bluuebunny/crossref_metadata_2025_split huggingface dataset:
A requirements elicitation process for a purposeful general aviation (GA) aircraft design based on emerging economies
Authors: Khandoker A. , Hamid M.A. , Shahriar A.S. , Rahman A.T.S. , Gessl G. 
Published: October 2021

AbstractDesign success mostly depends on understanding and realising product requirements, which are nested with different levels of stakeholders and specific market demands. Emerging markets are volatile and non-linear for understanding user-specific needs, particularly related to aircraft design. We attempt herein to elicit specific requirements through a proposed requirements elicitation process based on functional, physical and behavioural viewpoints. An evaluation of those critical requirements is also performed through Quality Function Deployment (QFD) to reveal the fitness of the customer requirements (raw requirements) in relation to the technical measures. After selecting all projected potential users, a Systems Modelling Language (SysML) use-case diagram is also summarised to illustrate the user’s relation to the system functions. Some raw requirements are verified through constraint analysis and cost examination as an exemplary approach to present the transformation from raw to final requirements. The data are collected and analysed to construct the aircraft’s key specifications. Most importantly, how to identify good requirements that define the needs, attainability, clarity and verifiability is demonstrated.In addition, it is demonstrated through this study that there is a need of a specific type of general aviation aircraft that may fulfil the unique demands of emerging economies by satisfying their socio-economic conditions.
Observation and modelling of stimulated Raman scattering driven by an optically smoothed laser beam in experimental conditions relevant for shock ignition
Authors: Cristoforetti G. , Hüller S. , Koester P. , Antonelli L. , Atzeni S. , Baffigi F. , Batani D. , Baird C. , Booth N. , Galimberti M. , Glize K. , Héron A. , Khan M. , Loiseau P. , Mancelli D. , Notley M. , Oliveira P. , Renner O. , Smid M. , Schiavi A. , Tran G. , Woolsey N. C. , Gizzi L. A. 
Published: October 2021

Abstract
We report results and modelling of an experiment performed at the Target Area West Vulcan laser facility, aimed at investigating laser–plasma interaction in conditions that are of interest for the shock ignition scheme in inertial confinement fusion (ICF), that is, laser intensity higher than

${10}^{16}$

$\mathrm{W}/{\mathrm{cm}}^2$

impinging on a hot (

$T>1$

keV), inhomogeneous and long scalelength pre-formed plasma. Measurements show a significant stimulated Raman scattering (SRS) backscattering (

$\sim 4\%{-}20\%$

of laser energy) driven at low plasma densities and no signatures of two-plasmon decay (TPD)/SRS driven at the quarter critical density region. Results are satisfactorily reproduced by an analytical model accounting for the convective SRS growth in independent laser speckles, in conditions where the reflectivity is dominated by the contribution from the most intense speckles, where SRS becomes saturated. Analytical and kinetic simulations well reproduce the onset of SRS at low plasma densities in a regime strongly affected by non-linear Landau damping and by filamentation of the most intense laser speckles. The absence of TPD/SRS at higher densities is explained by pump depletion and plasma smoothing driven by filamentation. The prevalence of laser coupling in the low-density profile justifies the low temperature measured for hot electrons (

$7\!{-}\!12$

keV), which is well reproduced by numerical simulations.
Impact of number of lumens in central-venous catheters on central-line bloodstream infection (CLABSI) and venous thromboembolism (VTE) risk in patients with acute leukemia
Authors: Varabyeva Alina , Lo Christabel Pui-See , Brancaccio Adamo , Perissinotti Anthony J. , Patel Twisha , Sandison Katie , Benitez Lydia L. , Pettit Kristen , Burke Patrick W. , Bixby Dale L. , Marini Bernard L. 
Published: October 2021

AbstractThis retrospective study was conducted to determine whether the number of peripherally inserted central-catheter lumens affected the rate of central-line associated bloodstream infections (CLABSIs) in adult patients with acute leukemia. The results show that CLABSI rates were not significantly different between patients with triple-lumen or double-lumen PICCs (22.1% vs 23.4%; P = .827).
Influence of fluid pressure changes on the reactivation potential of pre-existing fractures: a case study in the Archaean metavolcanics of the Chitradurga region, India
Authors: Bhowmick Sreyashi , Mondal Tridib Kumar 
Published: October 2021

AbstractThe metavolcanics of Chitradurga region host numerous shallow crustal veins and fractures and faults of multiple orientations. Several high and lowPfcycles have been recorded in the region, leading to the reactivation of most of the pre-existing fractures for highPfand selective reactivation of some well-oriented fractures under lowPfconditions. The pre-existing anisotropy (magnetic fabric) in the metavolcanics acted as the most prominent planar fabric for fracture propagation and vein emplacement under both conditions, thereby attaining maximum vein thickness. In this study, we emphasize the reactivation propensity of these pre-existing fracture planes under conditions of fluid pressure variation, related to the high and lowPfcycles. Multiple cycles of fluid-induced fracture reactivation make it difficult to quantify the maximum/minimum fluid pressure magnitudes. However, in this study we use the most appropriate fluid pressure magnitudes mathematically feasible for a shallow crustal depth of ∼2.4 km. We determine the changes in the reactivation potential with states of stress for the respective fracture orientations under both high and lowPfconditions. Dependence of fluid pressure variation on the opening angle of the fractures is also monitored. Finally, we comment on the failure mode and deformation behaviour of the fractures within the prevailing stress field inducing volumetric changes at the time of deformation. We find that deformation behaviour is directly related to the dip of the fracture planes.
Exploration of factors associated with spatial−temporal veterinary surveillance diagnoses of rumen fluke (Calicophoron daubneyi) infections in ruminants using zero-inflated mixed modelling
Authors: Jones Rhys Aled , Williams Hefin Wyn , Mitchell Sian , Robertson Sara , Macrelli Michele 
Published: October 2021

AbstractRumen fluke (Calicophoron daubneyi) has emerged as a prominent parasite of ruminants in Europe over the past decades. Epidemiological questions remain regarding this observed increase in prevalence as well as the prospect for future paramphistomosis risk. This study aimed to identify factors associated with the temporal−spatial prevalence of rumen fluke as measured by veterinary surveillance in a temperate region using zero-inflated negative binomial mixed modelling. Modelling revealed that summer rainfall, raindays and sunshine hours and mean winter temperature as significant positively associated climate variables for rumen fluke prevalence over space and time (P< 0.05). Rumen fluke prevalence was also higher in counties with higher cattle/sheep densities and was positively associated with rumen fluke case rates in the previous years (P< 0.05). Equivalent models for fasciolosis prevalence revealed no significant association with winter temperature and sunshine hours, (P> 0.05). These results confirm a strong association between rainfall and the prevalence of both fluke species in a temperate environment, likely due to the role ofGalba truncatulaas their intermediate snail host. It also highlights the potential added importance of winter temperature and sunshine hours in rumen fluke epidemiology when compared to liver fluke.
Organoids as host models for infection biology – a review of methods
Authors: Aguilar Carmen , Alves da Silva Marta , Saraiva Margarida , Neyazi Mastura , Olsson I. Anna S. , Bartfeld Sina 
Published: October 2021

AbstractInfectious diseases are a major threat worldwide. With the alarming rise of antimicrobial resistance and emergence of new potential pathogens, a better understanding of the infection process is urgently needed. Over the last century, the development of in vitro and in vivo models has led to remarkable contributions to the current knowledge in the field of infection biology. However, applying recent advances in organoid culture technology to research infectious diseases is now taking the field to a higher level of complexity. Here, we describe the current methods available for the study of infectious diseases using organoid cultures.
Organoids in image-based phenotypic chemical screens
Authors: Lukonin Ilya , Zinner Marietta , Liberali Prisca 
Published: October 2021

AbstractImage-based phenotypic screening relies on the extraction of multivariate information from cells cultured under a large variety of conditions. Technical advances in high-throughput microscopy enable screening in increasingly complex and biologically relevant model systems. To this end, organoids hold great potential for high-content screening because they recapitulate many aspects of parent tissues and can be derived from patient material. However, screening is substantially more difficult in organoids than in classical cell lines from both technical and analytical standpoints. In this review, we present an overview of studies employing organoids for screening applications. We discuss the promises and challenges of small-molecule treatments in organoids and give practical advice on designing, running, and analyzing high-content organoid-based phenotypic screens.
Gastrointestinal cancer organoids—applications in basic and translational cancer research
Authors: Seidlitz Therese , Stange Daniel E. 
Published: October 2021

AbstractCancer is a major health problem and a leading cause of death worldwide. Early cancer detection and continuous changes in treatment strategies have improved overall patient survival. The recent development of targeted drugs offers new opportunities for personalized cancer treatment. Nevertheless, individualized treatment is accompanied by the need for biomarkers predicting the response of a patient to a certain drug. One of the most promising breakthroughs in recent years that might help to overcome this problem is the organoid technology. Organoid cultures exhibit self-renewal capacity, self-organization, and long-term proliferation, while recapitulating many aspects of their primary tissue. Generated patient-derived organoid (PDO) libraries constitute “living” biobanks, allowing the in-depth analysis of tissue function, development, tumor initiation, and cancer pathobiology. Organoids can be derived from all gastrointestinal tissues, including esophageal, gastric, liver, pancreatic, small intestinal and colorectal tissues, and cancers of these tissues. PDOs are amenable to various techniques, including sequencing analyses, drug screening, targeted therapy testing, tumor microenvironment studies, and genetic engineering capabilities. In this review, we discuss the different applications of gastrointestinal organoids in basic cancer biology and clinical translation.
The culture of research communication in neonatal intensive care units: key stakeholder perspectives
Authors: Degl Jennifer , Ariagno Ronald , Aschner Judy , Beauman Sandra , Eklund Wakako , Faro Elissa , Iwami Hiroko , Jackson Yamile , Kenner Carole , Kim Ivone , Klein Agnes , Short Mary , Sorrells Keira , Turner Mark A. , Ward Robert , Winiecki Scott , Bucci-Rechtweg Christina ,   International Neonatal Consortium
Published: October 2021

Abstract
Objective
To assess the perspectives of neonatologists, neonatal nurses, and parents on research-related education and communication practices in the neonatal intensive care unit (NICU).

Study design
Questionnaire circulated through interest groups and administered using the internet.

Results
323 respondents responded to the survey. 52 were neonatologists, 188 were neonatal nurses, and 83 were parents of NICU graduates. Analysis was descriptive. Differences were noted between stakeholder groups with respect to whether current medications meet the needs of sick neonates, research as central to the mission of the NICU, availability of appropriate education/training for all members of the research team, and adequacy of information provided to parents before, during, and after a research study is completed.

Conclusion
Engagement of nurses and parents at all stages of NICU research is currently suboptimal; relevant good practices, including education, should be shared among neonatal units.
Appropriate exercise level attenuates gut dysbiosis and valeric acid increase to improve neuroplasticity and cognitive function after surgery in mice
Authors: Lai Zhongmeng , Shan Weiran , Li Jun , Min Jia , Zeng Xianzhang , Zuo Zhiyi 
Published: October 2021

AbstractPostoperative cognitive dysfunction (POCD) affects the outcome of millions of patients each year. Aging is a risk factor for POCD. Here, we showed that surgery induced learning and memory dysfunction in adult mice. Transplantation of feces from surgery mice but not from control mice led to learning and memory impairment in non-surgery mice. Low intensity exercise improved learning and memory in surgery mice. Exercise attenuated surgery-induced neuroinflammation and decrease of gut microbiota diversity. These exercise effects were present in non-exercise mice receiving feces from exercise mice. Exercise reduced valeric acid, a gut microbiota product, in the blood. Valeric acid worsened neuroinflammation, learning and memory in exercise mice with surgery. The downstream effects of exercise included attenuating growth factor decrease, maintaining astrocytes in the A2 phenotypical form possibly via decreasing C3 signaling and improving neuroplasticity. Similar to these results from adult mice, exercise attenuated learning and memory impairment in old mice with surgery. Old mice receiving feces from old exercise mice had better learning and memory than those receiving control old mouse feces. Surgery increased blood valeric acid. Valeric acid blocked exercise effects on learning and memory in old surgery mice. Exercise stabilized gut microbiota, reduced neuroinflammation, attenuated growth factor decrease and preserved neuroplasticity in old mice with surgery. These results provide direct evidence that gut microbiota alteration contributes to POCD development. Valeric acid is a mediator for this effect and a potential target for brain health. Low intensity exercise stabilizes gut microbiota in the presence of insult, such as surgery.
Inhibiting microcephaly genes as alternative to microtubule targeting agents to treat brain tumors
Authors: Iegiani Giorgia , Di Cunto Ferdinando , Pallavicini Gianmarco 
Published: October 2021

AbstractMedulloblastoma (MB) and gliomas are the most frequent high-grade brain tumors (HGBT) in children and adulthood, respectively. The general treatment for these tumors consists in surgery, followed by radiotherapy and chemotherapy. Despite the improvement in patient survival, these therapies are only partially effective, and many patients still die. In the last decades, microtubules have emerged as interesting molecular targets for HGBT, as various microtubule targeting agents (MTAs) have been developed and tested pre-clinically and clinically with encouraging results. Nevertheless, these treatments produce relevant side effects since they target microtubules in normal as well as in cancerous cells. A possible strategy to overcome this toxicity could be to target proteins that control microtubule dynamics but are required by HGBT cells much more than in normal cell types. The genes mutated in primary hereditary microcephaly (MCPH) are ubiquitously expressed in proliferating cells, but under normal conditions are selectively required during brain development, in neural progenitors. There is evidence that MB and glioma cells share molecular profiles with progenitors of cerebellar granules and of cortical radial glia cells, in which MCPH gene functions are fundamental. Moreover, several studies indicate that MCPH genes are required for HGBT expansion. Among the 25 known MCPH genes, we focus this review on KNL1, ASPM, CENPE, CITK and KIF14, which have been found to control microtubule stability during cell division. We summarize the current knowledge about the molecular basis of their interaction with microtubules. Moreover, we will discuss data that suggest these genes are promising candidates as HGBT-specific targets.
PDZD-8 and TEX-2 regulate endosomal PI(4,5)P2 homeostasis via lipid transport to promote embryogenesis in C. elegans
Authors: Jeyasimman Darshini , Ercan Bilge , Dharmawan Dennis , Naito Tomoki , Sun Jingbo , Saheki Yasunori 
Published: October 2021

AbstractDifferent types of cellular membranes have unique lipid compositions that are important for their functional identity. PI(4,5)P2 is enriched in the plasma membrane where it contributes to local activation of key cellular events, including actomyosin contraction and cytokinesis. However, how cells prevent PI(4,5)P2 from accumulating in intracellular membrane compartments, despite constant intermixing and exchange of lipid membranes, is poorly understood. Using the C. elegans early embryo as our model system, we show that the evolutionarily conserved lipid transfer proteins, PDZD-8 and TEX-2, act together with the PI(4,5)P2 phosphatases, OCRL-1 and UNC-26/synaptojanin, to prevent the build-up of PI(4,5)P2 on endosomal membranes. In the absence of these four proteins, large amounts of PI(4,5)P2 accumulate on endosomes, leading to embryonic lethality due to ectopic recruitment of proteins involved in actomyosin contractility. PDZD-8 localizes to the endoplasmic reticulum and regulates endosomal PI(4,5)P2 levels via its lipid harboring SMP domain. Accumulation of PI(4,5)P2 on endosomes is accompanied by impairment of their degradative capacity. Thus, cells use multiple redundant systems to maintain endosomal PI(4,5)P2 homeostasis.
Preclinical characterization of an intravenous coronavirus 3CL protease inhibitor for the potential treatment of COVID19
Authors: Boras Britton , Jones Rhys M. , Anson Brandon J. , Arenson Dan , Aschenbrenner Lisa , Bakowski Malina A. , Beutler Nathan , Binder Joseph , Chen Emily , Eng Heather , Hammond Holly , Hammond Jennifer , Haupt Robert E. , Hoffman Robert , Kadar Eugene P. , Kania Rob , Kimoto Emi , Kirkpatrick Melanie G. , Lanyon Lorraine , Lendy Emma K. , Lillis Jonathan R. , Logue James , Luthra Suman A. , Ma Chunlong , Mason Stephen W. , McGrath Marisa E. , Noell Stephen , Obach R. Scott , O’ Brien Matthew N. , O’Connor Rebecca , Ogilvie Kevin , Owen Dafydd , Pettersson Martin , Reese Matthew R. , Rogers Thomas F. , Rosales Romel , Rossulek Michelle I. , Sathish Jean G. , Shirai Norimitsu , Steppan Claire , Ticehurst Martyn , Updyke Lawrence W. , Weston Stuart , Zhu Yuao , White Kris M. , García-Sastre Adolfo , Wang Jun , Chatterjee Arnab K. , Mesecar Andrew D. , Frieman Matthew B. , Anderson Annaliesa S. , Allerton Charlotte 
Published: October 2021

AbstractCOVID-19 caused by the SARS-CoV-2 virus has become a global pandemic. 3CL protease is a virally encoded protein that is essential across a broad spectrum of coronaviruses with no close human analogs. PF-00835231, a 3CL protease inhibitor, has exhibited potent in vitro antiviral activity against SARS-CoV-2 as a single agent. Here we report, the design and characterization of a phosphate prodrug PF-07304814 to enable the delivery and projected sustained systemic exposure in human of PF-00835231 to inhibit coronavirus family 3CL protease activity with selectivity over human host protease targets. Furthermore, we show that PF-00835231 has additive/synergistic activity in combination with remdesivir. We present the ADME, safety, in vitro, and in vivo antiviral activity data that supports the clinical evaluation of PF-07304814 as a potential COVID-19 treatment.
GproDIA enables data-independent acquisition glycoproteomics with comprehensive statistical control
Authors: Yang Yi , Yan Guoquan , Kong Siyuan , Wu Mengxi , Yang Pengyuan , Cao Weiqian , Qiao Liang 
Published: October 2021

AbstractLarge-scale profiling of intact glycopeptides is critical but challenging in glycoproteomics. Data independent acquisition (DIA) is an emerging technology with deep proteome coverage and accurate quantitative capability in proteomics studies, but is still in the early stage of development in the field of glycoproteomics. We propose GproDIA, a framework for the proteome-wide characterization of intact glycopeptides from DIA data with comprehensive statistical control by a 2-dimentional false discovery rate approach and a glycoform inference algorithm, enabling accurate identification of intact glycopeptides using wide isolation windows. We further utilize a semi-empirical spectrum prediction strategy to expand the coverage of spectral libraries of glycopeptides. We benchmark our method for N-glycopeptide profiling on DIA data of yeast and human serum samples, demonstrating that DIA with GproDIA outperforms the data-dependent acquisition-based methods for glycoproteomics in terms of capacity and data completeness of identification, as well as accuracy and precision of quantification. We expect that this work can provide a powerful tool for glycoproteomic studies.
Inhibition of CBP synergizes with the RNA-dependent mechanisms of Azacitidine by limiting protein synthesis
Authors: Diesch Jeannine , Le Pannérer Marguerite-Marie , Winkler René , Casquero Raquel , Muhar Matthias , van der Garde Mark , Maher Michael , Herráez Carolina Martínez , Bech-Serra Joan J. , Fellner Michaela , Rathert Philipp , Brooks Nigel , Zamora Lurdes , Gentilella Antonio , de la Torre Carolina , Zuber Johannes , Götze Katharina S. , Buschbeck Marcus 
Published: October 2021

AbstractThe nucleotide analogue azacitidine (AZA) is currently the best treatment option for patients with high-risk myelodysplastic syndromes (MDS). However, only half of treated patients respond and of these almost all eventually relapse. New treatment options are urgently needed to improve the clinical management of these patients. Here, we perform a loss-of-function shRNA screen and identify the histone acetyl transferase and transcriptional co-activator, CREB binding protein (CBP), as a major regulator of AZA sensitivity. Compounds inhibiting the activity of CBP and the closely related p300 synergistically reduce viability of MDS-derived AML cell lines when combined with AZA. Importantly, this effect is specific for the RNA-dependent functions of AZA and not observed with the related compound decitabine that is only incorporated into DNA. The identification of immediate target genes leads us to the unexpected finding that the effect of CBP/p300 inhibition is mediated by globally down regulating protein synthesis.