bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative phylogenetic analysis of SARS-CoV-2 spike protein—possibility effect on virus spillover
Authors: Ghorbani Abozar , Samarfard Samira , Eskandarzade Neda , Afsharifar Alireza , Eskandari Mohammad Hadi , Niazi Ali , Izadpanah Keramatollah , Karbanowicz Thomas P
Published: March 2021

Coronavirus disease 2019 has developed into a dramatic pandemic with tremendous global impact. The receptor-binding motif (RBM) region of the causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), binds to host angiotensin-converting enzyme 2 (ACE2) receptors for infection. As ACE2 receptors are highly conserved within vertebrate species, SARS-CoV-2 can infect significant animal species as well as human populations. An analysis of SARS-CoV-2 genotypes isolated from human and significant animal species was conducted to compare and identify mutation and adaptation patterns across different animal species. The phylogenetic data revealed seven distinct phylogenetic clades with no significant relationship between the clades and geographical locations. A high rate of variation within SARS-CoV-2 mink isolates implies that mink populations were infected before human populations. Positions of most single-nucleotide polymorphisms (SNPs) within the spike (S) protein of SARS-CoV-2 genotypes from the different hosts are mostly accumulated in the RBM region and highlight the pronounced accumulation of variants with mutations in the RBM region in comparison with other variants. These SNPs play a crucial role in viral transmission and pathogenicity and are keys in identifying other animal species as potential intermediate hosts of SARS-CoV-2. The possible roles in the emergence of new viral strains and the possible implications of these changes, in compromising vaccine effectiveness, deserve urgent considerations.
FraGAT: a fragment-oriented multi-scale graph attention model for molecular property prediction
Authors: Zhang Ziqiao , Guan Jihong , Zhou Shuigeng
Published: March 2021

Motivation

Molecular property prediction is a hot topic in recent years. Existing graph-based models ignore the hierarchical structures of molecules. According to the knowledge of chemistry and pharmacy, the functional groups of molecules are closely related to its physio-chemical properties and binding affinities. So, it should be helpful to represent molecular graphs by fragments that contain functional groups for molecular property prediction.

Results

In this article, to boost the performance of molecule property prediction, we first propose a definition of molecule graph fragments that may be or contain functional groups, which are relevant to molecular properties, then develop a fragment-oriented multi-scale graph attention network for molecular property prediction, which is called FraGAT. Experiments on several widely used benchmarks are conducted to evaluate FraGAT. Experimental results show that FraGAT achieves state-of-the-art predictive performance in most cases. Furthermore, our case studies show that when the fragments used to represent the molecule graphs contain functional groups, the model can make better predictions. This conforms to our expectation and demonstrates the interpretability of the proposed model.

Availability and implementation

The code and data underlying this work are available in GitHub, at https://github.com/ZiqiaoZhang/FraGAT.

Supplementary information

Supplementary data are available at Bioinformatics online.
Oxidative stress promotes cellular damages in the cervix: implications for normal and pathologic cervical function in human pregnancy
Authors: Tantengco Ourlad Alzeus G , Vink Joy , Medina Paul Mark B , Menon Ramkumar
Published: March 2021

A physiologic increase in reactive oxygen species throughout pregnancy is required to remodel the cervix. Oxidative stress can cause cellular damage that contributes to dysfunctional tissue. This study determined the oxidative stress-induced cell fate of human cervical epithelial and cervical stromal cells. We treated the ectocervical and endocervical epithelial cells and cervical stromal cells with cigarette smoke extract, an oxidative stress inducer, for 48 h. Cell viability (crystal violet assay); cell cycle, apoptosis, and necrosis (flow cytometry); senescence (senescence-associated β-galactosidase staining); autophagy (staining for autophagosome protein, microtubule-associated protein 1 light chain 3B); stress signaler p38 mitogen-activated protein kinases pathway activation (western blot analyses); and inflammation by measuring interleukin-6 (enzyme-linked immunosorbent assay) were conducted after 48 h of cigarette smoke extract treatment. Oxidative stress induced reactive oxygen species production in cervical cells, which was inhibited by N-acetylcysteine. Oxidative stress promoted cell cycle arrest and induced necrosis in cervical cells. High senescence and low autophagy were observed in cervical stromal cells under oxidative stress. Conversely, senescence was low and autophagy was high in endocervical epithelial cells. Oxidative stress induced p38 mitogen-activated protein kinases (p38MAPK) activation in all cervical cells but only increased interleukin-6 production by the ectocervical epithelial cells. Inhibition of interleukin-6 production by a p38 mitogen-activated protein kinases inhibitor confirmed the activation of an oxidative stress-induced pathway. In conclusion, oxidative stress can promote cell death and sterile inflammation that is mediated by p38 mitogen-activated protein kinases activation in the cellular components of the cervix. These cellular damages may contribute to the normal and premature cervical ripening, which can promote preterm birth.
Why translation from basic discoveries to clinical applications is so difficult for atrial fibrillation and possible approaches to improving it
Authors: Nattel Stanley , Sager Philip T , Hüser Jörg , Heijman Jordi , Dobrev Dobromir
Published: March 2021

Atrial fibrillation (AF) is the most common sustained clinical arrhythmia, with a lifetime incidence of up to 37%, and is a major contributor to population morbidity and mortality. Important components of AF management include control of cardiac rhythm, rate, and thromboembolic risk. In this narrative review article, we focus on rhythm-control therapy. The available therapies for cardiac rhythm control include antiarrhythmic drugs and catheter-based ablation procedures; both of these are presently neither optimally effective nor safe. In order to develop improved treatment options, it is necessary to use preclinical models, both to identify novel mechanism-based therapeutic targets and to test the effects of putative therapies before initiating clinical trials. Extensive research over the past 30 years has provided many insights into AF mechanisms that can be used to design new rhythm-maintenance approaches. However, it has proven very difficult to translate these mechanistic discoveries into clinically applicable safe and effective new therapies. The aim of this article is to explore the challenges that underlie this phenomenon. We begin by considering the basic problem of AF, including its clinical importance, the current therapeutic landscape, the drug development pipeline, and the notion of upstream therapy. We then discuss the currently available preclinical models of AF and their limitations, and move on to regulatory hurdles and considerations and then review industry concerns and strategies. Finally, we evaluate potential paths forward, attempting to derive insights from the developmental history of currently used approaches and suggesting possible paths for the future. While the introduction of successful conceptually innovative new treatments for AF control is proving extremely difficult, one significant breakthrough is likely to revolutionize both AF management and the therapeutic development landscape.
Oviposition Response of Monarch Butterfly (Lepidoptera: Nymphalidae) to Imidacloprid-Treated Milkweed
Authors: Mullins Alexander N , Bradbury Steven P , Sappington Thomas W , Adelman James S
Published: March 2021

Monarch butterfly (Danaus plexippus) populations have declined over the last two decades, attributable in part to declines in its larval host plant, milkweed (Asclepias spp.), across its breeding range. Conservation efforts in the United States call for restoration of 1.3 billion milkweed stems into the Midwestern landscape. Reaching this goal will require habitat establishment in marginal croplands, where there is a high potential for exposure to agrochemicals. Corn and soybean crops may be treated with neonicotinoid insecticides systemically or through foliar applications to provide protection against insect pests. Here, we investigate whether ovipositing monarchs discriminate against milkweed plants exposed to the neonicotinoid insecticide imidacloprid, either systemically or through foliar application. In our first experiment, we placed gravid females in enclosures containing a choice of two cut stems for oviposition: one in 15 ml of a 0.5 mg/ml aqueous solution of imidacloprid and one in 15 ml water. In a second experiment, females were given a choice of milkweed plants whose leaves were treated with 30 µl of a 0.825 mg/ml imidacloprid-surfactant solution or plants treated with surfactant alone. To evaluate oviposition preference, we counted and removed eggs from all plants daily for 3 d. We also collected video data on a subset of butterflies to evaluate landing behavior. Results indicate that neither systemic nor foliar treatment with imidacloprid influenced oviposition behavior in female monarchs. The implications of these findings for monarch conservation practices will be informed by the results of ongoing egg and larval toxicity studies.
Long-term outcomes of patients with primary graft dysfunction after cardiac transplantation
Authors: Squiers John J , DiMaio J Michael , Van Zyl Johanna , Lima Brian , Gonzalez-Stawisnksi Gonzalo , Rafael Aldo E , Meyer Dan M , Hall Shelley A
Published: March 2021

OBJECTIVES

The International Society of Heart and Lung Transplantation (ISHLT) criteria for primary graft dysfunction (PGD) after cardiac transplantation have been shown to stratify patient outcomes up to 1 year after transplantation, but scarce data are available regarding outcomes beyond the 1st year. We sought to characterize survival of patients with PGD following cardiac transplantation beyond the 1st year.

METHODS

A retrospective review of consecutive patients undergoing isolated cardiac transplantation at a single centre between 2012 and 2015 was performed. Patients were diagnosed with none, mild, moderate or severe PGD by the ISHLT criteria. Survival was ascertained from the United Network for Organ Sharing database and chart review. Kaplan–Meier curves were plotted to compare survival. The hazard ratio for mortality associated with PGD severity was estimated using Cox-proportional hazards modelling, with a pre-specified conditional survival analysis at 90 days.

RESULTS

A total of 257 consecutive patients underwent cardiac transplantation during the study period, of whom 73 (28%) met ISHLT criteria for PGD: 43 (17%) mild, 12 (5%) moderate and 18 (7%) severe. Patients with moderate or severe PGD had decreased survival up to 5 years after transplantation (log-rank P < 0.001). Landmark analyses demonstrated that patients with moderate or severe PGD were at increased risk of mortality during the first 90-days after transplantation as compared to those with none or mild PGD [hazard ratio (95% confidence interval) 18.9 (7.1–50.5); P < 0.001], but this hazard did not persist beyond 90-days in survivors (P = 0.64).

CONCLUSIONS

A diagnosis of moderate or severe PGD is associated with increased mortality up to 5 years after cardiac transplantation. However, patients with moderate or severe PGD who survive to post-transplantation day 90 are no longer at increased risk for mortality as compared to those with none or mild PGD.
Joint multizonal transdimensional Bayesian inversion of surface wave dispersion and ellipticity curves for local near-surface imaging
Authors: Hallo Miroslav , Imperatori Walter , Panzera Francesco , Fäh Donat
Published: March 2021

Physical properties of near-surface soil and rock layers play a fundamental role in the seismic site effects analysis, being an essential element of seismic hazard assessment. Site-specific mechanical properties (i.e. shear- and compressional-wave velocities and mass density) can be inferred from surface wave dispersion and horizontal-to-vertical or ellipticity data by non-linear inversion techniques. Nevertheless, results typically exhibit significant inherent non-uniqueness as different models may fit the data equally well. Standard optimization inversion techniques minimize data misfit, resulting in a single representative model, rejecting other models providing similar misfit values. An alternative inversion technique can be formulated in the Bayesian framework, where the posterior probability density on the model space is inferred. This paper introduces an inversion approach of surface wave dispersion and ellipticity data based on a novel multizonal transdimensional Bayesian formulation. In particular, we parametrize 1-D layered velocity models by the varying number of Voronoi nuclei, allowing us to treat the number of layers as an unknown parameter of the inverse problem. The chosen parametrization leads to the transdimensional formulation of the model space, sampled by a reversible jump Markov chain Monte Carlo algorithm to provide an ensemble of random samples following the posterior probability density of model parameters. The used type of the sampling algorithm controls a model complexity (i.e. the number of layers) self-adaptively based on the measured data's information content. The method novelty lies in the parsimonious selection of sampling models and in the multizonal formulation of prior assumptions on model parameters, the latter allows including additional site-specific constraints in the inversion. These assumptions may be based on, e.g. stratigraphic logs, standard penetration tests, known water table, and bedrock depth. The multizonal formulation fully preserves the validity of the transdimensional one, as demonstrated analytically. The resultant ensemble of model samples is a discrete approximation of the posterior probability density function of model parameters and associated properties (e.g. VS30, quarter-wavelength average velocity profile and theoretical SH-wave amplification function). Although the ultimate result is the posterior probability density function, some representative models are selected according to data fit and maximum of the posterior probability density function. We first validate our inversion approach based on synthetic tests and then apply it to field data acquired from the active seismic survey and single-station measurements of ambient vibrations at the SENGL seismic station site in central Switzerland.
Evaluating an organizational innovation: evidence from the conglomerate merger wave
Authors: Klein Peter , Wuebker Robert , Chen Mo , Zoeller Kathrin
Published: March 2021

How do we assess new forms of economic organization? As with other innovations, the value of a new organizational form is initially unknown. When assets are traded in financial markets, the information embodied in prices represent one mechanism through which organizational innovations are evaluated. We apply an experimental-learning framework to explore the influence of the capital markets on economic organization, using the conglomerate merger wave of the 1960s and 1970s as an empirical context. In our setting, the initial market popularity of conglomerates, followed by their rapid decline, is indicative of investors attempting to determine the value of a new organizational form. We provide event-study evidence that investors systematically updated their beliefs about the value of the conglomerate form based on new information (positive or negative) about the largest and most newsworthy conglomerates. Our results suggest that financial market participants make judgments not only about specific companies, but about organizational structure itself.
Stress at Work: Individuals or Structures?
Authors: Davies A C L
Published: March 2021

Stress is a significant practical problem in modern workplaces. According to the Health and Safety Executive (HSE), more than half of all working days lost to ill health each year are attributed to stress, depression or anxiety. This article offers an overview of the occupational psychology literature on workplace stress, focussing on the job demands–resources or JD-R model, developed by Demerouti et al., and highlighting two important points: first, that stress at work is not just about excessive job ‘demands’ but also about inadequate ‘resources’ to cope with those demands; second, that stress-related ill-health is not just a matter of vulnerability on the part of the individual worker, but is also about the way in which the workplace is organised. The article then draws on these insights to offer a critique of the way in which health and safety law and tort law approach workplace stress, arguing that both bodies of law are overly focussed on treating stress as a matter of individual vulnerability. It concludes by drawing out some broader implications of the occupational psychology literature for areas of employment law less obviously related to workplace stress, and for casual or platform working.
Robotic Antimicrobial Susceptibility Platform (RASP): a next-generation approach to One Health surveillance of antimicrobial resistance
Authors: Truswell Alec , Abraham Rebecca , O’Dea Mark , Lee Zheng Zhou , Lee Terence , Laird Tanya , Blinco John , Kaplan Shai , Turnidge John , Trott Darren J , Jordan David , Abraham Sam
Published: March 2021

Background

Surveillance of antimicrobial resistance (AMR) is critical to reducing its wide-reaching impact. Its reliance on sample size invites solutions to longstanding constraints regarding scalability. A robotic platform (RASP) was developed for high-throughput AMR surveillance in accordance with internationally recognized standards (CLSI and ISO 20776-1:2019) and validated through a series of experiments.

Methods

Experiment A compared RASP’s ability to achieve consistent MICs with that of a human technician across eight replicates for four Escherichia coli isolates. Experiment B assessed RASP’s agreement with human-performed MICs across 91 E. coli isolates with a diverse range of AMR profiles. Additionally, to demonstrate its real-world applicability, the RASP workflow was then applied to five faecal samples where a minimum of 47 E. coli per animal (239 total) were evaluated using an AMR indexing framework.

Results

For each drug–rater–isolate combination in Experiment A, there was a clear consensus of the MIC and deviation from the consensus remained within one doubling dilution (the exception being gentamicin at two dilutions). Experiment B revealed a concordance correlation coefficient of 0.9670 (95% CI: 0.9670–0.9670) between the robot- and human-performed MICs. RASP’s application to the five faecal samples highlighted the intra-animal diversity of gut commensal E. coli, identifying between five and nine unique isolate AMR phenotypes per sample.

Conclusions

While adhering to internationally accepted guidelines, RASP was superior in throughput, cost and data resolution when compared with an experienced human technician. Integration of robotics platforms in the microbiology laboratory is a necessary advancement for future One Health AMR endeavours.
Ethidium bromide exposure unmasks an antibiotic efflux system in Rhodococcus equi
Authors: Rampacci Elisa , Marenzoni Maria Luisa , Cannalire Rolando , Pietrella Donatella , Sabatini Stefano , Giovagnoli Stefano , Felicetti Tommaso , Pepe Marco , Passamonti Fabrizio
Published: March 2021

Background

This study introduces a newly created strain (Rhodococcus equiEtBr25) by exposing R. equi ATCC 33701 to ethidium bromide (EtBr), a substrate for MDR transporters. Such an approach allowed us to investigate the resulting phenotype and genetic mechanisms underlying the efflux-mediated resistance in R. equi.

Methods

R. equi ATCC 33701 was stimulated with increasing concentrations of EtBr. The antimicrobial susceptibility of the parental strain and R. equiEtBr25 was investigated in the presence/absence of efflux pump inhibitors (EPIs). EtBr efflux was evaluated by EtBr-agar method and flow cytometry. The presence of efflux pump genes was determined by conventional PCR before to quantify the expression of 30 genes coding for membrane transporters by qPCR. The presence of erm(46) and mutations in 23S rRNA, and gyrA/gyrB was assessed by PCR and DNA sequencing to exclude the occurrence of resistance mechanisms other than efflux.

Results

R. equi EtBr25 showed an increased EtBr efflux. Against this strain, the activity of EtBr, azithromycin and ciprofloxacin was more affected than that of rifampicin and azithromycin/rifampicin combinations. Resistances were reversed by combining the antimicrobials with EPIs. Gene expression analysis detected a marked up-regulation of REQ_RS13460 encoding for a Major Facilitator Superfamily (MFS) transporter. G→A transition occurred in the transcriptional repressor tetR/acrR adjacent to REQ_RS13460.

Conclusions

Exposure of R. equi to EtBr unmasked an efflux-mediated defence against azithromycin and ciprofloxacin, which seemingly correlates with the overexpression of a specific MFS transporter. This genotype may mirror an insidious low-level resistance of clinically important isolates that could be countered by EPI-based therapies.
Japanese encephalitis vaccine cost: a major reason to be vaccinated in Bali
Authors: Wirawan I Md Ady
Published: March 2021

Travellers, especially long term and repeat, are increasingly opting to receive vaccines in destination countries. This report summarizes the high cost of Japanese encephalitis vaccination in their home country as a barrier to pre-travel uptake.
PaleoCodage—Enhancing machine-readable cuneiform descriptions using a machine-readable paleographic encoding
Authors: Homburg Timo
Published: March 2021

This publication introduces PaleoCodage, a new machine-readable way to capture cuneiform paleographic shapes. Many different systems of listing and describing cuneiform signs exist, but none of the systems can be used to describe the shape, i.e. paleographic features of cuneiform signs. PaleoCodage aims to fill this missing link of description which can benefit the Semantic Web community of linked open data dictionaries, the assyrologist community in documenting signs and their variants and the cuneiform image recognition community in providing a gold standard encoding to match against. The publication evaluates the encoding on more than 200 Unicode cuneiform signs, describes already available application cases, a linked data vocabulary for paleography and concludes by describing future work on further validating PaleoCodage and applying the paleographic vocabulary to more languages.
A Talmudic norms approach to many-valued logic
Authors: Lethen Tim
Published: March 2021

In three-valued logic, the third truth-value is often interpreted as undefined. However, the value of a logical term may be well defined if its ‘history’ is taken into account. Following this approach, the analogy to the Sorites paradox meets the eye, which in turn has recently been addressed by means of a ‘Talmudic Norms’ approach. This paper thus lays bare a religious contribution to the field of many-valued logic and implements a simplified dynamic model for the theory of Talmudic mixtures—and, thus, for the outlined Sorites logic—using standard AI search and planning techniques.
Z-Sequence: photometric redshift predictions for galaxy clusters with sequential random k-nearest neighbours
Authors: Chan Matthew C , Stott John P
Published: March 2021

We introduce Z-Sequence, a novel empirical model that utilizes photometric measurements of observed galaxies within a specified search radius to estimate the photometric redshift of galaxy clusters. Z-Sequence itself is composed of a machine learning ensemble based on the k-nearest neighbours algorithm. We implement an automated feature selection strategy that iteratively determines appropriate combinations of filters and colours to minimize photometric redshift prediction error. We intend for Z-Sequence to be a standalone technique but it can be combined with cluster finders that do not intrinsically predict redshift, such as our own DEEP-CEE. In this proof-of-concept study, we train, fine-tune, and test Z-Sequence on publicly available cluster catalogues derived from the Sloan Digital Sky Survey. We determine the photometric redshift prediction error of Z-Sequence via the median value of |Δ$z$|/(1 + $z$) (across a photometric redshift range of 0.05 ≤ $z$ ≤ 0.6) to be ∼0.01 when applying a small search radius. The photometric redshift prediction error for test samples increases by 30–50 per cent when the search radius is enlarged, likely due to line-of-sight interloping galaxies. Eventually, we aim to apply Z-Sequence to upcoming imaging surveys such as the Legacy Survey of Space and Time to provide photometric redshift estimates for large samples of as yet undiscovered and distant clusters.
Genomic editing of intronic enhancers unveils their role in fine-tuning tissue-specific gene expression in Arabidopsis thaliana
Authors: Meng Fanli , Zhao Hainan , Zhu Bo , Zhang Tao , Yang Mingyu , Li Yang , Han Yingpeng , Jiang Jiming
Published: March 2021

Enhancers located in introns are abundant and play a major role in the regulation of gene expression in mammalian species. By contrast, the functions of intronic enhancers in plants have largely been unexplored and only a handful of plant intronic enhancers have been reported. We performed a genome-wide prediction of intronic enhancers in Arabidopsis thaliana using open chromatin signatures based on DNase I sequencing. We identified 941 candidate intronic enhancers associated with 806 genes in seedling tissue and 1,271 intronic enhancers associated with 1,069 genes in floral tissue. We validated the function of 15 of 21 (71%) of the predicted intronic enhancers in transgenic assays using a reporter gene. We also created deletion lines of three intronic enhancers associated with two different genes using CRISPR/Cas. Deletion of these enhancers, which span key transcription factor binding sites, did not abolish gene expression but caused varying levels of transcriptional repression of their cognate genes. Remarkably, the transcriptional repression of the deletion lines occurred at specific developmental stages and resulted in distinct phenotypic effects on plant morphology and development. Clearly, these three intronic enhancers are important in fine-tuning tissue- and development-specific expression of their cognate genes.
FHY3 interacts with phytochrome B and regulates seed dormancy and germination
Authors: Liu Shuangrong , Yang Liwen , Li Jialong , Tang Weijiang , Li Jigang , Lin Rongcheng
Published: March 2021

Seed dormancy and germination are fundamental processes for plant propagation, both of which are tightly regulated by internal and external cues. Phytochrome B (phyB) is a major red/far-red-absorbing photoreceptor that senses light signals that modulate seed dormancy and germination. However, the components that directly transduce that signal downstream of phyB are mostly unknown. Here, we show that the transposase-derived transcription factor FAR-RED ELONGATED HYPOCOTYL3 (FHY3) inhibits seed dormancy and promotes phyB-mediated seed germination in Arabidopsis thaliana. FHY3 physically interacts with phyB in vitro and in vivo. RNA-sequencing and reverse transcription-quantitative polymerase chain reaction analyses showed that FHY3 regulates multiple downstream genes, including REVEILLE2 (RVE2), RVE7, and SPATULA (SPT). Yeast one-hybrid, electrophoresis mobility shift, and chromatin immunoprecipitation assays demonstrated that FHY3 directly binds these genes via a conserved FBS cis-element in their promoters. Furthermore, RVE2, RVE7, and GIBBERELLIN 3-OXIDASE 2 (GA3ox2) genetically act downstream of FHY3. Strikingly, light and phyB promote FHY3 protein accumulation. Our study reveals a transcriptional cascade consisting of phyB-FHY3-RVE2/RVE7/SPT-GA3ox2 that relays environmental light signals and thereby controls seed dormancy and germination.
Sensory, Motor, and Psychosocial Characteristics of Individuals With Chronic Neck Pain: A Case Control Study
Authors: Rampazo Érika Patrícia , da Silva Viviane Ribeiro , de Andrade Ana Laura Martins , Back Cláudio Gregório Nuernberg , Madeleine Pascal , Arendt-Nielsen Lars , Liebano Richard Eloin
Published: March 2021

Objective

Given the complex and unclear etiology of neck pain, it is important to understand the differences in central sensitization as well as psychosocial factors in individuals with chronic neck pain and healthy controls. The purpose of this study was to benchmark differences in central sensitization, psychosocial factors, and range of motion between people with nonspecific chronic neck pain and healthy controls and to analyze the correlation between pain intensity, neck disability, and psychosocial factors in people with chronic neck pain.

Methods

Thirty individuals with chronic neck pain and 30 healthy controls were included in this case–control study. Outcome measures were as follows: central sensitization (pressure pain threshold, temporal summation, and conditioned pain modulation), psychosocial factors (depressive symptoms, pain catastrophizing, and quality of life), and active cervical range of motion.

Results

People with neck pain had lower local pressure pain threshold, a decrease in conditioned pain modulation, more depressive symptoms, greater pain catastrophizing, lower quality of life, and reduced range of motion for neck rotation compared with healthy controls. In people with neck pain, moderate correlations were observed between pain intensity and quality of life (ρ = −0.479), disability and pain catastrophizing (ρ = 0.379), and disability and quality of life (ρ = −0.456).

Conclusion

People with neck pain have local hyperalgesia, impaired conditioning pain modulation, depressive symptoms, pain catastrophizing, low quality of life, and reduced active range of motion during neck rotation, which should be taken into account during assessment and treatment.

Impact

This study shows that important outcomes, such as central sensitization and psychosocial factors, should be considered during assessment and treatment of individuals with nonspecific chronic neck pain. In addition, pain intensity and neck disability are correlated with psychosocial factors.
Predictors of UK healthcare worker burnout during the COVID-19 pandemic
Authors: Ferry A V , Wereski R , Strachan F E , Mills N L
Published: March 2021

Background

The COVID-19 pandemic is putting health professionals under increasing pressure. This population is already acknowledged to be at risk of burnout.

Aim

We aim to provide a ‘snapshot’ of the levels of burnout, anxiety, depression and distress among healthcare workers during the COVID-19 pandemic.

Methods

We distributed an online survey via social media in June 2020 open to any UK healthcare worker. The primary outcome measure was symptoms of burnout measured using the Copenhagen Burnout Inventory. Secondary outcomes of depression, anxiety, distress and subjective measures of stress were also recorded. Multivariate logistic regression analysis was performed to identify factors associated with burnout, depression, anxiety and distress.

Results

A total of 539 persons responded to the survey; 90% female and 53% nurses. Participants with moderate-to-severe burnout were younger (49% vs. 33% under 40 years, P = 0.004), more likely to have pre-existing comorbidities (21% vs. 12%, P = 0.031), twice as likely to have been redeployed from their usual role (22% vs. 11%; P = 0.042), or to work in an area dedicated to COVID-19 patients (50% vs. 32%, P < 0.001) and were almost 4 times more likely to have previous depression (24% vs. 7%; P = 0.012).

Conclusion

Independent predictors of burnout were being younger, redeployment, exposure to patients with COVID-19, being female and a history of depression. Evaluation of existing psychological support interventions is required with targeted approaches to ensure support is available to those most at risk.
Quality evaluation of the underlying evidence in the updated treatment recommendations for systemic lupus erythematosus
Authors: Yavne Yarden , Edel Yonatan , Berman Julia , Eviatar Tali , Shepshelovich Daniel
Published: March 2021

Objectives

SLE is a multisystem autoimmune disorder known for its broad clinical spectrum. Recently, the European, British and Latin American rheumatology professional societies [EULAR, British Society for Rheumatology (BSR) and Pan-American League of Associations of Rheumatology (PANLAR)] published updated recommendations for SLE management. The objective of this study was to characterize the data supporting the updated recommendations, with the goal of highlighting areas that could benefit from additional high-quality research.

Methods

References were compiled from the recently published EULAR, BSR and PANLAR SLE treatment recommendations. Data collected from each study included publication year, treatment regimen, study design, sample size, inclusion and exclusion criteria and relevant SLE diagnostic criteria. Studies with less than 10 patients and those that did not specify the SLE diagnostic criteria used were excluded.

Results

Altogether, 250 studies were included in this study. The majority were prospective and retrospective cohorts (72%), with only a small percentage of randomized controlled trials (28%). The median (interquartile range) number of patients included was 37 (19–86). The revised ACR 1982 criteria were the most commonly used criteria for SLE diagnosis (52%), followed by the revised ACR criteria from 1997 (27%). Only a small proportion of studies included the use of disease activity scores when defining study population (15%).

Conclusion

Our study has indicated a scarcity of sufficiently powered high-quality research referenced in the recently published SLE treatment guidelines. Well-designed large-scale studies utilizing the updated 2019 SLE diagnostic criteria are needed to better inform healthcare professionals caring for patients with SLE.
Detection of Toxoplasma gondii bradyzoite genes in the peripheral blood mononuclear cells among patients with toxoplasmic chorioretinitis
Authors: Khanaliha Khadijeh , Hedayatfar Alireza , Minaeian Sara , Bokharaei-Salim Farah , Alemzadeh Sayyed Amirpooya , Garshasbi Saba , Fagheei Aghmiyuni Zeinab , Salemi Borna
Published: March 2021

Background

Toxoplasmic chorioretinitis may occur as a result of acquired toxoplasmosis or reactivated congenital toxoplasmosis. In this study, Toxoplasma gondii bradyzoite genes along with the B1 gene were evaluated to detect T. gondii DNA in serum and peripheral blood mononuclear cells (PBMCs) of patients with toxoplasmic chorioretinitis.

Methods

Blood samples were collected from 10 patients (7 cases of active chorioretinal lesions and 3 cases of old chorioretinal scars). The genomic DNA was extracted from the patients’ serum and PBMCs and a polymerase chain reaction (PCR) assay was performed using bradyzoite genes along with B1. The subjects were also evaluated in terms of the T. gondii antibodies.

Results

The PCR results were positive in four of seven patients (57.1%) with active ocular toxoplasmosis lesions. In three patients (42.8%), the PCR results were positive for MAG-1 and SAG-4 and in one patient (14.3%) the PCR results were only positive for the B1 gene. The PCR results were positive only in the PBMCs, whereas they were negative in the serum samples. Two patients with positive PCR results showed high Toxoplasma immunoglobulin G (IgG) antibody titres. However, none of the patients showed positive Toxoplasma IgM antibodies.

Conclusions

The PBMCs are suitable for evaluating toxoplasmic chorioretinitis. The present results showed that PCR with bradyzoite genes is useful in the diagnosis of toxoplasmic chorioretinitis in PBMCs.
Psychosocial factors related to BRCA1/2 disclosures
Authors: Timbs Mayanith
Published: March 2021

Patients who learn they carry breast cancer genes 1 and 2 (BRCA1/2) must decide if, when, and how they want to disclose this information to family members who may be affected. This article discusses the psychosocial factors that may influence patient decisions to disclose positive BRCA1/2 results to family members, as well as the role of nurses in educating and advocating for patients and their families.
Diabetic peripheral neuropathy
Authors: Anastasi Joyce K. , Klug Chloe
Published: March 2021

Patients with diabetes mellitus may experience painful and nonpainful diabetic peripheral neuropathy (DPN). This article offers an overview of DPN and the clinical assessment and management of patients with DPN, as well as the nurse's role in supporting these patients.
International Classification of Diseases (ICD) Codes Fail to Accurately Identify Injection Drug Use Associated Endocarditis Cases
Authors: Barnes Erin , Peacock James , Bachmann Laura
Published: March 2021

Objectives:

Infective endocarditis (IE) secondary to injection drug use (IDU-IE) is a disease with high morbidity, cost, and rapid demographic evolution. Studies frequently utilize combinations of International Statistical Classification of Diseases (ICD) codes to identify IDU-IE cases in electronic medical records. This is a validation of this identification strategy in a US cohort.

Methods:

Records from January 1, 2004 to September 31, 2015 for those aged ≥18yo with any ICD-coded IE encounter (inpatient or outpatient) were retrieved from the electronic medical record and then manually reviewed and classified as IDU-IE by strict and inclusive criteria. This registry was then used to assess the diagnostic accuracy of 10 identification algorithms that combined substance use, hepatitis C, and IE ICD codes.

Results:

IE was present in 629 of the 2055 manually reviewed records; 109 reported IDU within 3 months of IE diagnosis and an additional 32 during their lifetime (141 cases). In contrast, no algorithm identified more than 46 (33%) of these cases. Algorithms assessing encounters with both an IE and substance use code had specificities >99% but sensitivities ≤11% with negative predictive values of 83% to 84% and positive predictive values ranging from 75% to 91%. Use of a hepatitis C OR substance use code with an IE-coded encounter resulted in higher sensitivities of 22% to 32% but more false positives and overall positive predictive value of <70%. This algorithm limited to age ≤45yo had the best, but still low, discrimination ability with an area under the receiver operating characteristic curve of 0.62.

Conclusion:

Substance use and hepatitis C codes have poor ability to accurately classify an IE-coded encounter as IDU-IE or routine IE.
Assessing Stigma Towards Substance Use in Pregnancy: A Randomized Study Testing the Impact of Stigmatizing Language and Type of Opioid Use on Attitudes Toward Mothers With Opioid Use Disorder
Authors: Schiff Davida M. , Stoltman Jonathan J.K. , Nielsen Timothy C. , Myers Sara , Nolan Moira , Terplan Mishka , Patrick Stephen W. , Wilens Timothy E. , Kelly John
Published: March 2021

Objective:

To examine the extent to which colloquial phrases used to describe opioid-exposed mother-infant dyads affects attitudes toward mothers with opioid use disorder (OUD) to assess the role stigmatizing language may have on the care of mothers with OUD.

Methods:

We employed a randomized, cross-sectional, case vignette of an opioid-exposed dyad, varying on 2 factors: (1) language to describe newborn (“substance-exposed newborn” vs “addicted baby”) and (2) type of maternal opioid use (injection heroin vs nonmedical use of prescription opioids). Participants were recruited using an online survey platform. Substance-related stigma, punitive-blaming, and supportive scales were constructed to assess attitudes. Two-way analyses of variance were conducted to determine mean scale differences by vignette. Posthoc analyses assessed individual item-level differences.

Results:

Among 1227 respondents, we found a small statistical difference between language and opioid type factors for the supportive scale only (F = 4.31, η

2
 = .004, P = 0.038), with greater agreement with supportive statements when describing injection heroin use, compared to prescription opioid use, for the “substance-exposed newborn” vignette only. In posthoc analyses, greater than 85% of respondents agreed the mother was “responsible for her opioid use,” her “addiction was caused by poor choices,” and that she “put her baby in danger.”

Conclusions:

We found no major differences in attitudes regardless of vignette received. Overall, respondents supported opportunities for maternal recovery yet blamed women, describing mothers as culpable for causing harm to their newborn, showcasing internally conflicting views. These views could contribute to ongoing stigma and avoidance of care among pregnant women with OUD.
Statewide Availability of Buprenorphine/Naloxone in Acute Care Hospitals
Authors: Pham Susie , Haigh Alexandra , Barrett Eileen
Published: March 2021

Objectives:

Evaluate the availability of buprenorphine/naloxone for inpatients with opioid use disorder in a state's acute care hospitals.

Methods:

An audit study of all acute care hospitals in New Mexico was performed. Hospitals were surveyed on the availability of buprenorphine/naloxone on their inpatient formularies and their ability to obtain buprenorphine/naloxone within 1 day should a patient need it.

Results:

Of the surveyed hospitals, 45.5% did not have buprenorphine/naloxone on their inpatient formularies. Of the 26 counties in New Mexico with acute care hospitals, 10 did not have buprenorphine/naloxone available for inpatients. Three of these counties have drug overdose death rates equal to or higher than the state average.

Conclusions:

In 1 predominately rural state with an opioid overdose death rate higher than the national average, approximately half of acute care hospitals had buprenorphine/naloxone available to patients on their inpatient formulary. Efforts to increase buprenorphine/naloxone availability in hospitals are needed, particularly in rural areas where there may not be other locations to access treatment for opioid use disorder.
Low Threshold Telemedicine-based Opioid Treatment for Criminal Justice Involved Adults During the COVID-19 Pandemic: A Case Report
Authors: Flavin Lila , Tofighi Babak , Krawczyk Noa , Schatz Daniel , McNeely Jennifer , Butner Jenna
Published: March 2021

Criminal justice involved individuals have a high rate of opioid overdose death following release. In March 2020, New York City jails released over 1000 inmates due to concern of COVID-19 outbreaks in county jails. The closure of addiction treatment clinics further complicated efforts to expand access to medications for opioid use disorder among criminal justice involved adults. The New York City Health + Hospitals Virtual Buprenorphine Clinic established in March 2020 offered low-threshold telemedicine-based opioid treatment with buprenorphine-naloxone, specifically for criminal justice involved adults post-release. We describe a case report of the novel role of tele-conferencing for the provision of buprenorphine-naloxone for jail-released adults with opioid use disorder experiencing homelessness during the COVID-19 pandemic. The patient is a 49-year-old male with severe opioid use disorder released from New York City jail as part of its early release program. He then started using diverted buprenorphine-naloxone, and 1 month later a harm-reduction specialist at his temporary housing at a hotel referred him to an affiliated buprenorphine provider and then eventually to the New York City Health + Hospitals Virtual Buprenorphine Clinic, where he was continued on buprenorphine-naloxone, and was followed biweekly thereafter until being referred to an office-based opioid treatment program. For this patient, telemedicine-based opioid treatment offered a safe and feasible approach to accessing medication for opioid use disorder during the COVID-19 pandemic and following incarceration.
Recognizing and Reducing the Impact of Trauma of Hospitalization: Considerations for Persons Who Use Drugs
Authors: Messinger John C. , Suzuki Joji
Published: March 2021

Amidst the ongoing opioid crisis, the number of individuals with substance use disorders being hospitalized for acute medical illnesses has increased. There is now a growing recognition that these events may be psychologically traumatic, leading to the development of acute stress reactions, and post-traumatic stress disorder. Patients who use drugs may be particularly susceptible to being traumatized due to their underlying psychiatric comorbidities, prior trauma histories, inadequate treatment of the underlying substance use disorders, and stigmatization. Interventions such as early identification and screening, trauma-informed care, and specialized addiction services may help to mitigate the risks of trauma amongst this population. More research is needed to better guide hospitals to ensure people who use drugs receive optimal care.
Genetic Risk Assessment for Atherosclerotic Cardiovascular Disease: A Guide for the General Cardiologist
Authors: Belanger Matthew J. , Kelly Erik M. , Tahir Usman A. , Benson Mark D.
Published: March 2021

Genetic testing for cardiovascular (CV) disease has had a profound impact on the diagnosis and evaluation of monogenic causes of CV disease, such as hypertrophic and familial cardiomyopathies, long QT syndrome, and familial hypercholesterolemia. The success in genetic testing for monogenic diseases has prompted special interest in utilizing genetic information in the risk assessment of more common diseases such as atherosclerotic cardiovascular disease (ASCVD). Polygenic risk scores (PRS) have been developed to assess the risk of coronary artery disease, which now include millions of single-nucleotide polymorphisms that have been identified through genomewide association studies. Although these PRS have demonstrated a strong association with coronary artery disease in large cross-sectional population studies, there remains intense debate regarding the added value that PRS contributes to existing clinical risk prediction models such as the pooled cohort equations. In this review, we provide a brief background of genetic testing for monogenic drivers of CV disease and then focus on the recent developments in genetic risk assessment of ASCVD, including the use of PRS. We outline the genetic testing that is currently available to all cardiologists in the clinic and discuss the evolving sphere of specialized cardiovascular genetics programs that integrate the expertise of cardiologists, geneticists, and genetic counselors. Finally, we review the possible implications that PRS and pharmacogenomic data may soon have on clinical practice in the care for patients with or at risk of developing ASCVD.