bluuebunny/crossref_metadata_2025_split huggingface dataset:
AGILE: a seamless phase I/IIa platform for the rapid evaluation of candidates for COVID-19 treatment: an update to the structured summary of a study protocol for a randomised platform trial letter
Authors: Griffiths Gareth O. , FitzGerald Richard , Jaki Thomas , Corkhill Andrea , Reynolds Helen , Ewings Sean , Condie Susannah , Tilt Emma , Johnson Lucy , Radford Mike , Simpson Catherine , Saunders Geoffrey , Yeats Sara , Mozgunov Pavel , Tansley-Hancock Olana , Martin Karen , Downs Nichola , Eberhart Izabela , Martin Jonathan W. B. , Goncalves Cristiana , Song Anna , Fletcher Tom , Byrne Kelly , Lalloo David G. , Owen Andrew , Jacobs Michael , Walker Lauren , Lyon Rebecca , Woods Christie , Gibney Jennifer , Chiong Justin , Chandiwana Nomathemba , Jacob Shevin , Lamorde Mohammed , Orrell Catherine , Pirmohamed Munir , Khoo Saye ,   on behalf of the AGILE investigators
Published: July 2021

Abstract
Background
There is an urgent unmet clinical need for the identification of novel therapeutics for the treatment of COVID-19. A number of COVID-19 late phase trial platforms have been developed to investigate (often repurposed) drugs both in the UK and globally (e.g. RECOVERY led by the University of Oxford and SOLIDARITY led by WHO). There is a pressing need to investigate novel candidates within early phase trial platforms, from which promising candidates can feed into established later phase platforms. AGILE grew from a UK-wide collaboration to undertake early stage clinical evaluation of candidates for SARS-CoV-2 infection to accelerate national and global healthcare interventions.

Methods/design
AGILE is a seamless phase I/IIa platform study to establish the optimum dose, determine the activity and safety of each candidate and recommend whether it should be evaluated further. Each candidate is evaluated in its own trial, either as an open label single arm healthy volunteer study or in patients, randomising between candidate and control usually in a 2:1 allocation in favour of the candidate. Each dose is assessed sequentially for safety usually in cohorts of 6 patients. Once a phase II dose has been identified, efficacy is assessed by seamlessly expanding into a larger cohort. AGILE is completely flexible in that the core design in the master protocol can be adapted for each candidate based on prior knowledge of the candidate (i.e. population, primary endpoint and sample size can be amended). This information is detailed in each candidate specific trial protocol of the master protocol.

Discussion
Few approved treatments for COVID-19 are available such as dexamethasone, remdesivir and tocilizumab in hospitalised patients. The AGILE platform aims to rapidly identify new efficacious and safe treatments to help end the current global COVID-19 pandemic. We currently have three candidate specific trials within this platform study that are open to recruitment.

Trial registration
EudraCT Number: 2020-001860-27 14 March 2020
ClinicalTrials.gov Identifier: NCT04746183 19 February 2021
ISRCTN reference: 27106947
The TANDEM trial: protocol for the process evaluation of a randomised trial of a complex intervention for anxiety and/or depression in people living with chronic obstructive pulmonary disease (COPD)
Authors: Kelly Moira , Steed Liz , Sohanpal Ratna , Pinnock Hilary , Barradell Amy , Dibao-Dina Clarisse , Mammoliti Kristie-Marie , Wileman Vari , Rowland Vickie , Newton Sian , Moore Anna , Taylor Stephanie 
Published: July 2021

Abstract
Background
TANDEM is a randomised controlled trial of a complex healthcare intervention to improve the psychological and physical health of people living with chronic obstructive pulmonary disease (COPD) and anxiety and/or depression. Based on health psychology theory set out in a logic model, respiratory health professionals were recruited and trained to deliver a cognitive behavioural approach intervention (The TANDEM intervention) under the supervision of senior cognitive behavioural practitioners. Here, we describe the protocol for the process evaluation commissioned alongside the trial. A realist approach that includes attention to describing contexts and mechanisms has been adopted.

Methods
We set up a multi-disciplinary team to develop and deliver the process evaluation. The mixed-methods design incorporates quantitative process data; monitoring of intervention fidelity; qualitative interviews with patients, carers, health professionals (facilitators) and clinical supervisors about their perspectives on acceptability of the intervention; and exploration with all stakeholders (including management/policy-makers) on future implementation. Normalisation process theory (NPT) will inform data collection and interpretation with a focus on implementation. Quantitative process data will be analysed descriptively. Qualitative interview data will be analysed before the trial outcomes are known using analytic induction and constant comparison to develop themes. Findings from the different elements will be reported separately and then integrated.

Conclusion
Detailed description and analysis of study processes in a research trial such as TANDEM enables research teams to describe study contexts and mechanisms and to examine the relationship with outcomes. In this way, learning from the trial goes beyond the randomised control trial (RCT) model where effectiveness is prioritised and makes it possible to explore issues arising for post-trial study implementation.

Trial registration
ISRCTN ISRCTN59537391. Registered on 20 March 2017. Trial protocol version 6.0, 22 April 2018.
Process evaluation protocol version 4.0, 1 November 2020.
At the tip of an iceberg: citizen science and active surveillance collaborating to broaden the known distribution of Aedes japonicus in Spain
Authors: Eritja Roger , Delacour-Estrella Sarah , Ruiz-Arrondo Ignacio , González Mikel A. , Barceló Carlos , García-Pérez Ana L. , Lucientes Javier , Miranda Miguel Á. , Bartumeus Frederic 
Published: July 2021

Abstract
Background
Active surveillance aimed at the early detection of invasive mosquito species is usually focused on seaports and airports as points of entry, and along road networks as dispersion paths. In a number of cases, however, the first detections of colonizing populations are made by citizens, either because the species has already moved beyond the implemented active surveillance sites or because there is no surveillance in place. This was the case of the first detection in 2018 of the Asian bush mosquito, Aedes japonicus, in Asturias (northern Spain) by the citizen science platform Mosquito Alert.

Methods
The collaboration between Mosquito Alert, the Ministry of Health, local authorities and academic researchers resulted in a multi-source surveillance combining active field sampling with broader temporal and spatial citizen-sourced data, resulting in a more flexible and efficient surveillance strategy.

Results
Between 2018 and 2020, the joint efforts of administrative bodies, academic teams and citizen-sourced data led to the discovery of this species in northern regions of Spain such as Cantabria and the Basque Country. This raised the estimated area of occurrence of Ae. japonicus from < 900 km2 in 2018 to > 7000 km2 in 2020.

Conclusions
This population cluster is geographically isolated from any other population in Europe, which raises questions about its origin, path of introduction and dispersal means, while also highlighting the need to enhance surveillance systems by closely combining crowd-sourced surveillance with public health and mosquito control agencies’ efforts, from local to continental scales. This multi-actor approach for surveillance (either passive and active) shows high potential efficiency in the surveillance of other invasive mosquito species, and specifically the major vector Aedes aegypti which is already present in some parts of Europe.

Graphical abstract
Blood glucose promotes dengue virus infection in the mosquito Aedes aegypti
Authors: Weng Shih-Che , Tsao Po-Nien , Shiao Shin-Hong 
Published: July 2021

Abstract
Background
Dengue fever is the most rapidly spreading mosquito-borne viral disease globally. More than 2.5 billion people live in dengue-endemic areas. Previous studies suggested an interrelationship between diabetes mellitus (DM) and dengue hemorrhagic fever (DHF). Conversely, glycolysis is a critical metabolic pathway for optimal dengue virus (DENV) replication. However, little is known concerning the effect of glucose on DENV replication in mosquitoes. In this study, we investigated the impact of glucose on DENV replication in mosquitoes Aedes aegypti.

Methods
Mosquitoes (Ae. aegypti UGAL/Rockefeller strain) were orally infected with DENV (serotype 2, 16681 strain) through infectious blood feeding. The DENV infection and transmission rates were determined by examining mosquito bodies and saliva, respectively, for DENV positivity at different time points after infection. In addition, a reverse genetic approach was applied by introducing double-stranded RNA against genes of interest into the mosquitoes to inhibit gene expression.

Results
Our data revealed a significant increase of DENV genome levels in mosquitoes consuming an infectious blood meal supplemented with glucose, suggesting that blood glucose is an important factor for viral replication. Interestingly, a significant increase of DENV E protein levels was detected in the saliva 4 days faster in mosquitoes that consumed infectious blood meals supplemented with glucose than in those consuming infectious blood meals alone. Furthermore, we perform RNAi to silence AKT or TOR and investigate the molecular mechanism regulating the glucose-mediated enhancement of viral replication. Silencing of AKT or TOR significantly reduced DENV titers in mosquitoes.

Conclusions
This study suggested that blood glucose is beneficial to DENV replication and that it facilitates virus transmission in mosquitoes via AKT and TOR signaling. Therefore, our results strengthen our understanding of dengue fever and DM co-morbidity and possibly reveal new targets for specific antiviral therapies.

Graphical abstract
Automated procedure assessing the accuracy of HRCT–PET registration applied in functional virtual bronchoscopy
Authors: Opposits Gábor , Nagy Marianna , Barta Zoltán , Aranyi Csaba , Szabó Dániel , Makai Attila , Varga Imre , Galuska László , Trón Lajos , Balkay László , Emri Miklós 
Published: July 2021

Abstract
Background
Bronchoscopy serves as direct visualisation of the airway. Virtual bronchoscopy provides similar visual information using a non-invasive imaging procedure(s). Early and accurate image-guided diagnosis requires the possible highest performance, which might be approximated by combining anatomical and functional imaging. This communication describes an advanced functional virtual bronchoscopic (fVB) method based on the registration of PET images to high-resolution diagnostic CT images instead of low-dose CT images of lower resolution obtained from PET/CT scans. PET/CT and diagnostic CT data were collected from 22 oncological patients to develop a computer-aided high-precision fVB. Registration of segmented images was performed using elastix.

Results
For virtual bronchoscopy, we used an in-house developed segmentation method. The quality of low- and high-dose CT image registrations was characterised by expert’s scoring the spatial distance of manually paired corresponding points and by eight voxel intensity-based (dis)similarity parameters. The distribution of (dis)similarity parameter correlating best with anatomic scoring was bootstrapped, and 95% confidence intervals were calculated separately for acceptable and insufficient registrations. We showed that mutual information (MI) of the eight investigated (dis)similarity parameters displayed the closest correlation with the anatomy-based distance metrics used to characterise the quality of image registrations. The 95% confidence intervals of the bootstrapped MI distribution were [0.15, 0.22] and [0.28, 0.37] for ﻿insufficient and acceptable registrations, respectively. In case of any new patient, a calculated MI value of registered low- and high-dose CT image pair within the [0.28, 0.37] or the [0.15, 0.22] interval would suggest acceptance or rejection, respectively, serving as an aid for the radiologist.

Conclusion
A computer-aided solution was proposed in order to reduce reliance on radiologist’s contribution for the approval of acceptable image registrations.
The zeros of monotone operators for the variational inclusion problem in Hilbert spaces
Authors: Tianchai Pattanapong 
Published: July 2021

AbstractIn this paper, we introduce a regularization method for solving the variational inclusion problem of the sum of two monotone operators in real Hilbert spaces. We suggest and analyze this method under some mild appropriate conditions imposed on the parameters, which allow us to obtain a short proof of another strong convergence theorem for this problem. We also apply our main result to the fixed point problem of the nonexpansive variational inequality problem, the common fixed point problem of nonexpansive strict pseudocontractions, the convex minimization problem, and the split feasibility problem. Finally, we provide numerical experiments to illustrate the convergence behavior and to show the effectiveness of the sequences constructed by the inertial technique.
S-derivative of perturbed mapping and solution mapping for parametric vector equilibrium problems
Authors: Deng Xicai , Zhao Wei 
Published: July 2021

AbstractIn this paper, we deal with the sensitivity analysis in vector equilibrium problems by using the S-derivative of a set-valued mapping. We first investigate the S-derivative on a kind of set-valued gap function for the vector equilibrium problems. Based on these results, S-derivative estimations on a perturbed mapping for the parametric vector equilibrium problem are given. Moreover, we provide some examples to illustrate the obtained results. Finally, we derive the S-derivative estimations of a solutions mapping of the parametric vector equilibrium problems via S-derivative estimations of a kind of the parametric variational system.
Metadata schema and ontology for capturing and processing of 3D cultural heritage objects
Authors: Homburg Timo , Cramer Anja , Raddatz Laura , Mara Hubert 
Published: July 2021

Abstract
Motivated by the increased use of 3D acquisition of objects by cultural heritage institutions, we were investigating ontologies and metadata schemes for the acquisition process to provide details about the 3D capturing, which can be combined with preexisting ontologies describing an object. Therefore we divided the 3D capturing workflow into common steps starting with the object being placed in front of a 3D scanner to preparation and publication of the 3D datasets and/or derived images. While the proposed ontology is well defined on a coarse level of detail for very different techniques, e.g. Stucture from Motion and LiDAR we elaborated the metadata scheme in very fine detail for 3D scanners available at our institutions. This includes practical experiments with measurement data from past and current projects including datasets published at Zenodo as guiding examples and the source code for their computation. Additionally, the free and Open Source GigaMesh Software Framework’s analysis and processing methods have been extended to provide metadata about the 3D processing steps like mesh cleaning as well as 2D image generation. Finally, we discuss the current limitations and give an outlook about future extensions.
Interdisciplinary approach to studying written nomadic sources in the context of modern historiology
Authors: Ibrayeva Akmaral , Temirkhanova Assemgul , Kartova Zaure , Sadykov Tlegen , Abuov Nurbolat , Pleshakov Anatoliy 
Published: July 2021

Abstract
This article uses an interdisciplinary approach to analyze textual sources from nomadic civilization. Linguistic analysis has been increasingly used due to the emergence of a huge array of autochthonous and authentic written sources. It is impossible to extract the necessary historical information from those sources without using a new research method. This study aims to apply discourse analysis to medieval textual sources called edicts published in 1400–1635 by the leaders of the Central Asian states. This approach is expected to enable a detailed study of the structure of edicts, as well as speech patterns and terms used in the text. The results of the study revealed the structure of the examined edicts, as well as socio-cultural, economic, and communicative features of the nomadic society. First, the discourse repertoire of Edicts from Sygnak is rather unique, as evidenced by comparative analysis of patents from the cities of Sygnak, Sayram and Turkestan located in the Syr Darya basin. Second, edicts in this study reflect the result of the mutual influence of sedentary and mobile lifeways. Third, the arguments behind certain speech patterns used in the examined edicts emerged under the influence of Turkic traditions.
Net-exergetic, hydraulic and thermal optimization of coaxial heat exchangers using fixed flow conditions instead of fixed flow rates
Authors: Blanke Tobias , Hagenkamp Markus , Döring Bernd , Göttsche Joachim , Reger Vitali , Kuhnhenne Markus 
Published: July 2021

AbstractPrevious studies optimized the dimensions of coaxial heat exchangers using constant mass flow rates as a boundary condition. They show a thermal optimal circular ring width of nearly zero. Hydraulically optimal is an inner to outer pipe radius ratio of 0.65 for turbulent and 0.68 for laminar flow types. In contrast, in this study, flow conditions in the circular ring are kept constant (a set of fixed Reynolds numbers) during optimization. This approach ensures fixed flow conditions and prevents inappropriately high or low mass flow rates. The optimization is carried out for three objectives: Maximum energy gain, minimum hydraulic effort and eventually optimum net-exergy balance. The optimization changes the inner pipe radius and mass flow rate but not the Reynolds number of the circular ring. The thermal calculations base on Hellström’s borehole resistance and the hydraulic optimization on individually calculated linear loss of head coefficients. Increasing the inner pipe radius results in decreased hydraulic losses in the inner pipe but increased losses in the circular ring. The net-exergy difference is a key performance indicator and combines thermal and hydraulic calculations. It is the difference between thermal exergy flux and hydraulic effort. The Reynolds number in the circular ring is instead of the mass flow rate constant during all optimizations. The result from a thermal perspective is an optimal width of the circular ring of nearly zero. The hydraulically optimal inner pipe radius is 54% of the outer pipe radius for laminar flow and 60% for turbulent flow scenarios. Net-exergetic optimization shows a predominant influence of hydraulic losses, especially for small temperature gains. The exact result depends on the earth’s thermal properties and the flow type. Conclusively, coaxial geothermal probes’ design should focus on the hydraulic optimum and take the thermal optimum as a secondary criterion due to the dominating hydraulics.
Molar mass determination of lignins and characterization of their polymeric structures by multi-detector gel permeation chromatography
Authors: Gaugler Evamaria C. , Radke Wolfgang , Vogt Andrew P. , Smith Dawn A. 
Published: July 2021

AbstractMolar masses, Mark-Houwink-Sakurada (MHS) exponents, and refractive index increments (dn/dc) for three lignins were determined without derivatization by multi-detector gel permeation chromatography (GPC) in dimethylformamide (DMF) with 0.05 M lithium bromide (LiBr). The lack of effectiveness of fluorescence filters on molar mass determination by GPC-multi-angle laser light scattering (MALS) was confirmed for softwood kraft lignin (Indulin AT) and revealed for mixed hardwood organosolv lignin (Alcell) as well as soda straw/grass lignin (Protobind 1000). GPC with viscometry detection confirmed that these lignins were present as compact molecules. The MHS exponent α for Indulin AT and Alcell was in the order of 0.1. Additionally, the intrinsic viscosity of Protobind 1000 for a given molar mass was much lower than that of either Alcell or Indulin AT. This is the first report of dn/dc values for these three lignins in DMF with 0.05 M LiBr.
Effectiveness and costs of interventions to reduce the within-farm Toxoplasma gondii seroprevalence on pig farms in the Netherlands
Authors: Eppink Dorien M. , Wisselink Henk J. , Krijger Inge M. , van der Giessen Joke W.B. , Swanenburg Manon , van Wagenberg Coen P.A. , van Asseldonk Marcel A.P.M. , Bouwknegt Martijn 
Published: July 2021

AbstractBackgroundThe parasiteToxoplasma gondii (T. gondii)is recognized as one of the major foodborne pathogens with a high human disease burden. To controlT. gondiiinfections in pigs, European Food Safety Agency (EFSA) advises serological testing of pigs and audits of pig farms to identify risk factors forT. gondiiinfection. In line with this approach, the aim of the current study was to assess the effectiveness and costs of intervention measures implemented to reduce theT. gondiiseroprevalence on finishing pig farms in the Netherlands. A crossover clinical trial was conducted at five case farms were their own control and the cross-over moment was the implementation of interventions to reduce risk factors. Each of the case farms had a farm-specific intervention strategy with one principal intervention measure (neutering of cats, professional rodent control or covering food storage).ResultsAll finishing pig farms (n = 5) showed a reduction inT. gondiiseroprevalence within one year of implementing the intervention strategy. Cat neutering (n = 3) and feed coverage (n = 1) showed statistically significant reductions in seroprevalence. Rodent control (n = 1) did not show a statistically significant reduction. The estimated reduction in seroprevalence in response to the neutering of cats and feed coverage were 67 and 96 %, respectively.ConclusionsOur work demonstrates that it is possible to reduce the within-farmT. gondiiseroprevalence within one year after interventions were implemented to reduceT. gondiirisk factors. This information is essential and encouraging for policy makers, food business operators, and farmers to implement in their risk assessment and to apply to food safety control systems.