bluuebunny/crossref_metadata_2025 huggingface dataset:
AfucosylatedPlasmodium falciparum-specific IgG is induced by infection but not by subunit vaccination
Authors: Larsen Mads Delbo , Lopez-Perez Mary , Dickson Emmanuel Kakra , Ampomah Paulina , Ndam Nicaise Tuikue , Nouta Jan , Koeleman Carolien A M , Ederveen Agnes L Hipgrave , Mordmüller Benjamin , Salanti Ali , Nielsen Morten Agertoug , Massougbodji Achille , van der Schoot C. Ellen , Ofori Michael F. , Wuhrer Manfred , Hviid Lars , Vidarsson Gestur
Published: April 2021

IgG specific for members of thePlasmodium falciparumerythrocyte membrane protein 1(PfEMP1) family, which mediates receptor- and tissue-specific sequestration of infected erythrocytes (IEs), is a central component of naturally acquired malaria immunity. PfEMP1-specific IgG is thought to protect via inhibition of IE sequestration, and through IgG-Fc Receptor (FcγR) mediated phagocytosis and killing of antibody-opsonized IEs. The affinity of afucosylated IgG to FcγRIIIa is elevated up to 40-fold compared to fucosylated IgG, resulting in enhanced antibody-dependent cellular cytotoxicity. Most IgG in plasma is fully fucosylated, but afucosylated IgG is elicited in response to enveloped viruses and to paternal alloantigens during pregnancy. Here we show that naturally acquired PfEMP1-specific IgG is likewise markedly afucosylated in a stable and exposure-dependent manner, and efficiently induces FcγRIIIa-dependent natural killer (NK) cell degranulation. In contrast, immunization with a soluble subunit vaccine based on VAR2CSA-type PfEMP1 resulted in fully fucosylated specific IgG. These results have implications for understanding natural and vaccine-induced antibody-mediated protective immunity to malaria.

Afucosylated IgG has enhanced Fc-receptor affinity and functionality, and is formed specifically against membrane proteins of enveloped viruses. We show that this also applies toPlasmodium falciparumerythrocyte membrane-specific IgG induced by natural infection, but not by soluble PfEMP1 vaccination.
Narrative Event Segmentation in the Cortical Reservoir
Authors: Dominey Peter Ford
Published: April 2021

During continuous perception of movies or stories, awake humans display cortical activity patterns that reveal hierarchical segmentation of event structure. Sensory areas like auditory cortex display high frequency segmentation related to the stimulus, while semantic areas like posterior middle cortex display a lower frequency segmentation related to transitions between events (Baldassano et al. 2017). These hierarchical levels of segmentation are associated with different time constants for processing. Chien and Honey (2020) observed that when two groups of participants heard the same sentence in a narrative, preceded by different contexts, neural responses for the groups were initially different and then gradually aligned. The time constant for alignment followed the segmentation hierarchy: sensory cortices aligned most quickly, followed by mid-level regions, while some higher-order cortical regions took more than 10 seconds to align. These hierarchical segmentation phenomena can be considered in the context of processing related to comprehension. Uchida et al. (2021) recently described a model of discourse comprehension where word meanings are modeled by a language model pre-trained on a billion word corpus (Yamada et al 2020). During discourse comprehension, word meanings are continuously integrated in a recurrent cortical network. The model demonstrates novel discourse and inference processing, in part because of two fundamental characteristics: real-world event semantics are represented in the word embeddings, and these are integrated in a reservoir network which has an inherent gradient of functional time constants due to the recurrent connections. Here we demonstrate how this model displays hierarchical narrative event segmentation properties. The reservoir produces activation patterns that are segmented by the HMM of Baldassano et al (2017) in a manner that is comparable to that of humans. Context construction displays a continuum of time constants across reservoir neuron subset, while context forgetting has a fixed time constant across these subsets. Virtual areas formed by subgroups of reservoir neurons with faster time constants segmented with shorter events, while those with longer time constants preferred longer events. This neurocomputational recurrent neural network simulates narrative event processing as revealed by the fMRI event segmentation algorithm of Baldassano et al (2017), and provides a novel explanation of the asymmetry in narrative forgetting and construction observed by Chien and Honey (2020). The model extends the characterization of online integration processes in discourse to more extended narrative, and demonstrates how reservoir computing provides a useful model of cortical processing of narrative structure.
A gene duplication of a septin provides a developmentally-regulated filament length control mechanism
Authors: Cannon Kevin S. , Vargas-Muniz Jose M. , Billington Neil , Seim Ian , Ekena Joanne , Sellers James , Philippsen Peter , Gladfelter Amy. S.
Published: April 2021

Septins are a family of conserved filament-forming proteins that function in a variety of processes including cell cycle progression, cell morphogenesis and autophagy. Despite their conservation from yeast to humans, the number of septin genes within an organism varies and higher eukaryotes express many septin isoforms due to alternative splicing. It is unclear how variability in septin complex composition influences the biophysical properties of septin polymers. Here we report that a complex duplication event within theCDC11locus in the fungus,Ashbya gossypii, gave rise to two similar, but distinct Cdc11 proteins, Cdc11a and Cdc1b.CDC11btranscription is developmentally regulated producing different ratios of Cdc11a and b complexes duringAshbya’slifecycle. Moreover, deletion of eitherCDC11aorCDC11bresults in distinct cell polarity defects. Remarkably, despite substantial identity in amino acid sequence, Cdc11a and Cdc11b complexes have distinct biophysical properties with clear filament length and membrane-binding ability differences. Thus, septin subunit composition has functional consequences for filament properties and such functional plasticity can be exploited for distinct biophysical properties and cell functions.
CONET: Copy number event tree model of evolutionary tumor history for single-cell data
Authors: Markowska Magda , Cąkała Tomasz , Miasojedow Błażej , Juraeva Dilafruz , Mazur Johanna , Ross Edith , Staub Eike , Szczurek Ewa
Published: April 2021

Copy number alterations constitute important phenomena in tumor evolution. Whole genome single cell sequencing gives insight into copy number profiles of individual cells, but is highly noisy. Here, we propose CONET, a probabilistic model for joint inference of the evolutionary tree on copy number events and copy number calling. CONET employs an efficient MCMC procedure to search the space of possible model structures and parameters and utilizes both per-bin and per-breakpoint data. We introduce a range of model priors and penalties for efficient regularization. CONET achieves excellent performance on simulated data and for 260 cells from xenograft breast cancer sample.
The cannabinoid agonist CB-13 produces peripherally mediated analgesia in mice but elicits tolerance and signs of CNS activity with repeated dosing
Authors: Slivicki Richard A. , Yi Jiwon , Brings Victoria E. , Huynh Phuong Nhu , Gereau Robert W.
Published: April 2021

Activation of cannabinoid receptor type 1 (CB1) produces analgesia in a variety of preclinical models of pain; however, engagement of central CB1receptors is accompanied by unwanted side effects, such as tolerance and dependence. Efforts to develop novel analgesics have focused on targeting peripheral CB1receptors to circumvent central CB1-related side effects. In the present study, we evaluated the effects of acute and repeated dosing with the peripherally selective CB1-preferring agonist CB-13 on nociception and central CB1-related phenotypes in an inflammatory model of pain in mice. We also evaluated cellular mechanisms underlying CB-13-induced antinociceptionin vitrousing cultured mouse dorsal root ganglion (DRG) neurons. CB-13 reduced inflammation-induced mechanical allodynia in a peripheral CB1receptor-dependent manner and relieved inflammatory thermal hyperalgesia. In cultured mouse DRG neurons, CB-13 reduced TRPV1 sensitization and neuronal hyperexcitability induced by the inflammatory mediator prostaglandin E2, providing potential mechanistic explanations for the analgesic actions of peripheral CB1receptor activation. With acute dosing, phenotypes associated with central CB1receptor activation occurred only at a dose of CB-13 approximately 10-fold the ED50for reducing allodynia. Strikingly, repeated dosing resulted in both analgesic tolerance and CB1receptor dependence, even at a dose that did not produce central CB1receptor-mediated phenotypes on acute dosing. This suggests repeated CB-13 dosing leads to increased CNS exposure and unwanted engagement of central CB1receptors. Thus, caution is warranted regarding therapeutic use of CB-13 with the goal of avoiding CNS side effects. Nonetheless, the clear analgesic effect of acute peripheral CB1receptor activation suggests that peripherally restricted cannabinoids are a viable target for novel analgesic development.
Spatially coordinated heterochromatinization of distal short tandem repeats in fragile X syndrome
Authors: Zhou Linda , Ge Chunmin , Malachowski Thomas , Kim Ji Hun , Chandradoss Keerthivasan Raanin , Su Chuanbin , Wu Hao , Rojas Alejandro , Wallace Owen , Titus Katelyn R. , Gong Wanfeng , Phillips-Cremins Jennifer E.
Published: April 2021

Short tandem repeat (STR) instability is causally linked to pathologic transcriptional silencing in a subset of repeat expansion disorders. In fragile X syndrome (FXS), instability of a single CGG STR tract is thought to repressFMR1via local DNA methylation. Here, we report the acquisition of more than ten Megabase-sized H3K9me3 domains in FXS, including a 5-8 Megabase block aroundFMR1. Distal H3K9me3 domains encompass synaptic genes with STR instability, and spatially co-localize in trans concurrently withFMR1CGG expansion and the dissolution of TADs. CRISPR engineering of mutation-lengthFMR1CGG to normal-length preserves heterochromatin, whereas cut-out to pre-mutation-length attenuates a subset of H3K9me3 domains. Overexpression of a pre-mutation-length CGG de-represses bothFMR1and distal heterochromatinized genes, indicating that long-range H3K9me3-mediated silencing is exquisitely sensitive to STR length. Together, our data uncover a genome-wide surveillance mechanism by which STR tracts spatially communicate over vast distances to heterochromatinize the pathologically unstable genome in FXS.

One-Sentence Summary

Heterochromatinization of distal synaptic genes with repeat instability in fragile X is reversible by overexpression of a pre-mutation length CGG tract.
Translation of cellular protein localization by generative adversarial network
Authors: Shigene Kei , Hiasa Yuta , Otake Yoshito , Soufi Mazen , Janewanthanakul Suphamon , Nishimura Tamako , Sato Yoshinobu , Suetsugu Shiro
Published: April 2021

The protein localization in cells had been analyzed by the fluorescent labeling by indirect immunofluorescence and fluorescent protein tagging. However, the relationships between the localizations between different proteins had not been analyzed by artificial intelligence. In this study, we applied the generative adversarial network (GAN) to generate the protein localizations each other, in which the generation was dependent on the types of cells and the relationships between the proteins. Lamellipodia are one of the actin-dependent subcellular structures involved in cell migration and are mainly generated by the Wiskott-Aldrich syndrome protein (WASP)-family verprolin homologous protein 2 (WAVE2) and the membrane remodeling I-BAR domain protein IRSp53. Focal adhesions are another actin-based structure that contains vinculin protein and are essential for cell migration. In contrast, microtubules are not thought to be directly related to actin filaments. The GAN was trained using images of actin filaments paired with WAVE2, vinculin, IRSp53, and microtubules. Then, the generated images of WAVE2, vinculin, and IRSp53 by the GAN showed high similarity to the real images of WAVE2, vinculin, and IRSp53, respectively. However, the microtubule images generated from actin filament images were inferior, corroborating that the microscopic images of actin filaments provide more information about actin-related protein localization. Collectively, this study suggests that the image translation by the GAN can predict the localization of functionally related proteins.
Dermoscopic features of nail psoriasis: Positive correlation with the severity of psoriasis
Authors: Long FangYuan , Zhang ZhiQin , He Fang , Tu Jie , Yin Zhi , Xia JiPing , Lu Yan , Yin ZhiQiang
Published: April 2021

Dermoscopy is an efficient and non‐invasive technique which has been widely used in the diagnosis of nail disorders including nail psoriasis (NP). Many nail dermoscopic features are considered as clues to NP. The aim of this study was to investigate specific dermoscopic features of fingernail psoriasis and the correlation between the severity of nail lesions or systemic inflammation, and psoriasis severity of skin and nail. This observational study recruited 135 patients with fingernail psoriasis (1186 fingernails) and 30 patients with onychomycosis (80 fingernails). All of the involved fingernails were examined with a handheld dermatoscope. The Nail Psoriasis Severity Index score (NAPSI) score, Psoriasis Area and Severity Index (PASI) score, body surface area (BSA), and detailed history of patients with psoriasis were recorded. Mann–WhitneyU‐test, χ2‐test, Spearman’s correlation, and Kruskal–Wallis H‐test were used for statistical analysis, and the significance threshold wasp < 0.05. The trial registration number was 2020‐SR‐045. We identified onycholysis as the most common feature (93.3%) of fingernail psoriasis. Red lunula, longitudinal fissures, transverse grooves, nail plate crumbling, trachyonychia, oil‐dropping sign, erythematous border of an onycholytic area, subungual hyperkeratosis, and dilated streaky capillaries were relevant to NP severity (p < 0.05). Red lunula, transverse grooves, nail plate crumbling, trachyonychia, oil‐dropping sign, erythematous border of an onycholytic area, splinter hemorrhages, and dilated streaky capillaries were relevant to systemic inflammation severity (p < 0.05). The total NAPSI score was positively associated with the PASI score and BSA (p < 0.0001). The thumb had a higher NAPSI score than the other fingers (p < 0.05). In conclusion, dermoscopic features can improve the accuracy of diagnosis of nail psoriasis, and have correlations with psoriasis severity.
Unpacking the politics of legislative debates
Authors: FERNANDES JORGE M. , DEBUS MARC , BÄCK HANNA
Published: April 2021

Legislative debates are a thriving field in comparative politics. They make representation work by offering legislators the opportunity to take the floor and represent their constituents. In this paper, we review the key theoretical concepts and empirical findings in a maturing field. We begin by addressing what legislative debates are and why we should study them to learn about inter‐ and intra‐party politics. Next, we look at the contributions springing from Proksch and Slapin's ground‐breaking model. In so doing, our review suggests that recent work extends the original model to include further dimensions of legislative debates. Third, we examine the role of legislative debates as mechanisms of representation, focusing on gender. Four, we examine the challenges of the comparative analysis of legislative debates. Finally, we map the road ahead by discussing four avenues of future research and some key questions that remain unanswered.
Palatability and profitability of co‐occurring seeds alter indirect interactions among rodent‐dispersed trees
Authors: XIAO Zhishu , HOLYOAK Marcel , KREBS Charles J. , HUANG Xiaoqun
Published: April 2021

Beyond direct species interactions, seed dispersal is potentially affected by indirect seed–seed interactions among co‐occurring nut‐bearing trees which are mediated by scatter‐hoarding animals as shared seed dispersers. A relevant question in such systems is to what extent different functional traits related to food palatability and profitability affect the kinds of indirect interactions that occur among co‐occurring seeds, and the consequences for seed dispersal. We used field experiments to track seed dispersal with individually tagged seeds in both monospecific and mixed seed communities. We measured indirect effects based on 3 seed–seed species pairs from the family Fagaceae with contrasting seed size, tannin level, and dormancy in a subtropical forest in Southwest China. When all else was equal, the presence of adjacently placed seeds with contrasting seed traits created different indirect effects measured through a variety of dispersal‐related indicators. Apparent mutualism was reciprocal due to increasing seed dispersal in mixed seed patches with mixed differences in seed tannins and dormancy. However, differences in either seed size or dormancy in co‐occurring adjacently placed seeds caused apparent competition with reduced seed removal or seed dispersal (distance) in at least one species. Our study supports the hypothesis that different functional traits related to food palatability and profitability in co‐occurring seeds modify foraging decisions of scatter‐hoarding animals, and subsequently cause indirect effects on seed dispersal among rodent‐dispersed trees. We conclude that such indirect effects mediated by shared seed dispersers may act as an important determinant of seed dispersal for co‐fruiting animal‐dispersed trees in many natural forests.
Commentary: ‘Profitability’, Curated Narratives and Spatial Governance and their Impacts on Urban Migration and the Lives of Migrants
Authors: Aubrey Dyfed
Published: April 2021

This commentary reviews ‘The ‘Badlands’ of the ‘Balkan Route’: policy and spatial effects on urban refugee housing’, by Gemma Bird, Jelena Obradovic‐Wochnik, Amanda Beattie and Patrycja Rozbicka; ‘Walking in Jozi: Guided Tours, Insecurity and Urban Regeneration in Inner City Johannesburg’ by Lena Opfermann, and ‘Curating (im)mobility: Peri‐urban agency in the Lwandle Migrant Labour Museum’ by Stefanie Kappler, and explores common threads running through the three articles, namely ‘profitability’, curated narratives and spatial governance, and their impact on ‘othering’ migrants and entrenching inequality.
Unraveling Spaces of Exceptions through Durable Solutions
Authors: Del Ministro Teresa
Published: April 2021

This commentary offers a review of the article by Dr. Jutta Bakonyi “The Political Economy of Displacement: Rent Seeking, Dispossessions and Precarious Mobility in Somali Cities” (Global Policy 2020). It adds to the questions investigated by Dr. Bakonyi on spaces of exception, informal governance, accountability and how they play out in the political economy of informal settlements, and in relation to precarious land tenure and land dispossessions experienced by persons in a situation of displacement. The commentary presents a practitioner’s analysis and a short overview of the recent work conducted by durable solutions partners in Somalia to transform exclusionary dynamics into more inclusive processes, benefitting displacement affected communities.
Inequality and the Socioeconomic Dimensions of Mobility in Protests: The Cases of Quito and Santiago
Authors: Díaz Pabón Fabio Andrés , Palacio Ludeña María Gabriela
Published: April 2021

Mobility is a multifaceted concept with social, economic and political implications. This article reflects on the role of mobility and its relation to precarity in the emergence of protests in both Quito (Ecuador) and Santiago (Chile) in 2019 by examining the interplay between mobility and inequality. It argues that the announced increases in transport and fuel costs in Chile and Ecuador exposed obstacles to spatial and social mobility and existing inequalities. Although the protests arose in response to the announced reduction in fuel subsidies and possible increases in transport costs, we propose that they reflect a deeper issue, relating to the vulnerability of the livelihoods of significant segments of the population, despite the fact that both Quito and Santiago have seen improvements in several poverty and inequality indicators in recent years. We discuss how mobility and geography relate to patterns of structural marginalisation that are not necessarily evident from aggregate economic indicators, and how understanding inequality in terms of the ‘right to the city’ and access to public services explain the protests in both countries as a response to existing segregation and deep‐seated inequalities.
Precarity, Mobility and the City: Introduction to the Special Issue
Authors: Bakonyi Jutta , Kappler Stefanie , Nag Eva‐Maria , Opfermann Lena S.
Published: April 2021

Drawing on empirically rich and theoretically grounded case studies, the articles in this issue explore ways in which global governmental processes affect mobility and, similarly, how seemingly local movements impact upon global processes.
An Experimental Method in Juxtaposing Draft Picks and Active Players
Authors: Chandrakumaran Jemuel
Published: April 2021

Trading picks are a common transaction that is observed in sporting leagues that conduct player drafts. However, with its evolution, current iterations allow for the trading of picks and players, which in turn raises questions about valuing such trades. This study proposes a pick valuation system using survival analysis techniques, which was further extended to value players who were already enlisted. The model proved to be viable, allowing to evaluate trades involving both picks and players.
The Impact of Risk and the Potential for Loss on Managers' Demand for Audit Quality*
Authors: Hurley Patrick J. , Mayhew Brian W. , Obermire Kara M. , Tegeler Amy C.
Published: April 2021

This study uses experimental economic markets to investigate the impact of risk and the potential for loss on managers' demand for audit quality. We posit that these two important contextual factors influence managers' audit quality preferences. We study these factors because they are ubiquitous to companies, and we focus on their influence on managers because managers continue to play a significant role in the auditor hiring process and we know relatively little about their auditor preferences. We predict that risk, the potential for loss, and their interaction will each decrease manager demand for high audit quality due to a desire to achieve greater reporting flexibility. Experimental results are consistent with our predictions; specifically, increased risk, the potential for loss, and to a lesser extent their interaction, significantly reduce managers' likelihood of hiring the best available auditor in the market. Path analysis indicates that this reduction in audit quality demand leads to increases in misreporting. Finally, we observe investors overpaying for assets to a greater extent when managers hire lower‐quality auditors. Our results show that the contextual factors of risk and the potential for loss, which are ubiquitous to companies, can reduce demand for audit quality, which can increase misreporting behavior and ultimately harm investors.
Positive Spillovers from Negative Campaigning
Authors: Galasso Vincenzo , Nannicini Tommaso , Nunnari Salvatore
Published: April 2021

Negative advertising is frequent in electoral campaigns, despite its ambiguous effectiveness: Negativity may reduce voters' evaluation of the targeted politician but may have a backlash effect for the attacker. We study the effect of negative advertising in electoral races with more than two candidates with a large‐scale field experiment during an electoral campaign for mayor in Italy and a survey experiment in a fictitious mayoral campaign. In our field experiment, we find a strong, positive spillover effect on the third main candidate (neither the target nor the attacker). This effect is confirmed in our survey experiment, which creates a controlled environment with no ideological components or strategic voting. The negative ad has no impact on the targeted incumbent, has a sizable backlash effect on the attacker, and largely benefits the idle candidate. The attacker is perceived as less cooperative, less likely to lead a successful government, and more ideologically extreme.
A mathematical model to identify optimal combinations of drug targets for dupilumab poor responders in atopic dermatitis
Authors: Miyano Takuya , Irvine Alan D. , Tanaka Reiko J.
Published: April 2021

Background

Several biologics for atopic dermatitis (AD) have demonstrated good efficacy in clinical trials, but with a substantial proportion of patients being identified as poor responders. This study aims to understand the pathophysiological backgrounds of patient variability in drug response, especially for dupilumab, and to identify promising drug targets in dupilumab poor responders.

Methods

We conducted model‐based meta‐analysis of recent clinical trials of AD biologics and developed a mathematical model that reproduces reported clinical efficacies for nine biological drugs (dupilumab, lebrikizumab, tralokinumab, secukinumab, fezakinumab, nemolizumab, tezepelumab, GBR 830, and recombinant interferon‐gamma) by describing system‐level AD pathogenesis. Using this model, we simulated the clinical efficacy of hypothetical therapies on virtual patients.

Results

Our model reproduced reported time courses of %improved EASI and EASI‐75 of the nine drugs. The global sensitivity analysis and model simulation indicated the baseline level of IL‐13 could stratify dupilumab good responders. Model simulation on the efficacies of hypothetical therapies revealed that simultaneous inhibition of IL‐13 and IL‐22 was effective, whereas application of the nine biologic drugs was ineffective, for dupilumab poor responders (EASI‐75 at 24 weeks: 21.6% vs. max. 1.9%).

Conclusion

Our model identified IL‐13 as a potential predictive biomarker to stratify dupilumab good responders, and simultaneous inhibition of IL‐13 and IL‐22 as a promising drug therapy for dupilumab poor responders. This model will serve as a computational platform for model‐informed drug development for precision medicine, as it allows evaluation of the effects of new potential drug targets and the mechanisms behind patient variability in drug response.
A1 and A2A adenosine receptors play a protective role to reduce prevalence of autoimmunity following tissue damage
Authors: Riff Reut , Naamani Oshri , Mazar Julia , Haviv Yosef S , Chaimovitz Cidio , Douvdevani Amos
Published: April 2021

Adenosine is a potent modulator that has a tremendous effect on the immune system. Adenosine affects T cell activity, and is necessary in maintaining the T helper/regulatory T cell (Treg) ratio. Adenosine signalling is also involved in activating neutrophils and the formation of neutrophil extracellular traps (NETs), which has been linked to autoimmune disorders. Therefore, adenosine, through its receptors, is extremely important in maintaining homeostasis and involved in the development of autoimmune diseases. In this study, we aim to evaluate the role of adenosine A1 and A2A receptors in involvement of autoimmune diseases. We studied adenosine regulation by NETosis in vitro, and used two murine models of autoimmune diseases: type I diabetes mellitus (T1DM) induced by low-dose streptozotocin and pristane-induced systemic lupus erythematosus (SLE). We have found that A1R enhances and A2AR suppresses NETosis. In addition, in both models, A1R-knock-out (KO) mice were predisposed to the development of autoimmunity. In the SLE model in wild-type (WT) mice we observed a decline of A1R mRNA levels 6 h after pristane injection that was parallel to lymphocyte reduction. Following pristane, 43% of A1R-KO mice suffered from lupus-like disease while WT mice remained without any sign of disease at 36 weeks. In WT mice, at 10 days A2AR mRNA levels were significantly higher compared to A1R-KO mice. Similar to SLE, in the T1DM model the presence of A1R and A2AR was protective. Our data suggest that, in autoimmune diseases, the acute elimination of lymphocytes and reduction of DNA release due to NETosis depends upon A1R desensitization and long-term suppression of A2AR.
Optimization of indocyanine green angiography for colon perfusion during laparoscopic colorectal surgery
Authors: Ahn Hong‐min , Son Gyung Mo , Lee In Young , Park Sang‐Ho , Kim Nam Su , Baek Kwang‐Ryul
Published: April 2021

Aim

This study aims to evaluate the extrinsic effects of conditional factors affecting quantitative parameters and to establish the optimization of indocyanine green (ICG) angiography using in vitro experiments and a prospective observational study.

Method

In vitro experiments were performed to evaluate the correlation between conditional factors such as camera distance, surrounding lighting, fluorescence emission sources and ICG doses. The fluorescence intensity was measured from the ICG‐containing test tube in each condition. In the clinical study, ICG angiography was applied to patients with colorectal cancer (n = 164). The quantitative perfusion parameters were the maximal fluorescence intensity (FMAX), slope, T1/2MAX and perfusion time ratio (TR). Camera position, distance to colon, fluorescence emission source, surrounding lighting, site of angiography and ICG specific mode were considered as conditional factors and compared with the quantitative parameters to identify the optimal condition of ICG angiography.

Results

The fluorescence intensity had an inverse correlation with distance, and the transitional zone was shown at a distance of 4–5 cm by slope differential. FMAX, T1/2MAX and slope were affected significantly by camera distance, site of angiography, fluorescence emission source and ICG mode as conditional factors. On multivariate analysis, FMAX was independently associated with spectral ICG mode with red inversion, laser mode and camera distance. Conversely, TR was not related to any conditional factors.

Conclusion

Since quantitative parameters of ICG angiography are influenced by various conditions, a standardized protocol is required. The application of ICG specific modes with a constant distance of 4–5 cm can provide optimized fluorescence images.
Regulation of tissue regeneration by the circadian clock
Authors: Ruby Christina L. , Major Robert J. , Hinrichsen Robert D.
Published: April 2021

Circadian rhythms are regulated by a highly conserved transcriptional/translational feedback loop that maintains approximately 24‐hr periodicity from cellular to organismal levels. Much research effort is being devoted to understanding how the outputs of the master clock affect peripheral oscillators, and in turn, numerous biological processes. Recent studies have revealed roles for circadian timing in the regulation of numerous cellular behaviours in support of complex tissue regeneration. One such role involves the interaction between the circadian clockwork and the cell cycle. The molecular mechanisms that control the cell cycle create a system of regulation that allows for high fidelity DNA synthesis, mitosis and apoptosis. In recent years, it has become clear that clock gene products are required for proper DNA synthesis and cell cycle progression, and conversely, elements of the cell cycle cascade feedback to influence molecular circadian timing mechanisms. It is through this crosstalk that the circadian system orchestrates stem cell proliferation, niche exit and control of the signalling pathways that govern differentiation and self‐renewal. In this review, we discuss the evidence for circadian control of tissue homeostasis and repair and suggest new avenues for research.
Predicted climate‐induced reductions in scavenging in eastern North America
Authors: Marneweck Courtney J. , Katzner Todd E. , Jachowski David S.
Published: April 2021

Scavenging is an important function within ecosystems where scavengers remove organic matter, reduce disease, stabilize food webs, and generally make ecosystems more resilient to environmental changes. Global change (i.e., changing climate and increasing human impact) is currently influencing scavenger communities. Thus, understanding what promotes species richness in scavenger communities can help prioritize management actions. Using a long‐term dataset from camera traps deployed with animal carcasses as bait along a 1881 km latitudinal gradient in the Appalachian Mountains of eastern USA, we investigated the relative impact of climate and humans on the species richness and diversity of vertebrate scavengers. Our most supported models for both mammalian and avian scavengers included climatic, but not human, variables. The richness of mammalian and avian scavengers detected was highest during relatively warm (5–10°C) and dry (100–150 mm precipitation) winters, when food was likely limited and both reliance on and detection of carrion was high. The diversity of mammalian and avian scavengers detected was highest under drier conditions. We then used these results to project the future species richness of scavengers that would be detected within our sampling area and under the climate scenario of 2070 (emissions level RCP8.5). Our predictions suggest up to 80% and 67% reductions, respectively, in the richness of avian and mammalian scavengers that would be detected at baited sites. Climate‐induced shifts in behavior (i.e., reduction in scavenging, even if present) at this scale could have cascading implications for ecosystem function, resilience, and human health. Further, our study highlights the importance of conducting studies of scavenger community dynamics within ecosystems across wide spatial gradients within temperate environments. More broadly, these findings build upon our understanding of the impacts of climate‐induced adjustments in behavior that can likely have negative impacts on systems at a large scale.
Syndemic in a pandemic: An autoethnography of a COVID survivor
Authors: Wasdani Kishinchand Poornima
Published: April 2021

This paper provides my personal experience as a COVID‐19 survivor during and postrecovery periods. The stigma that my children and I underwent exposed us to the fragility of a social system that we struggle with all through our life to remain a part of. My story revealed a strong symbiotic relationship between the disease (COVID‐19) and the patient's low acceptance in society, primarily attributed to misinformation and xenophobia around the COVID‐19. This autoethnography speaks for several other COVID survivors who met with the same fate of being discriminated against and stigmatized. As a COVID patient and survivor, the traumatic experience was creating a fear psychosis in me, the effect of which I presume will stay beyond COVID‐19. This condition of a syndemic seems to linger and negatively affect my outlook toward society. If COVID survivors develop a syndemic condition in a pandemic situation, it will require significant efforts to reserve it or sometimes even become irreversible.
Management of patients receiving novel antithrombotic treatment in endodontic practice: Review and clinical recommendations
Authors: Lin Shaul , Hoffman Ron , Nabriski Omri , Moreinos Daniel , Dummer Paul M. H.
Published: April 2021

Cardiovascular diseases are a major component of non‐communicable diseases and death, with thrombosis constituting the most common underlying pathosis of the three major cardiovascular disorders: ischaemic heart disease (acute coronary syndrome), stroke and venous thromboembolism (VTE). The introduction of direct oral anticoagulants (DOACs) in recent years has necessitated a more complex approach to periprocedural and perioperative anticoagulation management and the need for revised management strategies and protocols. Currently, patients taking classic oral anticoagulants are advised to stop taking the drugs and have their INR values checked 72 h prior to dental surgery (e.g., apical surgery, tooth extraction, and periodontal surgery) and checked again 24 h prior to the procedure to ensure it is within the therapeutic range. However, the current incorporation of these novel DOACs in routine medical practice requires changes in the way patients are managed preoperatively in dentistry, and specifically in endodontic surgery. The methodology applied in this review included searching for relevant articles in the PubMed database using keywords listed in the Entree Terms databases. Articles published on human blood clotting mechanism, antithrombotic drugs, as well as treatment guidelines and recommendations for dentistry were retrieved. In addition, textbooks and guidelines that may not have surfaced in the online search were searched manually. The aim of this paper was to review the mechanisms of action of classic and novel antithrombotic medications and their impact on endodontic treatment and the management of local haemostasis in endodontics.
Reliability and validity of the Turkish version of the Barriers to Nurses' Use of Physical Assessment scale
Authors: Turan Nuray , Özsaban Aysel , Aydın Gülsün Özdemir , Türkoğlu Meryem , Kaya Hatice , Acaroğlu Rengin
Published: April 2021

Aim

This study aimed to translate the Barriers to Nurses' Use of Physical Assessment Scale into Turkish and assess the new version's validity and reliability.

Methods

This was a methodological study to verify the linguistic equivalence of the scale through the translation/back‐translation method. Twelve experts in health assessment confirmed the scale's content validity. Along with the Barriers to Nurses' Use of Physical Assessment Scale, an information form, including socio‐demographic features, was distributed to 380 nurses, who consented to participate in the research. Data were collected between July 2017 and April 2018. Internal consistency, factor analysis and test–retest reliability were used to determine consistency over time and intraclass correlations.

Results

The content validity index of the scale (0.963) was calculated following confirmation of its language equivalence. With the confirmatory factor analysis, it was determined that the fit index values were at an acceptable level and the model was suitable. The factor analysis clustered factors in seven domains. The overall internal consistency coefficient was 0.822. All subscales and the overall scale showed high intraclass correlations.

Conclusion

The Turkish version of the Barriers to Nurses' Use of Physical Assessment Scale is a valid and reliable instrument.
Factors affecting frontline Korean nurses’ mental health during the COVID‐19 pandemic
Authors: Cho Mijung , Kim Oksoo , Pang Yanghee , Kim Bohye , Jeong Hyunseon , Lee Jisun , Jung Heeja , Jeong Sun Young , Park Hyun‐Young , Choi Hansol , Dan Hyunju
Published: April 2021

Aim

To identify the factors affecting fear, anxiety and depressive symptoms among frontline nurses working with COVID‐19 patients or are in charge of COVID‐19 screening in Korea.

Background

Nurses are at a higher risk of COVID‐19 infection because they are in closer, longer‐duration contact with patients. These situations can negatively affect the mental health of nurses.

Methods

This study analysed data from COVID‐19 module in the Korean Nurses’ Health Study. Data from 906 participants were analysed. To identify the factors influencing mental health, descriptive statistics, Pearson’s correlation and hierarchical multiple regression analyses were performed.

Results

Caring for patients who are COVID‐19‐positive increased levels of fear, anxiety and depressive symptoms of nurses. The hospital safety climate influenced mental well‐being among nurses.

Conclusion

Caring for patients with COVID‐19 had a negative impact on fear, anxiety and depressive symptoms. However, the higher was the perceived hospital safety climate, the lower were the nurses’ psychological symptoms. Further research on the mental health of nurses is warranted.

Implications for nursing and health policy

Institutions should manage human resources to enable periodic rotation of nurses’ work and working periods related to COVID‐19. In addition, hospital managers should provide sufficient personal protective equipment, related education, and safety climate.
Differences in indentation and wear behaviors between the two sides of thermally tempered soda lime silica glass
Authors: He Hongtu , Liu Hongshen , Lin Yen‐Ting , Qu Conghang , Yu Jiaxin , Kim Seong H.
Published: April 2021

Thermal tempering is an industrial process widely used to make soda lime silica (SLS) glass panels stronger and tougher. During the tempering process, the upper and bottom sides of the glass may experience different cooling rates, and thus, their properties could be different. This study characterized changes in surface composition and subsurface glass network structures as well as indentation and wear resistance properties of the air‐ and tin‐sides of 6‐mm‐thick SLS window panels faced toward the upper and sliding roller sides during thermal tempering. The results showed that although the chemical and structural differences detected with X‐ray photoelectron spectroscopy and specular reflection infrared spectroscopy are subtle, there are large differences in nanoindentation behaviors and mechanochemical wear properties of the SLS glass surface. The findings of this study provide further insights into the performance difference between the air‐ and tin‐sides of the SLS glass panel treated with thermal tempering.
Mechanism study of the Mn‐substituted magnesium borate: Decreased sintering temperature and improved dielectric property
Authors: Peng Rui , Lu Yongcheng , Li Yuanxun , Su Hua , Shi Liang , Yu Guoliang , Lai Yuanming , Zhao Qiang , Shi Xiaolei , Zhang Huaiwu
Published: April 2021

The influence of manganese substitution on the sintering and dielectric properties of Mg3B2O6 (MBO) was studied, and the detailed mechanism of variation was discussed using density functional theory calculations. The characterization method involved a network analyser, differential–thermal analyses, thermomechanical analyses, X‐ray diffraction, and scanning electron microscopy. Manganese substitution formed a two‐phase system (MBO and Mg2B2O5), improved the dielectric property, densified the microstructure, lowered the activation energy, decreased the crystallite size, modified the band structure property, and strengthened the covalency of MgO6 octahedron. The 7% mole substitution of manganese to magnesium improved the dielectric properties of MBO to 7.06 for εr and 61 100 GHz at 15 GHz for Q × f, −54.8 ppm/°C for τf. The intrinsic densification temperature decreased from 1350 to 1175°C with 97.7% relative density.
Risk Capital: Theory and Applications
Authors: Erel Isil , Myers Stewart C. , Read James A.
Published: April 2021

After a brief review of the current theory and practice of risk capital by financial firms, the authors define the concept of risk capital and identify the costs and benefits of using more or less of it. Next, they present their procedure for allocating risk capital to assets and lines of business on the basis of marginal default values, and in a way designed to prevent risk shifting and internal arbitrage. Then, they show how allocations of risk capital are likely to be affected by, and in turn influence, a financial firm's decisions about both the scale and composition of its portfolio of businesses. Finally, the authors present a number of applications and consider their implications for maximizing the value of financial firms.

In so doing, the authors also show how their method produces very different allocations of risk capital than those based on two measures that have long been widely used by financial firms: value at risk (VaR) and risk‐adjusted return on capital (RAROC). Moreover, the adjusted present value (APV) rule for evaluating investment opportunities is shown to be workable for nonfinancial as well as financial firms.
A Practitioners’ Guide to Leverage through Downturns
Authors: Ruben Joshua
Published: April 2021

There is extensive research addressing questions of optimal capital structure. Studies typically focus on estimating the appropriate level of debt and the factors associated with financial leverage. This paper addresses a slightly different question: how does a company's choice of leverage affect its performance through an economic downturn and ensuing recovery?

This is precisely the question many companies were asking in 2019 when this paper was written, over a decade after the last recession. Corporate managers are increasingly trying to incorporate the possibility of a downturn in capital structure decisions today.

The author summarizes the findings of his analysis of the relative performance of three large‐cap portfolios constructed on the basis of leverage: high, medium, and low. It focuses on measuring both financial (share price return) and fundamental (growth and margins) performance.

During the period 2006‐2012, which aims to encompass a full downturn and recovery cycle, higher leverage had the expected effect of magnifying share price movements in both bull and bear markets. Nevertheless, these swings in share prices appear to have significantly exaggerated what amounted to negligible differences in the fundamental operating metrics that are most commonly associated with valuation.

The author's policy prescription: Despite the temptation to reduce leverage to reduce potential share price declines, management teams should not prioritize debt reduction over investment in anticipation of economic downturns. Instead, articulate a clear leverage policy that supports an overall growth strategy and stick with it. The risk of short‐term share price declines pales in comparison to the risk of prolonged subpar growth from underinvestment.
Making Economics More Useful: How Technological Eclecticism Could Help
Authors: Bhidé Amar
Published: April 2021

Keynes thought it would be “splendid” if economists became more like dentists. Disciplinary economics has instead become more like physics in focusing on concise, universal propositions verified through decisive tests. This focus, the author argues, limits the practical utility of the discipline because universal propositions form only a part of new policy recipes. The author further suggests that, as in engineering and medicine, developing economic recipes requires eclectic combinations of suggestive tests and judgment. Additionally, the author provides a detailed example of how a simulation model can help evaluate new policy combinations that affect the screening of loan applications.
Frailty and cognitive impairment are not reasons to withhold anticoagulation in people with atrial fibrillation but screening could guide management
Authors: Harrison Stephanie L. , Akpan Asangaedem , Lip Gregory Y. H.
Published: April 2021

This editorial comments on the article by Mailhot et al.
Metastatic perioral melanoma in a wild mountain gorilla (Gorilla beringei beringei)
Authors: Kambale Syaluha Eddy , Zimmerman Dawn , Ramer Jan , Gilardi Kirsten , Kabuyaya Martin , Cranfield Michael R. , Kent Michael S. , Corner Sarah M. , Yeh Natasha , Lowenstine Linda
Published: April 2021

A 30‐year‐old free‐ranging female mountain gorilla (Gorilla beringei beringei) developed a perioral mass that was surgically debulked and diagnosed as malignant melanoma. After tumor recurrence, a canine melanoma vaccine was administered. However, the gorilla died shortly thereafter, and metastases to lymph nodes, lung, liver, and kidney were found post‐mortem.