bluuebunny/crossref_metadata_2025 huggingface dataset:
Transferrin receptor targeting by de novo sheet extension
Authors: Sahtoe Danny D. , Coscia Adrian , Mustafaoglu Nur , Miller Lauren M. , Olal Daniel , Vulovic Ivan , Yu Ta-Yi , Goreshnik Inna , Lin Yu-Ru , Clark Lars , Busch Florian , Stewart Lance , Wysocki Vicki H. , Ingber Donald E. , Abraham Jonathan , Baker David
Published: April 2021

Significance

The de novo design of proteins that bind natural target proteins is useful for a variety of biomedical and biotechnological applications. We describe a design strategy to target proteins containing an exposed beta edge strand. We use the approach to design binders to the human transferrin receptor which shuttles back and forth across the blood–brain barrier. Such binders could be useful for the delivery of therapeutics into the brain.
DDX11 loss causes replication stress and pharmacologically exploitable DNA repair defects
Authors: Jegadesan Nanda Kumar , Branzei Dana
Published: April 2021

Significance

Replication stress can affect development and is a hallmark of cancers. Warsaw breakage syndrome is a developmental disorder caused by mutations in the conserved DDX11 DNA helicase. Here, using human cellular models of DDX11 deficiency, we report that DDX11 helicase prevents replication stress and mediates homology-directed repair via homologous recombination. Mechanistically, DDX11 promotes resection, enabling RPA and RAD51 focus formation, and acts nonredundantly with the RAD51 mediators BRCA1 and BRCA2. As a result, targeting DDX11 confers improved chemotherapy responsiveness in both chemotherapy-sensitive and drug-resistant BRCA1/2-mutated cancers that regained homologous recombination proficiency by suppressor mutation or somatic reversion. The results pinpoint DDX11 as a critical replication stress mitigating factor whose targeting can improve chemotherapeutic response in a range of cancers.
Surface plasmon mediates the visible light–responsive lithium–oxygen battery with Au nanoparticles on defective carbon nitride
Authors: Zhu Zhuo , Ni Youxuan , Lv Qingliang , Geng Jiarun , Xie Wei , Li Fujun , Chen Jun
Published: April 2021

Significance

Deployment of electric vehicles with long driving ranges demands new electrochemistry beyond the current Li-ion batteries. Aprotic lithium–oxygen batteries have gained considerable attention and promise to provide energy density of approximately three to five times that of state-of-the-art Li-ion batteries, but they are plagued by sluggish reaction kinetics at cathodes and induced large-voltage hysteresis. A photo-mediated strategy has been attempted to reduce the discharge/charge overvoltage, but it is obstructed by the limited ultraviolet light absorption and the inevitably high carrier recombination on semiconductor photocathodes. Here, a plasmonic heterojunction of gold nanoparticle-decorated carbon nitride with nitrogen vacancies is used as a bifunctional catalyst to accelerate the oxygen cathode reactions of the lithium–oxygen battery under visible light.
Paraphrase and parallel treebank for the comparison of French and Chinese syntax
Authors: Poiret Rafaël , Mille Simon , Liu Haitao
Published: April 2021

This paper proposes to study the contrastive syntax of French and Chinese through the lens of syntactic mismatches, and by making use of parallel treebanks. A syntactic mismatch is the non-similarity between the syntactic structures of one linguistic unit and its translation. Syntactic mismatches are formalized using the notion of paraphrase from the Meaning-Text Theory, which allows for capturing mismatches at different levels of the linguistic description (e.g. Semantic, Deep-Syntactic, and Surface-Syntactic). In this paper, we report in details on the types of paraphrases found in the seed corpus used, demonstrating that the Deep-Syntactic paraphrases constitute the best starting point for our study. Then, we show how, starting from the seed corpus, we semi-automatically constructed a multi-layer parallel treebank with the alignment and annotation of paraphrases.
Cost and responsibility sharing arrangements in the EU to prevent and control notifiable veterinary and phytosanitary risks.
Authors: Asseldonk M. A. P. M. van , Bergevoet R. H. M.
Published: April 2021

A cost and responsibility sharing scheme (CRSS) is gaining interest in Member States (MSs) to prevent and control notifiable veterinary and phytosanitary risks. A vital part of this is a public private partnership (PPP) in which farmers and national governments decide how costs and responsibilities are shared. A CRSS-PPP has the goal to raise more awareness, reduce risk exposure, provide incentives for rapid disclosure and increases support of control strategies if outbreaks occur. The main reason for farmers to participate in a CRSS is the responsibility sharing part. In many MSs, farmers lack influence on the decision-making process regarding prevention and control of outbreaks although they are most affected. However, implementing new CRSSs requires careful preparation, negotiations and trust building. An obligation for a gradual introduction of CRSSs by all MSs respecting certain harmonized criteria established at European Union level is not likely in the near future. A more dual approach is foreseen whereby individual MSs continue or establish CRSSs by means of PPPs while others will still opt for more hierarchical regulated disease policies.
Keeping it in the family: transgenerational memories of plant defence.
Authors: Prashant Singh Prashant Singh , Roberts M. R.
Published: April 2021

Plants possess a sophisticated array of systems with which to sense and respond to their internal and external environment. Biological changes triggered by such systems represent examples of phenotypic plasticity. One aspect of phenotypic plasticity that has recently emerged is transgenerational priming of plant defence responses - the persistence of induced resistance responses across generations. There has been a recent surge in interest in epigenetic mechanisms as a basis for phenotypic plasticity, including the ability for such epigenetic changes to be inherited across generations. In this review, we focus on the evidence that attack by pests and disease can stimulate plant defence responses that increase levels of resistance not only in attacked plants, but in their offspring, and discuss mechanisms by which environmental stress signals can be inherited. Finally, we consider the implications of transgenerational defence responses for plants in natural and agricultural systems.
Regulation of Golgi turnover by CALCOCO1-mediated selective autophagy
Authors: Nthiga Thaddaeus Mutugi , Shrestha Birendra Kumar , Bruun Jack-Ansgar , Larsen Kenneth Bowitz , Lamark Trond , Johansen Terje
Published: April 2021

The Golgi complex is essential for the processing, sorting, and trafficking of newly synthesized proteins and lipids. Golgi turnover is regulated to meet different cellular physiological demands. The role of autophagy in the turnover of Golgi, however, has not been clarified. Here we show that CALCOCO1 binds the Golgi-resident palmitoyltransferase ZDHHC17 to facilitate Golgi degradation by autophagy during starvation. Depletion of CALCOCO1 in cells causes expansion of the Golgi and accumulation of its structural and membrane proteins. ZDHHC17 itself is degraded by autophagy together with other Golgi membrane proteins such as TMEM165. Taken together, our data suggest a model in which CALCOCO1 mediates selective Golgiphagy to control Golgi size and morphology in eukaryotic cells via its interaction with ZDHHC17.
A Randomized, Single-Blind, Crossover Study Evaluating the Impact of OnabotulinumtoxinA Treatment on Mood and Appearance During the COVID-19 Pandemic
Authors: Cristel Robert T , Gandhi Nimit D , Issa Tariq Z , Kola Eljona , Demesh Daniel , Dayan Steven H
Published: April 2021

Background

The emergence of COVID-19 led rapidly to one of the most severe disease outbreaks in modern history. This caused many aesthetic practices to close temporarily, providing a unique opportunity to evaluate the impact of neurotoxin use in the setting of an ongoing pandemic.

Objectives

The aim of this study was to examine whether administration of onabotulinumtoxinA (BOTOX Cosmetic, Allergan plc, Dublin, Ireland) to regular users synergistically amplifies the elevation in mood/happiness, self-satisfaction with appearance, and overall satisfaction in the context of the ongoing pandemic.

Methods

A randomized, single-blind, crossover study was designed to evaluate the impact of neurotoxin treatment in the upper third of the face on mood, self-satisfaction with appearance, and overall satisfaction. The placebo group crossed over to treatment after 1 month. Surveys evaluating patient happiness, self-satisfaction with appearance, and overall efficacy were completed by both groups, and again by the placebo group following crossover to treatment.

Results

Forty-five subjects were enrolled: 30 in the treatment group and 15 in the control/crossover group. The placebo group demonstrated no change in happiness or self-satisfaction in appearance until crossover to the treatment group. Both groups, once receiving onabotulinumtoxinA, reported increased happiness, self-satisfaction with appearance, and overall treatment satisfaction.

Conclusions

OnabotulinumtoxinA treatment to the upper face in the midst of the COVID-19 pandemic was found to increase patient happiness, self-satisfaction with appearance, and overall treatment satisfaction.

Level of Evidence: 2
Quickomics: exploring omics data in an intuitive, interactive and informative manner
Authors: Gao Benbo , Zhu Jing , Negi Soumya , Zhang Xinmin , Gyoneva Stefka , Casey Fergal , Wei Ru , Zhang Baohong
Published: April 2021

We developed Quickomics, a feature-rich R Shiny-powered tool to enable biologists to fully explore complex omics statistical analysis results and perform advanced analysis in an easy-to-use interactive interface. It covers a broad range of secondary and tertiary analytical tasks after primary analysis of omics data is completed. Each functional module is equipped with customizable options and generates both interactive and publication-ready plots to uncover biological insights from data. The modular design makes the tool extensible with ease.

Availability and implementation

Researchers can experience the functionalities with their own data or demo RNA-Seq and proteomics datasets by using the app hosted at http://quickomics.bxgenomics.com and following the tutorial, https://bit.ly/3rXIyhL. The source code under GPLv3 license is provided at https://github.com/interactivereport/Quickomics for local installation.

Supplementary information

Supplementary data are available at Bioinformatics online.
Multimodality imaging of myocardial viability: an expert consensus document from the European Association of Cardiovascular Imaging (EACVI)
Authors: Almeida Ana G , Carpenter John-Paul , Cameli Matteo , Donal Erwan , Dweck Marc R , Flachskampf Frank A , Maceira Alicia M , Muraru Denisa , Neglia Danilo , Pasquet Agnès , Plein Sven , Gerber Bernhard L ,   Reviewers: This document was reviewed by members of the 2018–2020 EACVI Scientific Documents Committee:, Buechel Ronny , Buechel Ronny , Delgado Victoria , Sade Leyla Elif , Stankovic Ivan ,   chair of the 2018–2020 EACVI Scientific Documents Committee:, Cosyns Bernard ,   the 2018–2020 EACVI President:, Edvardsen Thor
Published: April 2021

In clinical decision making, myocardial viability is defined as myocardium in acute or chronic coronary artery disease and other conditions with contractile dysfunction but maintained metabolic and electrical function, having the potential to improve dysfunction upon revascularization or other therapy. Several pathophysiological conditions may coexist to explain this phenomenon. Cardiac imaging may allow identification of myocardial viability through different principles, with the purpose of prediction of therapeutic response and selection for treatment. This expert consensus document reviews current insight into the underlying pathophysiology and available methods for assessing viability. In particular the document reviews contemporary viability imaging techniques, including stress echocardiography, single photon emission computed tomography, positron emission tomography, cardiovascular magnetic resonance, and computed tomography and provides clinical recommendations for how to standardize these methods in terms of acquisition and interpretation. Finally, it presents clinical scenarios where viability assessment is clinically useful.
Echocardiographic phenogrouping by machine learning for risk stratification in the general population
Authors: Sabovčik František , Cauwenberghs Nicholas , Vens Celine , Kuznetsova Tatiana
Published: April 2021

Aims 

There is a need for better phenotypic characterization of the asymptomatic stages of cardiac maladaptation. We tested the hypothesis that an unsupervised clustering analysis utilizing echocardiographic indexes reflecting left heart structure and function could identify phenotypically distinct groups of asymptomatic individuals in the general population.

Methods and results 

We prospectively studied 1407 community-dwelling individuals (mean age, 51.2 years; 51.1% women), in whom we performed clinical and echocardiographic examination at baseline and collected cardiac events on average 8.8 years later. Cardiac phenotypes that were correlated at r > 0.8 were filtered, leaving 21 echocardiographic features, and systolic blood pressure for phenogrouping. We employed hierarchical and Gaussian mixture model-based clustering. Cox regression was used to demonstrate the clinical validity of constructed phenogroups. Unsupervised clustering analyses classified study participants into three distinct phenogroups that differed markedly in echocardiographic indexes. Indeed, cluster 3 had the worst left ventricular (LV) diastolic function (i.e. lowest e’ velocity and left atrial (LA) reservoir strain, highest E/e’, and LA volume index) and LV remodelling. The phenogroups were also different in cardiovascular risk factor profiles. We observed increase in the risk for incidence of adverse events across phenogroups. In the third phenogroup, the multivariable adjusted risk was significantly higher than the average population risk for major cardiovascular events (51%, P = 0.0028).

Conclusion 

Unsupervised learning algorithms integrating routinely measured cardiac imaging and haemodynamic data can provide a clinically meaningful classification of cardiac health in asymptomatic individuals. This approach might facilitate early detection of cardiac maladaptation and improve risk stratification.
Genetic diversity, population structure, and selection signature in Ethiopian sorghum [Sorghum bicolor L. (Moench)] germplasm
Authors: Wondimu Zeleke , Dong Hongxu , Paterson Andrew H , Worku Walelign , Bantte Kassahun
Published: April 2021

Ethiopia, the probable center of origin and diversity for sorghum [Sorghum bicolor L. (Moench)] and with unique ecogeographic features, possesses a large number of sorghum landraces that have not been well studied. Increased knowledge of this diverse germplasm through large-scale genomic characterization may contribute for understanding of evolutionary biology, and adequate use of these valuable resources from the center of origin. In this study, we characterized genetic diversity, population structure and selection signature in 304 sorghum accessions collected from diverse sorghum growing regions of Ethiopia using genotyping-by-sequencing. We identified a total of 108,107 high-quality single-nucleotide polymorphism (SNPs) markers that were evenly distributed across the sorghum genome. The average gene diversity among accessions was high (He = 0.29). We detected a relatively low frequency of rare alleles (26%), highlighting the potential of this germplasm for subsequent allele mining studies through genome-wide association studies. Although we found no evidence of genetic differentiation among administrative regions (FST = 0.02, P = 0.12), population structure and cluster analyses showed clear differentiation among six Ethiopian sorghum populations (FST = 0.28, P = 0.01) adapting to different environments. Analysis of SNP differentiation between the identified genetic groups revealed a total of 40 genomic regions carrying signatures of selection. These regions harbored candidate genes potentially involved in a variety of biological processes, including abiotic stress tolerance, pathogen defense and reproduction. Overall, a high level of untapped diversity for sorghum improvement remains available in Ethiopia, with patterns of diversity consistent with divergent selection on a range of adaptive characteristics.
On the use of GBLUP and its extension for GWAS with additive and epistatic effects
Authors: Zhang Jie , Liu Fang , Reif Jochen C , Jiang Yong
Published: April 2021

Genomic best linear unbiased prediction (GBLUP) is the most widely used model for genome-wide predictions. Interestingly, it is also possible to perform genome-wide association studies (GWAS) based on GBLUP. Although the estimated marker effects in GBLUP are shrunken and the conventional test based on such effects has low power, it was observed that a modified test statistic can be produced and the result of test was identical to a standard GWAS model. Later, a mathematical proof was given for the special case that there is no fixed covariate in GBLUP. Since then, the new approach has been called “GWAS by GBLUP”. Nevertheless, covariates such as environmental and subpopulation effects are very common in GBLUP. Thus, it is necessary to confirm the equivalence in the general case. Recently, the concept was generalized to GWAS for epistatic effects and the new approach was termed rapid epistatic mixed-model association analysis (REMMA) because it greatly improved the computational efficiency. However, the relationship between REMMA and the standard GWAS model has not been investigated. In this study, we first provided a general mathematical proof of the equivalence between “GWAS by GBLUP” and the standard GWAS model for additive effects. Then, we compared REMMA with the standard GWAS model for epistatic effects by a theoretical investigation and by empirical data analyses. We hypothesized that the similarity of the two models is influenced by the relative contribution of additive and epistatic effects to the phenotypic variance, which was verified by empirical and simulation studies.
Septate junction proteins are required for egg elongation and border cell migration during oogenesis in Drosophila
Authors: Alhadyian Haifa , Shoaib Dania , Ward Robert E
Published: April 2021

Protein components of the invertebrate occluding junction—known as the septate junction (SJ)—are required for morphogenetic developmental events during embryogenesis in Drosophila melanogaster. In order to determine whether SJ proteins are similarly required for morphogenesis during other developmental stages, we investigated the localization and requirement of four representative SJ proteins during oogenesis: Contactin, Macroglobulin complement-related, Neurexin IV, and Coracle. A number of morphogenetic processes occur during oogenesis, including egg elongation, formation of dorsal appendages, and border cell (BC) migration. We found that all four SJ proteins are expressed in egg chambers throughout oogenesis, with the highest and the most sustained levels in the follicular epithelium (FE). In the FE, SJ proteins localize along the lateral membrane during early and mid-oogenesis, but become enriched in an apical-lateral domain (the presumptive SJ) by stage 11. SJ protein relocalization requires the expression of other SJ proteins, as well as Rab5 and Rab11 like SJ biogenesis in the embryo. Knocking down the expression of these SJ proteins in follicle cells throughout oogenesis results in egg elongation defects and abnormal dorsal appendages. Similarly, reducing the expression of SJ genes in the BC cluster results in BC migration defects. Together, these results demonstrate an essential requirement for SJ genes in morphogenesis during oogenesis, and suggest that SJ proteins may have conserved functions in epithelial morphogenesis across developmental stages.
Mitochondrial genomes of the human pathogens Coccidioides immitis and Coccidioides posadasii
Authors: de Melo Teixeira Marcus , Lang B Franz , Matute Daniel R , Stajich Jason E , Barker Bridget M
Published: April 2021

Fungal mitochondrial genomes encode genes involved in crucial cellular processes, such as oxidative phosphorylation and mitochondrial translation, and the molecule has been used as a molecular marker for population genetics studies. Coccidioides immitis and C. posadasii are endemic fungal pathogens that cause coccidioidomycosis in arid regions across both American continents. To date, approximately 150 Coccidioides isolates have been sequenced to infer patterns of variation in nuclear genomes. However, less attention has been given to the mitochondrial genomes of Coccidioides. In this report, we describe the assembly and annotation of mitochondrial reference genomes for two representative strains of C. posadasii and C. immitis, as well as assess population variation among 77 selected genomes. The sizes of the circular-mapping molecules are 68.2 Kb in C. immitis and 75.1 Kb in C. posadasii. We identify 14 mitochondrial protein-coding genes common to most fungal mitochondria, which are largely syntenic across different populations and species of Coccidioides. Both Coccidioides species are characterized by a large number of group I and II introns, harboring twice the number of elements as compared to closely related Onygenales. The introns contain complete or truncated ORFs with high similarity to homing endonucleases of the LAGLIDADG and GIY-YIG families. Phylogenetic comparisons of mitochondrial and nuclear genomes show extensive phylogenetic discordance suggesting that the evolution of the two types of genetic material is not identical. This work represents the first assessment of mitochondrial genomes among isolates of both species of Coccidioides, and provides a foundation for future functional work.
Breast Arterial Calcifications on Mammography: A Survey of Practicing Radiologists
Authors: Collado-Mesa Fernando , Yepes Monica M , Arheart Kristopher
Published: April 2021

Objective

To explore current practice patterns of reporting and issuing recommendations based on the presence of breast arterial calcifications on mammography and existing knowledge of their prevalence and associated factors.

Methods

An online anonymous 19-question survey was distributed to 2583 practicing radiologists who were members of the Society of Breast Imaging. Questions covered demographics, breast imaging training, practice type, and knowledge regarding the epidemiology and potential clinical significance of breast arterial calcifications detected on mammograms. Differences between groups were calculated using the chi-square test or Fisher exact test. An α level of 0.05 was used to determine statistical significance.

Results

Response rate was 22% (364/1662). The median age of respondents was 51 years (range: 29–76) and most were female (248/323, 77%). The most prevalent characteristics among respondents were as follows: 69% (223/323) had completed a breast imaging fellowship, 55% (179/323) were in private practice, 49% (158/323) practiced dedicated breast imaging, and 38% (124/323) had been in practice for more than 20 years. The prevalence of breast arterial calcifications was correctly estimated to be 1%–30% by 39% (125/323) of respondents. Most respondents correctly recognized the growing evidence of an association between breast arterial calcifications and coronary artery disease (275/323, 85%). However, only 15% (48/323) always reported the presence of these calcifications, and of those who report them at any time, only 0.7% (2/274) always issued recommendations.

Conclusion

There are differences in both knowledge of the epidemiology of breast arterial calcifications and practices around their reporting amongst breast radiologists.
Association of Health-Care System With Prostate Cancer-Specific Mortality in African American and Non-Hispanic White Men
Authors: Klebaner Daniella , Courtney P Travis , Garraway Isla P , Einck John , Kumar Abhishek , Martinez Maria Elena , McKay Rana , Murphy James D , Parada Humberto , Sandhu Ajay , Stewart Tyler , Yamoah Kosj , Rose Brent S
Published: April 2021

Background

Disparities in prostate cancer-specific mortality (PCSM) between African American and non-Hispanic White (White) patients have been attributed to biological and systemic factors. We evaluated drivers of these disparities in the Surveillance, Epidemiology, and End Results (SEER) national registry and an equal-access system, the Veterans Health Administration (VHA).

Methods

We identified African American and White patients diagnosed with prostate cancer between 2004 and 2015 in SEER (n = 311 691) and the VHA (n = 90 749). We analyzed the association between race and metastatic disease at presentation using multivariable logistic regression adjusting for sociodemographic factors and PCSM using sequential competing-risks regression adjusting for disease and sociodemographic factors.

Results

The median follow-up was 5.3 years in SEER and 4.7 years in the VHA. African American men were more likely than White men to present with metastatic disease in SEER (adjusted odds ratio = 1.23, 95% confidence interval [CI] = 1.17 to 1.30) but not in the VHA (adjusted odds ratio = 1.07, 95% CI = 0.98 to 1.17). African American vs White race was associated with an increased risk of PCSM in SEER (subdistribution hazard ratio [SHR] = 1.32, 95% CI = 1.10 to 1.60) but not in the VHA (SHR = 1.00, 95% CI = 0.93 to 1.08). Adjusting for disease extent, prostate-specific antigen, and Gleason score eliminated the association between race and PCSM in SEER (aSHR = 1.04, 95% CI = 0.93 to 1.16).

Conclusions

Racial disparities in PCSM were present in a nationally representative registry but not in an equal-access health-care system, because of differences in advanced disease at presentation. Strategies to increase health-care access may bridge the racial disparity in outcomes. Longer follow-up is needed to fully assess mortality outcomes.
Video-assisted thoracoscopic surgery lobectomy and en bloc resection of the chest wall with incision of the costovertebral joints for non-small cell lung cancer
Authors: Yamamoto Shinichi , Sogabe Masaya , Endo Shunsuke
Published: April 2021

We describe a case of lung lobectomy and resection of the rib neck and head in a lung cancer patient with an invasion of the chest wall. The tumor was located in the upper lobe, adjacent to the neck of the third rib. We performed a right upper lobectomy and en bloc resection of the third rib, including the rib neck and head, by video-assisted thoracoscopic surgery with an additional 6 cm posterior incision along the right paravertebral line. The costovertebral joint incision procedure is a useful technique to ensure tumor-free margins in cases where the tumor is located close to the rib’s neck and head.
An analysis of the writing of ‘suicide cult’ members
Authors: Hodges Duncan , Paxton-Fear Katie
Published: April 2021

The infamous ‘Heaven’s Gate cult’ committed a mass suicide in 1995 believing members of the group would achieve salvation through bodily transformation and departure aboard UFOs. The group left a large volume of writing available as a book and a website which outlined their belief structure. This writing, largely by the group’s leaders Ti and Do, is supplemented by ‘exit statements’ written by the group members. We analysed these writings and demonstrated how the texts evolve from accessible texts for recruiting individuals into the group through more complex texts for cementing the belief structure and reinforcing the ingroup. We also identify differences in the ‘exit statements’ that demonstrate the ideas and concepts that gained traction with the group members.
X-ray binary accretion states in active galactic nuclei? Sensing the accretion disc of supermassive black holes with mid-infrared nebular lines
Authors: Fernández-Ontiveros Juan A , Muñoz-Darias Teo
Published: April 2021

Accretion states, which are universally observed in stellar mass black holes in X-ray binaries, might be expected in active galactic nuclei (AGN). This is the case at low luminosities, when the jet–corona coupling dominates the energy output in both populations. Previous attempts to extend this framework to a wider AGN population have been extremely challenging due to heavy hydrogen absorption of the accretion disc continuum and starlight contamination from the host galaxies. We present the luminosity–excitation diagram (LED), based on the [O iv]25.9 μm and [Ne ii]12.8 μm mid-infrared nebular line fluxes. This tool enables to probe the accretion disc contribution to the ionizing continuum. When applied to a sample of 167 nearby AGN, the LED recovers the characteristic q-shaped morphology outlined by individual X-ray binaries during a typical accretion episode, allowing us to tentatively identify the main accretion states. The soft state would include broad-line Seyferts and about half of the Seyfert 2 population, showing highly excited gas and radio-quiet cores consistent with disc-dominated nuclei, in agreement with previous studies. The hard state mostly includes low-luminosity AGN ($\lesssim 10^{-3}\, \rm {L_{Edd}}$) characterized by low-excitation radio-loud nuclei and a negligible disc contribution. The remaining half of Seyfert 2 nuclei and the bright LINERs show low excitation at high accretion luminosities and could be identified with the bright hard and intermediate states. Their hosts show ongoing star formation in the central kiloparsecs. We discuss the above scenario, its potential links with the galaxy evolution picture, and the possible presence of accretion state transitions in AGN, as suggested by the growing population of changing-look quasars.
FACT interacts with Set3 HDAC and fine-tunesGAL1transcription in response to environmental stimulation
Authors: Leng He , Liu Shaofeng , Lei Yang , Tang Yuantao , Gu Shijia , Hu Jiazhi , Chen She , Feng Jianxun , Li Qing
Published: April 2021

The histone chaperone facilitates chromatin transactions (FACT) functions in various DNA transactions. How FACT performs these multiple functions remains largely unknown. Here, we found, for the first time, that the N-terminal domain of its Spt16 subunit interacts with the Set3 histone deacetylase complex (Set3C) and that FACT and Set3C function in the same pathway to regulate gene expression in some settings. We observed that Spt16-G132D mutant proteins show defects in binding to Set3C but not other reported FACT interactors. At the permissive temperature, induction of the GAL1 and GAL10 genes is reduced in both spt16-G132D and set3Δ cells, whereas transient upregulation of GAL10 noncoding RNA (ncRNA), which is transcribed from the 3′ end of the GAL10 gene, is elevated. Mutations that inhibit GAL10 ncRNA transcription reverse the GAL1 and GAL10 induction defects in spt16-G132D and set3Δ mutant cells. Mechanistically, set3Δ and FACT (spt16-G132D) mutants show reduced histone acetylation and increased nucleosome occupancy at the GAL1 promoter under inducing conditions and inhibition of GAL10 ncRNA transcription also partially reverses these chromatin changes. These results indicate that FACT interacts with Set3C, which in turn prevents uncontrolled GAL10 ncRNA expression and fine-tunes the expression of GAL genes upon a change in carbon source.
COVID-19: Impact on Nurses and Nursing
Authors: Fauteux Nicole
Published: April 2021

Recent surveys provide clues to the pandemic's effect on the profession.
Progression from Prediabetes to Diabetes Uncommon in Older Adults
Authors: Rosenberg Karen
Published: April 2021

According to this study:

Despite the high prevalence of prediabetes among older adults, progression to diabetes is uncommon.
A Core Outcome Set for Research Evaluating Interventions to Prevent and/or Treat Delirium in Critically Ill Adults: An International Consensus Study (Del-COrS)
Authors: Rose Louise , Burry Lisa , Agar Meera , Campbell Noll L. , Clarke Mike , Lee Jacques , Marshall John C. , Devlin John W. , Blackwood Bronagh , Needham Dale M. , Siddiqi Najma , Page Valerie ,   for the Del-COrS Group
Published: April 2021

OBJECTIVES:

Delirium in critically ill adults is highly prevalent and has multiple negative consequences. To-date, trials of interventions to prevent or treat delirium report heterogenous outcomes. To develop international consensus among key stakeholders for a core outcome set for future trials of interventions to prevent and/or treat delirium in critically ill adults.

DESIGN:

Core outcome set development, as recommended by the Core Outcome Measures in Effectiveness Trials Handbook. Methods of generating items for the core outcome set included a systematic review and qualitative interviews with ICU survivors and family members. Consensus methods include a two-round web-based Delphi process and a face-to-face meeting using nominal group technique methods.

SUBJECTS:

International representatives from three stakeholder groups: 1) clinical researchers, 2) ICU interprofessional clinicians, and 3) ICU survivors and family members.

SETTING:

Telephone interviews, web-based surveys, and a face-to-face consensus meeting held at the 2019 European Delirium Association’s annual meeting in Edinburgh, Scotland.

INTERVENTION:

None.

MEASUREMENTS AND MAIN RESULTS:

Qualitative interviews with 24 ICU survivors and family members identified 36 potential outcomes; six were additional to the 97 identified from the systematic review. After item reduction, 32 outcomes were presented in Delphi Round 1; 179 experts participated, 38 ICU survivors/family members (21%), 100 clinicians (56%), 41 researchers (23%). Three additional outcomes were added to Round 2; 134 Round 1 participants (75%) completed it. Upon conclusion of the consensus building processes, the final core outcome set comprised seven outcomes: delirium occurrence (including prevalence or incidence); delirium severity; time to delirium resolution; health-related quality of life; emotional distress (i.e., anxiety, depression, acute and posttraumatic stress); cognition (including memory); and mortality.

CONCLUSIONS:

This core outcome set, endorsed by the American and Australian Delirium Societies and European Delirium Association, is recommended for future clinical trials evaluating delirium prevention or treatment interventions in critically ill adults.
Severe Acute Respiratory Syndrome Coronavirus 2 Convalescent Plasma Versus Standard Plasma in Coronavirus Disease 2019 Infected Hospitalized Patients in New York: A Double-Blind Randomized Trial*
Authors: Bennett-Guerrero Elliott , Romeiser Jamie L. , Talbot Lillian R. , Ahmed Tahmeena , Mamone Linda J. , Singh Sunitha M. , Hearing Janet C. , Salman Huda , Holiprosad Dishaw D. , Freedenberg Alex T. , Carter Jason A. , Browne Nicholas J. , Cosgrove Megan E. , Shevik Margaret E. , Generale Laura M. , Andrew Margaret A. , Nachman Sharon , Fries Bettina C.
Published: April 2021

OBJECTIVES:

Four peer-reviewed publications have reported results from randomized controlled trials of convalescent plasma for coronavirus disease 2019 infection; none were conducted in the United States nor used standard plasma as a comparator. To determine if administration of convalescent plasma to patients with coronavirus disease 2019 increases antibodies to severe acute respiratory syndrome coronavirus 2 and improves outcome.

DESIGN:

Double-blind randomized controlled trial.

SETTING:

Hospital in New York.

PATIENTS:

Patients with polymerase chain reaction documented coronavirus disease 2019 infection.

INTERVENTIONS:

Patients were randomized (4:1) to receive 2 U of convalescent plasma versus standard plasma. Antibodies to severe acute respiratory syndrome coronavirus 2 were measured in plasma units and in trial recipients.

MEASUREMENTS AND MAIN RESULTS:

Enrollment was terminated after emergency use authorization was granted for convalescent plasma. Seventy-four patients were randomized. At baseline, mean (sd) Acute Physiology and Chronic Health Evaluation II score (23.4 [5.6] and 22.5 [6.6]), percent of patients intubated (19% and 20%), and median (interquartile range) days from symptom onset to randomization of 9 (6–18) and 9 (6–15), were similar in the convalescent plasma versus standard plasma arms, respectively. Convalescent plasma had high neutralizing activity (median [interquartile range] titer 1:526 [1:359–1:786]) and its administration increased antibodies to severe acute respiratory syndrome coronavirus 2 by 14.4%, whereas standard plasma administration led to an 8.6% decrease (p = 0.005). No difference was observed for ventilator-free days through 28 days (primary study endpoint): median (interquartile range) of 28 (2–28) versus 28 (0–28; p = 0.86) for the convalescent plasma and standard plasma groups, respectively. A greater than or equal to 2 point improvement in the World Health Organization scale was achieved by 20% of subjects in both arms (p = 0.99). All-cause mortality through 90 days was numerically lower in the convalescent plasma versus standard plasma groups (27% vs 33%; p = 0.63) but did not achieve statistical significance. A key prespecified subgroup analysis of time to death in patients who were intubated at baseline was statistically significant; however, sample size numbers were small.

CONCLUSIONS:

Administration of convalescent plasma to hospitalized patients with coronavirus disease 2019 infection increased antibodies to severe acute respiratory syndrome coronavirus disease 2 but was not associated with improved outcome.
Anterior chamber depth variability between 2 hydrophobic acrylic 1-piece intraocular lenses: randomized trial
Authors: Ullrich Marlies , Ruiss Manuel , Hienert Julius , Pilwachs Caroline , Fisus Andreea Dana , Georgiev Stefan , Hirnschall Nino , Findl Oliver
Published: April 2021

Purpose:

To analyze the difference in anterior chamber depth (ACD) after uneventful cataract surgery between 2 hydrophobic acrylic 1-piece intraocular lenses (IOLs) with different material properties.

Setting:

Hanusch Hospital, Vienna, Austria.

Design:

Single-center, bilateral randomized paired-eye controlled study.

Methods:

Patients scheduled for bilateral cataract surgery were randomized to receive the Clareon IOL in 1 eye and the AcrySof IQ IOL (both Alcon Laboratories, Inc.) in the contralateral eye. Preoperatively, a slitlamp examination, optical biometry (IOLMaster 700, Carl Zeiss Meditec AG), refraction, and visual acuity measurements were performed. ACD was assessed 1 hour and 1 week postoperatively and with additional measurement of uncorrected (UDVA) and corrected distance visual acuity (CDVA) 6 months postoperatively.

Results:

80 eyes of 40 patients were analyzed in this study. ACD at the 6-month follow-up was 3.94 ± 0.30 mm for the Clareon IOL and 3.91 ± 0.32 mm for the AcrySof IQ IOL (P = .08). Statistically significant differences in the ACD shift between both IOLs were detected between 1 week and 6 months (P = .04) and 1 hour and 6 months (P = .04). There were no statistically significant differences between both IOLs in UDVA (P = .78), CDVA (P = .59), and spherical equivalent (SE, P = .39) at the 6-month visit. The mean absolute error between the measured and the aimed SE was not significant (P = .97).

Conclusions:

There was no clinically relevant difference in ACD between the Clareon IOL and the AcrySof IQ IOL in patients after uneventful cataract surgery. Both IOLs yielded good refraction and visual acuity outcomes.
Experience of resources management on coronavirus disease 2019 epidemic at a tertiary medical center in Northern Taiwan
Authors: Lan Kai-Ping , Hsu Yueh-Shuang , Chang Ching-I , Wei Pi-Ching , Guo Ti-Gen , Yen David Hung-Tsang , Hsu Teh-Fu , Tzeng Yuann-Meei , Ming Jin-Lain
Published: April 2021

Background:

Coronavirus disease 2019 (COVID-19) is a respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes infectious symptoms including fever, cough, respiratory and gastrointestinal symptoms, and even loss of smell/taste and to date had caused 489 000 people to be infected with 32 000 deaths. This article aims to develop some strategies in dealing with the COVID-19 epidemic to prevent nosocomial infection and ensure the safety of healthcare workforce and employees.

Methods:

This is a prospectively registered and retrospective descriptive study investigating the clinical characteristics, results of diagnostic tests, and patients’ disposition from February 1, 2020, to April 30, 2020, at a tertiary medical center in Northern Taiwan.

Results:

There is no nosocomial spreading of SARS-CoV-2 in our facility. The following strategies were followed: information transparency; epidemic prevention resources planning by authorities; multidisciplinary cooperation; informative technologies; immigration quarantine policies; travel restrictions; management of diversion/subdivision; self-health monitoring; social distancing; screening of travel, occupation, contact, and cluster (TOCC) history; traffic control bundling (TCB); training of using personal protective equipment; real-name visiting management; and employee care. The patients’ basic characteristics and diagnostic results were gathered. Of the 3832 cases, about 25.9% had travel history. Most of them were traveling to Asia (419 people/time, 10.9%) and from China (256 people/time, 6.7%). Meanwhile, healthcare personnel accounted for 316 people/time (8.3%) and cleaning personnel, 6 people/time (0.16%). The 36 cases who care or have contact with confirmed cases have negative results from the COVID-19 test. The most frequent symptoms were fever and upper respiratory infection followed by gastrointestinal symptoms.

Conclusion:

The above strategies were followed. Patients were stratified based on the risk of TOCC history assessment to ensure the safety of healthcare personnel and patients’ appropriate and timely medical services.
Animal models of dry eye: Their strengths and limitations for studying human dry eye disease
Authors: Chang Yu-An , Wu Yi-Ying , Lin Chung-Tien , Kawasumi Masaoki , Wu Cheng-Hsien , Kao Shou-Yen , Yang Yi-Ping , Hsu Chih-Chien , Hung Kai-Feng , Sun Yi-Chen
Published: April 2021

Dry eye disease (DED), also called the keratoconjunctivitis sicca, is one of the most common diseases in the ophthalmology clinics. While DED is not a life-threatening disease, life quality may be substantially affected by the discomfort and the complications of poor vision. As such, a large number of studies have made contributions to the investigation of the DED pathogenesis and novel treatments. DED is a multifactorial disease featured with various phenotypic consequences; therefore, animal models are valuable tools suitable for the related studies. Accordingly, selection of the animal model to recapitulate the clinical presentation of interest is important for appropriately addressing the research objective. To this end, we systemically reviewed different murine and rabbit models of DED, which are categorized into the quantitative (aqueous-deficient) type and the qualitative (evaporative) type, based on the schemes to establish. The clinical manifestations of dry eye on animal models can be induced by mechanical or surgical approaches, iatrogenic immune response, topical eye drops, blockage of neural pathway, or others. Although these models have shown promising results, each has its own limitation and cannot fully reproduce the pathophysiological mechanisms that occur in patients. Nonetheless, the animal models remain the best approximation of human DED and represent the valuable tool for the DED studies.
Lipid effects of sodium-glucose cotransporter 2 inhibitors
Authors: Lazarte Julieta , Kanagalingam Tharsan , Hegele Robert A.
Published: April 2021

Purpose of review

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are widely used antihyperglycemic drugs that show remarkable cardiorenal protective effects in patients with or without type 2 diabetes. Furthermore, they are effective among patients across a wide range of baseline renal and cardiac function. Numerous mechanisms have been evaluated to understand these remarkable clinical benefits. From an early stage, these agents were noted to affect the plasma lipid profile. Here we review lipid profile alterations attributable to SGLT2 inhibitors and also some mechanisms explored in model systems and human studies.

Recent findings

SGLT2 inhibitors given to patients with diabetes as monotherapy shift substrate utilization from carbohydrates to lipids, and have mild effects on the lipid profile. Increased LDL cholesterol appears to be associated with increased hepatic production and decreased catabolism. Increased HDL cholesterol and decreased triglycerides appear to be associated with improved insulin sensitivity and increased lipolysis. Lipid effects of SGLT2 inhibitors are further modulated by background therapy with other diabetes medications and statins.

The minor lipid profile alterations observed in patients treated with SGLT2 inhibitors are offset by the staggering range of beneficial pleiotropic mechanisms that likely explain the marked cardiorenal benefits of these agents.
The clinical epidemiology of coronavirus disease 2019 in children and adolescents mirrors the widening gap in healthcare disparities
Authors: Zirinsky Elissa , Paintsil Elijah , Oliveira Carlos R.
Published: April 2021

Purpose of review

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has exacerbated the longstanding racial/ethnic health disparities in the USA, with a disproportionately negative effect on children of color. This review summarizes recently published studies that describe the clinical epidemiology and racial/ethnic disparities associated with SARS-CoV-2 in children.

Recent findings

Children with SARS-CoV-2 infections manifest with a wide spectrum of disease. Most are either asymptomatic or mildly symptomatic with fever, gastrointestinal, and/or upper respiratory disease. Some children can progress to develop severe lower respiratory disease or a hyper-inflammatory, Kawasaki-like syndrome leading to cardiovascular shock. Although SARS-CoV-2-related deaths in children are rare, more children died within the first nine months of the pandemic than have died during any influenza season over the last decade.

Black and Hispanic children represent less than 41% of the US population but account for three out of every four SARS-CoV-2-related hospitalizations and deaths in the USA. The drivers of these disparities in children are complex and likely a combination of societal, biological, and behavioral influences.

This pandemic brought to light longstanding health disparities in historically marginalized populations, and minority children have suffered tremendously. It provides an opportunity to understand how a virus hijacked deep-rooted inequities, address these inequities, and work to prevent this outcome in future pandemics/epidemics.
The effect of COVID-19 on liver transplantation: impact, practice patterns, therapeutics, and next steps
Authors: Hutchison Alan L. , Pillai Anjana
Published: April 2021

Purpose of review

To assess the impact of coronavirus disease 2019 (COVID-19) and the pandemic on liver transplant candidates, recipients, and donors, and review guidelines and recommendations for integrating COVID-19 therapies into current practice.

Recent findings

COVID-19 has high morbidity and mortality for transplant candidates; interestingly, posttransplant comorbidities play a larger role than immunosuppression status. COVID-19 therapies and vaccinations are well tolerated in pre and postliver transplant patients with few exceptions, although further research is needed regarding effectiveness in this patient population. Provider practice patterns should evolve to minimize contagion during the current pandemic and prepare for an increase in liver disease due to after-shocks of missed diagnosis and progression of liver disease.

COVID-19 has spurred new research and technologies to ensure the safety of liver transplant candidates, recipients, and donors, and most COVID-19 therapies are safe in this patient population. Further work needs to be done regarding the use of COVID-19 positive organs and the efficacy of vaccines in the transplant population.