bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Balanced State of Application-oriented Public Research and Technology Organisations
Authors: Borsi Balázs 
Published: November 2020

AbstractAnalytical tools that systematically take into account the contexts and complexities of innovations can provide valuable insights. Public research and technology organizations (PROs) are at the intersection of contextual complexities involving business, government, and academia. Hence, studying and strategically managing them call for specific methods. In the article, the Triple Helix (TH) viewpoints of business, government, and academia are used to study activities and processes of PROs. Building on theories of academic capitalism, resource dependency, and related strategic management research, a TH-specific analytical framework is proposed to assist in establishing a common language and structural construct for PRO strategic management. Using the framework, a secondary analysis of nineteen case studies from eleven European countries and Japan points to the main elements of the balanced TH regime PROs. In the case of these specific, historically embedded organizations and during their ‘endless transition’, attention is called to the strategic need for fit between the external environments and internal capabilities and the TH-related factors facilitating strategic congruence.
Reconceptualizing Vulnerability and Safeguarding in the Humanitarian and Development Sector
Authors: Daoust Gabrielle , Dyvik Synne L 
Published: November 2020

Abstract
Since 2018, “safeguarding” has been hailed as the answer to abuse, exploitation, and harassment in the humanitarian and development sector. However, safeguarding as a concept relies on conceptions of vulnerability, which are rarely critically interrogated. Bringing feminist, postcolonial, and critical disability studies to bear on what is conventionally viewed as an apolitical policy response, we argue that the need for safeguarding should be located within wider racialized, gendered, ableist, and geographic structures of power within which the sector is embedded. We conclude with theoretical reflections and directions for change centering intersectional and repoliticized conceptualizations of vulnerability and thus safeguarding.
Myelination of Callosal Axons Is Hampered by Early and Late Forelimb Amputation in Rats
Authors: Vianna-Barbosa Rodrigo , Bahia Carlomagno P , Sanabio Alexandre , de Freitas Gabriella P A , Madeiro da Costa Rodrigo F , Garcez Patricia P , Miranda Kildare , Lent Roberto , Tovar-Moll Fernanda 
Published: November 2020

Abstract
Deafferentation is an important determinant of plastic changes in the CNS, which consists of a loss of inputs from the body periphery or from the CNS itself. Although cortical reorganization has been well documented, white matter plasticity was less explored. Our goal was to investigate microstructural interhemispheric connectivity changes in early and late amputated rats. For that purpose, we employed diffusion-weighted magnetic resonance imaging, as well as Western blotting, immunohistochemistry, and electron microscopy of sections of the white matter tracts to analyze the microstructural changes in the corticospinal tract and in the corpus callosum (CC) sector that contains somatosensory fibers integrating cortical areas representing the forelimbs and compare differences in rats undergoing forelimb amputation as neonates, with those amputated as adults. Results showed that early amputation induced decreased fractional anisotropy values and reduction of total myelin amount in the cerebral peduncle contralateral to the amputation. Both early and late forelimb amputations induced decreased myelination of callosal fibers. While early amputation affected myelination of thinner axons, late amputation disrupted axons of all calibers. Since the CC provides a modulation of inhibition and excitation between the hemispheres, we suggest that the demyelination observed among callosal fibers may misbalance this modulation.
Timing of Surgical Intervention for Dysphagia in Patients With Diffuse Idiopathic Skeletal Hyperostosis
Authors: Gendreau Julian L. , Sheaffer Kristin , Bennett Josiah , Abraham Mickey , Patel Nitesh V. , Herschman Yehuda , Ruh Nikki , Lindley James G. 
Published: November 2020

Study Design:
This was a systematic review and meta-analysis.

Objective:
The objective was (1) to measure rates of successful resolution of dysphagia in patients after undergoing surgical intervention for diffuse idiopathic skeletal hyperostosis (DISH); and (2) to determine if older age, longer duration of preoperative symptoms, or increased severity of disease was correlated with unsuccessful surgical intervention.

Summary of Background Data:
DISH, also known as Forestier disease, is an enthesopathy affecting up to 35% of the elderly population. Many patients develop osteophytes of the anterior cervical spine, which contribute to chronic symptoms of dysphagia causing debilitating weight loss and possibly resulting in the placement of a permanent gastrostomy feeding tube. For patients that fail conservative medical management, an increase in surgical interventions have been reported in the literature in the last 2 decades.

Materials and Methods:
A systematic search was performed on PubMed, Medline, Cochrane Library, and Embase. Studies measuring outcomes after surgical intervention for patients with dysphagia from DISH were selected for inclusion. Two independent reviewers screened and assessed all literature in accordance with Cochrane systematic reviewing standards.

Results:
In total, 22 studies reporting 119 patients were selected for inclusion. Successful relief of dysphagia was obtained in 89% of patients after surgical intervention. Failure to relieve dysphagia was associated with increased length of symptoms preoperatively (P<0.01) using logistic regression. Patients with more severe preoperative symptoms also seem to have an increased risk for treatment failure (risk ratio, 2.86; 95% confidence interval, 1.19–6.85; P=0.02). Treatment failure was not associated with patient age, use of intraoperative tracheostomy, implementation of additional fusion procedures, level of involved segments, or number of involved segments.

Conclusions:
Patients undergoing surgical intervention have a higher likelihood of failing surgery with increasing preoperative symptom length and increased preoperative symptom severity.

Level of Evidence:
Level III.
The association between indices of blood pressure waveforms (PTC1 and PTC2) and incident heart failure
Authors: Brumback Lyndia C. , Andrews Leah I.B. , Jacobs David R. , Duprez Daniel A. , Shah Sanjiv J. , Dougherty Cynthia M. , Denenberg Julie O. , Allison Matthew A. 
Published: November 2020

Objectives:
The radial artery pulse waveform is a continuous measure of pressure throughout the cardiac cycle, and thus can provide more information than just systolic and diastolic blood pressures. New indices based on a Windkessel model of the waveform, PTC1 and PTC2, are related to arterial compliance and add information for prediction of incident cardiovascular disease (coronary heart disease, stroke, myocardial infarction) but their association with heart failure is unknown.

Methods:
Among 6229 adults (mean age 62 years) from four race/ethnic groups who were initially free of clinical cardiovascular disease and heart failure in 2000–2002, we evaluated the associations of baseline PTC1 and PTC2 with incident heart failure.

Results:
Mean ± standard deviation PTC1 and PTC2 were 394 ± 334 and 94 ± 46 ms, respectively. During a median of 15.7 years follow-up, there were 357 heart failure events (148 with reduced, 150 with preserved, and 59 with unknown ejection fraction). After adjustment for traditional risk factors, the hazard ratio for heart failure per 1 standard deviation higher PTC2 was 0.73 (95% confidence interval: 0.63--0.85). Higher PTC2 was also significantly associated with lower risk of heart failure with reduced ejection fraction (hazard ratio = 0.67; 95% confidence interval: 0.56--0.80). There was no evidence of a significant association between PTC2 and heart failure with preserved ejection fraction or between PTC1 and heart failure.

Conclusion:
The PTC2 measure of the radial artery pulse waveform may represent a novel phenotype related to heart failure, especially heart failure with reduced ejection fraction.
Upper Lumbar Bone Stress Injuries in Elite Cricketers
Authors: Saw Richard , Saw Anna , Kountouris Alex , Orchard John 
Published: November 2020

Objective:
Describe the proportion of upper lumbar bone stress injuries (LBSI; T12-L3) relative to all LBSI, and the clinical presentation and diagnosis of upper LBSI in elite cricketers.

Design:
Case series.

Setting:
Professional domestic and international cricket teams over a 9-year period.

Participants:
Elite Australian cricketers.

Independent Variables:
Symptomatic upper LBSI diagnosed based on clinical findings and medical imaging.

Main Outcome Measures:
Prevalence, injury history, and clinical management.

Results:
Twenty-four pace bowlers (22 male and 2 female) sustained 39 cases of upper LBSI (T12:2, L1:3, L2:20, L3:14). Upper lumbar vertebrae were involved in 41% (95% CI 31-51) of all LBSI in this cohort. Twenty-seven (69%, 54-81) cases had an injury that occurred only on the side contralateral to the bowling arm. Ipsilateral injuries tended to occur secondary to a contralateral nonunited defect. In all 7 cases with known radiology follow-up that had a contralateral then ipsilateral LBSI, the contralateral injury did not achieve bony union before the onset of the ipsilateral LBSI. For stress fractures with imaging follow-up, those who achieved bony union took longer to return to bowling training [median 152 days (IQR 117-188)], compared to those who achieved partial or no union [median 68 days (IQR 46-115)].

Conclusions:
Upper LBSI in elite cricketers occurs in approximately 2 out of 5 cases of LBSI. Clinicians should allow sufficient time for upper LBSI to resolve and unite (if a fracture) because cases that returned to bowling training earlier were less likely to achieve bony union, and those that failed to unite commonly went on to have a recurrent LBSI.

Level of Evidence:
Therapy/prognosis/diagnosis level 2b.
Automatic reconstruction of metabolic pathways from identified biosynthetic gene clusters
Authors: Sulheim Snorre , Fossheim Fredrik A. , Wentzel Alexander , Almaas Eivind 
Published: November 2020

AbstractBackgroundA wide range of bioactive compounds are produced by enzymes and enzymatic complexes encoded in biosynthetic gene clusters (BGCs). These BGCs can be identified and functionally annotated based on their DNA sequence. Candidates for further research and development may be prioritized based on properties such as their functional annotation, (dis)similarity to known BGCs, and bioactivity assays. Production of the target compound in the native strain is often not achievable, rendering heterologous expression in an optimized host strain as a promising alternative. Genome-scale metabolic models are frequently used to guide strain development, but large-scale incorporation and testing of heterologous production of complex natural products in this framework is hampered by the amount of manual work required to translate annotated BGCs to metabolic pathways. To this end, we have developed a pipeline for an automated reconstruction of BGC associated metabolic pathways responsible for the synthesis of non-ribosomal peptides and polyketides, two of the dominant classes of bioactive compounds.ResultsThe developed pipeline correctly predicts 72.8% of the metabolic reactions in a detailed evaluation of 8 different BGCs comprising 228 functional domains. By introducing the reconstructed pathways into a genome-scale metabolic model we demonstrate that this level of accuracy is sufficient to make reliablein silicopredictions with respect to production rate and gene knockout targets. Furthermore, we apply the pipeline to a large BGC database and reconstruct 943 metabolic pathways. We identify 17 enzymatic reactions using high-throughput assessment of potential knockout targets for increasing the production of any of the associated compounds. However, the targets only provide a relative increase of up to 6% compared to wild-type production rates.ConclusionsWith this pipeline we pave the way for an extended use of genome-scale metabolic models in strain design of heterologous expression hosts. In this context, we identified generic knockout targets for the increased production of heterologous compounds. However, as the predicted increase is minor for any of the single-reaction knockout targets, these results indicate that more sophisticated strain-engineering strategies are necessary for the development of efficient BGC expression hosts.
Specific norovirus interaction with Lewis x and Lewis a on human intestinal inflammatory mucosa during refractory inflammatory bowel disease
Authors: Tarris Georges , de Rougemont Alexis , Estienney Marie , Charkaoui Maeva , Mouillot Thomas , Bonnotte Bernard , Michiels Christophe , Martin Laurent , Belliot Gael 
Published: November 2020

ABSTRACTInflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is related to immunological and microbial factors with the possible implication of enteric viruses. We characterize the interaction between human noroviruses (HuNoVs) and blood group antigens in refractory CD and UC using HuNoV Virus Like Particles (VLPs) and histological tissues. Immunohistochemistry was conducted on inflammatory tissue samples from the small intestine, colon and rectum in 15 CD and 9 UC patients. Analysis of the regenerative mucosa of the colon and rectum revealed strong expression of sialylated Lewis a (sLea) and Lewis x (sLex) antigens, and HuNoV VLP binding in the absence of ABO antigen expression in both UC and CD. Competition experiments using sialidase, lectins and monoclonal antibodies demonstrated that HuNoV attachment mostly involved Leaand to a lesser extent, Lexmoieties on regenerative mucosa in both UC and CD. Further studies will be required to understand the implications of specific HuNoV binding to regenerative mucosa in refractory IBD.IMPORTANCEInflammatory Bowel Disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are progressive diseases affecting millions of people each year. Flare-ups during IBD result in severe mucosal alterations of the small intestine (CD), colon and rectum (CD and UC). Immunohistochemical analysis of CD and UC samples showed strong expression of known tumoral markers, Sialyl-Lewis a (CA19.9) and Sialyl-Lewis x (CD15s) antigens on colonic and rectal regenerative mucosa, concurrent with strong human norovirus (HuNov) VLP GII.4 affinity. Sialidase treatment and competition experiments using HBGA-specific monoclonal antibodies and lectins clearly demonstrated the implication of the Lewis a moiety, and to a lesser extent Lewis x, in HuNov recognition in regenerative mucosa of CD and UC tissues. Further studies are required to explore the possible implications of enteric viruses in the impairment of epithelial repair and dysregulation of inflammatory pathways during severe IBD.
Explainable Machine Learning models for Rapid Risk Stratification in the Emergency Department: A multi-center study
Authors: van Doorn William P.T.M. , Helmich Floris , van Dam Paul M.E.L. , Jacobs Leo H.J. , Stassen Patricia M. , Bekers Otto , Meex Steven J.R. 
Published: November 2020

AbstractBackgroundRisk stratification of patients presenting to the emergency department (ED) is important for appropriate triage. Diagnostic laboratory tests are an essential part of the work-up and risk stratification of these patients. Using machine learning, the prognostic power and clinical value of these tests can be amplified greatly. In this study, we applied machine learning to develop an accurate and explainable clinical decision support tool model that predicts the likelihood of 31-day mortality in ED patients (the RISKINDEX). This tool was developed and evaluated in four Dutch hospitals.MethodsMachine learning models included patient characteristics and available laboratory data collected within the first two hours after ED presentation, and were trained using five years of data from consecutive ED patients from the Maastricht University Medical Centre+ (Maastricht), Meander Medical Center (Amersfoort), and Zuyderland (Sittard and Heerlen). A sixth year of data was used to evaluate the models using area-under-the-receiver-operating-characteristic curve (AUROC) and calibration curves. The SHapley Additive exPlanations (SHAP) algorithm was used to obtain explainable machine learning models.ResultsThe present study included 266,327 patients with 7.1 million laboratory results available. Models show high diagnostic performance with AUROCs of 0.94,0.98,0.88, and 0.90 for Maastricht, Amersfoort, Sittard and Heerlen, respectively. The SHAP algorithm was utilized to visualize patient characteristics and laboratory data patterns that underlie individual RISKINDEX predictions.ConclusionsOur clinical decision support tool has excellent diagnostic performance in predicting 31-day mortality in ED patients. Follow-up studies will assess whether implementation of these algorithm can improve clinically relevant endpoints.
Pupal cannibalism by worker honey bees contributes to the spread of Deformed wing virus
Authors: Posada-Florez Francisco , Lamas Zachary S. , Hawthorne David J. , Chen Yanping , Evans Jay D. , Ryabov Eugene V. 
Published: November 2020

AbstractTransmission routes impact pathogen virulence and genetics, therefore comprehensive knowledge of these routes and their contribution to pathogen circulation is essential for understanding host-pathogen interactions and designing control strategies. Deformed wing virus (DWV), a principal viral pathogen of honey bees associated with increased honey bee mortality and colony losses, became highly virulent with the spread of its vector, the ectoparasitic miteVarroa destructor. Reproduction ofVarroamites occurs in capped brood cells and mite-infested pupae from these cells usually have high levels of DWV. The removal of mite-infested pupae by worker bees,VarroaSensitive Hygiene (VSH), leads to cannibalization of pupae with high DWV loads, thereby offering an alternative route for virus transmission. We used genetically tagged DWV to investigate virus transmission to and between worker bees following pupal cannibalisation under experimental conditions. We demonstrated that cannibalization of DWV-infected pupae resulted in high levels of this virus in worker bees and that the acquired virus was then transmitted between bees via trophallaxis, allowing circulation ofVarroa-vectored DWV variants without the mites. Despite the known benefits of hygienic behaviour, it is possible that higher levels of VSH activity may result in increased transmission of DWV via cannibalism and trophallaxis.
Infertility and fecundity loss ofWolbachia-infectedAedes aegyptihatched from quiescent eggs is expected to alter invasion dynamics
Authors: Lau Meng-Jia , Ross Perran A. , Hoffmann Ary A. 
Published: November 2020

AbstractThe endosymbiotic bacteriumWolbachiashows viral blockage in its mosquito host, leading to its use in arboviral disease control. Releases withWolbachiastrainswMel andwAlbB infectingAedes aegyptihave taken place in several countries. Mosquito egg survival is a key factor influencing population persistence and this trait is also important when eggs are stored prior to releases. We therefore tested the viability of mosquitoes derived fromWolbachia wMel andwAlbB-infected as well as uninfected eggs after long-term storage under diurnal temperature cycles of 11-19°C and 22-30°C. Eggs stored at 11-19°C had higher hatch proportions than those stored at 22-30°C. AdultWolbachiadensity declined when they emerged from eggs stored for longer, which was associated with incomplete cytoplasmic incompatibility (CI) whenwMel-infected males were crossed with uninfected females.wAlbB-infected males continued to show complete CI. Females from stored eggs at both temperatures continued to show perfect maternal transmission ofWolbachia, but storage reduced the fecundity of bothwMel andwAlbB-infected females relative to uninfected mosquitoes. Furthermore, we found a very strong negative impact of thewAlbB infection on the fertility of females stored at 22-30°C, with almost 80% of females hatching after 11 weeks of storage being infertile. Our findings provide guidance for storingWolbachia-infectedAe. aegyptieggs to ensure high fitness adult mosquitoes for release. Importantly, they also highlight the likely impact of egg quiescence on the population dynamics ofWolbachia-infected populations in the field, and the potential forWolbachiato suppress mosquito populations through cumulative fitness costs across warm and dry periods, with expected effects on dengue transmission.
Extreme value theory as a general framework for understanding mutation frequency distribution in cancer genomes
Authors: Tokutomi Natsuki , Nakai Kenta , Sugano Sumio 
Published: November 2020

AbstractCurrently, there is no recognized population genetics framework describing the population dynamics of cancer cells that is applicable to real cancer genome data. By focusing on cancer as a Darwinian evolutionary system, we formulated and analyzed the observed mutation frequency among tumors (MFaT) as a proxy for the hypothesized sequence read frequency and beneficial fitness effect of a cancer driver mutation. Analogous to intestinal crypts, we assumed that sample donor patients are separate culture tanks where proliferating cells follow certain population dynamics described by extreme value theory (EVT). To validate this, we analyzed three large-scale cancer genome datasets, each harboring > 10 000 tumor samples and in total involving > 177 898 observed mutation sites. We clarified the necessary premises for the application of EVT in the strong selection and weak mutation (SSWM) regime in relation to cancer genome sequences at scale. We also confirmed that the stochastic distribution of MFaT is likely of the Fréchet type, which challenges the well-known Gumbel hypothesis of beneficial fitness effects. Based on statistical data analysis, we demonstrated the potential of EVT as a population genetics framework to understand and explain the stochastic behavior of driver-mutation frequency in cancer genomes as well as its applicability in real cancer genome sequence data.