bluuebunny/crossref_metadata_2025 huggingface dataset:
Overview study on challenges of additive manufacturing for a healthcare application
Authors: Adugna Y W , Akessa A D , Lemu H G
Published: November 2021

Additive manufacturing is a rapidly evolving manufacturing technology bringing numerous and wide opportunities for the design team involved in the process by creating intricate and customized products with saving labor, time, and other expenses. Innovative AM methods and numerous practical applications in aerospace, automotive, medical, energy, and other industries have been developed and commercialized through extensive research over the last two decades. One embraced industry among others that benefited from the advances of AM is the healthcare industry. This paper focuses on addressing the challenges and opportunities in Additive manufacturing for healthcare. Although there are advanced possibilities in AM, there are also numerous issues needed to be overcome. The paper is based upon the current state-of-the-art review and study visits. The purpose of this work has been to identify the opportunities and limitations associated with additive manufacturing in healthcare applications and to highlight the identified research needs.
Environment-assisted fatigue of steel bridges: A conceptual framework for life assessment
Authors: Sandviknes J S S , Adasooriya N D , Pavlou D , Hemmingsen T
Published: November 2021

This paper presents a framework based on a recently proposed fatigue strength curve of corroded steel to assess the life of an existing steel bridge exposed to environment-assisted fatigue. Environment-assisted cracking (EAC) and how it affects the structural integrity of steel bridges are introduced by the framework. Determination of both corroded and uncorroded details in a corrosive environment are also included in this framework. To conform the applicability and significance, a fatigue life of a railway bridge was assessed by methods given in the framework. The obtained fatigue lives were compared. The difference of the estimated fatigue lives emphasizes the importance of having this framework to consider the interaction of corrosion and fatigue mechanisms.
Mechanical response and strength characteristics of aluminum honeycomb sandwich panels for infrastructure engineering
Authors: Zaoutsos S P
Published: November 2021

The use of aluminium sandwich panels has been increased in a certain number of engineering applications from infrastructure systems and transportation to aircraft and naval engineering. Due to their structural efficiency these materials are ideal for applications where ratio of strength to weight is of crucial importance. In the current study the investigation of the strength characteristics of aluminium sandwich panels with aluminium honeycomb core and different types of skins is performed using both analytical models and experimental procedures. A series of strength tests such as tension, shear, three point bending and double cantilever beam were conducted on aluminium honeycomb-cored sandwich panel specimens with five different skins in order to examine the mode of failure and the mechanical behaviour of the structural elements. The experimental findings are compared to theoretical values while an attempt for the explanation of the mechanisms leading to failure such as buckling, delamination or debonding between core and skins is performed. The results occurring from the study are very useful for the enhancement of the mechanical behaviour of sandwich constructions, thus more intensive work must be carried out in order to understand the physical mechanisms leading to strength characteristics of sandwich panels.
Experimental and numerical evaluation of the axial capacity of cracked tubular members
Authors: Riise S , Vågen M R , Atteya M , Ersdal G
Published: November 2021

This paper presents the experimental and numerical results for the axial capacity of cracked tubular steel members. Experimental tests of 11 columns in compression with simulated cracks of different sizes, defined as the percentage of the circumference (12%, 23.5% and 38.5%). The crack-tips were further treated by drilling a crack arresting hole. These specimens were then modelled by finite element analysis which were verified to match the experimental test. The DNVGL-RP-C208 standard was used as basis for performing the numerical finite element analysis. In addition, the capacity of the columns was calculated according to the 2004 revision of the NORSOK N-004 standard. The experimental tests indicated that the capacity in compression did not change significantly with the presence of cracks and crack arresting holes. The results from the numerical finite element analysis show a good agreement with the experimental work. However, the compressive capacity according to NORSOK N-004 shows a significant deviation to the safe side.
Current methods of subsea production systems survey in the conditions of the Arctic region
Authors: Smirnov E , Kharchenko U
Published: November 2021

The development of deposits in the Arctic region and the Far Eastern shelf of Russia is complicated by the presence of ice conditions. The duration of the ice period can vary from 5 up to 9 months, during which the underwater equipment of the field is inaccessible for inspection and repair. This work discusses the methods of inspection and maintenance of subsea production systems that can be used in the development of Arctic deposits.
Status and needs for ice tank testing in a changing climate
Authors: Jochmann P , Ziemer G , Myland D , Reimer N , Hisette Q
Published: November 2021

150 years ago, the first modern icebreaker in the world was designed by the naval architect Carl Ferdinand Steinhaus and built for purpose of removing ice barriers on the river Elbe in Hamburg, Germany. No model tests were performed at that time. Later, in the first half of the 20th century, “model tests” for ships were carried out in natural ice on lakes. In the 1950th the first-generation ice model basins were put in operation and ice model testing became a standard method in the icebreaker design process. This paper discusses the influence of the economic and environmental development in arctic regions, driven by shipping and offshore activities in environmental changing Arctic Waters, on the ice model basin design, equipment and testing methods. The developments will be presented with examples from The Hamburg Ship Model Basin (HSVA). To complete the overview, an outlook to future trends is attempted.
Complex geodynamic indicators for forecasting hydrocarbon deposits in the arctic zone
Authors: Minaev V A , Stepanov R O , Faddeev A O
Published: November 2021

In the article, in relation to the Arctic zone of the Russian Federation, a new method of forecasting hydrocarbon deposits based on computer geodynamic modelling procedures is considered. It is less expensive compared to field and analytical methods. The approbation of the method on the example of the Laptev Sea shelf zone showed a good interpretability of its results and their compliance with the forecast obtained by other methods. The rationality of using six geodynamic indicators for forecasting: the distributions of vortex structures of the velocity vectors of horizontal shear deformations and vortex structures of normal linear deformations; the values of the velocity vectors of horizontal shear deformations and velocity vectors of horizontal normal linear deformations; the distributions of the anomalous gravitational field in isostatic reduction and the reduced temperature. The sequence of stages in determining the potential of hydrocarbon deposits in the studied territories is described, which is associated with the solution of six interrelated sequential tasks: the choice of local territorial areas of optimal size - the calculation of geodynamic indicators – the allocation of homogeneous territorial clusters – the detailing and improvement of geodynamic indicators – the determination of the potential of oil and gas fields in the cluster – the localization of oil and gas fields in each cluster – construction of a digital forecast map of the location of oil and gas fields in the study area.
Multi-functional oilfield production chemicals: maleic-based polymers for gas hydrate and corrosion inhibition
Authors: Kelland M A , Pomicpic J , Ghosh R , Undheim C , Hemmingsen T H , Zhang Q , Varfolomeev M A , Pavelyev R S , Vinogradova S S
Published: November 2021

Several chemical problems can occur during the production of oil and gas through flow lines. This includes corrosion, scale deposition and gas hydrate plugging. Three separate chemicals may be needed to treat these issues. Kinetic hydrate inhibitors (KHIs) are used in cold oil or natural gas production flow lines to prevent the formation and plugging of the line with gas hydrates. They are often injected concomitantly with other production chemicals such as corrosion and scale inhibitors. KHIs are specific low molecular weight water-soluble polymers with amphiphilic groups formulated with synergists and solvents. However, many corrosion inhibitors (CIs) are antagonistic to the KHI polymer, severely reducing the KHI performance. It would be preferable and economic if the KHI also could act as a CI. We have explored the use of maleic-based copolymers as KHIs as well as their use as film-forming CIs. KHIs were tested using a natural gas mixture in high pressure rocking cells using the slow constant cooling test method. A terpolymer from reaction of vinyl acetate:maleic anhydride copolymer with cyclohexy lamine and 3,3-di-n-butylaminopropylamine (VA:MA-60% cHex-40% DBAPA), gave excellent performance as a KHI, better than the commercially available poly(N-vinyl caprolactam) (PVCap). CO2 corrosion inhibition was measured by Linear Polarization Resistance (LPR) in a 1 litre CO2 bubble test equipment using C1018 steel coupons. The new terpolymer gave good CO2 corrosion inhibition in 3.6 wt% brine, significantly better than PVCap, but not as good as a commercial imidazoline-based surfactant corrosion inhibitor. The terpolymer also showed good corrosion inhibition efficiency at high salinity conditions, (density 1.12 g/cm3). VA:MA-60% cHex-40% DBAPA shifted the open-circuit potential to more positive values and significantly decreased the corrosion rate.
Top of line corrosion in gas-condensate pipelines
Authors: Seiersten M. , Dugstad A. , Nossen J. , Sendstad O.
Published: November 2021

Low alloyed carbon steel is the only viable material of construction for long pipelines transporting unprocessed gas-condensate. The water that condenses is highly corrosive because it contains dissolved acid gases, i.e., CO2, H2S and organic acids like acetic and formic acid. The high velocity gas also contains droplets of water and condensate, and these will deposit if they hit the steel surface. Monoethylene glycol (MEG) injected to prevent ice and hydrates must be considered when predicting the composition and corrosivity of the aqueous phases in the pipeline. The liquids gathering at the bottom of the pipe have a higher heat capacity than the gas, and the temperature at the top of the pipe will be slightly lower than at the bottom. As the produced fluids cool during the transport from the hot wells to the process plant, water will condense on the cold pipe surface and more at the top than at the bottom. The literature on Top-of-line corrosion (ToLC) has grown steadily since the first reported case in 1960. There are also several prediction models for ToLC. This review is an overview of the main factors that cause ToLC and how these are modelled. Mass transfer from the aqueous phase at the bottom to the top contribute to the condensation. Despite the low MEG to water ratio in the gas due to the difference in vapour pressure, the fraction of MEG in the condensing water may be considerable. The concentration of MEG in the aqueous phase at the top depends on the mass transfer from bottom. The same is the case for organic acids. Liquid droplets entrained in the gas may deposit top of line and contribute to the chemistry of the aqueous phase. Models for ToLC must thus not only predict the composition of the condensing phases but also the mass transfer to be able to estimate the corrosion rate.
Effectiveness of common water-reducing admixtures in alkali-activated slag pastes with different types of activator
Authors: Bilek V , Iliushchenko V , Hruby P , Kalina L
Published: November 2021

Rheology of alkali-activated slag (AAS) is a very complex issue, where the activator nature as well as its dose play an important role. Moreover, the use of water-reducing admixtures in these systems is an issue, as they often do not work properly. This could be attributed to the high pH as well as to the surface chemistry of AAS. Therefore, lignosulfonate-, polynaphthalene- and polycarboxylate-based superplasticizers were used to modify AAS pastes with sodium waterglass, hydroxide and carbonate activator. These pastes were tested using a rotational rheometer in an oscillatory shear mode of increasing shear strain to observe the evolution of viscoelastic moduli and to determine the oscillatory stress corresponding to the linear viscoelastic region limit (“yield point”) and to the crossover point, where the storage modulus equals the loss modulus (“flow point”). In most cases, the used plasticizers did not improve the rheological properties; the only exception was the lignosulfonate one in sodium hydroxide-activated slag.
Fracture parameters of fly ash geopolymer mortars with carbon black and graphite filler
Authors: Simonova H , Mizerova C , Rovnanik P , Lipowczan M , Schmid P
Published: November 2021

In this study, the effect of carbon black and graphite filler on the crack initiation and fracture parameters of fly ash geopolymer mortar is investigated. The carbon black was added in the amount of 0.5 and 1.0% and graphite powder in the amount of 5 and 10% relative to the fly ash mass. The reference mixture without any filler was also prepared. The fracture characteristics were determined based on the results of the three-point bending test of prismatic specimens provided with an initial central edge notch. The fracture experiments were conducted at the age of 48 days. The vertical force (F), the displacement measured in the middle of the span length (d), and the crack mouth opening displacement (CMOD) were continuously recorded during the test. The records of fracture tests were subsequently evaluated using the effective crack model, work-of-fracture method, and double-K fracture model. The addition of both fine fillers led to a decrease in monitored mechanical fracture parameters in comparison with reference mortar.
Fibre-reinforced cementitious composite: parameter identification using Ohno shear beam test
Authors: Lehký D , Pukl R , Novák D , Lipowczan M
Published: November 2021

Computational-experimental methodology based on artificial neural networks used to identify the material parameters of fibre-reinforced cementitious composite is presented and applied for Ohno shear beam test. The aim is to provide techniques for an advanced assessment of the mechanical fracture properties of these materials, and the subsequent numerical simulation of components/structures made from them. The paper describes the development of computational and material models utilized for efficient material parameter determination with regards to a studied composite. The data is used in inverse analysis based on artificial neural networks together with sensitivity analysis which plays an important role in the process. Developed software tool FRCID-S is also briefly described.
Long period fibre gratings inscribed by sinusoidal intensity modulated femtosecond laser
Authors: Zhao Xiaofan , Li Hongye , Rao Binyu , Wang Meng , Wu Baiyi , Wang Zefeng
Published: November 2021

To the best of our knowledge, this is the first study to propose and verify a novel and simple direct inscription method for long-period fibre gratings (LPFGs) with an arbitrary grating period using a sinusoidal intensity modulated femtosecond laser. This method induces a sine refractive index modulation, which makes the LPFGs have no higher-order harmonic resonance that exists in the normal square-wave modulation method. This is beneficial for reducing the insertion loss of the LPFGs and optimising the transmission spectrum. Using this method, we also conveniently realise the inscription of superimposed, apodised, and chirped LPFGs. This work presents a simple but effective inscription scheme for various types of LPFGs using a femtosecond laser.
Generating a 3D optical needle array with prescribed characteristics
Authors: Zeng Yongxi , Yu Yanzhong , Chen Musheng , Wu Pinghui , Huang Han
Published: November 2021

Unlike the general optical needle along the optical axis, we propose a method to generate a three-dimensional (3D) array formed by optical needles with prescribed length and polarization direction. Moreover, the geometric model of the created array can be specified. With the aid of antenna array pattern synthesis theory and time reversal technology, a virtual uniform line source (ULS) antenna array arranged regularly near the confocal region of two objectives of high numerical apertures is employed to obtain the required illumination in the pupil plane for creating the desired focal fields. Numerical results demonstrate that there is a one-to-one correspondence between the focal field and the elements of the virtual ULS antenna array The length and polarization direction of the optical needles depend on the length and spatial direction of the virtual ULS antenna. The peculiarities of the focal field array, such as the polarization, length, number, spatial position and array structure, can be customized according to application requirements. The created optical needle array can be used for such applications as 3D synchronous particle acceleration and manipulation, and 3D parallel fabrication.
Layer and material-type dependent photoresponse in WSe2/WS2 vertical heterostructures
Authors: Fu ZhuangEn , Hill Josh W , Parkinson Bruce , Hill Caleb M , Tian Jifa
Published: November 2021

Transition metal dichalcogenide (TMD) heterostructures are promising for a variety of applications in photovoltaics and photosensing. Successfully exploiting these heterostructures will require an understanding of their layer-dependent electronic structures. However, there is no experimental data demonstrating the layer-number dependence of photovoltaic effects (PVEs) in vertical TMD heterojunctions. Here, by combining scanning electrochemical cell microscopy (SECCM) with optical probes, we report the first layer-dependence of photocurrents in WSe2/WS2 vertical heterostructures as well as in pristine WS2 and WSe2 layers. For WS2, we find that photocurrents increase with increasing layer thickness, whereas for WSe2 the layer dependence is more complex and depends on both the layer number and applied bias (Vb
). We further find that photocurrents in the WSe2/WS2 heterostructures exhibit anomalous layer and material-type dependent behaviors. Our results advance the understanding of photoresponse in atomically thin WSe2/WS2 heterostructures and pave the way to novel nanoelectronic and optoelectronic devices.
Tannin-furanic foams used as biomaterial substrates for SERS sensing in possible wastewater filter applications
Authors: Sabathi Gebhard , Reyer Andreas , Cefarin Nicola , Sepperer Thomas , Eckardt Jonas , Neubauer Jonas , Jan Wendisch Fedja , D’Amico Francesco , Vaccari Lisa , Tondi Gianluca , Musso Maurizio
Published: November 2021

Simple substrates for surface enhanced Raman spectroscopy (SERS), producible in a cost-efficient way, are of growing interest both for scientific and for environmental applications. In this study, we demonstrate the use of three types of bio-based tannin-furanic rigid foams as precursor materials for SERS substrates. Coated with a silver layer, these substrates allowed the detection of several well-known analytes in the mM regime by Raman spectroscopy. Specific optimization of the standard tannin-furanic foam morphology by tuning the chemical synthesis led to a smaller and more homogeneously distributed pore structure, supplying more active hot spot areas. Thus, we obtained a significant increase and a lower relative standard deviation (RSD) of the SERS signal recorded over the mapped SERS substrate area, for several analytes, in particular for Malachite Green dye. This work represents a feasibility study opening several potential applications of this biopolymers in fields such as the detection of water pollutants, virtually combining filtration and SERS capabilities driven by a controlled porosity.
Study on the hydrogen-induced delayed fracture behavior of Q-P980 and MS980
Authors: Zhao Wei-yan , Chen Wei-jian , Zhao Zheng-zhi , Kuang Shuang , Liu Jing-bao , Sun Lu
Published: November 2021

In this paper, the hydrogen diffusion behavior and hydrogen induced delayed fracture (HIDF) of Q-P980 (Q-P: Quenching and Partitioning) and MS980 (MS: Martensitic steel) steels were investigated using hydrogen penetration, slow strain rate tensile (SSRT) tests, thermal desorption spectroscopy (TDS) tests, fracture analysis, and microstructural examination in this paper. The austenite in Q-P980 is massive retained-austenite (RA) with low stability. The TRIP (Transformation Induced Plasticity) effect will occur in the process of strain and change into high carbon martensite. HIDF is caused by a substantial amount of surplus hydrogen being enriched at the border and flaws. The fracture has a broad cleavage surface and is a typical quasi-cleavage fracture. MS980 has been sufficiently tempered, resulting in a substantial quantity of distributed spherical cementite (150nm) precipitating around the lath martensite. This size and form of cementite may successfully trap hydrogen while maintaining the material’s mechanical characteristics. And tempering can effectively reduce the local stress level of steel, so MS980 has a very low HE susceptibility. HIDF is related to local stress and hydrogen accumulation. We suppose that Z is a constant and Z
C is a critical value which associated to σ and C
H (the local stress and local hydrogen concentration), rising as σ and C
H rises. The atomic bonds at the crack tip, lattice position and the phase interface will fracture when Z
C reaches a particular value Z. Tempering to minimize local stress and carbide precipitation to capture hydrogen are two strategies for reducing hydrogen embrittlement (HE) susceptibility, particularly for dislocation strengthened steel. Microalloying elements can generate precipitates that function as hydrogen traps and obstruct the HELP (Hydrogen Enhanced Localized Plasticity) process, lowering local stress and hydrogen accumulation.
Numerical study of POD-Galerkin-DEIM reduced order modeling of cardiac monodomain formulation
Authors: Khan Riasat , Ng Kwong T
Published: November 2021

The three-dimensional cardiac monodomain model with inhomogeneous and anisotropic conductivity characterizes a complicated system that contains spatial and temporal approximation coefficients along with a nonlinear ionic current term. These complexities make its numerical modeling computationally challenging, and therefore, the formation of an efficient computational approximation is important for studying cardiac propagation. In this paper, a reduced order modeling approach has been developed for the simplified cardiac monodomain model, which yields a significant reduction of the full order dynamics of the cardiac tissue, reducing the required computational resources. Additionally, the discrete empirical interpolation technique has been implemented to accurately estimate the nonlinearity of the ionic current of the cardiac monodomain scheme. The proper orthogonal decomposition technique has been utilized, which transforms a given dataset called ‘snapshots’ to a new coordinate system. The snapshots are computed first from the original system, and they encapsulate all the information observed over both time and parameter variations. Next, the proper orthogonal decomposition provides a reduced order basis for projecting the original solution onto a low-dimensional orthonormal subspace. Finally, a reduced set of unknowns of the forward problem is obtained for which the solution involves significant computational savings compared to that for the original system of unknowns. The efficiency of the model order reduction technique for finite difference solution of cardiac electrophysiology is examined concerning simulation time, error potential, activation time, maximum temporal derivative, and conduction velocity. Numerical results for the monodomain show that its solution time can be reduced by a significant factor, with only 0.474 mV RMS error between the full order and reduced dimensions solution.
Male courtship reduces the risk of female aggression in web-building spiders but varies in structure
Authors: Wignall Anne E , Herberstein Marie E
Published: November 2021

Male courtship serves multiple functions in addition to inducing females to accept them as a mate. In predatory species, male courtship can function to reduce the risk of sexual cannibalism. This is particularly important in web-building spiders in which males risk being mistaken for prey when they enter the female’s predatory trap—the web—in order to commence courtship. Male spiders generate vibrations by shuddering in the female’s web. Shudder vibrations can delay female aggression, even toward prey struggling in the web. We predicted that shudder vibrations are highly conserved across species of web-building spider as males all face the same constraint of not being mistaken for prey by females. We examined how conserved shudder vibrations are across web-building spiders by testing whether female Trichonephila plumipes delay aggressive behavior toward real prey struggling in the web during playback of conspecific or heterospecific (Argiope keyserlingi) male shudder vibrations. We found that while conspecific shudder vibrations do indeed delay female predatory behavior, heterospecific male shudder vibrations do not. There is evidence of shudder or shudder-like vibrations in male courtship behavior across web-building spider families, but these vary in structure. This suggests that despite strong constraints on courtship signal design to separate predatory responses from sexual responses, there is additional selection driving the divergence of signals across distantly related spider species.
Mapping the Matrix: Understanding the Structure and Position of Social Work in Mental Health Services in England and Wales
Authors: Tucker Laura , Webber Martin , Jobling Hannah
Published: November 2021

Social work is one of the core professions within mental health services in the UK, though its position as local authority ‘outsider’ excludes it from health-based workforce planning, leaving the exact national composition of mental health social work shrouded in mystery. In the context of increasing demand and limited resources, this lack of clarity precludes effective use of the mental health workforce. This study aimed to map the provision of mental health social work across England and Wales. A cross-sectional design was used, with brief surveys issued to all local authorities and National Health Service trusts responsible for providing social work or mental health services. These surveys collected the number of mental health social workers in each agency and their employment contexts for subsequent descriptive statistical analysis. Responses were received from 96.6 percent of agencies, employing 6,584 social workers. Findings indicated that mental health social work varies widely across both nations, with little clear rationale for, or consistency in, how social work is structured within mental health services. While these findings establish the first robust framework for understanding the size and scope of mental health social work provision, further research is required to establish temporal and contextual understandings to inform future service planning.
Predicting children’s math skills from task-based and resting-state functional brain connectivity
Authors: Lynn Andrew , Wilkey Eric D , Price Gavin R
Published: November 2021

A critical goal of cognitive neuroscience is to predict behavior from neural structure and function, thereby providing crucial insights into who might benefit from clinical and/or educational interventions. Across development, the strength of functional connectivity among a distributed set of brain regions is associated with children’s math skills. Therefore, in the present study we use connectome-based predictive modeling to investigate whether functional connectivity during numerical processing and at rest “predicts” children’s math skills (N = 31, Mage = 9.21 years, 14 Female). Overall, we found that functional connectivity during symbolic number comparison and rest, but not during nonsymbolic number comparison, predicts children’s math skills. Each task revealed a largely distinct set of predictive connections distributed across canonical brain networks and major brain lobes. Most of these predictive connections were negatively correlated with children’s math skills so that weaker connectivity predicted better math skills. Notably, these predictive connections were largely nonoverlapping across task states, suggesting children’s math abilities may depend on state-dependent patterns of network segregation and/or regional specialization. Furthermore, the current predictive modeling approach moves beyond brain–behavior correlations and toward building models of brain connectivity that may eventually aid in predicting future math skills.
Hippocampal asymmetry of regional development and structural covariance in preterm neonates
Authors: Ge Xinting , Zheng Yuanjie , Qiao Yuchuan , Pan Ningning , Simon Julia Pia , Lee Mitchell , Jiang Wenjuan , Kim Hosung , Shi Yonggang , Liu Mengting
Published: November 2021

Premature birth is associated with a high prevalence of neurodevelopmental impairments in surviving infants. The hippocampus is known to be critical for learning and memory, yet the putative effects of hippocampal dysfunction remain poorly understood in preterm neonates. In particular, while asymmetry of the hippocampus has been well noted both structurally and functionally, how preterm birth impairs hippocampal development and to what extent the hippocampus is asymmetrically impaired by preterm birth have not been well delineated. In this study, we compared volumetric growth and shape development in the hippocampal hemispheres and structural covariance (SC) between hippocampal vertices and cortical thickness in cerebral cortex regions between two groups. We found that premature infants had smaller volumes of the right hippocampi only. Lower thickness was observed in the hippocampal head in both hemispheres for preterm neonates compared with full-term peers, though preterm neonates exhibited an accelerated age-related change of hippocampal thickness in the left hippocampi. The SC between the left hippocampi and the limbic lobe of the premature infants was severely impaired compared with the term-born neonates. These findings suggested that the development of the hippocampus during the third trimester may be altered following early extrauterine exposure with a high degree of asymmetry.
Glycosylation site Asn168 is important for slow in vivo clearance of recombinant human diamine oxidase heparin-binding motif mutants
Authors: Gludovacz Elisabeth , Resch Marlene , Schuetzenberger Kornelia , Petroczi Karin , Maresch Daniel , Hofbauer Stefan , Jilma Bernd , Borth Nicole , Boehm Thomas
Published: November 2021

Elevated plasma and tissues histamine concentrations can cause severe symptoms in mast cell activation syndrome, mastocytosis or anaphylaxis. Endogenous and recombinant human diamine oxidase (rhDAO) can rapidly and completely degrade histamine, and administration of rhDAO represents a promising new treatment approach for diseases with excess histamine release from activated mast cells. We recently generated heparin-binding motif mutants of rhDAO with considerably increased in vivo half-lives in rodents compared with the rapidly cleared wildtype protein. Herein, we characterize the role of an evolutionary recently added glycosylation site asparagine 168 in the in vivo clearance and the influence of an unusually solvent accessible free cysteine 123 on the oligomerization of diamine oxidase (DAO). Mutation of the unpaired cysteine 123 strongly reduced oligomerization without influence on enzymatic DAO activity and in vivo clearance. Recombinant hDAO produced in ExpiCHO-S™ cells showed a 15-fold reduction in the percentage of glycans with terminal sialic acid at Asn168 compared with Chinese hamster ovary (CHO)-K1 cells. Capping with sialic acid was also strongly reduced at the other glycosylation sites. The high abundance of terminal mannose and N-acetylglucosamine residues in the four glycans expressed in ExpiCHO-S™ cells compared with CHO-K1 cells resulted in rapid in vivo clearance. Mutation of Asn168 or sialidase treatment also significantly increased clearance. Intact N-glycans at Asn168 seem to protect DAO from rapid clearance in rodents. Full processing of all glycoforms is critical for preserving the improved in vivo half-life characteristics of the rhDAO heparin-binding motif mutants.
The tumor-associated Tn antigen fosters lung metastasis and recruitment of regulatory T cells in triple negative breast cancer
Authors: Festari María Florencia , da Costa Valeria , Rodríguez-Zraquia Santiago A , Costa Monique , Landeira Mercedes , Lores Pablo , Solari-Saquieres Patricia , Kramer M Gabriela , Freire Teresa
Published: November 2021

Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths. Among breast cancers (BC) subtypes, triple-negative (TN) BC is characterized by metastatic progression and poor patient prognosis. Although, TNBC is initially sensitive to chemotherapy, many TNBC patients rapidly develop resistance, at which point metastatic disease is highly lethal. Cancer cells present phenotypic changes or molecular signatures that distinguish them from healthy cells. The Tn antigen (GalNAc-O-Thr/Ser), which constitutes a powerful tool as tumor marker, was recently reported to contribute to tumor growth. However, its role in BC-derived metastasis has not yet been addressed. In this work, we generated a pre-clinical orthotopic Tn+ model of metastatic TNBC, which mimics the patient surgical treatment and is useful to study the role of Tn in metastasis and immunoregulation. We obtained two different cell clones, which differed in their Tn antigen expression: a high Tn-expressing and a non-expressing clone. Interestingly, the Tn-positive cell line generated significantly larger tumors and higher degree of lung metastases associated with a lower survival rate than the Tn-negative and parental cell line. Furthermore, we also found that both tumors and draining-lymph nodes from Tn+-tumor-bearing mice presented a higher frequency of CD4+ FoxP3+ T cells, while their splenocytes expressed higher levels of IL-10. In conclusion, this work suggests that the Tn antigen participates in breast tumor growth and spreading, favoring metastases to the lungs that are associated with an immunoregulatory state, suggesting that Tn-based immunotherapy could be a strategy of choice to treat these tumors.
Pneumonectomy for primary lung cancer: contemporary outcomes, risk factors and model validation
Authors: Brunswicker Annemarie , Taylor Marcus , Grant Stuart W , Abah Udo , Smith Matthew , Shackcloth Michael , Granato Felice , Shah Rajesh , Rammohan Kandadai ,   the North West Thoracic Surgery Collaborative (NWTSC)†, Argus Leah , Michael Sarah , Mason Sabrina , Bhullar Dilraj , Obale Emmanuel , Fritsch NilsCristopher
Published: November 2021

OBJECTIVES

Despite the increased rate of adverse outcomes compared to lobectomy, for selected patients with lung cancer, pneumonectomy is considered the optimal treatment option. The objective of this study was to identify risk factors for mortality in patients undergoing pneumonectomy for primary lung cancer.

METHODS

Data from all patients undergoing pneumonectomy for primary lung cancer at 2 large thoracic surgical centres between 2012 and 2018 were analysed. Multivariable logistic and Cox regression analyses were used to identify risk factors associated with 90-day and 1-year mortality and reduced long-term survival, respectively.

RESULTS

The study included 256 patients. The mean age was 65.2 (standard deviation 9.4) years. In-hospital, 90-day and 1-year mortality were 6.3% (n = 16), 9.8% (n = 25) and 28.1% (n = 72), respectively. The median follow-up time was 31.5 months (interquartile range 9–58 months). Patients who underwent neoadjuvant therapy had a significantly increased risk of 90-day [odds ratio 6.451, 95% confidence interval (CI) 1.867–22.291, P = 0.003] and 1-year mortality (odds ratio 2.454, 95% CI 1.079–7.185, P = 0.044). Higher Performance Status score was associated with higher 1-year mortality (odds ratio 2.055, 95% CI 1.248–3.386, P = 0.005) and reduced overall survival (hazard ratio 1.449, 95% CI 1.086–1.934, P = 0.012). Advanced (stage III/IV) disease was associated with reduced overall survival (hazard ratio 1.433, 95% CI 1.019–2.016, P = 0.039). Validation of a pneumonectomy-specific risk model demonstrated inadequate model performance (area under the curve 0.54).

CONCLUSIONS

Pneumonectomy remains associated with a high rate of perioperative mortality. Neoadjuvant chemoradiotherapy, Performance Status score and advanced disease emerged as the key variables associated with adverse outcomes after pneumonectomy in our cohort.
Mortality among rough sleepers, squatters, residents of homeless shelters or hotels and sofa-surfers: a pooled analysis of UK birth cohorts
Authors: White James , Fluharty Meg , de Groot Rosa , Bell Steven , Batty G David
Published: November 2021

Background

Homelessness encompasses a wide spectrum of experience. Rough sleepers and people attending homeless shelters have been found to be at an increased risk of mortality. It is unclear whether risks are also elevated in those squatting, living temporarily in low-cost hotels or ‘sofa-surfing’ with friends or family members. This study examines mortality in a representative nationwide sample of people who have slept rough, squatted, lived in shelters or low-cost hotels and sofa-surfed.

Methods

Using unpublished data from two national birth cohorts, namely the National Child Development Study and the 1970 British Birth Cohort study, Cox proportional-hazards models and random-effects meta-analyses were used to analyse associations between homelessness and different types of homeless experience (rough sleeping, squatting, staying in a homeless shelter or low-cost hotel, and sofa-surfing) and mortality.

Results

Out of the 23 678 participants, 1444 (6.1%) reported having been homeless and 805 (3.4%) deaths occurred. Homelessness was associated with an increased risk of mortality [hazard ratio (HR) 1.68, 95% confidence interval (CI) 1.24–2.26]. Mortality risk was raised across the spectrum of homeless experience, from sleeping rough (HR 4.71, 95% CI 2.38–9.30), to squatting (HR 6.35, 95% CI 2.73–14.75), staying in a homeless shelter (HR 4.89, 95% CI 2.36–10.11), staying in a low-cost hotel (HR 3.38, 95% CI 1.30–8.79 through to sofa-surfing (HR 2.86, 95% CI 1.84–4.42). Associations remained after separate control for socio-economic status, mental health, substance use, accidents and assaults, and criminality.

Conclusions

Mortality rates were raised across all types of homeless experience. This included squatting and sofa-surfing that have not previously been reported. Studies that have omitted the less severe, but more prevalent, use of low-cost hotels and sofa-surfing may have underestimated the impacts of homelessness on mortality.
A scoping review of the use of e-learning and e-consultation for healthcare workers in low- and middle-income countries and their potential complementarity
Authors: Ionescu Alma , de Jong Peter G M , Drop Stenvert L S , van Kampen Sanne C
Published: November 2021

Objective

Although the provision of e-learning (EL) training for healthcare workers (HCWs) and provider-to-HCW e-consultation (EC) is considered useful for health outcomes, research on their joint use is limited. This scoping review aimed to create an overview of what is currently known in the literature about the use and implementation of EC and EL by HCWs in LMICs and to answer the question of whether there is evidence of complementarity.

Materials and Methods

Scientific databases were searched and peer-reviewed papers were reviewed systematically according to predefined inclusion/exclusion criteria. Data were extracted including the study focus (EC/EL), year of publication, geographical location, target population, target disease(s) under study, type(s) of study outcomes, and article type.

Results

A total of 3051 articles were retrieved and screened for eligibility, of which 96 were kept for analysis. Of these, only 3 addressed both EL and EC; 54 studies addressed EL; and 39 addressed EC. Most studies looked at gain in knowledge/skills usability, efficiency, competence, and satisfaction of HCW, or barriers/challenges to implementation. Descriptive studies focused on the application of EL or EC for targeting specific health conditions. Factors contributing to the success of EC or EL networks were institutional anchoring, multiple partnership, and capacity building of local experts.

Conclusions

Our review found an important gap in the literature in relation to the complementary role of EL and EC for HCWs in LMICs evidenced by outcome measures. There is an important role for national and international academic institutions, learned medical societies, and networks to support regional experts in providing EL and EC for added value that will help the clinical performance of HCWs and improve health outcomes.
Cosmology from clustering, cosmic shear, CMB lensing, and cross correlations: combining Rubin observatory and Simons Observatory
Authors: Fang Xiao , Eifler Tim , Schaan Emmanuel , Huang Hung-Jin , Krause Elisabeth , Ferraro Simone
Published: November 2021

In the near future, the overlap of the Rubin Observatory Legacy Survey of Space and Time (LSST) and the Simons Observatory (SO) will present an ideal opportunity for joint cosmological data set analyses. In this paper, we simulate the joint likelihood analysis of these two experiments using six two-point functions derived from galaxy position, galaxy shear, and CMB lensing convergence fields. Our analysis focuses on realistic noise and systematics models and we find that the dark energy Figure of merit (FoM) increases by 53 per cent (92 per cent) from LSST-only to LSST+SO in Year 1 (Year 6). We also investigate the benefits of using the same galaxy sample for both clustering and lensing analyses, and find the choice improves the overall signal to noise by ${\sim}30{-}40{{\ \rm per\ cent}}$, which significantly improves the photo-z calibration and mildly improves the cosmological constraints. Finally, we explore the effects of catastrophic photo-z outliers finding that they cause significant parameter biases when ignored. We develop a new mitigation approach termed ‘island model’, which corrects a large fraction of the biases with only a few parameters while preserving the constraining power.
The formation and early evolution of embedded star clusters in spiral galaxies
Authors: Rieder Steven , Dobbs Clare , Bending Thomas , Liow Kong You , Wurster James
Published: November 2021

We present Ekster, a new method for simulating star clusters from birth in a live galaxy simulation that combines the smoothed-particle hydrodynamics (SPH) method Phantom with the N-body method PeTar. With Ekster, it becomes possible to simulate individual stars in a simulation with only moderately high resolution for the gas, allowing us to study whole sections of a galaxy rather than be restricted to individual clouds. We use this method to simulate star and star cluster formation in spiral arms, investigating massive giant molecular clouds (GMCs) and spiral arm regions with lower mass clouds, from two galaxy models with different spiral potentials. After selecting these regions from pre-run galaxy simulations, we re-sample the particles to obtain a higher resolution. We then re-simulate these regions for 3 Myr to study where and how star clusters form. We analyse the early evolution of the embedded star clusters in these regions. We find that the massive GMC regions, which are more common with stronger spiral arms, form more massive clusters than the sections of spiral arms containing lower mass clouds. Clusters form both by accreting gas and by merging with other proto-clusters, the latter happening more frequently in the denser GMC regions.
Inhibition mechanisms of CRISPR-Cas9 by AcrIIA17 and AcrIIA18
Authors: Wang Xiaoshen , Li Xuzichao , Ma Yongjian , He Jiaqi , Liu Xiang , Yu Guimei , Yin Hang , Zhang Heng
Published: November 2021

Mobile genetic elements such as phages and plasmids have evolved anti-CRISPR proteins (Acrs) to suppress CRISPR-Cas adaptive immune systems. Recently, several phage and non-phage derived Acrs including AcrIIA17 and AcrIIA18 have been reported to inhibit Cas9 through modulation of sgRNA. Here, we show that AcrIIA17 and AcrIIA18 inactivate Cas9 through distinct mechanisms. AcrIIA17 inhibits Cas9 activity through interference with Cas9-sgRNA binary complex formation. In contrast, AcrIIA18 induces the truncation of sgRNA in a Cas9-dependent manner, generating a shortened sgRNA incapable of triggering Cas9 activity. The crystal structure of AcrIIA18, combined with mutagenesis studies, reveals a crucial role of the N-terminal β-hairpin in AcrIIA18 for sgRNA cleavage. The enzymatic inhibition mechanism of AcrIIA18 is different from those of the other reported type II Acrs. Our results add new insights into the mechanistic understanding of CRISPR-Cas9 inhibition by Acrs, and also provide valuable information in the designs of tools for conditional manipulation of CRISPR-Cas9.
Grouped-seq for integrated phenotypic and transcriptomic screening of patient-derived tumor organoids
Authors: Wu Yushuai , Li Kaiyi , Li Yaqian , Sun Tao , Liu Chang , Dong Chunhui , Zhao Tian , Tang Decong , Chen Xiaojie , Chen Xiaofang , Liu Peng
Published: November 2021

Patient-derived tumor organoids (PDOs) have emerged as a reliable in vitro model for drug discovery. However, RNA sequencing-based analysis of PDOs treated with drugs has not been realized in a high-throughput format due to the limited quantity of organoids. Here, we translated a newly developed pooled RNA-seq methodology onto a superhydrophobic microwell array chip to realize an assay of genome-wide RNA output unified with phenotypic data (Grouped-seq). Over 10-fold reduction of sample and reagent consumption together with a new ligation-based barcode synthesis method lowers the cost to ∼$2 per RNA-seq sample. Patient-derived colorectal cancer (CRC) organoids with a number of 10 organoids per microwell were treated with four anti-CRC drugs across eight doses and analyzed by the Grouped-seq. Using a phenotype-assisted pathway enrichment analysis (PAPEA) method, the mechanism of actions of the drugs were correctly derived, illustrating the great potential of Grouped-seq for pharmacological screening with tumor organoids.