bluuebunny/crossref_metadata_2025_split huggingface dataset:
The inequity of targeted cystic fibrosis reproductive carrier screening tests in Australia
Authors: Shum Bennett O. V. , Sng Letitia M. F. , Ruseckaite Rasa , Henner Ilya , Twine Natalie , Bauer Denis C. , Wilgen Urs , Pretorius Carel , Barahona Paulette , Ungerer Jacobus P. J. , Bennett Glenn 
Published: December 2022

AbstractObjectiveEuropean and Australian guidelines for cystic fibrosis (CF) reproductive carrier screening recommend testing a small number of high frequency CF causing variants, rather than comprehensive CFTR sequencing. The study objective was to determine variant detection rates of commercially available targeted reproductive carrier screening tests in Australia.MethodsNext‐generation DNA sequencing of the CFTR gene was performed on 2552 individuals from a whole population sample to identify CF causing variants. The variant detection rates of two commercially available Australian reproductive carrier screening tests, which target 50 or 175 CF causing variants, in this population were calculated. The ethnicity of individuals was determined using principal component analysis.ResultsVariant detection rates of the tests for 50 and 175 CF causing variants were 88.2% and 90.8%, respectively. No CF causing variants in individuals of East Asian ethnicity (n = 3) were detected by either test, while >86.6% (n = 69) of CF causing variants in Europeans would be identified by either test.ConclusionsReproductive carrier screening tests for a targeted set of high frequency CF variants are unable to detect approximately 10% of CF variants in a multiethnic Australian population, and individuals of East Asian ethnicity are disproportionally affected by this test limitation.
Examining the clinical impact of rapid multiplex polymerase chain reaction‐based diagnostic testing for bloodstream infections in a national cohort of the Veterans Health Administration
Authors: Britt Nicholas S. , Khader Karim , He Tao , Willson Tina M. , Effiong Atim , Timbrook Tristan T. , Potter Emily M. , Lodise Thomas P. 
Published: December 2022

AbstractStudy ObjectiveBloodstream infections (BSIs) are a significant cause of mortality. Use of a rapid multiplex polymerase chain reaction‐based blood culture identification panel (BCID) may improve antimicrobial utilization and clinical outcomes by shortening the time to appropriate therapy and de‐escalating antibiotics among patients on overly broad‐spectrum empiric therapy. The effect of BCID on clinical outcomes across varying institutional antimicrobial stewardship program (ASP) practices is unclear. This study evaluated clinical outcomes associated with the “real‐world” implementation of BCID in a national health system with varying ASP practices.DesignNational, multicenter, retrospective, pre–post quasi‐experimental study of hospitalized patients admitted from 2015 to 2020 to VHA facilities, which introduced the BCID for ≥1 year.SettingUnited States Veterans Health Administration (VHA) hospitals with BCID.PatientsHospitalized VHA patients with ≥1 blood culture positive for bacteria featured on the BCID panel.InterventionComparison of outcomes between the pre‐ and post‐BCID implementation groups.MeasurementsOutcomes evaluated included early antimicrobial de‐escalation within 48 h, defined as reduction in antimicrobial spectrum scores, time to appropriate therapy, and 30‐day mortality.Main ResultsA total of 4138 patients (pre‐BCID, n = 2100; post‐BCID, n = 2038) met the study criteria. Implementation of BCID was associated with significant improvements in early antimicrobial de‐escalation (34.6%: pre‐BCID vs. 38.1%: post‐BCID; p = 0.022), which persisted after adjusting for other covariates (adjusted risk ratio [aRR], 1.11; 95% confidence interval [CI], 1.02–1.20; p = 0.011). Median time to appropriate therapy was shorter in the post‐BCID implementation group relative to the pre‐BCID group (9 h: pre‐BCID vs. 8 h: post‐BCID, respectively, p = 0.005), and a greater percentage of patients received early appropriate antimicrobial therapy within 48 h in the post‐BCID implementation group (91.7%: pre‐BCID vs. 93.8%: post‐BCID; p = 0.008). In the multivariable regression analysis, BCID implementation was significantly associated with a higher likelihood of appropriate therapy within 48 h (aRR, 1.02; 95% CI, 1.01–1.08; p = 0.020). There was no difference in 30‐day mortality between groups overall (12.6% pre‐BCID vs. 11.2% post‐BCID; p = 0.211).ConclusionsIn a “real‐world” clinical setting, the implementation of BCID was associated with clinical improvements in antimicrobial utilization. The BCID platform may serve as a useful adjunct for BSI management in facilities with ASP.
Evaluation of acyllysine isostere interactions with the aromatic pocket of the AF9 YEATS domain
Authors: Travis Christopher R. , Francis Denver Y. , Williams David C. , Waters Marcey L. 
Published: December 2022

AbstractAmide−π interactions, in which an amide interacts with an aromatic group, are ubiquitous in biology, yet remain understudied relative to other noncovalent interactions. Recently, we demonstrated that an electrostatically tunable amide−π interaction is key to recognition of histone acyllysine by the AF9 YEATS domain, a reader protein which has emerged as a therapeutic target due to its dysregulation in cancer. Amide isosteres are commonly employed in drug discovery, often to prevent degradation by proteases, and have proven valuable in achieving selectivity when targeting epigenetic proteins. However, like amide−π interactions, interactions of amide isosteres with aromatic rings have not been thoroughly studied despite widespread use. Herein, we evaluate the recognition of a series of amide isosteres by the AF9 YEATS domain using genetic code expansion to evaluate the amide isostere−π interaction. We show that compared to the amide−π interaction with the native ligand, each isostere exhibits similar electrostatic tunability with an aromatic residue in the binding pocket, demonstrating that the isosteres maintain similar interactions with the aromatic residue. We identify a urea‐containing ligand that binds with enhanced affinity for the AF9 YEATS domain, offering a promising starting point for inhibitor development. Furthermore, we demonstrate that carbamate and urea isosteres of crotonyllysine are resistant to enzymatic removal by SIRT1, a protein that cleaves acyl post‐translational modifications, further indicating the potential of amide isosteres in YEATS domain inhibitor development. These results also provide experimental precedent for interactions of these common drug discovery moieties with aromatic rings that can inform computational methods.
Selective incorporation of 5‐hydroxytryptophan blocks long range electron transfer in oxalate decarboxylase
Authors: Pastore Anthony John , Montoya Alvaro , Kamat Manasi , Basso Kari B. , Italia James S. , Chatterjee Abhishek , Drosou Maria , Pantazis Dimitrios A. , Angerhofer Alexander 
Published: December 2022

AbstractOxalate decarboxylase from Bacillus subtilis is a binuclear Mn‐dependent acid stress response enzyme that converts the mono‐anion of oxalic acid into formate and carbon dioxide in a redox neutral unimolecular disproportionation reaction. A π‐stacked tryptophan dimer, W96 and W274, at the interface between two monomer subunits facilitates long‐range electron transfer between the two Mn ions and plays an important role in the catalytic mechanism. Substitution of W96 with the unnatural amino acid 5‐hydroxytryptophan leads to a persistent EPR signal which can be traced back to the neutral radical of 5‐hydroxytryptophan with its hydroxyl proton removed. 5‐Hydroxytryptophan acts as a hole sink preventing the formation of Mn(III) at the N‐terminal active site and strongly suppresses enzymatic activity. The lower boundary of the standard reduction potential for the active site Mn(II)/Mn(III) couple can therefore be estimated as 740 mV against the normal hydrogen electrode at pH 4, the pH of maximum catalytic efficiency. Our results support the catalytic importance of long‐range electron transfer in oxalate decarboxylase while at the same time highlighting the utility of unnatural amino acid incorporation and specifically the use of 5‐hydroxytryptophan as an energetic sink for hole hopping to probe electron transfer in redox proteins.
Isoliquiritigenin inhibits microglia‐mediated neuroinflammation in models of Parkinson's disease via JNK/AKT/NFκB signaling pathway
Authors: Bai Yuyan , Zhou Jin , Zhu Han , Tao Yanlin , Wang Lupeng , Yang Liu , Wu Hui , Huang Fei , Shi Hailian , Wu Xiaojun 
Published: December 2022

AbstractIsoliquiritigenin (ISL) is a flavonoid with numerous pharmacological properties, including anti‐inflammation, yet its role in Parkinson's disease (PD) with microglia‐mediated neuroinflammation remains unknown. In this study, the effects of ISL on inhibiting microglia‐mediated neuroinflammation in PD were evaluated in the 1‐methyl‐4‐phenylpyridinium (MPTP)‐induced mouse model of PD and in lipopolysaccharide (LPS)‐stimulated BV‐2 microglia. Our results showed that ISL prevented behavioral deficits and excessive microglial activation in MPTP‐treated mice. Moreover, ISL was found to prevent the elevation of inducible nitric oxide synthase (iNOS) and cyclooxygenase‐2 (COX‐2), and mitigate the phosphorylation of c‐Jun N‐terminal protein kinase (JNK), protein kinase B (AKT), nuclear factor kappa light‐chain enhancer of activated B cells (NFκB), and inhibitor of NFκB protein ɑ (IκBɑ) in the substantia nigra and striatum of MPTP‐treated mice and LPS‐stimulated BV‐2 cells. Meanwhile, in LPS‐stimulated BV‐2 cells, ISL inhibited the production of inflammatory mediators such as interleukin (IL)‐1β, IL‐6 and tumor necrosis factor alpha (TNF‐α). In addition, the agonist of JNK partly abolished the inhibitory effects of ISL in LPS‐treated BV‐2 cells. Our results demonstrated that ISL inhibits microglia‐mediated neuroinflammation in PD models probably through deactivating JNK/AKT/NFκB signaling pathways. The novel findings suggest the therapeutic potential of ISL for microglia‐mediated neuroinflammation in PD.
Safety of varicella vaccination strategies: An overview of reviews
Authors: Ahern Susan , Walsh Kieran A. , Paone Simona , Browne John , Carrigan Marie , Harrington Patricia , Murphy Aileen , Teljeur Conor , Ryan Máirín 
Published: December 2022

AbstractThe safety of new vaccines under development as well as existing vaccines is a key priority for national and international public health agencies. A number of countries have implemented universal childhood varicella vaccination programmes over the past 30 years. However, strategies differ in terms of the number of doses, type of vaccine(s) recommended, age at vaccination and interval between doses for a two‐dose schedule. An overview of reviews was undertaken to assess the existing systematic review evidence of the safety of varicella vaccination strategies. The review was restricted to immunocompetent children aged 9 months to 6 years inclusive. A comprehensive search of databases, registries and grey literature was conducted up to 2 February 2022. Two reviewers independently screened, extracted data and assessed the methodological quality of included reviews. Overlap of included reviews was also assessed. A total of 17 reviews, incorporating both the monovalent varicella only and quadrivalent measles‐mumps‐rubella‐varicella (MMRV) vaccines were included in the overview; six assessed the safety of one‐dose strategies, four assessed the safety of two‐dose strategies and 14 reviews did not specify the dosing strategy. The evidence suggests that mild local and systemic reactions are relatively common with varicella vaccination. Febrile seizures are also possible adverse effects of both the monovalent and quadrivalent MMRV vaccine, but serious adverse reactions are rare. While most reviews contained methodological flaws, and analysis by vaccine type and dosing strategy was restricted due to lack of detail in reporting of the reviews, there was clear and consistent evidence from a substantial evidence base, comprising 34 randomised controlled trials and 62 other primary studies/reviews, that varicella vaccination is safe.
Value chains and sustainable development: A perspective of sustainable coffee value chains in East Africa
Authors: Canwat Vincent 
Published: December 2022

AbstractSustainable development concerns have been integrated into global value chains through the enforcement of sustainability standards, making the chains sustainable. Understanding the sustainability effects of sustainable value chains has been limited by the narrow focus on one standard, few larger comparative perspectives, methodological weaknesses, and diversity of contexts. This article analyses how sustainable coffee value chains contribute to sustainable development. Systematically, the study reviewed peer‐reviewed publications based on causal methodologies and primary data collected from Uganda, Kenya, Tanzania, and Ethiopia. The paper shows that sustainable value chains promote sustainable development, but their effects vary across sustainability dimensions and standards. Fairtrade has a higher contribution to social sustainability because it emphasizes social issues. Organic standards and the Rainforest Alliance also have a higher contribution to ecological sustainability because they emphasize ecological conservation. Sustainable coffee value chains have more contributions to social and ecological sustainability than economic sustainability because of the trade‐offs that ensues from conversion to sustainable value chains. However, combining standards reduces trade‐offs. The sustainability effects of sustainable value chains also vary across cooperatives because of their heterogeneity.
Toward a readiness model for secure software coding
Authors: Humayun Mamoona , Niazi Mahmood , Jhanjhi Noor Zaman , Mahmood Sajjad , Alshayeb Mohammad 
Published: December 2022

AbstractThe heart of the application's secure operation is its software code. If the code contains flaws, the entire program might be hacked. The issue with software vulnerabilities is that they reveal coding flaws that hackers could exploit. The prevention of cybersecurity issues begins with the program code itself. When writing software code, a software developer must consider expressing the application's architecture and design requirements, keeping the code streamlined and efficient, and ensuring the code is safe. Secure code helps save the system from various cyber‐attacks by eliminating the weaknesses that many hacks rely on. To assist the software organization in Secure Software Coding (SSC), this article proposes a readiness model for SSC, namely SSCRM. The proposed model has five levels; SSC challenges and best practices (BP) are mapped at each level. The proposed model will help the organizations better understand SSC challenges and BPs and provide a roadmap for developing secure software code. The proposed model was evaluated using three case studies. The findings demonstrate that the proposed approach helps determine an organization's SSC level.
How a novel partnership, to support rural healthcare teams, changed how we define what it means to be a practicing statistician
Authors: Rolfes Jennifer , McEachern Edward , Yturriondobeitia Jennifer , Klarc Hilary 
Published: December 2022

AbstractRural healthcare teams face many challenges and resource constraints which have been exacerbated during the global pandemic. Often without the technical expertise required to meet mandatory reporting requirements defined by multiple stakeholders, providers become too overwhelmed to focus their time on patient care. At the same time, the healthcare industry is moving away from a fee‐for‐service business model to a value‐based contract model, requiring provider organizations to enhance their reporting capabilities and optimize workflows. The novel partnership developed between a payer and a non‐profit allowed for a repeatable framework to be established to deploy technical resources and solve problems. Statisticians and data scientists are at the core intersection of the tools for connecting healthcare organizations with their data, and the processes allowing providers to use data and tools effectively and efficiently. It is also critical to identify the right statistical consultants since flexibility and empathy are required for this work. Through this pilot project, there has been meaningful success across quality measure reporting, patient outcomes, provider engagement, behavioural health and cancer screening and automation of solutions. Teams work together across disciplines to design sustainable solutions to a wide range of problems, all in service to the quadruple aim.
The impact of kidnapping on foreign ownership of firms in Nigeria
Authors: Ede Obiajulu , Okafor Godwin 
Published: December 2022

AbstractNigeria is one of the countries in Sub‐Saharan Africa (SSA) that has faced high incidents of kidnapping. As a result of that, some studies have investigated its determinants and economic consequences in Nigeria. However, no study is yet to investigate its impact on the foreign ownership of firms. This is a research void that this article has attempted to fill. Using the World Bank Enterprise Survey and the United Nations Office on Drugs and Crime, we found empirical evidence of the negative impact of kidnapping on the foreign ownership of firms. An increase in the kidnapping rate by one (1 per 100,000 of population) will reduce the foreign ownership of firms by 4.855–10.098% depending on the econometric model. There is also empirical evidence that the impact of kidnapping on foreign ownership will vary by geographical regions in Nigeria and by firm size. Policy implications were deduced from our findings.
The Phenomenon of Entrepreneurship in Reindeer Husbandry in Yamal: Assessment of the Situation, Paradoxes, and Contradictions
Authors: Pilyasov Alexander Nickolaevich , Kibenko Valeriy Aleksandrovich 
Published: December 2022

AbstractThe chapter considers the development of domestic reindeer herding in the Yamal-Nenets Autonomous Region over the past 30 years in terms of an entrepreneurial paradigm. Individual reindeer herding families own almost 60% of all domestic reindeer in the region. The chapter describes two types of nomadic entrepreneurs: economically independent and those relying on state support as well as differences in their behavior patterns, cultural values, and nomadic routes. Two reindeer herding models are presented: the ‘meat model’ of the Yamalsky district and the ‘antler model’ of the Tazovsky and Priuralsky districts in Yamal. Both models determine the differences in terms of size, dynamics and structure of the herd, length of nomadic routes, structure of production income. Unlike the dominant point of view blaming irresponsible reindeer herders for the depletion of pastures, the authors of the article see the problem as an institutional one – the result of public policies that created wrong incentives for reindeer herding entrepreneurs in recent decades. This policy transferred them to the position of hired herders equal to the state workers. The authors propose reforms in Yamal reindeer herding that will ensure a decisive transition to an entrepreneurial model in reindeer husbandry and an algorithm for the reforms in the state support system.
Sámi Traditional Reindeer Herding Knowledge Throughout a Year: Herding Periods on Snow-Covered Ground
Authors: Eira Inger Marie Gaup , Turi Ellen Inga , Turi Johan Mathis 
Published: December 2022

AbstractSámi traditional reindeer herding knowledge is the basis decisions in time and space made by Sámi reindeer herders with emphasis on periods and cycles and related to reindeer husbandry on snow-covered land. This chapter outlines aspects of the Sámi traditional knowledge used by reindeer herders in Western Finnmark performing reindeer herding during periods with snow on the ground. We will highlight the periods from October till April, as these constitute the critical bottlenecks in the annual herding cycle. Using methods for communicating with herders and co-production of knowledge between reindeer herders and science, this chapter outlines traditional reindeer herding periods and cycles through the year focusing particularly on aspects of herding on snow-covered ground. Reindeer herding strategies and practices are highly complicated and systematic enterprises containing different types of knowledge on how the biological and gender-based behavioral aspects of reindeer and the movement of the reindeer in time and space are connected to climate, temperature, and snow metamorphism. This includes knowledge about the different seasons, cycles, and periods in a reindeer year. Reindeer herding periods and cycles contain different sub-cycles that are a part of a larger system based on the year, the lunar month and day/night, e.g., cycles related to the use of areas throughout the year; the biological cycles of reindeer, like rutting season, calving season, dropped or cast antlers and moulting fur; sexual behavioral cycles; cycles relative to climate and snow, the cycles of sexual maturity, cycles of extreme years and cycles that include reindeer herding periods throughout the year.
Learning by Herding – Transmission of Sámi Reindeer Herding Knowledge and Skills
Authors: Bongo Mathis Persen , Eira Inger Marie Gaup 
Published: December 2022

AbstractThe chapter addresses the issues of disseminating the knowledge and skills of the Sámi reindeer herders: frameworks, methodologies, and ways of knowledge transmission in reindeer husbandry. The chapter overviews existing teaching practices, learning levels, and learning arenas, comparing traditional knowledge transmission and academic curriculum. The authors discuss lifelong learning, systematic learning methods, and responsibilities. The chapter findings are based on the interviews with the Sámi reindeer herders from Guovdageaidnu/Kautokeino, a literature review, and author’s reindeer herding experiences.
Trends and Effects of Climate Change on Reindeer Husbandry in the Republic of Sakha (Yakutia)
Authors: Popova Lena , Avelova Svetlana , Gerasimova Alena , Lutz Julia , Mathiesen Svein Disch , Moiakunova Anisiia , Petrova Alexandra , Pogodaev Mikhail , Shadrin Vyacheslav , Shishigina Anna N. , Zhozhikov Anatoly V. 
Published: December 2022

AbstractThe Republic of Sakha (Yakutia), like other Arctic regions, faces severe climatic and environmental changes and hazards such as temperature increase, permafrost thaw, intense forest fires, earlier melting, and flooding. Significant climate and environmental changes over the past decades pose risks to the preservation of the traditional way of life of Indigenous peoples, including reindeer husbandry. Understanding trends and effects of climate change in the Republic of Sakha is needed to project and manage the future of reindeer husbandry, the resilience of Indigenous communities, and plan their economic adaptation. In this article, we analyze meteorological data from four weather stations located in different reindeer herding areas of Yakutia focusing on snow cover formation, permafrost conditions, and forest fires; provide the results of in-depth interviews with local people on the impact of climate change on reindeer herding. The financing of resilience development in the Republic is discussed. In conclusion, suggest necessary measures that can be taken for adaptation and overcoming emerging threats and challenges for further development of reindeer husbandry which is the central basis of the identity of the Indigenous peoples of the North.