bluuebunny/crossref_metadata_2025 huggingface dataset:
PF4-Dependent Immunoassays in Patients with Vaccine-Induced Immune Thrombotic Thrombocytopenia: Results of an Interlaboratory Comparison
Authors: Tiede Andreas , Althaus Karina , Sachs Ulrich J. , Cooper Nina , Czwalinna Andreas , Müller Jens , Pötzsch Bernd
Published: June 2021

Background Coronavirus disease 2019 vaccine ChAdOx1 nCov-19 may rarely lead to vaccine-induced thrombotic thrombocytopenia (VITT). Antibody-mediated, platelet factor 4 (PF4)-dependent platelet activation appears to resemble a key mechanism in VITT, partially comparable to heparin-induced thrombocytopenia. The use of PF4/heparin immunoassays has been proposed as part of a diagnostic approach, but their sensitivity has not been established.

Methods Sera from 12 well-defined VITT patients were first studied by two different laboratories in functional assays. Sera where then used for an interlaboratory comparison, in which five different PF4/heparin immunoassays were used by four laboratories.

Results Results for functional testing were highly concordant. VITT antibodies were also reliably detected by PF4/heparin enzyme-linked immunosorbent assays (ELISAs) (92–100%). In contrast, only 25% of VITT antibodies were reactive in a particle gel immunoassay (PaGIA), and 8% in a lateral flow assay (LFA). An automated chemiluminescence immunoassay (CLIA) was negative for all sera tested (0%).

Conclusion It seems feasible to establish functional antibody testing for the confirmation of VITT. For the initial screening of suspected VITT cases, PaGIA, LFA, and CLIA are useless when applied as single tests. Only ELISA-based PF4/heparin immunoassays are sensitive enough to be incorporated in the diagnostic workup. However, a combination of a positive ELISA and a negative CLIA may be useful to identify VITT antibodies in the absence of confirmatory functional assays.
Admission Anion Gap Metabolic Acidosis and Its Impact on Patients in Medical Intensive Care Unit
Authors: Dafal Akshay , Kumar Sunil , Agrawal Sachin , Acharya Sourya , Nirmal Apoorva
Published: June 2021

Introduction Anion gap (AG) metabolic acidosis is common in critically ill patients. The relationship between initial AG at the time of admission to the medical intensive care unit (MICU) and mortality or length of stay is unclear. This study was undertaken to evaluate this relationship.

Materials and Method We prospectively examined the acid–base status of 500 consecutive patients at the time of MICU admission and outcome was measured in terms of mortality, length of ICU stay, need of ventilator, and laboratory parameters. The patients were divided into four stages based on the severity of AG. Outcome based on the severity of AG was measured, and comparisons that adjusted for baseline characteristics were performed.

Results This study showed that increased AG was associated with the higher mortality. Patients with the highest AG also had the longest length of stay in the MICU, and patients with normal acid–base status had the shortest ICU length of stays (p < 0.05).

Conclusion A high AG at the time of admission to the MICU was associated with higher mortality and length of stays. Initial risk stratification based on AG and metabolic acidosis may help guide appropriate patient disposition (especially in patients without other definitive criteria for MICU admission) and assist with prognosis.
Characteristics, Treatment, and Prognosis of Cracked Teeth: A Comparison with Data from 10 Years Ago
Authors: Lee Tae Yeon , Yang Sung Eun , Kim Hye Min , Kye Min Joo
Published: June 2021

Objectives The purpose of this study was to analyze and to compare retrospectively the characteristics, the treatment process, and the prognosis of cracked teeth by comparing recent data with data from 10 years ago.

Materials and Methods Sixty-eight cracked teeth from March 2009 to June 2010 (2009 data) and 185 cracked teeth from March 2019 to June 2020 (2019 data) were analyzed. The characteristics of cracked teeth and the treatment method depending on probing depth, caries, and symptoms, and prognosis depending on pocket depth and apical lesions were analyzed using R version 3.3.3 (R Foundation for Statistical Computing, Vienna, Austria) and T&F version 3.0 (YooJin BioSoft, Korea). To compare proportions, the two-sample proportion test was performed. The distribution of proportions within the samples from 2009 and 2019 data was analyzed using the Chi-square test or binomial test. A p-value <0.05 was considered to indicate statistical significance.

Results Significantly fewer cracked teeth received root canal treatment before crown in 2019 than in 2009 (p = 0.032). In both 2009 and 2019, symptomatic cracked teeth and those with deep periodontal pockets (>6 mm) were significantly more likely to receive root canal treatment. In both years, cracked teeth with a probing depth less than 6 mm or without an apical lesion were significantly more likely to be asymptomatic at 3-month and 6-month follow-ups (p < 0.001).

Conclusion Cracked teeth with a deep periodontal pocket or symptoms had a higher likelihood of endodontic treatment, and the presence of a deep periodontal pocket or apical lesion was associated with a higher risk of persistent symptoms. Therefore, clinicians should consider these factors when planning treatment and predicting patients’ prognosis.
The Impact of the COVID-19 Pandemic on Head and Neck Surgery Training: A Brazilian National Survey
Authors: Leite Ana Kober , Matos Leandro Luongo , Cernea Claudio R. , Kowalski Luiz Paulo
Published: June 2021

Introduction The COVID-19 pandemic has had a high impact on surgical training around the world due to required measures regarding the suspension of elective procedures and the dismissal of nonessential personnel.

Objectives To understand the impact the pandemic had on head and neck surgery training in Brazil.

Methods We conducted a 29-question online survey with head and neck surgery residents in Brazil, assessing the impact the pandemic had on their training.

Results Forty-six residents responded to the survey, and 91.3% of them reported that their residency was affected by the pandemic, but most residents were not assigned to work directly with patients infected with the new coronavirus (71.4%). All residents reported decrease in clinic visits and in surgical procedures, mostly an important reduction of ∼ 75%. A total of 56.5% of the residents described that the pandemic has had a negative impact on their mental, health and only 4 (8.7%) do not have any symptoms of burnout. The majority (78.3%) of the residents reported that educational activities were successfully adapted to online platforms, and 37% were personally infected with the virus.

Conclusion Most surgical residencies were greatly affected by the pandemic, and residents had an important decrease in surgical training. Educational activities were successfully adapted to online modalities, but the residency programs should search for ways of trying to compensate for the loss of practical activities.
Rapid Release of Interleukin-1β from Human Platelets Is Independent of NLRP3 and Caspase
Authors: Pennings Gabrielle J. , Reddel Caroline J. , Traini Mathew , Lam Magdalena , Kockx Maaike , Chen Vivien M. , Kritharides Leonard
Published: June 2021

Objective Platelets are critical in mediating both rapid responses to injury and the development and progression of coronary disease. Several studies have shown that, after prolonged exposure to agonists, they produce and release inflammatory mediators including interleukin-1β (IL-1β), via the classical pathway (NLRP3 inflammasome and caspase-1 cleavage to release active IL-1β) as described for leukocytes. This study aimed to determine whether there is rapid release of IL-1β in response to soluble platelet agonists and whether such rapid release is NLRP3- and caspase-1-dependent.

Methods and Results Using flow cytometry to detect platelet activation (and release of α and dense granule contents) and the combination of Western blotting, enzyme-linked-immunosorbent assay, and immunogold labeling transmission electron and immunofluorescence microscopy, we identified that resting human platelets contain mature IL-1β. Platelets release IL-1β within minutes in response to adenosine diphosphate (ADP), collagen, and thrombin receptor agonists, but not in response to conventional NLRP3 inflammasome agonists—lipopolysaccharide and adenosine triphosphate. The rapid release of IL-1β in response to ADP and thrombin receptor agonists was independent of caspases (including caspase-1) and NLRP3. Immature and mature IL-1β were identified as low-abundance proteins on transmission electron microscopy of human platelets, and were localized to the platelet cytosol, open canalicular system, and the periphery of α granules.

Conclusion Unlike monocytes and neutrophils, human platelets are capable of rapid agonist- and time-dependent release of IL-1β by a mechanism which is independent of caspase-1 and NLRP3.
Elastic modulus and internal friction of thermoelectric composites: Enthalpy–entropy compensation
Authors: Masut Remo A. , Vasilevskiy Dimitri , Keshavarz Mohsen K.
Published: June 2021

Mechanical spectroscopy measurements are reported on rods of (Bi1−xSbx)2Te3 and (Bi1−xSbx)2(Te1−ySey)3 polycrystalline thermoelectric (TE) composite alloys produced by mechanical alloying and hot extrusion. Low internal friction (Q−1) and large stiffness coefficients obtained in the 293–573 K range corroborate the improved elastic properties of these hot extruded and highly textured polycrystalline materials that have enhanced TE properties. Their stiffness shows a quadratic (decreasing) temperature dependence, and the value for most composites is larger than that of conventional single-phase random alloys and hot extruded bismuth telluride. One particular damping mechanism in Q−1, believed to be due to grain boundary motion, is thermally activated at temperatures higher than 420 K. The prefactor of the Arrhenius law correlates with the activation enthalpy (Δh) for every composite. It varies exponentially with Δh for more than six orders of magnitude for activation enthalpies up to 0.9 eV. The observation of this enthalpy–entropy compensation effect results from the existence of a maximum in energy dissipation in a linear regime of weak perturbations. This simple explanation is proposed to apply to this ubiquitous effect which has been observed in many areas of physics, chemistry, and biology.
Three-dimensional acoustic lensing with a bubbly diamond metamaterial
Authors: Lanoy Maxime , Lemoult Fabrice , Lerosey Geoffroy , Tourin Arnaud , Leroy Valentin , Page John H.
Published: June 2021

A sound wave travelling in water is scattered by a periodic assembly of air bubbles. The local structure matters even in the low frequency regime. If the bubbles are arranged in a face-centered cubic (fcc) lattice, a total bandgap opens near the Minnaert resonance frequency. If they are arranged in the diamond structure, which one obtains by simply adding a second bubble to the unit cell, one finds an additional branch with a negative slope (optical branch). For a single specific frequency, the medium behaves as if its refractive index (relative to water) is exactly n=−1. We show that a slab of this material can be used to design a three-dimensional flat lens. We also report super-resolution focusing in the near field of the slab and illustrate its potential for imaging in three dimensions.
Terahertz emission spectroscopy of GaN-based heterostructures
Authors: Mannan Abdul , Yamahara Kota , Bagsican Filchito Renee G. , Serita Kazunori , Murakami Hironaru , Kawayama Iwao , Higashiwaki Masataka , Tonouchi Masayoshi
Published: June 2021

This study investigates the band bending profile of gallium-nitride-based heterostructures with respect to the change in the direction of the induced current in the out-of-plane plane direction, which gives the phase of the terahertz emission peak and can be detected by laser THz emission microscopy. We use a wavelength-tunable laser THz emission spectroscope to observe the transport of charges within the band bending regions, excitation of nearby photocarriers, and carrier scattering. We observe flip-flop peak-to-peak THz emission waveforms for a GaN heterostructure field-effect transistor (FET) compared to a strong THz emission radiated from an Al0.3Ga0.7N/GaN high-electron-mobility-transistor (HEMT). The flip-flop THz emission indicates the emission from various interfaces inside the FET structure, and intense THz emission from the HEMT structure indicates band-edge excitation. Our results provide a valuable perspective for characterizing complex heterostructures that provide insight into possible defects, carrier mobilities, and band bending of multilayer interface electronic devices.
Effects of stress on the evolution of Σ-shaped dislocation arrays in a 4H-SiC epitaxial layer
Authors: Na Moonkyong , Bahng Wook , Jang Hyemin , Kim Jung Min , Jung Hyundon
Published: June 2021

Five Σ-shaped dislocation arrays in 100-mm-diameter, 12-μm-thick 4H-SiC epitaxial wafers were observed using photoluminescence mapping. The structure of the Σ-shaped dislocation arrays was characterized using nondestructive analytical techniques of photoluminescence mapping, microphotoluminescence spectroscopy, and x-ray topography. Each Σ-shaped dislocation array consists of two basal plane dislocations (BPDs) at the interfacial dislocation terminal points and two half-loop arrays. The interfacial dislocation pairs nucleate from BPDs in the substrate. Three independent stresses lead to interfacial dislocations: thermal stress (τT), stress induced by misfit strain (τM), and interaction force (τI). The main cause of interfacial dislocation formation is attributed to the development of τT within the wafer due to temperature nonuniformity. τM and τI also contribute to the formation of interfacial dislocations. Larger stresses increase the BPD glide velocity in the interfacial dislocations, thereby producing longer Σ-shaped dislocation arrays.
Large-area CsPbBr3 perovskite films grown with effective one-step RF-magnetron sputtering
Authors: Xu Fan , Li Yujiao , Yuan Beilei , Zhang Yongzheng , Wei Haoming , Wu Yangqing , Cao Bingqiang
Published: June 2021

In this work, we demonstrated the large-area film growth of all-inorganic perovskite CsPbBr3 with semiconductor industry compatible radio frequency magneton sputtering technology. This approach avoids the use of toxic organic solvents, which are required extensively for the solution growth process of these perovskite films. Even on ordinary glass substrates, the CsPbBr3 film of 100 cm2 with a single phase and ultra-smooth surface can be grown under optimized sputtering conditions, among which the substrate temperature is proved very important. Temperature-dependent photoluminescence spectra and femtosecond transient absorption spectra studies show that no subband defect levels are observed in such perovskite films. The temperature-dependent resistivity measurement exhibits a typical thermally activated electrical behavior, and a bandgap of 2.24 eV is obtained, which is consistent with the optical measurements. Therefore, both the optical and electrical studies indicate that the CsPbBr3 film with high optical quality can be grown with effective one-step sputtering technology.
Systematic improvement of molecular excited state calculations by inclusion of nuclear quantum motion: A mode-resolved picture and the effect of molecular size
Authors: Hele Timothy J. H. , Monserrat Bartomeu , Alvertis Antonios M.
Published: June 2021

The energies of molecular excited states arise as solutions to the electronic Schrödinger equation and are often compared to experiment. At the same time, nuclear quantum motion is known to be important and to induce a redshift of excited state energies. However, it is thus far unclear whether incorporating nuclear quantum motion in molecular excited state calculations leads to a systematic improvement of their predictive accuracy, making further investigation necessary. Here, we present such an investigation by employing two first-principles methods for capturing the effect of quantum fluctuations on excited state energies, which we apply to the Thiel set of organic molecules. We show that accounting for zero-point motion leads to much improved agreement with experiment, compared to “static” calculations that only account for electronic effects, and the magnitude of the redshift can become as large as 1.36 eV. Moreover, we show that the effect of nuclear quantum motion on excited state energies largely depends on the molecular size, with smaller molecules exhibiting larger redshifts. Our methodology also makes it possible to analyze the contribution of individual vibrational normal modes to the redshift of excited state energies, and in several molecules, we identify a limited number of modes dominating this effect. Overall, our study provides a foundation for systematically quantifying the shift of excited state energies due to nuclear quantum motion and for understanding this effect at a microscopic level.
Recent advances in the use of phytochemicals to manage gastrointestinal oxidative stress in poultry and pigs
Authors: Cottrell J. J. , Le H. H. , Artaiz O. , Iqbal Y. , Suleria H. A. , Ali A. , Celi P. , Dunshea F. R.
Published: June 2021

Plants are integral components of pig and poultry feed, and aside from their raw nutritive value, some phytochemicals contain bioactive compounds. The aim of the present paper is to review recent advances in the use of some phytochemicals in pig and poultry feed, focusing on the examples of isoquinoline alkaloids, polyphenol rich sugarcane extracts and superoxide dismutase-rich melon pulp extracts. As gut health is critical for efficient production, the review will focus on recent results modulating oxidative stress within the gastrointestinal tract and the potential mechanisms of action.
PLDα1 and GPA1 are involved in the stomatal closure induced by Oridonin in
Authors: Zhang Yue , Liu Ruirui , Zhou Yaping , Wang Simin , Zhang Bianfeng , Kong Juantao , Zheng Sheng , Yang Ning
Published: June 2021

Oridonin is an important diterpenoid, which plays an important role in plant growth and development. PLDα1 and GPA1 are involved in many biotic or abiotic stresses. In this study, using the seedlings of Arabidopsis thaliana L. wild type (WT), PLDα1 defective mutant (pldα1), GPA1 defective mutant (gpa1) and pldα1/gpa1 double mutant as materials, the effect of stomatal apertures responding to Oridonin and the functions of PLDα1 and GPA1 in this response were investigated. The results showed that 60 μmol·L–1 of Oridonin induced stomatal closure and significantly increased the relative expression levels of GPA1 and PLDα1. Oridonin increased H2O2 accumulation in guard cells by inhibiting the antioxidant enzymes. The increase of H2O2 caused the expression of OST1, which is a positive regulatory gene for stomatal closure. Both PLDα1 and GPA1 were involved in Oridonin-induced stomatal closure and PLDα1 acted downstream of GPA1. The results suggested that Oridonin caused stomatal closure by affecting GPA1 and promoting PLDα1 to produce PA, and further accumulating H2O2 to upregulate gene OST1.
Quantifying blue carbon and nitrogen stocks in surface soils of temperate coastal wetlands
Authors: Asanopoulos Christina H. , Baldock Jeff A. , Macdonald Lynne M. , Cavagnaro Timothy R.
Published: June 2021

Coastal wetlands are carbon and nutrient sinks that capture large amounts of atmospheric CO2 and runoff of nutrients. ‘Blue carbon’ refers to carbon stored within resident vegetation (e.g. mangroves, tidal marshes and seagrasses) and soil of coastal wetlands. This study aimed to quantify the impact of vegetation type on soil carbon stocks (organic and inorganic) and nitrogen in the surface soils (0–10 cm) of mangroves and tidal marsh habitats within nine temperate coastal blue carbon wetlands in South Australia. Results showed differences in surface soil organic carbon stocks (18.4 Mg OC ha–1 for mangroves; 17.6 Mg OC ha–1 for tidal marshes), inorganic carbon (31.9 Mg IC ha–1 for mangroves; 35.1 Mg IC ha–1 for tidal marshes), and total nitrogen (1.8 Mg TN ha–1 for both) were not consistently driven by vegetation type. However, mangrove soils at two sites (Clinton and Port Augusta) and tidal marsh soils at one site (Torrens Island) had larger soil organic carbon (SOC) stocks. These results highlighted site-specific differences in blue carbon stocks between the vegetation types and spatial variability within sites. Further, differences in spatial distribution of SOC within sites corresponded with variations in soil bulk density (BD). Results highlighted a link between SOC and BD in blue carbon soils. Understanding the drivers of carbon and nitrogen storage across different blue carbon environments and capturing its spatial variability will help improve predictions of the contribution these ecosystems to climate change mitigation.
Social finance as cultural evolution, transmission bias, and market dynamics
Authors: Akçay Erol , Hirshleifer David
Published: June 2021

The thoughts and behaviors of financial market participants depend upon adopted cultural traits, including information signals, beliefs, strategies, and folk economic models. Financial traits compete to survive in the human population and are modified in the process of being transmitted from one agent to another. These cultural evolutionary processes shape market outcomes, which in turn feed back into the success of competing traits. This evolutionary system is studied in an emerging paradigm, social finance. In this paradigm, social transmission biases determine the evolution of financial traits in the investor population. It considers an enriched set of cultural traits, both selection on traits and mutation pressure, and market equilibrium at different frequencies. Other key ingredients of the paradigm include psychological bias, social network structure, information asymmetries, and institutional environment.
Structural differences in the FAD-binding pockets and lid loops of mammalian CRY1 and CRY2 for isoform-selective regulation
Authors: Miller Simon , Srivastava Ashutosh , Nagai Yoshiko , Aikawa Yoshiki , Tama Florence , Hirota Tsuyoshi
Published: June 2021

Significance

CRY1 and CRY2 regulate circadian rhythms, and their dysfunction has been associated with many diseases. Since they have not only similar but also independent functions, understanding of intrinsic differences between these highly similar proteins is required. Here, we determined CRY1 and CRY2 static and dynamic structures that exhibited conformational isomerism in their ligand-binding FAD pockets and neighboring lid loops, allowing mechanistic insight into structural features specific to each isoform. Structure-guided mutations supported important roles of interactions between a key “gatekeeper” tryptophan residue in the FAD pocket and lid loop residues in determining the effects of isoform-selective compounds. Our results provide insight into how near-identical ligand-binding pockets can intrinsically regulate compound selectivity through unique interactions with neighboring structural elements.
Developmental regionalism and the success prospects of Africa’s continental free trade area (CFTA): lessons from Africa’s early integration experience
Authors: Nubong G. F.
Published: June 2021

This paper argues that Africa needs to adopt a more pragmatic approach to its regional integration agenda in order to increase the prospects of the objectives of the Continental Free Trade Area. The paper examines the political economy realities of Africa’s integration and highlights certain contextual challenges that have created a gap between the continent’s regional integration stated intentions and objectives as contained in the Abuja Treaty forming the African Economic Community (AEC) and the attainment of the identified integration milestones within the identified timeframes. The disparity between identified objectives and implementation realities requires that Africa should evaluate its chosen approach to integration before embarking upon another project like the Continental Free Trade Area (CFTA) in order not to repeat the failures of the past. Such an evaluation should bring the continent to revisit its current disproportionate emphasis on market integration and pursuit of a trade liberalization agenda in favour of a developmental regionalism approach to integration. A developmental regionalism approach is one that seeks to promote mutually beneficial trade amongst African Union member states while placing an equal amount of emphasis on industrial development and the upgrading of regional value chains that are a prerequisite for transformative industrialization. For the CFTA to succeed, Africa would need to place much emphasis on cooperation on cross border infrastructure investment and development, while continuing its efforts aimed at the harmonisation of standards and related trade facilitation measures. This change of emphasis to adopt a developmental regionalism approach it is argued would yield greater developmental benefits and increase the success prospects of the CFTA.
Governing from the opposition?’: tracing the impact of EFF’s ‘niche populist politics’ on ANC policy shifts
Authors: Batsani-Ncube Innocent
Published: June 2021

In December 2017, South Africa’s ruling party, the ANC, announced that they will adopt expropriation of land without compensation and free higher education for 90% of students. These policy positions had been associated with the radical left-wing EFF party. This article asks whether the EFF influenced the ANC policy shifts and if they did, how? Leveraging Williams (2006)’s theory of peripheral party impact and the process tracing method, the study finds evidence of EFF direct causal contribution on ANC policy shift on land reform and strong grounds for inferring indirect influence of the EFF on ANC policy shift on higher education funding. Data sources included policy documents, manifestos, speeches by ANC and EFF political leaders and parliamentary motions. The study contributes to the literature on peripheral party impact and understanding populism in Africa.
Incentivizing Replication Is Insufficient to Safeguard Default Trust
Authors: Desmond Hugh
Published: June 2021

Philosophers of science and metascientists alike typically model scientists’ behavior as driven by credit maximization. In this article I argue that this modeling assumption cannot account for how scientists have a default level of trust in each other’s assertions. The normative implication of this is that science policy should not focus solely on incentive reform.
All loop structures in supergravity amplitudes on AdS5 × S5 from CFT
Authors: Bissi Agnese , Fardelli Giulia , Georgoudis Alessandro
Published: June 2021

We compute a set of structures which appear in the four-point function of protected operators of dimension two in

N
=
4

super Yang Mills with SU(N) gauge group, at any order in a large N expansion. They are determined only by leading order CFT data. By focusing on a specific limit, we make connection with the dual supergravity amplitude in flat space, where such structures correspond to iterated s-cuts. We make several checks and we conjecture that the same interpretation holds for supergravity amplitudes on AdS5 × S5.
Free vibration analysis of composite conical shells using Walsh series method
Authors: Guo Shibai , Hu Ping , Li Sheng
Published: June 2021

As a typical structure of underwater vehicles, the vibration characteristics of the conical shell are of great significance to the selection of structural design parameters. This paper aims at the free vibration of composite conical shells with general boundary conditions by presenting a simple yet efficient solution based on the Walsh series (WS). The theoretical model is formulated on the basis of the first-order shear deformation shell theory. Elastic boundary conditions are equivalent by introducing weight parameters at boundary positions. The governing differential equation and boundary equation are obtained directly by the Hamilton principle, and decomposed by separating variables. Then Walsh series (WS) is applied for the axial direction and the Fourier series is assumed with respect to the circumferential direction. The unknown constants generated during integration can be determined by boundary conditions, and thus the partial differential equations are transformed into algebraic equations. By solving these algebraic equations, then natural frequencies and mode shapes of the composite conical shells are obtained. Compared with the existing solutions, the accuracy and reliability of the proposed method are verified. The effects of geometric and material parameters on the natural frequencies of composite conical shells are studied.
Effects of Sn addition on dynamic grain growth in a binary Mg-1Ca alloy
Authors: Rashed H M M A , Mesbah M B
Published: June 2021

The possibility of dynamic grain growth of a binary Mg-1Ca alloy with minor tin contents was investigated at various conditions of temperature and strain rate. Mg-1Ca, Mg-1Ca-1Sn and Mg-1Ca-2Sn alloys were cast and homogenized at 410 °C followed by hot-rolling at 400 °C with equal strains. Calcium contributed to refining of grains, with an additional support from tin. In the as-cast alloys, tin was found to promote dendrite formation. Though presence of Ca2Sn phase was predicted by thermodynamic modelling, microstructurally a ternary phase MgCaSn was predominantly found. This ternary phase was also comparatively coarser in size. Uniaxial tensile test of rolled samples was carried out at temperatures 300, 350, 400 and 450 °C, and at two different strain rates 5 × 10−4 s−1 and 1 × 

10

−
4

s

−
1

.

Variation of grain distribution was also measured at the grip and gauge regions at different locations. Samples were taken from six different locations of the deformed samples. Even at faster deformation, the grains were not elongated. At slower strain rate condition, extent of dynamic grain growth was higher compared to that of the higher strain rate condition. Mg2Ca particles were not effective in restricting movement of grain boundaries. Mg2Sn particles were dissolved in the matrix at the elevated temperatures, and the grain growth limiting was profoundly dominated by the presence of MgCaSn phase.
4. Horror and the mind
Authors: Jones Darryl
Published: June 2021

‘Horror and the mind’ looks at ideas of madness and the mind in horror. The lunatic asylum is one of the classic locations of horror, and our fears of insanity, or of the strangeness of our own minds to ourselves, is one of its recurring themes. The ‘double’ refers to the literalizing of ideas of the divided or split self. There are a number of psychos and slashers who have populated horror culture. Why are we obsessed with the figure of the serial killer?
Enduring images
Authors: Slack Paul
Published: June 2021

‘Enduring images’ describes the various images which have been attached to plague. These include graphic metaphors, like the arrows of Apollo and the swords of biblical angels, which symbolize its causes; and literary conventions, such as those of Thucydides and Boccaccio about the disruption of families and societies, which summarize its consequences. Over time, new icons have been added to them, such as plague-saints and plague-doctors, and metaphors were borrowed from other contexts, like the Dance of Death and visions of the Apocalypse. Taken together, they determined how plague was imagined in the past. Ultimately, images of plague have a continuous history, invented and then elaborated over the centuries.
Productive Social Engagement as a Vehicle to Promote Activity and Neuro-Cognitive Health in Later Adulthood
Authors: Carlson Michelle C
Published: June 2021

Objective

We have witnessed two key findings that shift our understanding of human brain aging in new directions. First, we learned that the adult brain remains plastic beyond childhood development, generating new neurons in response to activity and new experiences, particularly in regions that integrate memories in social contexts. The second emerging finding is the importance of physical activity and social engagement to cognitive aging. I integrate these and other empirical findings with our understanding of brain development over the life span and the later-life developmental need to give back to younger generations to posit the importance of maintaining our “social” brain through retirement and into later life when activity remains beneficial to brain health.

Conclusions

Opportunities for improved cognitive and brain health that can be brought to scale need to capitalize on aging adults’ need to remain socially relevant and on community infrastructures so that those with lower neighborhood access to activity can safely engage. Evidence is summarized here from one such community-based model of social engagement through school-based, volunteer service, entitled Experience Corps®. This program seeks to increase daily physical, cognitive, and social activity to promote cognitive and mental health.
Systematic evaluation of transcriptomics-based deconvolution methods and references using thousands of clinical samples
Authors: Nadel Brian B , Oliva Meritxell , Shou Benjamin L , Mitchell Keith , Ma Feiyang , Montoya Dennis J , Mouton Alice , Kim-Hellmuth Sarah , Stranger Barbara E , Pellegrini Matteo , Mangul Serghei
Published: June 2021

Estimating cell type composition of blood and tissue samples is a biological challenge relevant in both laboratory studies and clinical care. In recent years, a number of computational tools have been developed to estimate cell type abundance using gene expression data. Although these tools use a variety of approaches, they all leverage expression profiles from purified cell types to evaluate the cell type composition within samples. In this study, we compare 12 cell type quantification tools and evaluate their performance while using each of 10 separate reference profiles. Specifically, we have run each tool on over 4000 samples with known cell type proportions, spanning both immune and stromal cell types. A total of 12 of these represent in vitro synthetic mixtures and 300 represent in silico synthetic mixtures prepared using single-cell data. A final 3728 clinical samples have been collected from the Framingham cohort, for which cell populations have been quantified using electrical impedance cell counting. When tools are applied to the Framingham dataset, the tool Estimating the Proportions of Immune and Cancer cells (EPIC) produces the highest correlation, whereas Gene Expression Deconvolution Interactive Tool (GEDIT) produces the lowest error. The best tool for other datasets is varied, but CIBERSORT and GEDIT most consistently produce accurate results. We find that optimal reference depends on the tool used, and report suggested references to be used with each tool. Most tools return results within minutes, but on large datasets runtimes for CIBERSORT can exceed hours or even days. We conclude that deconvolution methods are capable of returning high-quality results, but that proper reference selection is critical.
TimeCycle: topology inspired method for the detection of cycling transcripts in circadian time-series data
Authors: Ness-Cohn Elan , Braun Rosemary
Published: June 2021

Motivation

The circadian rhythm drives the oscillatory expression of thousands of genes across all tissues. The recent revolution in high-throughput transcriptomics, coupled with the significant implications of the circadian clock for human health, has sparked an interest in circadian profiling studies to discover genes under circadian control.

Result

We present TimeCycle: a topology-based rhythm detection method designed to identify cycling transcripts. For a given time-series, the method reconstructs the state space using time-delay embedding, a data transformation technique from dynamical systems theory. In the embedded space, Takens’ theorem proves that the dynamics of a rhythmic signal will exhibit circular patterns. The degree of circularity of the embedding is calculated as a persistence score using persistent homology, an algebraic method for discerning the topological features of data. By comparing the persistence scores to a bootstrapped null distribution, cycling genes are identified. Results in both synthetic and biological data highlight TimeCycle’s ability to identify cycling genes across a range of sampling schemes, number of replicates and missing data. Comparison to competing methods highlights their relative strengths, providing guidance as to the optimal choice of cycling detection method.

Availabilityand implementation

A fully documented open-source R package implementing TimeCycle is available at: https://nesscoder.github.io/TimeCycle/.

Supplementary information

Supplementary data are available at Bioinformatics online.
Placebo effect in pharmacological management of fibromyalgia: a meta-analysis
Authors: Migliorini Filippo , Maffulli Nicola , Eschweiler Jörg , Betsch Marcel , Tingart Markus , Colarossi Giorgia
Published: June 2021

Introduction

The management of fibromyalgia involves a combination of pharmacological and non-pharmacological treatments.

Source of data

Recently published literature in PubMed, Google Scholar and Embase databases.

Areas of agreement

Several pharmacological and non-pharmacological strategies have been proposed for the management of fibromyalgia. However, the management of fibromyalgia remains controversial. The administration of placebo has proved to be more effective than no treatment in many clinical settings and evidence supports the ‘therapeutic’ effects of placebo on a wide range of symptoms.

Areas of controversy

The placebo effect is believed to impact the clinical outcomes, but its actual magnitude is controversial.

Growing points

A meta-analysis comparing pharmacological management versus placebo administration for fibromyalgia was conducted.

Areas timely for developing research

Drug treatment resulted to be more effective than placebo administration for the management of fibromyalgia. Nevertheless, placebo showed a beneficial effect in patients with fibromyalgia. Treatment-related adverse events occurred more frequently in the drug treatment.

Level of evidence

I, Bayesian network meta-analysis of double-blind randomized clinical trials.
Seasonal and environmental effects on upper thermal limits of eastern sand darter (Ammocrypta pellucida)
Authors: Firth Britney L , Drake D Andrew R , Power Michael
Published: June 2021

Anthropogenic stressors are predicted to increase water temperature, which can influence physiological, individual, and population processes in fishes. We assessed the critical thermal maximum (CTmax) of eastern sand darter (Ammocrypta pellucida), a small benthic fish listed as threatened under the Species at Risk Act in Canada. Field trials were conducted stream side June–November 2019 in the Grand River, Ontario, to encompass a range of ambient water temperatures (7–25°C) for which agitation temperature (Tag) and CTmax were determined. Additional measures were taken in the comparatively more turbid Thames River to test the effect of turbidity on both measures. In the Grand, Tag and CTmax ranged from 23°C to 33°C and 27°C to 37°C, respectively, and both significantly increased with ambient water temperature, with a high acclimation response ratio (0.49). The thermal safety margin (difference between ambient temperatures and CTmax) was smallest in July and August (~11°C) indicating that eastern sand darter lives closer to its physiological limit in summer. The between-river comparison indicated that turbidity had no significant influence on Tag and CTmax. Comparison of CTmax with in-river temperatures suggested that mean stream temperature 24 hours before the trial was most important for determining CTmax. Fish mass, temperature variance and maximum temperature in the 24-hour period prior to the CTmax trial were also shown to have some effect on determining CTmax. Overall, study results better define the sensitivity of eastern sand darter to temperature changes across the growing season and provide information to assess the availability of suitable thermal habitat for conservation purposes.
Inflammatory Bowel Disease Increases the Risk of Venous Thromboembolism in Children: A Population-Based Matched Cohort Study
Authors: Kuenzig M Ellen , Bitton Alain , Carroll Matthew W , Kaplan Gilaad G , Otley Anthony R , Singh Harminder , Nguyen Geoffrey C , Griffiths Anne M , Stukel Therese A , Targownik Laura E , Jones Jennifer L , Murthy Sanjay K , McCurdy Jeffrey D , Bernstein Charles N , Lix Lisa M , Peña-Sánchez Juan Nicolás , Mack David R , Jacobson Kevan , El-Matary Wael , Dummer Trevor J B , Fung Stephen G , Spruin Sarah , Nugent Zoann , Tanyingoh Divine , Cui Yunsong , Filliter Christopher , Coward Stephanie , Siddiq Shabnaz , Benchimol Eric I
Published: June 2021

Background and Aims

Although venous thromboembolism [VTE] is a well-known complication of inflammatory bowel disease [IBD] in adults, limited data exist on the risk in children. We report the incidence of VTE among children with and without IBD.

Methods

We conducted a matched cohort study within a distributed network of population-based Canadian provincial health administrative databases. Children <16 years diagnosed with IBD were identified using validated algorithms from administrative data in Alberta, Manitoba, Nova Scotia, Ontario and Québec and compared to age- and sex-matched children without IBD. Hospitalizations for VTE within 5 years of IBD diagnosis were identified. Generalized linear mixed-effects models were used to pool province-specific incidence rates and incidence rate ratios [IRR] with 95% confidence intervals [CI]. Hazard ratios [HR] from Cox proportional hazards models were pooled with fixed-effects meta-analysis.

Results

The 5-year incidence of VTE among 3593 children with IBD was 31.2 [95% CI 23.7–41.0] per 10 000 person-years [PY] compared to 0.8 [95% CI 0.4–1.7] per 10 000 PY among 16 289 children without IBD [unadjusted IRR 38.84, 95% CI 16.59–90.83; adjusted HR 22.91, 95% CI 11.50–45.63]. VTE was less common in Crohn’s disease than ulcerative colitis [unadjusted IRR 0.47, 95% CI 0.27–0.83; adjusted HR 0.52, 95% CI 0.29–0.94]. The findings were similar for deep vein thrombosis and pulmonary embolism when comparing children with and without IBD.

Conclusions

The risk of VTE is much higher in children with IBD than controls without IBD. While the absolute risk is low, we found a higher incidence rate than previously described in the pediatric literature.

Conference Presentation: An abstract based on the data included in this paper was presented at Canadian Digestive Diseases Week [Montréal, Canada] in March 2020.
Vitamin D Is Associated with α4β7+ Immunophenotypes and Predicts Vedolizumab Therapy Failure in Patients with Inflammatory Bowel Disease
Authors: Gubatan John , Rubin Samuel J S , Bai Lawrence , Haileselassie Yeneneh , Levitte Steven , Balabanis Tatiana , Patel Akshar , Sharma Arpita , Sinha Sidhartha R , Habtezion Aida
Published: June 2021

Background and Aims

Vitamin D downregulates the in vitro expression of the gut-tropic integrin α4β7 on immune cells. The clinical relevance of this finding in patients with inflammatory bowel disease [IBD] is unclear. We tested the hypothesis that vitamin D is associated with α4β7 immunophenotypes and risk of vedolizumab [anti-α4β7] failure in IBD.

Methods

We performed single-cell immunophenotyping of peripheral and intestinal immune cells using mass cytometry [CyTOF] in vedolizumab-naïve patients with IBD [N = 48]. We analysed whole-genome mucosal gene expression [GSE73661] from GEMINI I and GEMINI long-term safety [LTS] to determine the association between vitamin D receptor [VDR] and integrin alpha-4 [ITGA4] and beta-7 [ITGB7] genes. We estimated the odds of vedolizumab failure with low pre-treatment vitamin D in a combined retrospective and prospective IBD cohort [N = 252] with logistic regression.

Results

Immunophenotyping revealed that higher 25[OH]D was associated with decreased α4β7+ peripheral blood mononuclear cells [R = -0.400, p <0.01] and α4β7+ intestinal leukocytes [R = -0.538, p = 0.03]. Serum 25[OH]D was inversely associated with α4β7+ peripheral B cells and natural killer [NK] cells and α4β7+ intestinal B cells, NK cells, monocytes, and macrophages. Mucosal expression of VDR was inversely associated with ITGA4 and ITGB7 expression. In multivariate analysis, 25[OH]D <25 ng/mL was associated with increased vedolizumab primary non-response during induction (odds ratio [OR] 26.10, 95% confidence interval [CI] 14.30–48.90, p <0.001) and failure at 1-year follow-up [OR 6.10, 95% CI 3.06–12.17, p <0.001].

Conclusions

Low serum 25[OH]D is associated with α4β7+ immunophenotypes and predicts future vedolizumab failure in patients with IBD.

Podcast

This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast
Weekend vs. weekday admission and clinical outcomes in heart failure patients with and without atrial fibrillation in Taiwan
Authors: Hu Wei-Syun , Lin Cheng-Li
Published: June 2021

Aims

We conducted this study to explore the associations of weekend and weekday admission with the clinical events among heart failure (HF) patients with and without comorbid atrial fibrillation (AF).

Methods and results

In this study, we recruited 57 919 HF patients without AF hospitalized on weekends and 57 919 HF patients without AF hospitalized on weekdays. There were 21407 and 21407 HF patients with AF hospitalized on weekends and weekdays, respectively. The outcomes of interest included all-cause mortality, cardiovascular (CV) death, and HF recurrence requiring admission. The Cox proportional hazard regression model was applied to estimate the hazard ratio. Variables found to be statistically significant in a univariable Cox proportional hazard regression model were further examined in a multivariable Cox proportional hazard regression model. The cumulative incidence curves were obtained by the Kaplan–Meier method and assessed by the log-rank test. HF patients with AF and hospitalized on weekends had the highest incidence rates of rehospitalization due to HF (233.8 per 1000 person-years) and CV death (23.9 per 1000 person-years) among four groups. The Kaplan–Meier method shows that HF patients with AF had the higher cumulative incidence of rehospitalization due to HF than the patients without AF.

Conclusion

HF patients with AF and hospitalized on weekends are at highest risk of HF recurrence requiring hospitalization among these four groups.
A novel technique for Endobronchial Watanabe Spigot placement for bronchopleural fistula: a traction method
Authors: Date Naoki , Komatsu Teruya , Fujinaga Takuji
Published: June 2021

Empyema with bronchopleural fistula is a challenging condition that often requires open-window thoracostomy. Bronchial occlusion with Endobronchial Watanabe Spigot is an effective and less invasive procedure to close the fistula; however, delivering a spigot into the target bronchus requires high technical skills. Herein, we report a case of bronchopleural fistula occluded with a spigot using a new ‘traction method’ in which the spigot is tied as an anchor to a guidewire and pulled into the target bronchus. Our method allows selective and steady placement of the spigot for patients who undergo open-window thoracostomy for the treatment of bronchopleural fistula.