bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-invasive transcutaneous vagal nerve stimulation improves myocardial performance in doxorubicin-induced cardiotoxicity
Authors: Lai Yanqiu , Zhou Xiaoya , Guo Fuding , Jin Xiaoxing , Meng Guannan , Zhou Liping , Chen Hu , Liu Zhihao , Yu Lilei , Jiang Hong
Published: June 2021

Aims

The clinical use of antitumour agent doxorubicin (DOX) is hampered by its dose-dependent cardiotoxicity. Development of highly efficient and safe adjuvant intervention for preventing DOX-induced adverse cardiac events is urgently needed. We aimed to investigate whether transcutaneous vagal nerve stimulation (tVNS) plays a cardio-protective role in DOX-induced cardiotoxicity.

Methods and results

Healthy male adult Sprague Dawley rats were used in the experiment and were randomly divided into four groups including control, DOX, tVNS, and DOX+tVNS groups. A cumulative dose of 15 mg/kg DOX was intraperitoneally injected into rats to generate cardiotoxicity. Non-invasive tVNS was conducted for 6 weeks (30 min/day). After 6-week intervention, the indices from the echocardiography revealed that tVNS significantly improved left ventricular function compared to the DOX group. The increased malondialdehyde and Interleukin-1β, and decreased superoxide dismutase were observed in the DOX group, while tVNS significantly prevented these changes. From cardiac histopathological analysis, the DOX+tVNS group showed a mild myocardial damage, and decreases in cardiac fibrosis and myocardial apoptosis compared to the DOX group. Heart rate variability analysis showed that tVNS significantly inhibited DOX-induced sympathetic hyperactivity compared to the DOX group. Additionally, the results of RNA-sequencing analysis showed that there were 245 differentially expressed genes in the DOX group compared to the control group, among which 39 genes were down-regulated by tVNS and most of these genes were involved in immune system. Moreover, tVNS significantly down-regulated the relative mRNA expressions of chemokine-related genes and macrophages recruitment compared to the DOX group.

Conclusion

These results suggest that tVNS prevented DOX-induced cardiotoxicity by rebalancing autonomic tone, ameliorating cardiac dysfunction and remodelling. Notably, crosstalk between autonomic neuromodulation and innate immune cells macrophages mediated by chemokines might be involved in the underlying mechanisms.
Perception of Cancer Risk and Management Practice for Colitis-associated Dysplasia Is Influenced by Colonoscopy Experience and Workplace Affiliation: Results of an International Clinician Survey
Authors: Kabir Misha , Thomas-Gibson Siwan , Hart Ailsa L , Wilson Ana
Published: June 2021

Background and Aims

A successful colitis cancer surveillance programme requires effective action to be taken when dysplasia is detected. This is the first international cross-sectional study to evaluate clinician understanding of dysplasia-cancer risk and management practice since the most recent international guidelines were introduced in 2015.

Methods

A 15-item international online survey was disseminated to gastroenterologists and colorectal surgeons.

Results

A total of 294 clinicians [93.5% gastroenterologists] from 60 countries responded; 23% did not have access to high-definition chromoendoscopy. University hospitals were more likely than non-academic workplaces to provide second expert histopathologist review [67% vs 46%; p = 0.002] and formal multidisciplinary team meeting discussion [73% vs 52%; p = 0.001] of dysplasia cases. Perceptions of 5-year cancer risk associated with endoscopically unresectable low-grade dysplasia varied between 0% and 100%. Non-academic hospital affiliation was predictive of lower perceived cancer risks. Although most [98.4%] respondents advised a colectomy for endoscopically unresectable visible high-grade dysplasia, only 34.4% advised a colectomy for unresectable visible low-grade dysplasia. Respondents from university hospitals were more likely to consider colectomy for multifocal low-grade dysplasia (odds ratio [OR] 2.17). If invisible unifocal low-grade dysplasia was detected, continued surveillance over colectomy was the preferred management among clinicians working mainly in private clinics [OR 9.4] and least preferred in those who had performed more than 50 surveillance colonoscopies [OR 0.41].

Conclusions

Clinicians with less surveillance colonoscopy experience and from non-academic centres appear to have lower cancer risk perceptions and are less likely to advocate colectomy for higher-risk low-grade dysplasia. Further education may align current management practice with clinical guidelines.
Interspecies signaling affects virulence related morphological characteristics of Streptococcus pyogenes M3
Authors: Banerji Rajashri , Saroj Sunil D
Published: June 2021

Streptococcus pyogenes is a Gram-positive human-specific pathogen that asymptomatically colonizes the human respiratory tract. The factors affecting the colonization to the host is not clearly understood. Adherence of the pathogen to host epithelial cell is the initial step for a successful colonization process. In the host, bacteria live in a polymicrobial community; thus, the signaling mediated between the bacteria plays a significant role in the colonization of the pathogen to the host. Thus, the effect of acyl-homoserine lactone, secreted by Gram-negative bacteria on the adhesion properties of S. pyogenes M3 strain was examined. N-(3-Oxododecanoyl)-L-homoserine lactone (Oxo-C12) increased the cell size as well as hydrophobicity of S. pyogenes. qPCR data revealed that the expression of sagA and hasA was negatively affected by Oxo-C12. Moreover, Oxo-C12 leads to changes in the morphological characteristic of S. pyogenes, further promoting adherence to host epithelia and biofilm formation on abiotic surface. The study demonstrates the role of Oxo-C12 as a factor that can promote virulence in S. pyogenes M3.
CHH Methylation Islands: A Nonconserved Feature of Grass Genomes That Is Positively Associated with Transposable Elements but Negatively Associated with Gene-Body Methylation
Authors: Martin Galen T , Seymour Danelle K , Gaut Brandon S
Published: June 2021

Methylated CHH (mCHH) islands are peaks of CHH methylation that occur primarily upstream to genes. These regions are actively targeted by the methylation machinery, occur at boundaries between heterochromatin and euchromatin, and tend to be near highly expressed genes. Here we took an evolutionary perspective by studying upstream mCHH islands across a sample of eight grass species. Using a statistical approach to define mCHH islands as regions that differ from genome-wide background CHH methylation levels, we demonstrated that mCHH islands are common and associate with 39% of genes, on average. We hypothesized that islands should be more frequent in genomes of large size, because they have more heterochromatin and hence more need for defined boundaries. We found, however, that smaller genomes tended to have a higher proportion of genes associated with 5′ mCHH islands. Consistent with previous work suggesting that islands reflect the silencing of the edge of transposable elements (TEs), genes with nearby TEs were more likely to have mCHH islands. However, the presence of mCHH islands was not a function solely of TEs, both because the underlying sequences of islands were often not homologous to TEs and because genic properties also predicted the presence of 5′ mCHH islands. These genic properties included length and gene-body methylation (gbM); in fact, in three of eight species, the absence of gbM was a stronger predictor of a 5′ mCHH island than TE proximity. In contrast, gene expression level was a positive but weak predictor of the presence of an island. Finally, we assessed whether mCHH islands were evolutionarily conserved by focusing on a set of 2,720 orthologs across the eight species. They were generally not conserved across evolutionary time. Overall, our data establish additional genic properties that are associated with mCHH islands and suggest that they are not just a consequence of the TE silencing machinery.
Mitochondrial perturbation reduces susceptibility to xenobiotics through altered efflux in Candida albicans
Authors: Hossain Saif , Veri Amanda O , Liu Zhongle , Iyer Kali R , O’Meara Teresa R , Robbins Nicole , Cowen Leah E
Published: June 2021

Candida albicans is a leading human fungal pathogen, which can cause superficial infections or life-threatening systemic disease in immunocompromised individuals. The ability to transition between yeast and filamentous forms is a major virulence trait of C. albicans, and a key regulator of this morphogenetic transition is the molecular chaperone Hsp90. To explore the mechanisms governing C. albicans morphogenesis in response to Hsp90 inhibition, we performed a functional genomic screen using the gene replacement and conditional expression collection to identify mutants that are defective in filamentation in response to the Hsp90 inhibitor, geldanamycin. We found that transcriptional repression of genes involved in mitochondrial function blocked filamentous growth in response to the concentration of the Hsp90 inhibitor used in the screen, and this was attributable to increased resistance to the compound. Further exploration revealed that perturbation of mitochondrial function reduced susceptibility to two structurally distinct Hsp90 inhibitors, geldanamycin and radicicol, such that filamentous growth was restored in the mitochondrial mutants by increasing the compound concentration. Deletion of two representative mitochondrial genes, MSU1 and SHY1, enhanced cellular efflux and reduced susceptibility to diverse intracellularly acting compounds. Additionally, screening a C. albicans efflux pump gene deletion library implicated Yor1 in the efflux of geldanamycin and Cdr1, in the efflux of radicicol. Deletion of these transporter genes restored sensitivity to Hsp90 inhibitors in MSU1 and SHY1 homozygous deletion mutants, thereby enabling filamentation. Taken together, our findings suggest that mitochondrial dysregulation elevates cellular efflux and consequently reduces susceptibility to xenobiotics in C. albicans.
Multi-stage malaria parasite recognition by deep learning
Authors: Li Sen , Du Zeyu , Meng Xiangjie , Zhang Yang
Published: June 2021

Motivation

Malaria, a mosquito-borne infectious disease affecting humans and other animals, is widespread in tropical and subtropical regions. Microscopy is the most common method for diagnosing the malaria parasite from stained blood smear samples. However, this technique is time consuming and must be performed by a well-trained professional, yet it remains prone to errors. Distinguishing the multiple growth stages of parasites remains an especially challenging task.

Results

In this article, we develop a novel deep learning approach for the recognition of malaria parasites of various stages in blood smear images using a deep transfer graph convolutional network (DTGCN). To our knowledge, this is the first application of graph convolutional network (GCN) on multi-stage malaria parasite recognition in such images. The proposed DTGCN model is based on unsupervised learning by transferring knowledge learnt from source images that contain the discriminative morphology characteristics of multi-stage malaria parasites. This transferred information guarantees the effectiveness of the target parasite recognition. This approach first learns the identical representations from the source to establish topological correlations between source class groups and the unlabelled target samples. At this stage, the GCN is implemented to extract graph feature representations for multi-stage malaria parasite recognition. The proposed method showed higher accuracy and effectiveness in publicly available microscopic images of multi-stage malaria parasites compared to a wide range of state-of-the-art approaches. Furthermore, this method is also evaluated on a large-scale dataset of unseen malaria parasites and the Babesia dataset.

Availability

Code and dataset are available at https://github.com/senli2018/DTGCN_2021 under a MIT license.
Physical activity advice in the UK bowel cancer screening setting: qualitative healthcare professional perspectives
Authors: Semper Kelly , Hernon James , Wynter Trevor , Baker Katherine , Saxton John M
Published: June 2021

Providing physical activity advice in the bowel cancer screening setting could help to reduce the risk of cancer and cardiometabolic disease in older adults. This study investigated the views of healthcare professionals (HCPs) regarding the provision of physical activity advice as part of the UK Bowel Cancer Screening Programme. A purposive sample of HCPs (aged 22–63 years, with 1–26 years of experience) from four bowel cancer screening disciplines (four endoscopists, four colorectal surgeons, four staff nurses and four specialist screening practitioners) were recruited from a large National Health Service gastroenterology unit. Data collection used individual interviews and focus groups, with topics being guided by an a priori topic guide. All interviews and focus groups were audio-recorded and transcribed verbatim. Three key themes, which contextualize the views and perceptions of HCPs recruited to the study, emerged from the framework analysis: (i) appraisal of the concept; (ii) perceived barriers to implementation; (iii) steps to implementation. While the general concept was viewed positively, there were differences of opinion and a range of perceived barriers were revealed. Ideas for effective implementation were also presented, taking into consideration the need for time efficiencies and importance of optimizing effectiveness. This qualitative study provided important insights into the perceptions of HCPs regarding the provision of physical activity advice in the bowel cancer screening setting, and yielded novel ideas for effective implementation.
Ten-eleven translocation 2 modulates allergic inflammation by 5-hydroxymethylcytosine remodeling of immunologic pathways
Authors: Meng Cuida , Gu Lei , Li Yujing , Li Ronghua , Cao Yiqu , Li Ziyi , Allen Emily G , Zhu Dongdong , Jin Peng
Published: June 2021

Allergic rhinitis (AR) is an allergen-specific immunoglobulin E-mediated inflammatory disease. Both genetic and environmental factors could play a role in the pathophysiology of AR. 5-methylcytosine (5mC) can be converted to 5-hydroxymethylcytosine (5hmC) by the ten-eleven translocation (Tet) family of proteins as part of active deoxyribonucleic acid (DNA) demethylation pathway. 5hmC plays an important role in the regulation of gene expression and differentiation in immune cells. Here, we show that loss of Tet protein 2 (Tet2) could impact the severity of AR in the ovalbumin-induced mouse model. Genome-wide 5hmC profiling of both wild-type and Tet2 KO mice in response to AR revealed that the loss of Tet2 could lead to 5hmC alteration at specific immune response genes. Both partial loss and complete loss of Tet2 alters the 5hmC dynamic remodeling for the adaptive immune pathway as well as cytokines. Thus, our results reveal a new role of Tet2 in immunology, and Tet2 may serve as a promising target in regulating the level of immune response.
Macrolide-associated ototoxicity: a cross-sectional and longitudinal study to assess the association of macrolide use with tinnitus and hearing loss
Authors: Vanoverschelde Anna , Oosterloo Berthe C , Ly Nelly F , Ikram M Arfan , Goedegebure André , Stricker Bruno H , Lahousse Lies
Published: June 2021

Background

Macrolides are widely prescribed antibiotics for many different indications. However, there are concerns about adverse effects such as ototoxicity.

Objectives

To investigate whether macrolide use is associated with tinnitus and hearing loss in the general population.

Methods

Cross-sectional (n = 4286) and longitudinal (n = 636) analyses were performed within the population-based Rotterdam Study. We investigated with multivariable logistic regression models the association between macrolides and tinnitus, and with multivariable linear regression models the association between macrolides and two different hearing thresholds (both ears, averaged over 0.25, 0.5, 1, 2, 4 and 8 kHz and 2, 4 and 8 kHz). Both regression models were adjusted for age, sex, systolic blood pressure, alcohol, smoking, BMI, diabetes, education level, estimated glomerular filtration rate and other ototoxic or tinnitus-generating drugs. Cumulative exposure to macrolides was categorized according to the number of dispensed DDDs and duration of action.

Results

In the fully adjusted model, ever use of macrolides was associated with a 25% higher likelihood of prevalent tinnitus (OR = 1.25; 95% CI 1.07–1.46). This association was more prominent in participants with a cumulative dose of more than 14 DDDs and among users of intermediate- or long-acting macrolides. Macrolide use in between both assessments was associated with more than a 2-fold increased risk on incident tinnitus. No general association between macrolides and hearing loss was observed. A borderline significant higher hearing threshold in very recent users (≤3 weeks) was found.

Conclusions

Macrolide use was significantly associated with both prevalent and incident tinnitus. Macrolide-associated tinnitus was likely cumulative dose-dependent.
Rise of the Machines: Artificial Intelligence and the Clinical Laboratory
Authors: Haymond Shannon , McCudden Christopher
Published: June 2021

Background

Artificial intelligence (AI) is rapidly being developed and implemented to augment and automate decision-making across healthcare systems. Being an essential part of these systems, laboratories will see significant growth in AI applications for the foreseeable future.

Content

In laboratory medicine, AI can be used for operational decision-making and automating or augmenting human-based workflows. Specific applications include instrument automation, error detection, forecasting, result interpretation, test utilization, genomics, and image analysis. If not doing so today, clinical laboratories will be using AI routinely in the future, therefore, laboratory experts should understand their potential role in this new area and the opportunities for AI technologies. The roles of laboratorians range from passive provision of data to fuel algorithms to developing entirely new algorithms, with subject matter expertise as a perfect fit in the middle. The technical development of algorithms is only a part of the overall picture, where the type, availability, and quality of data are at least as important. Implementation of AI algorithms also offers technical and usability challenges that need to be understood to be successful. Finally, as AI algorithms continue to become available, it is important to understand how to evaluate their validity and utility in the real world.

This review provides an overview of what AI is, examples of how it is currently being used in laboratory medicine, different ways for laboratorians to get involved in algorithm development, and key considerations for AI algorithm implementation and critical evaluation.
Transgender data collection in the electronic health record: Current concepts and issues
Authors: Kronk Clair A , Everhart Avery R , Ashley Florence , Thompson Hale M , Schall Theodore E , Goetz Teddy G , Hiatt Laurel , Derrick Zackary , Queen Roz , Ram A , Guthman E Mae , Danforth Olivia M , Lett Elle , Potter Emery , Sun Simón(e) D , Marshall Zack , Karnoski Ryan
Published: June 2021

There are over 1 million transgender people living in the United States, and 33% report negative experiences with a healthcare provider, many of which are connected to data representation in electronic health records (EHRs). We present recommendations and common pitfalls involving sex- and gender-related data collection in EHRs. Our recommendations leverage the needs of patients, medical providers, and researchers to optimize both individual patient experiences and the efficacy and reproducibility of EHR population-based studies. We also briefly discuss adequate additions to the EHR considering name and pronoun usage. We add the disclaimer that these questions are more complex than commonly assumed. We conclude that collaborations between local transgender and gender-diverse persons and medical providers as well as open inclusion of transgender and gender-diverse individuals on terminology and standards boards is crucial to shifting the paradigm in transgender and gender-diverse health.
Effect of Subcutaneous Topical Ozone Therapy on Second-Degree Burn Wounds in Rats: An Experimental Study
Authors: Karakaya Emre , Akdur Aydincan , Ayvazoğlu Soy Ebru , Araz Coşkun , Ok Atilgan Alev , Özturan Özer Eda , Şençelikel Tuğçe , Haberal Mehmet
Published: June 2021

Burns are one of the most severe traumas, causing coagulative destruction of the skin. The use of various products that accelerate wound healing in patients with burns may affect rates of patient survival and reduce complications. We studied the effects of subcutaneous ozone injection on second-degree burn wounds in an animal model. For this study, 72 Sprague–Dawley male rats were divided randomly into the following three groups: control group, silver sulfadiazine group, and ozone group; each group was then divided randomly into two subgroups (day 7 or day 14 examination and euthanized). Superficial partial-thickness burns were created on the lower back. In the control group, subcutaneous 0.9% serum saline was injected daily into the burn area. In the silver sulfadiazine group, burns were dressed daily with silver sulfadiazine. In the ozone group, subcutaneous ozone was injected daily into the burn area. We performed tissue hydroxyproline level measurements and histopathological evaluations. When groups were compared in terms of weight change, no significant difference was found between day 7 and day 14. With regard to tissue hydroxyproline levels, the ozone group had significantly higher levels on both days 7 and 14 (P < .001). In histopathological evaluations, we determined that wound healing in the ozone group was significantly higher than in the other groups. We found that subcutaneous ozone therapy was more effective than silver sulfadiazine in the healing process of second-degree burn wounds and could be safely used in the treatment of burn wounds.
Needs Assessment for Corn Insect Pest Management in Iowa
Authors: Dean Ashley N , Hodgson Erin W , Rieck-Hinz Angela , Anderson Meaghan
Published: June 2021

Corn, Zea mays L. (Cyperales: Poaceae), production is essential to Iowa’s economy and provides food, feed, and fuel beyond the state. Farmers face a number of challenges in corn production, including insect pests, and understanding farmers’ perceptions and concerns is critical for extension personnel to provide adequate and relevant programming. The Iowa State University Agriculture and Natural Resources Crops Team conducted a survey of Iowa farmers and agribusiness professionals during the 2019–2020 extension season. The goal was to understand farmer perceptions of corn pests and whether farmers experienced challenges with resistance to Bt traits or insecticides. Additionally, we aimed to realize farmers’ confidence in developing resistance management plans and discussing those needs with their input suppliers and advisors. Our survey revealed that northern corn rootworm, Diabrotica barberi Smith & Lawrence (Coleoptera: Chrysomelidae), was the pest of greatest concern across the state. People were generally more concerned about belowground Bt trait performance than aboveground traits, though only 12% of respondents reported Bt trait failure for corn rootworms. In general, people were not concerned about the performance of seed treatments or soil- or foliar-applied insecticides. Farmers generally felt very confident in developing a resistance management plan and discussing their needs with their advisors. The results of this survey will be used to target extension programming throughout the state and increase confidence for farmers and agribusiness employees to discuss resistance management plans together.
The emergence of systematic argument distinctions in artificial sign languages
Authors: Motamedi Yasamin , Smith Kenny , Schouwstra Marieke , Culbertson Jennifer , Kirby Simon
Published: June 2021

Word order is a key property by which languages indicate the relationship between a predicate and its arguments. However, sign languages use a number of other modality-specific tools in addition to word order such as spatial agreement, which has been likened to verbal agreement in spoken languages, and role shift, where the signer takes on characteristics of propositional agents. In particular, data from emerging sign languages suggest that, though some use of a conventional word order can appear within a few generations, systematic spatial modulation as a grammatical feature takes time to develop. We experimentally examine the emergence of systematic argument marking beyond word order, investigating how artificial gestural systems evolve over generations of participants in the lab. We find that participants converge on different strategies to disambiguate clause arguments, which become more consistent through the use and transmission of gestures; in some cases, this leads to conventionalized iconic spatial contrasts, comparable to those found in natural sign languages. We discuss how our results connect with theoretical issues surrounding the analysis of spatial agreement and role shift in established and newly emerging sign languages, and the possible mechanisms behind its evolution.
Aboveground net primary productivity and soil respiration display different responses to precipitation changes in desert grassland
Authors: Zhang Lihua , Wang Junfeng , Zhao Ruifeng , Guo Yafei , Hao Lianyi
Published: June 2021

Precipitation (PPT) changes affect both aboveground vegetation dynamics and belowground carbon cycling processes, particularly in arid and semiarid regions. However, it remains unclear how extreme PPT variation can affect soil carbon sequestration potential. A 3-year PPT manipulation experiment with five levels (±40%, ±20% and ambient PPT) was conducted in a desert grassland of western Loess Plateau. Aboveground net primary productivity (ANPP) and soil respiration (Rs) were measured to examine whether the responses of ANPP and Rs to PPT changes displayed a double asymmetry model. The ANPP was more sensitive to extreme drought than extreme wet treatments in wet and dry years, which displayed a negative asymmetric model. The change in ANPP was mainly due to the direct effect of PPT change, and plant density variation also exerted some influence in the dry year. In contrast, Rs displayed a positive asymmetry response to PPT change in dry year. This may be ascribed to enhanced autotrophic respiration due to the enhanced positive responses of plant growth and ANPP to wet treatments as well as stronger birch effect of rainfall events on heterotrophic respiration. The saturating response of Rs to extreme drought (−40% PPT treatment) was also found in the dry year. Nevertheless, the response of Rs to PPT change displayed a negative asymmetry model in wet years. The contrasting models for ANPP and Rs in response to altered PPT regime suggest that extreme wet or dry treatments may increase soil C pools effluxes toward debt in this desert grassland.
Males With Traumatic Lower Limb Loss Differ in Body Fat Distribution Compared to Those Without Limb Loss
Authors: Spain David R , Andrews Anne M , Crews Sara A , Khan Joetta M
Published: June 2021

Objectives

The primary objective was to examine body fat composition in males with traumatic lower limb loss and a comparison group without limb loss. A secondary objective was to determine if there are differences in body fat composition by traumatic limb loss level.

Research Methods and Procedures

Cross-sectional analyses of baseline in-person intake data was completed at a large military medical center. Data were collected from 2011 to 2020, and analysis was conducted in 2020. Participants (n = 89) included males who sustained traumatic lower limb loss (n = 50) and an age-matched comparison group without limb loss (n = 39). Mean age of participants was 36.0 ± 13.2 years. Main outcomes measured included age, height, body mass index, weight, body fat mass and percent, android fat mass and percent, gynoid fat mass and percent, and android/gynoid percent fat ratio. Differences between groups were assessed using t-tests or Mann–Whitney U tests. Differences between limb loss levels were assessed using one-way ANOVA or Wilcoxon signed-rank test.

Results

Body fat percent (P = .001), gynoid fat percent (P = .010), android fat mass (P = .01), and percent (P = .02) were higher in the group with limb loss. There were no differences in body fat composition between limb loss levels (P > .05).

Conclusion

Males with traumatic lower limb loss had a higher body fat percent compared to those without limb loss. Given higher body fat composition in individuals with limb loss and the relationship between body fat composition and cardiovascular disease risk, including body composition analysis with clinical screening could identify changes and allow for early intervention.
Magnetic dynamos in white dwarfs – II. Relating magnetism and pollution
Authors: Schreiber Matthias R , Belloni Diogo , Gänsicke Boris T , Parsons Steven G
Published: June 2021

We investigate whether the recently suggested rotation and crystallization driven dynamo can explain the apparent increase of magnetism in old metal polluted white dwarfs. We find that the effective temperature distribution of polluted magnetic white dwarfs is in agreement with most/all of them having a crystallizing core, and increased rotational velocities are expected due to accretion of planetary material that is evidenced by the metal absorption lines. We conclude that a rotation and crystallization driven dynamo offers not only an explanation for the different occurrence rates of strongly magnetic white dwarfs in close binaries but also for the high incidence of weaker magnetic fields in old metal polluted white dwarfs.
Chromosome Fusion Affects Genetic Diversity and Evolutionary Turnover of Functional Loci but Consistently Depends on Chromosome Size
Authors: Cicconardi Francesco , Lewis James J , Martin Simon H , Reed Robert D , Danko Charles G , Montgomery Stephen H
Published: June 2021

Major changes in chromosome number and structure are linked to a series of evolutionary phenomena, including intrinsic barriers to gene flow or suppression of recombination due to chromosomal rearrangements. However, chromosome rearrangements can also affect the fundamental dynamics of molecular evolution within populations by changing relationships between linked loci and altering rates of recombination. Here, we build chromosome-level assembly Eueides isabella and, together with a recent chromosome-level assembly of Dryas iulia, examine the evolutionary consequences of multiple chromosome fusions in Heliconius butterflies. These assemblies pinpoint fusion points on 10 of the 20 autosomal chromosomes and reveal striking differences in the characteristics of fused and unfused chromosomes. The ten smallest autosomes in D. iulia and E. isabella, which have each fused to a longer chromosome in Heliconius, have higher repeat and GC content, and longer introns than predicted by their chromosome length. When fused, these characteristics change to become more in line with chromosome length. The fusions also led to reduced diversity, which likely reflects increased background selection and selection against introgression between diverging populations, following a reduction in per-base recombination rate. We further show that chromosome size and fusion impact turnover rates of functional loci at a macroevolutionary scale. Together these results provide further evidence that chromosome fusion in Heliconius likely had dramatic effects on population level processes shaping rates of neutral and adaptive divergence. These effects may have impacted patterns of diversification in Heliconius, a classic example of an adaptive radiation.
Diverse high-affinity DNA aptamers for wild-type and B.1.1.7 SARS-CoV-2 spike proteins from a pre-structured DNA library
Authors: Li Jiuxing , Zhang Zijie , Gu Jimmy , Stacey Hannah D , Ang Jann C , Capretta Alfredo , Filipe Carlos D M , Mossman Karen L , Balion Cynthia , Salena Bruno J , Yamamura Deborah , Soleymani Leyla , Miller Matthew S , Brennan John D , Li Yingfu
Published: June 2021

We performed in vitro selection experiments to identify DNA aptamers for the S1 subunit of the SARS-CoV-2 spike protein (S1 protein). Using a pool of pre-structured random DNA sequences, we obtained over 100 candidate aptamers after 13 cycles of enrichment under progressively more stringent selection pressure. The top 10 sequences all exhibited strong binding to the S1 protein. Two aptamers, named MSA1 (Kd = 1.8 nM) and MSA5 (Kd = 2.7 nM), were assessed for binding to the heat-treated S1 protein, untreated S1 protein spiked into 50% human saliva and the trimeric spike protein of both the wildtype and the B.1.1.7 variant, demonstrating comparable affinities in all cases. MSA1 and MSA5 also recognized the pseudotyped lentivirus of SARS-CoV-2 with respective Kd values of 22.7 pM and 11.8 pM. Secondary structure prediction and sequence truncation experiments revealed that both MSA1 and MSA5 adopted a hairpin structure, which was the motif pre-designed into the original library. A colorimetric sandwich assay was developed using MSA1 as both the recognition element and detection element, which was capable of detecting the pseudotyped lentivirus in 50% saliva with a limit of detection of 400 fM, confirming the potential of these aptamers as diagnostic tools for COVID-19 detection.
Accurate prediction ofcis-regulatory modules reveals a prevalent regulatory genome of humans
Authors: Ni Pengyu , Su Zhengchang
Published: June 2021

cis-regulatory modules(CRMs) formed by clusters of transcription factor (TF) binding sites (TFBSs) are as important as coding sequences in specifying phenotypes of humans. It is essential to categorize all CRMs and constituent TFBSs in the genome. In contrast to most existing methods that predict CRMs in specific cell types using epigenetic marks, we predict a largely cell type agonistic but more comprehensive map of CRMs and constituent TFBSs in the gnome by integrating all available TF ChIP-seq datasets. Our method is able to partition 77.47% of genome regions covered by available 6092 datasets into a CRM candidate (CRMC) set (56.84%) and a non-CRMC set (43.16%). Intriguingly, the predicted CRMCs are under strong evolutionary constraints, while the non-CRMCs are largely selectively neutral, strongly suggesting that the CRMCs are likely cis-regulatory, while the non-CRMCs are not. Our predicted CRMs are under stronger evolutionary constraints than three state-of-the-art predictions (GeneHancer, EnhancerAtlas and ENCODE phase 3) and substantially outperform them for recalling VISTA enhancers and non-coding ClinVar variants. We estimated that the human genome might encode about 1.47M CRMs and 68M TFBSs, comprising about 55% and 22% of the genome, respectively; for both of which, we predicted 80%. Therefore, the cis-regulatory genome appears to be more prevalent than originally thought.
Varicella-zoster virus aseptic meningitis: an atypical presentation in an immunocompetent male patient
Authors: Platanaki Christina , Leonidou Leonidia , Siagkris Dimitrios , Giannopoulou Ιoanna , Paliogianni Fotini , Velissaris Dimitrios
Published: June 2021

Varicella-zoster virus (VZV) reactivation causes a relatively common disease in immunocompromised patients characterized by rash and radiating pain. Aseptic meningitis is a rare complication of VZV infection and commonly is associated with exanthem and neurological signs. We present an atypical case of VZV meningitis in a healthy 56-year-old male who was initially presented with persistent headache as the only symptom. Anti-VZV immunoglobulin G titer both in serum and in cerebrospinal fluid (CSF) and the polymerase chain reaction (PCR) CSF analysis revealed VZV infection. Our case highlights the importance of considering VZV aseptic meningitis in immunocompetent individuals even in the absence of the typical presentation of meningitis. Screening techniques such as CSF, PCR as well as anti-VZV antibodies in CSF show that VZV meningitis is a common cause of aseptic meningitis and allows the early recognition of CNS involvement in the VZV infection.
Pembrolizumab dramatically resolves choroidal metastatis from esophageal adenocarcinoma and restores vision: a case report
Authors: Barrett Dianne , Sumnicht Andrew , Chalam KV , Rauser Micheal
Published: June 2021

Esophageal adenocarcinoma historically is an aggressive cancer with poor long-term survival. Ocular metastasis secondary to gastrointestinal malignancy is rare. In managing patients with ocular metastasis, quality of life (specifically vision preservation) is one of the most important factors patients and providers consider when deciding on a treatment regimen. Anti-programmed cell death-1 (PD-1) and PD-1 ligand (PD-L1) inhibitors such as pembrolizumab have shown promising results as second-line therapy for patient with metastatic malignancy. We describe a novel case of a functionally monocular patient with known metastatic esophageal adenocarcinoma who developed poor vision and a large choroidal lesion in his better seeing eye. The lesion regressed and vision restored to 20/20 after treatments with pembrolizumab in this case report.
Introduction
Authors: Anderson Kristin J.
Published: June 2021

The introduction lays out the thesis of Enraged, Rattled, and Wronged. In order to understand the political and social backlash against efforts toward equality of the last few decades, culminating in the election of Donald Trump for US president, we must understand entitlement. The introduction begins with the inexplicable election of Donald Trump in 2016. White voters, both women and men, put Donald Trump in the Whitehouse. His campaign of entitled resentment resonated with these voters. This book is not about Donald Trump, however. Rather, it is about those who have been traditionally advantaged due to their social identity of maleness and whiteness and yet believe they are being shut out of the American dream. They are the victims of supposed progress. The introduction ends with an outline of each chapter.
Harnessing NKT cells for vaccination
Authors: Burn Olivia K , Pankhurst Theresa E , Painter Gavin F , Connor Lisa M , Hermans Ian F
Published: June 2021

Lay Summary

Vaccine-induced immune responses generally involve activation of immune cells called T and B cells that have a variety of mechanisms to limit the infection. Each T or B cell has a randomly generated receptor for binding pathogen-derived antigens, but only a few cells with an individual’s repertoire of cells will recognize a given pathogen; the aim of vaccination is therefore to induce these few cells to undergo significant division to meet the demands of eliminating infection. However, some T cells called natural killer T (NKT) cells have receptors of similar structure that recognize specific glycolipids, and are found in high numbers in the tissues where immune reactions take place. Here we describe studies that show that these glycolipids can be added to vaccines to activate NKT cells, which have the net effect of improving vaccine responses. This is because NKT cells are poised to provide molecular signals that initiate a cascade of cellular interactions that ultimately improve the capacity of pathogen-specific T and B cells to divide and function. We describe different techniques that can be used to incorporate these compounds into vaccines, some limitations on their use, and new strategies to overcome these limitations.
I, VOLKSWAGEN
Authors: Collins Stephanie
Published: June 2021

Philosophers increasingly argue that collective agents can be blameworthy for wrongdoing. Advocates tend to endorse functionalism, on which collectives are analogous to complicated robots. This is puzzling: we don’t hold robots blameworthy. I argue we don’t hold robots blameworthy because blameworthiness presupposes the capacity for a mental state I call ‘moral self-awareness’. This raises a new problem for collective blameworthiness: collectives seem to lack the capacity for moral self-awareness. I solve the problem by giving an account of how collectives have this capacity. The trick is to take seriously individuals’ status as flesh-and-blood material constituents of collectives. The idea will be: under certain conditions that I specify, an individual can be the locus of a collective's moral self-awareness. The account provides general insights concerning collectives’ dependence on members, the boundaries of membership, and the locus of collectives’ phenomenology.
Inorganic pyrophosphate is reduced in patients with systemic sclerosis
Authors: Hsu Vivien M , Kozák Eszter , Li Qiaoli , Bocskai Márta , Schlesinger Naomi , Rosenthal Ann , McClure Scott T , Kovács László , Bálint László , Szamosi Szilvia , Szücs Gabriella , Carns Mary , Aren Kathleen , Goldberg Isaac , Váradi András , Varga John
Published: June 2021

Objective

The pathogenesis of calcinosis cutis, a disabling complication of SSc, is poorly understood and effective treatments are lacking. Inorganic pyrophosphate (PPi) is a key regulator of ectopic mineralization, and its deficiency has been implicated in ectopic mineralization disorders. We therefore sought to test the hypothesis that SSc may be associated with reduced circulating PPi, which might play a pathogenic role in calcinosis cutis.

Methods

Subjects with SSc and age-matched controls without SSc were recruited from the outpatient rheumatology clinics at Rutgers and Northwestern Universities (US cohort), and from the Universities of Szeged and Debrecen (Hungarian cohort). Calcinosis cutis was confirmed by direct palpation, by imaging or both. Plasma PPi levels were determined in platelet-free plasma using ATP sulfurylase to convert PPi into ATP in the presence of excess adenosine 5’ phosphosulfate.

Results

Eighty-one patients with SSc (40 diffuse cutaneous, and 41 limited cutaneous SSc) in the US cohort and 45 patients with SSc (19 diffuse cutaneous and 26 limited cutaneous SSc) in the Hungarian cohort were enrolled. Calcinosis was frequently detected (40% of US and 46% of the Hungarian cohort). Plasma PPi levels were significantly reduced in both SSc cohorts with and without calcinosis (US: P = 0.003; Hungarian: P < 0.001).

Conclusions

Circulating PPi are significantly reduced in SSc patients with or without calcinosis. Reduced PPi may be important in the pathophysiology of calcinosis and contribute to tissue damage with chronic SSc. Administering PPi may be a therapeutic strategy and larger clinical studies are planned to confirm our findings.
More than Rocks and Stone: Confederate Monuments, Memory Movements, and Race
Authors: O’Connell Heather A
Published: June 2021

Iexamine why Confederate monuments were built in public spaces in counties throughout the US South with particular attention to connections to race. I use event history analysis to examine the overall likelihood of erecting the first monument in a county while accounting for dimensions of time. The data include a comprehensive accounting of public Confederate monuments, covariates spanning 150 years, and several unique historical variables. This is the first study to assess competing explanations for the construction of Confederate monuments in a generalizable analysis. Results provide support for understanding Confederate monuments as part of a larger “memory movement.” Moreover, this movement was strongly related to the relationship between race and power within a county. However, my analyses offer limited support for viewing Confederate monuments as part of a countermovement in response to local racial tensions. Incorporating the nuances of how race relates to Confederate monuments will be valuable to future research as scholars develop an understanding of their links to contemporary society.
Meritocracy at Work?: Merit-Based Reward Systems and Gender Wage Inequality
Authors: Mun Eunmi , Kodama Naomi
Published: June 2021

It is widely believed that meritocratic employment practices reduce gender inequality by limiting managers’ reliance on nonmerit factors, such as biases. An emerging stream of research, however, questions the belief, arguing that meritocratic practices often fail to reduce inequality and may paradoxically increase it. Despite these opposing predictions, we still lack convincing empirical findings to adjudicate between them. Typically relying on data from a single organization or industry, most previous studies suffer from limited generalizability and cannot properly account for the large variation in the implementation of merit-based reward systems across organizations, let alone identify the origins of the variation. We attempt to overcome the limitations by constructing large-scale linked employer–employee data and by investigating the impact of merit-based systems on different components of compensation. Analyzing our panel data on 400 large Japanese companies and 400,000 employees of these companies over 12 years, we found evidence in support of the meritocracy paradox. The gender gap in bonus pay was greater, not smaller, in workplaces with a merit-based system compared to workplaces without it. But this paradoxical expansion of the gender gap was observed only in bonus pay but not in total compensation. We further found that a transition to merit-based systems has varying impacts on different employee groups; it widened the gender pay gap for young workers but reduced the gap for managers. Our research contributes to understanding gender inequality in times of shifting employment relations and the rise of meritocracy.
Reliability and validity of a 3-min psychomotor vigilance task in assessing sensitivity to sleep loss and alcohol: fitness for duty in aviation and transportation
Authors: Benderoth Sibylle , Hörmann Hans-Jürgen , Schießl Caroline , Elmenhorst Eva-Maria
Published: June 2021

Study Objectives

The psychomotor vigilance task (PVT) is a widely used objective method to measure sustained attention, but the standard 10-min version is often impractical in operational settings. We investigated the reliability and validity of a 3-min PVT administered on a portable handheld device assessing sensitivity to sleep loss and alcohol in relation to a 10-min PVT and to applied tasks.

Methods

A total of 47 healthy volunteers underwent a 12 consecutive days sleep lab protocol. A cross-over design was adopted including total sleep deprivation (38 h awake), sleep restriction (SR, 4 h sleep opportunity), acute alcohol consumption, and SR after alcohol intake (SR/Alc 4 h sleep opportunity). Participants performed a 10-min and 3-min PVT and operationally relevant tasks related to demands in aviation and transportation.

Results

Sleep loss resulted in significant performance impairments compared with baseline measurements detected by both PVT versions—particularly for mean speed (both p < 0.001)—and the operationally relevant tasks. Similar effects were observed due to alcohol intake (speed: both p < 0.001). The 3-min and 10-min PVT results were highly correlated (speed: between r = 0.72 and r = 0.89). Three of four aviation-related tasks showed robust correlations with the 3-min PVT. Correlations with the parameters of the task related to transportation were lower, but mainly significant.

Conclusion

The 3-min PVT showed a high reliability and validity in assessing sleep loss and alcohol-induced impairments in cognitive performance. Thus, our results underline its usefulness as potential fitness for duty self-monitoring tool in applied settings.