bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comprehensive review of hydroxyurea for β-haemoglobinopathies: the role revisited during COVID-19 pandemic
Authors: Yasara Nirmani , Premawardhena Anuja , Mettananda Sachith 
Published: March 2021

Abstract
Background
Hydroxyurea is one of the earliest drugs that showed promise in the management of haemoglobinopathies that include β-thalassaemia and sickle cell disease. Despite this, many aspects of hydroxyurea are either unknown or understudied; specifically, its usefulness in β-thalassaemia major and haemoglobin E β-thalassaemia is unclear. However, during COVID-19 pandemic, it has become a valuable adjunct to transfusion therapy in patients with β-haemoglobinopathies. In this review, we aim to explore the available in vitro and in vivo mechanistic data and the clinical utility of hydroxyurea in β-haemoglobinopathies with a special emphasis on its usefulness during the COVID-19 pandemic.

Main body
Hydroxyurea is an S-phase-specific drug that reversibly inhibits ribonucleoside diphosphate reductase enzyme which catalyses an essential step in the DNA biosynthesis. In human erythroid cells, it induces the expression of γ-globin, a fetal globin gene that is suppressed after birth. Through several molecular pathways described in this review, hydroxyurea exerts many favourable effects on the haemoglobin content, red blood cell indices, ineffective erythropoiesis, and blood rheology in patients with β-haemoglobinopathies. Currently, it is recommended for sickle cell disease and non-transfusion dependent β-thalassaemia. A number of clinical trials are ongoing to evaluate its usefulness in transfusion dependent β-thalassaemia. During the COVID-19 pandemic, it was widely used as an adjunct to transfusion therapy due to limitations in the availability of blood and logistical disturbances. Thus, it has become clear that hydroxyurea could play a remarkable role in reducing transfusion requirements of patients with haemoglobinopathies, especially when donor blood is a limited resource.

Conclusion
Hydroxyurea is a well-tolerated oral drug which has been in use for many decades. Through its actions of reversible inhibition of ribonucleoside diphosphate reductase enzyme and fetal haemoglobin induction, it exerts many favourable effects on patients with β-haemoglobinopathies. It is currently approved for the treatment of sickle cell disease and non-transfusion dependent β-thalassaemia. Also, there are various observations to suggest that hydroxyurea is an important adjunct in the treatment of transfusion dependent β-thalassaemia which should be confirmed by randomised clinical trials.
Pre-positioning an evaluation of cash assistance programming in an acute emergency: strategies and lessons learned from a study in Raqqa Governorate, Syria
Authors: Falb Kathryn , Annan Jeannie 
Published: March 2021

Abstract
Background
Conducting ethical and rigorous research to measure the effectiveness of humanitarian programs is urgently needed given the global level of displacement and conflict, yet traditional approaches to evaluation research may be too slow and disruptive for acute humanitarian settings. The current case study utilizes an experience of implementing a mixed methods evaluation conducted between March–August 2018 in northern Raqqa Governorate, Syria. The key research objectives were to examine the influence of an unconditional, three-month cash transfer program on household basic needs and women’s wellbeing, including experiences of violence. This setting was selected for the research as it shared many aspects of an acute emergency within a protracted conflict given its recent opening of access to humanitarian aid programming following the withdrawal of ISIS as well as influxes of internally displaced persons fleeing airstrikes and fighting in Raqqa City in late 2017.

Discussion
The current case study was scientifically important as the use of cash assistance in emergencies has increased exponentially in recent years. Yet, little is still known about how cash assistance designed to help households meet their basic needs may also influence women’s overall wellbeing in the home. Challenges of conducting the research included selecting an emergency site appropriate for research, implementing an evaluation that would not delay or disrupt critical cash assistance programming, and measurement of sensitive violence against women outcomes. Four strategies were identified to meet the challenges of conducting an evaluation in such a setting, which included: (1) developing clear decision-making criteria for assessing feasibility; (2) frontloading processes to reduce time lag in launching research; (3) integrating the research approach within programming; and (4) closely collaborating with practitioners throughout the study, especially for research on sensitive topics like violence against women. Conclusions
Advance consideration of these factors through a pre-positioning process will allow for timely, ethical, and rigorous research to be implemented in the immediate aftermath of a crisis. Such studies should be prioritized to ensure the highest effectiveness and efficiency of humanitarian aid for populations grappling with acute emergencies.
Cancer-associated fibroblasts promote the survival of irradiated nasopharyngeal carcinoma cells via the NF-κB pathway
Authors: Huang Weiqiang , Zhang Longshan , Yang Mi , Wu Xixi , Wang Xiaoqing , Huang Wenqi , Yuan Lu , Pan Hua , Wang Yin , Wang Zici , Wu Yuting , Huang Jihong , Liang Huazhen , Li Shaoqun , Liao Liwei , Liu Laiyu , Guan Jian 
Published: March 2021

Abstract
Background
Irradiation has emerged as a valid tool for nasopharyngeal carcinoma (NPC) in situ treatment; however, NPC derived from tissues treated with irradiation is a main cause cancer-related death. The purpose of this study is to uncover the underlying mechanism regarding tumor growth after irradiation and provided potential therapeutic strategy.

Methods
Fibroblasts were extracted from fresh NPC tissue and normal nasopharyngeal mucosa. Immunohistochemistry was conducted to measure the expression of α-SMA and FAP. Cytokines were detected by protein array chip and identified by real-time PCR. CCK-8 assay was used to detect cell proliferation. Radiation-resistant (IRR) 5-8F cell line was established and colony assay was performed to evaluate tumor cell growth after irradiation. Signaling pathways were acquired via gene set enrichment analysis (GSEA). Comet assay and γ-H2AX foci assay were used to measure DNA damage level. Protein expression was detected by western blot assay. In vivo experiment was performed subcutaneously.

Results
We found that radiation-resistant NPC tissues were constantly infiltrated with a greater number of cancer-associated fibroblasts (CAFs) compared to radiosensitive NPC tissues. Further research revealed that CAFs induced the formation of radioresistance and promoted NPC cell survival following irradiation via the IL-8/NF-κB pathway to reduce irradiation-induced DNA damage. Treatment with Tranilast, a CAF inhibitor, restricted the survival of CAF-induced NPC cells and attenuated the of radioresistance properties.

Conclusions
Together, these data demonstrate that CAFs can promote the survival of irradiated NPC cells via the NF-κB pathway and induce radioresistance that can be interrupted by Tranilast, suggesting the potential value of Tranilast in sensitizing NPC cells to irradiation.
Effect of patient-controlled intravenous analgesia combined with flurbiprofen axetil and dezocine on postoperative analgesia for lobectomy (EPIC-FAD): a trial protocol
Authors: Zhou Jian , Pu Qiang , Lin Lin , Chong Weelic , Chen Boran , Hai Yang , Liu Fei , Liu Lunxu 
Published: March 2021

Abstract
Background
The optimal analgesic strategy for surgical pain after lobectomy remains undefined. To compare the combination of flurbiprofen axetil and dezocine with flurbiprofen axetil alone and dezocine alone, in post-lobectomy patients.

Methods
A single-center, parallel-design double-blind superiority trial, with 5 groups (1:1:1:1:1 ratio) with different combinations of flurbiprofen and dezocine. Patients scheduled for lobectomy will be recruited. The primary outcome is total sufentanil use in patient-controlled intravenous analgesia within the first 24 postoperative hours. Secondary outcomes include pain numeric rating scales at 6th, 12th, 24th, 48th, and 72th postoperative hours, and on the 1st, 3rd, and 6th postoperative months at rest and during coughing, adverse effects from experimental drug treatment, sufentanil use at other time points, analgesia cost, time to chest tube removal, length of hospital stay, time to pass first flatus, and serum level of cytokines. Doctors, patients, and nurses are blinded, and only the manager is unblinded. Analysis is intention-to-treat. Statistical analysis is pre-specified. Statistical comparison of the treatment groups includes one-way analysis of variance followed by Tukey’s post hoc test.

Discussion
Trial did not begin to recruit. Participant recruitment start date is planned to be June 1, 2020. Approximate recruitment end date is May 31, 2021. If successful, the trial may shed light on the use of certain analgesic combinations in post-lobectomy pain control.

Trial registration
Chinese Clinical Trial Registry ChiCTR1800018563. Registered on September 25, 2018.
Effect of early treatment with polyvalent immunoglobulin on acute respiratory distress syndrome associated with SARS-CoV-2 infections (ICAR trial): study protocol for a randomized controlled trial
Authors: Mazeraud Aurélien , Gonçalves Bruno , Aegerter Philippe , Mancusi Letizia , Rieu Christine , Bozza Fernando , Sylla Khaoussou , Siami Shidasp , Sharshar Tarek 
Published: March 2021

Abstract
Background
As of mid-June 2020, 7,500,000 people were infected with SARS-CoV-2 worldwide and 420,000 people died, mainly from coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS). COVID-19-related ARDS is subject to a mortality rate of 50% and prolonged period of mechanical ventilation, with no specific pharmacological treatment currently available (Infection au nouveau Coronavirus (SARS-CoV-2), COVID-19, France et Monde. https://www.santepubliquefrance.fr/dossiers/coronavirus-covid-19). Because of its immunomodulatory action, we propose to evaluate the efficacy and safety of intravenous immunoglobulin (IVIG) administration in patients developing COVID-19-related ARDS.

Methods
The trial is a phase III double-blind, randomized, multicenter, parallel group, concurrent, controlled study in hospitalized participants with COVID-19 requiring mechanical ventilation using a sequential design. Participants in the treatment group will receive infusions of polyvalent immunoglobulin for 4 consecutive days, and the placebo group will receive an equivalent volume of sodium chloride 0.9% for the same duration. The primary outcome is the number of ventilator-free days up to the 28th day. Secondary objectives are to evaluate the effect of IVIG on (1) organ failure according to the Sequential Organ Failure Assessment (SOFA) score at 14 and 28 days, (2) lung injury score at 14 and 28 days, (3) the occurrence of grade 3 or 4 adverse events of IVIG, (4) length of intensive care unit (ICU) stay, (5) length of hospital stay, (6) functional outcomes at day 90 defined by the activities of daily living and instrumental activities of the daily living scales, and (7) 90-day survival. One hundred thirty-eight subjects will be randomized in a 1:1 ratio to IVIG or placebo groups (69 in each group), considering 90% power, alpha level 0.05 (two sides), and 0.67 effect size level.

Discussion
The ICAR trial investigates the effect of IVIG in COVID-19-related ARDS. We expect an increase in the survival rate and a reduction in the duration of mechanical ventilation, which is associated with significant morbidity.

Trial registration
EudraCT 2020-001570-30. ClinicalTrials.gov NCT04350580. Registered on 17 April 2020
UKCTOCS update: applying insights of delayed effects in cancer screening trials to the long-term follow-up mortality analysis
Authors: Burnell Matthew , Gentry-Maharaj Aleksandra , Skates Steven J. , Ryan Andy , Karpinskyj Chloe , Kalsi Jatinderpal , Apostolidou Sophia , Singh Naveena , Dawnay Anne , Woolas Robert , Fallowfield Lesley , Campbell Stuart , McGuire Alistair , Jacobs Ian J. , Parmar Mahesh , Menon Usha 
Published: March 2021

Abstract
Background
During trials that span decades, new evidence including progress in statistical methodology, may require revision of original assumptions. An example is the continued use of a constant-effect approach to analyse the mortality reduction which is often delayed in cancer-screening trials. The latter led us to re-examine our approach for the upcoming primary mortality analysis (2020) of long-term follow-up of the United Kingdom Collaborative Trial of Ovarian Cancer Screening (LTFU UKCTOCS), having initially (2014) used the proportional hazards (PH) Cox model.

Methods
We wrote to 12 experts in statistics/epidemiology/screening trials, setting out current evidence, the importance of pre-specification, our previous mortality analysis (2014) and three possible choices for the follow-up analysis (2020) of the mortality outcome: (A) all data (2001–2020) using the Cox model (2014), (B) new data (2015–2020) only and (C) all data (2001–2020) using a test that allows for delayed effects.

Results
Of 11 respondents, eight supported changing the 2014 approach to allow for a potential delayed effect (option C), suggesting various tests while three favoured retaining the Cox model (option A). Consequently, we opted for the Versatile test introduced in 2016 which maintains good power for early, constant or delayed effects. We retained the Royston-Parmar model to estimate absolute differences in disease-specific mortality at 5, 10, 15 and 18 years.

Conclusions
The decision to alter the follow-up analysis for the primary outcome on the basis of new evidence and using new statistical methodology for long-term follow-up is novel and has implications beyond UKCTOCS. There is an urgent need for consensus building on how best to design, test, estimate and report mortality outcomes from long-term randomised cancer screening trials.

Trial registration
ISRCTN22488978. Registered on 6 April 2000.
Label information and consumer behaviour: evidence on drinking milk sector
Authors: Marchini Andrea , Riganelli Chiara , Diotallevi Francesco , Polenzani Bianca 
Published: March 2021

AbstractThe purpose of the research is to evaluate the impact of different kinds of information disclosures of milk labels, investigating the interest among consumers based on their consumption behaviours and characteristics. In this research, all the actions which lead to a healthiness, become expressions of a production process, among which consumers’ food choices, purchase, preparation, and also self-production. Therefore, in the “health creation” production process, information and knowledge about food become “investments”. In this context, label disclosures become a tangible expression of this kind of “investment”. The research question is: what impact do purchase preferences and consumers’ characteristics have on their interest towards the label information provided? Several information disclosures, both mandatory and voluntary, are investigated. Therefore, some choice attributes will be analysed as indicators of the consumer’s behaviour in relation to his investment in food information. The methodology used for the analysis is an Ordered Logit. The analysis of the consumer’s behaviour has been performed by transposing Ménard’s analysis of firm corporate governance (Ménard, Agribus. 34:142–160, 2018) to the consumer as producer of welfare equity. The reduction of information asymmetry is a cost for the producer, and this research may be able to measure how much it would be convenient to invest in this reduction, based on the analysis of the consumer’s behaviour toward his personal investment in food information acquisition.
Real-time data assimilation and control on mechanical systems under uncertainties
Authors: Rubio Paul-Baptiste , Chamoin Ludovic , Louf François 
Published: March 2021

AbstractThis research work deals with the implementation of so-called Dynamic Data-Driven Application Systems (DDDAS) in structural mechanics activities. It aims at designing a real-time numerical feedback loop between a physical system of interest and its numerical simulator, so that (i) the simulation model is dynamically updated from sequential and in situ observations on the system; (ii) the system is appropriately driven and controlled in service using predictions given by the simulator. In order to build such a feedback loop and take various uncertainties into account, a suitable stochastic framework is considered for both data assimilation and control, with the propagation of these uncertainties from model updating up to command synthesis by using a specific and attractive sampling technique. Furthermore, reduced order modeling based on the Proper Generalized Decomposition (PGD) technique is used all along the process in order to reach the real-time constraint. This permits fast multi-query evaluations and predictions, by means of the parametrized physics-based model, in the online phase of the feedback loop. The control of a fusion welding process under various scenarios is considered to illustrate the proposed methodology and to assess the performance of the associated numerical architecture.
Understanding why apprentices consider dropping out: longitudinal prediction of apprentices’ workplace interest and anxiety
Authors: Powers Tim E. , Watt Helen M. G. 
Published: March 2021

AbstractAlthough apprenticeships ease the school-to-work transition for youth, many apprentices seriously consider dropping out. While associated with noncompletions, dropout considerations are important to study in their own right, because they reflect a negative quality of apprenticeship experience and can impact apprentices’ quality of learning and engagement. Few studies have addressed apprentices’ dropout considerations using comprehensive theoretical frameworks. To address this gap, this study examined how apprentices’ interest and anxiety growth trajectories predicted dropout considerations and associated with perceived resources and demands, grounded in expectancy-value theory (EVT) and the job demands-resources (JD-R) model. Australian apprentices (N = 2387) were surveyed at 6-month intervals utilising an accelerated longitudinal design, on their workplace interest and anxiety, job-related resources (role model, timing of choice, employer teaching, expertise, job security, and training wages) and demands (lack of information, career indecision, and excessive work). Latent growth models (LGM) within a structural equation modelling framework showed apprentices began with high interest which declined over time, and low anxiety which increased in the latter half of their first year until the end of their second year. Apprentices’ dropout considerations were predicted by initial interest and anxiety levels (at the beginning of their apprenticeship), and by interest losses during their apprenticeship (but, not by increases in anxiety). Almost half the variance in interest and anxiety trajectories was explained by apprentices’ perceived resources and demands: resources had a greater effect on promoting interest than reducing anxiety, whereas demands were more important in exacerbating anxiety.
Research under the GDPR – a level playing field for public and private sector research?
Authors: Quinn Paul 
Published: March 2021

AbstractScientific research is indispensable inter alia in order to treat harmful diseases, address societal challenges and foster economic innovation. Such research is not the domain of a single type of organization but can be conducted by a range of different entities in both the public and private sectors. Given that the use of personal data may be indispensable for many forms of research, the data protection framework will play an important role in determining not only what types of research may occur but also which types of actors may carry it out. This article looks at the role the EU’s General Data Regulation plays in determining which types of actors can conduct research with personal data. In doing so it focuses on the various legal bases that are available and attempts to discern whether the GDPR can be said to favour research in either the public or private domains. As this article explains, the picture is nuanced, with either type of research actor enjoying advantages and disadvantages in specific contexts.
Structural, functional, and evolutionary analysis of Cry toxins of Bacillus thuringiensis: an in silico study
Authors: Das Sujit Kumar , Pradhan Sukanta Kumar , Samal Kailash Chandra , Singh Nihar Ranjan 
Published: March 2021

Abstract
Background
Bacillus thuringiensis (Bt) is a gram-positive spore-forming soil bacterium that synthesizes crystalline (Cry) protein, which is toxic and causing pathogenicity against mainly three insect orders: Coleoptera, Diptera, and Lepidoptera. These crystalline protein inclusions, i.e., δ-endotoxins are successfully used as a bio-control agent against insect pests.

Main body
A total of 58 various Cry proteins belonging to these 3 insect orders were retrieved from SwissProt database and are categorized into different groups. Structural and functional analysis were performed to understand the functional domain arrangements at sequence level as well as at structural level involving both experimental and predicted 3-dimensional models. Besides, the analysis of evolutionary relationship involving all 58 observed Cry proteins at the sequence, domain, and structural levels were done using different bioinformatics tools. Evolutionary analysis revealed that some Cry proteins having toxicity for a specific insect order are found to be clustered for another different insect order, which concludes that they might have toxicity for more than one insect order. Three-dimensional (3D) structure analysis of both experimental and predicted models revealed that proteins might have toxicity for a specific insect order differ in their structural arrangements and was observed in Cry proteins belonging to 3 different insect orders.

Conclusions
It could be hypothesized that an inner-molecular domain shift or domain insertion/deletion might have taken place during the evolutionary process, which consequently causes structural and functional divergence of Bt. The study output may be helpful for understanding the diversity as well as specificity of the analyzed insecticidal proteins and their application as a biopesticide in the field of agriculture.
A language to analyze, describe, and explore collections of visual art
Authors: Pflüger Hermann 
Published: March 2021

AbstractA vast quantity of art in existence today is inaccessible to individuals. If people want to know the different types of art that exist, how individual works are connected, and how works of art are interpreted and discussed in the context of other works, they must utilize means other than simply viewing the art. Therefore, this paper proposes a language to analyze, describe, and explore collections of visual art (LadeCA). LadeCA combines human interpretation and automatic analyses of images, allowing users to assess collections of visual art without viewing every image in them. This paper focuses on the lexical base of LadeCA. It also outlines how collections of visual art can be analyzed, described, and explored using a LadeCA vocabulary. Additionally, the relationship between LadeCA and indexing systems, such as ICONCLASS or AAT, is demonstrated, and ways in which LadeCA and indexing systems can complement each other are highlighted.