bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiscale modelling of Potts shunt as a potential palliative treatment for suprasystemic idiopathic pulmonary artery hypertension: a paediatric case study
Authors: Pant Sanjay , Sizarov Aleksander , Knepper Angela , Gossard Gaëtan , Noferi Alberto , Boudjemline Younes , Vignon-Clementel Irene 
Published: January 2022

AbstractPotts shunt (PS) was suggested as palliation for patients with suprasystemic pulmonary arterial hypertension (PAH) and right ventricular (RV) failure. PS, however, can result in poorly understood mortality. Here, a patient-specific geometrical multiscale model of PAH physiology and PS is developed for a paediatric PAH patient with stent-based PS. In the model, 7.6mm-diameter PS produces near-equalisation of the aortic and PA pressures and $$Q_p/Q_s$$

Q
p

/

Q
s

(oxygenated vs deoxygenated blood flow) ratio of 0.72 associated with a 16% decrease of left ventricular (LV) output and 18% increase of RV output. The flow from LV to aortic arch branches increases by 16%, while LV contribution to the lower body flow decreases by 29%. Total flow in the descending aorta (DAo) increases by 18% due to RV contribution through the PS with flow into the distal PA branches decreasing. PS induces 18% increase of RV work due to its larger stroke volume pumped against lower afterload. Nonetheless, larger RV work does not lead to increased RV end-diastolic volume. Three-dimensional flow assessment demonstrates the PS jet impinging with a high velocity and wall shear stress on the opposite DAo wall with the most of the shunt flow being diverted to the DAo. Increasing the PS diameter from 5mm up to 10mm results in a nearly linear increase in post-operative shunt flow and a nearly linear decrease in shunt pressure-drop. In conclusion, this model reasonably represents patient-specific haemodynamics pre- and post-creation of the PS, providing insights into physiology of this complex condition, and presents a predictive tool that could be useful for clinical decision-making regarding suitability for PS in PAH patients with drug-resistant suprasystemic PAH.
Flight plan for the future: floatplane pilots and researchers team up to predict invasive species dispersal in Alaska
Authors: Schwoerer Tobias , Dial Roman J. , Little Joseph M. , Martin Aaron E. , Morton John M. , Schmidt Jennifer I. , Ward Eric J. 
Published: January 2022

AbstractAircraft can transport aquatic invasive species (AIS) from urban sources to remote waterbodies, yet little is known about this long-distance pathway. In North America and especially Alaska, aircraft with landing gear for water called floatplanes are used for recreation access to remote, often road-less wilderness destinations. Human-mediated dispersal of AIS is particularly concerning for the conservation of pristine wildlands, yet resource managers are often challenged by limited monitoring and response capacity given the vast areas they manage. We collected pathway data through a survey with floatplane pilots and used a Bayesian hierarchical model to inform early detection in a data-limited situation. The study was motivated by Alaska’s first known AIS, Elodea spp. (Elodea) and its floatplane-related dispersal. For 682 identified floatplane destinations, a Bayesian hierarchical model predicts the chance of flights originating from AIS source locations in freshwater and estimates the expected number of flights from these sources. Model predictions show the potential for broad spread across remote regions currently not known to have Elodea and informed monitoring and early detection efforts. Our result underlines the small window of opportunity for Arctic conservation strategies targeting an AIS free Arctic. We recommend management that focuses on long-distance connectivity, keeping urban sources free of AIS. We discuss applicability of the approach for other data-limited situations supporting data-informed AIS management responses.
“You Have to be Resilient”: A Qualitative Study Exploring Advice Newcomer Youth Have for Other Newcomer Youth
Authors: Smith Alexandra C. G. , Crooks Claire V. , Baker Linda 
Published: January 2022

AbstractResearch infrequently includes the perspectives of vulnerable and marginalized youth. As the population of newcomer youth in Canada continues to grow, it is imperative that attention is devoted not only to challenges they experience, but also to resilience factors they perceive to support their adjustment and well-being. To address this gap, this qualitative research explored newcomer youths’ experiences and advice for other newcomer youth who have recently arrived in Canada. Thirty-seven newcomer youth from two medium-sized cities in Ontario participated in focus groups. Participants ranged from 14 to 22 in age and identified mostly as female refugees from the Middle East. Through thematic analysis, five overarching themes were found across groups: (1) moving to a new country is hard, (2) maintain a healthy mindset, (3) take an active role in the adjustment process, (4) stay true to who you are, (5) and you are not alone. Youth described hardships that make moving to a new country difficult including lack of belonging due to racism and bullying, insufficient orientation to new systems, language barriers, and high levels of stress. Findings demonstrated youths’ resilience, coping skills, and strategies to lead meaningful lives. Youth discussed resilience strategies such as maintaining a connection with home culture and religion, reframing thinking to be positive, receiving emotional support, accessing community support at newcomer agencies, and building language proficiency. Findings provide implications for professionals working with newcomer youth and reflect the importance of addressing structural barriers and racism. The opportunity for newcomer youth to share experiences as experts in research may also help to promote resilience.
Synthesis and characterization of TEMPO-oxidized peptide-cellulose conjugate biosensors for detecting human neutrophil elastase
Authors: Mackin Robert T. , Fontenot Krystal R. , Edwards J. Vincent , Prevost Nicolette T. , Grimm Casey , Condon Brian D. , Liebner Falk , Jordan Jacobs H. , Easson Michael W. , French Alfred D. 
Published: January 2022

AbstractHere we describe the synthesis and characterization of a peptide-cellulose conjugate biosensor based on TEMPO-oxidized nanofibrillated cellulose (tNFC) for detecting elevated levels of human neutrophil elastase (HNE) in chronic wounds. The fluorescent peptide HNE substrate constructed from n-succinyl-Ala-Pro-Ala-7-amino-4-methyl-coumarin was attached to the TEMPO-oxidized cellulose surface via polyethylene glycol linker. The characterization of the biosensor conjugate shows a high degree of peptide incorporation onto the surface with the degree of substitution of 0.057. The relatively small crystallite size of 26.0 Å compared to other cellulose- and nanocellulose-based materials leads to a large specific surface area which can promote access of HNE to the enzyme substrates due to decreased steric interactions. Likewise, the porosity for tNFC was found to be higher than all other samples, including the nanocellulosic aerogel, lending to its hydrogel-like nature. The properties of tNFC were compared to other cellulose-based materials. The volume of each crystallite and volume ratio to the largest sample was calculated. tNFC was found to occupy the smallest space resulting in high amounts of sensors per crystallite unit volume. With a small crystallite volume and large number of sensors, the tNFC peptide-cellulose conjugate biosensor could provide a more sensitive system and is a good candidate for point of care diagnostic devices for detecting elevated protease levels in humans.
The effect of the low stromal ratio induced by neoadjuvant chemotherapy on recurrence patterns in borderline resectable pancreatic ductal adenocarcinoma
Authors: Kawahara Kenji , Takano Shigetsugu , Furukawa Katsunori , Takayashiki Tsukasa , Kuboki Satoshi , Ohtsuka Masayuki 
Published: January 2022

AbstractThe optimal regimens of neoadjuvant chemotherapy (NAC) and its biological and physiological modification of the tumor microenvironment (TME) in patients with borderline resectable pancreatic ductal adenocarcinoma (BR PDAC) remain unknown. A deeper understanding of the complex stromal biology of the TME will identify new avenues to establish treatment strategies for PDAC patients. Herein, we sought to clarify whether stromal remodeling by NAC affects recurrence patterns and prognosis in BR PDAC patients. We retrospectively analyzed data from 104 BR PDAC patients who underwent pancreatectomy with or without NAC (upfront surgery [UpS], n = 44; gemcitabine + nab-paclitaxel [GnP], n = 28; and gemcitabine + S-1 [GS], n = 32) to assess the correlations of treatment with early recurrence, the stromal ratio, and Ki-67 levels. Eighty-six patients experienced recurrence, and those with liver metastasis had significantly shorter recurrence-free survival than those with other recurrence patterns. The frequency of liver metastasis was significantly higher in patients with a low stromal ratio than in those with a high stromal ratio in the NAC group but not in the UpS group. Patients in the GnP group had significantly higher Ki-67 than those in the GS and UpS groups. A low stromal ratio was positively correlated with high Ki-67 in the NAC group but not in the UpS group. The low stromal ratio induced by NAC promoted early liver metastasis in patients with BR PDAC. Our findings provide new insights into the complexity of stromal biology, leading to consideration of the optimal NAC regimen.
The Denotation of Copredicative Nouns
Authors: Ortega-Andrés Marina 
Published: January 2022

AbstractCopredication is the phenomenon whereby two or more predicates seem to require that their argument denotes different things. The denotation of words that copredicate has been broadly discussed. In this paper, I investigate the metaphysics behind this question. Thus, mereological theories of dot objects claim that these nouns denote complex entities; Asher (Lexical
meaning in context, Cambridge University Press, 2011, https://doi.org/10.1017/CBO9780511793936) thinks that they denote bare particulars; and the Activation Package Theory contends that they stand for multiple denotations. According to the Activation Package Theory, copredicative nouns stand for complex knowledge structures that offer a range of multiple potential denotations. In this paper, I claim that the Activation Package Theory contributes to solve some of the metaphysical questions that arise from copredication.
Exploring the folding energy landscapes of heme proteins using a hybrid AWSEM-heme model
Authors: Chen Xun , Lu Wei , Tsai Min-Yeh , Jin Shikai , Wolynes Peter G. 
Published: January 2022

AbstractHeme is an active center in many proteins. Here we explore computationally the role of heme in protein folding and protein structure. We model heme proteins using a hybrid model employing the AWSEM Hamiltonian, a coarse-grained forcefield for the protein chain along with AMBER, an all-atom forcefield for the heme. We carefully designed transferable force fields that model the interactions between the protein and the heme. The types of protein–ligand interactions in the hybrid model include thioester covalent bonds, coordinated covalent bonds, hydrogen bonds, and electrostatics. We explore the influence of different types of hemes (heme b and heme c) on folding and structure prediction. Including both types of heme improves the quality of protein structure predictions. The free energy landscape shows that both types of heme can act as nucleation sites for protein folding and stabilize the protein folded state. In binding the heme, coordinated covalent bonds and thioester covalent bonds for heme c drive the heme toward the native pocket. The electrostatics also facilitates the search for the binding site.
Seasonal Betacoronavirus Antibodies’ Expansion Post-BNT161b2 Vaccination Associates with Reduced SARS-CoV-2 VoC Neutralization
Authors: Dispinseri Stefania , Marzinotto Ilaria , Brigatti Cristina , Pirillo Maria Franca , Tolazzi Monica , Bazzigaluppi Elena , Canitano Andrea , Borghi Martina , Gallinaro Alessandra , Caccia Roberta , Vercesi Riccardo , McKay Paul F. , Ciceri Fabio , Piemonti Lorenzo , Negri Donatella , Cinque Paola , Cara Andrea , Scarlatti Gabriella , Lampasona Vito 
Published: January 2022

AbstractSARS-CoV-2 vaccination is known to induce antibodies that recognize also variants of concerns (VoCs) of the virus. However, epidemiological and laboratory evidences indicate that these antibodies have a reduced neutralization ability against VoCs. We studied binding and neutralizing antibodies against the Spike protein domains and subunits of the Wuhan-Hu-1 virus and its alpha, beta, delta VoCs and of seasonal betacoronaviruses (HKU1 and OC43) in a cohort of 31 health care workers prospectively followed post-vaccination with BNT162b2-Comirnaty. The study of sequential samples collected up to 64 days post-vaccination showed that serological assays measuring IgG against Wuhan-Hu-1 antigens were a poor proxy for VoC neutralization. In addition, in subjects who had asymptomatic or mild COVID-19 prior to vaccination, the loss of nAbs following disease could be rapid and accompanied by post-vaccination antibody levels similar to those of naïve vaccinees. Interestingly, in health care workers naïve for SARS-CoV-2 infection, vaccination induced a rapid and transient reactivation of pre-existing seasonal coronaviruses IgG responses that was associated with a subsequent reduced ability to neutralize alpha and beta VoCs.
Development of a Blueprint for Integrated Care for Vulnerable Pregnant Women
Authors: Harmsen van der Vliet-Torij H. W. , Venekamp A. A. , van Heijningen-Tousain H. J. M. , Wingelaar-Loomans E. , Scheele J. , de Graaf J. P. , Lambregtse-van den Berg M. P. , Steegers E. A. P. , Goumans M. J. B. M. 
Published: January 2022

Abstract
Purpose
There has been increasing awareness of perinatal health and organisation of maternal and child health care in the Netherlands as a result of poor perinatal outcomes. Vulnerable women have a higher risk of these poor perinatal outcomes and also have a higher chance of receiving less adequate care. Therefore, within a consortium, embracing 100 organisations among professionals, educators, researchers, and policymakers, a joint aim was defined to support maternal and child health care professionals and social care professionals in providing adequate, integrated care for vulnerable pregnant women.

Description
Within the consortium, vulnerability is defined as the presence of psychopathology, psychosocial problems, and/or substance use, combined with a lack of individual and/or social resources. Three studies focussing on population characteristics, organisation of care and knowledge, skills, and attitudes of professionals regarding vulnerable pregnant women, were carried out. Outcomes were discussed in three field consultations.

Assessment
The outcomes of the studies, followed by the field consultations, resulted in a blueprint that was subsequently adapted to local operational care pathways in seven obstetric collaborations (organisational structures that consist of obstetricians of a single hospital and collaborating midwifery practices) and their collaborative partners. We conducted 12 interviews to evaluate the adaptation of the blueprint to local operational care pathways and its’ embedding into the obstetric collaborations.

Conclusion
Practice-based research resulted in a blueprint tailored to the needs of maternal and child health care professionals and social care professionals and providing structure and uniformity to integrated care provision for vulnerable pregnant women.
Translational Modeling of Chloroquine and Hydroxychloroquine Dosimetry in Human Airways for Treating Viral Respiratory Infections
Authors: Kolli Aditya R. , Calvino-Martin Florian , Hoeng Julia 
Published: January 2022

Abstract
Purpose
Chloroquine and hydroxychloroquine are effective against respiratory viruses in vitro. However, they lack antiviral efficacy upon oral administration. Translation of in vitro to in vivo exposure is necessary for understanding the disconnect between the two to develop effective therapeutic strategies.

Methods
We employed an in vitro ion-trapping kinetic model to predict the changes in the cytosolic and lysosomal concentrations of chloroquine and hydroxychloroquine in cell lines and primary human airway cultures. A physiologically based pharmacokinetic model with detailed respiratory physiology was used to predict regional airway exposure and optimize dosing regimens.

Results
At their reported in vitro effective concentrations in cell lines, chloroquine and hydroxychloroquine cause a significant increase in their cytosolic and lysosomal concentrations by altering the lysosomal pH. Higher concentrations of the compounds are required to achieve similar levels of cytosolic and lysosomal changes in primary human airway cells in vitro. The predicted cellular and lysosomal concentrations in the respiratory tract for in vivo oral doses are lower than the in vitro effective levels. Pulmonary administration of aerosolized chloroquine or hydroxychloroquine is predicted to achieve high bound in vitro-effective concentrations in the respiratory tract, with low systemic exposure. Achieving effective cytosolic concentrations for activating immunomodulatory effects and adequate lysosomal levels for inhibiting viral replication could be key drivers for treating viral respiratory infections.

Conclusion
Our analysis provides a framework for extrapolating in vitro effective concentrations of chloroquine and hydroxychloroquine to in vivo dosing regimens for treating viral respiratory infections.

Graphical abstract
Integrating in vitro metabolomics with a 96-well high-throughput screening platform
Authors: Malinowska Julia M. , Palosaari Taina , Sund Jukka , Carpi Donatella , Bouhifd Mounir , Weber Ralf J. M. , Whelan Maurice , Viant Mark R. 
Published: January 2022

Abstract
Introduction
High-throughput screening (HTS) is emerging as an approach to support decision-making in chemical safety assessments. In parallel, in vitro metabolomics is a promising approach that can help accelerate the transition from animal models to high-throughput cell-based models in toxicity testing.

Objective
In this study we establish and evaluate a high-throughput metabolomics workflow that is compatible with a 96-well HTS platform employing 50,000 hepatocytes of HepaRG per well.

Methods
Low biomass cell samples were extracted for metabolomics analyses using a newly established semi-automated protocol, and the intracellular metabolites were analysed using a high-resolution spectral-stitching nanoelectrospray direct infusion mass spectrometry (nESI-DIMS) method that was modified for low sample biomass.

Results
The method was assessed with respect to sensitivity and repeatability of the entire workflow from cell culturing and sampling to measurement of the metabolic phenotype, demonstrating sufficient sensitivity (> 3000 features in hepatocyte extracts) and intra- and inter-plate repeatability for polar nESI-DIMS assays (median relative standard deviation < 30%). The assays were employed for a proof-of-principle toxicological study with a model toxicant, cadmium chloride, revealing changes in the metabolome across five sampling times in the 48-h exposure period. To allow the option for lipidomics analyses, the solvent system was extended by establishing separate extraction methods for polar metabolites and lipids.

Conclusions
Experimental, analytical and informatics workflows reported here met pre-defined criteria in terms of sensitivity, repeatability and ability to detect metabolome changes induced by a toxicant and are ready for application in metabolomics-driven toxicity testing to complement HTS assays.
Prenatal depression exposure alters white matter integrity and neurodevelopment in early childhood
Authors: Roos Annerine , Wedderburn Catherine J. , Fouche Jean-Paul , Joshi Shantanu H , Narr Katherine L , Woods Roger P , Zar Heather J , Stein Dan J. , Donald Kirsten A. 
Published: January 2022

AbstractPrenatal exposure to maternal depression increases the risk for onset of emotional and behavioral disorders in children. We investigated the effects of exposure to prenatal depression on white matter microstructural integrity at birth and at 2-3 years, and associated neurodevelopment. Diffusion-weighted images were acquired for children of the Drakenstein Child Health Study at 2-4 weeks postpartum (n=70, 47% boys) and at 2-3 years of age (n=60, 58% boys). Tract-Based Spatial Statistics was used to compare, using an ROI based approach, diffusion tensor metrics across groups defined by presence (>19 on Beck’s Depression Inventory and/or >12 on the Edinburgh Postnatal Depression Scale) or absence (below depression thresholds) of depression, and associations with neurodevelopmental measures at age 2-3 years were determined. We did not detect group differences in white matter integrity at neonatal age, but at 2-3 years, children in the exposed group demonstrated higher fractional anisotropy, and lower mean and radial diffusivity in association tracts compared to controls. This was notable in the sagittal stratum (radial diffusivity: p<0.01). Altered white matter integrity metrics were also observed in projection tracts, including the corona radiata, which associated with cognitive and motor outcomes in exposed 2-3-year-olds (p<0.05). Our findings of widespread white matter alterations in 2-3-year-old children with prenatal exposure to depression are consistent with previous findings, as well as with neuroimaging findings in adults with major depression. Further, we identified novel associations of altered white matter integrity with cognitive development in depression-exposed children, suggesting that these neuroimaging findings may have early functional impact.
Capacities of local maize seed enterprises in Mexico: Implications for seed systems development
Authors: Donovan Jason , Rutsaert Pieter , Domínguez Ciro , Peña Meliza 
Published: January 2022

AbstractWhere maize plays a critical role in food security, governments and donors have invested heavily in support of local, privately owned, often small and medium sized, maize seed enterprises (maize SMEs). Underpinning these investments are strong assumptions about maize SMEs’ capacity to produce and distribute seed to smallholders. This study assesses the capacities of 22 maize SMEs in Mexico that engaged with MasAgro—a large-scale development program initiated in 2011 that has provided maize SMEs with improved genetic material and technical assistance. Data were collected onsite from in-depth interviews with enterprise owners and managers and complemented with other primary and secondary sources. Overall, maize SMEs showed high levels of absorptive capacity for seed production, but limited signs of learning and innovation in terms of business organization and strategic seed marketing. Asset endowments varied widely among the SMEs, but generally they were lowest among the smaller enterprises, and access to business development services beyond MasAgro was practically nonexistent. Results highlighted the critical role of MasAgro in reinvigorating the portfolios of seeds produced by maize SMEs, as well as the challenges ahead for maize SMEs to scale the new technologies in a competitive market that has long been dominated by multinational seed enterprises. Among these challenges were limited investment in seed marketing, weak infrastructure for seed production, and limited experience in business management. Achieving the food security goals through maize SMEs will require making national maize seed industry development a strategic imperative.