bluuebunny/crossref_metadata_2025 huggingface dataset:
Natural Resources, International Commodity Prices and Economic Performance in Sub-Saharan Africa (1990–2019)
Authors: Katoka Ben , Dostal Jörg Michael
Published: June 2021

In this paper, we investigate the link between windfall gains and losses of income associated with commodity exports and economic performance in a panel of 45 sub-Saharan African (SSA) countries over the period from 1990 to 2019. Windfall gains and losses of income are measured in terms of fluctuations in a country-specific commodity terms of trade (CTOT) index in which each commodity is weighted by the ratio of exports of that commodity in the country’s gross domestic product (GDP). The CTOT index therefore reflects the commodity export specialisation for individual countries. The data on CTOT are taken from the International Monetary Fund. Additionally, we use changes in real GDP per capita as our SSA economic performance measure. We employ a random coefficient model that yields individual estimates for each of the countries included in the analysis. Our approach is based on the assumption that the effect of windfall gains and losses on real GDP per capita growth varies across different SSA countries. Our main conclusion can be elaborated as follows: first, natural resources have undoubtedly contributed to higher economic growth in SSA countries since 1990. Second, when SSA countries are analytically divided into two groups depending on their commodity export specialisation, we find that resource-rich countries—in particular oil rich—are the best economic growth performers during the observation period. Finally, we find that windfall gains from commodity exports are not significantly associated with increased real GDP per capita growth in most agriculture-exporting countries.
Analyzing security issues of android mobile health and medical applications
Authors: Tangari Gioacchino , Ikram Muhammad , Sentana I Wayan Budi , Ijaz Kiran , Kaafar Mohamed Ali , Berkovsky Shlomo
Published: June 2021

Objective

We conduct a first large-scale analysis of mobile health (mHealth) apps available on Google Play with the goal of providing a comprehensive view of mHealth apps’ security features and gauging the associated risks for mHealth users and their data.

Materials and Methods

We designed an app collection platform that discovered and downloaded more than 20 000 mHealth apps from the Medical and Health & Fitness categories on Google Play. We performed a suite of app code and traffic measurements to highlight a range of app security flaws: certificate security, sensitive or unnecessary permission requests, malware presence, communication security, and security-related concerns raised in user reviews.

Results

Compared to baseline non-mHealth apps, mHealth apps generally adopt more reliable signing mechanisms and request fewer dangerous permissions. However, significant fractions of mHealth apps expose users to serious security risks. Specifically, 1.8% of mHealth apps package suspicious codes (eg, trojans), 45.0% rely on unencrypted communication, and as much as 23.0% of personal data (eg, location information and passwords) is sent on unsecured traffic. An analysis of the app reviews reveals that mHealth app users are largely unaware of the surfaced security issues.

Conclusion

Despite being better aligned with security best practices than non-mHealth apps, mHealth apps are still far from ensuring robust security guarantees. App users, clinicians, technology developers, and policy makers alike should be cognizant of the uncovered security issues and weigh them carefully against the benefits of mHealth apps.
Identifying Genomic Regions Targeted During Eggplant Domestication Using Transcriptome Data
Authors: Page Anna M L , Chapman Mark A
Published: June 2021

Identifying genes and traits that have diverged during domestication provides key information of importance for maintaining and even increasing yield and nutrients in existing crops. A “bottom-up” population genetics approach was used to identify signatures of selection across the eggplant genome, to better understand the process of domestication. RNA-seq data were obtained for 4 wild eggplants (Solanum insanum L.) and 16 domesticated eggplants (S. melongena L.) and mapped to the eggplant genome. Single-nucleotide polymorphism (SNPs) exhibiting signatures of selection in domesticates were identified as those exhibiting high FST between the 2 populations (evidence of significant divergence) and low π for the domesticated population (indicative of a selective sweep). Some of these regions appear to overlap with previously identified quantitative trait loci for domestication traits. Genes in regions of linkage disequilibrium surrounding these SNPs were searched against the Arabidopsis thaliana and tomato genomes to find orthologs. Subsequent gene ontology (GO) enrichment analysis identified over-representation of GO terms related to photosynthesis and response to the environment. This work reveals genomic changes involved in eggplant domestication and improvement, and how this compares to observed changes in the tomato genome, revealing shared chromosomal regions involved in the domestication of both species.
Exploitation of ammonia-inducible promoters for enzyme overexpression in Bacillus licheniformis
Authors: Shen Peili , Niu Dandan , Permaul Kugen , Tian Kangming , Singh Suren , Wang Zhengxiang
Published: June 2021

Ammonium hydroxide is conventionally used as an alkaline reagent and cost-effective nitrogen source in enzyme manufacturing processes. However, few ammonia-inducible enzyme expression systems have been described thus far. In this study, genomic-wide transcriptional changes in Bacillus licheniformis CBBD302 cultivated in media supplemented with ammonia were analyzed, resulting in identification of 1443 differently expressed genes, of which 859 genes were upregulated and 584 downregulated. Subsequently, the nucleotide sequences of ammonia-inducible promoters were analyzed and their functionally-mediated expression of amyL, encoding an α-amylase, was shown. TRNA_RS39005 (copA), TRNA_RS41250 (sacA), TRNA_RS23130 (pdpX), TRNA_RS42535 (ald), TRNA_RS31535 (plp), and TRNA_RS23240 (dfp) were selected out of the 859 upregulated genes and each showed higher transcription levels (FPKM values) in the presence of ammonia and glucose than that of the control. The promoters, PcopA from copA, PsacA from sacA, PpdpX from pdpX, Pald from ald, and Pplp from plp, except Pdfp from dfp, were able to mediate amyL expression and were significantly induced by ammonia. The highest enzyme expression level was mediated by Pplp and represented 23% more α-amylase activity after induction by ammonia in a 5-L fermenter. In conclusion, B. licheniformis possesses glucose-independent ammonia-inducible promoters, which can be used to mediate enzyme expression and therefore enhance the enzyme yield in fermentations conventionally fed with ammonia for pH adjustment and nitrogen supply.
Nested sampling with any prior you like
Authors: Alsing Justin , Handley Will
Published: June 2021

Nested sampling is an important tool for conducting Bayesian analysis in Astronomy and other fields, both for sampling complicated posterior distributions for parameter inference, and for computing marginal likelihoods for model comparison. One technical obstacle to using nested sampling in practice is the requirement (for most common implementations) that prior distributions be provided in the form of transformations from the unit hyper-cube to the target prior density. For many applications – particularly when using the posterior from one experiment as the prior for another – such a transformation is not readily available. In this letter, we show that parametric bijectors trained on samples from a desired prior density provide a general purpose method for constructing transformations from the uniform base density to a target prior, enabling the practical use of nested sampling under arbitrary priors. We demonstrate the use of trained bijectors in conjunction with nested sampling on a number of examples from cosmology.
CROssBAR: comprehensive resource of biomedical relations with knowledge graph representations
Authors: Doğan Tunca , Atas Heval , Joshi Vishal , Atakan Ahmet , Rifaioglu Ahmet Sureyya , Nalbat Esra , Nightingale Andrew , Saidi Rabie , Volynkin Vladimir , Zellner Hermann , Cetin-Atalay Rengul , Martin Maria , Atalay Volkan
Published: June 2021

Systemic analysis of available large-scale biological/biomedical data is critical for studying biological mechanisms, and developing novel and effective treatment approaches against diseases. However, different layers of the available data are produced using different technologies and scattered across individual computational resources without any explicit connections to each other, which hinders extensive and integrative multi-omics-based analysis. We aimed to address this issue by developing a new data integration/representation methodology and its application by constructing a biological data resource. CROssBAR is a comprehensive system that integrates large-scale biological/biomedical data from various resources and stores them in a NoSQL database. CROssBAR is enriched with the deep-learning-based prediction of relationships between numerous data entries, which is followed by the rigorous analysis of the enriched data to obtain biologically meaningful modules. These complex sets of entities and relationships are displayed to users via easy-to-interpret, interactive knowledge graphs within an open-access service. CROssBAR knowledge graphs incorporate relevant genes-proteins, molecular interactions, pathways, phenotypes, diseases, as well as known/predicted drugs and bioactive compounds, and they are constructed on-the-fly based on simple non-programmatic user queries. These intensely processed heterogeneous networks are expected to aid systems-level research, especially to infer biological mechanisms in relation to genes, proteins, their ligands, and diseases.
DNA methylation profiling as a model for discovery and precision diagnostics in neuro-oncology
Authors: Pratt Drew , Sahm Felix , Aldape Kenneth
Published: June 2021

Recent years have witnessed a shift to more objective and biologically-driven methods for central nervous system (CNS) tumor classification. The 2016 world health organization (WHO) classification update (“blue book”) introduced molecular diagnostic criteria into the definitions of specific entities as a response to the plethora of evidence that key molecular alterations define distinct tumor types and are clinically meaningful. While in the past such diagnostic alterations included specific mutations, copy number changes, or gene fusions, the emergence of DNA methylation arrays in recent years has similarly resulted in improved diagnostic precision, increased reliability, and has provided an effective framework for the discovery of new tumor types. In many instances, there is an intimate relationship between these mutations/fusions and DNA methylation signatures. The adoption of methylation data into neuro-oncology nosology has been greatly aided by the availability of technology compatible with clinical diagnostics, along with the development of a freely accessible machine learning-based classifier. In this review, we highlight the utility of DNA methylation profiling in CNS tumor classification with a focus on recently described novel and rare tumor types, as well as its contribution to refining existing types.
BOIN: a novel Bayesian design platform to accelerate early phase brain tumor clinical trials
Authors: Yuan Ying , Wu Jing , Gilbert Mark R
Published: June 2021

Despite decades of extensive research, the progress in developing effective treatments for primary brain tumors lags behind that of other cancers, largely due to the unique challenges of brain tumors (eg, the blood-brain barrier and high heterogeneity) that limit the delivery and efficacy of many therapeutic agents. One way to address this issue is to employ novel trial designs to better optimize the treatment regimen (eg, dose and schedule) in early phase trials to improve the success rate of subsequent phase III trials. The objective of this article is to introduce Bayesian optimal interval (BOIN) designs as a novel platform to design various types of early phase brain tumor trials, including single-agent and combination regimen trials, trials with late-onset toxicities, and trials aiming to find the optimal biological dose (OBD) based on both toxicity and efficacy. Unlike many novel Bayesian adaptive designs, which are difficult to understand and complicated to implement by clinical investigators, the BOIN designs are self-explanatory and user friendly, yet yield more robust and powerful operating characteristics than conventional designs. We illustrate the BOIN designs using a phase I clinical trial of brain tumor and provide software (freely available at www.trialdesign.org) to facilitate the application of the BOIN design.
Australian Indigenous Ochres
Authors: Huntley Jillian
Published: June 2021

Aboriginal Australians use ochre in varied cultural practices. It is found in the earliest to most recent archaeological sites and geographically across the wide-ranging geological and climatic contexts of the continent. Ochre’s importance in Aboriginal societies, coupled with its availability across Australia and its long-term durability, has led to a ubiquitous archaeological presence with considerable potential to study past cultural landscapes and intergroup interactions, including long-distance trade and exchange. Concentrating on scientific sourcing analyses, this article highlights the benefits of archaeopigment research, defining key terms (ochre, provenience, and provenance) and the technicalities of sourcing studies before discussing theoretical frameworks used in interpretations of ochre distribution patterns. The article argues that as we move away from novel studies on ethnographically well-known source locations into applied research, exceptional Australian records are well placed to investigate territoriality, mobility, intergroup and human–landscape interactions, and to explore the catalysts driving cultural diversity.
Discourses of Disease: The Lifeworld, the Healthworld, and HIV/AIDS
Authors: Higgins Christina
Published: June 2021

Research on HIV/AIDS in linguistics, linguistic anthropology, and literacy studies has followed the course of the pandemic from when it first became widely known in the United States, where early research focused on gay men and their communications with doctors, counselors, and each other in relation to risk and transmission. As time progressed, research shifted to sub-Saharan Africa and South Asia to focus on the discourse of prevention campaigns and public responses to risk reduction strategies. More recently, researchers have examined how people communicate about HIV/AIDS, focusing on how individuals interact with public health discourse in participatory approaches that change the way that HIV/AIDS is framed in educational and institutional contexts. Decades of research has shown a recurring gap in health communication about HIV/AIDS due to the imposition of a biomedical understanding of HIV/AIDS (the “healthworld”) on individuals’ situated perspectives and lived experiences within particular sociocultural contexts (the “lifeworld”).
Reproduction and Language
Authors: Han Sallie
Published: June 2021

The aim of this chapter is to demonstrate the importance and necessity of bringing together the considerations of language and reproduction. While other topics of sexuality have aroused interest in sociolinguistics and linguistic anthropology, the ideas, practices, and experiences of human reproduction, notably pregnancy, remain understudied. At the same time, a discussion of language has been largely absent from the anthropology of reproduction, which has emerged in the last twenty years as an especially vibrant area of cultural and social study. The chapter examines the metaphors and discourses in “talk about” reproduction; the interactions and “talk between” people, like pregnant women and medical health care providers, which shapes the ordinary experiences of reproduction; the “talk to” parties (specifically, fetuses and imagined children) who themselves become constituted through talk; and reproduction as literacy event or one that is mediated and experienced in relation to texts. It is asserted that language is a practice of reproduction.
Resignifications: Linguistic Resistance and Queer Expressions of Latinidad
Authors: Ferrada Juan Sebastian
Published: June 2021

The resignification of language practices among LGBTQIA+ communities has seen the reclamation of terms like queer, dyke, and faggot enter mainstream discourse. Marginalized communities who view the reclamation of language as a form of empowerment also have a long history of resignifying certain forms of pejorative language to revalorize meanings along ethnic and racial lines. This chapter provides an overview of contributions from queer theory, queer studies, and queer linguistics that center the reclamation of historically pejorative terms used for queer communities, but situates these queer resignifications within the context of linguistic reclamations enacted around ethnic and racial affiliations. The chapter specifically focuses on the reclamation of the Spanish terms joto/a/x and jotería by Latinx communities in the United States—terms that have historically been used to denigrate men performing traits associated with femininity—to illustrate how linguistic reclamation provides an avenue for resistance by creating and maintaining new worlds of possibility.
Empire, Postcolonial Criticism, and Biblical Studies
Authors: Jacob Sharon
Published: June 2021

When it comes to the relationship between the Bible and ancient empires, the focus for the most part remains on the past and on the imperial contexts in which these texts were written. It must be noted that even though historical-critical scholarship has drawn our attention to historical contexts, empires continued to remain in the background in biblical studies. This chapter focuses on the relationship between the Bible and empire, not only of the past but also the present. It examines in depth the works of biblical scholars who have made a conscious attempt to expand the field of Biblical studies. Furthermore, by highlighting the points of convergence and divergence between the Bible and precolonial, colonial, and postcolonial empires, scholars can begin to see the ways in which the relationship between the Bible and empire has constantly evolved, transformed, and mutated as scholars transgress boundaries and draw on the work of one another.
The Social Construction of Peace
Authors: Wallis Joanne
Published: June 2021

Peace is socially constructed; it is the product of human agency, and ideas and practices relating to peace are constituted and instantiated within intersubjective social contexts. A constructivist analysis of peace takes a reflexive approach to analyzing peace in order to rethink the tacit ontological assumptions on which dominant international analyses of peace are premised. It suggests that we need to make less certain, more dynamic, contingent, and flexible ontological assumptions regarding how peace is understood and practiced in conflict-affected societies. While acknowledging the ethical issues involved in seeking to know local knowledge, this suggests that we should expand our analysis to consider the everyday lived experiences, beliefs, feelings, ideas, and understandings of those affected by conflict.
Informality in International Political Economy
Authors: Vabulas Felicity
Published: June 2021

Informality is increasingly defining outcomes in an international political economy that has previously been defined by precise treaties and large bureaucracies. Nonetheless, research in the budding area of “informality in IPE” is still nascent. This chapter brings some cohesion to the literature by discussing how soft law, informal governance, and informal intergovernmental organizations are affecting our global economy. By overviewing informality in the areas of international finance, international trade, and international economic institutions, it underscores how important bodies such as the G7, Financial Action Task Force, and Basel Committee are increasingly shaping how states interact. It underscores that informality is neither normatively better nor worse than its formal brethren, but instead that informality will have different effects on international relations. The chapter ends by highlighting ripe areas for more “informality in IPE” research going forward, including a better understanding of how topics such as block chain technologies, informal sanctions, and informal migration affect global politics. Nonetheless, a deeper investigation of these important areas will continue to be challenged by the things that define informality itself—a lack of transparency, working around the rules, and fluidity.
Hedging: Organizational Responses to the Formulation, Implementation, and Enforcement of Government Mandated Changes
Authors: Marcus Alfred , Malen Joel
Published: June 2021

This chapter develops a process model of the hedging behavior of organizations in response to government mandates. To better align the behavior of organizations with the interests of society, governments make many demands on organizations to change their behavior. However, the changes governments require generally do not correspond to the changes organizations want to make, or those that they actually end up making. The process model describes how the variety of external requirements imposed on organizations by government leads to hedging behavior—that is a tendency to simultaneously take actions that align with the regulation while simultaneously taking actions to resist the regulation.
Phosphatidylserine Is Required for the Normal Progression of Cell Plate Formation in Arabidopsis Root Meristems
Authors: Yamaoka Yasuyo , Shin Seungjun , Lee Yuree , Ito Masaki , Lee Youngsook , Nishida Ikuo
Published: June 2021

Phosphatidylserine (PS) is involved in various cellular processes in yeast and animals. However, PS functions in plants remain unclear. In Arabidopsis, PS is relatively enriched in flower and root tissues, and the genetic disturbance of PS biosynthesis in phosphatidylserine synthase1 (PSS1)/ pss1 heterozygotes induces sporophytic and gametophytic defects during pollen maturation. This study functionally characterized PS in Arabidopsis roots and observed that pss1 seedlings exhibited a short-root phenotype by reducing the meristem size and cell elongation capacity. Confocal microscopy imaging analyses of PS with GFP-LactC2 and the endocytic activity with FM 4-64 revealed that although GFP-LactC2 (or PS) was localized in the plasma membrane and endocytic membranes, the lack of PS in pss1 roots did not affect the constitutive endocytosis. Instead, a fluorescence imaging analysis of the cytokinetic phases in the dividing zone of pss1-2 roots revealed a significant delay in telophase progression, requiring active cargo vesicle trafficking for cell plate formation. Confocal microscopy imaging analysis of transgenic GFP-LactC2 root cells with developing cell plates indicated that GFP-LactC2 was localized at the cell plate. Moreover, confocal microscopy images of transgenic pss1-2 and PSS1 roots expressing the cell plate-specific syntaxin construct ProKNOLLE:eGFP-KNOLLE showed abnormal cell plate development in pss1-2ProKNOLLE:eGFP-KNOLLE roots. These results suggested that PS is required for root cytokinesis, possibly because it helps mediate the cargo vesicular trafficking required for cell plate formation.
The metabolomic landscape of rice heterosis highlights pathway biomarkers for predicting complex phenotypes
Authors: Dan Zhiwu , Chen Yunping , Li Hui , Zeng Yafei , Xu Wuwu , Zhao Weibo , He Ruifeng , Huang Wenchao
Published: June 2021

Understanding the molecular mechanisms underlying complex phenotypes requires systematic analyses of complicated metabolic networks and contributes to improvements in the breeding efficiency of staple cereal crops and diagnostic accuracy for human diseases. Here, we selected rice (Oryza sativa) heterosis as a complex phenotype and investigated the mechanisms of both vegetative and reproductive traits using an untargeted metabolomics strategy. Heterosis-associated analytes were identified, and the overlapping analytes were shown to underlie the association patterns for six agronomic traits. The heterosis-associated analytes of four yield components and plant height collectively contributed to yield heterosis, and the degree of contribution differed among the five traits. We performed dysregulated network analyses of the high- and low-better parent heterosis hybrids and found multiple types of metabolic pathways involved in heterosis. The metabolite levels of the significantly enriched pathways (especially those from amino acid and carbohydrate metabolism) were predictive of yield heterosis (area under the curve = 0.907 with 10 features), and the predictability of these pathway biomarkers was validated with hybrids across environments and populations. Our findings elucidate the metabolomic landscape of rice heterosis and highlight the potential application of pathway biomarkers in achieving accurate predictions of complex phenotypes.
Current and emerging biological therapy in adult-onset Still’s disease
Authors: Ma Yuning , Meng Jianfen , Jia Jinchao , Wang Mengyan , Teng Jialin , Zhu Dehao , Yang Chengde , Hu Qiongyi
Published: June 2021

Adult-onset Still’s disease (AOSD) is a rare, but characteristic non-familial, multi-genic systemic auto-inflammatory disorder, characterized by high spiking fever, salmon-like evanescent skin rash, polyarthritis, sore throat, hyperferritinemia and leucocytosis. The hallmark of AOSD is a cytokine storm triggered by dysregulation of inflammation. Nowadays, with advances in anti-cytokine biologic agents, the treatment of AOSD is no longer limited to NSAIDs, glucocorticoids or conventional synthetic DMARDs. In this review, we focussed on the roles of these cytokines in the pathogenesis of AOSD and summarized the current and emerging biological therapy.
SARS-CoV-2 in eight municipalities of the Colombian tropics: high immunity, clinical and sociodemographic outcomes
Authors: Garay Evelin , Serrano-Coll Héctor , Rivero Ricardo , Gastelbondo Bertha , Faccini-Martínez Álvaro , Berrocal José , Pérez Alejandra , Badillo María , Martínez-Bravo Caty , Botero Yesica , Arrieta Germán , Calderón Alfonso , Galeano Ketty , López Yesica , Miranda Jorge , Guzmán Camilo , Contreras Verónica , Arosemena Alejandra , Contreras Héctor , Brango-Tarra Eimi , Oviedo Misael , Mattar Salim
Published: June 2021

Background

Serological evaluation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an alternative that allows us to determine the prevalence and dynamics of this infection in populations. The goal of this study was to determine the clinical and sociodemographic dynamics of SARS-CoV-2 infection in a region of the Colombian Caribbean.

Methods

Between July and November 2020, a cross-sectional observational study was carried out in Córdoba, located in northeast Colombia in the Caribbean area. Eight municipalities with the largest populations were chosen and 2564 blood samples were taken. A commercial enzyme-linked immunosorbent assay was used with the recombinant protein antigen N of SARS-CoV-2. The people included in the study were asked for sociodemographic and clinical data, which were analysed by statistical methods.

Results

A seroprevalence of 40.8% was obtained for SARS-CoV-2 in the Córdoba region. In the bivariate analysis, no differences were observed in seropositivity against SARS-CoV-2 for gender or age range (p>0.05). Higher seropositivity was found in low socio-economic status and symptomatic patients (p<0.0001). A total of 30.7% of the asymptomatic patients were seropositive for SARS-CoV-2, which could be linked to the spread of this infection. In the multivariate analysis, seroconversion was related to poverty and clinical manifestations such as anosmia and ageusia (p<0.05).

Conclusions

The high seropositivity in Córdoba is due to widespread SARS-CoV-2 in this population. The relationship between seropositivity and socio-economic status suggests a higher exposure risk to the virus caused by informal economic activities in low-income groups. Clinical manifestations such as anosmia and ageusia could be clinical predictors of infection by the new emergent coronavirus.
Inches, Centimeters, and Yards
Authors: Dasgupta Nabarun , Wang Yanning , Bae Jungjun , Kinlaw Alan C. , Chidgey Brooke A. , Cooper Toska , Delcher Chris
Published: June 2021

Objective:

Morphine-standardized doses are used in clinical practice and research to account for molecular potency. Ninety milligrams of morphine equivalents (MME) per day are considered a “high dose” risk threshold in guidelines, laws, and by payers. Although ubiquitously cited, the “CDC definition” of daily MME lacks a clearly defined denominator. Our objective was to assess denominator-dependency on “high dose” classification across competing definitions.

Methods:

To identify definitional variants, we reviewed literature and electronic prescribing tools, yielding 4 unique definitions. Using Prescription Drug Monitoring Programs data (July to September 2018), we conducted a population-based cohort study of 3,916,461 patients receiving outpatient opioid analgesics in California (CA) and Florida (FL). The binary outcome was whether patients were deemed “high dose” (>90 MME/d) compared across 4 definitions. We calculated I
2 for heterogeneity attributable to the definition.

Results:

Among 9,436,640 prescriptions, 42% overlapped, which led denominator definitions to impact daily MME values. Across definitions, average daily MME varied 3-fold (range: 17 to 52 [CA] and 23 to 65 mg [FL]). Across definitions, prevalence of “high dose” individuals ranged 5.9% to 14.2% (FL) and 3.5% to 10.3% (CA). Definitional variation alone would impact a hypothetical surveillance study trying to establish how much more “high dose” prescribing was present in FL than CA: from 39% to 84% more. Meta-analyses revealed strong heterogeneity (I
2 range: 86% to 99%). In sensitivity analysis, including unit interval 90.0 to 90.9 increased “high dose” population fraction by 15%.

Discussion:

While 90 MME may have cautionary mnemonic benefits, without harmonization of calculation, its utility is limited. Comparison between studies using daily MME requires explicit attention to definitional variation.
Preclinical Safety of a 3D-Printed Hydroxyapatite-Demineralized Bone Matrix Scaffold for Spinal Fusion
Authors: Plantz Mark , Lyons Joseph , Yamaguchi Jonathan T. , Greene Allison C. , Ellenbogen David J. , Hallman Mitchell J. , Shah Vivek , Yun Chawon , Jakus Adam E. , Procissi Daniele , Minardi Silvia , Shah Ramille N. , Hsu Wellington K. , Hsu Erin L.
Published: June 2021

Study Design.

Prospective, randomized, controlled preclinical study.

Objective.

The objective of this study was to compare the host inflammatory response of our previously described hyperelastic, 3D-printed (3DP) hydroxyapatite (HA)-demineralized bone matrix (DBM) composite scaffold to the response elicited with the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in a preclinical rat posterolateral lumbar fusion model.

Summary of Background Data.

Our group previously found that this 3D-printed HA-DBM composite material shows promise as a bone graft substitute in a preclinical rodent model, but its safety profile had yet to be assessed.

Methods.

Sixty female Sprague-Dawley rats underwent bilateral posterolateral intertransverse lumbar spinal fusion using with the following implants: 1) type I absorbable collagen sponge (ACS) alone; 2) 10 μg rhBMP-2/ACS; or 3) the 3DP HA-DBM composite scaffold (n = 20). The host inflammatory response was assessed using magnetic resonance imaging, while the local and circulating cytokine expression levels were evaluated by enzyme-linked immunosorbent assays at subsequent postoperative time points (N = 5/time point).

Results.

At both 2 and 5 days postoperatively, treatment with the HA-DBM scaffold produced significantly less soft tissue edema at the fusion bed site relative to rhBMP-2-treated animals as quantified on magnetic resonance imaging. At every postoperative time point evaluated, the level of soft tissue edema in HA-DBM-treated animals was comparable to that of the ACS control group. At 2 days postoperatively, serum concentrations of tumor necrosis factor-α and macrophage chemoattractant protein-1 were significantly elevated in the rhBMP-2 treatment group relative to ACS controls, whereas these cytokines were not elevated in the HA-DBM-treated animals.

Conclusion.

The 3D-printed HA-DBM composite induces a significantly reduced host inflammatory response in a preclinical spinal fusion model relative to rhBMP-2.

Level of Evidence: N/A
Setting the Beta-Lactam Therapeutic Range for Critically Ill Patients: Is There a Floor or Even a Ceiling?
Authors: Barreto Erin F. , Webb Andrew J. , Pais Gwendolyn M. , Rule Andrew D. , Jannetto Paul J. , Scheetz Marc H.
Published: June 2021

OBJECTIVES:

Beta-lactam antibiotics exhibit high interindividual variability in drug concentrations in patients with critical illness which led to an interest in the use of therapeutic drug monitoring to improve effectiveness and safety. To implement therapeutic drug monitoring, it is necessary to define the beta-lactam therapeutic range—in essence, what drug concentration would prompt a clinician to make dose adjustments up or down. This objective of this narrative review was to summarize evidence for the “floor” (for effectiveness) and “ceiling” (for toxicity) for the beta-lactam therapeutic range to be used with individualized therapeutic drug monitoring.

DATA SOURCES:

Research articles were sourced from PubMed using search term combinations of “pharmacokinetics,” “pharmacodynamics,” “toxicity,” “neurotoxicity,” “therapeutic drug monitoring,” “beta-lactam,” “cefepime,” “meropenem,” “piperacillin/tazobactam,” “ICU,” and “critical illness.”

STUDY SELECTION:

Articles were selected if they included preclinical, translational, or clinical data on pharmacokinetic and pharmacodynamic thresholds for effectiveness and safety for beta-lactams in critical illness.

DATA SYNTHESIS:

Experimental data indicate a beta-lactam concentration above the minimum inhibitory concentration of the organism for greater than or equal to 40–60% of the dosing interval is needed, but clinical data indicate that higher concentrations may be preferrable. In the first 48 hours of critical illness, a free beta-lactam concentration at or above the susceptibility breakpoint of the most likely pathogen for 100% of the dosing interval would be reasonable (typically based on Pseudomonas aeruginosa). After 48 hours, the lowest acceptable concentration could be tailored to 1–2× the observed minimum inhibitory concentration of the organism for 100% of the dosing interval (often a more susceptible organism). Neurotoxicity is the primary dose-dependent adverse effect of beta-lactams, but the evidence remains insufficient to link a specific drug concentration to greater risk.

CONCLUSIONS:

As studies advance the understanding of beta-lactam exposure and response in critically ill patients, it is essential to clearly define the acceptable therapeutic range to guide regimen selection and adjustment.
Operationalizing Ethical Guidance for Ventilator Allocation in Minnesota: Saving the Most Lives or Exacerbating Health Disparities?
Authors: Kesler Sarah M. , Wu Joel T. , Kalland Krystina R. , Peter Logan G. , Wothe Jillian K. , Needle Jennifer K. , Wang Qi , Weinert Craig R.
Published: June 2021

OBJECTIVES:

A statewide working group in Minnesota created a ventilator allocation scoring system in anticipation of functioning under a Crisis Standards of Care declaration. The scoring system was intended for patients with and without coronavirus disease 2019. There was disagreement about whether the scoring system might exacerbate health disparities and about whether the score should include age. We measured the relationship of ventilator scores to in-hospital and 3-month mortality. We analyzed our findings in the context of ethical and legal guidance for the triage of scarce resources.

DESIGN:

Retrospective cohort study.

SETTING:

Multihospital within a single healthcare system.

PATIENTS:

Five-hundred four patients emergently intubated and admitted to the ICU.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

The Ventilator Allocation Score was positively associated with higher mortality (p < 0.0001). The 3-month mortality rate for patients with a score of 6 or higher was 96% (42/44 patients). Age was positively associated with mortality. The 3-month mortality rate for patients 80 and older with scores of 4 or greater was 93% (40/43 patients). Of patients assigned a score of 5, those with end stage renal disease had lower mortality than patients without end stage renal disease although the difference did not achieve statistical significance (n = 27; 25% vs 58%; p = 0.2).

CONCLUSIONS:

The Ventilator Allocation Score can accurately identify patients with high rates of short-term mortality. However, these high mortality patients only represent 27% of all the patients who died, limiting the utility of the score for allocation of scarce resources. The score may unfairly prioritize older patients and inadvertently exacerbate racial health disparities through the inclusion of specific comorbidities such as end stage renal disease. Triage frameworks that include age should be considered. Purposeful efforts must be taken to ensure that triage protocols do not perpetuate or exacerbate prevailing inequities. Further work on the allocation of scarce resources in critical care settings would benefit from consensus on the primary ethical objective.
ICU Survivorship—The Relationship of Delirium, Sedation, Dementia, and Acquired Weakness
Authors: Mart Matthew F. , Pun Brenda T. , Pandharipande Pratik , Jackson James C. , Ely E. Wesley
Published: June 2021

The advent of modern critical care medicine has revolutionized care of the critically ill patient in the last 50 years. The Society of Critical Care Medicine (was formed in recognition of the challenges and need for specialized treatment for these fragile patients. As the specialty has grown, it has achieved impressive scientific advances that have reduced mortality and saved lives. With those advances, however, came growing recognition that the burden of critical illness did not end at the doorstep of the hospital. Delirium, once thought to be a mere by-product of critical illness, was found to be an independent predictor of mortality, prolonged mechanical ventilation, and long-lasting cognitive impairment. Similarly, deep sedation and immobility, so often used to keep patients “comfortable” and to facilitate mechanical ventilation and recovery, worsen mortality and lead to the development of ICU-acquired weakness. The realization that these outcomes are inextricably linked to one another and how we manage our patients has helped us recognize the need for culture change. We, as a specialty, now understand that although celebrating the successes of survival, we now also have a duty to focus on those who survive their diseases. Led by initiatives such as the ICU Liberation Campaign of the Society of Critical Care Medicine, the natural progression of the field is now focused on getting patients back to their homes and lives unencumbered by disability and impairment. Much work remains to be done, but the futures of our most critically ill patients will continue to benefit if we leverage and build on the history of our first 50 years.
Simultaneous Application of High-Intensity Focused Electromagnetic and Synchronized Radiofrequency for Fat Disruption: Histological and Electron Microscopy Porcine Model Study
Authors: Weiss Robert A. , Bernardy Jan , Tichy Frantisek
Published: June 2021

BACKGROUND

Radiofrequency (RF) and high-intensity focused electromagnetic (HIFEM) technologies are used for noninvasive body shaping as standalone modalities.

OBJECTIVE

To examine the effects of novel synchronized RF and HIFEM on subcutaneous adipose tissue in a porcine animal model.

MATERIALS AND METHODS

Seven large white pigs aged 6 months received 3 abdominal treatments of simultaneous application of synchronized RF and HIFEM (30 minutes, once per week). Punch biopsies of treated and control subcutaneous tissue were collected at the baseline, 4 days, 2 weeks, 1 month, and 2 months. Specimens were examined by light and scanning electron microscopy. Adipocyte volume was analyzed. Fat tissue temperature was measured in situ (fiber optic probes) and superficially (thermal imager).

RESULTS

Fat layer was heated to temperatures of 42 to 45°C. Signs of fat apoptosis (shape alternations and pyknotic nuclei) appeared at day 4 and peaked between 2 weeks and 1 month. Adipocyte volume decreased significantly (p < .001) by 31.1% at 2 weeks, 1 month (−23.6%), and 2 months (−22.0%). Control samples showed healthy adipocytes. Scanning electron microscopy micrographs corroborated histology findings, showing flattened, volume-depleted and disrupted adipocytes.

CONCLUSION

Synchronized RF with HIFEM procedure resulted in a significant and sustained fat reduction with no adverse events.
Long-Term Utility of Follicular Unit Excision in Lichen Planopilaris—Correlation of Graft Survival With Histopathological and Ultrasound Biomicroscopic Parameters
Authors: Daruwalla Sanober Burzin , Dhurat Rachita , Ghate Smita , Bhatt Kalpana
Published: June 2021

BACKGROUND

Hair transplantation in scarring alopecia is challenging and transplant surgeons are hesitant due to fear of poor graft survival apart from the risk of reactivating the disease.

OBJECTIVE

Survival rate of hair follicles transplanted in cases of lichen planopilaris (LPP). To correlate histopathological and ultrasonography findings and their impact on graft survival.

METHODS

In 32 patients of inactive LPP included, a 5-cm2 recipient area was tattooed. The follicular unit density of the transplanted area was 20 to 25 FU/cm2. Postoperative follow-up was conducted at 6, 12, and 24 months. The recipient area density and ultrasound biomicroscopic parameters were assessed at each follow-up visit.

RESULTS

The survival of grafts was 78.62% at 12 months, and 79.96% at 24 months. Histopathology variables studied at the time of transplantation such as epidermal atrophy, fibrosis, and inflammatory infiltrate were not found to have any effect on the graft survival. Ultrasonography parameters of the involved scalp skin were found to be markedly improved on follow-up. This suggests that the overall health of the scalp improved after hair transplantation.

CONCLUSION

Follicular unit excision is a ray of hope for cases of primary cicatricial alopecia such as LPP because the result is satisfying to both the patient as well as the doctor.
Patterns of Usage of Complementary and Alternative Medicine Among Adults Visiting Health Care Centers in Mysuru, India
Authors: Krupa N. C. , Thippeswamy H. M. , Chandrashekar B. R.
Published: June 2021

The study intended to assess extent of complementary and alternative medicine use among patients visiting health care facilities in Mysuru, India, and factors influencing its choice. Prevalence of complementary and alternative medicine use was 33% and was not influenced by sociodemographic factors and individual health perceptions and habits.
Ten-Year Follow-up of Lamellar Keratoplasty Treatment With Acellular Porcine Corneal Stroma: A Case Report
Authors: Xiao Yu-Ting , Zhao Xin-Yue , Liu Xin , Xie Hua-Tao , Zhang Ming-Chang
Published: June 2021

Purpose:

To report a 10-year follow-up case of the first lamellar keratoplasty treatment with acellular porcine corneal stroma (APCS).

Methods:

A 62-year-old woman was diagnosed with a fungal corneal ulcer and received lamellar keratoplasty treatment with APCS in 2010. The 10-year follow-up results were evaluated by slit lamp biomicroscopy, anterior segment optical coherence tomography, in vivo confocal microscopy, and corneal biomechanics analysis.

Results:

The APCS graft maintained good biocompatibility and physical properties in transparency, stromal regeneration, elasticity, and deformation resistance. However, some disadvantages were observed, including a protracted course to eventual clearing, a decreased thickness, corneal depositions, sparsely distributed neural fibers, and low stiffness.

Conclusions:

This case indicated that APCS remains stable over a 10-year follow-up period. APCS can serve as a functional stromal surrogate where donor human corneal tissue is unavailable.
Keratoconus: Diagnosis and Staging
Authors: Belin Michael W. , Jang Hyun Soo , Borgstrom Mark
Published: June 2021

The advent of refractive surgery and corneal cross-linking for ectatic disease has further highlighted the need to recognize early or subclinical ectatic disease. Historical systems depend on anterior corneal changes that occur late in the disease course and are commonly associated with visual loss. Tomographic imaging allows for the acquisition of posterior corneal surface data and corneal thickness distribution. This led to the development of modalities to diagnose early or subclinical keratoconus and to screen patients for refractive surgery.

This article reviews the modern methods for assessing changes in posterior corneal surface and pachymetric distribution, now accepted by the major cornea societies to be the hallmarks of ectatic disease. Screening tools utilized by the commonly used tomographic imaging devices are discussed, and the difference between screening for ectasia and diagnosing keratoconus is highlighted. The Belin ABCD staging and classification system and the ABCD Progression Display are reviewed as a new grading and monitoring system that can be used for earlier intervention and prevention of visual loss in keratoconus.
Effectiveness of a Tele-Ophthalmology Vision Center in Treating Corneal Disorders and Its Associated Economic Benefits
Authors: Komal Sangoi , Radhakrishnan Naveen , Vardhan S Ashok , Prajna N. Venkatesh
Published: June 2021

Purpose:

The aim of this study was to study the clinical and economic impact of a teleophthalmology-based vision center (VC) in the management of corneal diseases in rural south India.

Methods:

Data of patients with corneal disorders who visited the VC in the year 2019 were analyzed for the total number of outpatient visits, the proportion of corneal cases that were treated at the VC, those referred to the base hospital (BH), and the costs of treatment.

Results:

In 2019, 1131 (10%) of 10,850 patients who visited the VC were diagnosed with corneal disorders. Of these, 950 (84%) patients were treated at the VC itself and did not require to be referred. The remaining 181 (16%) were referred to the BH. Of these 1131 patients, 836 (74%) patients presented with a painful acute corneal disorder. The most common painful acute corneal disorders included corneal foreign body (376, 33%), epithelial abrasions (205, 18%), and infectious keratitis (124, 11%). A patient can save approximately a minimum of INR 1200 (USD 16) by attending the VC rather than the BH. In 2019, by treating 950 patients, the VC saved approximately INR 114,0000 (USD 15,200) for the community. A similar calculation extrapolated to a 10-year period (2009–2019) revealed that by providing care for these corneal disorders at the community level, the VC saved approximately INR 705,8400 (USD 94,112) for the community.

Conclusions:

VC reduces the barriers to care by increasing the accessibility and affordability of treatment for patients with corneal disorders, resulting in a significant cost saving to the community.