bluuebunny/crossref_metadata_2025 huggingface dataset:
Virulence potential of Rickettsia amblyommatis for spotted fever pathogenesis in mice
Authors: Yen Wan-Yi , Stern Kayla , Mishra Smruti , Helminiak Luke , Sanchez-Vicente Santiago , Kim Hwan Keun
Published: April 2021

Rickettsia amblyommatis belongs to the spotted fever group of Rickettsia and infects Amblyomma americanum (Lone Star ticks) for transmission to offspring and mammals. Historically, the geographic range of A. americanum was restricted to the southeastern USA. However, recent tick surveys identified the progressive northward invasion of A. americanum, contributing to the increased number of patients with febrile illnesses of unknown etiology after a tick bite in the northeastern USA. While serological evidence strongly suggests that patients are infected with R. amblyommatis, the virulence potential of R. amblyommatis is not well established. Here, we performed a bioinformatic analysis of three genome sequences of R. amblyommatis and identified the presence of multiple putative virulence genes whose products are implicated for spotted fever pathogenesis. Similar to other pathogenic spotted fever rickettsiae, R. amblyommatis replicated intracellularly within the cytoplasm of tissue culture cells. Interestingly, R. amblyommatis displayed defective attachment to microvascular endothelial cells. The attachment defect and slow growth rate of R. amblyommatis required relatively high intravenous infectious doses to produce dose-dependent morbidity and mortality in C3H mice. In summary, our results corroborate clinical evidence that R. amblyommatis can cause mild disease manifestation in some patients.
Effectiveness of hospital payment reforms in low- and middle-income countries: a systematic review
Authors: Ghazaryan Emma , Delarmente Benjo A , Garber Kent , Gross Margaret , Sriudomporn Salin , Rao Krishna D
Published: April 2021

Payment mechanisms have attracted substantial research interest because of their consequent effect on care outcomes, including treatment costs, admission and readmission rates and patient satisfaction. Those mechanisms create the incentive environment within which health workers operate and can influence provider behaviour in ways that can facilitate achievement of national health policy goals. This systematic review aims to understand the effects of changes in hospital payment mechanisms introduced in low- and middle-income countries (LMICs) on hospital- and patient-level outcomes. A standardised search of seven databases and a manual search of the grey literature and reference lists of existing reviews were performed to identify relevant articles published between January 2000 and July 2019. We included original studies focused on hospital payment reforms and their effect on hospital and patient outcomes in LMICs. Narrative descriptions or studies focusing only on provider payments or primary care settings were excluded. The authors used the Risk of Bias in Non-Randomized Studies of Interventions tool to assess the risk of bias and quality. Results were synthesized in a narrative description due to methodological heterogeneity. A total of 24 articles from seven middle-income countries were included, the majority of which are from Asia. In most cases, hospital payment reforms included shifts from passive (fee-for-service) to active payment models—the most common being diagnosis-related group payments, capitation and global budget. In general, hospital payment reforms were associated with decreases in hospital expenditures, out-of-pocket payments, length of hospital stay and readmission rates. The majority of the articles scored low on quality due to weak study design. A shift from passive to active hospital payment methods in LMICs has been associated with lower hospital and patient costs as well as increased efficiency without any apparent compromise on quality. However, there is an important need for high-quality studies in this area.
Value of a national burden-of-disease study: a comparison of estimates between the Australian Burden of Disease Study 2015 and the Global Burden of Disease Study 2017
Authors: Zhao Chenkun , Choi Ching , Laws Paula , Gourley Michelle , Dobson Annette , Driscoll Tim , Kirkland Laura , Moon Lynelle , Juckes Richard
Published: April 2021

Background

Estimates of burden of disease are important for monitoring population health, informing policy and service planning. Burden estimates for the same population can be reported differently by national studies [e.g. the Australian Burden of Disease Study (ABDS) and the Global Burden of Disease Study (GBDS)].

Methods

Australian ABDS 2015 and GBDS 2017 burden estimates and methods for 2015 were compared. Years of life lost (YLL), years lived with disability (YLD) and disability-adjusted life years (DALY) measures were compared for overall burden and ‘top 50’ causes. Disease-category definitions (based on ICD-10), redistribution algorithms, data sources, disability weights, modelling methods and assumptions were reviewed.

Results

GBDS 2017 estimated higher totals than ABDS 2015 for YLL, YLD and DALY for Australia. YLL differences were mainly driven by differences in the allocation of deaths to disease categories and the redistribution of implausible causes of death. For YLD, the main drivers were data sources, severity distributions and modelling strategies. Most top-50 diseases for DALY had a similar YLL:YLD composition reported.

Conclusions

Differences in the ABDS and GBDS estimates reflect the different purposes of local and international studies and differences in data and modelling strategies. The GBDS uses all available evidence and is useful for international comparisons. National studies such as the ABDS have the flexibility to meet local needs and often the advantage of access to unpublished data. It is important that all data sources, inputs and models be assessed for quality and appropriateness. As studies evolve, differences should be accounted for through increased transparency of data and methods.
Erratum: “Breaking the 3/2 barrier for unit distances in three dimensions”
Authors: Sharir Micha , Zahl Joshua
Published: April 2021

We wish to correct an error in the paper “Breaking the 3/2 barrier for unit distances in three dimensions.” Lemma 3.2 of this paper contained an incorrect claim about the intersection patterns of ellipses obtained by projecting circles from three dimensions to the plane. In this erratum we state and prove a correct version of this statement.
Insulating Peace: Managerial Coordination in Durable Security Complexes
Authors: Travlos Konstantinos
Published: April 2021

I argue that insulation via managerial coordination is a key element in any explanation about the formation of political regions among states. The key role it plays is as a tool for the maintenance of intra-regional pacific relations in the face of diffusion and contagion processes, resulting from continued security linkages with excluded extra-regional states. In order to explore these dynamics, I propose a new reconceptualization of the concept of managerial coordination based on the basic framework concept mapping tool. This leads to clarity about what managerial coordination does as a dimension of insulation. It also necessitates a revamp of the scale of interstate managerial coordination as a measuring instrument of the intensity of collective intentionality toward insulation among the members of a region. I then map the region concept of durable security complex (DSC) as the scope for the enactment of managerial coordination, based on a review of existing region concepts in the new regionalist literature. I then conduct an ideographic proof-of-concept exercise on three DSCs in the presence or absence of managerial coordination. These are the Scandinavian states, the South Asian regional security complex, and the South American Norther Tier local hierarchy. The exercise provides indicators for a number of theoretical propositions worthy of future evaluation.
The feasibility of implementing antibiotic restrictions for fluoroquinolones and cephalosporins: a mixed-methods study across 15 Veterans Health Administration hospitals
Authors: Livorsi Daniel J , Suda Katie J , Cunningham Goedken Cassie , Hockett Sherlock Stacey , Balkenende Erin , Chasco Emily E , Scherer Aaron M , Goto Michihiko , Perencevich Eli N , Goetz Matthew Bidwell , Reisinger Heather Schacht ,   Veterans Affairs-Centers for Disease Control and Prevention Practice-Based Research Network
Published: April 2021

Introduction

The optimal method for implementing hospital-level restrictions for antibiotics that carry a high risk of Clostridioides difficile infection has not been identified. We aimed to explore barriers and facilitators to implementing restrictions for fluoroquinolones and third/fourth-generation cephalosporins.

Methods

This mixed-methods study across a purposeful sample of 15 acute-care, geographically dispersed Veterans Health Administration hospitals included electronic surveys and semi-structured interviews (September 2018 to May 2019). Surveys on stewardship strategies were administered at each hospital and summarized with descriptive statistics. Interviews were performed with 30 antibiotic stewardship programme (ASP) champions across all 15 sites and 19 additional stakeholders at a subset of 5 sites; transcripts were analysed using thematic content analysis.

Results

The most restricted agent was moxifloxacin, which was restricted at 12 (80%) sites. None of the 15 hospitals restricted ceftriaxone. Interviews identified differing opinions on the feasibility of restricting third/fourth-generation cephalosporins and fluoroquinolones. Some participants felt that restrictions could be implemented in a way that was not burdensome to clinicians and did not interfere with timely antibiotic administration. Others expressed concerns about restricting these agents, particularly through prior approval, given their frequent use, the difficulty of enforcing restrictions and potential unintended consequences of steering clinicians towards non-restricted antibiotics. A variety of stewardship strategies were perceived to be effective at reducing the use of these agents.

Conclusions

Across 15 hospitals, there were differing opinions on the feasibility of implementing antibiotic restrictions for third/fourth-generation cephalosporins and fluoroquinolones. While the perceived barrier to implementing restrictions was frequently high, many hospitals were effectively using restrictions and reported few barriers to their use.
Impact of the 2015 Health Information Technology Certification Edition on Interoperability among Hospitals
Authors: Pylypchuk Yuriy , Barker Wesley , Encinosa William , Searcy Talisha
Published: April 2021

Objective

Most nonfederal acute care hospitals use electronic health records (EHRs) certified by the Office of the National Coordinator for Health Information Technology. In 2015, the Office of the National Coordinator for Health Information Technology finalized the 2015 Health IT Certification Edition and adoption by hospitals began in 2016. We examine the impact of the 2015 Edition on rates of interoperable exchange among nonfederal acute hospitals.

Materials and Methods

The study applies a standard difference-in-differences design and a recently developed fixed effects estimator that relaxes the assumption of treatment effects being constant across groups and time. In the analysis, we identify separate effects of the 2015 Edition for hospitals that switched EHR developers and forecast hospitals’ interoperability over 2015 Edition adoption rates.

Results

The adoption of the 2015 Edition increased hospitals’ rates of interoperable exchange and especially benefited hospitals that switched EHR developers in the post-implementation period. Forecasting results indicate that if all hospitals adopted the 2015 Edition, 53% to 61% of hospitals would engage in interoperable health information exchange compared with the current rate of 46%.

Discussion

Hospitals’ levels of interoperability have been rising over the last few years. Adoption of newer technology improved hospitals’ interoperability and accounts for up to 12% of the rise in interoperability.

Conclusions

Certified technology is one mechanism to ensure providers use recent and safe technologies for interoperable exchange. Adoption of certified EHRs improves the nation’s interoperable exchange; however, it has a clear limited effect. Other mechanisms are necessary for achieving comprehensive interoperable exchange.
Cell engineering for the production of hybrid-type N-glycans in HEK293 cells
Authors: Leng Ji-Xiong , Ren Wei-Wei , Li Yuqing , Yang Ganglong , Gao Xiao-Dong , Fujita Morihisa
Published: April 2021

Glycoprotein therapeutics are among the leading products in the biopharmaceutical industry. The heterogeneity of glycans in therapeutic proteins is an issue for maintaining quality, activity and safety during bioprocessing. In this study, we knocked out genes encoding Golgi α-mannosidase-II, MAN2A1 and MAN2A2 in human embryonic kidney 293 (HEK293) cells, establishing an M2D-KO cell line that can produce recombinant proteins mainly with hybrid-type N-glycans. Furthermore, FUT8, which encodes α1,6-fucosyltransferase, was knocked out in the M2D-KO cell line, establishing a DF-KO cell line that can express noncore fucosylated hybrid-type N-glycans. Two recombinant proteins, lysosomal acid lipase and constant fragment of human IgG1, were expressed in the M2D-KO and DF-KO cell lines. Glycan structural analysis revealed that complex-type N-glycans were removed in both M2D-KO and DF-KO cells. Our results suggest that these cell lines are suitable for the production of therapeutic proteins with hybrid-type N-glycans. Moreover, KO cell lines would be useful as models for researching the mechanism of antimetastatic effects in human tumours by swainsonine treatment.
Coinfection ofIxodes scapularis(Acari: Ixodidae) Nymphs WithBabesiaspp. (Piroplasmida: Babesiidae) andBorrelia burgdorferi(Spirochaetales: Spirochaetaceae) in Wisconsin
Authors: Zembsch T E , Lee X , Bron G M , Bartholomay L C , Paskewitz S M
Published: April 2021

Borrelia burgdorferi, the spirochete that causes Lyme disease, is endemic and widespread in Wisconsin. Research in the northeastern United States has revealed a positive association between Babesia microti, the main pathogen that causes babesiosis in humans, and Bo. burgdorferi in humans and in ticks. This study was conducted to examine associations between the disease agents in the Upper midwestern United States. Ixodes scapularis Say nymphs (N = 2,858) collected between 2015 and 2017 from nine locations in Wisconsin were tested for Babesia spp. and Borrelia spp. using real-time PCR. Two species of Babesia were detected; Ba. microti and Babesia odocoilei (a parasite of members of the family Cervidae). Prevalence of infection at the nine locations ranged from 0 to 13% for Ba. microti, 11 to 31% for Bo. burgdorferi sensu stricto, and 5.7 to 26% for Ba. odocoilei. Coinfection of nymphs with Bo. burgdorferi and Ba. odocoilei was detected in eight of the nine locations and significant positive associations were observed in two of the eight locations. The prevalence of nymphal coinfection with both and Bo. burgdorferi and Ba. microti ranged from 0.81 to 6.5%. These two pathogens were significantly positively associated in one of the five locations where both pathogens were detected. In the other four locations, the observed prevalence of coinfection was higher than expected in all but one site-year. Clinics and healthcare providers should be aware of the association between Ba. microti and Bo. burgdorferi pathogens when treating patients who report tick bites.
Vector Specificity of the Relapsing Fever Spirochete Borrelia hermsii (Spirochaetales: Borreliaceae) for the Tick Ornithodoros hermsi (Acari: Argasidae) Involves Persistent Infection of the Salivary Glands
Authors: Schwan Tom G
Published: April 2021

The relapsing fever spirochetes Borrelia hermsii and Borrelia turicatae are each maintained and transmitted in nature by their specific tick vectors, Ornithodoros hermsi Wheeler (Acari: Argasidae) and Ornithodoros turicata (Duges), respectively. The basis for this spirochete and vector specificity is not known, but persistent colonization of spirochetes in the tick’s salivary glands is presumed to be essential for transmission by these long-lived ticks that feed in only minutes on their warm-blooded hosts. To examine this hypothesis further, cohorts of O. hermsi and O. turicata were infected with B. hermsii and examined 7–260 d later for infection in their midgut, salivary glands, and synganglion. While the midgut from all ticks of both species at all time points examined were infected with spirochetes, the salivary glands of only O. hermsi remained persistently infected. The salivary glands of O. turicata were susceptible to an early transient infection. However, no spirochetes were observed in these tissues beyond the first 32 d after acquisition. Ticks of both species were fed on mice 112 d after they acquired spirochetes and only those mice fed upon by O. hermsi became infected. Thus, the vector competency for B. hermsii displayed by O. hermsi but not O. turicata lies, in part, in the persistent infection of the salivary glands of the former but not the latter species of tick. The genetic and biochemical mechanisms supporting this spirochete and vector specificity remain to be identified.
Larval Conditioning and Aging of Sand Fly Rearing Medium Affect Oviposition Site Selection in Phlebotomus papatasi (Diptera: Psychodidae) Sand Flies
Authors: Faw Lindsey R , Raymann Kasie , Romo Bechara Nayma , Wasserberg Gideon
Published: April 2021

Sand fly larvae develop in sheltered humid habitats containing decaying organic matter on which they feed. Previously, we showed that gravid females of Phlebotomus papatasi Scopoli (Diptera: Psychodidae) are attracted to and stimulated to lay eggs on larval rearing medium containing larvae. That study, however, did not control for the possible effect of medium aging. Our goal in this study was to evaluate the effect of larval substrate conditioning on attraction and oviposition responses of Ph. papatasi sand flies while controlling for the effect of substrate aging. Initially, we confirmed that the pretreatment fresh larval food sources (to be used as larval conditioned and unconditioned media) did not differ with respect to their effect on attraction and oviposition responses. The larval conditioned medium was produced by rearing larvae to the second/third-instar stage over 3 wk using the same larval food source. To produce larval unconditioned medium, the same amount of fresh larval food was added to a control rearing cup that did not contain larvae but was aged under identical time and conditions. Two-choice bioassays were conducted to evaluate gravid female’s attraction and oviposition response to larval conditioned and unconditioned media. We found that gravid females were significantly attracted (P < 0.05) to larval conditioned medium when compared with unconditioned medium under the same amount of time and conditions. However, no such difference was found with respect to oviposition response. Both attraction and oviposition responses were significantly increased for larval conditioned and unconditioned media in comparison to the initial fresh larval food source.
Sexual differences and sex ratios of dioecious plants under stressful environments
Authors: Liu Miao , Korpelainen Helena , Li Chunyang
Published: April 2021

Dioecious plants exhibit sexual dimorphism in both sexual features (reproductive organs) and secondary sex characteristics (vegetative traits). Sexual differences in secondary traits, including morphological, physiological and ecological characters, have been commonly associated with trade-offs between the cost of reproduction and other plant functions. Such trade-offs may be modified by environmental stressors, although there is evidence that sexually dimorphic responses to stress do not always exist in all plant species. When sexual dimorphism exists, sexually different responses appear to depend on the species and stress types. Yet, further studies on dioecious plant species are needed to allow the generalization of stress effects on males and females. Additionally, sexual dimorphism may influence the frequency and distribution of the sexes along environmental gradients, likely causing niche differentiation and spatial segregation of sexes. At the present, the causes and mechanisms governing sex ratio biases are poorly understood. This review aims to discuss sex-specific responses and sex ratio biases occurring under adverse conditions, which will advance our knowledge of sexually dimorphic responses to environmental stressors.
Effects of resource sharing directionality on physiologically integrated clones of the invasive Carpobrotus edulis
Authors: Portela Rubén , Barreiro Rodolfo , Roiloa Sergio R
Published: April 2021

Aims

One of the key traits associated with clonal growth in plants is the capacity for physiological integration, which allows resource sharing between connected ramets within a clonal system. Resource transport is expected to occur following a source–sink relationship: from ramets established in rich patches to ramets growing in poor patches. However, some experiments have shown that acropetal transport (from basal to apical modules) usually exceeds basipetal transport (from apical to basal ramets). In this study, we aimed to determine the resource transport directionality in physiologically integrated modules of the invader Carpobrotus edulis.

Methods

We conducted two manipulative experiments under common garden conditions that studied the effect of different nutrient levels located at different positions (basal, medial and apical) on connected and disconnected clonal systems of C. edulis. We compared the biomass partitioning patterns and final biomass of ramets to elucidate whether the effect of physiological integration is affected by the directionality of the resource transport.

Important Findings

Results indicate a prevalent acropetal transport of resources in C. edulis, with a developmentally programmed division of labor where basal ramets were specialized in obtaining soil-based resources and apical ramets specialized in aboveground growth. This biomass partitioning pattern was not affected by the nutrient conditions in which basal or apical ramets were growing, although the highest benefit was achieved by apical ramets growing under the most stressed conditions. This developmentally programmed division of labor is expected to increase the lateral growth of C. edulis, and therefore could have meaningful implications for the expansion of this invasive species.
Plus One: Who Decides Who is One’s Significant Other?
Authors: Shakargy Sharon
Published: April 2021

The law respects essential relationships, most notably marriage. Family members receive various benefits to support the family unit and the relationships within it. While the protection of parental relationships is easily understandable, spousal benefits may be questioned. In the western historical tradition, granting benefits exclusively to marital relationships were justified and practical. Nowadays, this seems less obvious. This article suggests that like wedding invitations, the law too should be open to various ‘plus ones’ so it will reflect, respect, and support the reality of life and not base itself on overly-broad, sometimes unjustified, assumptions founded solely on one traditional official relationship (and its modern variations).
D/H in the refractory organics of comet 67P/Churyumov-Gerasimenko measured by Rosetta/COSIMA
Authors: Paquette J A , Fray N , Bardyn A , Engrand C , Alexander C M O'D , Siljeström S , Cottin H , Merouane S , Isnard R , Stenzel O J , Fischer H , Rynö J , Kissel J , Hilchenbach M
Published: April 2021

The D/H ratio is a clue to the origin and evolution of hydrogen-bearing chemical species in Solar system materials. D/H has been observed in the coma of many comets, but most such measurements have been for gaseous water. We present the first in situ measurements of the D/H ratios in the organic refractory component of cometary dust particles collected at very low impact speeds in the coma of comet 67P/Churyumov-Gerasimenko (hereafter 67P) by the COSIMA instrument onboard Rosetta. The values measured by COSIMA are spatial averages over an approximately 35 × 50 µm2 area. The average D/H ratio for the 25 measured particles is (1.57 ± 0.54) × 10−3, about an order of magnitude higher than the Vienna Standard Mean Ocean Water (VSMOW), but more than an order of magnitude lower than the values measured in gas-phase organics in solar-like protostellar regions and hot cores. This relatively high averaged value suggests that refractory carbonaceous matter in comet 67P is less processed than the most primitive insoluble organic matter (IOM) in meteorites, which has a D/H ratio in the range of about 1 to 7 × 10−4. The cometary particles measured in situ also have a higher H/C ratio than the IOM. We deduce that the measured D/H in cometary refractory organics is an inheritance from the presolar molecular cloud from which the Solar system formed. The high D/H ratios observed in the cometary particles challenges models in which high D/H ratios result solely from processes that operated in the protosolar disc.
3D simulations of photochemical hazes in the atmosphere of hot Jupiter HD 189733b
Authors: Steinrueck Maria E , Showman Adam P , Lavvas Panayotis , Koskinen Tommi , Tan Xianyu , Zhang Xi
Published: April 2021

Photochemical hazes have been suggested as candidate for the high-altitude aerosols observed in the transmission spectra of many hot Jupiters. We present 3D simulations of the hot Jupiter HD 189733b to study how photochemical hazes are transported by atmospheric circulation. The model includes spherical, constant-size haze particles that gravitationally settle and are transported by the winds as passive tracers, with particle radii ranging from 1 nm to 1 $\mu$m. We identify two general types of haze distribution based on particle size: In the small-particle regime (<30 nm), gravitational settling is unimportant, and hazes accumulate in two large mid-latitude vortices centred on the nightside that extend across the morning terminator. Therefore, small hazes are more concentrated at the morning terminator than at the evening terminator. In the large-particle regime (>30 nm), hazes settle out quickly on the nightside, resulting in more hazes at the evening terminator. For small particles, terminator differences in haze mass mixing ratio and temperature considered individually can result in significant differences in the transit spectra of the terminators. When combining both effects for HD 189733b, however, they largely cancel out each other, resulting in very small terminator differences in the spectra. Transit spectra based on the GCM-derived haze distribution fail to reproduce the steep spectral slope at short wavelengths in the current transit observations of HD 189733b. Enhanced sub-grid scale mixing and/or optical properties of hazes differing from soot can explain the mismatch between the model and observations, although uncertainties in temperature and star spots may also contribute to the spectral slope.
Conservation of Aging and Cancer Epigenetic Signatures across Human and Mouse
Authors: Pérez Raúl F , Tejedor Juan Ramón , Santamarina-Ojeda Pablo , Martínez Virginia López , Urdinguio Rocío G , Villamañán Lucía , Candiota Ana Paula , Sarró Noemí Vidal , Barradas Marta , Fernandez-Marcos Pablo Jose , Serrano Manuel , Fernández Agustín F , Fraga Mario F
Published: April 2021

Aging and cancer are two interrelated processes, with aging being a major risk factor for the development of cancer. Parallel epigenetic alterations have been described for both, although differences, especially within the DNA hypomethylation scenario, have also been recently reported. Although many of these observations arise from the use of mouse models, there is a lack of systematic comparisons of human and mouse epigenetic patterns in the context of disease. However, such comparisons are significant as they allow to establish the extent to which some of the observed similarities or differences arise from pre-existing species-specific epigenetic traits. Here, we have used reduced representation bisulfite sequencing to profile the brain methylomes of young and old, tumoral and nontumoral brain samples from human and mouse. We first characterized the baseline epigenomic patterns of the species and subsequently focused on the DNA methylation alterations associated with cancer and aging. Next, we described the functional genomic and epigenomic context associated with the alterations, and finally, we integrated our data to study interspecies DNA methylation levels at orthologous CpG sites. Globally, we found considerable differences between the characteristics of DNA methylation alterations in cancer and aging in both species. Moreover, we describe robust evidence for the conservation of the specific cancer and aging epigenomic signatures in human and mouse. Our observations point toward the preservation of the functional consequences of these alterations at multiple levels of genomic regulation. Finally, our analyses reveal a role for the genomic context in explaining disease- and species-specific epigenetic traits.
Vaxign2: the second generation of the first Web-based vaccine design program using reverse vaccinology and machine learning
Authors: Ong Edison , Cooke Michael F , Huffman Anthony , Xiang Zuoshuang , Wong Mei U , Wang Haihe , Seetharaman Meenakshi , Valdez Ninotchka , He Yongqun
Published: April 2021

Vaccination is one of the most significant inventions in medicine. Reverse vaccinology (RV) is a state-of-the-art technique to predict vaccine candidates from pathogen's genome(s). To promote vaccine development, we updated Vaxign2, the first web-based vaccine design program using reverse vaccinology with machine learning. Vaxign2 is a comprehensive web server for rational vaccine design, consisting of predictive and computational workflow components. The predictive part includes the original Vaxign filtering-based method and a new machine learning-based method, Vaxign-ML. The benchmarking results using a validation dataset showed that Vaxign-ML had superior prediction performance compared to other RV tools. Besides the prediction component, Vaxign2 implemented various post-prediction analyses to significantly enhance users’ capability to refine the prediction results based on different vaccine design rationales and considerably reduce user time to analyze the Vaxign/Vaxign-ML prediction results. Users provide proteome sequences as input data, select candidates based on Vaxign outputs and Vaxign-ML scores, and perform post-prediction analysis. Vaxign2 also includes precomputed results from approximately 1 million proteins in 398 proteomes of 36 pathogens. As a demonstration, Vaxign2 was used to effectively analyse SARS-CoV-2, the coronavirus causing COVID-19. The comprehensive framework of Vaxign2 can support better and more rational vaccine design. Vaxign2 is publicly accessible at http://www.violinet.org/vaxign2.
Increased expression of tryptophan and tyrosine tRNAs elevates stop codon readthrough of reporter systems in human cell lines
Authors: Beznosková Petra , Bidou Laure , Namy Olivier , Valášek Leoš Shivaya
Published: April 2021

Regulation of translation via stop codon readthrough (SC-RT) expands not only tissue-specific but also viral proteomes in humans and, therefore, represents an important subject of study. Understanding this mechanism and all involved players is critical also from a point of view of prospective medical therapies of hereditary diseases caused by a premature termination codon. tRNAs were considered for a long time to be just passive players delivering amino acid residues according to the genetic code to ribosomes without any active regulatory roles. In contrast, our recent yeast work identified several endogenous tRNAs implicated in the regulation of SC-RT. Swiftly emerging studies of human tRNA-ome also advocate that tRNAs have unprecedented regulatory potential. Here, we developed a universal U6 promotor-based system expressing various human endogenous tRNA iso-decoders to study consequences of their increased dosage on SC-RT employing various reporter systems in vivo. This system combined with siRNA-mediated downregulations of selected aminoacyl-tRNA synthetases demonstrated that changing levels of human tryptophan and tyrosine tRNAs do modulate efficiency of SC-RT. Overall, our results suggest that tissue-to-tissue specific levels of selected near-cognate tRNAs may have a vital potential to fine-tune the final landscape of the human proteome, as well as that of its viral pathogens.
Platypus: an open-access software for integrating lymphocyte single-cell immune repertoires with transcriptomes
Authors: Yermanos Alexander , Agrafiotis Andreas , Kuhn Raphael , Robbiani Damiano , Yates Josephine , Papadopoulou Chrysa , Han Jiami , Sandu Ioana , Weber Cédric , Bieberich Florian , Vazquez-Lombardi Rodrigo , Dounas Andreas , Neumeier Daniel , Oxenius Annette , Reddy Sai T
Published: April 2021

High-throughput single-cell sequencing (scSeq) technologies are revolutionizing the ability to molecularly profile B and T lymphocytes by offering the opportunity to simultaneously obtain information on adaptive immune receptor repertoires (VDJ repertoires) and transcriptomes. An integrated quantification of immune repertoire parameters, such as germline gene usage, clonal expansion, somatic hypermutation and transcriptional states opens up new possibilities for the high-resolution analysis of lymphocytes and the inference of antigen-specificity. While multiple tools now exist to investigate gene expression profiles from scSeq of transcriptomes, there is a lack of software dedicated to single-cell immune repertoires. Here, we present Platypus, an open-source software platform providing a user-friendly interface to investigate B-cell receptor and T-cell receptor repertoires from scSeq experiments. Platypus provides a framework to automate and ease the analysis of single-cell immune repertoires while also incorporating transcriptional information involving unsupervised clustering, gene expression and gene ontology. To showcase the capabilities of Platypus, we use it to analyze and visualize single-cell immune repertoires and transcriptomes from B and T cells from convalescent COVID-19 patients, revealing unique insight into the repertoire features and transcriptional profiles of clonally expanded lymphocytes. Platypus will expedite progress by facilitating the analysis of single-cell immune repertoire and transcriptome sequencing.
Deferring Amputation in Diabetic Foot Osteomyelitis: Doing More Harm Than Good?
Authors: Zhou Shiwei , Schmidt Brian M , Henig Oryan , Kaye Keith S
Published: April 2021

In a cohort of patients with diabetic foot osteomyelitis who were recommended to undergo below-knee amputation, those who deferred amputation and chose medical therapy were more likely to die during the follow-up time compared with those who proceeded with amputation.
In Silico Evaluation of Cyclophilin Inhibitors as Potential Treatment for SARS-CoV-2
Authors: Laurie Kyle , Holcomb David , Kames Jacob , Komar Anton A , DiCuccio Michael , Ibla Juan C , Kimchi-Sarfaty Chava
Published: April 2021

Background

The advent of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) provoked researchers to propose multiple antiviral strategies to improve patients’ outcomes. Studies provide evidence that cyclosporine A (CsA) decreases SARS-CoV-2 replication in vitro and decreases mortality rates of coronavirus disease 2019 (COVID-19) patients. CsA binds cyclophilins, which isomerize prolines, affecting viral protein activity.

Methods

We investigated the proline composition from various coronavirus proteomes to identify proteins that may critically rely on cyclophilin’s peptidyl-proline isomerase activity and found that the nucleocapsid (N) protein significantly depends on cyclophilin A (CyPA). We modeled CyPA and N protein interactions to demonstrate the N protein as a potential indirect therapeutic target of CsA, which we propose may impede coronavirus replication by obstructing nucleocapsid folding.

Results

Finally, we analyzed the literature and protein–protein interactions, finding evidence that, by inhibiting CyPA, CsA may impact coagulation proteins and hemostasis.

Conclusions

Despite CsA’s promising antiviral characteristics, the interactions between cyclophilins and coagulation factors emphasize risk stratification for COVID patients with thrombosis dispositions.
Professional Responsibility: Conceptual Rescue and Plea for Reform
Authors: Delacroix Sylvie
Published: April 2021

For as long as knowledge asymmetry continues to be deemed the defining characteristic of the lay-professional relationship, the courts’ delineation of obligations meant to address lay vulnerability will too frequently end up compounding the layperson’s non-epistemic, ‘sense of self’ vulnerability. The proposed re-conceptualisation of professional responsibility calls for reform on several fronts: among these, an expanded ‘duty to consult’ (beyond do-not-resuscitate-orders) is uniquely placed as a justiciable criterion capable of addressing such a situational, ‘sense of self’ vulnerability.
The Resection of a Thalamic Pilocytic Astrocytoma Through the Transchoroidal Fissure, Transcallosal Approach: 2-Dimensional Operative Video
Authors: Kadri Paulo A S , Ibn Essayed Walid , Al-Mefty Ossama
Published: April 2021

Surgical resection is the primary treatment of pilocytic astrocytomas and total removal can be curative. However, these lesions occur in critical areas, such as the thalamus, being surrounded by critical life neurovascular structures, which imposes a surgical challenge.
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Exhaustive acquisition and meticulous interpretation of preoperative radiological exams; reliable surgical orientation based on profound microneurosurgical anatomic knowledge and judicious discernment of the neuroanatomic distortions on the surface and deep-seated structures inflicted by the neuropathological entity; embracing and comprehensive application of the vast scope of available intraoperative guidance imaging and neurophysiological monitoring; in alliance with the mastered carefully microsurgical technique supported by endoscopic visualization are the keystones to the pursed duet “cure with quality of life” in the treatment of these lesions.

We present the case of a 17-yr-old young lady with a progressive motor deficit in her right hemibody for over 2 yr. Her radiological investigation demonstrated a left thalamic lesion displacing the projection fibers (corticospinal tract) within the internal capsule laterally. The patient consented to the surgical procedure. The surgical strategy, intraoperative findings, and microsurgical and endoscopic technique, as well as the postoperative radiological and clinical evaluation are presented.

The patient gave her informed consent for the publication of the case.
The Effect of Changing Political Contexts on Public Opinion in Japan, 1945–2020
Authors: Maeda Yukio
Published: April 2021

The role of public opinion in Japan has changed dramatically in response to major shifts in party politics over the past seventy years. This chapter explains how the creation and disintegration of a dominant pattern in elite political discourse shaped people’s understanding of and response to public affairs. It also describes how polling and the electorate developed side-by-side in a newly democratic Japan. During the early postwar period, Japanese people were preoccupied with achieving economic security. The party system was initially very unstable, but constitutional revision and the security treaty with the US became central issues due to the Korean War and other Cold War conflicts. A bipolar political competition over these issues drove public opinion from 1955 to the mid-1990s. The “conservative” and “progressive” ideologies were diametrically opposed over constitutional revision and the US-Japan Security Treaty. This ideological divide was institutionalized in a decades-long conflict between two political camps in the legislature. Ordinary people understood public affairs through the rhetoric of these two ideologies. In the current post–Cold War, post-reform era that began in the mid-1990s, the conflict between the conservative and progressive ideologies no longer provides signals for understanding politics. Political parties differ mostly in the fact that one group is in government and the others are in opposition. Without guiding principles to organize political discourse, short-term policy concerns and perceptions of incumbent government performance influence public opinion the most. At the same time, whether a government remains in power depends on public approval more than ever before.
Supply Chain Management
Authors: Choi Thomas Y. , Li Julie Juan , Rogers Dale S. , Schoenherr Tobias , Wagner Stephan M.
Published: April 2021

Supply chain management strives to add fundamental value to society by working to provide needed products and services. To facilitate the delivery of these products and services, organizations form relationships, and these relationships represent a valuable managerial resource that give organizations competitive advantage. The Oxford Handbook of Supply Chain Management considers such managerial issues in supply chain management and captures them across the five categories of people and welfare, data and technology, moving goods and services, structure and strategy, and growing and sustaining. As such, this handbook is intended to provide supply chain researchers further motivation to investigate how they can contribute to solving the world’s big and pressing issues.
The Development (and Imagined Reinvention) of Australian Archaeology in the Twentieth Century
Authors: Urwin Chris , Spriggs Matthew
Published: April 2021

Most histories of Australian archaeology written in the past three decades imagine that the discipline came of age in (approximately) the year 1960. We are led to believe that systematic archaeological research, nuanced interpretations, and advocacy for the conservation of Aboriginal cultural heritage all date to the post-1960 era. Yet archaeological research in Australia has a lengthier and more complex genealogy. Here we use a series of case studies to explore the gradual development of the discipline during the twentieth century. We unpack key moments and projects during the early to mid-twentieth century and examine the extent to which the so-called professional archaeologists of the 1960s overlapped with and depended on the work of “amateur” scholars. We conclude by suggesting that the period of most rapid and significant change in archaeological thought and practice was precipitated by Aboriginal activism leading up to the 1980s. Australia’s First Peoples demanded control of research into their cultural heritage, a project that continues today. Our discipline must encourage a culture of reflexivity on its current practices by coming to terms with—rather than silencing—its history, whether good, bad, or ugly.
Ways of the Mind
Authors: Nitzberg Dotan , Bakan Michael B.
Published: April 2021

This chapter proposes a progressive approach to research at the intersection of autism studies and music studies, one through which scientific frames of objectivity-aspiring, anonymizing representation are replaced by ethnographic and phenomenological frames of personhood-aspiring, individual re-presentation. Through a case study of the musical experiences of first author Dotan Nitzberg, a concert pianist on the autism spectrum, and through the re-presentation of dialogues between Nitzberg and the chapter’s second author, ethnomusicologist Michael Bakan, the commonplace practice of objectifying and dehumanizing autistic individuals, including musicians, is challenged. The authors posit that phenomenological approaches, and those informed by a Levinasian philosophy of alterity in particular, have the capacity to leverage this challenge in affirming the agency and humanity of people on the autism spectrum, fostering an appreciation for their difference and contributing to a larger activist agenda of reducing the stigma and marginalization to which they have historically been subjected.
Science Fiction Futures and (Re)visions of the Anthropocene
Authors: Gibson Julia D. , Whyte Kyle Powys
Published: April 2021

This chapter discusses how humans envision futures, especially environmental futures, including the climate crisis, the Anthropocene, and mass extinctions. Although the philosophy of technology has traditionally examined the forecasting of technological risk and arguments about whether to embrace or reject the growth of technological mediation of human lives, the field has yet to fully investigate environmental futurisms and imagination. To begin a conversation for the philosophy of technology, philosophies of science fiction narrative discuss the different roles that imagination plays in projecting our concerns with the present onto futures that have not occurred and future generations who are not yet living. One of the key issues that the chapter explores is how science fiction imagination is based on assumptions and values about the history of technological change, including industrialization, capitalism, and colonialism. These issues reveal ways in which technology, future narrative, and climate justice are related.
Contemporary Partnerships
Authors: Janzen Russell
Published: April 2021

This chapter seeks to determine what makes for a contemporary partnership on the ballet stage through an examination of gender roles and choreographic invention in three works created for the New York City Ballet in 2017. While choreographers often strive to make new, of-the-moment dances, traditional ballet training still holds strong, turning out dancers whose bodies and abilities adhere to ideals established long ago. This perpetuation of antiquated ideas of masculinity and femininity limits the ways in which ballet partnerships are able to reflect the world of today. After a brief overview of the expectations put on men and women in ballet, with an emphasis on partnering class and partnering techniques, the chapter looks at how Pontus Lidberg, Justin Peck, and Lauren Lovette, each utilizing different approaches, used choreography to craft contemporary partnerships in their new works for the New York City Ballet in 2017.
Performing the Past in the Present
Authors: McLelland Rowan
Published: April 2021

This chapter explores the conscious adoption, reformation, and indigenization of ballet in China in the mid-twentieth century to foreground how this historical development has contributed to the creation of a new genre of ballet unique to China in the contemporary period. Using The Red Detachment of Women (1964, [红色娘子军]) and the more recent Eight Heroines (2015, [八女投江]), the chapter highlights ballet’s contemporaneity in China at the convergence of the unique legacy of the sociopolitical reimagining of the form with tangible links to both the past and the present in ballet in the Global North as a modern transnational practice. It concludes that it is in its very divergence from the style of contemporary ballet more commonly performed in the West that Chinese contemporary ballet embodies the pluralistic cosmopolitan values that contemporary ballet adopts.
Costume
Authors: O’Brien Caroline
Published: April 2021

Dress is integral to the performance of ballet, carefully considered in the collaboration between the choreographer and the designer. This chapter offers a broad introduction to thinking about “costume” as a term that is reserved for and relates to garments used for performance. It examines contemporary ballet costume through the conventions evidenced in the component parts of garments while emphasizing a tradition of making. Uniform is used in the training of a dancer so that dress is embedded in bodily practice, becoming a symbiotic partner in the dance. Contemporary ballet abandoned the form of the classical tutu and features leotards, bare legs, and pointe shoes or canvas slippers, flattening the hierarchy and blurring the gender lines.