bluuebunny/crossref_metadata_2025 huggingface dataset:
Whole Genome Selective Sweeps Analysis in Pakistani Kamori Goat
Authors: Saif Rashid , Henkel Jan , Mahmood Tania , Ejaz Aniqa , Zia Saeeda
Published: January 2021

Natural and artificial selection fix certain genomic regions of reduce heterozygosity which is an initial process in breed development. Primary goal of the current study is to identify these genomic selection signatures under positive selection and harbor genes in Pakistani Kamori goat breed. High throughput whole genome pooled-seq of Kamori (n = 12) and Bezoar (n = 8) was carried out. Raw fastq files were undergone quality checks, trimming and mapping process against ARS1 reference followed by calling variant allele frequencies. Selection sweeps were identified by applying pooled heterozygosity (Hp) and Tajima’s D (TD) on Kamori while regions under divergent selection between Kamori & Bezoar were observed by Fixation Index (FST) analysis. Genome sequencing yielded 619,031,812 reads of which, 616,624,284 were successfully mapped. Total 98,574 autosomal selection signals were detected; 32,838 fromHpand 32,868 from each FST& TD statistics. Annotation of the regions with threshold (−ZHp≥ 5, TD ≤ −2.72 & FST≤ 0.09) detected 60 candidate genes. The top hits harbor Chr.1, 6, 8 & 21 having genes associated with body weight (GLIS3, ASTE1), coat color (DOCK8,MIPOL1) & body height (SLC25A21). Other significant windows harbor milk production, wool production, immunity, adaptation and reproduction trait related genes. Current finding highlighted the under-selection genomic regions of Kamori breed and likely to be associated with its vested traits and further useful in breed improvement, and may be also propagated to other undefined goat breeds by adopting targeted breeding policies to improve the genetic potential of this valued species.
Redefining the roles of UDP-glycosyltransferases in auxin metabolism and homeostasis during plant development
Authors: Mateo-Bonmatí Eduardo , Casanova-Sáez Rubén , Šimura Jan , Ljung Karin
Published: January 2021

The levels of the important plant growth regulator indole-3-acetic acid (IAA) are tightly controlled within plant tissues to spatiotemporally orchestrate concentration gradients that drive plant growth and development. Metabolic inactivation of bioactive IAA is known to participate in the modulation of IAA maxima and minima. IAA can be irreversibly inactivated by oxidation and conjugation to Aspartate and Glutamate. Usually overlooked because its reversible nature, the most abundant inactive IAA form is the IAA-glucose (IAA-glc) conjugate. Glycosylation of IAA is reported to be carried out by the UDP-glycosyltransferase 84B1 (UGT84B1), while UGT74D1 has been implicated in the glycosylation of the irreversibly formed IAA catabolite oxIAA. Here we demonstrate that both UGT84B1 and UGT74D1 modulate IAA levels throughout plant development by dual IAA and oxIAA glycosylation. Moreover, we identify a novel UGT subfamily whose members modulate IAA homeostasis during skotomorphogenesis by redundantly mediating the glycosylation of oxIAA.
A novel SARS-CoV-2 related coronavirus in bats from Cambodia
Authors: Hul Vibol , Delaune Deborah , Karlsson Erik A , Hassanin Alexandre , Tey Putita Ou , Baidaliuk Artem , Gámbaro Fabiana , Tu Vuong Tan , Keatts Lucy , Mazet Jonna , Johnson Christine , Buchy Philippe , Dussart Philippe , Goldstein Tracey , Simon-Lorière Etienne , Duong Veasna
Published: January 2021

Knowledge of the origin and reservoir of the coronavirus responsible for the ongoing COVID-19 pandemic is still fragmentary. To date, the closest relatives to SARS-CoV-2 have been detected inRhinolophusbats sampled in the Yunnan province, China. Here we describe the identification of SARS-CoV-2 related coronaviruses in twoRhinolophus shamelibats sampled in Cambodia in 2010. Metagenomic sequencing identified nearly identical viruses sharing 92.6% nucleotide identity with SARS-CoV-2. Most genomic regions are closely related to SARS-CoV-2, with the exception of a small region corresponding to the spike N terminal domain. The discovery of these viruses in a bat species not found in China indicates that SARS-CoV-2 related viruses have a much wider geographic distribution than previously understood, and suggests that Southeast Asia represents a key area to consider in the ongoing search for the origins of SARS-CoV-2, and in future surveillance for coronaviruses.
Crystal structures of [Cu(phen)(H2O)3(MF6)]·H2O (M = Ti, Zr, Hf) and [Cu(phen)(H2O)2F]2[HfF6]·H2O
Authors: Nisbet Matthew L. , Poeppelmeier Kenneth R.
Published: January 2021

The crystal structures of three bridged bimetallic molecular compounds, namely, triaqua-2κ3
O-μ-fluorido-pentafluorido-1κ5
F-(1,10-phenanthroline-2κ2
N,N′)copper(II)titanium(IV) monohydrate, [Cu(TiF6)(phen)(H2O)3]·H2O (phen is 1,10-phenanthroline, C12H8N2), (I), triaqua-2κ3
O-μ-fluorido-pentafluorido-1κ5
F-(1,10-phenanthroline-2κ2
N,N′)copper(II)zirconium(IV) monohydrate, [Cu(ZrF6)(phen)(H2O)3]·H2O, (II), and triaqua-2κ3
O-μ-fluorido-pentafluorido-1κ5
F-(1,10-phenanthroline-2κ2
N,N′)copper(II)hafnium(IV) monohydrate, [Cu(HfF6)(phen)(H2O)3]·H2O, (III), and one molecular salt, bis[diaquafluorido(1,10-phenanthroline-κ2
N,N′)copper(II)] hexafluoridohafnate(IV) dihydrate, [CuF(phen)(H2O)2]2[HfF6]·2H2O, (IV), are reported. The bridged bimetallic compounds adopt Λ-shaped configurations, with the octahedrally coordinated copper(II) center linked to the fluorinated early transition metal via a fluoride linkage. The extended structures of these Λ-shaped compounds are organized through both intra- and intermolecular hydrogen bonds and intermolecular π–π stacking. The salt compound [Cu(phen)(H2O)2F]2[HfF6]·H2O displays an isolated square-pyramidal Cu(phen)(H2O)2F+ complex linked to other cationic complexes and isolated HfF6
2− anions through intermolecular hydrogen-bonding interactions.
Crystal structure of 1,2-bis(4-fluorophenyl)-1-hydroxy-2,3,8-trimethoxyacenaphthene: formation of a five-membered intramolecular O—H...O hydrogen-bonded ring
Authors: Iitsuka Hiroaki , Li Kun , Kobayashi Miyuki , Iida Kikuko , Yonezawa Noriyuki , Okamoto Akiko
Published: January 2021

The structure of the title compound, C27H22F2O4, at 193 K has triclinic (P\overline{1}) symmetry. The hydroxy and methoxy groups at the 1,2-positions of the acenaphthene core display a cis configuration. Both substituents are involved in the formation of a five-membered intramolecular O—H...O hydrogen-bonded ring. The 4-fluorophenyl rings make dihedral angles of 87.02 (7) and 51.86 (8)° with the naphthalene ring system. In the crystal, a pair of non-classical C—H...O hydrogen bonds forms centrosymmetric dimeric structures. The dimeric aggregates are linked in the ac plane through non-classical C—H...F hydrogen bonds and C—H...π interactions.
Crystal structure of a 1,1-dibutyl-1H,3H-naphtho[1,8-cd][1,2,6]oxastannaborinin-3-ol
Authors: Breitwieser Kevin , Chen Peter
Published: January 2021

The title oxastannaborininol compound, [Sn(C4H9)2(C10H7BO2)], has been synthesized and crystallized. While heterocycles containing a C–O–B group are common, heterocycles containing an E–O–B unit, where E is an element of the carbon group except for carbon, are rare. In fact, while heterocycles containing Si–O–B units are occasionally reported (although without crystal structures), there are no reports for the corresponding germanium, tin or lead analogues. Herein, the first synthesis and crystal structure of a heterocycle containing an Sn–O–B unit is described. The asymmetric unit contains one molecule showing a notable disorder of the tin atom and the butyl groups. They occupy two sets of positions with site-occupancy factors of 0.295 (6) and 0.705 (6).
The experimental manipulation of atmospheric drought: Teasing out the role of microclimate in biodiversity experiments
Authors: Aguirre Beatriz A. , Hsieh Brian , Watson Samantha J. , Wright Alexandra J.
Published: January 2021

Drought occurrence is increasing due to anthropogenic climate change. Drought can negatively affect plants via reduced water below‐ground and increased evaporative demand or vapour pressure deficit (VPD) above‐ground. Past work has shown that plant diversity can ameliorate the negative effects of drought in plant communities, but these results are inconsistent between experimental and natural drought studies. Furthermore, while studies on the negative effects of reduced soil moisture on plant growth in drought experiments are abundant, the effects of predicted increases in atmospheric VPD have been neglected.

We directly manipulated atmospheric relative humidity in a biodiversity and drought experiment at the California State University, Los Angeles (CA, USA) under three atmospheric conditions (ambient, dehumidified and humidified), two treatments of native perennial grass diversity (monoculture and eight species polyculture) and two soil drought treatments (control and drought). We assessed both polyculture plant community and individual species (Poa secunda) responses to atmospheric drought and soil drought.

We found that soil drought only limits above‐ground biomass production when atmospheric conditions are also dry. We also found that P. secunda was limited by increased competition in polyculture when ambient atmospheric conditions were humid but was facilitated by diversity when atmospheric conditions were dry.

Synthesis. Higher diversity ecosystems may be capable of protecting individual species from the negative effects of drought (facilitation). Without careful experimental manipulation of atmospheric drought, this important mechanism will be missed.
Quantifying nectar production by flowering plants in urban and rural landscapes
Authors: Tew Nicholas E. , Memmott Jane , Vaughan Ian P. , Bird Stephanie , Stone Graham N. , Potts Simon G. , Baldock Katherine C. R.
Published: January 2021

Floral resources (nectar and pollen) provide food for insect pollinators but have declined in the countryside due to land use change. Given widespread pollinator loss, it is important that we quantify their food supply to help develop conservation actions. While nectar resources have been measured in rural landscapes, equivalent data are lacking for urban areas, an important knowledge gap as towns and cities often host diverse pollinator populations.

We quantified the nectar supply of urban areas, farmland and nature reserves in the UK by combining floral abundance and nectar sugar production data for 536 flowering plant taxa, allowing us to compare landscape types and assess the spatial distribution of nectar sugar among land uses within cities.

The magnitude of nectar sugar production did not differ significantly among the three landscapes. In urban areas the nectar supply was more diverse in origin and predominantly delivered by non‐native flowering plants. Within cities, urban land uses varied greatly in nectar sugar production. Gardens provided the most nectar sugar per unit area and 85% of all nectar at a city scale, while gardens and allotments produced the most diverse supplies of nectar sugar. Floral abundance, commonly used as a proxy for pollinators’ food supply, correlated strongly with nectar resources, but left a substantial proportion of the variation in nectar supply unexplained.

Synthesis. We show that urban areas are hotspots of floral resource diversity rather than quantity and their nectar supply is underpinned by the contribution of residential gardens. Individual gardeners have an important role to play in pollinator conservation as ornamental plants, usually non‐native in origin, are a key source of nectar in towns and cities.
The potential value of dequalinium chloride in the treatment of cancer: Focus on malignant glioma
Authors: Pan Yuehai , Zhao Shuai , Chen Fan
Published: January 2021

Dequalinium chloride has been known as one kind of antibiotic that displays a broad antimicrobial spectrum and has been clinically proven to be very safe. In recent years, studies have shown that dequalinium chloride can inhibit the growth of malignant tumours, and reports were mainly used for solid tumours. Glioblastoma is the most common malignant neuroepithelial tumour of the central nervous system in adults, and the prognosis of glioblastoma is poor as it has a high resistance to apoptosis. This review summarizes the current understanding of dequalinium chloride‐induced cancer cell apoptosis and its potential role in glioblastoma resistance and progression. Particularly, we focus on dequalinium chloride as it exerts a wide range of anti‐cancer activity through its ability to target and accumulate in the mitochondria, and it effectively inhibits the growth of glioblastoma cells in vitro and vivo. Dequalinium chloride is an inhibitor of XIAP and can also act as a mitochondrial targeting agent, which gives it an interesting perspective regarding recent advances in the treatment of malignant glioma.
Scavenging by fishers in relation to season and other scavengers
Authors: Allen Maximilian L. , Elbroch L. Mark , Wittmer Heiko U.
Published: January 2021

Carrion is an energy‐rich resource that benefits many organisms, but scavenging involves both profits and risks. Fishers (Pekania pennanti) are forest‐specialists that scavenge large carcasses but quantitative assessments of their scavenging are lacking. We quantified three characteristics of scavenging behavior by fishers: (a) whether fishers visited a carcass; (b) the time to first visitation of a carcass by fishers; and (c) how long fishers fed at a carcass. We then evaluated the importance of habitat characteristics, cues from other scavenger species, and season on the scavenging behaviors of fishers. Fishers scavenged 25 of the 89 deer carcasses we monitored, and visited carcasses more frequently in winter (n = 22, 34%) than in summer (n = 3, 12%). Time to the first fisher visit to a carcass averaged 4.7 (±1.1 SE) days. On average fishers made 26 (±9 SE) repeat visits to each carcass they found and fed for 118.1 min (±42.3 SE) over an average of 6 days; season also influenced their feeding times (120.3 ± 46.0 SE min in winter versus 63.7 ± 44.7 SE min in summer). Fishers had a crepuscular activity pattern while scavenging, but initial visits peaked mid‐day in addition to a peak near sunset. Our results suggested that fishers may use cues from other scavengers to detect carrion, but that habitat characteristics did not affect exploitation of carrion more than other variables. These results highlight the potential importance of carrion for the foraging ecology of fishers, particularly during times of resource scarcity. Further research based on identifiable individuals is needed to quantify fitness consequences of scavenging for fishers, including possible negative effects of intraguild predation at carrion.
Chitosan modulates Pochonia chlamydosporia gene expression during nematode egg parasitism
Authors: Suarez‐Fernandez Marta , Sambles Christine , Lopez‐Moya Federico , Nueda María J. , Studholme David J. , Lopez‐Llorca Luis Vicente
Published: January 2021

Climate change makes plant‐parasitic nematodes (PPN) an increasing threat to commercial crops. PPN can be managed sustainably by the biocontrol fungus Pochonia chlamydosporia (Pc). Chitosan generated from chitin deacetylation enhances PPN parasitism by Pc. In this work, we investigate the molecular mechanisms of Pc for chitosan resistance and root‐knot nematode (RKN) parasitism, using transcriptomics. Chitosan and RKN modify the expression of Pc genes, mainly those involved in oxidation–reduction processes. Both agents significantly modify the expression of genes associated to 113 GO terms and 180 Pc genes. Genes encoding putative glycoproteins (Pc adhesives) to nematode eggshell, as well as genes involved in redox, carbohydrate and lipid metabolism trigger the response to chitosan. We identify genes expressed in both the parasitic and endophytic phases of the Pc lifecycle; these include proteases, chitosanases and transcription factors. Using the Pathogen—Host Interaction database (PHI‐base), our previous RNA‐seq data and RT‐PCR of Pc colonizing banana we have investigated genes expressed both in the parasitic and endophytic phases of Pc lifecycle.
The phylogenetic and global distribution of bacterial polyhydroxyalkanoate bioplastic‐degrading genes
Authors: Viljakainen V. R. , Hug L. A.
Published: January 2021

Polyhydroxyalkanoates (PHAs) are a family of microbially made polyesters commercialized as biodegradable plastics. PHA production rates are predicted to increase as concerns around environmental plastic contamination and limited fossil fuel resources have increased the importance of biodegradable and bio‐based plastic alternatives. Microbially produced PHA depolymerases are the key enzymes mediating PHA biodegradation, but only a few PHA depolymerases have been well‐characterized and screens employing metagenomic sequence data are lacking. Here, we used 3078 metagenomes to analyse the distribution of PHA depolymerases in microbial communities from diverse aquatic, terrestrial and waste management systems. We significantly expand the recognized diversity of this protein family by screening 1914 Gb of sequence data and identifying 13 869 putative PHA depolymerases in 1295 metagenomes. Our results indicate that PHA depolymerases are unevenly distributed across environments. We predicted the highest frequency of PHA depolymerases in wastewater systems and the lowest in marine and thermal springs. In tandem, we screened 5290 metagenome‐assembled genomes to describe the phylogenetic distribution of PHA depolymerases, which is substantially broader compared with current cultured representatives. The Proteobacteria and Bacteroidota are key lineages encoding PHA depolymerases, but PHA depolymerases were predicted from members of the Bdellovibrionota, Methylomirabilota, Actinobacteriota, Firmicutes, Spirochaetota, Desulfobacterota, Myxococcota and Planctomycetota.
Evaluation of the chemical qualities and microstructural changes of Lentinula edodes caused by airborne ultrasonic treatment combined with microwave vacuum drying
Authors: Lei Yanping , Wang Weiwei , Zhang Chong , Wang Danni , Zhuang Weijing , Zheng Baodong , Lo Y. Martin , Tian Yuting
Published: January 2021

This study analyzed a new drying method using airborne ultrasound combined with microwave vacuum to study its effect on the quality characteristics and microstructure of dehydrated L. edodes. Ultrasonic treatment resulted in many micropores in the product, forming the sponge effect caused by ultrasonic waves, which can promote the rapid evaporation of water in the product. Samples of Lentinula edodes individuals were dried using four methods: hot air drying (HAD), microwave vacuum drying (MVD), microwave vacuum drying after ultrasonic pretreatment (US+MVD) and airborne ultrasonic treatment combined with microwave vacuum drying (USMVD). The results showed that USMVD can reduced the loss of total sugar, total phenol, and total antioxidants in L. edodes, and increased the relative content of ergosterol, sulfur compounds, and free amino acids (p < 0.05). Scanning electron microscope observation revealed that USMVD resulted in a uniform reticular porous structure, which could better maintain desirable levels of nutrients. Therefore, USMVD can produce high quality products.

Practical Application

Airborne ultrasonic waves combined with MVD provides an innovative drying method for mushrooms, which has not been studied at present. The mixed drying method has great potential in maintaining product quality. It provides a theoretical basis for studying drying technology in the future.
Targeting age‐specific changes in CD4+ T cell metabolism ameliorates alloimmune responses and prolongs graft survival
Authors: Nian Yeqi , Iske Jasper , Maenosono Ryoichi , Minami Koichiro , Heinbokel Timm , Quante Markus , Liu Yang , Azuma Haruhito , Yang Jinrui , Abdi Reza , Zhou Hao , Elkhal Abdallah , Tullius Stefan G.
Published: January 2021

Age impacts alloimmunity. Effects of aging on T‐cell metabolism and the potential to interfere with immunosuppressants have not been explored yet. Here, we dissected metabolic pathways of CD4+ and CD8+ T cells in aging and offer novel immunosuppressive targets. Upon activation, CD4+ T cells from old mice failed to exhibit adequate metabolic reprogramming resulting into compromised metabolic pathways, including oxidative phosphorylation (OXPHOS) and glycolysis. Comparable results were also observed in elderly human patients. Although glutaminolysis remained the dominant and age‐independent source of mitochondria for activated CD4+ T cells, old but not young CD4+ T cells relied heavily on glutaminolysis. Treating young and old murine and human CD4+ T cells with 6‐diazo‐5‐oxo‐l‐norleucine (DON), a glutaminolysis inhibitor resulted in significantly reduced IFN‐γ production and compromised proliferative capacities specifically of old CD4+ T cells. Of translational relevance, old and young mice that had been transplanted with fully mismatched skin grafts and treated with DON demonstrated dampened Th1‐ and Th17‐driven alloimmune responses. Moreover, DON diminished cytokine production and proliferation of old CD4+ T cells in vivo leading to a significantly prolonged allograft survival specifically in old recipients. Graft prolongation in young animals, in contrast, was only achieved when DON was applied in combination with an inhibition of glycolysis (2‐deoxy‐d‐glucose, 2‐DG) and OXPHOS (metformin), two alternative metabolic pathways. Notably, metabolic treatment had not been linked to toxicities. Remarkably, immunosuppressive capacities of DON were specific to CD4+ T cells as adoptively transferred young CD4+ T cells prevented immunosuppressive capacities of DON on allograft survival in old recipients. Depletion of CD8+ T cells did not alter transplant outcomes in either young or old recipients. Taken together, our data introduce an age‐specific metabolic reprogramming of CD4+ T cells. Targeting those pathways offers novel and age‐specific approaches for immunosuppression.
Stability of Posttreatment Reductions in World Health Organization (WHO) Drinking Risk Levels and Posttreatment Functioning in Older Adults with DSM‐5 Alcohol Use Disorder: Secondary Data Analysis of the Elderly Study
Authors: Mejldal Anna , Andersen Kjeld , Behrendt Silke , Bilberg Randi , Bogenschutz Michael , Braun‐Michl Barbara , Bühringer Gerhard , Søgaard Nielsen Anette
Published: January 2021

Background

Studies have found that reductions in World Health Organization (WHO) drinking risk levels may be a stable outcome of treatment for alcohol use disorder (AUD) and associated with functional improvements. The aim of this study was to investigate whether posttreatment reductions in WHO drinking risk levels are stable over time among older adults and associated with a decrease in consequences of drinking and AUD symptoms and improved quality of life.

Methods

Participants. Individuals 60+ years old, suffering from DSM‐5 AUD (n = 693), and seeking outpatient treatment.

Measurements. WHO drinking risk levels, prior to treatment and at all follow‐up points up to 1 year after treatment start, were assessed with Form 90. Outcomes at follow‐up included consequences of drinking (Drinker Inventory of Consequences), quality of life (WHOQOL‐BREF), and DSM‐5 AUD symptoms (Mini International Neuropsychiatric Interview). Logistic regression and linear mixed models were used to examine the probability of maintaining risk‐level reductions at follow‐up and the association between risk‐level reductions and outcomes, respectively.

Results

Reductions in risk levels were maintained over time (at least 1 level: OR 5.39, 95% CI 3.43, 8.47; at least 2 levels: OR 9.30, 95% CI 6.14, 14.07). Reductions were associated with reduced consequences of drinking and number of AUD symptoms, and minor, but statistically significant, improvements in quality of life.

Conclusions

Maintaining reductions in WHO risk levels appears achievable for older adults seeking treatment for AUD. The small reduction of AUD symptoms and improvement of quality of life indicates that these reductions may not be adequate as the only treatment goal.
Three Weeks of Binge Alcohol Drinking Generates Increased Alcohol Front‐Loading and Robust Compulsive‐Like Alcohol Drinking in Male and Female C57BL/6J Mice
Authors: Bauer Meredith R. , McVey Megan M. , Boehm Stephen L.
Published: January 2021

Background

Current models of compulsive‐like quinine‐adulterated alcohol (QuA) drinking in mice, if improved, could be more useful for uncovering the neural mechanisms of compulsive‐like alcohol drinking. The purpose of these experiments was to further characterize and improve the validity of a model of compulsive‐like QuA drinking in C57BL/6J mice. We sought to determine whether compulsive‐like alcohol drinking could be achieved following 2 or 3 weeks of Drinking‐in‐the‐Dark (DID), whether it provides evidence for a robust model of compulsive‐like alcohol drinking by inclusion of a water control group and use of a highly concentrated QuA solution, whether repeated QuA exposures alter compulsive‐like drinking, and whether there are sex differences in compulsive‐like alcohol drinking.

Methods

Male and Female C57BL/6J mice were allowed free access to either 20% alcohol or tap water for 2 hours each day for approximately 3 weeks. After 2 or 3 weeks, the mice were given QuA (500 μM) and the effect of repeated QuA drinking sessions on compulsive‐like alcohol drinking was assessed. 3‐minute front‐loading, 2 hour binge‐drinking, and blood alcohol concentrations were determined.

Results

Compulsive‐like QuA drinking was achieved after 3 weeks, but not 2 weeks, of daily alcohol access as determined by alcohol history mice consuming significantly more QuA than water history mice and drinking statistically nondifferent amounts of QuA than nonadulterated alcohol at baseline. Thirty‐minute front‐loading of QuA revealed that alcohol history mice front‐loaded significantly more QuA than water history mice, but still found the QuA solution aversive. Repeated QuA exposures did not alter these patterns, compulsive‐like drinking did not differ by sex, and BACs for QuA drinking were at the level of a binge.

Conclusions

These data suggest that compulsive‐like QuA drinking can be robustly achieved following 3 weeks of DID and male and female C57BL/6J mice do not differ in compulsive‐like alcohol drinking.
Low‐dose polypharmacology targeting dopamine D1 and D3 receptors reduces cue‐induced relapse to heroin seeking in rats
Authors: Ewing Scott T. , Dorcely Chris , Maidi Rivka , Paker Gulsah , Schelbaum Eva , Ranaldi Robert
Published: January 2021

Chemical compounds that target dopamine (DA) D1 or D3 receptors have shown promise as potential interventions in animal models of cue‐induced relapse. However, undesirable side effects or pharmacodynamic profiles have limited the advancement of new compounds in preclinical studies when administered as independent treatments. In this series of experiments, we explored the effects of coadministration of a D1‐receptor partial agonist (SKF 77434) and a D3‐receptor antagonist (NGB 2904) in heroin‐seeking rats within a “conflict” model of abstinence and cue‐induced relapse. Rats were first trained to press a lever to self‐administer heroin, and drug delivery was paired contingently with cues (e.g., light and pump noise). Self‐initiated abstinence was facilitated by applying electrical current to the flooring in front of the levers. Lastly, a relapse response was provoked by noncontingent presentation of conditioned cues. Prior to provocation, rats received a systemic injection of SKF 77434, NGB 2904, or a combination of both compounds to assess treatment effects on lever pressing. Results indicated that the coadministration of low (i.e., independently ineffective) doses of both compounds was more effective in reducing cue‐induced relapse to heroin seeking than either compound alone, with some evidence of drug synergism. Follow‐up studies indicated that this reduction was not due to motoric impairment nor enhanced sensitivity to the electrified flooring and that this treatment did not significantly affect motivation for food. Implications for the treatment of opiate use disorder and recommendations for further research are discussed.
Effect of simulation‐based team training in airway management: a systematic review
Authors: Nielsen R. P. , Nikolajsen L. , Paltved C. , Aagaard R.
Published: January 2021

Major complications associated with airway management are rare but often have serious consequences. Complications frequently result from failures in communication and teamwork. We performed a systematic review on the effect of simulation‐based team training on patient outcomes, healthcare professionals' clinical performance and preparedness for airway management. We included studies with simulation‐based team training in airway management as the educational intervention, using any comparator, outcome and design. Two authors independently selected articles and assessed risk of bias using the Medical Education Research Study Quality Instrument and Newcastle–Ottawa Scale‐Education. We screened 1248 titles and evaluated 116 full‐text articles. Twenty‐two studies were included. The Kirkpatrick model for evaluation of training was used to organise outcomes. Four studies reported patient‐centred outcomes (Kirkpatrick level 4), and three studies' outcomes related to healthcare professionals' clinical performance (Kirkpatrick level 3). The results were ambiguous and the studies had significant methodological limitations, making it difficult to draw conclusions on the effect of simulation‐based team training. To describe preparedness for airway management, we used outcomes related to participants' attitudes or perceptions and outcomes related to knowledge or skills demonstrated in a test setting (Kirkpatrick level 2). Most studies reporting these outcomes were in favour of simulation‐based team training, but were prone to bias. We consider the current evidence to be weak and recommend that future research should be based on randomised study designs and patient‐centred outcomes.
Agreement between careHPV and hybrid capture 2 in detecting high‐risk HPV in women in Tanzania
Authors: Katanga Johnson , Kjaer Susanne K. , Manongi Rachel , Pembe Andrea B. , Iftner Thomas , Waldstrom Marianne , Mwaiselage Julius , Rasch Vibeke
Published: January 2021

Introduction

Visual inspection of the cervix with acetic acid is used to control the burden of cervical cancer in low‐ and middle‐income countries. This method has some limitations and HPV DNA testing may be an alternative, but it is expensive and requires a laboratory setup. Cheaper and faster HPV tests have been developed. This study describe the agreement between a fast HPV test (careHPV) and hybrid capture 2 (HC2) in detection of high‐risk HPV among Tanzanian women.

Material and methods

The study involved women attending routine cervical cancer screening at the Ocean Road Cancer Institute and Kilimanjaro Christian Medical Centre in Tanzania. The women were offered HIV testing. Two cervical samples were subsequently obtained; the first sample was processed at the clinics using careHPV and the second sample was transported to Denmark and Germany for cytology and HC2 analysis. Kappa statistic was calculated to assess the agreement between careHPV and HC2. The sensitivity, specificity and predictive values of careHPV were calculated using HC2 as reference. The analyses were done for the overall study population and stratified by testing site and HIV status.

Results

A total of 4080 women were enrolled, with 437 being excluded due to invalid information, lack of careHPV or HC2 results. Overall agreement between the tests was substantial with a kappa value of 0.69 (95% confidence interval [CI] 0.66‐0.72). The sensitivity and specificity of careHPV was 90.7% (95% CI 89.6‐91.8) and 84.2% (95% CI 81.2–86.8), respectively. The agreement was similar in the stratified analyses where the kappa values were 0.75 (95% CI 0.70‐0.79) in women aged 25‐34, 0.66 (95% CI 0.62‐0.70) in women aged 35–60, 0.73 (95% CI 0.70‐0.77) at the Ocean Road Cancer Institute, 0.64 (95% CI 0.60‐0.69) at the Kilimanjaro Christian Medical Center, 0.73 (95% CI 0.68‐0.79) in HIV‐positive and 0.66 (95% CI 0.63‐0.70) in HIV‐negative women. The kappa value of 0.64 (95% CI 0.39‐0.88) for cervical high‐grade lesions indicates a substantial agreement between careHPV and HC2 in detecting HPV among women with cervical high‐grade lesions.

Conclusions

A substantial agreement was found between careHPV and HC2 in detecting HPV overall as well as detecting HPV among women with cervical high‐grade lesions. However, given the limited resources available in low and middle‐income countries, the HPV testing assay should be weighed against the cost‐effectiveness of the test.
Who prescribes drugs to patients: A Danish register‐based study
Authors: Pottegård Anton , Olesen Morten , Christensen Bo , Christensen Morten Bondo , Hallas Jesper , Rasmussen Lotte
Published: January 2021

We describe the distribution of prescriber types responsible for issuing prescriptions in Denmark. Using a 20% random sample of all Danes alive during 2000–2018 (n = 1 515 025) and all their prescriptions filled at community pharmacies (n = 182 143 707), we found that general practitioners issued 88% of all prescriptions, followed by hospital physicians (7.4%) and private practicing specialists (4.2%). These values were stable over the study period. With increasing patient age, general practitioners were responsible for a larger proportion of prescriptions (e.g. 68% for patients aged 0–17 y and 89% for patients ≥51 y). General practitioners were responsible for 84% of all treatment initiation (first prescription) and 90% of all maintenance treatment. Corresponding values for hospital physicians were 9.5 and 6.3%, and for private practicing specialists 5.3 and 3.6%. In conclusion, general practitioners are responsible for the vast majority of prescribing in Denmark, including both treatment initiation and continuation, in particular among the elderly.
Therapeutic efficacy of α7 ligands after acute ischaemic stroke is linked to conductive states of α7 nicotinic ACh receptors
Authors: Gaidhani Nikhil , Tucci Fabio C. , Kem William R. , Beaton Graham , Uteshev Victor V.
Published: January 2021

Background and Purpose

Targeting α7 nicotinic ACh receptors (nAChRs) in neuroinflammatory disorders including acute ischaemic stroke holds significant therapeutic promise. However, therapeutically relevant signalling mechanisms remain unidentified. Activation of neuronal α7 nAChRs triggers ionotropic signalling, but there is limited evidence for it in immunoglial tissues. The α7 ligands which are effective in reducing acute ischaemic stroke damage promote α7 ionotropic activity, suggesting a link between their therapeutic effects for treating acute ischaemic stroke and activation of α7 conductive states.

Experimental Approach

This hypothesis was tested using a transient middle cerebral artery occlusion (MCAO) model of acute ischaemic stroke, NS6740, a known selective non‐ionotropic agonist of α7 nAChRs and 4OH‐GTS‐21, a partial α7 agonist. NS6740‐like ligands exhibiting low efficacy/potency for ionotropic activity will be referred to as non‐ionotropic agonists or “metagonists”.

Key Results

4OH‐GTS‐21, used as a positive control, significantly reduced neurological deficits and brain injury after MCAO as compared to vehicle and NS6740. By contrast, NS6740 was ineffective in identical assays and reversed the effects of 4OH‐GTS‐21 when these compounds were co‐applied. Electrophysiological recordings from acute hippocampal slices obtained from NS6740‐injected animals demonstrated its remarkable brain availability and protracted effects on α7 nAChRs as evidenced by sustained (>8 h) alterations in α7 ionotropic responsiveness.

Conclusion and Implications

These results suggest that α7 ionotropic activity may be obligatory for therapeutic efficacy of α7 ligands after acute ischaemic stroke yet, highlight the potential for selective application of α7 ligands to disease states based on their mode of receptor activation.
Detrimental effects of adolescent escalating low‐dose Δ9‐tetrahydrocannabinol leads to a specific bio‐behavioural profile in adult male rats
Authors: Poulia Nafsika , Delis Foteini , Brakatselos Charalampos , Polissidis Alexia , Koutmani Yassemi , Kokras Nikolaos , Dalla Christina , Politis Panagiotis K. , Antoniou Katerina
Published: January 2021

Background and Purpose

Adolescent cannabis use is associated with adult psychopathology. When Δ9‐tetrahydrocannabinol (THC), mainly in high doses, is administered to adolescence rats there are also long lasting effects in adults. This study aims to determine the specific adult bio‐behavioural profile after adolescent low‐dose THC, which better mirrors adolescent recreational cannabis use.

Experimental Approach

Adolescent male Sprague–Dawley rats were treated with escalating low‐dose of THC. In adulthood, they were evaluated for their spontaneous locomotion, sensorimotor gating, higher order and spatial cognitive functions. Dopaminergic activity and cannabinoid receptor expression were measured in distinct brain regions. Hippocampal neurogenic activity of neural stem cells was determined and protein levels of neuroplasticity‐related biomarkers were quantified. Adolescent low‐dose THC exposure increased spontaneous open‐field activity, without affecting prepulse inhibition and attentional set‐shifting performance. Region‐specific dopaminergic alterations and CB1 receptor up‐regulation in the prefrontal cortex were observed. Impaired spatial memory, as assessed with the object location task and Morris water maze test, was associated with significantly decreased proliferative activity (SOX2‐positive cells), neurogenic potential (decreased doublecortin‐positive cells) in the adult hippocampus and defective neuroplasticity, including reduced BDNF expression in the hippocampus and prefrontal cortex.

Key Results

Our findings reveal the adverse impact of adolescent low‐dose THC on the psychomotor profile, dopaminergic neurotransmission, compensatory cannabinoid receptor response, cognition‐related neurobiological and behavioural functions.

Conclusion and Implications

Our adolescent low‐dose THC animal model does not induce tangible psychotic‐like effects, such as those reported in high‐dose THC studies, but it impairs cognitive functions and points to hippocampal vulnerability and disrupted neurogenesis.
A combined abdominal and transanal minimally invasive (TAMIS) approach in redo anastomoses for severe refractory rectal strictures
Authors: Seow‐En Isaac , Ke Tao‐Wei , Chen Yi‐Chang , Tzu‐Liang Chen William
Published: January 2021

Aim

Anastomotic stricture following anterior resection is an uncommon but challenging problem. Endoscopic dilatation and transanal endoscopic surgery (TES) are proven methods of treatment. However, a small proportion of patients repeatedly fail transanal local therapy for underlying reasons of tension, insufficient blood supply or irradiated tissue, eventually necessitating a complete anastomotic excision. We aimed to combine transanal minimally invasive surgery (TAMIS) with an abdominal approach in redo anastomoses for severe refractory anastomotic strictures.

Method

For the TAMIS phase, we use a Lonestar® retractor with a GelPOINT® Path transanal access platform. A circumferential full thickness rectotomy is performed and the dissection is continued proximally in the mesorectal fascial plane past the strictured segment to meet the abdominal dissection or until the peritoneal cavity is entered, facilitating mobilization of the rectum. The abdominal phase is performed as usual with sufficient mobilization of the left colon to enable tension‐free redo anastomosis. An accompanying video demonstrates this technique.

Results

Two patients with refractory anastomotic strictures following a previous low anterior resection underwent the procedure. One patient had laparoscopy followed by TAMIS and the other had TAMIS followed by laparotomy. Both cases were performed by surgeons experienced in laparoscopy and TES. One patient had postoperative ileus which resolved conservatively. Both anastomoses were widely patent on follow‐up.

Conclusion

TAMIS combined with a conventional abdominal approach offers significant technical advantages over a totally abdominal approach for the definitive management of patients with severe anastomotic strictures refractory to first‐line methods of therapy. The operator should already be proficient with TES.
New disazo dyes derived from aminopyrazoles: synthesis, spectroscopic properties, computational study and structural properties
Authors: Yıldırım Fati , Demirçalı Aykut , Taşlı Pınar Tunay , Karcı Fikret
Published: January 2021

In this study, five new pyrazolyazo pyrazole dyestuff syntheses are reported. For this purpose, 5‐amino‐4‐arylazo‐3‐methyl‐1H‐pyrazoles were diazotised and coupled with 3‐amino‐5‐hydroxy‐1H‐pyrazole. Fourier Transform–infrared, ultraviolet‐visible and proton nuclear magnetic resonance spectroscopy were used to investigate the properties of aminopyrazole‐based dyes obtained in this study. The maximum absorption wavelengths of these dyes in various solvents were determined. The theoretical calculations of the molecules in the ground state were performed with the density functional theory/Becke 3‐parameter and Lee–Yang–Parr/6‐311G(d,p) method by using the Gaussian 0.9 W program. The results were compared with the corresponding experimental data. Acid‐base and substituent effects on the absorption spectra of dyes were also examined and reported.
A physiological perspective of the associations between hydration status and CTP neuroimaging parameters in hyper‐acute ischaemic stroke patients
Authors: Buoite Stella Alex , Ajčević Miloš , Furlanis Giovanni , Lugnan Carlo , Gaio Marina , Cillotto Tommaso , Scali Ilario , Caruso Paola , Cova Maria Assunta , Naccarato Marcello , Manganotti Paolo
Published: January 2021

Hypohydration may be associated with vascular diseases, poor prognosis and worse outcomes in stroke. The underlying mechanisms have not yet been completely investigated, although some studies suggested potential associations with brain perfusion and collaterals status. Despite the potentially different mechanisms promoting serum or urine biomarkers of hypohydration, few studies have investigated both markers separately. A prospective descriptive study was conducted in stroke patients admitted to a stroke unit <4.5 h from symptoms onset. All patients underwent neurological evaluation and whole‐brain computed tomography perfusion (CTP) upon admission. Blood and urine samples were immediately collected at admission, and patients were defined as “hypohydrated” (HYP) if blood urea nitrogen‐to‐creatinine ratio was >15 and “underhydrated” (UND) if urine osmolality was >500 mOsm/kg. CTP images were processed to calculate core, penumbra, their mismatch and total hypoperfused volume. Forty‐six patients were included and were grouped according to hydration status. Despite no different NIHSS at baseline, at CTP HYP was independently associated with core‐penumbra mismatch (β: −0.157, 95% CI: −0.305 to −0.009; p = .04), while UND was independently associated with the total hypoperfused volume (β: 31.502, 95% CI: 8.522‒54.481; p = .01). Using CTP imaging, this study proposes a physiological insight of some possible mechanisms associated with the better outcomes observed in acute stroke patients when properly hydrated. These results suggest different associations between hydration status and CTP parameters depending on serum or urine biomarkers in the hyper‐acute phase and encourage the association between hydration status and stroke characteristics.
Association between insulin resistance and BMI with FEV1 in non‐hypoxemic COPD out‐patients
Authors: Zuberi Faisal Faiyaz , Bader Nimrah , Rasheed Tazeen , Zuberi Bader Faiyaz
Published: January 2021

Objectives

This study was conducted to determine the impact of insulin resistance using Homeostatic Model Assessment of Insulin Resistance (HOMA‐IR) score and BMI in non‐hypoxemic out‐patients with COPD on FEV1 using linear and polynomial regressions and to determine their correlation.

Methods

COPD patients of both genders were included after informed consent. Fasting blood sugar and serum insulin were done to calculate HOMA‐IR, which were segregated into two groups of ≥ 3 and < 3 labeled insulin resistance present and absent, these were compared with BMI. Patients were segregated into GOLD Grade 1–4 per GOLD Guidelines and compared with HOMA‐IR and BMI. Curve and linear regressions, multivariate and univariate analysis of HOMA‐IR with BMI, FVC, and FEV1 were done.

Results

A total of 273 subjects were inducted after informed consent. There was a linear correlation between HOMA‐IR and BMI (r2 0.498, P < 0.001) and nonlinear correlation between HOMA‐IR and FEV1 (r2 0. 617, P < 0.001) which showed little evidence of association above FEV1 > 60 predicted, but a clear negative association below that. Significant increase in HOMA‐IR was seen from GOLD‐2 to 3 and from GOLD‐3 to 4 classes. The impact of HOMA‐IR on FEV1 was 49.9% (P < 0.001) on FVC was 43.7%.

Conclusions

The results indicate that there is a high prevalence of IR in non‐hypoxemic COPD. A nonlinear association is present between FEV1 and HOMA‐IR which is most evident with FEV1 <60% predicted.
Human–crocodilian interactions in Latin America and the Caribbean region
Authors: Pooley Simon , Siroski Pablo Ariel , Fernandez Lucía , Sideleau Brandon , Ponce‐Campos Paulino
Published: January 2021

Mitigating harmful interactions with wildlife requires an understanding of the interactions between predators, domesticated animals and humans. Large‐scale transformations of crocodilian habitats across the Latin America and Caribbean region, alongside significant use of crocodilians as a resource, and retaliatory killing of crocodilians following (or to prevent) attacks on humans and their animals, are generating significant conservation challenges. This matters because this is the world's most biodiverse region for crocodilians. Because there is little information on specific situations across this vast and complex region, in 2018 we initiated a biannual questionnaire survey to establish a reporting network. In this article, we summarize the findings of surveys conducted in 2018 and 2020. We triangulate this feedback with croc attack data, and consultation with regional experts, to produce this very preliminary overview. We identify trends in negative human–crocodilian interactions at country level, the most reported causes of these, and identify the key species and regions of concern. We surveyed attitudes to management policies and responses to negative interactions including direct action and outreach activities. We acknowledge (and clarify) knowledge gaps, and motivate for improved regional cooperation with regard to policies and management (notably monitoring and evaluation) and data collection and sharing.