bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of gelatin and thymol‐loaded nanostructured lipid carrier on physicochemical, rheological, and sensory properties of sesame paste/date syrup blends as a snack bar
Authors: Baqeri Forod , Nejatian Mohammad , Abbaszadeh Sepideh , Taghdir Maryam
Published: February 2020

The development of a novel snack bar based on sesame paste (SP) and date syrup (DS) was investigated. The aim of this study was to evaluation the effects of SP/DS ratio and encapsulated thymol (thymol‐loaded nanostructured lipid carrier [TNLC]) on physicochemical, textural, rheological, and sensorial properties of snack bars. The effect of butylated hydroxytoluene (BHT), thymol, and TNLC showed that the addition of 100 ppm TNLC could improve the oxidative stability of SP/DS mixtures even better than BHT, while a higher concentration of TNLC had a negative effect. The unpleasant taste and odor of thymol could be overcome by its encapsulation in nanostructured lipid carriers. The textural properties of the formulations with different SP/DS ratios (1:2, 1:1, 2:1) and an overall concentration of 7 g of gelatin/kg of mixtures were evaluated. The texture profile analysis showed that the sample with an SP/DS ratio of 1:1 had higher hardness, adhesiveness, springiness, cohesiveness, and gumminess in comparison with the other ratios. From the sensory evaluation data, the bar prepared with an SP/DS ratio of 1:1 had the most acceptable texture. According to the results, the SP/DS ratio of 1:1 with gelatin and 100 ppm TNLC can be used in developing SP/DS blends as a highly acceptable functional food.
A novel septal protein of multicellular heterocystous cyanobacteria is associated with the divisome
Authors: Springstein Benjamin L. , Arévalo Sergio , Helbig Andreas O. , Herrero Antonia , Stucken Karina , Flores Enrique , Dagan Tal
Published: February 2020

Cyanobacteria are unique among the eubacteria as they possess a hybrid Gram phenotype, having an outer membrane but also a comparably thick peptidoglycan sheet. Furthermore, the cyanobacterial divisome includes proteins specific for both the Gram types as well as cyanobacteria‐specific proteins. Cells in multicellular cyanobacteria share a continuous periplasm and their cytoplasms are connected by septal junctions that enable communication between cells in the filament. The localization of septal junction proteins depends on interaction with the divisome, however additional yet unknown proteins may be involved in this process. Here, we characterized Alr3364 (termed SepI), a novel septal protein that interacts with the divisome in the multicellular heterocystous cyanobacterium Anabaena sp. strain PCC 7120. SepI localized to the Z‐ring and the intercellular septa but did not interact with FtsZ. Instead, SepI interacted with the divisome proteins ZipN, SepF and FtsI and with the septal protein SepJ. The inactivation of sepI led to a defect in cell filament integrity, colony and cell morphology, septum size, nanopore formation and peptidoglycan biogenesis, and inability to differentiate heterocysts. Our results show that SepI plays a role in intercellular communication and furthermore indicate that SepI functions in the coordination of septal junction localization during cell division.
Addiction and the self
Authors: Pickard Hanna
Published: February 2020

Addiction is standardly characterized as a neurobiological disease of compulsion. Against this characterization, I argue that many cases of addiction cannot be explained without recognizing the value of drugs to those who are addicted; and I explore in detail an insufficiently recognized source of value, namely, a sense of self and social identity as an addict. For people who lack a genuine alternative sense of self and social identity, recovery represents an existential threat. Given that an addict identification carries expectations of continued consumption despite negative consequences, there is therefore a parsimonious explanation of why people who identify as addicts continue to use drugs despite these consequences: they self‐identify as addicts and that is what addicts are supposed to do. I conclude by considering how it is nonetheless possible to overcome addiction despite this identity, in part by imagining and enacting a new one. Importantly, this possibility requires the availability of social support and material resources that are all too frequently absent in the lives of those who struggle with addiction.
The bZIP transcription factor VdAtf1 regulates virulence by mediating nitrogen metabolism in Verticillium dahliae
Authors: Tang Chen , Li Tianyu , Klosterman Steven J. , Tian Chengming , Wang Yonglin
Published: February 2020

The fungus Verticillium dahliae causes vascular wilt disease on hundreds of plant species. Homologs of the bZIP transcription factor Atf1 are required for virulence in most pathogenic fungi, but the molecular basis for their involvement is largely unknown.

We performed targeted gene deletion, expression analysis, biochemistry and pathogenicity assays to demonstrate that VdAtf1 governs pathogenesis via the regulation of nitrosative resistance and nitrogen metabolism in V. dahliae.

VdAtf1 controls pathogenesis via the regulation of nitric oxide (NO) resistance and inorganic nitrogen metabolism rather than oxidative resistance and is important for penetration peg formation in V. dahliae. VdAtf1 affects ammonium and nitrate assimilation in response to various nitrogen sources. VdAtf1 may be involved in regulating the expression of VdNut1. VdAtf1 responds to NO stress by strengthening the fungal cell wall, and by causing over‐accumulation of methylglyoxal and glycerol, which in turn impacts NO detoxification. We also verified that the VdAtf1 ortholog in Fusarium graminearum mediates nitrogen metabolism, suggesting conservation of this function in related plant pathogenic fungi.

Our findings revealed new functions of VdAtf1 in pathogenesis, response to nitrosative stress and nitrogen metabolism in V. dahliae. The results provide novel insights into the regulatory mechanisms of the transcription factor VdAtf1 in virulence.
Dual Character Art Concepts
Authors: Liao Shen‐yi , Meskin Aaron , Knobe Joshua
Published: February 2020

Our goal in this paper is to articulate a novel account of the ordinary concept art. At the core of our account is the idea that a puzzle surrounding our thought and talk about art is best understood as just one instance of a far broader phenomenon. In particular, we claim that one can make progress on this puzzle by drawing on research from cognitive science on dual character concepts. Thus, we suggest that the very same sort of phenomenon that is associated with art can also be found in a broad class of other dual character concepts, including scientist, Christian, and many others. Instead of focusing narrowly on the case of art, we try to offer a more general account of these concepts and the puzzles to which they give rise. Then, drawing on the general theory, we introduce a series of hypotheses about art concepts and put those hypotheses to the test in three experimental studies.
Location‐Routing with Conflicting Objectives: Coordinating eBeam Phytosanitary Treatment and Distribution of Mexican Import Commodities
Authors: Geismar H. Neil , Huang Yiwei , Pillai Suresh D. , Sriskandarajah Chelliah , Youn Seokjun
Published: February 2020

We study a generalized location‐routing problem in which the key decisions are made by supply chain partners with conflicting objectives. The context of our problem is the irradiation by electron beam (eBeam) of fresh produce imported from Mexico to reduce the threat of insects and pests to the U.S. agriculture. Because too few irradiation facilities exist to serve the current demand, we focus on two parties to be coordinated: the eBeam Services Provider, who will choose the facilities’ locations and capacities, and the Distributor, who will determine routes for transporting fruits from Mexico to commercial hubs in the United States via these facilities. We demonstrate the value of cooperation and how that cooperation can be achieved and enforced for a supply chain that must coordinate the independent companies by the strategic decisions of facility location and capacity construction, as opposed to the more common coordination by capacity allocation or pricing. The parties’ interactions are modeled as a sequential game with perfect information. Specifically, we formulate the sequential and cooperative decision‐making problems as mixed‐integer programs, analyze the computational complexity of the problems, and conduct extensive computational experiments. Additionally, we detail three schemes by which the parties can engage in profitable and enforceable cooperation. These methods progressively increase each party’s commitment as trust is built and profits rise. Total cooperation increases overall profit by an average of 8.6%. Further, a stochastic program that uses sample average approximation is applied to demonstrate the results’ robustness to nature’s supply variations while maximizing the supply chain’s overall profit.
The Kindness of Commenters: An Empirical Study of the Effectiveness of Perceived and Received Support for Weight‐Loss Outcomes
Authors: Yan Lu (Lucy)
Published: February 2020

Social media‐based online communities are becoming increasingly popular for various social interactions, including those for healthcare and health‐related activities. The benefits from these activities, however, are constrained by how a platform is designed, as a platform's design defines what activities can be done and how individuals can engage and interact on the platform. In this study, we focus on weight‐loss communities and social tools that facilitate social communication and establish a variety of relationships between users. In particular, we examine the effectiveness of one‐way and two‐way social relationships on individuals’ weight‐loss management. Drawing from theories of social support, social reciprocity, and social indebtedness, we use two‐way friendship relationships to proxy perceived support and one‐way commenting relationships to proxy received support and conjecture that they work through different pathways. We find, through empirical analyses, that both types of social relationships as well as self‐monitoring are effective in promoting weight loss, but perceived and received support have different impacts. Whereas both perceived and received support are positively related to weight‐loss outcomes, the effect of received support is found to be higher than that of perceived support and the difference is statistically significant. Moreover, we find that received support is positively associated with self‐monitoring behaviors, whereas perceived support is not. These findings provide insights for platform providers to improve the social design aspect of online services and for healthcare practitioners in their efforts to advise individuals on weight self‐management. Our results also can be used to design and implement more effective online interventions.
Gender Attitudes and Public Opinion Towards Electoral Gender Quotas in Brazil
Authors: Batista Pereira Frederico , Porto Nathália F. F.
Published: February 2020

Research on public opinion towards affirmative action shows that citizens often support the principle of equality while simultaneously rejecting policies that promote it in a pattern described as the “principle‐policy puzzle.” The scholarship also shows that ideology and prejudice towards the targeted group explain the puzzle with respect to racial affirmative action. In this article, we use unique survey questions included in the 2014 round of the AmericasBarometer in Brazil to show that citizens tend to support electoral gender quotas while rejecting gender‐based egalitarianism in a reversed version of the “principle‐policy puzzle.” We argue that a different type of gender attitudes, namely benevolent sexism, shapes support for gender quotas as well as for the principle of equality. While benevolent sexists tend to reject gender equality based on views about gender complementarity and stereotypes about women's purity, they also support quotas as policies to foster such values. Our findings suggest that even though the political and scholarly debates can provide sound normative reasons for the adoption of quotas across different contexts, public support for them often relies on paternalistic views and expectations about the role of women in politics.
Clostridium bifermentans and C. subterminale are associated with kiwifruit vine decline, known as moria, in Italy
Authors: Spigaglia Patrizia , Barbanti Fabrizio , Marocchi Fabio , Mastroleo Marco , Baretta Marco , Ferrante Patrizia , Caboni Emilia , Lucioli Simona , Scortichini Marco
Published: February 2020

Since 2012, a new pathogenic syndrome has frequently been observed in many areas of kiwifruit cultivation in Italy. The main symptoms include an initial withering of the leaves followed by a total and sudden collapse of plants, mainly occurring during summer. The withered leaves fall and the main and secondary feeder roots appear rotten, sometimes showing a reddish‐brown discoloration. The disease, that affects both the green and yellow‐fleshed cultivars, has been called kiwifruit vine decline and is locally known as moria. The syndrome has been found consistently associated with soil waterlogging, which frequently occurs either after the traditional agronomical practice of irrigating orchards through surface irrigation or after very heavy rainfall. So far, the role played by bacteria in this syndrome has not been investigated. In the present study, Clostridium spp. were isolated from both rotten roots and soils obtained from Italian kiwifruit orchards affected by the syndrome, indicating for the first time that anaerobic bacteria are able to cause damage to woody crops. C. bifermentans and C. subterminale incited symptoms in kiwifruit in both in vivo and in vitro pathogenicity tests. Soil waterlogging seems to potentially favour colonization of kiwifruit roots by anaerobic bacteria, probably because saturation of the soil can facilitate proliferation and persistence of these bacteria during long periods of the vegetative growth of the crop. The occurrence of anaerobic bacteria does not exclude the possibility that other microorganisms can play additional/synergic role(s) in causing the kiwifruit vine decline.
Caring for alcohol‐intoxicated patients in an emergency department from the nurses’ point of view – focus on attitudes and skills
Authors: Hakala Tiina , Kylmä Jari , Mäkelä Kaisu‐Leena , Noppari Eija , Koivunen Marita
Published: February 2020

Background

Healthcare professionals have a key role in detecting health risks from alcohol use. The earlier the alcohol misuse is identified and addressed, the lower the risk of harm and the need for actual drug treatment. Positive attitudes and high motivation on the part of nurses are needed for achieving success in the care of intoxicated patients.

Aim

The aim of the study was to describe nurses’ skills to care for and attitudes towards the care of patients with alcohol intoxication in emergency departments (EDs).

Method

The data were collected from nursing staff who participated in online training related to the care of alcohol‐intoxicated patients in the EDs (N = 20, n = 17). As part of the training, nurses wrote two essays. The essays made up the data of this study which were analysed using inductive content analysis.

Results

Three main categories emerged from the nurses’ descriptions of their skills in caring for and attitudes towards the care of patients with alcohol intoxication: nurse’s lack of commitment to intoxicated patient care; nurse’s commitment to intoxicated patient care; and nurse’s skills in intervention methods.

Conclusion

Many different factors influence nurses’ commitment or lack of commitment in the care of intoxicated patients. Nurses’ attitudes and skills are linked to the success of care of intoxicated patients in ED.

Implications for nursing of alcohol‐intoxicated patients

Increasing awareness of alcohol‐related issues seems to help nurses to understand better the situation of a patient with alcohol intoxication, make their attitudes more positive and help them to use the intervention methods.
Conflicting signal in transcriptomic markers leads to a poorly resolved backbone phylogeny of chalcidoid wasps
Authors: Zhang Junxia , Lindsey Amelia R.I. , Peters Ralph S. , Heraty John M. , Hopper Keith R. , Werren John H. , Martinson Ellen O. , Woolley James B. , Yoder Matt J. , Krogmann Lars
Published: February 2020

Chalcidoidea (Hymenoptera) are a megadiverse superfamily of wasps with astounding variation in both morphology and biology. Most species are parasitoids and important natural enemies of insects in terrestrial ecosystems. In this study, we present a transcriptome‐based phylogeny of Chalcidoidea; we found that poorly resolved relationships could only be marginally improved by adding more genes (a total of 5591) and taxa (a total of 65), proof‐checking for errors of homology and contamination, and decreasing missing data. Concatenation analyses consistently place Mymaridae and Trichogrammatidae sister to remaining Chalcidoidea. However, our coalescent analyses provide a different hypothesis with a grouping of (Mymaridae (((Trichogrammatidae, Eulophidae), (Encyrtidae, Aphelinidae)), remaining Chalcidoidea)). This hypothesis complicates our hypothesis of egg parasitism as being the ancestral state in Chalcidoidea. At the deeper nodes, the results uncovered a wide spectrum of gene discordance in the transcriptomic markers and identified a strong signal of functional bias in genes supporting alternative phylogenies. These deeper nodes of the phylogeny are thus strongly influenced by biased support from different functional gene complexes. Shallower nodes showed similar gene discordance, but without strong functional bias. Understanding and identifying mechanisms that result in gene tree discordance may be beneficial and even essential for elucidating deeper relationships, especially for groups that have undergone extremely rapid radiation.
Partial cystectomy with a bipolar sealing device in seven dogs with naturally occurring bladder tumors
Authors: Milovancev Milan , Scharf Valery F. , Townsend Katy L. , Singh Ameet , Tremolada Giovanni , Worley Deanna , Schmiedt Chad W.
Published: February 2020

Objective

To describe the use of a bipolar sealing device (BSD) for partial cystectomy in dogs undergoing excision of bladder tumors.

Study design

Multicenter, prospective, clinical pilot study.

Sample population

Seven client‐owned dogs with nontrigonal urinary bladder lesions.

Methods

Dogs underwent a sealed partial cystectomy with a BSD, with or without cystoscopic guidance of the resection. The sealed cystectomy site was oversewn with a single‐layer simple continuous pattern with monofilament absorbable suture.

Results

Sealed partial cystectomy was successfully performed in all dogs, with a median surgical duration of 69 minutes (range, 50‐120). Lesions were located at the apex in six dogs and on the ventral midbody of the bladder in one dog. No urine leakage from the BSD luminal seal was visible prior to suture closure in three dogs, while varying amounts of urine leaked from the sealed site in four dogs. Suture was placed over the seal in grossly normal bladder tissue in six dogs and in the BSD peripheral thermal effect zone in one dog; in this latter dog, revision cystorrhaphy was required 3 days later because of uroabdomen. The other six dogs had no clinical evidence of urinary bladder healing complications.

Conclusion

The integrity of the seal generated by the BSD tested here on partial cystectomies varied between dogs and was unpredictable.

Clinical significance

Sealed partial cystectomy with a BSD may reduce exposure of urinary bladder luminal contents to the surgical site. However, the placement of sutures over the seal and through grossly normal bladder tissue is recommended to prevent postoperative uroabdomen.
The Great Drama, Global Warming and Its Mechanism
Authors: Lane Jan-Erik
Published: February 2020

Well-known professor Johan Rockström at Stockholm University claims that we are in control of things, now that the Earth Sciences have proven the biological  limits of our existing civilisations. But we do not know or have not begun the necessary large global adjustments towards a sustainable Planet Earth. The failure of the UN COP framework is blatant stating the ends but not the means of reducing significantly CO2 emissions. All major countries plan for much more energy in coming decades treating renewable energy sources as merely compliment to fossil fuels,  not substitutes. To accomplish the Paris Accord objevties (COP 21), coal power should be phased out.
Corpos e territórios negros: representações da religiosidade afro-brasileira no documentário Orí (1989)
Authors: Ferreira Ceiça
Published: February 2020

Este artigo tem como objetivo principal analisar as representações da religiosidade afro-brasileira do documentário Orí (1989), dirigido pela cineasta Raquel Gerber, com narração e textos da historiadora Beatriz Nascimento, situando-o no contexto da produção cinematográfica nacional. A partir dos estudos culturais, do pensamento negro brasileiro e da metodologia de análise fílmica, investiga-se a construção narrativa e estética desse filme, que tem como ideia central a pesquisa de Beatriz Nascimento sobre o quilombo, suas origens africanas, sua continuidade histórica no Brasil no período colonial e sua ressignificação nos anos de 1970, quando passa a designar espacialidades como as escolas de samba, os bailes black, os movimentos negros e os terreiros de candomblé. Foi estudado como a religiosidade afro-brasileira tem um papel central nesses territórios negros, nos quais se dá a reconstrução das identidades negras, a tomada de consciência por meio do orí, palavra de origem iorubá, que significa “fazer a cabeça”, fazer o rito de iniciação no candomblé, ou seja, uma possibilidade de renascimento. Conclui-se que tal documentário oferece representações da religiosidade afro-brasileira como um sistema de pensamento, que se inscreve na tessitura fílmica por meio da pluralidade de vozes, da centralidade visual de corpos negros em transe, das relações de pertencimento dentro do terreiro, e da ligação com a terra e com a ancestralidade.
Poéticas de otros/as: resistencias caníbales a la guerra total
Authors: Morales Saro Cristina
Published: February 2020

Este artículo es un ejercicio de comprensión de nuestro presente a partir de las propuestas antropofágicas de Oswald de Andrade, Suely Rolnik y Eduardo Viveiros de Castro, entre otros/as. Vamos a ver si por el camino nos permitimos, o se nos impone, la experimentación de algunos modos de ser que, entre las formas y las fuerzas (Rolnik), no tengan que regirse por los dispositivos de alienación y explotación a los que el capitalismo global quiere acostumbrarnos. Queremos aquí replantear, sobre todo, la continuidad entre la cuestión ética y aquella política. Continuidad que, desde la enunciación antropofágica, nos abre a una idea peculiarmente cósmica sobre la comunidad y sobre nosotros/as mismos/as que da al traste con el proyecto socioatómico que amenaza con totalizar el globo. Las exigencias de depredación que actuamos y hacemos crecer en nuestra relación con la tierra y con los/as otros/as para satisfacer los estándares de las sociedades de la información en el contexto del capitalismo avanzado nos obliga, ¿es así?, a detenernos y a reflexionar. En este punto, la línea caníbal tiene la ventaja de proveernos de un estilo especial para llevar a cabo esta reflexión tan necesaria. Se trata del modo poético, modo a partir del cual el pensamiento toma conciencia, no solo de sus poderes creativos y performáticos, sino de su poder de dislocación y quebranto de unas cuántas lógicas atenazantes, quizá demasiado humanas.
Un dibujante + una mujer que posa + una mesa + una pantalla + una cuadrícula o dos cortes en la sustancia del mundo
Authors: Lozano Rocha Ana María
Published: February 2020

Este artículo plantea develar el eje antrópico de la mirada hegemónica occidental para comprender cómo opera y de qué manera este genera una mirada. Los objetivos de tal deconstrucción tienen que ver con llevar a cabo un proceso de análisis sobre qué muestra y qué no dicho eje antrópico, y así conocer más sobre la imagen, su creador y su observador. Por otra parte, busca presentar las posibilidades de establecer otro aparato de ver que permita ver al otro, sacar al humano del centro de las coordenadas perceptivas y entender al humano como viviente entre vivientes, cuyas vidas merecen ser vividas. Es importante establecer que una de las maneras como se construyó el discurso de la excepcionalidad del humano pasó por la construcción del cubo perspéctico, aparato de ver estructurante y estructurador de las formas de comprensión del mundo posteriores a esa invención. Este, como todo aparato, es social, produce a su usuario y a su cuerpo. Con ello, genera perspectiva, formas de descripción del mundo, formas de intelección de los fenómenos, esto es, construye una episteme o lo que llamamos una mirada. Este artículo une herramientas epistemológicas provenientes de la teoría de la imagen, de la filosofía, de la historia del arte y de los estudios visuales para llevar a cabo la comprensión de la máquina de ver producida por el Renacimiento y sus manifestaciones de pervivencia en el mundo actual.
Fluid-Structure Interaction Simulation of Lactating Human Breast
Authors: Azarnoosh Jamasp , Hassanipour Fatemeh
Published: February 2020

This study presents a 3-D Fluid-Structure Interaction (FSI) simulation of breastfeeding mechanism to provide a better understanding of the milk flow behavior in the ductal system of the human breast as the breast interacts with the infant's oral cavity. The breast geometry consists of one lobe with three-bifurcation levels. The boundary conditions include: (1) The intraoral vacuum pressure, obtained from the clinical measurements, (2) Dynamic motion of the tongue, nipple, and jaw (maxilla and mandible) motion captured by ultrasound images. Simulation is conducted from the instance of latching and continues for two cycles of periodic tongue motion and in various boundary conditions and mouthing positions. The results from the simulation show that milk removal is not only due to the negative pressure applied by the infant sucking, but also the tongue movement and mouthing and squeezing of nipple and breast, i.e. a positive force deforming the nipple is responsible for the expression of milk. The developed model can contribute to a better understanding of breastfeeding complications due to physical infant and/or breast abnormalities and the design of medical devices such as artificial teats and breast pumps.
Effect of Oscillating Water Column Chamber Inclination on the Performance of a Savonius Rotor
Authors: Prasad Deepak D. , Ahmed M. Rafiuddin , Lee Young-Ho
Published: February 2020

The power potential in the waves that hit all the coasts worldwide has been estimated to be of the order of 1 TW. Each wave crest transmits 10–50 kW/m of energy, which is 15–20 times higher than wind or solar energies. The availability of wave energy is 90% compared to 30% for wind and solar energies. The oscillating water column (OWC), which is the most investigated wave energy converter consists of a partially submerged hollow structure positioned either vertically or inclined. The bidirectional airflow above the water column drives a turbine. The conventional OWCs experience flow separation at the sharp corners of the chamber. To address this issue, researchers have proposed inclining the chamber at an angle with respect to the incident waves to improve the flow characteristics. In the present work, the effect of OWC inclination on rotor performance is studied using the computational fluid dynamics (CFD) code ansys-cfx. The results highlight that the 55 deg inclined OWC showed improved performance compared to the conventional OWC and modified OWC (optimized in a previous work). The maximum power for the inclined OWC was 13% higher than that for the rotor in the modified OWC and 28% than that in the conventional OWC at mean wave condition. The 55 deg inclined OWC recorded peak rotor power of 23.2 kW with an efficiency of 27.6% at the mean sea state. The peak power and efficiency at maximum sea state were 26.5 kW and 21.5%, respectively.
Posturing Responses in Concussions Sustained by Elite American Football Players
Authors: Bruce Scott L. , Dorney Kyra
Published: February 2020

Current literature indicates loss of consciousness occurs in about 10% of concussions. Posturing presentations represent brain injuries and a loss of consciousness. The purpose of this study was to observe video evidence of football-game-related concussions to determine the rate in which a posturing presentation occurs in reported concussion. Over the course of three National Football League and three National Collegiate Athletic Association football seasons, 103 videos of 805 reported concussions met the inclusion criteria; 35 videos demonstrated a posturing presentation, for a rate of 33.98%. Our study indicates that the published statistic regarding loss of consciousness (occurring only about 10% of the time) may be too conservative.
Mus musculus Papillomavirus 1: a New Frontier in Animal Models of Papillomavirus Pathogenesis
Authors: Spurgeon Megan E. , Lambert Paul F.
Published: February 2020

Animal models of viral pathogenesis are essential tools in human disease research. Human papillomaviruses (HPVs) are a significant public health issue due to their widespread sexual transmission and oncogenic potential. Infection-based models of papillomavirus pathogenesis have been complicated by their strict species and tissue specificity. In this Gem, we discuss the discovery of a murine papillomavirus, Mus musculus papillomavirus 1 (MmuPV1), and how its experimental use represents a major advancement in models of papillomavirus-induced pathogenesis/carcinogenesis, and their transmission.
Data Mining a Medieval Medical Text Reveals Patterns in Ingredient Choice That Reflect Biological Activity against Infectious Agents
Authors: Connelly Erin , del Genio Charo I. , Harrison Freya
Published: February 2020

We used established methodologies from network science to identify patterns in medicinal ingredient combinations in a key medieval text, the 15th-centuryLylye of Medicynes, focusing on recipes for topical treatments for symptoms of microbial infection. We conducted experiments screening the antimicrobial activity of selected ingredients. These experiments revealed interesting examples of ingredients that potentiated or interfered with each other’s activity and that would be useful bases for future, more detailed experiments. Our results highlight (i) the potential to use methodologies from network science to analyze medieval data sets and detect patterns of ingredient combination, (ii) the potential of interdisciplinary collaboration to reveal different aspects of the ethnopharmacology of historical medical texts, and (iii) the potential development of novel therapeutics inspired by premodern remedies in a time of increased need for new antibiotics.
Rapid Freezing Enables Aminoglycosides To Eradicate Bacterial Persisters via Enhancing Mechanosensitive Channel MscL-Mediated Antibiotic Uptake
Authors: Zhao Yanna , Lv Boyan , Sun Fengqi , Liu Jiafeng , Wang Yan , Gao Yuanyuan , Qi Feng , Chang Zengyi , Fu Xinmiao
Published: February 2020

Antibiotics have long been used to successfully kill bacterial pathogens, but antibiotic resistance/tolerance usually has led to the failure of antibiotic therapy, and it has become a severe threat to human health. How to improve the efficacy of existing antibiotics is of importance for combating antibiotic-resistant/tolerant pathogens. Here, we report that 10-s rapid freezing with liquid nitrogen dramatically enhanced the bactericidal action of aminoglycoside antibiotics by 2 to 6 orders of magnitude against many bacterial pathogens
in vitro
and also in a mouse skin wound model. In particular, such combined treatment was able to effectively kill persister cells of
Escherichia coli
and
Pseudomonas aeruginosa
, which are
per se
tolerant of conventional treatment with bactericidal antibiotics for several hours. We also demonstrated that freezing-induced aminoglycoside potentiation was apparently linked to freezing-induced cell membrane damage that may have activated the mechanosensitive ion channel MscL, which, in turn, was able to effectively uptake aminoglycoside antibiotics in a proton motive force-independent manner. Our report sheds light on the development of a new strategy against bacterial pathogens by combining existing antibiotics with a conventional physical treatment or with MscL agonists.
Update on acute flaccid myelitis: recognition, reporting, aetiology and outcomes
Authors: Hardy Duriel , Hopkins Sarah
Published: February 2020

Acute flaccid myelitis, defined by acute flaccid limb weakness in the setting of grey matter lesions of the spinal cord, became increasingly recognised in 2014 following outbreaks in Colorado and California, temporally associated with an outbreak of enterovirus D68 respiratory disease. Since then, there have been biennial increases in late summer/early fall. A viral infectious aetiology, most likely enteroviral, is strongly suspected, but a definitive connection has yet to be established. Patients typically present with asymmetric weakness, maximal proximally, in the setting of a febrile illness. MRI demonstrates T2/FLAIR abnormalities in the central grey matter of the spinal cord, and cerebrospinal fluid typically shows a lymphocytic pleocytosis with variable elevation in protein. The weakness may be progressive over several days and involve respiratory muscles, making early recognition and close monitoring essential. Other complications in the acute period may include autonomic instability and bowel/bladder involvement. There is no clear recommended treatment at this time, although intravenous immunoglobulin, steroids and plasma exchange have been used. Intensive therapies and rehab services have shown benefit in maximising function, and surgical interventions may be considered in cases without optimal response to therapies. Close attention should also be paid to psychosocial factors. Prognosis is generally guarded, and additional factors that predict final outcome, including host factors and treatment effects, have yet to be elucidated. Multicentre collaborative efforts will be required to provide answers about this rare but serious disorder.
Branding of subjects affected with genetic syndromes of severe short stature in developing countries
Authors: Guevara-Aguirre Jaime , Guevara Carolina , Guevara Alexandra , Gavilanes Antonio AWD
Published: February 2020

In Ecuador, a developing South American country, subjects affected with genetic syndromes of severe short stature are commonly referred to as dwarfs or midgets. Furthermore, and because in earlier studies some patients had evidenced mental retardation, such abnormality is assumed to exist in all affected subjects. Herein, we present two discrete instances in which this type of branding occurs. The first is that of individuals with Laron syndrome who are still called ‘dwarfs’ and considered as having a degree of mental retardation despite evidence showing otherwise. A similar problem, that of a girl affected with a genetic syndrome of short stature, which might include mental retardation, is also discussed. Considering that stigmatising is a form of discrimination, it concerns us all. Hence, the use of derogatory terms such as midget, dwarf or cretin, that might unintentionally occur even when delivering the best and most devoted medical care, must be eliminated.
Atypical presentation of acute rheumatic fever (ARF) in a 25-year-old woman in the Caribbean: a challenging diagnosis
Authors: Bordes Stephen John , Murray Ian Victor Joseph , Sylvester Johansen A
Published: February 2020

A 25-year-old woman presented a challenging diagnosis of acute rheumatic fever (ARF). Initial symptoms included dry cough and three minor Jones criteria (unabating fever (38.4°C, 0d), elevated acute phase reactants (C-reactive protein, 13d) and joint pain (monoarthralgia) in her neck (0d)). ARF was diagnosed only after presentation of two major Jones criteria (polyarthritis/polyarthralgia (16d) and erythema marginatum (41d)) and positive antistreptolysin O titre (44d). Parotid swelling, peripheral oedema, elevated liver enzymes and diffuse lymphadenopathy complicated the diagnosis. Throat swab, chorea and carditis were negative or absent. Atypical ARF is challenging to recognise. There is no diagnostic test and its presentation is similar to that of other diseases. While the 2015 Jones criteria modification increased specificity of ARF diagnosis, atypical cases may still be missed, especially by physicians in developed countries. Suspicion of atypical ARF, especially after travel to high incidence regions, would allow for earlier treatment and prevention of rheumatic heart disease.
Digital ischaemia secondary to adalimumab-induced antiphospholipid syndrome
Authors: Cheemalavagu Shashank , McCoy Sara S , Knight Jason S
Published: February 2020

A 50-year-old woman with a history of Crohn’s disease treated with adalimumab presented with left hand pain and duskiness. Angiogram showed non-filling of the radial and digital arteries of the hand. Antiphospholipid antibody testing was positive, leading to a diagnosis of antitumour necrosis factor-induced antiphospholipid syndrome. Adalimumab was discontinued, and she was treated with the vitamin K antagonist warfarin and low-dose aspirin. Upon resolution of the antiphospholipid antibodies, she was transitioned to aspirin alone without recurrence of thrombosis.
Tandem occlusion involving accessory middle cerebral artery in acute ischaemic stroke: management strategies
Authors: Ray Nirmalya , Dhanasekaran Jagadeesan , Joseph Santhosh , Jella Laxmikanth
Published: February 2020

Occlusion of both the limbs of accessory middle cerebral artery (AMCA) poses a unique challenge in management of acute ischaemic stroke by mechanical thrombectomy. The patient is a 30-year-old man, presenting with acute onset of left-sided hemiparesis for 4 hours. Non-contrast CT brain showed no bleed and three-dimensional CT angiogram of head and neck vessels showed dissection involving right carotid bulb and tandem occlusion of right MCA with presence of two MCA stumps. Aspiration thrombectomy was done using a reperfusion catheter, advanced separately into both the MCA stumps and complete recanalisation of both the limbs of MCAs was achieved, which was found to be AMCA. Balloon angioplasty for the internal carotid artery dissection was performed. Although occlusion of AMCA in acute ischaemic stroke is a chance occurrence, it is important to identify this variant as recanalisation of both the limbs by mechanical thrombectomy is required for favourable outcome after the procedure.
Spontaneous pneumomediastinum: an unusual complication of hyperemesis gravidarum
Authors: Foley David , Holmes Heather J , Kauffman Robert P
Published: February 2020

A 21-year-old first trimester primagravida woman with hyperemesis gravidarum was noted to have incidental subcutaneous emphysema during thyroid ultrasound. Follow-up radiograph demonstrated supraclavicular subcutaneous emphysema, left apical pneumothorax and pneumomediastinum. The patient was transferred to the intensive care unit and evaluated for esophageal rupture. Because no defects were seen on swallow studies/endoscopy and the patient was stable, she was treated conservatively with antibiotics and monitored. The patient’s condition improved, and she was discharged on hospital day 6. Subcutaneous emphysema secondary to hyperemesis gravidarum is a rare but potentially life-threatening condition in which the source of the mediastinal leak needs to be immediately determined. After the more serious sources of mediastinal air have been excluded, conservative management is suitable.
Enhanced efficacy and limited systemic cytokine exposure with membrane-anchored interleukin-12 T-cell therapy in murine tumor models
Authors: Zhang Ling , Davies John S , Serna Carylinda , Yu Zhiya , Restifo Nicholas P , Rosenberg Steven A , Morgan Richard A , Hinrichs Christian S
Published: February 2020

Background

Interleukin-12 (IL-12) is a potent, proinflammatory cytokine that holds promise for cancer immunotherapy, but its clinical use has been limited by its toxicity. To minimize systemic exposure and potential toxicity while maintaining the beneficial effects of IL-12, we developed a novel IL-12-based therapeutic system that combines tumor-specific T-cell-mediated delivery of IL-12 with membrane-restricted IL-12 localization and inducible IL-12 expression.

Methods

Therapeutic T cells targeting a tumor antigen were genetically engineered to express membrane-anchored IL-12 (aIL-12). Expression, function, and shedding of the aIL-12 molecule was assessed in vitro. Tumor treatment efficacy was assessed in vivo with T cell receptor (TCR) transgenic murine tumor models and a tumor xenograft model. Key outcomes were change in tumor size, circulating levels of IL-12 and other cytokines, and survival. Toxicity was assessed via change in body weight. Tumor growth curve measurements were compared using repeated-measures two-way analyses of variance.

Results

Retroviral gene transfer resulted in cell membrane expression of aIL-12 by transduced T cells. In each of two transgenic murine tumor models, tumor-specific T cells constitutively expressing aIL-12 demonstrated increased antitumor efficacy, low circulating IL-12 and interferon-γ, and no weight loss. Expression of aIL-12 via aNFAT-inducible promoter resulted in coordinate expression of aIL-12 with T cell activation. In an OT-I TCR transgenic murine tumor model, theNFAT-inducible aIL-12 molecule improved tumor treatment and did not result in detectable levels of IL-12 in serum or in weight loss. In a human tumor xenograft model, theNFAT-inducible aIL-12 molecule improved antitumor responses by human T cells coexpressing a tumor-specific engineered TCR. Serum IL-12 levels were undetectable with theNFAT-inducible construct in both models.

Conclusion

Expression of aIL-12 by tumor-targeting therapeutic T cells demonstrated low systemic exposure and improved efficacy. This treatment strategy may have broad applications to cellular therapy with tumor-infiltrating lymphocytes, chimeric antigen receptor T cells, and TCR T cells.
Intracerebral implantation of human neural stem cells and motor recovery after stroke: multicentre prospective single-arm study (PISCES-2)
Authors: Muir Keith W , Bulters Diederik , Willmot Mark , Sprigg Nikola , Dixit Anand , Ward Nick , Tyrrell Pippa , Majid Arshad , Dunn Laurence , Bath Philip , Howell Julian , Stroemer Paul , Pollock Kenneth , Sinden John
Published: February 2020

Background

Human neural stem cell implantation may offer improved recovery from stroke. We investigated the feasibility of intracerebral implantation of the allogeneic human neural stem cell line CTX0E03 in the subacute—chronic recovery phase of stroke and potential measures of therapeutic response in a multicentre study.

Methods

We undertook a prospective, multicentre, single-arm, open-label study in adults aged >40 years with significant upper limb motor deficits 2–13 months after ischaemic stroke. 20 million cells were implanted by stereotaxic injection to the putamen ipsilateral to the cerebral infarct. The primary outcome was improvement by 2 or more points on the Action Research Arm Test (ARAT) subtest 2 at 3 months after implantation.

Findings

Twenty-three patients underwent cell implantation at eight UK hospitals a median of 7 months after stroke. One of 23 participants improved by the prespecified ARAT subtest level at 3 months, and three participants at 6 and 12 months. Improvement in ARAT was seen only in those with residual upper limb movement at baseline. Transient procedural adverse effects were seen, but no cell-related adverse events occurred up to 12 months of follow-up. Two deaths were unrelated to trial procedures.

Interpretation

Administration of human neural stem cells by intracerebral implantation is feasible in a multicentre study. Improvements in upper limb function occurred at 3, 6 and 12 months, but not in those with absent upper limb movement at baseline, suggesting a possible target population for future controlled trials.

Funding

ReNeuron, Innovate UK (application no 32074-222145).

Trial registration number

EudraCT Number: 2012-003482-18
Prevalence of spirometry-defined airflow obstruction in never-smoking working US coal miners by pneumoconiosis status
Authors: Kurth Laura , Laney Anthony S , Blackley David J , Halldin Cara N
Published: February 2020

Introduction

This study estimated the prevalence of spirometry-defined airflow obstruction and coal workers’ pneumoconiosis (CWP) among never-smoking coal miners participating in the National Institute for Occupational Safety and Health (NIOSH) Coal Workers’ Health Surveillance Program (CWHSP).

Methods

Data were from working miners screened by a CWHSP mobile unit who had valid spirometry and chest radiography results. Spirometry-defined airflow obstruction was determined when the ratio of forced expiratory volume in the first second to forced vital capacity is less than the lower limit of normal. Chest radiographs were classified according to the International Labour Office system to identify pneumoconiosis, including the most severe form of pneumoconiosis, progressive massive fibrosis (PMF).

Results

Prevalence of airflow obstruction among never-smoking coal miners in this sample was 7.7% overall, 16.4% among miners with CWP and 32.3% among miners with PMF. Airflow obstruction was significantly associated with CWP and PMF.

Conclusions

There was a higher prevalence of airflow obstruction among never-smoking coal miners with pneumoconiosis compared with those without pneumoconiosis. These findings support prior research on airflow obstruction and smoking and show pneumoconiosis might present with an obstructive pattern regardless of smoking status.
Improving Access to Psychological Therapies for older adults: auditing management of newly diagnosed mild and moderate depression in six general practices within the Birmingham and Solihull CCG
Authors: Laake Jean Pierre , Parratt Jemma , Majeed Nadia
Published: February 2020

Background

The first-line treatments for mild–moderate and moderate–severe depression according to the National Institute for Health and Care Excellence clinical guidelines for the management of depression in adults are psychological therapies followed by or alongside pharmacological treatment. We conducted an audit of patient records (as recorded by general practitioners (GPs)) to compare practice to the guidelines.

Methods

Incident cases were retrospectively identified from electronic primary care records (SystmOne). From 40 320 registered patients, cases were identified based on previously coded new diagnoses of depression in the 2016–2017 and 2017–2018 Quality and Outcomes Framework (QOF) years. Patient notes were screened for exclusion criteria (mental health problems that would alter management pathway) and for records of management discussions (pharmacological or psychological therapies) at the diagnostic appointment.

Results

In 2016–2017 (n=315), psychological therapies for depression were discussed at 63.2% of diagnostic appointments, they were most discussed at appointments with those aged 18–29 years (70.8%), but this decreased with age to 56.3% of appointments with those aged ≥65 years. In 2017–2018 (n=244), psychological therapies were discussed at 70.9% of diagnostic appointments but were discussed at more appointments with those aged 18–29 years (81.6%) and at less appointments with those aged ≥65 years (39.4%). Discussion of pharmacological management was similar for all age groups in 2016–2017 (89.9%) and 2017–2018 (93.0%).

Implications

For patients aged ≥65 years, psychological therapies are featuring less in management discussions with GPs or are not being recorded. Recommendations for change implemented at the practice included feedback of results and professional reminders throughout the 2019-2020 QOF year.