bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Amortization of Funding Gene Therapies: Making the “Intangibles” Tangible for Patients
Authors: Dabbous Monique , Toumi Mondher , Simoens Steven , Wasem Juergen , Wang Yitong , Huerta Osuna José , François Clément , Annemans Lieven , von der Schulenburg Johann-Matthias Graf , Sola-Morales Oriol , Malone Daniel , Garrison Louis P. 
Published: April 2021

AbstractGene replacement therapies (GRTs) are increasingly expected to reach the market. Current healthcare systems are struggling to fund such valuable, costly therapies. GRTs are highly valuable as they extend life through sustained, long-term efficacy or by saving on the costs of a current high-cost standard of care. Some payers have implemented payment models, which do not address the budget impact on the year of acquisition or administration of costly GRTs. This study aims to (1) introduce amortization as an accounting tool within the context of healthcare, specifically for GRTs, (2) present a systematic literature review (SLR) on the amortization or depreciation of pharmaceuticals and medical devices, (3) assess the rationale and feasibility as well as the pros and cons of the amortization of GRTs, and (4) provide recommendations for future steps for the introduction of amortization for GRTs. The limited literature, identified in the SLR, has proposed amortization as a solution for costly, highly valuable GRT funding, but did not fully investigate and detail amortization and its feasibility. This paper further details and illustrates amortization as a promising method for these GRTs by facilitating market and patient access. Current accounting principles and guidelines must evolve to apply amortization to GRTs.
Skin imprints to provide noninvasive metabolic profiling of COVID-19 patients
Authors: Delafiori Jeany , Siciliano Rinaldo Focaccia , de Oliveira Arthur Noin , Nicolau José Carlos , Sales Geovana Manzan , Dalçóquio Talia Falcão , Busanello Estela Natacha Brandt , Eguti Adriana , de Oliveira Diogo Noin , Bertolin Adriadne Justi , dos Santos Luiz Augusto , Salsoso Rocío , Marcondes-Braga Fabiana G , Durán Nelson , Perroud Maurício Wesley , Sabino Ester Cerdeira , Reis Leonardo Oliveira , Fávaro Wagner José , Catharino Rodrigo Ramos 
Published: April 2021

ABSTRACTAs the current COVID-19 pandemic progresses, more symptoms and signals related to how the disease manifests in the human body arise in the literature. Skin lesions and coagulopathies may be confounding factors on routine care and patient management. We analyzed the metabolic and lipidic profile of the skin from COVID-19 patients using imprints in silica plates as a non-invasive alternative, in order to better understand the biochemical disturbances caused by SARS-CoV-2 in the skin. One hundred and one patients (64 COVID-19 positive patients and 37 control patients) were enrolled in this cross-sectional study from April 2020 to June 2020 during the first wave of COVID-19 in São Paulo, Brazil. Fourteen biomarkers were identified related to COVID-19 infection (7 increased and 7 decreased in COVID-19 patients). Remarkably, oleamide has shown promising performance, providing 79.0% of sensitivity on a receiver operating characteristic curve model. Species related to coagulation and immune system maintenance such as phosphatidylserines were decreased in COVID-19 patients; on the other hand, cytokine storm and immunomodulation may be affected by molecules increased in the COVID-19 group, particularly primary fatty acid amides and N-acylethanolamines, which are part of the endocannabinoid system. Our results show that skin imprints may be a useful, noninvasive strategy for COVID-19 screening, by electing a pool of biomarkers with diagnostic potential.
Whole exome sequencing improves mutation detection in Hailey–Hailey disease
Authors: Wang Zhe , Wang Zhenzhen , Sun Lele , Yu Xueping , Pang Zheng , Liu Hong , Zhang Furen 
Published: April 2021

AbstractHailey–Hailey disease (HHD) is an autosomal dominant monogenic disease that is defective in the ATP2C1 gene. In previous studies, Sanger sequencing was the main method applied to detect mutations in HHD patients, and no mutations in the ATP2C1 gene were found in 12–55% of those reported. The aim of our study was to carry out whole exome sequencing (WES) for the HHD patients in whom efforts to identify mutations by Sanger sequencing had failed, and to find a new pathogenic gene. WES was performed using genomic DNA from 13 HHD patients and 364 in‐house healthy controls. Potential pathogenic mutations were subsequently validated by Sanger sequencing. As a result, eight mutations in the ATP2C1 gene were identified using WES. In the remaining five patients, we found one mutation in the ATP2A2 gene which was the causal gene of Darier’s disease. Four patients had no detectable mutations in ATP2C1 and the other ATPase genes. Together with our previous study in 2019, the total mutation rate was calculated to be 47/52 (90.4%). These findings demonstrate that WES is capable of improving the mutation detection sensitivity in HHD compared with Sanger sequencing.
Effect of natural antimicrobial agent (MicroGARD) combined with edible coating (NatureSeal) treatment on fresh‐cut butternut squash
Authors: Yang En , Fan Lihua , Jiang Yueming , Doucette Craig , Fillmore Sherry , Han Qinqin 
Published: April 2021

AbstractTo improve fresh‐cut produce quality and shelf life, 0.5% or 1.0% MicroGARD® 730 (MG) as a natural alternative to synthetic chemical preservatives, 2.5% NatureSeal® (NS) product (vitamin/mineral‐based blends), 0.5% MG combined with 2.5% NS, and 1% MG combined with 2.5% NS were used to treat fresh‐cut butternut squash (Cucurbita moschata). The 240 g samples were put into food grade bags and stored at 4 or 7 °C. Microbial population, including aerobic plate counts (APCs), yeast and molds, total coliforms, and quality parameters, including head space O2/CO2 concentration in package, pH, soluble solids, color, and conductivity, were evaluated after 0, 3, 6, 9, 12, and 20 days of storage. Results showed that after 6 days of storage at 7 °C, APC of check and control samples reached to 2.6 × 108 and 1.5 × 107 CFU/g, respectively; while they were kept at 104 CFU/g (3 to 4 log reduction) in the squash samples treated with 0.5% or 1% MG combined with NS at 7 °C. Similar results were found on squash samples stored at 4 °C for 9 days. The cut squash treated with MG combined with NS had APC ≤ 107 CFU/g at 4 °C for about 20 days compared to 9 days in controls or 0.5% MG‐treated samples, and 12 days in 1% MG‐treated or NS‐treated samples, respectively. Considering overall quality and extended shelf life, MG combined with NS was recommended to apply to cut squashes stored at 4 °C.Practical ApplicationThis research provided useful information and practical treatment application for developing fresh‐cut produce with good quality and extended shelf life up to 20 days at 4 °C.
Severe simulated herbivory constrains Sclerocarya birrea saplings regardless of resource availability
Authors: Scogings Peter F. , De Fortier An 
Published: April 2021

AbstractAllocation of carbon to growth and defences in plants is affected by resource availability and herbivory, two determinants of woody plant abundance in savannas. Both factors are critical at the sapling stage of woody plants, yet their combined effects on sapling growth and defence have been poorly studied in savannas. Sclerocarya birrea is an iconic keystone species in southern African savannas, widely used by herbivores and humans. We hypothesised that low resource availability or high herbivory intensity would reduce growth and nutritional value for herbivores, but high resource availability or low herbivory intensity would increase growth and nutritional value. Support for our hypothesis would imply that any level of browsing intensity (relative to unbrowsed plants), regardless of resource availability, would potentially hold saplings in a browser trap because of reduced growth or improved nutritional value. We explored responses of S. birrea saplings to five levels of nutrient fertiliser and six levels of simulated browsing intensity. Low fertiliser application rates did not affect growth, but the highest fertiliser rate increased canopy growth. The most severe intensities of simulated browsing negatively affected growth and nutritional value. Our results suggested that either resource limitation throughout the growing season, or extremely intense browsing early in the growing season, is potentially able to retard long‐term growth of saplings and delay recruitment of adults. Although saplings that are severely browsed early in the growing season might not be re‐browsed later in the same season because of their reduced nutritional value, their weakened nitrogen status would be an additional limitation to regrowth. No significant interactions between resource availability and herbivory intensity were detected, which we suggest resulted from responses to resource availability and herbivory operating at different temporal scales. We recommend that future experiments of this type include carefully timed measurements to detect transient responses.
The effect of Lactiplantibacillus plantarum 299v together with a low dose of iron on iron status in healthy pregnant women: A randomized clinical trial
Authors: Axling Ulrika , Önning Gunilla , Martinsson Niskanen Titti , Larsson Niklas , Hansson Stefan R. , Hulthén Lena 
Published: April 2021

AbstractIntroductionIron deficiency during pregnancy is a global health problem and is associated with adverse pregnancy outcomes. The aim of this randomized, double‐blind, placebo‐controlled study was to evaluate the effect of Lactiplantibacillus plantarum 299v (Lp299v, 1010 colony forming units), 4.2 mg iron, 12 mg ascorbic acid and 30 µg folic acid (Lp) on iron status in healthy, non‐anemic, pregnant Swedish women.Material and methodsA total of 326 women were randomized to receive Lp (n = 161) or placebo (n = 165) twice daily from gestational week 10–12 until end of pregnancy or until the potential start of iron therapy. The primary endpoint was serum ferritin at week 28.ResultsIntake of Lp attenuated the decrease in serum ferritin from baseline to week 28 (p = 0.003) and week 35 (p ˂ 0.001) and resulted in reduced prevalence of iron deficiency (59% vs 78%, p = 0.017) and iron deficiency anemia (7.4% vs 21%, p = 0.023) at week 35. Intake of Lp also resulted in beneficial effects on the soluble transferrin receptor (p = 0.011) and total body iron (p ˂ 0.001) at week 35. Gestational length and birthweight were comparable between groups. The proportion of women reporting adverse events during the study was comparable between groups.ConclusionsIntake of Lp from early pregnancy was safe, attenuated the loss of iron stores and improved iron status in healthy pregnant women.
Mining in Africa after the supercycle: New directions and geographies
Authors: Bowman Andrew , Frederiksen Tomas , Bryceson Deborah Fahy , Childs John , Gilberthorpe Emma , Newman Susan 
Published: April 2021

AbstractMining in Africa is at a pivotal moment. For most of the period 2000 to 2012, the extractive industries were in a “supercycle” of sustained high commodity prices. Driven by resource‐intensive growth in emerging market economies, these high commodity prices were anticipated to continue for decades to come. However, this “supercycle” ended in 2012 and there followed a severe slump in mineral prices from 2014 onwards. On the one hand, a new era of commodity market dynamics has begun, with changing patterns of economic activity, minerals governance, and environmental regulation. On the other hand, the end of the supercycle has continued or intensified pre‐existing trends towards mechanisation, automation, and enclavity, while distributive pressures on companies by local communities and host nations increase. We argue that the end of the supercycle has reconfigured the geographies of extraction in ways that are not yet reflected in existing research or taken into consideration in policy implementation, particularly around corporate strategy, state–business relations, and models for mineral‐based development strategies. In this paper we map the terrain of research on the supercycle in Africa and identify emerging post‐supercycle trends – some of which have overtaken research. The paper is structured around examining four themes: (1) new geographies of investment and extraction; (2) new geographies of struggle; (3) national minerals‐based development; and (4) labour and livelihoods, for which we identify key trends during the supercycle and post‐supercycle and areas for future research and policy development.
Long access to cocaine self‐administration dysregulates the glutamate synapse in the nucleus accumbens core of serotonin transporter knockout rats
Authors: Caffino Lucia , Mottarlini Francesca , Targa Giorgia , Verheij Michel M. M. , Homberg Judith , Fumagalli Fabio 
Published: April 2021

Background and PurposeIt is well established that the nucleus accumbens and glutamate play a critical role in the motivation to take drugs of abuse. We have previously demonstrated that rats with ablation of the serotonin (5‐HT) transporter (SERT−/− rats) show increased cocaine intake reminiscent of compulsivity.Experimental ApproachBy comparing SERT−/− to SERT+/+ rats, we set out to explore whether SERT deletion influences glutamate neurotransmission under control conditions as well as after short access (1 h/session) or long access (6 h/session) to cocaine self‐administration.Key ResultsRats were killed at 24 h after the final self‐administration session for ex vivo molecular analyses of the glutamate system (vesicular and glial transporters, post‐synaptic subunits of NMDA and AMPA receptors and their related scaffolding proteins). Such analyses were undertaken in the nucleus accumbens core. In cocaine‐naïve animals, SERT deletion evoked widespread abnormalities in markers of glutamatergic neurotransmission that, overall, indicate a reduction of glutamate signalling. These results suggest that 5‐HT is pivotal for the maintenance of accumbal glutamate homeostasis. We also found that SERT deletion altered glutamate homeostasis mainly after long access, but not short access, to cocaine.Conclusion and ImplicationsOur findings reveal that SERT deletion may sensitize the glutamatergic synapses of the nucleus accumbens core to the long access but not short access, intake of cocaine.LINKED ARTICLESThis article is part of a themed issue on New discoveries and perspectives in mental and pain disorders. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.17/issuetoc
Use, Exchange, and Speculation: The Politics of Inhabitance and the Right to the City in Urban Peru
Authors: Skrabut Kristin 
Published: April 2021

AbstractThe protagonist of Lefebvre’s “Right to the City” is the citaden, a citizen‐denizen whose rights are produced through residency and incumbent contributions to everyday urban life. Yet, in the shantytowns of Lima where people have long believed that residency generates rights, what it means to “do residency” (hacer vivencia) is itself contested. Drawing on twenty‐one months of fieldwork in the Limeño shantytown of Pachacútec, Peru, I show that “inhabitance” is a multidimensional construct and that the relationship between inhabitance and rights to spatial appropriation and political participation is a primary source of conflict, generating questions about community belonging, democratic representation, and the moral status of property transfers. Far from neatly resolving the inequalities generated by capitalist property relations, this case demonstrates that Lefebvre’s “right to the city” entails many of its own questions: What actions constitute residency? Do people have differential rights based on differential contributions to community life? And can rights to space be earned, leading to tenure security, or must they always be actively performed? As Peruvians answer these questions in the course of building their cities and their lives, they illuminate the ambiguities and challenges inherent in realizing the “right to the city” in Latin America's urban peripheries.
Iconicity and Diachronic Language Change
Authors: Monaghan Padraic , Roberts Seán G. 
Published: April 2021

AbstractIconicity, the resemblance between the form of a word and its meaning, has effects on behavior in both communicative symbol development and language learning experiments. These results have invited speculation about iconicity being a key feature of the origins of language, yet the presence of iconicity in natural languages seems limited. In a diachronic study of language change, we investigated the extent to which iconicity is a stable property of vocabulary, alongside previously investigated psycholinguistic predictors of change. Analyzing 784 English words with data on their historical forms, we found that stable words are higher in iconicity, longer in length, and earlier acquired during development, but that the role of frequency and grammatical category may be less important than previously suggested. Iconicity is revealed as a feature of ultra‐conserved words and potentially also as a property of vocabulary early in the history of language origins.
Corporate venture capital, disclosure, and financial reporting
Authors: Hamm Sophia J. W. , Jung Michael J. , Park Min 
Published: April 2021

AbstractResearch Question/IssueCorporate venture capital (CVC) is one of the most important avenues for corporate innovation today, yet there can be unintended consequences related to anticompetitive practices. Recent scrutiny from regulators and policymakers underscores their growing desire for more information about firms' CVC investment activities, even of those previously believed to be too small to matter.Research Findings/InsightsUsing a comprehensive sample of 115 publicly listed US parent firms that owned 133 CVC firms, we document that for almost half of the firm‐years in our sample, parent firms do not disclose any information about their CVC program. Among the parent firms that do disclose their CVC activities, we find that they disclose less when they make investments in industries outside of their core industry. Firms with a CVC program, relative to similar firms without a CVC program, tend to make more future acquisitions and report less future goodwill asset write‐downs.Theoretical/Academic ImplicationsVariation in details of CVC disclosures explained by within‐industry versus outside‐industry investments is consistent with theories on voluntary/discretionary disclosure. Future research can examine other characteristics of CVC investments that explain how parent firms report their CVC activities.Practitioner/Policy ImplicationsThis study documents the current state of affairs with respect to the amount of publicly available CVC information for a large sample of firms, an important starting point for regulators and policymakers to conduct an informed debate about whether disclosure requirements should be expanded. Our focus on investment disclosures can apply to other settings in which the investing public could benefit from greater transparency, such as Special Purpose Acquisition Companies (SPACs).
Machine learning on microbiome research in gastrointestinal cancer
Authors: Cheung Henley , Yu Jun 
Published: April 2021

AbstractGastrointestinal cancer maintains the highest incidence and mortality rate among all cancers globally. In addition to genetic causes, it has been reported that individuals' diet and composition of the gastrointestinal microbiome have profound impacts on gastrointestinal cancer development. Microbiome research has risen in popularity to provide alternative insights into cancer development and potential therapeutic effect. However, there is a lack of an effective analytical tool to comprehend the massive amount of data generated from high‐throughput sequencing methods. Artificial intelligence is another rapidly developing field that has strong application potential in microbiome research. Deep learning and machine learning are two subfields under the umbrella of artificial intelligence. Here we discuss the current approaches to study the gut microbiome, as well as the applications and challenges of implementing artificial intelligence in microbiome research.
Toll‐interacting protein polymorphisms in viral bronchiolitis outcomes
Authors: Törmänen Sari , Teräsjärvi Johanna , Nuolivirta Kirsi , He Qiushui , Korppi Matti , Lauhkonen Eero 
Published: April 2021

AbstractBackgroundToll‐interacting protein is a key factor in regulating innate immunity responses via gatekeeping Toll‐like receptors. Genetic variance in innate immunity has been linked with susceptibility to infections. Children with viral bronchiolitis in infancy are at increased risk of later asthma. The aim was to evaluate the role of toll‐interacting protein gene point mutations in severity of bronchiolitis and subsequent risk of asthma.MethodsInfants less than 6 months old were recruited during hospitalization due to bronchiolitis. In all, 166 children were prospectively followed up to age of 1.5, 6, and 11 years. Clinical data on viral etiology and severity markers, and further post‐bronchiolitis asthma and lung function outcomes were compared with genetic differences in two single‐nucleotide point mutations rs116938768 and rs5743854 in the toll‐interacting protein gene.ResultsToll‐interacting protein rs116938768 or rs5743854 did not show significant associations with severity markers or viral etiology of bronchiolitis. Follow‐up data on current asthma or lung function at 6 or 11 years of age after bronchiolitis were not associated with the investigated mutations.ConclusionToll‐interacting protein gene point mutations in rs116938768 or rs5743854 were not involved with the clinical course of viral bronchiolitis in early infancy, and did not predict post‐bronchiolitis asthma or lung function reduction by the age of 11 years.
Contextual analyticity
Authors: Bochner Gregory 
Published: April 2021

AbstractMy double aim in this paper is to argue for the claims that, when they are formed in certain ways, some judgements expressed by “I am here now” are both (a) apriori (although not solely in virtue of their meaning), and (b) necessary (albeit trivially so). I will submit that such judgements are “analytic” in the same sense that some judgements are “immune to error through misidentification” when this notion is understood in a relativistic way: in both cases, no component of the content determines the referents upon which the truth of the corresponding judgement depends. I will attempt to show that, beyond conventionally‐analytic sentences which are supposed to be (known apriori to be) true just in virtue of (knowledge of their) meaning, there are also contextuallyanalytic judgements that are (known apriori to be) true in virtue of (apriori knowledge of the) reflexive relation between the context of the judgement and the circumstance of evaluation which it targets.