bluuebunny/crossref_metadata_2025 huggingface dataset:
Custodianship of wildlife on private land to support conservation – an Australian model
Authors: Wilson George , Edwards Melanie , Byron Neil
Published: October 2020

A large proportion of the world’s extinctions have occurred in Australia, and threatened species lists continue to grow, notwithstanding government and philanthropic efforts. Most losses have been on private land, so relying on national parks and reserves is not enough to reverse trends and meet Australia’s responsibilities. This paper proposes a model that could increase abundance and distribution of Australia’s biodiversity, while providing financial incentives to private landholders to do so. It addresses the question, can landholder management of wildlife, and a form of private ownership, remedy shortfalls in government funding for biodiversity conservation and the resulting consequences of vast biodiversity losses? Landholders currently invest in propagating introduced livestock species, but they are prevented by current regulations from investing in a similar manner in threatened Australian native species. Market-based incentives could increase the distribution and abundance of species on private land and help protect the habitat of other biodiversity. The enabling changes would be contentious to some people but are consistent with the International Union for the Conservation of Nature’s Sustainable Use policy. Different versions of wildlife privatisation have been successfully applied internationally: there is urgency for Australia to draw on these experiences and develop its own model to encourage and support wildlife on private freehold land. The model proposed in this paper focuses on: identifying locally overabundant populations or captive-bred populations as sources of supply; finding landholders and philanthropists who would like to have custodianship of species; enabling entrepreneurs to respond to demand; and bringing the two together where there is scope for a market-based sharing economy. Encouraging wildlife custodianship on private freehold land would be mutually beneficial, as it would not only result in an increase in biodiversity, but the economic value of wildlife could provide an income to landholders as well as enhancing Australia’s conservation system.
Two classes of active transcription sites and their roles in developmental regulation
Authors: Robinson-Thiewes Sarah , McCloskey John , Kimble Judith
Published: October 2020

Significance

Transcription occurs at chromosomal sites known as active transcription sites (ATS). We report that ATS can exist in two classes when assessed at key regulatory genes in their natural context: these “iATS” and “cATS” possess incomplete and complete nascent transcripts, respectively. Frequencies of the two classes are patterned within the developing tissue in a gene-, developmental stage-, and sex-specific manner, revealing ATS class regulation. Moreover, cATS frequency, not iATS frequency, corresponds to mRNA abundance, indicating that regulation of ATS class impacts gene expression. The iATS signature—presence of a long first intron but lacking exons—suggests slowing or pausing of transcriptional progression midway through the gene. We suggest that ATS class regulation can pattern gene expression during development.
Central vestibular sensitivity affects motion sick susceptibility through the efficacy of the velocity storage mechanism
Authors: Chua Wei De Kenneth , Kek Tze Ling
Published: October 2020

Background

Slow-phase eye velocity–time constant (SPEV–TC) and perceived rotational duration (PRD) are measurable objective outcomes of the rotational chair step-velocity test. These two variables are dependent on the efficacy of the central velocity storage. If sensory conflict from the step-velocity of the rotational chair elicits motion sickness, the SPEV–TC and PRD in individuals with varying susceptibility to motion sickness should be affected.

Objective

To determine if central vestibular sensitivity (CVS) characteristics differ among individuals with a range of motion sickness susceptibility (MSS).

Methods

Participants were allocated to two groups based on MSS (low and high) as identified in the short version of the Motion Sick Susceptibility Questionnaire (MSSQ-S). We evaluated the specific relationship between MSS and the characteristics of CVS through the SPEV–TC and PRD from the step-velocity test.

Results

Results showed significant differences in the PRD between these two groups. 180°/s pre-rotatory PRD is most significantly different (p = .005) followed by 50°/s post-rotatory PRD (counter clock-wise [CCW], p = .007; clock-wise [CW], p = .021) and log of 180°/s post-rotatory PRD (p = .042). Multiple regression analysis indicated that CCW post-rotatory PRD at 50°/s was a strong predictor of MSS.

Conclusions

High MSS individuals were observed with elevated PRD in general, indirectly suggesting greater velocity storage efficiency, hence, greater CVS; CVS is therefore positively correlated with MSS. PRD could be a reliable clinical indicator of motion sick susceptibility and may help with the selection of personnel working in motion sick environments and with the verification of motion sickness therapeutic interventions.
Beamed and Unbeamed Emission of γ-Ray Blazars
Authors: Pei Zhiyuan , Fan Junhui , Yang Jianghe , Bastieri Denis
Published: October 2020

A two-component model of radio emission has been used to explain some radio observational properties of Active Galactic Nuclei (AGNs) and, in particular, of blazars. In this work, we extend the two-component idea to the γ-ray emission and assume that the total γ-ray output of blazars consists of relativistically beamed and unbeamed components. The basic idea leverages the correlation between the radio core-dominance parameter and the γ-ray beaming factor. To do so, we evaluate this correlation for a large sample of 584 blazars taken from the fourth source catalog of the Fermi Large Area Telescope (Fermi-LAT) and correlated their γ-ray core-dominance parameters with radio core-dominance parameters. The γ-ray beaming factor is then used to estimate the beamed and unbeamed components. Our analysis confirms that the γ-ray emission in blazars is mainly from the beamed component.
Classifying discharge scenarios to improve understanding and care
Authors: Hyslop Brent
Published: October 2020

Hospital discharge planning is valuable in improving care and avoiding discharge delays. This is highly relevant to older people. Although usual discharge planning is now well understood and applicable to most patients, a range of different discharge scenarios exist that involve different considerations. These less common scenarios appear less well understood and can be challenging for clinical staff. To improve understanding and care, this Commentary suggests a basic classification of six discharge planning scenarios. These are: usual discharge planning, premature discharge, rehabilitation selection, safety concerns, reluctant discharge and delayed discharge. Clinical and system responses to each scenario are briefly discussed. This classification could potentially be useful in clinical education and quality improvement.
Caloric restriction mimetics for the treatment of cardiovascular diseases
Authors: Sciarretta Sebastiano , Forte Maurizio , Castoldi Francesca , Frati Giacomo , Versaci Francesco , Sadoshima Junichi , Kroemer Guido , Maiuri Maria Chiara
Published: October 2020

Caloric restriction mimetics (CRMs) are emerging as potential therapeutic agents for the treatment of cardiovascular diseases. CRMs include natural and synthetic compounds able to inhibit protein acetyltransferases, to interfere with acetyl coenzyme A biosynthesis, or to activate (de)acetyltransferase proteins. These modifications mimic the effects of caloric restriction, which is associated with the activation of autophagy. Previous evidence demonstrated the ability of CRMs to ameliorate cardiac function and reduce cardiac hypertrophy and maladaptive remodelling in animal models of ageing, mechanical overload, chronic myocardial ischaemia, and in genetic and metabolic cardiomyopathies. In addition, CRMs were found to reduce acute ischaemia–reperfusion injury. In many cases, these beneficial effects of CRMs appeared to be mediated by autophagy activation. In the present review, we discuss the relevant literature about the role of different CRMs in animal models of cardiac diseases, emphasizing the molecular mechanisms underlying the beneficial effects of these compounds and their potential future clinical application.
Microbial selenium metabolism: a brief history, biogeochemistry and ecophysiology
Authors: Wells Michael , Stolz John F
Published: October 2020

Selenium is an essential trace element for organisms from all three domains of life. Microorganisms, in particular, mediate reductive transformations of selenium that govern the element's mobility and bioavailability in terrestrial and aquatic environments. Selenium metabolism is not just ubiquitous but an ancient feature of life likely extending back to the universal common ancestor of all cellular lineages. As with the sulfur biogeochemical cycle, reductive transformations of selenium serve two metabolic functions: assimilation into macromolecules and dissimilatory reduction during anaerobic respiration. This review begins with a historical overview of how research in both aspects of selenium metabolism has developed. We then provide an overview of the global selenium biogeochemical cycle, emphasizing the central role of microorganisms in the cycle. This serves as a basis for a robust discussion of current models for the evolution of the selenium biogeochemical cycle over geologic time, and how knowledge of the evolution and ecophysiology of selenium metabolism can enrich and refine these models. We conclude with a discussion of the ecophysiological function of selenium-respiring prokaryotes within the cycle, and the tantalizing possibility of oxidative selenium transformations during chemolithoautotrophic growth.
Exploring microbial determinants of apple replant disease (ARD): a microhabitat approach under split-root design
Authors: Balbín-Suárez Alicia , Lucas Maik , Vetterlein Doris , Sørensen Søren J , Winkelmann Traud , Smalla Kornelia , Jacquiod Samuel
Published: October 2020

Apple replant disease (ARD) occurs worldwide in apple orchards and nurseries and leads to a severe growth and productivity decline. Despite research on the topic, its causality remains unclear. In a split-root experiment, we grew ARD-susceptible ‘M26’ apple rootstocks in different substrate combinations (+ARD: ARD soil; -ARD: gamma-irradiated ARD soil; and Control: soil with no apple history). We investigated the microbial community composition by 16S rRNA gene amplicon sequencing (bacteria and archaea) along the soil–root continuum (bulk soil, rhizosphere and rhizoplane). Significant differences in microbial community composition and structure were found between +ARD and -ARD or +ARD and Control along the soil–root continuum, even for plants exposed simultaneously to two different substrates (-ARD/+ARD and Control/+ARD). The substrates in the respective split-root compartment defined the assembly of root-associated microbial communities, being hardly influenced by the type of substrate in the respective neighbor compartment. Root-associated representatives from Actinobacteria were the most dynamic taxa in response to the treatments, suggesting a pivotal role in ARD. Altogether, we evidenced an altered state of the microbial community in the +ARD soil, displaying altered alpha- and beta-diversity, which in turn will also impact the normal development of apple rhizosphere and rhizoplane microbiota (dysbiosis), concurring with symptom appearance.
A Characteristic Map for the Symmetric Space of Symplectic Forms Over a Finite Field
Authors: He Jimmy
Published: October 2020

The characteristic map for the symmetric group is an isomorphism relating the representation theory of the symmetric group to symmetric functions. An analogous isomorphism is constructed for the symmetric space of symplectic forms over a finite field, with the spherical functions being sent to Macdonald polynomials with parameters $(q,q^2)$. An analogue of parabolic induction is interpreted as a certain multiplication of symmetric functions. Applications are given to Schur positivity of skew Macdonald polynomials with parameters $(q,q^2)$ as well as combinatorial formulas for spherical function values.
Accountability, secrecy, and innovation in AI-enabled clinical decision software
Authors: Rai Arti K , Sharma Isha , Silcox Christina
Published: October 2020

This article employs analytical and empirical tools to dissect the complex relationship between secrecy, accountability, and innovation incentives in clinical decision software enabled by machine learning (ML-CD). Although secrecy can provide incentives for innovation, it can also diminish the ability of third parties to adjudicate risk and benefit responsibly. Our first aim is descriptive. We address how the interrelated regimes of intellectual property law, Food and Drug Administration (FDA) regulation, and tort liability are currently shaping information flow and innovation incentives. We find that developers regard secrecy over training data and details of the trained model as central to competitive advantage. Meanwhile, neither FDA nor adopters are currently asking for these types of details. In addition, in some cases, it is not clear whether developers are being asked to provide rigorous evidence of performance. FDA, Congress, developers, and adopters could all do more to promote information flow, particularly as ML-CD models move into areas of higher risk. We provide specific suggestions for how FDA regulation, patent law, and tort liability could be tweaked to improve information flow without sacrificing innovation incentives.
Screening for Viruses and Lemur-Associated Filara in Wild-Caught Mosquitoes From Madagascar
Authors: Klein Annette , Strube Christina , Becker Stefanie C , Naccache Fanny
Published: October 2020

Madagascar is a hotspot of biodiversity, but poverty and population growth provoke a high risk of conflict between food security and biodiversity conservation in this tropical country. Numerous vector-borne diseases, including viral infections, affect public health in Madagascar and a continuous expansion of anthropogenically used areas intensifies contact on the human–wildlife interface. However, data on human and animal pathogens in potential insect vectors is limited. Therefore, we conducted a parasitological and virological survey of 785 adult female mosquitoes between March and May 2016 at the Ankarafantsika National Park in northwestern Madagascar. Screening included Alpha-, Phlebo-, and Flaviviridae and the recently described filarial nematode species, Lemurfilaria lemuris. The predominant mosquito genus was Culex (91%), followed by Mansonia (4.1%), Anopheles (3.4%), and Aedes (0.9%). Viral screening revealed no arboviruses, but an insect-specific flavivirus in two Culex sitiens pools. No pools screened positive for the lemur-specific filarial nematode L. lemuris.
Permethrin Resistance Status and Associated Mechanisms inAedes albopictus(Diptera: Culicidae) From Chiapas, Mexico
Authors: Janich Ashley J , Saavedra-Rodriguez Karla , Vera-Maloof Farah Z , Kading Rebekah C , Rodríguez Américo D , Penilla-Navarro Patricia , López-Solis Alma D , Solis-Santoyo Francisco , Perera Rushika , Black William C
Published: October 2020

There are major public health concerns regarding the spread of mosquito-borne diseases such as dengue, Zika, and chikungunya, which are mainly controlled by using insecticides against the vectors, Aedes aegypti (Linnaeus) and Aedes albopictus (Skuse). Pyrethroids are the primary class of insecticides used for vector control, due to their rapid knockdown effect and low toxicity to vertebrates. Unfortunately, continued use of pyrethroids has led to widespread insecticide resistance in Ae. aegypti; however, we lack information for Ae. albopictus—a sympatric species in Chiapas since 2002. In this study, we evaluated the permethrin resistance status of Ae. albopictus collected from Mexico and Texas. We also selected for permethrin resistance in the laboratory and investigated the potential mechanisms conferring resistance in this species. Knockdown resistance mutations, specifically F1534C, in the voltage-gated sodium channel gene, and increased activity of detoxifying enzymes were evaluated. Low levels of permethrin resistance (<2.4-fold) were observed in our field populations of Ae. albopictus and the F1534C mutation was not detected in any of the sites. Low levels of resistance were also observed in the artificially selected strain. There was significantly higher cytochrome P450 activity in our permethrin-selected and nonselected strains from Mexico compared to the control strain. Our results suggest the Ae. albopictus sampled from 2016 are mostly susceptible to pyrethroids. These results contrast with the high levels of permethrin resistance (>58-fold) found in Ae. aegypti from the same sites in Mexico. This research indicates the importance of continued monitoring of Ae. albopictus populations to prevent resistance from developing in the future.
The international glycan repository GlyTouCan version 3.0
Authors: Fujita Akihiro , Aoki Nobuyuki P , Shinmachi Daisuke , Matsubara Masaaki , Tsuchiya Shinichiro , Shiota Masaaki , Ono Tamiko , Yamada Issaku , Aoki-Kinoshita Kiyoko F
Published: October 2020

Glycans serve important roles in signaling events and cell-cell communication, and they are recognized by lectins, viruses and bacteria, playing a variety of roles in many biological processes. However, there was no system to organize the plethora of glycan-related data in the literature. Thus GlyTouCan (https://glytoucan.org) was developed as the international glycan repository, allowing researchers to assign accession numbers to glycans. This also aided in the integration of glycan data across various databases. GlyTouCan assigns accession numbers to glycans which are defined as sets of monosaccharides, which may or may not be characterized with linkage information. GlyTouCan was developed to be able to recognize any level of ambiguity in glycans and uniquely assign accession numbers to each of them, regardless of the input text format. In this manuscript, we describe the latest update to GlyTouCan in version 3.0, its usage, and plans for future development.
Screening for functional transcriptional and splicing regulatory variants with GenIE
Authors: Cooper Sarah E , Schwartzentruber Jeremy , Bello Erica , Coomber Eve L , Bassett Andrew R
Published: October 2020

Genome-wide association studies (GWAS) have identified numerous genetic loci underlying human diseases, but a fundamental challenge remains to accurately identify the underlying causal genes and variants. Here, we describe an arrayed CRISPR screening method, Genome engineering-based Interrogation of Enhancers (GenIE), which assesses the effects of defined alleles on transcription or splicing when introduced in their endogenous genomic locations. We use this sensitive assay to validate the activity of transcriptional enhancers and splice regulatory elements in human induced pluripotent stem cells (hiPSCs), and develop a software package (rgenie) to analyse the data. We screen the 99% credible set of Alzheimer's disease (AD) GWAS variants identified at the clusterin (CLU) locus to identify a subset of likely causal variants, and employ GenIE to understand the impact of specific mutations on splicing efficiency. We thus establish GenIE as an efficient tool to rapidly screen for the role of transcribed variants on gene expression.
KEGG: integrating viruses and cellular organisms
Authors: Kanehisa Minoru , Furumichi Miho , Sato Yoko , Ishiguro-Watanabe Mari , Tanabe Mao
Published: October 2020

KEGG (https://www.kegg.jp/) is a manually curated resource integrating eighteen databases categorized into systems, genomic, chemical and health information. It also provides KEGG mapping tools, which enable understanding of cellular and organism-level functions from genome sequences and other molecular datasets. KEGG mapping is a predictive method of reconstructing molecular network systems from molecular building blocks based on the concept of functional orthologs. Since the introduction of the KEGG NETWORK database, various diseases have been associated with network variants, which are perturbed molecular networks caused by human gene variants, viruses, other pathogens and environmental factors. The network variation maps are created as aligned sets of related networks showing, for example, how different viruses inhibit or activate specific cellular signaling pathways. The KEGG pathway maps are now integrated with network variation maps in the NETWORK database, as well as with conserved functional units of KEGG modules and reaction modules in the MODULE database. The KO database for functional orthologs continues to be improved and virus KOs are being expanded for better understanding of virus-cell interactions and for enabling prediction of viral perturbations.
FLAIRectomy in Supramarginal Resection of Glioblastoma Correlates With Clinical Outcome and Survival Analysis: A Prospective, Single Institution, Case Series
Authors: Certo Francesco , Altieri Roberto , Maione Massimiliano , Schonauer Claudio , Sortino Giuseppe , Fiumanò Giuseppa , Tirrò Elena , Massimino Michele , Broggi Giuseppe , Vigneri Paolo , Magro Gaetano , Visocchi Massimiliano , Barbagallo Giuseppe M V
Published: October 2020

Background

Extent of tumor resection (EOTR) in glioblastoma surgery plays an important role in improving survival.

Objective

To analyze the efficacy, safety and reliability of fluid-attenuated inversion-recovery (FLAIR) magnetic resonance (MR) images used to guide glioblastoma resection (FLAIRectomy) and to volumetrically measure postoperative EOTR, which was correlated with clinical outcome and survival.

Methods

A total of 68 glioblastoma patients (29 males, mean age 65.8) were prospectively enrolled. Hyperintense areas on FLAIR images, surrounding gadolinium-enhancing tissue on T1-weighted MR images, were screened for signal changes suggesting tumor infiltration and evaluated for supramaximal resection. The surgical protocol included 5-aminolevulinic acid (5-ALA) fluorescence, neuromonitoring, and intraoperative imaging tools. 5-ALA fluorescence intensity was analyzed and matched with the different sites on navigated MR, both on postcontrast T1-weighted and FLAIR images. Volumetric evaluation of EOTR on T1-weighted and FLAIR sequences was compared.

Results

FLAIR MR volumetric evaluation documented larger tumor volume than that assessed on contrast-enhancing T1 MR (72.6 vs 54.9 cc); residual tumor was seen in 43 patients; postcontrast T1 MR volumetric analysis showed complete resection in 64 cases. O6-methylguanine-DNA methyltransferase promoter was methylated in 8/68 (11.7%) cases; wild type Isocytrate Dehydrogenase-1 (IDH-1) was found in 66/68 patients. Progression free survival and overall survival (PFS and OS) were 17.43 and 25.11 mo, respectively. Multiple regression analysis showed a significant correlation between EOTR based on FLAIR, PFS (R2 = 0.46), and OS (R2 = 0.68).

Conclusion

EOTR based on FLAIR and 5-ALA fluorescence is feasible. Safety of resection relies on the use of neuromonitoring and intraoperative multimodal imaging tools. FLAIR-based EOTR appears to be a stronger survival predictor compared to gadolinium-enhancing, T1-based resection.
Anterior Lumbar Interbody Fusion With Cage Retrieval for the Treatment of Pseudarthrosis After Transforaminal Lumbar Interbody Fusion: A Single-Institution Case Series
Authors: Safaee Michael M , Tenorio Alexander , Haddad Alexander F , Wu Bian , Hu Serena S , Tay Bobby , Burch Shane , Berven Sigurd H , Deviren Vedat , Dhall Sanjay S , Chou Dean , Mummaneni Praveen V , Eichler Charles M , Ames Christopher P , Clark Aaron J
Published: October 2020

BACKGROUND

The treatment of pseudarthrosis after transforaminal lumbar interbody fusion (TLIF) can be challenging, particularly when anterior column reconstruction is required. There are limited data on TLIF cage removal through an anterior approach.

OBJECTIVE

To assess the safety and efficacy of anterior lumbar interbody fusion (ALIF) as a treatment for pseudarthrosis after TLIF.

METHODS

ALIFs performed at a single academic medical center were reviewed to identify cases performed for the treatment of pseudarthrosis after TLIF. Patient demographics, surgical characteristics, perioperative complications, and 1-yr radiographic data were collected.

RESULTS

A total of 84 patients were identified with mean age of 59 yr and 37 women (44.0%). A total of 16 patients (19.0%) underwent removal of 2 interbody cages for a total of 99 implants removed with distribution as follows: 1 L2/3 (0.9%), 6 L3/4 (5.7%), 37 L4/5 (41.5%), and 55 L5/S1 (51.9%). There were 2 intraoperative venous injuries (2.4%) and postoperative complications were as follows: 7 ileus (8.3%), 5 wound-related (6.0%), 1 rectus hematoma (1.1%), and 12 medical complications (14.3%), including 6 pulmonary (7.1%), 3 cardiac (3.6%), and 6 urinary tract infections (7.1%). Among 58 patients with at least 1-yr follow-up, 56 (96.6%) had solid fusion. There were 5 cases of subsidence (6.0%), none of which required surgical revision. Two patients (2.4%) required additional surgery at the level of ALIF for pseudarthrosis.

CONCLUSION

ALIF is a safe and effective technique for the treatment of TLIF cage pseudarthrosis with a favorable risk profile.
The Problem of Compliance and the Turn to Quantification
Authors: Merry Sally Engle
Published: October 2020

Compliance with law is an inevitable problem, but it is particularly challenging for international legal regulation. An increasingly popular way of tackling this problem is to develop quantitative measures of performance that provide an apparently objective measure of compliance. However, a closer look at how quantitative measures such as indicators work show that they are often oversimplified, inaccurate, and politically influenced. This chapter discusses indicators for corporate social responsibility, human rights, trafficking, and the UN system of Sustainable Development Goals, showing that they are all efforts to produce objective data, but that the results are far from certainty. The difficulty of defining these broad social concepts clearly, the complexity of measuring them in a wide variety of national and local contexts, and widespread limitations on funding for data collection undermine their capacity to provide a full and accurate picture. Statistical knowledge provides one way of promoting global governance through law, but it is hindered by the difficulty of converting such complex social phenomena into numbers. Nor can it entirely escape the influence of politics or the shortage of funds to support adequate data collection.
Critique of Punitive Reason
Authors: Fassin Didier
Published: October 2020

As the world is going through a punitive age, characterized by an increase in the prison population, independently of the evolution of crime, four questions are addressed in this chapter: What is punishment? Why is punishment associated with the infliction of suffering? Which arguments are provided to justify punishment? How is punishment distributed in society? These questions have long been posed by moral philosophers and legal scholars. Here, rather than reiterating their normative stances, a critical approach is proposed based on ethnographic work and genealogical analysis.
Legal Pluralism in Postcolonial, Postnational, and Postdemocratic Times
Authors: Darian-Smith Eve
Published: October 2020

Since the nineteenth century anthropologists have been fascinated by law and legal practices in far-off cultures and lands. Legal anthropology, as a subfield of the discipline, has contributed enormously to contemporary sociolegal analyses of legal pluralism across the academy. Be that as it may, this chapter suggests that anthropology’s contribution is ultimately limited by the enduring analytical framing of legal pluralism within colonial/postcolonial contexts. Moreover, this analytical constraint prevents scholars from seeing other forms of legal pluralism of immense importance in analysing contemporary societies in which genealogies of colonialism and modernist units of analysis and assumptions of state power are not so evident or significant. The essay calls for anthropologists to think about legal pluralism in terms, and along lines of inquiry, that move beyond the discipline’s colonial legacies and conventional sites of research and to appreciate the global contexts in which all legal pluralism should be analysed.
DETERMINATION OF EFFECTIVE DOSE FIFTY (ED50) OF SCORPION ANTIVENOM AGAINST SCORPION ENVENOMATION USING THE NEWLY DEVELOPED FORMULA
Authors: Saganuwan Saganuwan Alhaji
Published: October 2020

About 50 species of scorpions caused fatal scorpionism across the globe, mostly from members of buthidae family, which include but not limited to Mesobuthus eupeus, Androctonus crassicauda, Leiurus abdullahbayrami, Leiurus quinquestriatus, Tityus pachyurus and Androctonus australis. In view of this, literature search was carried out with a view to modifying the formula (LD50‐ = for calculation of LD50 and ED50 of scorpion venom and antivenom, respectively. Whereas Human Equivalent Dose (HED) formula was used to extrapolate LD50 and ED50 from animals to human. The findings showed that the newly developed formula (LD50 = ED501/3 × Wm × 10−4) and HED formula can provide effective doses of scorpion antivenoms. However, the new formula provided ED50 values that are very much close to therapeutic values, confirming the applicability of the formula in treatment of scorpionism.

Support or Funding Information: None

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Alternative ELISA Using a RNA Aptamer against Calf Intestinal Alkaline Phosphatase
Authors: Huynh Vincent , Wei Eric , Ellington Andrew , Stovall Gwendolyn
Published: October 2020

Alkaline Phosphatase (AP) is extensively used in enzyme‐linked immunosorbent assays(ELISA), most requiring expensive and time‐intensive reagents to generate (such as AP‐conjugated antibodies). In addition, these antibodies may have reduced immunoreactivity when conjugated with AP. We seek to address these problems by developing an alternative AP ligand in the form of an aptamer (nucleic acid binding species) against Calf Intestinal AP (CIAP). This CIAP‐aptamer will lead to the development of an alternative reagent that is readily amendable to conjugation, such as conjugation to a primary antibody or perhaps another aptamer.

Anti‐CIAP aptamers were isolated using Systematic Evolution of Ligands by Exponential Enrichment (SELEX). A diversified pool of RNA (“R50” pool) was used and iterative rounds of selection were performed to wash away the non‐binding RNA species and enrich RNA species specifically bound to CIAP. After nine rounds of selection, a reoccurring 14‐mer RNA motif (named VDH2.14 and identified in 15 of 40 clones sequenced) presented itself in a similar loop structure for the majority of RNA sequences. Furthermore, aptamers 4‐3, 4‐9, and 3‐6 were bound to CIAP with Kd values of 5 nM, 9.4 nM, 10.8 nM, respectively. In addition, a minimized variant was designed and bound to CIAP with a Kd value of 6.8 nM. The development of anti‐CIAP aptamers will allow us to generate an inexpensive and robust CIAP‐conjugated reagent for ELISA work and additional molecular techniques that are AP‐dependent.
Risk Factors Associated With Failure to Reach Minimal Clinically Important Difference After Correction Surgery in Patients With Degenerative Lumbar Scoliosis
Authors: Yuan Lei , Zeng Yan , Chen Zhongqiang , Li Weishi , Zhang Xinling , Ni Jiajun
Published: October 2020

Study Design.

A retrospective study.

Objective.

The aim of this study was to evaluate the factors affecting health-related quality of life (HRQOL) after surgery in patients with degenerative lumbar scoliosis (DLS) by minimum clinically important difference (MCID).

Summary of Background Data.

MCID has been introduced in the adult spinal deformity to quantify the absolute minimum change that can be considered a success. There are limited data available to identify factors affecting reaching MCID after DLS surgery.

Methods.

This study reviewed a cohort of 123 DLS patients after correction surgery and with a minimum 2-year follow-up (FU). Inclusion criteria included age ≥40 and minimum five vertebrae fused and the availability of Scoliosis Research Society (SRS)-22 scores and radiographic data at baseline (BL) and FU. Using a multivariate analysis, two groups were compared to identify possible risk factors: those who reached MCID in the all four SRS domains (N = 65) at the last FU and those who missed MCID (N = 58).

Results.

At baseline, patients differed significantly from matched normative data in all SRS-22 domains. The baseline HRQOL was comparable in reached MCID and missed MCID group patients (P > 0.05). The HRQOL scores at FU were significantly higher than those at baseline. Of 123 included patients, 77.2% (N = 95), 72.4% (N = 89), 76.4% (N = 94), and 89.4% (N = 110) reached MCID in SRS pain, activity, appearance, and mental domain, respectively. Pelvic incidence (PI) >55°, lumbar lordosis (LL) loss >4.65°, coronal imbalance at FU, sagittal vertical axis (SVA) at FU >80 mm, and presence of proximal junctional kyphosis (PJK) and distal junctional problem (DJP) had negative effects on the recovery process.

Conclusion.

Factors affecting reaching MCID after surgery for DLS were higher PI, LL loss, coronal imbalance, severe sagittal imbalance, and the occurrence of PJK and DJP.

Level of Evidence: 4
The Prevalence of Back and Leg Pain and the Cross-sectional Association With Adverse Health Outcomes in Community Dwelling Older Adults in England
Authors: Williamson Esther , Sanchez Santos Maria T. , Morris Alana , Garrett Angela , Conway Oliver , Boniface Graham , Fairbank Jeremy , Lamb Sarah E.
Published: October 2020

Study Design.

Cross-sectional analysis of the Oxford Pain, Activity and Lifestyle (OPAL) Cohort Study.

Objective.

The aim of this study was to assess the prevalence of back pain (BP) and leg pain and determine their relationship with adverse health states among older adults in England.

Summary of Background Data.

Epidemiological data describing the prevalence of BP and leg pain in older adults in England is lacking.

Methods.

A total of 5304 community-dwelling adults (aged 65–100 years) enrolled in the OPAL cohort study who provided data on BP and leg pain were included. Participants were classified into four groups based on reports of back and leg pain: no BP, BP only, BP and leg pain which was likely to be neurogenic claudication (NC), and BP and leg pain which was not NC. Adverse health states were frailty, falls, mobility decline, low walking confidence, poor sleep quality, and urinary incontinence. We collected demographic and socioeconomic information, health-related quality of life, and existing health conditions, and estimated the association between BP presentations and adverse health states using regression analysis.

Results.

Thirty-four percent of participants (1786/5304) reported BP only, 11.2% (n = 594/5304) reported BP and NC and 8.3% (n = 441/5304) reported BP and non-NC leg pain. Participants with BP had worse quality of life compared to those without BP. All BP presentations were significantly associated with adverse health states. Those with NC were most affected. In particular, there was greater relative risk (RR) of low walking confidence (RR 3.11, 95% confidence interval [CI] 2.56–3.78), frailty (RR 1.88, 95% CI 1.67–2.11), and mobility decline (RR 1.74, 95% CI 1.54–1.97) compared to no BP.

Conclusion.

Back and leg pain is a common problem for older adults and associated with reduced quality of life and adverse health states. Findings suggest a need to develop more effective treatment for older adults with BP especially for those with neurogenic claudication.

Level of Evidence: 2
Improvement in Gait Pattern and its Relationship With Preoperative Pelvic Compensation After Surgery in Patients With Sagittal Plane Deformity
Authors: Kim Ho-Joong , Park Sang-Min , Kwon Oh Sang , Han Heesoo , Kang Kyoung-Tak , Yeom Jin S.
Published: October 2020

Study Design.

Prospective observational study.

Objective.

The aim of this study was to investigate the improvement in gait parameters after surgery and whether corrective surgery for sagittal imbalance would be influenced by preoperative pelvic compensation.

Summary of Background Data.

There have been no other studies investigating the influence of preoperative pelvic compensation on surgical outcomes.

Methods.

A total of 32 patients who were scheduled to undergo corrective surgery for sagittal plane deformity were included and were followed-up for 1 year after surgery. Radiological parameters were measured on biplanar full-body imaging. Before surgery and 6 months after surgery, three-dimensional motion analyses were performed to estimate center of gravity (CoG) deviation from the center of mass (CoM), mean trunk kyphosis (TK) angle, gait deviation index (GDI), and kinematic parameters. Before surgery, the patients were classified into CoG+ and CoG− groups. “+” and “−” representing increases and decreases in the distance of CoG from CoM of the pelvic segment from first to third trials, respectively. Oswestry Disability Index (ODI) and EuroQol-5D (EQ-5D) were measured for 1 year after surgery.

Results.

All radiological parameters improved significantly after surgery. For gait parameters, CoG from CoM, mean TK angle, and minimum angle of the hip and knee joints in the stance phase during walking were significantly decreased after surgery and GDI scores significantly improved after surgery. The mean changes of the CoG distance from the CoG and the mean TK from first to third trials of gait analysis significantly decreased postoperatively. There were no significant differences in ODI and EQ-5D scores over 1-year follow-up assessment between CoG+ and CoG− groups.

Conclusion.

Preoperative abnormal stooping gait, and progressive worsening of sagittal imbalance in patients with sagittal plane deformity improved after corrective surgery. Patients with preoperative dynamic sagittal imbalance could have similar surgical results to those without it after corrective surgery.

Level of Evidence: 3
Denosumab Treatment for Giant Cell Tumor of the Spine Including the Sacrum
Authors: Bukata Susan V. , Blay Jean-Yves , Rutkowski Piotr , Skubitz Keith , Henshaw Robert , Seeger Leanne , Dai Tian , Jandial Danielle , Chawla Sant
Published: October 2020

Study Design.

This was a subanalysis of an international, multicenter, open-label study.

Objective.

The aim of this study was to assess the efficacy and safety of denosumab in a subset of patients with giant cell tumors of bone (GCTB) of the spine including the sacrum from an international, open-label, single-arm, phase 2 study (ClinicalTrials.gov: NCT00680992).

Summary of Background Data.

Standard GCTB treatment is surgical removal, either by curettage or resection, combined with intraoperative adjuvant therapy; however, some sites may not be amenable to resection (e.g., skull, spine).

Methods.

Adults or skeletally mature adolescents with pathologically confirmed GCTB of the spine including the sacrum, and radiologically measurable evidence of active disease, were included. Patients received denosumab (120 mg subcutaneously) once every 4 weeks during the treatment phase, with loading doses on days 8 and 15 of the first cycle. Patients had surgically unsalvageable GCTB (Cohort 1), had planned surgery expected to result in severe morbidity (Cohort 2), or were enrolled from a previous GCTB study (Cohort 3).

Results.

Overall, 132 patients were included in the safety analysis (103 in Cohort 1, 24 in Cohort 2, and five in Cohort 3); 131 patients were included in the efficacy analysis. Kaplan-Meier estimated probabilities of disease progression or recurrence were 3% (95% confidence interval [CI], 0.0–6.2) at year 1 and 7.4% (95% CI, 2.1–12.7) at years 3 and 5 in Cohort 1, and not estimable in Cohorts 2 and 3. Of 23 patients (Cohort 2) with surgery planned at baseline, 10 (43%) had on-study surgery; of these, one patient had reported disease progression or recurrence after the on-study surgery. Clinical benefit was reported in 83% of patients overall (all cohorts).

Conclusion.

Results from the analysis suggest that denosumab is potentially effective treatment for patients with GCTB of the spine including the sacrum. The adverse event profile was consistent with the full study population.

Level of Evidence: 2
A Nationwide Analysis of Geriatric Odontoid Fracture Incidence, Complications, Mortality, and Cost
Authors: Alluri Ram , Bouz Gabriel , Solaru Samantha , Kang Hyunwoo , Wang Jeffrey , Hah Raymond J.
Published: October 2020

Study Design.

Retrospective database analysis.

Objective.

To identify nationwide temporal trends in management of geriatric odontoid fractures and to compare comorbidities, inpatient complications, hospital characteristics, and cost between patients receiving operative versus nonoperative management.

Summary of Background Data.

The treatment of geriatric odontoid fractures remains controversial with some studies demonstrating decreased mortality and improved functional outcomes associated with operative management and significant morbidity associated with halo devices during nonoperative management.

Methods.

Patients between ages 65 to 90 years with odontoid fractures who underwent operative or nonoperative management between the years 2003 and 2017 were identified in the National Inpatient Sample (NIS) database. Year of injury, demographic variables, comorbidities, inpatient complications, mortality, length of stay, inpatient cost, and hospital characteristics were compared between operative and nonoperative treatment groups.

Results.

Thirty two thousand four hundred nineteen patients (average age 77 yr, 54% female) were included in the final analysis. Operative treatment occurred in 21,954 (67%) patients and nonoperative treatment occurred in 10,465 (32%). In 2003, operative treatment occurred in 46% of patients and nearly doubled to 86% in 2017, with an average increase of 3.7% per year (P < 0.001). Patients undergoing operative management had a lower prevalence of at least one major medical comorbidity (76% vs. 83%, P < 0.001). Patients undergoing operative treatment demonstrated higher odds of developing most complications, particularly pulmonary, gastrointestinal, and renal (P < 0.01). Inpatient mortality was 3.6% in patients receiving operative treatment and 5.9% in patients receiving nonoperative treatment (P < 0.001). Average cost per episode of care during the study period was $131,855 for operative treatment and $65,374 for nonoperative treatment (P < 0.001).

Conclusion.

This study demonstrates a clear national paradigm shift in the management of geriatric odontoid fractures, wherein operative management nearly doubled from 46% in 2003 to 86% in 2017.

Level of Evidence: 3
Impact of Preoperative Platelet Count on Bleeding Risk and Allogeneic Transfusion in Multilevel Spine Surgery
Authors: Chow Jonathan H. , Chancer Zackary , Mazzeffi Michael A. , McNeil John S. , Sokolow Michael J. , Gaines Tyler M. , Reif Michaella M. , Trinh Anthony T. , Wellington Ian J. , Camacho Jael E. , Bruckner Jacob J. , Tanaka Kenichi A. , Ludwig Steven
Published: October 2020

Study Design.

This was an observational cohort study of patients receiving multilevel thoracic and lumbar spine surgery.

Objective.

The aim of this study was to identify which patients are at high risk for allogeneic transfusion which may allow for better preoperative planning and employment of specific blood management strategies.

Summary of Background Data.

Multilevel posterior spine surgery is associated with a significant risk for major blood loss, and allogeneic blood transfusion is common in spine surgery.

Methods.

A univariate logistic regression model was used to identify variables that were significantly associated with intraoperative allogeneic transfusion. A multivariate forward stepwise logistic regression model was then used to measure the adjusted association of these variables with intraoperative transfusion.

Results.

Multilevel thoracic and lumbar spine surgery was performed in 921 patients. When stratifying patients by preoperative platelet count, patients with pre-operative thrombocytopenia and severe thrombocytopenia had a significantly higher rate of transfusion than those who were not thrombocytopenic. Furthermore, those with severe thrombocytopenia had a higher rate of red blood cells, fresh frozen plasma, and platelet transfusion than those with higher platelet counts. Multivariate logistic regression found that preoperative platelet count was the most significant contributor to transfusion, with a platelet count ≤100 having an adjusted odds ratio (OR) of transfusion of 4.88 (95% confidence interval [CI] 1.58–15.02, P = 0.006). Similarly, a platelet count between 101and 150 also doubled the risk of transfusion with an adjusted OR of 2.02 (95% CI 1.01–4.04, P = 0.047). The American Society of Anesthesiologists classification score increased the OR of transfusion by 2.5 times (OR = 2.52, 95% CI 1.54–4.13), whereas preoperative prothrombin time and age minimally increased the risk.

Conclusion.

Preoperative thrombocytopenia significantly contributes to intraoperative transfusion in multilevel thoracic lumbar spine surgery. Identifying factors that may increase the risk for transfusion could be of great benefit in better preoperative counseling of patients and in reducing overall cost and postoperative complications by implementing strategies and techniques to reduce blood loss and blood transfusions.

Level of Evidence: 2
SRY-related high-mobility-group box 6 suppresses cell proliferation and is downregulated in breast cancer
Authors: Zhang Lei , Niu Xiaochen , Zhang Xinxin , Zhan Guanqun , Xue Xuanji , Wang Xiaofei , Zhang Hui , Guo Zengjun
Published: October 2020

Breast cancer is one of the most common cancers endangering women’s health. SRY-related high-mobility-group box 6 (SOX6) is associated with many cancers, though its role has not been reported in breast cancer. Here, we aimed to explore the expression and function of SOX6 in breast cancer. On the basis of the analysis of SOX6 in The Cancer Genome Atlas, Cancer Cell Line Encyclopedia and Genotype-Tissue Expression databases, we revealed that SOX6 was downregulated in breast cancer, and we verified the results at the cellular level by means of western blotting and quantitative real-time PCR. When SOX6 was overexpressed, the proliferation of breast cancer cells was inhibited, and apoptosis was promoted. Moreover, the methylation level of the SOX6 promoter in breast cancer was significantly higher than that in normal tissues. 5′-Aza-2′-deoxycytidine reversed the high level of methylation that was caused by decreased expression of SOX6. This evidence suggests that SOX6 is a tumor suppressor gene associated with breast cancer. This study could provide a new target for breast cancer treatment.