bluuebunny/crossref_metadata_2025 huggingface dataset:
Pneumocytes are distinguished by highly elevated expression of the ER stress biomarker GRP78, a co-receptor for SARS-CoV-2, in COVID-19 autopsies
Authors: Puzyrenko Andrii , Jacobs Elizabeth R. , Sun Yunguang , Felix Juan , Sheinin Yuri , Ge Linna , Lai Shuping , Dai Qiang , Nanchal Rahul , North Paula , Simpson Pippa , Rui Hallgeir , Benjamin Ivor J.
Published: June 2021

Vaccinations are widely credited with reducing death rates from COVID-19 but the underlying host-viral mechanisms/interactions for morbidity and mortality of SARS-CoV-2 infection remain poorly understood. Acute respiratory distress syndrome (ARDS) describes the severe lung injury, which is pathologically associated with alveolar damage, inflammation, non-cardiogenic edema, and hyaline membrane formation. Because proteostatic pathways play central roles in cellular protection, immune modulation, protein degradation and tissue repair, we examined the pathological features for the unfolded protein response (UPR) using the surrogate biomarker glucose regulated protein 78 (GRP78) and co-receptor for SARS-CoV-2. At autopsy, immunostaining of COVID-19 lungs showed highly elevated expression of GRP78 in both pneumocytes and macrophages compared to non-COVID control lungs. GRP78 expression was detected in both SARS-CoV-2 infected and un-infected pneumocytes as determined by multiplexed immunostaining for nucleocapsid protein. In macrophages, immunohistochemical staining for GRP78 from deceased COVID-19 patients was increased but overlapped with GRP78 expression taken from surgical resections of non-COVID-19 controls. In contrast, the robust in situ GRP78 immunostaining of pneumocytes from COVID-19 autopsies exhibited no overlap and was independent of age, race/ethnicity and gender compared with non-COVID-19 controls. Our findings bring new insights for stress-response pathways involving the proteostatic network implicated for host resilience and suggest that targeting of GRP78 expression might afford an alternative therapeutic strategy to modulate host-viral interactions during SARS-CoV-2 infections.
REACT-1 round 12 report: resurgence of SARS-CoV-2 infections in England associated with increased frequency of the Delta variant
Authors: Riley Steven , Wang Haowei , Eales Oliver , Haw David , Walters Caroline E. , Ainslie Kylie E. C. , Atchison Christina , Fronterre Claudio , Diggle Peter J. , Page Andrew J. , Prosolek Sophie J. , Trotter Alexander J. , Le Viet Thanh , Alikhan Nabil-Fareed , Jackson Leigh M , Ludden Catherine ,   The COVID-19 Genomics UK (COG-UK) Consortium, Ashby Deborah , Donnelly Christl A. , Cooke Graham , Barclay Wendy , Ward Helen , Darzi Ara , Elliott Paul
Published: June 2021

Background

England entered a third national lockdown from 6 January 2021 due to the COVID-19 pandemic. Despite a successful vaccine rollout during the first half of 2021, cases and hospitalisations have started to increase since the end of May as the SARS-CoV-2 Delta (B.1.617.2) variant increases in frequency. The final step of relaxation of COVID-19 restrictions in England has been delayed from 21 June to 19 July 2021.

Methods

The REal-time Assessment of Community Transmision-1 (REACT-1) study measures the prevalence of swab-positivity among random samples of the population of England. Round 12 of REACT-1 obtained self-administered swab collections from participants from 20 May 2021 to 7 June 2021; results are compared with those for round 11, in which swabs were collected from 15 April to 3 May 2021.

Results

Between rounds 11 and 12, national prevalence increased from 0.10% (0.08%, 0.13%) to 0.15% (0.12%, 0.18%). During round 12, we detected exponential growth with a doubling time of 11 (7.1, 23) days and an R number of 1.44 (1.20, 1.73). The highest prevalence was found in the North West at 0.26% (0.16%, 0.41%) compared to 0.05% (0.02%, 0.12%) in the South West. In the North West, the locations of positive samples suggested a cluster in Greater Manchester and the east Lancashire area. Prevalence in those aged 5-49 was 2.5 times higher at 0.20% (0.16%, 0.26%) compared with those aged 50 years and above at 0.08% (0.06%, 0.11%). At the beginning of February 2021, the link between infection rates and hospitalisations and deaths started to weaken, although in late April 2021, infection rates and hospital admissions started to reconverge. When split by age, the weakened link between infection rates and hospitalisations at ages 65 years and above was maintained, while the trends converged below the age of 65 years. The majority of the infections in the younger group occurred in the unvaccinated population or those without a stated vaccine history. We observed the rapid replacement of the Alpha (B.1.1.7) variant of SARS-CoV-2 with the Delta variant during the period covered by rounds 11 and 12 of the study.

Discussion

The extent to which exponential growth continues, or slows down as a consequence of the continued rapid roll-out of the vaccination programme, including to young adults, requires close monitoring. Data on community prevalence are vital to track the course of the epidemic and inform ongoing decisions about the timing of further lifting of restrictions in England.
Large-scale screening of asymptomatic for SARS-CoV-2 variants of concern and rapid P.1 takeover, Curitiba, Brazil
Authors: Adamoski Douglas , de Oliveira Jaqueline Carvalho , Bonatto Ana Claudia , Wassem Roseli , Nogueira Meri Bordignon , Raboni Sonia Mara , Trindade Edvaldo da Silva , Souza Emanuel Maltempi ,   SCB-UFPR COVID-19 team, Gradia Daniela Fiori
Published: June 2021

To provide a safer environment for individuals working on-site at the Federal University of Paraná, Curitiba, Brazil, we performed a large-scale mass testing SARS-CoV-2 program coupled with variant genotyping using two PCR-based approaches. We observed a fast dominance of the Gamma variant, displacing other variants in less than three months.

Article Summary Line

Coronavirus variants of concern may use asymptomatic population as silent spreaders to perform a fast displacement of previous established strains.
Gaze-Related Activity in Primate Frontal Cortex Predicts and Mitigates Spatial Uncertainty
Authors: Bharmauria Vishal , Schütz Adrian , Khoozani Parisa Abedi , Yan Xiaogang , Wang Hongying , Bremmer Frank , Crawford J. Douglas
Published: June 2021

A remarkable feature of primate behavior is the ability to predict future events based on past experience and current sensory cues. To understand how the brain plans movements in the presence of unstable cues, we recorded gaze-related activity in the frontal cortex of two monkeys engaged in a quasi-predictable cue-conflict task. Animals were trained to look toward remembered visual targets in the presence of a landmark that shifted with fixed amplitude but randomized direction. As simulated by a probabilistic model based on known physiology/behavior, gaze end points assumed a circular distribution around the target, mirroring the possible directions of the landmark shift. This predictive strategy was reflected in frontal cortex activity (especially supplementary eye fields), which anticipated future gaze distributions before the actual landmark shift. In general, these results implicate prefrontal cortex in the predictive integration of environmental cues and their learned statistical properties to mitigate spatial uncertainty.
G Protein-Coupled Receptor-Ligand Dissociation Rates and Mechanisms from τRAMD Simulations
Authors: Kokh Daria B. , Wade Rebecca C.
Published: June 2021

There is a growing appreciation of the importance of drug-target binding kinetics for lead optimization. For G protein-coupled receptors (GPCRs), which mediate signaling over a wide range of timescales, the drug dissociation rate is often a better predictor of in vivo efficacy than binding affinity, although it is more challenging to compute. Here, we assess the ability of the τ-Random Acceleration Molecular Dynamics (τRAMD) approach to reproduce relative residence times and reveal dissociation mechanisms and the effects of allosteric modulation for two important membrane-embedded drug targets: the β2-adrenergic receptor and the muscarinic acetylcholine receptor M2. The dissociation mechanisms observed in the relatively short RAMD simulations (in which molecular dynamics (MD) simulations are performed using an additional force with an adaptively assigned random orientation applied to the ligand) are in general agreement with much more computationally intensive conventional MD and metadynamics simulations. Remarkably, although decreasing the magnitude of the random force generally reduces the number of egress routes observed, the ranking of ligands by dissociation rate is hardly affected and agrees well with experiment. The simulations also reproduce changes in residence time due to allosteric modulation and reveal associated changes in ligand dissociation pathways.

TABLE OF CONTENTS GRAPHIC
High-accuracy alignment ensembles enable unbiased assessments of sequence homology and phylogeny
Authors: Edgar Robert C.
Published: June 2021

Multiple sequence alignments (MSAs) are widely used to infer evolutionary relationships, enabling inferences of structure, function, and phylogeny. Standard practice is to construct one MSA by some preferred method and use it in further analysis; however, undetected MSA bias can be problematic. I describe Muscle5, a novel algorithm which constructs an ensemble of high-accuracy MSAs with diverse biases by perturbing a hidden Markov model and permuting its guide tree. Confidence in an inference is assessed as the fraction of the ensemble which supports it. Applied to phylogenetic tree estimation, I show that ensembles can confidently resolve topologies with low bootstrap according to standard methods, and conversely that some topologies with high bootstraps are incorrect. Applied to the phylogeny of RNA viruses, ensemble analysis shows that recently adopted taxonomic phyla are probably polyphyletic. Ensemble analysis can improve confidence assessment in any inference from an MSA.
easyFulcrum: An R package to process and analyze ecological sampling data generated using the Fulcrum mobile application
Authors: Di Bernardo Matteo , Crombie Timothy A. , Cook Daniel E. , Andersen Erik C.
Published: June 2021

Large-scale ecological sampling can be difficult and costly, especially for organisms that are too small to be easily identified in a natural environment by eye. Typically, these microscopic floral and fauna are sampled by collecting substrates from nature and then separating organisms from substrates in the laboratory. In many cases, diverse organisms can be identified to the species-level using molecular barcodes. To facilitate large-scale ecological sampling of microscopic organisms, we used a geographic data-collection platform for mobile devices called Fulcrum that streamlines the organization of geospatial sampling data, substrate photographs, and environmental data at natural sampling sites. These sampling data are then linked to organism isolation data from the laboratory. Here, we describe the easyFulcrum R package, which can be used to clean, process, and visualize ecological field sampling and isolation data exported from the Fulcrum mobile application. We developed this package for wild nematode sampling, but it is extensible to other organisms. The advantages of using Fulcrum combined with easyFulcrum are (1) the elimination of transcription errors by replacing manual data entry and/or spreadsheets with a mobile application, (2) the ability to clean, process, and visualize sampling data using a standardized set of functions in the R software environment, and (3) the ability to join disparate data to each other, including environmental data from the field and the molecularly defined identities of individual specimens isolated from samples.
Structural mechanism of calcium-mediated hormone recognition and Gβ interaction by the human melanocortin-1 receptor
Authors: Ma Shanshan , Chen Yan , Dai Antao , Yin Wanchao , Guo Jia , Yang Dehua , Zhou Fulai , Jiang Yi , Wang Ming-Wei , Xu H. Eric
Published: June 2021

Melanocortins are peptide hormones critical for stress response, energy homeostasis, inflammation, and skin pigmentation. Their functions are mediated by five G protein-coupled receptors (MC1R to MC5R), predominately through the stimulatory G protein (Gs). MC1R, the founding member of melanocortin receptors, is mainly expressed in melanocytes and is involved in melanogenesis. Dysfunction of MC1R is associated with the development of melanoma and skin cancer. Here we present three cryo-electron microscopy structures of the MC1R-Gs complexes bound to endogenous hormone α-MSH, a marketed drug afamelanotide, and a synthetic agonist SHU9119. These structures reveal the orthosteric binding pocket for the conserved HFRW motif among melanocortins and the crucial role of calcium ion in ligand binding. They also demonstrate the basis of differential activities among different ligands. In addition, unexpected interactions between MC1R and the Gβ subunit were discovered from these structures. Together, our results provide a conserved mechanism of calcium-mediated ligand recognition, specific mode of G protein coupling, and a universal activation pathway of melanocortin receptors.
Opioid antagonism reduces wanting by strengthening frontostriatal connectivity
Authors: Soutschek Alexander , Weber Susanna C. , Kahnt Thorsten , Quednow Boris B. , Tobler Philippe N.
Published: June 2021

Goal-directed behavior depends on both motivational (“wanting”) and hedonic (“liking”) dimensions of rewards. Previous animal and human research linked wanting and liking to anatomically and neurochemically distinct brain mechanisms, but it remains unknown as to how the different brain regions and neurotransmitter systems interact in processing distinct reward dimensions. Here, we assessed how pharmacological manipulations of opioid and dopamine receptor activation modulate the neural processing of wanting and liking in humans in a randomized, placebo-controlled, double-blind clinical trial. Blocking opioid receptor activation with naltrexone selectively reduced wanting of rewards, which on a neural level was reflected by stronger coupling between dorsolateral prefrontal cortex and the striatum under naltrexone compared with placebo. Our findings thus provide insights into how opioid receptors mediate frontostriatal gating of specifically motivational, not hedonic, aspects of rewards.
Luminosity thresholds of colored surfaces are determined by their upper-limit luminances empirically internalized in the visual system
Authors: Morimoto Takuma , Numata Ai , Fukuda Kazuho , Uchikawa Keiji
Published: June 2021

We typically have a fairly good idea whether a given object is self-luminous or illuminated, but it is not fully understood how we make this judgement. This study aimed to identify determinants of the luminosity threshold, a luminance level at which a surface begins to appear self-luminous. We specifically tested a hypothesis that our visual system knows the maximum luminance level that a surface can reach under the physical constraint that a surface cannot reflect more light than any incident light and applies this prior to determine the luminosity thresholds. Observers were presented with a 2-degree circular test field surrounded by numerous overlapping colored circles and luminosity thresholds were measured as a function of (i) the chromaticity of the test field, (ii) the shape of surrounding color distribution and (iii) the color of the illuminant of the surrounding colors. We found that the luminosity thresholds peaked around the chromaticity of test illuminants and decreased as the purity of the test chromaticity increased. However, the loci of luminosity thresholds across chromaticities were nearly invariant to the shape of the surrounding color distribution and generally resembled the loci drawn from theoretical upper-limit luminances and upper-limit luminance boundaries of real objects. These trends were particularly evident for illuminants on the black-body locus and did not hold well under atypical illuminants such as magenta or green. These results support the idea that our visual system empirically internalizes the gamut of surface colors under natural illuminants and a given object appears self-luminous when its luminance exceeds this internalized upper-limit luminance.
Reprogramming and redifferentiation of mucosal-associated invariant T cells reveals tumor inhibitory activity
Authors: Sugimoto Chie , Murakami Yukie , Ishi Eisuke , Fujita Hiroyoshi , Wakao Hiroshi
Published: June 2021

Mucosal-associated invariant T (MAIT) cells belong to a family of innate-like T cells that bridge innate and adaptive immunities. Although MAIT cells have been implicated in tumor immunity, it currently remains unclear whether they function as tumor promoting or inhibitory cells. Therefore, we herein used induced pluripotent cell (iPSC) technology to investigate this issue. Murine MAIT cells were reprogrammed into iPSCs and redifferentiated towards MAIT-like cells (m-reMAIT cells). m-reMAIT cells were activated by an agonist and MR1-tetramer, a reagent to detect MAIT cells, in the presence and absence of antigen-presenting cells. This activation accompanied protein tyrosine phosphorylation and the production of T helper (Th)1-, Th2-, and Th17-cytokines and inflammatory chemokines. Upon adoptive transfer, m-reMAIT cells migrated to different organs with maturation in mice. Furthermore, m-reMAIT cells prolonged mouse survival upon tumor inoculation through the NK cell-mediated reinforcement of cytolytic activity. Collectively, the present results demonstrated the utility and role of m-reMAIT cells in tumor immunity, and will contribute to insights into the function of MAIT cells in immunity.
“What a wonderful world!”: human relatedness, social space and accountability through action in a top-level amateur choir
Authors: De Loo Ivo , Kamminga Pieter
Published: June 2021

Purpose

During choir rehearsals, a conductor continuously holds choir members accountable for what they do and how they sing. Hence, members are held accountable through action. This allows a conductor to emphasize his/her expertise and underline his/her authority. Choir members typically respond in certain ways when this is done, for instance by commenting on the feedback they receive or by trying to improve their singing. The interplay between these accounts, how they develop over time, and what they (do not) accomplish in terms of human relatedness are the focus of this study. We use Bauman's (1993) conceptualization of social space to investigate these issues.

Design/methodology/approach

By providing reasons for their conduct and behaving in a certain way, a conductor and choir members, but also a choir's management, can alter their position in social space. Thereby, they solidify or change how they relate to other individuals in the choir. Bauman assumes that processes of social spacing require so-called “misunderstandings”. We examine seven misunderstandings that occurred in a particular rehearsal of a top-level amateur choir, analyzing their impact on human relatedness. Video analysis methods, interviews and photo-elicitation are the main research methods used.

Findings

We find both short-term and long-term effects of misunderstandings on human relatedness, and offer two extensions of Bauman's (1993) conception of social space. Firstly, we assert that there is a reflective side to processes of social spacing that needs to be taken into account when changes in human relatedness are discussed. Secondly, we find that the emotional impact of accountability on how individuals behave ought not to be underestimated, as this can have lasting effects on how people relate to one another.

Originality/value

This research makes two contributions to the extant literature. It is shown how accountability through action unfolds when people engage in leisurely activity, and how this affects the way they relate to one another – in sometimes unintentional and unpredictable ways. It also extends a well-known theoretical framework on social space that has seen little application in the accounting literature. This framework is adapted so that it may be used more fruitfully in future accounting studies.
What is good work in a hybrid organization? On the efforts of sequencing registers of valuation
Authors: Schrøder Ida , Cederberg Emilia , Hauge Amalie M.
Published: June 2021

Purpose

This paper investigates how different and sometimes conflicting approaches to performance evaluations are hybridized in the day-to-day activities of a disciplined hybrid organization–i.e. a public child protection agency at the intersection between the market and the public sector.

Design/methodology/approach

The paper is based on a one-year ethnography of how employees achieve to qualify their work as “good work” in situations with several and sometimes conflicting ideals of what “good work” is. Fieldwork material was collected by following casework activities across organizational boundaries. By combining accounting literature on hybridization with literature on practices of valuation, the paper develops a novel theoretical framework which allows for analyses of the various practices of valuation, when and where they clash and how they persist over time in everyday work.

Findings

Throughout the study, four distinct registers of valuation were identified: feeling, theorizing, formalizing and costing. To denote the meticulous efforts of pursuing good work in all four registers of valuation, the authors propose the notion of sequencing. Sequencing is an ongoing process of moving conflicting registers away from each other and bringing them back together again. Correspondingly, at the operational level of a hybrid organization, temporary compartmentalization is a means of avoiding clashes, and in doing so, making it possible for different and sometimes conflicting ways of achieving good results to continuously hybridize and persist together.

Research limitations/implications

The single-case approach allows for analytical depth, but limits the findings to theoretical, rather than empirical, generalizability. The framework the authors propose, however, is well-suited for mobilization and potential elaboration in further empirical contexts.

Originality/value

The paper provides a novel theoretical framework as well as rich empirical material from the highly political field of child protection work, which has seldomly been studied within accounting research.
Evaluating farm and export competitiveness of the Irish dairy industry: post-quota analysis
Authors: Cele Lungelo Prince , Hennessy Thia , Thorne Fiona
Published: June 2021

Purpose

This paper aims to examine the competitiveness trends and rankings of the Irish dairy sector at the farm and trade levels, relative to selected European Union (EU) Member States, in the context of the removal of the EU milk quota in 2015.

Design/methodology/approach

Competitiveness indicators including partial productivity measures and accountancy-based indicators were used for farm competitiveness, and net export market share and normalised revealed comparative advantage (NRCA) were used for export competitiveness.

Findings

Amongst the countries examined, Ireland had the highest growth in partial productivity indicators and was ranked first with the lowest total costs and cash costs per kg of milk solids post-quota. However, the total economic cost sub-components showed that Irish dairy farmers had high opportunity costs for owned land and labour. While Irish dairy products such as butter and powders have demonstrated growth potential in competitiveness post-quota with Irish butter and whey ranked in top three relative to other countries, other products, i.e. cheese and liquid milk have declined in competitiveness according to key export competitiveness indicators used.

Practical implications

The challenge for Irish dairy farmers is how to mitigate relatively high land and labour costs, which can limit farm competitiveness in the long run. The key players in the Irish dairy industry can now better position themselves in the global dairy market, recognizing the competitiveness dynamics of the different dairy products and their competitors. Policy implications and further areas of research have been identified to help improve the overall competitiveness position. It is surprising that Irish butter is a leader in the EU, yet not much research has been done to understand the market dynamics of this sector.

Originality/value

To the best of the authors’ knowledge, this study is the first of its kind to use both farm and export competitiveness measures to analyse the Irish dairy industry relative to other countries in the context of quota abolition. Unlike previous studies on dairy export competitiveness, this study has disaggregated the processed dairy products, which allowed for the ranking of countries and comparability across countries using NRCA.
Effects of deglycosylation and the Maillard reaction on conformation and allergenicity of the egg ovomucoid
Authors: Ma Junjie , Zhou Jinru , Chen Lerong , Zhang Hong , Wang Yanbo , Fu Linglin
Published: June 2021

Ovomucoid (OVM), known as the major allergen in egg white, has gained increasing concerns in industrialized countries. Here, we found the deglycosylation and Maillard reaction with galactooligosaccharide (GOS) and fructooligosaccharide (FOS) can induce conformational transformation of OVM from other structures (β‐turn, strang, and random coils) to α‐helix. We also introduced an approach to reduce the allergenicity of Gallus domesticus OVM by Maillard reaction with GOS and FOS. However, the OVM glycated by mannosan (MOS) and deglycosylated OVM exhibited higher allergenicity than native OVM. Therefore, GOS and FOS, especially GOS, could be applied in the reduction of the potential allergenicity of OVM through glycation. Furthermore, these findings may provide new insights into the development of hypoallergenic egg products.

Practical Application

In this study, the allergenicity and conformation of OVM treated with deglycosylation and glycation (GOS, FOS, and MOS) were investigated. The results would provide a better understanding of the effects of deglycosylation and Maillard reaction with different reducing sugars on the molecular characteristics of OVM and further provide new insights into the development of hypoallergenic egg products.
Patterns of use of oral health care services in Australian rural adults: the Crossroads‐II Dental sub‐study
Authors: Mariño R , Glenister K , Bourke L , Morgan M , Atala‐Acevedo C , Simmons D
Published: June 2021

Background

As part of a larger study, the Crossroads‐II Dental sub‐study determined the patterns of, and barriers to, oral health care service utilization in a rural area of Victoria.

Methods

In this cross‐sectional sub‐study predisposing, enabling, needs‐related, and oral health variables were considered in association with patterns of oral health care utilization. A logistic regression was performed to explain the use of oral health care services.

Results

Overall, 574 adults participated, with 50.9% reporting having visited an oral health care service in the previous 12 months. Age, number of chronic health conditions and holding a health card; were associated with increased visit to a dentist (OR = 1.01; 95% CI: 1.00–1.03; OR = 1.08; 95% CI: 1.01–1.16; OR = 2.06; 95% CI: 1.26–3.36, respectively). Perceived barriers to care and number of missing teeth decreased the odds of using services (OR = 0.46; 95% CI: 0.36–0.58; OR = 0.95; 95% CI: 0.92–0.98, respectively).

Conclusions

Results suggest that use of oral health care services is associated with a range of financial, educational, health and structural barriers. Increasing the use of oral health care services in rural populations requires additional efforts beyond the reduction of financial barriers.
Limited long‐term treatment persistence of first anti‐TNF therapy in 538 patients with inflammatory bowel diseases: a 20‐year real‐world study
Authors: Blesl Andreas , Binder Lukas , Högenauer Christoph , Wenzl Heimo , Borenich Andrea , Pregartner Gudrun , Berghold Andrea , Mestel Sigrid , Kump Patrizia , Baumann‐Durchschein Franziska , Petritsch Wolfgang
Published: June 2021

Background

Anti‐TNF antibodies were the first biologic treatment option for patients with inflammatory bowel diseases.

Aims

To assess length of treatment persistence of first anti‐TNF therapy and influencing factors used in the standard care of patients with inflammatory bowel diseases.

Methods

Single‐centre, retrospective study from a register including patients who received anti‐TNF therapy in the last 20 years at the study centre. Kaplan‐Meier analysis with log‐rank test was used to describe treatment persistence. With multivariable Cox regression analysis, risk factors for treatment failure were investigated.

Results

Five hundred thirty‐eight patients (CD, Crohn's disease: 367, UC, ulcerative colitis: 147, inflammatory bowel disease unclassified: 24) with a median follow‐up of 8.1 years were included. Median (95% confidence interval) treatment persistence in the total cohort was 2.3 years (28 [22, 38] months), and nearly half of patients withdrew from treatment within 2 years. Male patients were treated longer than females (male: 37 [25, 48] months, female: 23 [14, 33] months, P = 0.002). Treatment persistence was longer in CD compared to UC (CD: 39 [30, 50] months, UC: 13 [9, 19] months, P < 0.001), and patients with CD remained longer on adalimumab than on infliximab treatment (adalimumab: 67 [55, 95] months, infliximab: 19 [14, 31] months, P < 0.001). Treatment failure (52%) and side effects (25%) were the most common reasons for withdrawal from therapy; 14% withdrew due to remission. Female sex was identified as independent predictor for treatment failure in UC (hazard ratio [CI]: 1.73 [1.02‐2.92], P = 0.04).

Conclusion

Long‐term treatment persistence of first anti‐TNF therapy was limited in patients with inflammatory bowel diseases, primarily due to treatment failure and side effects.
Preschool Children Rarely Seek Empirical Data That Could Help Them Complete a Task When Observation and Testimony Conflict
Authors: Hermansen Tone K. , Ronfard Samuel , Harris Paul L. , Zambrana Imac M.
Published: June 2021

Children (N = 278, 34–71 months, 54% girls) were told which of two figurines turned on a music box and also observed empirical evidence either confirming or conflicting with that testimony. Children were then asked to sort novel figurines according to whether they could make the music box work or not. To see whether children would explore which figurine turned on the music box, especially when the observed and testimonial evidence conflicted, children were given access to the music box during their sorting. However, children rarely explored. Indeed, they struggled to disregard the misleading testimony both when sorting the figurines and when asked about a future attempt. In contrast, children who explored the effectiveness of the figurines dismissed the misleading testimony.
Clinical and neuroimaging findings in MOGAD–MRI and OCT
Authors: Bartels Frederik , Lu Angelo , Oertel Frederike Cosima , Finke Carsten , Paul Friedemann , Chien Claudia
Published: June 2021

Myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD) are rare in both children and adults, and have been recently suggested to be an autoimmune neuroinflammatory group of disorders that are different from aquaporin-4 autoantibody-associated neuromyelitis optica spectrum disorder and from classic multiple sclerosis. In-vivo imaging of the MOGAD patient central nervous system has shown some distinguishing features when evaluating magnetic resonance imaging of the brain, spinal cord and optic nerves, as well as retinal imaging using optical coherence tomography. In this review, we discuss key clinical and neuroimaging characteristics of paediatric and adult MOGAD. We describe how these imaging techniques may be used to study this group of disorders and discuss how image analysis methods have led to recent insights for consideration in future studies.
The significance of epidermal involvement in primary cutaneous gamma/delta (γδ) T‐cell lymphoma: A systematic review and meta‐analysis
Authors: Goyal Amrita , O'Leary Daniel , Duncan Lyn M.
Published: June 2021

Background

Primary cutaneous gamma/delta (γδ) T‐cell lymphoma (PCGDTCL) is a rare, aggressive peripheral T‐cell lymphoma. There is evidence that patients with epidermotropic PCGDTCL may have an improved prognosis compared with those with only dermal and/or subcutaneous involvement.

Methods

Systematic review of the literature and application of inclusion criteria yielded 48 manuscripts detailing the cases of 104 patients.

Results

Of the 104 patients, 57 were male (51.4%) and 47 were female (48.5%) Based on provided histopathologic descriptions, 57 cases (54.8%) had no epidermotropism, 47 cases (45.2%) patients demonstrated any degree of epidermotropism, and 25 cases were predominantly epidermotropic (25/104, 24%). Five‐year overall survivals for patients with no epidermotropism, any epidermotropism, and predominantly epidermotropic presentation were 32.8%, 28.9%, and 40.0%, respectively (p = 0.40). The most commonly performed immunohistochemical markers were CD3, CD4, CD8, CD5, CD7, CD30, CD56, TCR beta, TCR γ, and TCR δ. There was no statistically significant difference in immunophenotype between groups. Lesion morphology was described in the majority of cases (85/104, 80.9%); most cases presented as a combination of nodules, plaques, and tumors (77.4%). Several cases had more atypical presentations, including “mycosis‐fungoides‐like” and ulcerated.

Conclusion

In PCGDTCL, neither epidermotropism nor predominantly epidermotropic phenotype predict a better prognosis. In addition, the case report literature in dermatology and dermatopathology is rich and highly valuable.
occCite: Tools for querying and managing large biodiversity occurrence datasets
Authors: Owens Hannah L. , Merow Cory , Maitner Brian S. , Kass Jamie M. , Barve Vijay , Guralnick Robert P.
Published: June 2021

The amount of observational and specimen‐based biodiversity data available to researchers is increasing exponentially, yet the ability to manage and cite large, complex biodiversity datasets lags behind. This management and citation gap impedes reproducibility for data users and the ability for data publishers to track use and accumulate use citations, ultimately harming the longer‐term sustainability of the still‐emerging enterprise of research data‐sharing. Here we present an R package, occCite (v. 0.4.7), to aid researchers in querying large species occurrence data aggregators (specifically, the Global Biodiversity Information Facility, GBIF, and the Botanical Information and Ecology Network, BIEN), and store metadata such as primary data providers, database accession dates, DOIs, and the taxonomic source used for search terms. occCite also includes tools to summarize and visualize query results and generate citation lists of all data providers and software packages used during the query process. We provide examples of a basic occurrence search and citation workflow as well as an advanced workflow using features for custom optimized searches, visualization, and summary procedures. occCite improves upon existing R packages by uniting data from powerful API‐based query packages (rgbif and BIEN) into a unified object‐based framework, while maintaining metadata vital to best‐practice recommendations for documenting biodiversity analysis workflows. occCite aims to efficiently close the gap in the citation cycle between primary data providers and final research products, allowing researchers to meet dataset documentation standards without sacrificing time and resources to the demands of providing increasing levels of detail on their datasets.
Variable strength of predator‐mediated effects on species occurrence in an arctic terrestrial vertebrate community
Authors: Duchesne Éliane , Lamarre Jean‐François , Gauthier Gilles , Berteaux Dominique , Gravel Dominique , Bêty Joël
Published: June 2021

Indirect effects resulting from species sharing the same enemy can shape spatio‐temporal variations in species occurrence. The strength of such effects remains poorly known in natural communities composed of species from different trophic levels interacting in heterogeneous landscapes. Benefiting from a well‐known arctic vertebrate community and marked spatio‐temporal variations in the density of key prey species, we examined the effects of direct predator‐prey and indirect predator‐mediated effects on species occurrence in the landscape. We found both positive effects of one prey (lemmings), as well as negative indirect effects of another prey (colonial nesting snow geese) on the occurrence of species (ground‐nesting birds) belonging to different guilds and trophic levels but sharing a common predator (arctic fox). However, species using prey refuges available in the landscape were not or less affected by predator‐mediated effects. Similarly, the smallest (a passerine) and the largest and most dangerous species (an owl) for the shared predator were not affected by these effects. Our study provides one of the rare empirical evidence of predator‐mediated effects ascending the food web (i.e. negative indirect effect of an herbivore on avian predators) and underlines how habitat structure and species traits can modulate the strength of indirect effects in natural communities.
Some like it tailor‐made: The effectiveness of personalized coupons for lower‐calorie food choices at a university canteen
Authors: Nguyen Minh T. T. , Emberger‐Klein Agnes , Menrad Klaus
Published: June 2021

As an emerging marketing tool that targets shoppers individually based on their purchase histories, personalized price promotion is likely to address the limitations of untargeted price reductions. However, there is no prior evidence to support the effectiveness of this approach in promoting low‐calorie food choices, and which consumer‐specific characteristics influence its performance. In this study, we analyze the effectiveness of personalized and non‐personalized coupons for lower‐calorie menus at a university canteen. In addition, we examine the interaction between psychological factors and promotional responses, as well as subsequent dietary outcomes. Overall, personalized price promotion performs better than the untargeted approach in encouraging shoppers to redeem the offered coupons and make menu choices with more healthy items and fewer calories. Factors such as calorie concerns, convenience orientation, and the resistance to change eating habits have significant effects on coupon redemption. The role of coupon redemption in mediating the association between such psychological predictors and dietary changes proves the effectiveness of price reductions. This study highlights the potential of personalized price promotion as a healthy eating intervention and sets the groundwork for developing and evaluating this instrument.
Congenital long QT syndrome: a clinician's guide
Authors: Lankaputhra Malanka , Voskoboinik Aleksandr
Published: June 2021

Congenital long QT syndrome (LQTS) is a familial cardiac ion channelopathy first described over 60 years ago. It is characterised by prolonged ventricular repolarisation (long QT on electrocardiography), ventricular arrhythmias and associated syncope or sudden cardiac death. As the most closely studied cardiac channelopathy, over the decades we have gained a deep appreciation of the complex genetic model of LQTS. Variability in genetic expression and incomplete penetrance leads to a heterogeneous phenotype that can be challenging to classify clinically. In recent times, progress has been made in diagnostic method, risk stratification and treatment options. This review has been written as a guide for the general cardiologist to understand the basic pathophysiology, diagnosis and management priorities for the most encountered LQTS subtypes: LQT1, LQT2 and LQT3.
Outcomes of the CT2 study: A ‘one‐stop‐shop’ for community‐based hepatitis C testing and treatment in Yangon, Myanmar
Authors: Draper Bridget Louise , Htay Hla , Pedrana Alisa , Yee Win Lei , Howell Jessica , Pyone Kyi Khin , Naing Win , Sanda Aung Khin , Markby Jessica , Easterbrook Philippa , Bowring Anna , Aung Win , Sein Yi Yi , Nwe Nwe , Myint Kyi Thar , Shilton Sonjelle , Hellard Margaret
Published: June 2021

Background

With the advent of low‐cost generic direct‐acting antivirals (DAA), hepatitis C (HCV) elimination is now achievable even in low‐/middle‐income settings. We assessed the feasibility and effectiveness of a simplified clinical pathway using point‐of‐care diagnostic testing and non‐specialist‐led care in a decentralized, community‐based setting.

Methods

This feasibility study was conducted at two sites in Yangon, Myanmar: one for people who inject drugs (PWID), and the other for people with liver disease. Participants underwent on‐site rapid anti‐HCV testing and HCV RNA testing using GeneXpert(R). General practitioners determined whether participants started DAA therapy immediately or required specialist evaluation. Primary outcome measures were progression through the HCV care cascade, including uptake of RNA testing and treatment, and treatment outcomes.

Findings

All 633 participants underwent anti‐HCV testing; 606 (96%) were anti‐HCV positive and had HCV RNA testing. Of 606 tested, 535 (88%) were RNA positive and had pre‐treatment assessments; 30 (6%) completed specialist evaluation. Of 535 RNA positive participants, 489 (91%) were eligible to initiate DAAs, 477 (98%) completed DAA therapy and 421 achieved SVR12 (92%; 421/456). Outcomes were similar by site: PWID site: 91% [146/161], and liver disease site: 93% [275/295]). Compensated cirrhotic patients were treated in the community; they achieved an SVR12 of 83% (19/23). Median time from RNA test to DAA initiation was 3 days (IQR 2‐5).

Conclusions

Delivering a simplified, non‐specialist‐led HCV treatment pathway in a decentralized community setting was feasible in Yangon, Myanmar; retention in care and treatment success rates were very high. This care model could be integral in scaling up HCV services in Myanmar and other low‐ and middle‐income settings.
Transcription regulates ribosome hibernation
Authors: Feaga Heather A. , Dworkin Jonathan
Published: June 2021

Most bacteria are quiescent, typically as a result of nutrient limitation. In order to minimize energy consumption during this potentially prolonged state, quiescent bacteria substantially attenuate protein synthesis, the most energetically costly cellular process. Ribosomes in quiescent bacteria are present as dimers of two 70S ribosomes. Dimerization is dependent on a single protein, hibernation promoting factor (HPF), that binds the ribosome in the mRNA channel. This interaction indicates that dimers are inactive, suggesting that HPF inhibits translation. However, we observe that HPF does not significantly affect protein synthesis in vivo suggesting that dimerization is a consequence of inactivity, not the cause. The HPF–dimer interaction further implies that re‐initiation of translation when the bacteria exit quiescence requires dimer resolution. We show that ribosome dimers quickly resolve in the presence of nutrients, and this resolution is dependent on transcription, indicating that mRNA synthesis is required for dimer resolution. Finally, we observe that ectopic HPF expression in growing cells where mRNA is abundant does not significantly affect protein synthesis despite stimulating dimer formation, suggesting that dimerization is dynamic. Thus, the extensive transcription that occurs in response to nutrient availability rapidly re‐activates the translational apparatus of a quiescent cell and induces dimer resolution.
Janzen–Connell effects partially supported in reef‐building corals: adult presence interacts with settler density to limit establishment
Authors: Sims Carrie A. , Sampayo Eugenia M. , Mayfield Margaret M. , Staples Timothy L. , Dalton Steven J. , Gutierrez‐Isaza Nataly , Pandolfi John M.
Published: June 2021

In many plant and sessile marine invertebrate (SMI) taxa, population and community dynamics are heavily influenced by processes occurring during the dispersal and establishment phases. The Janzen–Connell (J–C) hypothesis predicts increased survival of early life stages with decreasing conspecific density and increased distance from conspecific adults. Evidence of J–C effects in maintaining diversity is common in plant communities, but its importance in SMI communities remains unclear. Under controlled aquarium conditions, we examined the effect of density‐dependence and adult conspecific water treatments (absent/present) on propagule settlement success and settler post‐settlement survival, along with associated spatial patterns, for six broadcast‐spawning, reef‐building coral species from three families. We also tested if settlement success was linked to increasing propagule species diversity for three coral species from two families. We found that the probability of settlement was density independent and not influenced by adult present water treatments. Yet, adult present water treatments and settler density did have a synergistic negative effect on the probability of short‐term settler survival for all species examined. Settlers also showed greater spatial aggregation as their numbers increased, but were less aggregated in adult present water treatments compared to those in adult absent water treatments. We further show evidence of significant species interactions among propagules, as settlement in single‐species trials was four‐fold higher compared to mixed‐species trials. Our findings from controlled experimental arenas indicate that the early establishment of corals was predominantly limited by density‐dependent settler–adult interactions among conspecifics and propagule–propagule interactions among heterospecifics. Thus, the proximity to established conspecific adults, settler density and species diversity of propagules are relevant drivers of local coral community diversity and structure. Based on these outcomes, we suggest that the J–C hypothesis, with demonstrated importance for plants, is partially upheld for reef corals.
Multifocal capillary malformation with segmental distribution and central atrophy: A case in a 12‐year‐old girl
Authors: Rollan María Paz , Fajre Ximena , Giordano Consuelo , Whittle Carolina , Castro Álex
Published: June 2021

We present a 12‐year‐old girl with multiple geographic capillary malformations in a segmental distribution over the left trunk and arm that were present at birth and evolved over years with ulceration, atrophy, and subsequent scarring. Our case is clinically consistent with the recently described entity “multifocal capillary malformation with segmental distribution and central atrophy.” To our knowledge, our patient is the oldest reported to date.
Hybrid analytical-numerical optimization design methodology of acoustic metamaterials for sound insulation
Authors: Vazquez Torre Javier Hernan , Brunskog Jonas , Cutanda Henriquez Vicente , Jung Jaesoon
Published: June 2021

Acoustic metamaterials are becoming promising solutions for many industry applications, but the gap between theory and practice is still difficult to close. This research proposes an optimization methodology of acoustic metamaterial designs for sound insulation that aims to start bridging this gap. The proposed methodology takes advantage of a hybrid analytical-numerical approach for computing the sound transmission loss of the designs efficiently. As a result, the implementation of optimization techniques on numerical model designs becomes practically possible. This is exemplified with two test cases: (i) optimization of the sound transmission loss of a single gypsum board panel and (ii) optimization of the noise reduction of outdoor HVAC units. Two resonator designs, one used previously for sound radiation in flat panel speakers and the other for enhancing the sound transmission loss at the mass-air-mass resonance of double panels, are here optimized for the two test cases. This shows how an existing resonator can be adapted for new purposes, thus making the design of acoustic metamaterials efficient. The optimized metamaterials outperform the original designs as well as traditional approaches to sound insulation.