DNA damage in human PSC is replication associated. In this capacity, the DNA fiber assay has enabled the development of an advanced nucleoside‐enriched culture medium that increases replication fork progression and decreases DNA damage and mitotic errors in human PSC cultures.

The DNA fiber assay allows for the study of replication fork dynamics at single‐molecule resolution. The assay relies on cells incorporating nucleotide analogs into nascent DNA during replication, which are then measured to monitor several replication parameters. Here we provide an optimized protocol for the fiber assay intended for use with human PSC, and describe the methods employed to analyze replication fork parameters. © 2020 Wiley Periodicals LLC.

Basic Protocol 1: DNA fiber labeling

Basic Protocol 2: DNA fiber spreading

Basic Protocol 3: Immunostaining

Support Protocol 1: Microscopy/data acquisition

Support Protocol 2: Data analysis
Novel quantum‐dot cellular automata implementation of flip‐flop and phase‐frequency detector based on nand‐nor‐inverter gates
Authors: Alamdar Hani , Ardeshir Gholamreza , Gholami Mohammad
Published: June 2020

CMOS technology faces fundamental challenges such as frequency and power consumption due to the impossibility of further reducing dimensions. For these reasons, researchers have been thinking replacement of this technology with other technologies such as quantum‐dot cellular automata (QCA) technology. Many studies have been done to design digital circuits using QCA technology. Phase‐frequency detector (PFD) is one of the main blocks in electrical and communication circuits. In this paper, a novel structure for PFDs in QCA technology is proposed. In the proposed design, the novel D flip‐flop (D‐FF) with reset ability is used. The D‐FF is designed by the proposed D latch which is based on nand‐nor‐inverter (NNI) and an inverter gate. This proposed D latch has 22 cells and 0.5 clock cycle latency and 0.018‐μm2 area. The inverter gate of the D‐FF has output signal with high polarization level and lower area than previous inverters, and the NNI gate of the D‐FF is a universal gate. The proposed PFD has 141 cells, 0.17‐μm2 occupied area, and two clock cycle latency that is smaller compared with PFD and is based on common inverter and majority gates.
Assessing accessibility: Universal Design for university websites
Authors: Huffington Dennis , Copeland Boyd , Devany Katie , Parker‐Gills Anthony , Patel Jasmin
Published: June 2020

The number of students with disabilities attending colleges and universities is growing nationally. Statistics on the number of individuals affected by disability vary, but a consensus exists that the number of those affected is staggering. In the United States alone, 57 million individuals, or 18.7% of the population, report a disability. The World Health Organization reports that 15% of the world population experience some form of disability, a percentage that represents one billion individuals. This number may continue to increase as the population ages and those who are not currently disabled become disabled.
Plastome phylogenomics and phylogenetic diversity of endangered and threatened grassland species (Poaceae) in a North American tallgrass prairie
Authors: Pischl Phyllis H. , Burke Sean V. , Bach Elizabeth M. , Duvall Melvin R.
Published: June 2020

Native grasslands are one of the most endangered ecosystems in North America. In this study, we examined the ecological and evolutionary roles of endangered and threatened (e/t) grasses by establishing robust evolutionary relationships with other nonthreatened native and introduced grass species of the community. We hypothesized that the phylogenomic distribution of e/t species of grasses in Illinois would be phylogenetically clustered because closely related species would be vulnerable to the same threats and have similar requirements for survival. This study presents the first time a phylogeny based on complete plastome DNA of Poaceae was analyzed by phylogenetic diversity analysis. To avoid the disturbance of e/t populations, DNA was extracted from herbarium specimens. Next‐generation sequencing (NGS) techniques were used to sequence DNA of plastid genomes (plastomes). The resulting phylogenomic tree was analyzed by phylogenetic diversity metrics. The extracted DNA successfully produced complete plastomes demonstrating that herbarium material is a practical source of DNA for genomic studies. The phylogenomic tree was strongly supported and defined Dichanthelium as a separate clade from Panicum. The phylogenetic metrics revealed phylogenetic clustering of e/t species, confirming our hypothesis.
Linking fish assemblages to hydro‐morphological units in a large regulated river
Authors: Wegscheider Bernhard , Linnansaari Tommi , Monk Wendy A. , Curry R. Allen
Published: June 2020

Flow‐related changes of physical habitat represent a potentially significant environmental filter determining the presence and composition of fish assemblages in rivers. The mesoscale (100–103 m) of river habitat has been identified as an appropriate resolution to model linkages between fish and their abiotic environment that are relevant yet logistically feasible for management of large rivers with complex habitats and diverse fish assemblages. This study identified well‐defined mesohabitat types (i.e. hydro‐morphological units) that influence the fish community of the lower Saint John River, New Brunswick, downstream of a large hydropower generating station (the Mactaquac Generating Station). Four hydro‐morphological units or habitats (i.e. pool, riffle, run and slack water) were identified and linked to three distinct fish assemblages. Eurytopic species represent habitat generalists that were common among all habitats throughout the study area. Rheophilic species preferred fast‐flowing run habitat, whereas limnophilic species were mainly associated with slack water habitat. Riffle habitats that frequently run dry during low flows were mostly vacant of fish species, suggesting that fish assemblages that would naturally occur in these environments could be affected by fluctuations in flow (i.e. hydropeaking) due to dam operation. Our improved understanding of the relationship between fish assemblages and hydro‐morphological units is a fundamental first step to develop meaningful habitat models that can facilitate the effective evaluation of flow management options regarding hydropower and other flow manipulation activities in large rivers with diverse fish fauna.
Synthesis, Characterization, and Reactivity of Cyclometalated Gold(III) Dihalide Complexes in Aqua Regia
Authors: Levchenko Volodymyr A. , Nova Ainara , Øien‐Ødegaard Sigurd , Balcells David , Tilset Mats
Published: June 2020

A range of N,C‐chelated, cyclometalated gold(III) complexes Au(ppyR)X2 have been prepared and characterized by spectroscopic, crystallographic, and computational means. Here, ppyH is 2‐phenylpyridine dicarboxylic acid (series 1), ppyEt is diethyl 2‐phenylpyridine dicarboxylate (series 2), and X is trifluoroacetate OAcF (a), Cl (b), Br (c), or I (d) anion. The dihalo complexes 1b‐d and 2b‐d are obtained when Au(ppyR)(OAcF)2 (1a and 2a) are treated with HNO3/HX mixtures (aqua regiaX). Good to high yields are obtained with short reaction times (< 30 min) and simple work‐up. Notably, the strongly acidic medium does not cause protolytic cleavage of the Au–C or Au–N bonds in the chelate, nor is ester hydrolysis of complexes 2b‐d seen. Ethylene inserts into an Au–O bond of 1a and 1b, and the resulting trifluoroacetoxyethyl–Au complexes can be further elaborated in aqua regia without cleavage of the two Au–C bonds in the molecule. Facile, mutual halide exchange reactions between complexes with different halides (1b and 1d, 1c and 1d) were observed and led to formation of mixed‐halide complexes Au(ppyH)(X)(Y). These exchange reactions occurred with complete stereoselectivity. The stereoisomer produced was the one expected based on the relative trans influence of the halides (I > Br > Cl), i.e. the highest trans influence halide was located trans to N which is the lowest trans influence end of the chelate. These thermodynamic preferences were also investigated by DFT computations.
Nanoparticle‐Catalysed 1,3‐Dipolar Cycloadditions
Authors: Ponti Alessandro , Molteni Giorgio
Published: June 2020

The 1,3‐dipolar cycloadditions of azomethine‐ylides and ‐imines, nitrones, nitrilimines, and azides catalysed by inorganic nanoparticles are described. Emphasis is given to the nanometric catalysts involved, their structure, characterisation, and recyclability and, when remarkable, their preparation. Whenever possible, the improvements with respect to cycloadditions performed with the usual (non‐nano) catalysts are discussed.
Market mindset impacts moral decisions: The exposure to market relationships makes moral choices more utilitarian by means of proportional thinking
Authors: Zaleskiewicz Tomasz , Gasiorowska Agata , Kuzminska Anna O. , Korotusz Przemyslaw , Tomczak Pawel
Published: June 2020

We show that exposure to market relationships increases people’s tendency to make utilitarian moral choices by means of proportional thinking—the definitional feature of the market mindset. In Experiment 1, participants primed with market relationships made more utilitarian choices in both the trolley and the footbridge dilemmas. In Experiment 2, priming market mindset led to more utilitarian moral choices and to greater focus on the proportion of survivors to victims. Experiment 3 showed that the effect of market mindset on utilitarian choices held only when the numbers of potential deaths and saved lives were clearly specified. A preregistered Experiment 4 demonstrated that the motivation to use proportional thinking mediates the relationship between market mindset and making utilitarian choices. Experiment 5, also preregistered, showed that the main effect we demonstrated is not due to suppressed emotions and that proportional thinking increases utilitarian choices as part of a broader orientation on rationality.
Recovery of Pt(IV) from aqueous solutions by spent brewer's yeast‐functionalized zeolite (SBYFZ): A batch and column study
Authors: Mosai Alseno K. , Chimuka Luke , Cukrowska Ewa M. , Kotzé Izak A. , Tutu Hlanganani
Published: June 2020

Mineral commodities in Earth's crust, such as platinum, palladium, and gold have to be sustained especially since their ore deposits have been dramatically declining, due to intensive mining, motivated by high demand. The mining of these commodities results in large amounts of wastewater containing traces of precious elements. The current study presents on the recovery of Pt(IV) from aqueous solutions using spent brewer's yeast‐functionalized zeolite (SBYFZ). Batch and column experiments were conducted at different conditions. Two‐ and three‐parameter isotherm and kinetic models were fitted using adsorption data. Pt(IV) was significantly (p < .05) recovered from aqueous solutions within 300 min of contact time, using 10 g/L adsorbent dosage and 2 mg/L at pH 2. The platinum uptake was reduced by 5% when incorporated with adsorption competing ions. Other platinum group elements were successfully removed from aqueous solutions along with Pt(IV). Column studies indicated that breakthrough times were proportional to increasing bed height, highly acidic pH, and low influent concentration. The recovery of Pt(IV) was through mass transfer as concluded from column adsorption models. These results indicated that SBYFZ was excellent for the significant recovery of Pt(IV) from aqueous solutions. Thus, SBYFZ can be used in wastewaters with optimum conditions.
A seismic monitoring approach to detect and quantify river sediment mobilization by steelhead redd‐building activity
Authors: Dietze Michael , Losee James , Polvi Lina , Palm Daniel
Published: June 2020

The role of spawning salmonids in altering river bed morphology and sediment transport is significant, yet poorly understood. This is due, in large part, to limitations in monitoring the redd‐building process in a continuous and spatially extended way. A complementary approach may be provided through the use of a small seismic sensor network analysing the ground motion signals generated by the agitation of sediment during the redd‐building process. We successfully tested the viability of this approach by detecting and locating artificially generated redd signals in a reach of the Mashel River, Washington State, USA. We then utilize records of 17 seismic stations, in which we automatically detected seismic events that were subsequently manually checked, yielding a catalogue of 45 potential redd‐building events. Such redd‐building events typically lasted between 1 and 20 min and consisted of a series of clusters of 50–100 short energetic pulses in the 20–60 Hz frequency range. The majority (>90%) of these redd‐building events occurred within 11 days, predominantly during the early morning and late afternoon. The seismically derived locations of the signals were in agreement with independently mapped redds. Improved network geometry and installation conditions are required for more efficient detection, robust location and improved energetic insights into redd‐building processes in larger reaches. The passive and continuous nature of the seismic approach in detecting redds and describing fish behaviour provides a novel tool for fish biologists and fisheries managers, but also for fluvial geomorphologists, interested in quantifying the amount of sediment mobilized by this ecosystem engineer. When complemented with classic approaches, it could allow for a more holistic picture of the kinetics and temporal patterns (at scales from seconds to multiple seasons) of a key phase of salmonid life cycles. © 2020 The Authors. Earth Surface Processes and Landforms published by John Wiley & Sons Ltd
Gender differences in resources related to depressive symptoms during the early years of retirement: A Swedish population‐based study
Authors: Hed Sara , Berg Anne Ingeborg , Hansson Isabelle , Kivi Marie , Waern Margda
Published: June 2020

Objectives

To examine levels of depressive symptoms during the early years of retirement in men and women and to investigate potential gender differences in associations with self‐reported health, financial insecurity, social network and psychological resources.

Methods

Data was drawn from the first wave in the Health, Aging and Retirement Transitions in Sweden‐study (HEARTS) including a total sample of 1148 retirees, aged 60 to 66. Level of depressive symptoms and associations with health, financial insecurity, social network and psychological resources were investigated in regression analyses in the total sample and in bivariate correlation analyses in the subgroup at risk of depression as defined by a cut‐off ≥9 on the Center for Epidemiologic Studies Depression Scale (CES‐D).

Results

Mean CES‐D scores were similar in men and women in the entire sample. The CES‐D identified 144 individuals at risk of depression (men 14%, women 11%, n.s.). Although the pattern of related resources was similar in men and women, a greater proportion of the variance was explained in the male group (51% vs 37%). Health, quality of social network, social support and competence satisfaction were all correlated with depressive symptoms in men in the high risk group, but no associations were seen in women.

Conclusions

Similar levels of depressive symptoms were observed in women and men in the retirement transition. However, the relevance of the selected resources may be greater in men. Research on the management of depressive symptoms in the transition between midlife and aging needs to take gender into consideration.
Approximate analytical approach to unsteady conducting micropolar fluid flow in the presence of buoyant forces and reactive species
Authors: Dash A. K. , Mishra S. R.
Published: June 2020

The present analysis studied the significance of free convective flow of an unsteady non‐Newtonian fluid through a semi‐infinite vertical porous plate embedded in a porous medium. The thermal transport equation is enhanced by incorporating the heat source/sink and mass transfer in the chemical reaction parameters. The plate moves at a constant velocity and the velocity near the free stream varies exponentially, which allows perturbation laws. Such a model has relevance to a few industrial and engineering applications. In particular, a micropolar fluid is used as a lubricant in various gadgets, also, in polymeric suspensions as well as in animal blood, the phenomena are used to define the local structure and micromotion of the particles. Transformed nondimensional governing equations are solved analytically employing the perturbation method. Influences of the characterizing parameters are presented via graphs and computations for the coefficients of quantities of interest obtained and shown in a table. Also, validation of the present results in a particular case such as the case of Newtonian fluid is obtained with an earlier study and found to be in good agreement. The major findings are laid down here; an increase in plate velocity enhances the velocity profile near the plate and a destructive chemical reaction restrains the fluid concentration in the entire flow domain.
Do postpartum anxiety and breastfeeding self‐efficacy and bonding at early postpartum predict postpartum depression and the breastfeeding method?
Authors: Minamida Tomoko , Iseki Atsuko , Sakai Hiroko , Imura Masumi , Okano Tadaharu , Tanii Hisashi
Published: June 2020

We investigated whether postpartum anxiety (PPA) and breastfeeding self‐efficacy and bonding at the early postpartum period can be used to predict postpartum depression and the breastfeeding method, and we sought to identify factors related to postpartum depression. Of the 510 eligible women, 185 (36%) returned the questionnaire on all three occasions (1 day, 3 days, and 1 month after childbirth). The mothers' progress on the State‐Trait Anxiety Inventory (STAI), Breastfeeding Self‐Efficacy Scale Short Form (BFSES‐SF), and Postnatal Bonding Questionnaire (PBQ) was observed over three periods. A repeated‐measures ANOVA revealed that the mothers at high risk of developing postpartum depression (PPD) were those who did not show an increase in BFSES‐SF score at early postpartum, and mothers whose bonding disorders have deteriorated rapidly. The results of the logistic regression analysis revealed a significant difference in employment as a factor related to postpartum depression. Compared to Regular, Part‐time status was 4.4 times more likely and Unemployed status was 2.3 times more likely to cause postpartum depression. For the early detection of PPD, it is necessary to identify (1) mothers who do not show an increase in the BFSES‐SF score, (2) mothers whose bonding disorders have deteriorated rapidly, and (3) part‐time or unemployed mothers as characteristic of postpartum depression.
A novel role of the miR‐152‐3p/ERRFI1/STAT3 pathway modulates the apoptosis and inflammatory response after acute kidney injury
Authors: Ma Piyong , Zhang Chunmei , Huo Pengfei , Li Yan , Yang Hailing
Published: June 2020

Acute kidney injury (AKI) is one of the most common and serious complications in the development of sepsis. Many microRNAs are closely related to the occurrence, development, and prognosis of sepsis AKI (but the effect and mechanism of miR‐152‐3p in it is unclear). Meanwhile, the ERBB receptor feedback inhibitor 1 (ERRFI1) has a negative regulatory effect on signal transducer and activator of transcription 3 (STAT3) phosphorylation on uterine epithelial cells. But, the relationship between miR‐152‐3p and renal function, inflammatory factors, prognosis in AKI, and the mechanism is not clear. Analyzing sepsis‐induced AKI rats and the cell model, our results revealed that miR‐152‐3p was upregulated in septic AKI patients and positively correlated with serum creatinine, urea nitrogen, interleukin 1β (IL‐1β) and tumor necrosis factor α (TNF‐α). Downregulation of miR‐152‐3p with the inhibitor could dramatically attenuate caspase‐3, bromodeoxyuridine and IL‐1β, and TNF‐α in the AKI rats' model. Furthermore, downregulation of miR‐152‐3p attenuated lipopolysaccharide‐induced apoptosis and inflammatory response in HK‐2 and HEK293 cells. To further explore the mechanisms, we found ERRFI1 was appreciably downregulated and STAT3 was upregulated in AKI, whereas ERRFI1 was radically upregulated and STAT3 was greatly downregulated after the addition of miR‐152‐3p inhibitor, no matter in vivo or in vitro. Summarily, our study confirmed that miR‐152‐3p could promote the expression of STAT3 by targeting ERRFI1, aggravate cell apoptosis and inflammatory response, and thereby aggravate kidney injury in sepsis AKI.
Retracted: The systemic inflammatory response syndrome in acute antipsychotic poisoning
Authors: Zhang Yaqun , Qiu Shengnu , Orlova Ekaterina
Published: June 2020

The purpose of this study was to investigate the mutual effect of systemic inflammatory response syndrome (SIRS) accompanied with fibrinolysis, endotoxemia, and coagulation in severe cases of antipsychotic poisoning. A total of 199 patients were examined, of which 71 were men and 128 were women. The age of the patients was from 22 to 63 years, (45.3 ± 6.1 years on average). According to the results of the course of therapy, the patients were divided into two groups. In the blood plasma, the content of C‐reactive protein, fibrinogen and its proteolysis products (oligopeptides, D‐dimers), interleukin‐6 were determined. In the first 1 to 3 days, in group 1, the level of interleukin‐6 decreased and approached the normal level (P ≤ .05). The opposite trend continued throughout the observation of patients from group 2—their levels of interleukin‐6 increased day by day (P ≤ .05). The concentration of D‐dimer already in 1 day after admission to intensive care in patients from group 2 exceeded the norm by 14 times (P ≤ .05). The level of D‐dimer correlated with the level of oligopeptides in blood plasma upon admission, as well as for 3 and 5 days after admission to intensive care: 0.36, 0.76 at P ≤ .05, 0.94 at P ≤ .01, respectively. Similar correlations were obtained for the content of oligopeptides in urine and the level of D‐dimer: 0.55, 0.85 at P ≤ .05, 0.93 at P ≤ .01. In this regard, the most pronounced correlation is that between the SIRS score, plasma D‐dimer level, and the plasma level of the D‐dimer derivatives, oligopeptides.
Carbohydrate response element‐binding protein regulates lipid metabolism via mTOR complex1 in diabetic nephropathy
Authors: Chen Nan , Mu Lin , Yang Zhifen , Du Chunyang , Wu Ming , Song Shan , Yuan Chen , Shi Yonghong
Published: June 2020

Lipid deposition caused by the disorder of renal lipid metabolism is involved in diabetic nephropathy (DN). Carbohydrate response element‐binding protein (ChREBP) is a key transcription factor in high glucose‐induced cellular fat synthesis. At present, the regulation and mechanism of ChREBP on fat metabolism in diabetic kidneys are still unclear. In this study, we showed that lack of ChREBP significantly improved renal injury, inhibited oxidative stress, lipid deposition, fatty acid synthase (FASN), acetyl‐CoA carboxylase (ACC) and thioredoxin‐interacting protein (TXNIP) expression, as well as the activity of mammalian target of rapamycin complex 1 (mTORC1) in diabetic kidneys. Meanwhile, ChREBP deficiency upregulated the expression of peroxisome proliferator‐activated receptor‐α (PPARα), carnitine palmitoyltransferaser 1A (CPT1A) and acyl‐coenzyme A oxidase 1 (ACOX1) in diabetic kidneys. In vitro, knockdown of ChREBP attenuated lipid deposition, mTORC1 activation, and expression of FASN and ACC, increased PPARα, CPT1A, and ACOX1 expression in HK‐2 cells and podocytes under high glucose (HG) conditions. Moreover, HG‐induced lipid deposition, increased expression of FASN and ACC and decreased expression of PPARα, CPT1A, and ACOX1 were reversed by rapamycin, a specific inhibitor of mTORC1, in HK‐2 cells. These results indicate that ChREBP deficiency alleviates diabetes‐associated renal lipid accumulation by inhibiting mTORC1 activity and suggest that reduction of ChREBP is a potential therapeutic strategy to treat DN.
Extrapulmonary Surfactant Therapy: Review of Available Data and Research/Development Issues
Authors: Foligno Silvia , Loi Barbara , Pezza Lucilla , Piastra Marco , Autilio Chiara , De Luca Daniele
Published: June 2020

Since the discovery of surfactant, a large amount of knowledge has been accumulated about its biology and pharmacology. Surfactant is the cornerstone of neonatal respiratory critical care, but its proteins and phospholipids are produced in various tissues and organs, with possible roles only partially similar to that played in the alveoli. As surfactant research is focused mainly on its respiratory applications, knowledge about the possible role of surfactant in extrapulmonary disorders has never been summarized. Here we aim to comprehensively review the data about surfactant biology and pharmacology in organs other than the lung, especially focusing in the more promising surfactant extrapulmonary roles. We also review any preclinical or clinical data available about the therapeutic use of surfactant in these contexts. We offer a summary of knowledge and research/development milestones, as possible useful guidance for researchers of multidisciplinary background.
Clinical Pharmacology Considerations for Developing Small‐Molecule Treatments for COVID‐19
Authors: Brunsdon Priya , Saluja Bhawana , Sahajwalla Chandrahas
Published: June 2020

Numerous drugs are being investigated for the treatment of COVID‐19, including antivirals and therapies targeting complications related to COVID‐19. The clinical presentation of COVID‐19 varies from mild fever, cough, and dyspnea in the early stages of disease to severe complications such as acute respiratory distress syndrome, systemic hyperinflammation, and sepsis. A thorough understanding of the disease pathogenesis and the disease complications is essential to developing effective therapies to treat this potentially life‐threatening disease. This review offers key clinical pharmacology considerations involved in the development of small molecules for the treatment of COVID‐19. They are based on the major observed disease complications that impact drug absorption, distribution, metabolism, and elimination. We also address considerations regarding potential drug interactions, alternative routes and methods of administration, and dosing in patients on hemodialysis.
Lectin binding sites on the plasma membranes of Orthoptera Tettigonioidea spermatodesms
Authors: Pecoraro Roberta , Scalisi Maria Elena , Brundo Maria Violetta
Published: June 2020

In many Vertebrate and invertebrate, the interaction mechanisms among gametes are based on a high affinity and specificity of recognition and link between specific saccharidic residues and receptors present on the surface of gametes. Literature data also suggest that Insects could use this strategy. In particular, Orthoptera Tettigoniidae spermatodesms and sperms undergo radical changes passing through the male to the female genital tracts that may be interpreted as well as a capacitation process. These changes could also concern the presence and distribution of surface glycoconjugates. Our study aims to highlight the presence and distribution of saccharide residues on the spermatozoa surface in five species of Orthoptera Tettigoniidae using a battery of lectins Fluorescein Isothiocyanate Conjugated and Gold Conjugated. The results of this investigation have shown that on the surface of the male gametes are present saccharide residues whose nature and distribution are species‐specific, during their transfer to the female genital tract, they significantly undergo a change. These results let us hypothesize that also for this group of Insects, the glycoconjugates play a significant role in the process of interaction between gametes.
Impacts of preferential flow and agroecosystem management on subsurface particulate phosphorus loadings in tile‐drained landscapes
Authors: Nazari Saeid , Ford William I. , King Kevin W.
Published: June 2020

Recent research on tile‐drainage has placed emphasis on dissolved reactive phosphorus (DRP) delivery and transport pathways but less emphasis on particulate P (PP), resulting in its exclusion from agricultural water management models. In this study, we quantified the fluxes, mechanisms, and factors driving PP delivery into tiles through statistical analysis of a long‐term hydrologic and water quality dataset. The dataset includes 5 yr of surface and tile discharge, total P (TP), DRP, total nitrogen (TN), and dissolved inorganic N concentrations from two edge‐of‐field study sites with contrasting soil and management practices. Hydrograph recession techniques were coupled with multiple linear regression for understanding hydrologic flow pathways, and empirical mode decomposition (EMD) time‐series analysis was used to determine the significance of PP seasonality processes and the effect of management practices. The analysis of hydrologic flow pathways demonstrated that quickflow contributed 66 and 36% of subsurface discharge in the clay and loam sites, respectively. Phosphorus loading analysis showed that macropore flow plays a significant role in PP delivery to subsurface P loading and that PP significantly contributed to TP and DRP delivery; however, greater PP loadings were observed at the clay site despite greater subsurface discharge and soil test P levels at the loam site. Furthermore, PP delivery was significantly affected by environmental conditions and management practices. We highlight the efficacy of hydrograph recession analysis for identifying macropore and diffuse drainage, of P/N ratios to characterize sediment delivery mechanisms in tiles, and of EMD to detect management impacts on TP and DRP at the field scale.
Prognostic value of expanded liver transplantation criteria—the 5‐5‐500 rule—in patients with hepatic resection for intermediate‐stage hepatocellular carcinoma
Authors: Shinkawa Hiroji , Tanaka Shogo , Takemura Shigekazu , Amano Ryosuke , Kimura Kenjiro , Kinoshita Masahiko , Miyazaki Toru , Kubo Shoji
Published: June 2020

Background

This study aimed to evaluate the prognostic impact of the 5‐5‐500 rule in patients after hepatic resection for the intermediate stage of hepatocellular carcinoma (HCC; The Barcelona Clinic Liver Cancer classification [BCLC] B).

Methods

177 patients had hepatic resection for BCLC‐B HCC. The 5‐5‐500 rule was defined by tumor size ≤5 cm in diameter, tumor number ≤5, and α‐fetoprotein ≤500 ng/mL.

Results

The 3‐, 5‐, and 7‐year recurrence‐free survival rates were 22%, 14%, and 11% in patients within the 5‐5‐500 rule, and 16%, 10%, and 10% in patients beyond the 5‐5‐500 rule, respectively (P = .015). The 3‐, 5‐, and 7‐year overall survival rates were 72%, 47%, and 34% in patients within the 5‐5‐500 rule, and 52%, 31%, and 25% in patients beyond the 5‐5‐500 rule, respectively (P = .035). Being beyond the 5‐5‐500 rule and liver cirrhosis were independent prognostic factors for recurrence‐free survival. For overall survival, being beyond the 5‐5‐500 rule, age ≥65 years, Child–Pugh class B, and anti‐hepatitis C antibody positive were identified as independent prognostic factors.

Conclusions

The 5‐5‐500 rule could predict prognosis in BCLC‐B patients with hepatic resection. Hepatic resection might provide survival benefit for selected patients with BCLC‐B HCC within the 5‐5‐500 rule.
Treatment with buprenorphine prior to EcoHIV infection of mice prevents the development of neurocognitive impairment
Authors: Jaureguiberry-Bravo Matias , Kelschenbach Jennifer , Murphy Aniella , Carvallo Loreto , Hadas Eran , Tesfa Lydia , Scott Travis M , Rivera-Mindt Monica , Cunningham Chinazo O , Arnsten Julia H , Volsky David J , Berman Joan W
Published: June 2020

Approximately 15–40% of people living with HIV develop HIV-associated neurocognitive disorders, HAND, despite successful antiretroviral therapy. There are no therapies to treat these disorders. HIV enters the CNS early after infection, in part by transmigration of infected monocytes. Currently, there is a major opioid epidemic in the United States. Opioid use disorder in the context of HIV infection is important because studies show that opioids exacerbate HIV-mediated neuroinflammation that may contribute to more severe cognitive deficits. Buprenorphine is an opioid derivate commonly prescribed for opiate agonist treatment. We used the EcoHIV mouse model to study the effects of buprenorphine on cognitive impairment and to correlate these with monocyte migration into the CNS. We show that buprenorphine treatment prior to mouse EcoHIV infection prevents the development of cognitive impairment, in part, by decreased accumulation of monocytes in the brain. We propose that buprenorphine has a novel therapeutic benefit of limiting the development of neurocognitive impairment in HIV-infected opioid abusers as well as in nonabusers, in addition to decreasing the use of harmful opioids. Buprenorphine may also be used in combination with HIV prevention strategies such as pre-exposure prophylaxis because of its safety profile.
A recombinant protein rLZ-8, originally extracted from Ganoderma lucidum, ameliorates OVA-induced lung inflammation by regulating Th17/Treg balance
Authors: Liu Huazhen , Qiu Feifei , Wang Yuanyuan , Liang Feng , Liang Jian , Lin Chengchuan , Liang Jiandong , Gong Boliang , Chan Shamyuen , De Zhang Zhong- , Lai Xiaoping , Hou Shaozhen , Dai Zhenhua
Published: June 2020

Asthma is one of the most common chronic and inflammatory respiratory diseases, which is estimated to affect 1–10% of the population in different regions across the world. Previous studies have shown that recombinant Ling-Zhi 8 (rLZ-8), an immunoregulatory protein originally extracted from Ganoderma lucidum, plays multiple roles in regulating murine immune cells, including T cells. Here, we examined whether rLZ-8 would ameliorate pulmonary inflammation in a model of asthma-like mice. We found that rLZ-8 significantly inhibited the lung inflammation and reduced infiltration of inflammatory cells, including dendritic cells and eosinophils, in OVA-induced asthmatic mice. It also deceased IL-17A level but increased IL-10 level in bronchoalveolar lavage fluid (BALF) while reducing RORγt mRNA expression and enhancing Foxp3 mRNA level in the lung tissue. Flow cytometry studies demonstrated that rLZ-8 remarkably down-regulated Th17 cells but upregulated Foxp3+ regulatory T (Treg) cells, rather than influencing Th1 versus Th2 cells. Experiments in vitro also showed that rLZ-8 suppressed murine CD3+ T cell proliferation and reduced the frequency of Th17 cells while promoting the differentiation of CD4+Foxp3+ Tregs. Moreover, rIL-8 similarly altered human Th17/Treg generation or their balance in vitro. Finally, we found that rLZ-8 suppressed signaling pathways of both STAT3 and NF-κB (P100/P52) in murine lung tissue as well as cultured T cells. Thus, we have demonstrated that rLZ-8 attenuates pulmonary inflammation through regulating the balance of Th17/Treg cells in OVA-induced asthmatic mice and that rLZ-8 may be a potential therapeutic agent for the treatment of asthma in clinic.
Green and enhanced extraction of coumarins from Cortex Fraxini by ultrasound‐assisted deep eutectic solvent extraction
Authors: Wang Yinan , Hu Youhui , Wang Hui , Tong Minghui , Gong Yinhan
Published: June 2020

Green and enhanced extraction of bioactive ingredients from medicinal plants has become a hot research field, and deep eutectic solvents have been considered as a novel kind of sustainable solvents in the extraction process. In this study, hydrogen bond acceptor (choline chloride, etc.) and hydrogen bond donor (l‐malic acid, etc.) were used to prepare different kinds of deep eutectic solvents to extract coumarins from Cortex Fraxini. The extraction conditions, including the composition and moisture content of deep eutectic solvents, extraction time, and liquid‐solid ratio, were systematically optimized basing on the extraction yield of coumarins. To further investigate the extraction mechanism, Fourier transform infrared spectroscopy was performed, and the microstructures of Cortex Fraxini powders were observed before and after extraction using scanning electron microscope. Results showed that the novel ultrasound‐assisted extraction with conditions of deep eutectic solvent containing betaine/glycerin (1:3), aqueous solution (20%), solid‐liquid ratio (15 mg/mL), and extraction time (30 min) exhibited the best extraction yields for the four target coumarins and much better extraction efficiency than with conventional solvent extractions. This suggests that the new ultrasound‐assisted deep eutectic solvent extraction could be used as a green and high‐efficient approach for extraction of the main coumarins from Cortex Fraxini.
Feasibility of Semiautomatic Fetal Intelligent Navigation Echocardiography for Different Fetal Spine Positions
Authors: Gembicki Michael , Hartge David R. , Fernandes Theresa , Weichert Jan
Published: June 2020

Objectives

We investigated the feasibility of a semiautomatic approach for assessments of the fetal heart (fetal intelligent navigation echocardiography [FINE]) in cases of optimal and unfavorable fetal spine positions.

Methods

In this study, a total of 1693 spatiotemporal image correlation volumes of first‐, second‐, and third‐trimester fetuses were evaluated by experts using the FINE approach. The data were analyzed regarding proper reconstruction of the diagnostic cardiac planes depending on the fetal spine position.

Results

A total of 1531 volumes were included. The volumes were divided into 4 groups depending on the fetal spine position: 5–7 o'clock, 4 + 8 o'clock, 3 + 9 o'clock, and 2 + 10 o'clock. In total, 93.2% of the diagnostic planes were displayed properly. Between 5 and 7 o'clock, 94.9% of the diagnostic planes were displayed properly. The correct depiction rates in the other groups were 92.4% (4 + 8 o'clock; n = 538; P = 0.0027), 88.3% (3 + 9 o'clock; n = 156; P < .0001), and 87.3% (2 + 10 o'clock; n = 41; P = .0139). In total, the highest dropout rates were found in the sagittal planes: ductal arch, 13.9%; aortic arch, 10.5%; and venae cavae, 12.0%.

Conclusions

Based on our results, the FINE technique is an effective method, but its feasibility depends on the fetal position. The use of this semiautomatic work flow–based approach supports evaluation of the fetal heart in a standardized manner. Semiautomatic evaluation of the fetal heart might be useful in facilitating the detection of fetal cardiac anomalies.
Applications of the Pharmacophore Concept in Natural Product inspired Drug Design
Authors: Seidel Thomas , Wieder Oliver , Garon Arthur , Langer Thierry
Published: June 2020

Pharmacophore‐based techniques are nowadays an important part of many computer‐aided drug design workflows and have been successfully applied for tasks such as virtual screening, lead optimization and de novo design. Natural products, on the other hand, can serve as a valuable source for unconventional molecular scaffolds that stimulate ideas for novel lead compounds in a more diverse chemical space that does not follow the rules of traditional medicinal chemistry. The first part of this review provides a brief introduction to the pharmacophore concept, the methods for pharmacophore model generation, and their applications. The second, concluding part, presents examples for recent, pharmacophore method related research in the field of natural product chemistry. The selected examples show, that pharmacophore‐based methods which get mainly applied on synthetic drug‐like molecules work equally well in the realm of natural products and thus can serve as a valuable tool for researchers in the field of natural product inspired drug design.
The Multidisciplinary Approach to The Study of Chronic Pelvic Pain (MAPP) Research Network*: Design and implementation of the Symptom Patterns Study (SPS)
Authors: Clemens J. Quentin , Kutch Jason J. , Mayer Emeran A. , Naliboff Bruce D. , Rodriguez Larissa V. , Klumpp David J. , Schaeffer Anthony J. , Kreder Karl J. , Clauw Daniel J. , Harte Steven E. , Schrepf Andrew D. , Williams David A. , Andriole Gerald L. , Lai H. Henry , Buchwald Dedra , Lucia M. Scott , van Bokhoven Adrie , Mackey Sean , Moldwin Robert M. , Pontari Michel A. , Stephens‐Shields Alisa J. , Mullins Chris , Landis J. Richard
Published: June 2020

Aims

The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network initiated a second observational cohort study—the Symptom Patterns Study (SPS)—to further investigate the underlying pathophysiology of Urologic Chronic Pelvic Pain Syndrome (UCPPS) and to discover factors associated with longitudinal symptom changes and responses to treatments.

Methods

This multisite cohort study of males and females with UCPPS features a run‐in period of four weekly web‐based symptom assessments before a baseline visit, followed by quarterly assessments up to 36 months. Controls were also recruited and assessed at baseline and 6 months. Extensive clinical data assessing urological symptoms, nonurological pain, chronic overlapping pain syndromes, and psychosocial factors were collected. Diverse biospecimens for biomarker and microbiome studies, quantitative sensory testing (QST) data under multiple stimuli, and structural and functional neuroimaging scans were obtained under a standardized protocol.

Results

Recruitment was initiated (July 2015) and completed (February 2019) at six discovery sites. A total of 620 males and females with UCPPS and 73 Controls were enrolled, including 83 UCPPS participants who re‐enrolled from the first MAPP Network cohort study (2009‐2012). Baseline neuroimaging scans, QST measures, and biospecimens were obtained on 578 UCPPS participants. The longitudinal follow‐up of the cohort is ongoing.

Conclusions

This comprehensive characterization of a large UCPPS cohort with extended follow‐up greatly expands upon earlier MAPP Network studies and provides unprecedented opportunities to increase our understanding of UCPPS pathophysiology, factors associated with symptom change, clinically relevant patient phenotypes, and novel targets for future interventions.
Ceftriaxone inhibits stress‐induced bladder hyperalgesia and alters cerebral micturition and nociceptive circuits in the rat: A multidisciplinary approach to the study of urologic chronic pelvic pain syndrome research network study
Authors: Holschneider Daniel P. , Wang Zhuo , Chang Huiyi , Zhang Rong , Gao Yunliang , Guo Yumei , Mao Jackie , Rodriguez Larissa V.
Published: June 2020

Aims

Emotional stress plays a role in the exacerbation and development of interstitial cystitis/bladder pain syndrome (IC/BPS). Given the significant overlap of brain circuits involved in stress, anxiety, and micturition, and the documented role of glutamate in their regulation, we examined the effects of an increase in glutamate transport on central amplification of stress‐induced bladder hyperalgesia, a core feature of IC/BPS.

Methods

Wistar‐Kyoto rats were exposed to water avoidance stress (WAS, 1 hour/day x 10 days) or sham stress, with subgroups receiving daily administration of ceftriaxone (CTX), an activator of glutamate transport. Thereafter, cystometrograms were obtained during bladder infusion with visceromotor responses (VMR) recorded simultaneously. Cerebral blood flow (CBF) mapping was performed by intravenous injection of [14C]‐iodoantipyrine during passive bladder distension. Regional CBF was quantified in autoradiographs of brain slices and analyzed in three dimensional reconstructed brains with statistical parametric mapping.

Results

WAS elicited visceral hypersensitivity during bladder filling as demonstrated by a decreased pressure threshold and VMR threshold triggering the voiding phase. Brain maps revealed stress effects in regions noted to be responsive to bladder filling. CTX diminished visceral hypersensitivity and attenuated many stress‐related cerebral activations within the supraspinal micturition circuit and in overlapping limbic and nociceptive regions, including the posterior midline cortex (posterior cingulate/anterior retrosplenium), somatosensory cortex, and anterior thalamus.

Conclusions

CTX diminished bladder hyspersensitivity and attenuated regions of the brain that contribute to nociceptive and micturition circuits, show stress effects, and have been reported to demonstrated altered functionality in patients with IC/BPS. Glutamatergic pharmacologic strategies modulating stress‐related bladder dysfunction may be a novel approach to the treatment of IC/BPS.
Obstructed infracardiac total anomalous pulmonary venous connection: The challenge of palliative stenting for the stenotic vertical vein
Authors: Al‐Mutairi Mansour , Aselan Adnan , Al‐Muhaya Mustafa , Abo‐Haded Hany
Published: June 2020

Introduction

Obstructed total anomalous pulmonary venous connection (TAPVC) is one of the commonest seen emergencies in pediatric cardiology centers.

Case presentation

Our case was diagnosed to have this anomaly, showing early respiratory distress resulting from severe pulmonary congestion. Palliative stenting of the obstruction was done, which helped in stabilizing the debilitated hemodynamics of the baby before surgery, thus a good surgical outcome and prognosis are expected.

Conclusion

This intervention may be listed as a vital measurement in the preoperative cardiac stabilization plan for infants with obstructed TAPVC.