bluuebunny/crossref_metadata_2025 huggingface dataset:
Orbitofrontal-hypothalamic projections are disrupted in hypermetabolic murine ALS model and human patients
Authors: Bayer David , Antonucci Stefano , Müller Hans-Peter , Dupuis Luc , Boeckers Tobias , Ludolph Albert , Kassubek Jan , Roselli Francesco
Published: November 2020

Increased catabolism is a new clinical manifestation of Amyotrophic Lateral Sclerosis. A dysfunction of lateral hypothalamus may drive hypermetabolism in ALS; however, Its causes and anatomical substrates are unknown. We hypothesize that disruption cortico-hypothalamic circuits may impair energy homeostasis in ALS. We used rAAV2 for large-scale projection mapping and image analysis pipeline based on Wholebrain and Ilastik to quantify projections from the forebrain to the latera hypothalamus of the SOD1(G93A) ALS mouse model as well as of the FusΔNLSALS mouse model. Expanded projections from agranular Insula, ventrolateral orbitofrontal and secondary motor cortex to lateral hypothalamus were found in two independent cohorts of the hypermetabolic SOD1(G93A) ALS model. The non-hypermetabolic FusΔNLSALS mouse model display a loss of projections from motor cortex but no change in projections from insula and orbitofronal cortex. 3T DTI-MRI data on 83 ALS patients and 65 controls confirmed the disruption of the orbitofrontal-hypothalamic tract in ALS patients. Converging murine and human data demonstrate the selective disruption of hypothalamic inputs in ALS as a factor contributing to the origin of hypermetabolism.

Significance statement

We provide a circuit perspective of the recently identified and medically relevant hyper-metabolic phenotype of Amyotrophic Lateral Sclerosis. We demonstrate the selective involvement of orbitofrontal, insular and motor cortex projections to hypothalamus in murine ALS models and in human patients. The enhanced pipeline for large-scale registration, segmentation projections mapping, the identification of new circuits target of neurodegeneration, and the relevance of these circuits in metabolic disturbances make this work relevant not only for the investigation of ALS but also for other neurodegenerative disease as well as for all conditions characterized by systemic energy imbalances.
The non-adrenergic imidazoline-1 receptor protein Nischarin is a key regulator of astrocyte glutamate uptake
Authors: Gupta Swati , Bazargani Narges , Drew James , Modi Souvik , Marie Hélène , Attwell David , Kittler Josef T.
Published: November 2020

Astrocytic GLT-1 is the main glutamate transporter involved in glutamate buffering in the brain, pivotal for glutamate removal at excitatory synapses to terminate neurotransmission and for preventing excitotoxicity. We show here that the surface expression and function of GLT-1 can be rapidly modulated through the interaction of its N-terminus with the nonadrenergic imidazoline-1 receptor protein, Nischarin. The phox domain of Nischarin is critical for interaction and internalization of surface GLT-1. Using live super-resolution imaging, we found that glutamate accelerated Nischarin-GLT-1 internalization into endosomal structures. The surface GLT-1 level increased in Nischarin knockout astrocytes, and this correlated with a significant increase in transporter uptake current. Furthermore, Nischarin knockout in astrocytes is neuroprotective against glutamate excitotoxicity. These data provide new molecular insights into regulation of GLT-1 surface level and function and suggest novel drug targets for the treatment of neurological disorders.

Highlights

The phox domain of Nischarin interacts with the N-terminal tail of the main astrocyte glutamate transporter, GLT-1.

Nischarin promotes internalization of GLT-1 to endosomes.

Glutamate modulates GLT-1 surface levels via regulation of the Nischarin-GLT-1 interaction.

Genetic loss of Nischarin significantly increases GLT-1 surface expression, resulting in increased glutamate transport currents and enhanced neuroprotection.
Stool serology: development of a non-invasive immunological method for the detection of Enterovirus-specific antibodies in Congo gorilla faeces
Authors: Sereme Youssouf , Zarza Sandra Madariaga , Medkour Hacène , Amona Inestin , Fenollar Florence , Akiana Jean , Mezouar Soraya , Orain Nicolas , Vitte Joana , Davoust Bernard , Raoult Didier , Mediannikov Oleg
Published: November 2020

The incidence of poliovirus has significantly reduced by as much as 99.9% globally. Alongside this, however, vaccine-associated paralytic poliomyelitis has emerged. Recently, a new recombinant virus (Enterovirus C/Poliovirus) was identified in humans working as eco-guards and in gorillas in Democratic Republic of Congo, including one gorilla with polio-like sequelae. A strain of this recombinant virus (Ibou002) was also isolated from gorilla faeces. In order to assess the potential role of poliovirus infection, we have developed and optimised a protocol, based on the lyophilisation and solubilisation of small volumes of stool extracts, to detect specific antibodies. First, total immunoglobulins was detected in the concentrated stool extracts. Specific antibodies were then detected in 4/16 gorilla samples and 2/3 human samples by western blot using both the polio vaccine antigen and the Ibou002 antigen and by ELISA using the polio vaccine antigen. Humoral responses were greater with the Ibou002 antigen. We therefore suggest that this recombinant virus could lead to a polio-like disease in the endangered western lowland gorilla. The development of a non-invasive method to detect microorganism-specific immunoglobulins from faecal samples opens up new perspectives for the exploration of humoral responses of pathogens in animals and a greater understanding of zoonotic infectious diseases.
A phage satellite tunes inducing phage gene expression using a domesticated endonuclease to balance inhibition and virion hijacking
Authors: Netter Zoe , Boyd Caroline M. , Silvas Tania V. , Seed Kimberley D.
Published: November 2020

Bacteria persist under constant threat of predation by bacterial viruses (phages). Bacteria-phage conflicts result in evolutionary arms races often driven by mobile genetic elements (MGEs). One such MGE, a phage satellite in Vibrio cholerae called PLE, provides specific and robust defense against a pervasive lytic phage, ICP1. The interplay between PLE and ICP1 has revealed strategies for molecular parasitism allowing PLE to hijack ICP1 processes in order to mobilize. Here, we describe the mechanism of PLE-mediated transcriptional manipulation of ICP1 structural gene transcription. PLE encodes a novel DNA binding protein, CapR, that represses ICP1’s capsid morphogenesis operon. Although CapR is sufficient for the degree of capsid repression achieved by PLE, its activity does not hinder the ICP1 lifecycle. We explore the consequences of repression of this operon, demonstrating that more stringent repression achieved through CRISPRi restricts both ICP1 and PLE. We also discover that PLE transduces in modified ICP1-like particles. Examination of CapR homologs led to the identification of a suite of ICP1-encoded homing endonucleases, providing a putative origin for the satellite-encoded repressor. This work unveils a facet of the delicate balance of satellite-mediated inhibition aimed at blocking phage production while successfully mobilizing in a phage-derived particle.
Rare Genetic Variation Underlying Human Diseases and Traits: Results from 200,000 Individuals in the UK Biobank
Authors: Jurgens Sean J. , Choi Seung Hoan , Morrill Valerie N. , Chaffin Mark , Pirruccello James P. , Halford Jennifer L. , Weng Lu-Chen , Nauffal Victor , Roselli Carolina , Hall Amelia W. , Aragam Krishna G. , Lunetta Kathryn L. , Lubitz Steven A. , Ellinor Patrick T.
Published: November 2020

Background

Many human diseases are known to have a genetic contribution. While genome-wide studies have identified many disease-associated loci, it remains challenging to elucidate causal genes. In contrast, exome sequencing provides an opportunity to identify new disease genes and large-effect variants of clinical relevance. We therefore sought to determine the contribution of rare genetic variation in a curated set of human diseases and traits using a unique resource of 200,000 individuals with exome sequencing data from the UK Biobank.

Methods and Results

We included 199,832 participants with a mean age of 68 at follow-up. Exome-wide gene-based tests were performed for 64 diseases and 23 quantitative traits using a mixed-effects model, testing rare loss-of-function and damaging missense variants. We identified 51 known and 23 novel associations with 26 diseases and traits at a false-discovery-rate of 1%. There was a striking risk associated with many Mendelian disease genes including:MYPBC3with over a 100-fold increased odds of hypertrophic cardiomyopathy,PKD1with a greater than 25-fold increased odds of chronic kidney disease, andBRCA2, BRCA1, ATMandPALB2with 3 to 10-fold increased odds of breast cancer. Notable novel findings included an association betweenGIGYF1and type 2 diabetes (OR 5.6,P=5.35×10−8), elevated blood glucose, and lower insulin-like-growth-factor-1 levels. Rare variants inCCAR2were also associated with diabetes risk (OR 13,P=8.5×10−8), whileCOL9A3was associated with cataract (OR 3.4,P=6.7×10−8). Notable associations for blood lipids and hypercholesterolemia includedNR1H3, RRBP1, GIGYF1, SCGN, APH1A, PDE3BandANGPTL8. A number of novel genes were associated with height, includingDTL, PIEZO1, SCUBE3, PAPPAandADAMTS6, whileBSNwas associated with body-mass-index. We further assessed putatively pathogenic variants in known Mendelian cardiovascular disease genes and found that between 1.3 and 2.3% of the population carried likely pathogenic variants in known cardiomyopathy, arrhythmia or hypercholesterolemia genes.

Conclusions

Large-scale population sequencing identifies known and novel genes harboring high-impact variation for human traits and diseases. A number of novel findings, includingGIGYF1,represent interesting potential therapeutic targets. Exome sequencing at scale can identify a meaningful proportion of the population that carries a pathogenic variant underlying cardiovascular disease.
Effect of the transversal-spacing of stirrup-legs on the behavior and strength of shallow concealed RC beams
Authors: Alluqmani Ayed Eid
Published: November 2020

Purpose

Shallow concealed reinforced concrete (RC) beams (wide beams) make parts of a structure and are used in the construction industry, especially in ribbed and waffle slab systems. They are designed based on the requirements and provisions of structural codes of practice, which are applicable for shallow dropped RC beams (narrow beams). The main concern in regard to the behavior of these shallow concealed RC beams is transversal-spacing of stirrup-legs across their width. This paper aims to investigate the transversal-spacing of stirrups-legs (Sw) for two shallow concealed RC beams, namely, WB-SC and WB-EC.

Design/methodology/approach

The beams are tested under a three point-loading system. Their design has been performed to the SBC304 for beam WB-SC (Saudi Building Code for concrete structures) and comparison to EC2 for beam WB-EC (Eurocode-2 for concrete structures) is addressed in terms of flexural and shear strength design requirements. Experimental behavior and results of both beams are analyzed and conclusions are provided; also, a comparison of these codes is performed. Both beams had dimensions of 3,400 mm length, 700 mm width and 350 mm height.

Findings

Experimentally, beam WB-SC failed in flexure while beam WB-EC failed shear. The investigation concludes in favor of a safer design for SBC304 Code compared to EC2 Code for designing shallow concealed RC beams.

Originality/value

This study recommends that the transversal-spacing of stirrups-legs of these beams has an influence on their strength and behavior and should not exceed the lesser of 0.56(d) or 170 mm (6.7 in.).
Seismic data interpolation using deep learning with generative adversarial networks
Authors: Kaur Harpreet , Pham Nam , Fomel Sergey
Published: November 2020

We propose an algorithm for seismic trace interpolation using generative adversarial networks, a type of deep neural network. The method extracts feature vectors from the training data using self‐learning and does not require any pre‐processing to create the training labels. The algorithm also does not make any prior explicit assumptions about linearity of seismic events or sparsity of the data, which are often required in the traditional interpolation methods. We create the training labels by removing traces from different receiver indices of the original datasets to simulate the effect of missing traces. We adopt the framework of the generative adversarial networks to train the network and add additional loss functions to regularize the model. Numerical examples using land and marine field datasets demonstrate the validity and effectiveness of the proposed approach. With minimal computational burden and proper training, the proposed method can be applied to three‐dimensional seismic datasets to achieve accurate interpolation results.
Constrained optimization of landscape indices in conservation planning to support ecological restoration in New Caledonia
Authors: Justeau‐Allaire Dimitri , Vieilledent Ghislain , Rinck Nicolas , Vismara Philippe , Lorca Xavier , Birnbaum Philippe
Published: November 2020

Curbing habitat loss, reducing fragmentation and restoring connectivity are frequent concerns of conservation planning. In this respect, the incorporation of spatial constraints, fragmentation and connectivity indices into optimization procedures is an important challenge for improving decision support.

Here we present a novel optimization approach developed to accurately represent a broad range of conservation planning questions with spatial constraints and landscape indices. Relying on constraint programming, a technique from artificial intelligence based on automatic reasoning, this approach provides both constraint satisfaction and optimality guarantees.

We applied this approach in a real case study to support managers of the ‘Côte Oubliée – ‘Woen Vùù – Pwa Pereeù’ provincial park project, in the biodiversity hotspot of New Caledonia. Under budget, accessibility and equitable allocation constraints, we identified restorable areas optimal for reducing forest fragmentation and improving inter‐patch structural connectivity, respectively measured with the effective mesh size and the integral index of connectivity.

Synthesis and applications. Our work contributes to more effective and policy‐relevant conservation planning by providing a spatially explicit and problem‐focused optimization approach. By allowing an exact representation of spatial constraints and landscape indices, it can address new questions and ensure whether the solutions will be socio‐economically feasible, through optimality and satisfiability guarantees. Our approach is generic and flexible, thus applicable to a wide range of conservation planning problems, such as ecological restoration planning, reserve or corridor design.
Review article: Implicit bias towards Aboriginal and Torres Strait Islander patients within Australian emergency departments
Authors: Quigley Alyssa , Hutton Jennie , Phillips Georgina , Dreise Darlene , Mason Toni , Garvey Gail , Paradies Yin
Published: November 2020

Aboriginal and Torres Strait Islander peoples continue to suffer adverse experiences in healthcare, with inequitable care prevalent in emergency settings. Individual, institutional and systemic factors play a significant part in these persisting healthcare disparities, with biases remaining entrenched in healthcare institutions. This includes implicit racial bias which can result in stereotyping of racial minorities and premature diagnostic closure. Furthermore, it may contribute to distrust of medical professionals resulting in higher rates of leave events and hinder racial minorities from seeking care or following treatment recommendations. The aim of this review is to analyse the effect of implicit bias on patient outcomes in the ED in international literature and explore how these studies correlate to an Australian context.
Development of a nanoparticle delivery system based on zein/polysaccharide complexes
Authors: Li Ming , Yu Meihui
Published: November 2020

Zein, an alcohol‐soluble protein in corn, can self‐assemble into spherical nanoparticles, which makes it an ideal carrier material for the encapsulation of hydrophobic bioactive molecules. However, zein nanoparticles easily aggregate in water and are sensitive to enzymatic degradation in the digestive system. A strategy to overcome their limitations is the incorporation of polysaccharides as a second polymer layer that provides stability to zein nanoparticles. This review introduces the characteristics of zein as they relate to understanding the formation of zein/polysaccharide nanoparticles. Particular attention is paid to the preparation methods for the zein/polysaccharide nanoparticles, as well as to the morphological observation methods and detection mechanism. Moreover, the properties and applications of zein/polysaccharide nanoparticles are highlighted.
Recent advances in the use of edible coatings for preservation of avocados: A review
Authors: Garcia Franciela , Davidov‐Pardo Gabriel
Published: November 2020

Avocados (Persea americana) are a fruit, whose shelf‐life is jeopardized by rapid ripening and fungal diseases, which heighten the necessity for postharvest treatments. The use of refrigeration during storage and transport helps delay the ripening process and phytopathogen growth but it is not enough to attenuate the problem, especially once avocados are placed in ambient temperatures. Fungicides are effective in controlling fungal prevalence, but their possible adverse environmental and human health effects have spurred interest in finding safer, natural substitutes. The objective of this paper is to review recent advances and trends in the use of edible coatings as a safe alternative to preserve and extend avocados shelf‐life.

Edible biopolymer coatings have gained considerable attention due to their ability to extend fruit and vegetable shelf‐life. These coatings are a novel type of biodegradable primary packaging made from biological compounds like polysaccharides, proteins, lipids, and other polymers. Coatings are considered nonactive if they only form a physical barrier, separating avocados from their immediate environment, controlling gas and moisture transfer. Active coatings can contain supplementary ingredients with additional properties like antioxidant and antifungal activity. The application of edible coatings shows promising potential in extending avocado shelf‐life, replacing synthetic fungicides and reducing economic losses from avocado spoilage.
Sensitivity of oat protein solubility to changing ionic strength and pH
Authors: Li Runnan , Xiong Youling L.
Published: November 2020

Understanding the relationship between ionic strength and protein solubility is essential to the utilization of salt in the formulation design of plant protein‐based food and beverage products. In this study, suspensions of oat protein isolate (OPI) were treated with two kinds of common salts (sodium chloride NaCl; sodium phosphate NaP) at different ionic strengths (I). Electrical conductivity, protein solubility, particle size, and protein profile (sodium dodecyl sulfate–polyacrylamide gel electrophoresis) were analyzed. The results showed the highest protein solubility at extremely low I (< 0.005 for NaCl; < 0.012 for NaP) and a minimum solubility at I 0.03 to 0.2 depending on the type of salt. Particle size and electrophoretic patterns supported the solubility profile. The combination effect of ionic strength and pH was also investigated. A characteristic U‐shaped solubility curve observed within pH 2.0 to 8.0 at low ionic strengths (I < 0.01) was altered by increasing the salt concentration. The findings demonstrate that ionic strength and ion species play a crucial role in oat protein solubility, and the ionic effect can be modified by changing the pH. Therefore, the application of appropriate salt concentrations is vitally important to the manufacture of oat protein‐based food products.

Practical Application

Sodium chloride and phosphate are two of the most widely utilized salts in food processing. This study highlights the relationship between ionic strength of the two salts and oat protein solubility at different pH levels, providing useful information for selecting proper salt concentrations in the manufacture of oat protein‐based food products.
Kappa‐carrageenan and its oligosaccharides maintain the physicochemical properties of myofibrillar proteins in shrimp mud (Xia‐Hua) during frozen storage
Authors: Shui Shan‐shan , Qi He , Shaimaa Hatab , Aubourg Santiago P. , Zhang Bin
Published: November 2020

As a popular hot‐pot ingredient, Chinese‐style shrimp mud (Xia‐Hua) is usually transported and stored frozen. However, frozen storage leads to decreased quality of Xia‐Hua products caused by the variations in physicochemical and functional properties of myofibrillar proteins (MPs). Κ‐carrageenan and its oligosaccharides are reported as antioxidants and antifreeze and can stabilize proteins in whole shrimp, but their effects on MPs in Xia‐Hua remain poorly understood. Compared to the control and Na4P2O7 treatments, the physicochemical properties of MPs in κ‐carrageenan and its oligosaccharides‐incorporated Xia‐Hua were evaluated during 120 days of frozen storage. The results showed that cold stress increased the susceptibility of MPs to denaturation and oxidation during frozen storage. Carrageenan oligosaccharides maintained the turbidity, emulsifying activity, stability, and foaming capacity of MPs. Oxidation analysis showed that the incorporation of carrageenan oligosaccharides significantly retarded the rapid decrease of Ca2+‐ATPase activity, total sulphydryl and active sulphydryl contents, and also effectively inhibited the increases of carbonyl content and surface hydrophobicity of MPs. Thermal stability results confirmed that the oligosaccharides improved the denaturation temperature and enthalpy of MPs compared to the control, Na4P2O7, and carrageenan treatments. This study suggests that κ‐carrageenan and its oligosaccharides maintain the properties of MPs in Xia‐Hua during frozen storage.

Practical Application

The cryoprotection and antioxidant effects of carrageenan oligosaccharides on the stability of MPs in frozen shrimp mud can be used to extend the shelf‐life and maintain the quality of frozen Xia‐Hua products. Furthermore, it can drive the development of aquatic product health industry, improve the quality and safety of aquatic products, reduce the occurrence of public food safety incidents, and maintain social stability.
The impact of ferritin on the disassociation of HbA1c and mean plasma glucose
Authors: Li Yufeng , Zhang Fang , Zhang Xiuying , Fu Zuodi , Wang Lianying , Zhao Cuiling , Guo Guangxia , Zhou Xianghai , Ji Linong
Published: November 2020

Objective

To explore the impact of ferritin level on the disassociation of glycated hemoglobin A1c (HbA1c) and mean plasma glucose (MPG).

Reseach Design and Methods

We used a 2012‐2013 cross‐sectional survey conducted in Pinggu district, Beijing including 3095 Chinese participants aged 25‐75 years. We categorized their glycemic status by interviewing for diagnosed diabetes and by measuring HbA1c, fasting plasma glucose (FPG), and 2‐hours post‐load plasma glucose (2‐hours PPG). We fitted a multivariable regression model to explore the impact of ferritin on the association of HbA1c or glycated albumin (GA) and mean plasma glucose.

Results

A total of 5.65% of participants were diagnosed as diabetes using HbA1c criteria, and 9.79% using oral glucose tolerance test criteria. Compared with males, females had significantly lower hemoglobin levels (159.82 ± 11.56 vs 135.93 ± 12.62) and lower ferritin levels (113.00 [68.55, 185.50] vs 33.40 [12.40, 70.13]). Linear regression analysis performed in different groups classified by different diagnose criterion indicated that the correlation between MPG and HbA1c differs in different tertiles of ferritin (lowest vs middle vs highest: R2 = 0.507 vs 0.645 vs 0.687 in female; R2 = 0.415 vs 0.715 vs 0.615 in male), and the association between MPG and HbA1c diminished in the lowest tertile of ferritin.

Conclusions

Ferritin level might affect the association between glucose and HbA1c, which should be taken into account when using HbA1c as a diagnosis criterion for diabetes and prediabetes.
Clinically meaningful changes on depressive symptom measures and patient‐reported outcomes in patients with treatment‐resistant depression
Authors: Turkoz Ibrahim , Alphs Larry , Singh Jaskaran , Jamieson Carol , Daly Ella , Shawi May , Sheehan John J. , Trivedi Madhukar H. , Rush A. John
Published: November 2020

Objective

To use the Clinical Global Impression‐Severity (CGI‐S) scale to estimate clinically meaningful and clinically substantial changes as measured using the Montgomery‐Åsberg Depression Rating Scale (MADRS), the Sheehan Disability Scale (SDS), and the Patient Health Questionnaire‐9 (PHQ‐9) in patients with treatment‐resistant depression (TRD).

Methods

Pooled data were derived from two 4‐week, randomized, active‐controlled studies evaluating esketamine nasal spray (ESK) plus oral antidepressant (OAD) or OAD plus placebo nasal spray (PBO) in adults with TRD (N = 565). CGI‐S, MADRS, SDS, and PHQ‐9 scores were obtained at baseline and over 4 weeks of treatment. In this post hoc analysis, change scores on the MADRS, SDS, and PHQ‐9 that corresponded to a clinically meaningful (1‐point) or clinically substantial (2‐point) change on the CGI‐S scale were identified.

Results

Clinically meaningful changes in CGI‐S scores after 28 days corresponded to 6‐, 4‐, and 3‐point changes from baseline on the MADRS, SDS, and PHQ‐9, respectively. Similarly, a 2‐point CGI‐S score change (clinically substantial change) corresponded to a 12‐, 8‐, and 6‐point change on the MADRS, SDS, and PHQ‐9, respectively. The proportion of patients showing substantial clinical improvement in the ESK plus OAD group versus the OAD plus PBO group after 28 days of treatment favored ESK plus OAD: 69.0% vs 55.3% (MADRS), 64.5% vs 48.9% (SDS), and 77.1% vs 64.7% (PHQ‐9).

Conclusion

We provide a basis for identifying clinically meaningful and clinically substantial changes as assessed with commonly used outcome measures for depression to facilitate the translation of clinical trial results into clinical practice.
Ecological niche modeling reveals manta ray distribution and conservation priority areas in the Western Central Atlantic
Authors: Garzon F. , Graham R. T. , Witt M. J. , Hawkes L. A.
Published: November 2020

The Western Central Atlantic (WCA) hosts a population of manta rays whose distribution and habitat preference is poorly understood. Addressing this lack of knowledge will be essential to aid the effective implementation of targeted conservation measures. Here, we use ensemble ecological niche modeling to predict the monthly distribution of manta rays in the WCA using multiple sources of species occurrence data, and consequently identify core areas, which represent suitable habitat in all months of the year. Models suggest a seasonal cycle of expansion and contraction of suitable habitat from coastal areas in spring‐summer, to open ocean in autumn‐winter. Core areas are concentrated along the coast of the USA, Mexico, and Venezuela. Only 24% of predicted suitable habitat is encompassed by the present regional network of MPAs, and is intersected by numerous, heavily trafficked shipping lanes. Manta rays are slow‐growing animals that only produce a limited number of offspring; as such, this species is sensitive to even moderate increases in mortality rates. For this reason, the existing regional network of MPAs may offer them limited protection. As manta rays in the WCA are challenged by a complex landscape of threats and protective measures, future marine conservation planning in the region should explicitly address the conservation of manta rays, focusing on areas identified as key habitats for the species.
Calcium hydroxide paste removal strategies and bond strengths of epoxy‐ and silicate‐based sealers
Authors: Tavella e Silva Nathalia Cristina , Gibin Janaina Tosta , Rivera Izabela Cristina Maurício Moris , Rached Junior Fuad Jacob Abi , Leoni Graziela Bianchi , Raucci‐Neto Walter
Published: November 2020

This study evaluated the syringe/needle (SN), passive ultrasonic irrigation (PUI) and XP‐endo Finisher (XP) in the removal of Ca(OH)2‐based paste and the bond strength (BS) values of an epoxy resin (AH Plus) and silicate (MTA)‐based sealers to root dentin. Eighty lower premolars were assigned: control group (CT), SN, PUI and XP, and subdivided according to the sealer (n = 10) for BS. SN has the lowest removal followed by PUI and XP. AH Plus had higher BS for CT compared with SN in all root thirds. CT and XP presented similar BS in the apical and middle thirds and higher than SN and PUI. For MTA, similar BS was observed in the cervical and apical thirds, and in the middle third, CT, PUI and XP presented similar values and higher than SN. PUI and XP methods presented higher efficiency in the Ca(OH)2 removal, and the residual Ca(OH)2 provides a reduction in BS of the AH Plus.
Notes on the gross anatomy of the heart of the broad‐snouted caiman, Caiman latirostris (Daudin, 1802)
Authors: de Oliveira Lima Mariana , Nóbrega Yhuri Cardoso , de Deus Santos Marcelo Renan , de Carvalho Nunes Louisiane , Figueiredo Rodrigo Giesta , da Silva Maria Aparecida
Published: November 2020

The broad‐snouted caiman, Caiman latirostris (Daudin, 1802), is one of the six crocodilian species from Brazil. The topography, morphology and morphometry of the broad‐snouted caiman heart were studied. Data were obtained from the necropsy of four adult animals, three females and one male. The hearts were removed from the coelomic cavity and fixed in 10% formalin for 48 hr for morphological and morphometric description. The heart is in the cranial mediastinum. It is caudally involved by the liver cranial margins, and ventrally by the ribs, intercostal muscles, and sternum and dorsally by the lungs. The four‐chambered morphology is typical with two (right and left) atria and ventricles. Right and left aortic, pulmonary and subclavian arteries branch from the truncus arteriosus. Gubernaculum cordis is present as ligamentous folds uniting the heart apex to the pericardium. Main morphometric means are the apex‐to‐base length (49.86 mm), circumference (105.25 mm) and heart weight (45.03 g). The right atrium is craniocaudally longer with thicker walls, whereas the left ventricle is narrower. The topography, morphology and morphometry of the heart of C. latirostris are consistent with the anatomy of other crocodilian species.
Cold urticaria – What we know and what we do not know
Authors: Maltseva Natalya , Borzova Elena , Fomina Daria , Bizjak Mojca , Terhorst‐Molawi Dorothea , Košnik Mitja , Kulthanan Kanokvalai , Meshkova Raisa , Thomsen Simon Francis , Maurer Marcus ,   the COLD‐CE Steering Committee
Published: November 2020

Cold urticaria (ColdU) is a common form of chronic inducible urticaria characterized by the development of wheals, angioedema or both in response to cold exposure. Recent research and guideline updates have advanced our understanding and management of ColdU. Today, its pathophysiology is thought to involve the cold‐induced formation of autoallergens and IgE to these autoallergens, which provoke a release of proinflammatory mediators from skin mast cells. The classification of ColdU includes typical and atypical subtypes. We know that cold‐induced wheals usually develop on rewarming and resolve within an hour and that anaphylaxis can occur. The diagnosis relies on the patient's history and cold stimulation testing. Additional diagnostic work‐up, including a search for underlying infections, should only be done if indicated by the patient's history. The management of ColdU includes cold avoidance, the regular use of nonsedating antihistamines and the off‐label use of omalizumab. However, many questions regarding ColdU remain unanswered. Here, we review what is known about ColdU, and we present important unanswered questions on the epidemiology, underlying pathomechanisms, clinical heterogeneity and treatment outcomes. Our aim is to guide future efforts that will close these knowledge gaps and advance the management of ColdU.
Full compliance with Respiratory syncytial virus prophylaxis was associated with fewer respiratory‐related hospital admissions in preterm children: A cohort study
Authors: Torchin Heloise , Charkaluk Marie‐Laure , Rousseau Jessica , Marchand‐Martin Laetitia , Treluyer Ludovic , Nuytten Alexandra , Truffert Patrick , Jarreau Pierre‐Henri , Ancel Pierre‐Yves
Published: November 2020

Aim

Although well documented in randomised trials, the efficacy of prophylaxis against respiratory syncytial virus (RSV) in real‐word conditions is less studied. The objective was to assess the impact of partial versus full RSV prophylaxis for acute respiratory infections (ARIs) and ARI‐related hospital admissions in preterm children.

Methods

This study included children born preterm in 2011 in France who were eligible for RSV prophylaxis and received at least one palivizumab dose from October 2011 to March 2012. Full prophylaxis was defined as receiving at least one palivizumab dose for each month of RSV exposure in the community. Children with full and partial prophylaxis were matched, and odds of ARIs and ARI‐related hospital admission were compared by logistic regression.

Results

Full prophylaxis concerned 861/1083 (80%) children. As compared with full prophylaxis, partial prophylaxis was not associated with ARI occurrence (odds ratio OR 1.3, 95% confidence interval CI 0.9‐1.9) but was significantly associated with ARI‐related hospital admission during the RSV epidemic (OR 1.9, 95% CI 1.2‐2.9).

Conclusion

During the 2011‐2012 RSV epidemic, hospital admission rates were higher for preterm children with partial than full RSV prophylaxis. Improving compliance could help alleviate the burden of RSV on healthcare systems.
The regulation of gastric ghrelin secretion
Authors: Nunez‐Salces Maria , Li Hui , Feinle‐Bisset Christine , Young Richard L. , Page Amanda J.
Published: November 2020

Abstract

Ghrelin is a gastric hormone with multiple physiological functions, including the stimulation of food intake and adiposity. It is well established that circulating ghrelin levels are closely associated with feeding patterns, rising strongly before a meal and lowering upon food intake. However, the mechanisms underlying the modulation of ghrelin secretion are not fully understood. The purpose of this review is to discuss current knowledge on the circadian oscillation of circulating ghrelin levels, the neural mechanisms stimulating fasting ghrelin levels and peripheral mechanisms modulating postprandial ghrelin levels. Furthermore, the therapeutic potential of targeting the ghrelin pathway is discussed in the context of the treatment of various metabolic disorders, including obesity, type 2 diabetes, diabetic gastroparesis and Prader‐Willi syndrome. Moreover, eating disorders including anorexia nervosa, bulimia nervosa and binge‐eating disorder are also discussed.
Rain, Rain Go Away! A Diary Study on Morning Weather and Affective Well‐Being at Work
Authors: Venz Laura , Pundt Alexander
Published: November 2020

Weather determines a number of affective experiences in everyday life. Although affective events theory positions environmental features such as the weather as important in determining affective well‐being also at work, research in this regard has mainly focused on predictors within the person or work context. Addressing this gap, we studied how daily morning weather relates to day‐specific affective well‐being at work. Specifically, we examined vigor and job satisfaction as positive well‐being states, and negative affect and burnout as negative well‐being states. Additionally, we examined individual weather sensitivity and positive/negative affectivity as person‐level moderators of the daily weather–well‐being relationship. Using data gathered in a diary study with 115 employees reporting on 457 workdays, we found morning weather to be related to state vigor and job satisfaction, but not to negative affect and burnout. Positive affectivity moderated the relationships between morning weather and job satisfaction as well as burnout. Weather sensitivity moderated the relationship between morning weather and vigor, while negative affectivity did not moderate any relationship between morning weather and well‐being at work. Our results contribute to the understanding of affective well‐being at work by pointing at the role environmental factors such as weather conditions can play.
Managing Pandemics—Demands, Resources, and Effective Behaviors Within Crisis Management Teams
Authors: Thielsch Meinald T. , Röseler Stefan , Kirsch Julia , Lamers Christoph , Hertel Guido
Published: November 2020

Pandemics, such as the COVID‐19 crisis, are very complex emergencies that can neither be handled by individuals nor by any single municipality, organization or even country alone. Such situations require multidisciplinary crisis management teams (CMTs) at different administrative levels. However, most existing CMTs are trained for rather local and temporary emergencies but not for international and long‐lasting crises. Moreover, CMT members in a pandemic face additional demands due to unknown characteristics of the disease and a highly volatile environment. To support and ensure the effectiveness of CMTs, we need to understand how CMT members can successfully cope with these multiple demands. Connecting teamwork research with the job demands and resources approach as starting framework, we conducted structured interviews and critical incident analyses with 144 members of various CMTs during the COVID‐19 pandemic. Content analyses revealed both perceived demands as well as perceived resources in CMTs. Moreover, structuring work processes, open, precise and regular communication, and anticipatory, goal‐oriented and fast problem solving were described as particularly effective behaviors in CMTs. We illustrate our findings in an integrated model and derive practical recommendations for the work and future training of CMTs.
Courtwatching: Visibility, publicness, witnessing, and embodiment in legal activism
Authors: Gill Nick , Hynes Jo
Published: November 2020

The paper sets out what courtwatching is and gives some examples from various countries. It argues that a closer engagement with courtwatching in legal geography will yield insights into the issues of visibility, publicness, witnessing, and embodiment that surround court observations.
The expression levels of long non‐coding RNA KIAA0125 are associated with distinct clinical and biological features in myelodysplastic syndromes
Authors: Hung Sheng‐Yu , Lin Chien‐Chin , Hsu Chia‐Lang , Yao Chi‐Yuan , Wang Yu‐Hung , Tsai Cheng‐Hong , Hou Hsin‐An , Chou Wen‐Chien , Tien Hwei‐Fang
Published: November 2020

Long non‐coding RNAs (lncRNAs) have important functions in cancer biology. Among them, lncRNA KIAA0125 is one of the genes proposed to play a critical role in leukaemia stem cell (LSC). In this study, we aimed to investigate the clinical relevance of the expression levels of lncRNA KIAA0125 in myelodysplastic syndromes (MDS), a disease with highly heterogeneous clinical and biological features. Using RNA arrays, we measured the expression of KIAA0125 in 176 primary MDS patients. We found that higher KIAA0125 expression was associated with higher risk MDS, based on the revised International Prognostic Scoring System (IPSS‐R), mutations in ASXL1 and NRAS, and predicted poorer overall survival (OS) and leukaemia‐free survival (LFS). Multivariate analysis revealed that higher KIAA0125 expression was an independent, unfavourable prognostic factor for OS and LFS, irrespective of IPSS‐R and mutation status. Further global gene expression profile analysis suggested a close association of higher KIAA0125 expressions with LSC signatures. The expression of KIAA0125 may be a potential biomarker to guide the treatment choice in MDS patients, especially those with lower risk subtypes, in whom palliative treatment is usually used.
Comparative analysis of gene expression platforms for cell‐of‐origin classification of diffuse large B‐cell lymphoma shows high concordance
Authors: Ahmed Sophia , Glover Paul , Taylor Jan , Sha Chulin , Care Matthew A. , Tooze Reuben , Davies Andrew , Westhead David R. , Johnson Peter W. M. , Burton Catherine , Barrans Sharon L.
Published: November 2020

Cell‐of‐origin subclassification of diffuse large B cell lymphoma (DLBCL) into activated B cell‐like (ABC), germinal centre B cell‐like (GCB) and unclassified (UNC) or type III by gene expression profiling is recommended in the latest update of the World Health Organization’s classification of lymphoid neoplasms. There is, however, no accepted gold standard method or dataset for this classification. Here, we compare classification results using gene expression data for 68 formalin‐fixed paraffin‐embedded DLBCL samples measured on four different gene expression platforms (Illumina wG‐DASLTM arrays, Affymetrix PrimeView arrays, Illumina TrueSeq RNA sequencing and the HTG EdgeSeq DLBCL Cell of Origin Assay EU using an established platform agnostic classification algorithm (DAC) and the classifier native to the HTG platform, which is CE marked for in vitro diagnostic use (CE‐IVD). Classification methods and platforms show a high level of concordance, with agreement in at least 80% of cases and rising to much higher levels for classifications of high confidence. Our results demonstrate that cell‐of‐origin classification by gene expression profiling on different platforms is robust, and that the use of the confidence value alongside the classification result is important in clinical applications.
Controversies in the use of new bone‐modifying therapies in multiple myeloma
Authors: Terpos Evangelos , Ntanasis‐Stathopoulos Ioannis
Published: November 2020

Bone‐modifying therapies are essential in the treatment of patients with multiple myeloma. Zoledronic acid is preferred over other bisphosphonates due to its superiority in reducing the incidence of skeletal‐related events and improving survival. The anti‐receptor activator of nuclear factor‐κΒ ligand (RANKL)‐targeted agent denosumab has shown its non‐inferiority compared to bisphosphonates in preventing skeletal‐related events among newly diagnosed patients with myeloma bone disease. Denosumab may confer a survival benefit in patients eligible for autologous transplantation. Denosumab may present a safer profile for patients with renal impairment. Discontinuation of bone‐directed therapies can be considered for patients with deep responses and after an adequate time period on treatment; however, a rebound effect may become evident especially in the case of denosumab. Three‐monthly infusions of zoledronic acid or at‐home denosumab administration should be considered during the coronavirus disease 2019 (COVID‐19) pandemic. Measures to prevent hypocalcaemia, renal toxicity and osteonecrosis of the jaw are important for all bone‐modifying agents.
Beyond the gardens: The extended mutualism from ant‐garden ants to nectary‐bearing plants growing in Amazon tree‐fall gaps
Authors: da Silva‐Viana Camila Benedita , Vicente Ricardo E. , Kaminski Lucas A. , Izzo Thiago J.
Published: November 2020

The regime of frequent small disturbances, such as the formation of tree‐fall gaps, is an important mechanism maintaining the diversity in tropical forests. Occurring primarily in forest gaps, or in riparian vegetation, ant gardens (hereafter AGs) are mutualistic associations involving several epiphytic plant species and ants. In the Amazon rainforest, a widespread AGs association is assembled by two aggressive species of parabiotic ants (Camponotus femoratus and Crematogaster levior). Working together, these ants aggressively monopolize food resources and attack any intruder on the AGs. Here, we demonstrated the extended protective effect of parabiotic ants on the leaf herbivory of neighboring plants, contrasting plants with and without extrafloral nectaries (hereafter EFNs). We performed the fieldwork in South Amazonia where we found 33 forest gaps, 16 with and 17 without AGs. Independently of the presence of AGs, plants possessing EFNs have less area removed by herbivores and fewer leaves with herbivore marks than those without EFNs. This decrease in herbivory was remarkable on EFN‐plants growing in gaps that also harbor AGs. Additional manipulative experiments confirmed this pattern: The AG‐ants were more efficient than no‐AG ants in removing live termite baits placed on EFN‐plants, but few attacks were observed on plants without EFNs. Thus, AG‐ants can extend their role in defending ant gardens from other plants growing in the same area, particularly those with EFNs. This extension of the mutualism benefits can affect the dynamics of the ecological succession and coevolutionary process in the Amazon forest.

Abstract in Portuguese is available with online material
The effects of recombinant human insulin‐like growth factor‐1/insulin‐like growth factor binding protein‐3 administration on lipid and carbohydrate metabolism in recreational athletes
Authors: Guha Nishan , Nevitt Simon P. , Francis Michael , Böhning Walailuck , Böhning Dankmar , Sönksen Peter H. , Holt Richard I. G.
Published: November 2020

Objective

Previous studies suggested that recombinant human IGF‐1 (rhIGF‐1) administration affects carbohydrate and lipid metabolism in healthy people and in people with diabetes. This study aimed to determine the effects of rhIGF‐1/rhIGF binding protein‐3 (rhIGFBP‐3) administration on glucose homeostasis and lipid metabolism in healthy recreational athletes.

Design and Setting

Randomized, double‐blind, placebo‐controlled rhIGF‐1/rhIGFBP‐3 administration study at Southampton General Hospital, UK.

Participants

56 recreational athletes (30 men, 26 women).

Methods

Participants were randomly assigned to receive placebo, low‐dose rhIGF‐1/rhIGFBP‐3 (30 mg/day) or high‐dose rhIGF‐1/rhIGFBP‐3 (60 mg/day) for 28 days. The following variables were measured before and immediately after the treatment period: fasting lipids, glucose, insulin, C‐peptide and glycated haemoglobin. The homeostatic model assessment (HOMA‐IR) was used to estimate insulin sensitivity and indirect calorimetry to assess substrate oxidation rates. The general linear model approach was used to compare treatment group changes with the placebo group.

Results

Compared with the placebo group, there was a significant reduction in fasting triglycerides in participants treated with high‐dose rhIGF‐1/rhIGFBP‐3 (p = .030), but not in the low‐dose group (p = .390). In women, but not in men, there were significant increases in total cholesterol (p = .003), HDL cholesterol (p = .001) and LDL cholesterol (p = .008). These lipid changes were associated with reduced fasting insulin (p = .010), C‐peptide (p = .001) and HOMA‐IR (p = .018) in women and reduced C‐peptide (p = .046) in men.

Conclusions

rhIGF‐1/rhIGFBP‐3 administration for 28 days reduced insulin concentration, improved insulin sensitivity and had significant effects on lipid profile including decreased fasting triglycerides.