bluuebunny/crossref_metadata_2025 huggingface dataset:
Functionalized graphene oxide tablets for sample preparation of drugs in biological fluids: Extraction of ritonavir, a HIV protease inhibitor, from human saliva and plasma using LC–MS/MS
Authors: Zohdijamil Zeynab , Hashemi Mahdi , Abdel‐Rehim Abbi , Laxman Karthik , Uheida Abdusalam , Dutta Joydeep , Abdel‐Rehim Mohamed
Published: March 2021

In this work, graphene oxide–based tablets (GO‐Tabs) were prepared by applying a thin layer of functionalized GO on a polyethylene substrate. The GO was functionalized with amine groups (–NH2) by poly(ethylene glycol)bis(3‐aminopropyl) terminated (GO‐NH2‐PEG‐NH2). The functionalized GO‐Tabs were used for the extraction of ritonavir (RTV) in human saliva samples. RTV in plasma and saliva samples was analyzed using LC–MS/MS. Gradient LC system with MS/MS in the positive‐ion mode [electrospray ionization (ESI+)] was used. The transitions m/z 721 → 269.0 and m/z 614 → 421 were used for RTV and the internal standard indinavir, respectively. This study determined the human immunodeficiency virus protease inhibitor RTV in human saliva samples using functionalized GO‐Tab and LC–MS/MS, and the method was validated. The standard calibration curve for plasma and saliva samples was constructed from 5.0 to 2000 nmol L−1. The limit of detection was 0.1 nmol L−1, and the limit of quantification was 5.0 nmol L−1 in both plasma and saliva matrices. The intra‐ and inter‐assay precision values were found to be between 1.5 and 5.8%, and the accuracy values ranged from 88.0 to 108% utilizing saliva and plasma samples. The extraction recovery was more than 80%, and the presented functionalized GO‐Tabs could be reused for more than 10 extractions without deterioration in recovery.
Inverse association of mortality and body mass index in patients with left ventricular systolic dysfunction of both ischemic and non‐ischemic etiologies
Authors: Brazile Tiffany , Mulukutla Suresh , Thoma Floyd , Estes N. A. Mark , Jain Sandeep , Saba Samir
Published: March 2021

Background

Obesity is a worldwide epidemic that has been associated with poor outcomes. Previous studies have demonstrated an inverse relationship between body mass index (BMI) and outcomes, the 'obesity paradox', in several diseases.

Hypothesis

We sought to evaluate whether the obesity paradox is present in patients with left ventricular systolic dysfunction (LVSD) of all etiologies, using all‐cause mortality as the primary endpoint and hospitalization as the secondary endpoint.

Methods

We conducted a retrospective cohort study of LVSD patients (n = 18 003) seen within the University of Pittsburgh Medical Center network between January 2011 and December 2017. Patients were divided into four BMI categories (underweight, normal weight, overweight, and obese) and stratified by left ventricular ejection fraction (LVEF): <20%, 20–35%, and 35–50%.

Results

Over a median follow‐up of 2.28 years, higher BMI (mean 28.9 ± 6.8) was associated with better survival for the overall cohort and within LVEF strata (p < .0001). The most common cause of hospitalization was subendocardial infarction among underweight and normal weight patients and heart failure among overweight and obese patients. Cox proportional hazards model showed that BMI, age, and comorbid conditions of diabetes mellitus, chronic obstructive pulmonary disease, chronic kidney disease, and prior myocardial infarction are independent predictors of death.

Conclusions

Our results support the existence of an obesity paradox impacting all‐cause mortality in patients with LVSD of ischemic and non‐ischemic etiologies even after adjusting for LVEF and comorbidities. Additional research is needed to understand the effect of weight loss on survival once a diagnosis of LVSD is established.
Blockchain‐based smart contract for issuance of country of origin certificate for Indian Customs Exports Clearance
Authors: Tyagi Nitin K. , Goyal Mukta
Published: March 2021

The imports and exports are the major activity of any customs department of the country. Customs officers have to verify all the documents as per the customs act of the country, requirements, and give clearance for exports and imports. But due to the limited period and ease of doing business initiatives, it is impossible to verify each produced paper. Sometimes, forged documents may be produced by parties, and based on illegal documents; illegal exports and imports can be taken place. Due to existing message exchange and application program interface (API)‐based information interchange among participating parties having their centralized server, the possibility of delay in message and authenticity of the sender, information mutation may occur. So the concept of blockchain overcomes these issues by enabling secured, encrypted, immutable transactions among participating parties such as exporter/importer, banks, customs, shipping lines, international parties, and so forth. Thus, this paper proposes a blockchain‐based Business process model and notation (BPMN) framework and smart contract for the country of origin certificate management system against forged certificate in Indian customs and international usage and usage of IPFS (Inter Planetary File System) for sharing multilateral agreement files on the blockchain network.
How environmental stressors affect reproductive potential in a saltmarsh plant species Plantago maritima
Authors: Lazarus Magdalena , Mazur Jacek , Wszałek‐Rożek Katarzyna , Zwolicki Adrian
Published: March 2021

We examined whether the presence or absence of different environmental stressors influenced the reproductive potential of a saltmarsh species—Plantago maritima. We focused on total seed output, seed quality, and biomass of progeny. So far, there are no studies trying to answer the question of how different saltmarsh management affects the quality of seed in saltmarsh species. For the purposes of the study, plots subjected to light mowing, light or heavy grazing, trampling, or rooting were designated in three nature reserves in Poland. On each plot, the abundance of infructescences per sq. meter was calculated. Mature infructescences were collected, and their length and number of fruit capsules were measured. The seeds obtained from fruit capsules were weighted and sown in controlled conditions. The germination rate and the final germination percentage were calculated. A representative number of sprouts were grown. After a period of 2 months, the individuals of P. maritima were harvested and their total dry mass was measured. It was found that heavy grazing had the greatest effect on all of the studied characteristics. The presence of this factor resulted in shorter infructescences with a smaller number of fruit capsules. However, this phenomenon was compensated by the higher abundance of infructescences per sq. meter. At the same time, seeds produced by grazed individuals were significantly lighter. Interestingly, intensive trampling by people affected P. maritima individuals in a similar way to heavy grazing, while mowing and rooting had less impact on the considered characteristics. Although a positive correlation between seed mass and germination success was found, the altogether lower seed mass had a negligible effect on germination parameters. Also, the differences in seed parameters did not affect dry mass of obtained progeny grown in laboratory conditions. Synthesis and applications: Different environmental stressors, such as grazing and mowing, have an effect on reproductive potential of a saltmarsh species P. maritima. In the case of habitats created anthropogenically, such as brackish saltmarshes, the role of management is crucial for their conservation. Therefore, searching for the best active protection methods is important. In light of the results obtained, extensive or rotational grazing appears to be the best form of saltmarsh management.
Janus kinase signaling as risk factor and therapeutic target for severe SARS‐CoV‐2 infection
Authors: Solimani Farzan , Meier Katharina , Ghoreschi Kamran
Published: March 2021

Cytokine signaling, especially interferon (IFN) signaling is closely linked to several aspects of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. During initial SARS‐CoV‐2 infection, symptomatic patients present with impaired type I/III IFN‐mediated antiviral responses. Interestingly, IFNs regulate the cellular entry receptor for SARS‐CoV‐2 on epithelial and endothelial cells. As reported recently, critically ill COVID‐19 patients show genetic polymorphisms in one IFN receptor gene (IFNRA2) and in a gene locus near the Janus kinase (JAK) TYK2, which is key for IFN, interleukin (IL)‐12 and IL‐23 signaling, and T helper (Th) 1/Th17 cell‐mediated antiviral immune responses. In the advanced stage of the disease, critically ill COVID‐19 patients develop a cytokine storm where many inflammatory mediators using the JAK/STAT signaling pathway such as IL‐6, IFN‐γ, the granulocyte colony‐stimulating factor (G‐CSF) or IL‐2, and chemokines result in an influx of macrophages and neutrophils damaging the lung tissue. The knowledge on the cytokine and JAK/STAT signaling pathways in severe COVID‐19 disease explains the promising first results with JAK inhibitors like baricitinib, which not only dampen the inflammation but in the case of baricitinib also affect virus replication and endocytosis in target cells. Here, we summarize the current immunological associations of SARS‐CoV‐2 infection with cytokine signaling, the JAK/STAT pathway, and the current clinical stage of JAK inhibitors for improving severe COVID‐19 disease.
Insight Gained from Using Machine Learning Techniques to Predict the Discharge Capacities of Doped Spinel Cathode Materials for Lithium‐Ion Batteries Applications
Authors: Wang Guanyu , Fearn Tom , Wang Tengyao , Choy Kwang-Leong
Published: March 2021

The electrochemical potentials of spinel lithium manganese oxide (LMO) have long been plagued by the significant Mn3+ dissolution during long cycle discharging, resulting in rapid capacity fading and short cycle life. Although the doping mechanisms are effective in suppressing these reactions, the correlations of their effects on the material properties and the improved discharging performance still remain uncovered. In this study, seven machine learning (ML) methods are applied to a manually curated dataset of 102 doped LMO spinel systems to predict the initial discharge capacities (IC) and 20th cycle end discharge capacities (EC) from fundamental system properties like material molar mass and crystal structure dimension. Gradient boosting models achieved the best prediction powers for IC and EC with their errors estimated to be 11.90 and 11.77 mAhg−1, respectively. Besides, a higher formula molar mass of doped LMO can improve both capacities and additionally, a shorter crystal lattice dimension with a dopant with smaller electronegativity can slightly improve the value of the IC and EC, respectively. This study demonstrates the great potential of using ML models to both predict the discharging performance of doped spinel cathodes and identify the governing material properties for controlling the discharging performance.
MLLPA: A Machine Learning‐assisted Python module to study phase‐specific events in lipid membranes
Authors: Walter Vivien , Ruscher Céline , Benzerara Olivier , Thalmann Fabrice
Published: March 2021

Machine Learning‐assisted Lipid Phase Analysis (MLLPA) is a new Python 3 module developed to analyze phase domains in a lipid membrane based on lipid molecular states. Reading standard simulation coordinate and trajectory files, the software first analyze the phase composition of the lipid membrane by using machine learning tools to label each individual molecules with respect to their state, and then decompose the simulation box using Voronoi tessellations to analyze the local environment of all the molecules of interest. MLLPA is versatile as it can read from multiple format (e.g., GROMACS, LAMMPS) and from either all‐atom (e.g., CHARMM36) or coarse‐grain models (e.g., Martini). It can also analyze multiple geometries of membranes (e.g., bilayers, vesicles). Finally, the software allows for training with more than two phases, allowing for multiple phase coexistence analysis.
Electron Beam Lithography Nanopatterning of Plasma Polymers
Authors: Askew Hannah J. , Jarvis Karyn L. , Jones Robert T. , McArthur Sally L.
Published: March 2021

Chemically patterned surfaces for biotechnology applications often require sub‐micron patterns to match specific sub‐cellular structures and control the presentation of proteins to single cell arrays. Plasma polymer coatings are used extensively in the biotechnology sector for biomaterials, cell culture and tissue engineering, but their patterning has not been investigated at the sub‐micron level. The resolution limit of plasma polymerized patterns with designed line widths of 900 to 20 nm is investigated via dual chemistry patterns of plasma polymerized acrylic acid and allylamine created with poly (methyl methacrylate) resist and electron beam lithography (EBL). Line widths are characterized via scanning electron microscopy and atomic force microscopy with surface chemistry analysis via time‐of‐flight secondary‐ion mass spectrometry (ToF‐SIMS). The smallest line width measured is 29 nm for a designed line width of 20 nm. High‐resolution nanoscale imaging is achieved using ToF‐SIMS, with lines down to ≈60 nm in width visible. This work demonstrates the successful fabrication and characterization of sub 100 nm dual plasma polymer patterns using EBL, establishing a clear route for large scale production of plasma polymerized nanopatterning.
Evaluation of irregular breathing effects on internal target volume definition for lung cancer radiotherapy
Authors: Wikström Kenneth A. , Isacsson Ulf M. , Pinto Marta C. , Nilsson Kristina M. , Ahnesjö Anders
Published: March 2021

Purpose

Irregular breathing may compromise the treated volume for free‐breathing lung cancer patients during radiotherapy. We try to find a measure based on a breathing amplitude surrogate that can be used to select the patients who need further investigation of tumor motion to ensure that the internal target volume (ITV) provides reliant coverage of the tumor.

Material and methods

Fourteen patients were scanned with four‐dimensional computed tomography (4DCT) during free‐breathing. The breathing motion was detected by a pneumatic bellows device used as a breathing amplitude surrogate. In addition to the 4DCT, a breath‐hold (BH) scan and three cine CT imaging sessions were acquired. The cine images were taken at randomized intervals at a rate of 12 per minute for 8 minutes to allow tumor motion determination during a typical hypo‐fractionated treatment scenario. A clinical target volume (CTV) was segmented in the BH CT and propagated over all cine images and 4DCT bins. The center‐of‐volume of the translated CTV (CTVCOV) in the ten 4DCT bins were interconnected to define the 4DCT determined tumor trajectory (4DCT‐TT). The volume of CTV inside ITV for all cine CTs was calculated and reported at the 10th percentile (VCTV10%). The deviations between CTVCOV in the cine CTs and the 4DCT‐TT were calculated and reported at its 90th percentile (d90%). The standard deviation of the bellows amplitude peaks (SDP) and the ratio between large and normal inspirations, κrel, were tested as surrogates for VCTV10% and d90%.

Results

The values of d90% ranged from 0.6 to 5.2 mm with a mean of 2.2 mm. The values of VCTV10% ranged from 59–93% with a mean of 78 %. The SDP had a moderate correlation (r = 0.87) to d90%. Less correlation was seen between SDP and VCTV10% (r = 0.77), κrel and d90% (r = 0.75) and finally κrel and VCTV10% (r = 0.75).

Conclusions

The ITV coverage had a large variation for some patients. SDP seems to be a feasible surrogate measure to select patients that needs further tumor motion determination.
Understanding the factors affecting the seal integrity in heat sealed flexible food packages: A review
Authors: Ilhan Ilknur , Turan Deniz , Gibson Ian , ten Klooster Roland
Published: March 2021

Seal area represents the most problematic part in food packaging for controlling the moisture and gas ingress and preserving product quality. Understanding the mechanism of heat sealing, which is a widely used method in flexible packaging, is critical for maintaining product quality throughout the storage and preventing food waste. Likewise, understanding the factors causing the leak formation in the seal interface helps to avoid failures and increase integrity for all seal types produced by heat sealing methods. This review looks at heat sealing and its mechanisms in flexible food packaging materials and particularly focuses on the reasons behind the encountered seal integrity problems that have a detrimental effect on food quality and shelf life. Heat sealing mechanisms, form fill seal systems and seal types were analyzed. Then, factors affecting the leak formation have been grouped as process parameters, material properties, contaminants, and further processes, which is uncharted territory in open literature. Finally, the details of these groups and their interrelationships were examined and discussed. Revealed key factors as shown in this study are expected to guide future research for understanding leak formation mechanisms in flexible food packaging.
Jet tagging in the Lund plane with graph networks
Authors: Dreyer Frédéric A. , Qu Huilin
Published: March 2021

Abstract

The identification of boosted heavy particles such as top quarks or vector bosons is one of the key problems arising in experimental studies at the Large Hadron Collider. In this article, we introduce LundNet, a novel jet tagging method which relies on graph neural networks and an efficient description of the radiation patterns within a jet to optimally disentangle signatures of boosted objects from background events. We apply this framework to a number of different benchmarks, showing significantly improved performance for top tagging compared to existing state-of-the-art algorithms. We study the robustness of the LundNet taggers to non-perturbative and detector effects, and show how kinematic cuts in the Lund plane can mitigate overfitting of the neural network to model-dependent contributions. Finally, we consider the computational complexity of this method and its scaling as a function of kinematic Lund plane cuts, showing an order of magnitude improvement in speed over previous graph-based taggers.
Anomaly Non-renormalization in Interacting Weyl Semimetals
Authors: Giuliani Alessandro , Mastropietro Vieri , Porta Marcello
Published: March 2021

Weyl semimetals are 3D condensed matter systems characterized by a degenerate Fermi surface, consisting of a pair of ‘Weyl nodes’. Correspondingly, in the infrared limit, these systems behave effectively as Weyl fermions in $$3+1$$

3
+
1

dimensions. We consider a class of interacting 3D lattice models for Weyl semimetals and prove that the quadratic response of the quasi-particle flow between the Weyl nodes is universal, that is, independent of the interaction strength and form. Universality is the counterpart of the Adler–Bardeen non-renormalization property of the chiral anomaly for the infrared emergent description, which is proved here in the presence of a lattice and at a non-perturbative level. Our proof relies on constructive bounds for the Euclidean ground state correlations combined with lattice Ward Identities, and it is valid arbitrarily close to the critical point where the Weyl points merge and the relativistic description breaks down.
Raman temperature and density measurements in supersonic jets
Authors: Wernet Mark P. , Georgiadis Nicholas J. , Locke Randy J.
Published: March 2021

Prediction of flow-field properties in supersonic jets using computational fluid dynamics (CFD) code predictions has become routine; however, obtaining accurate solutions becomes more challenging when there is a significant temperature difference between the jet core and the ambient air and/or compressibility effects are significant. Benchmark sets of flow field property data are required in order to assess current CFD capabilities and develop better modeling approaches for these turbulent flow fields where accurate calculation of temperatures and turbulent heat flux is important. Particle Image Velocimetry, spontaneous rotational Raman scattering spectroscopy, and Background-Oriented Schlieren (BOS) have been previously used to acquire measurements of the mean and root-mean-square (rms) velocities, the mean and rms gas temperatures, and density gradients in subsonic jet flows and film cooling flows. In this work, the ability to measure density is added to the list of measurands available using the acquired Raman spectra. The suite of measurement techniques are now applied to supersonic jet flows. The computation of the local gas pressure in the potential core of an over-expanded jet is demonstrated using the Raman measured gas temperature and density. Additionally, a unique density feature in temperature matched, perfectly expanded jet flow shear layers identified using BOS was verified using the Raman measurement technique. These non-intrusive flow measurements are compared against RANS predictions of the supersonic jet flow properties as a means of assessing their prediction accuracy.

Graphic abstract
Analysis and manufacturing of bistable metallic profiles
Authors: Pavliuchenko Pavlo , Hirt Gerhard , Teller Marco
Published: March 2021

Bistable metal sheets with a coiled transport geometry and an unfolded profile as second stable state, are of great interest as lightweight components. It is well known that a specific distribution of residual stresses is necessary to enable bistable properties. With the help of numerical FE models, the optimal process parameters for production of such sheets are evaluated. Afterwards, incremental bending and roll forming experiments are conducted in order to analyse possible continuous production methods for bistable metallic profiles. Finally, the influence of bending and rolling radii on bistability and profile geometries in stable states are investigated.
The Role of the Cerebellum in Swallowing
Authors: Sasegbon Ayodele , Hamdy Shaheen
Published: March 2021

Swallowing is a complex activity requiring a sophisticated system of neurological control from neurones within the brainstem, cerebral cortices and cerebellum. The cerebellum is a critical part of the brain responsible for the modulation of movements. It receives input from motor cortical and sensory areas and fine tunes these inputs to produce coordinated motor outputs. With respect to swallowing, numerous functional imaging studies have demonstrated increased activity in the cerebellum during the task of swallowing and damage to the cerebellum following differing pathological processes is associated with dysphagia. Single pulses of transcranial magnetic stimulation (TMS) have been applied to the cerebellum and have been shown to evoke motor responses in the pharynx. Moreover, repetitive TMS (rTMS) over the cerebellum can modulate cerebral motor (pharyngeal) cortical activity. Neurostimulation has allowed a better understanding of the connections that exist between the cerebellum and cerebral swallowing motor areas in health and provides a potential treatment for neurogenic dysphagia in illness. In this review we will examine what is currently known about the role of the cerebellum in the control of swallowing, explore new findings from neurostimulatory and imaging studies and provide an overview of the future clinical applications of cerebellar stimulation for treating dysphagia.
Two-scale shape optimisation based on numerical homogenisation techniques and variational sensitivity analysis
Authors: Kijanski Wojciech , Barthold Franz-Joseph
Published: March 2021

This contribution presents a theoretical and computational framework for two-scale shape optimisation of nonlinear elastic structures. Particularly, minimum compliance optimisation problems with composite (matrix-inclusion) microstructures subjected to static loads and volume-type design constraints are focused. A homogenisation-based FE$$^2$$

2

scheme is extended by an enhanced formulation of variational (shape) sensitivity analysis based on Noll’s intrinsic, frame-free formulation of continuum mechanics. The obtained overall two-scale sensitivity information couples shape variations across micro- and macroscopic scales. A numerical example demonstrates the capabilities of the proposed variational sensitivity analysis and the (shape) optimisation framework. The investigations involve a mesh morphing scheme for the design parametrisation at both macro- and microscopic scales.
Hypothesis derivation and its verification by a wholly automated many-objective evolutionary optimization system
Authors: Chiba Kazuhisa , Sawahara Masataka , Sumimoto Tsuyoshi , Hatta Taiki , Kanazaki Masahiro
Published: March 2021

This study has constructed a fully automated multidisciplinary and many-objective evolutionary design optimization system independent of computer environments to evaluate objective functions; the research applied it to a geometric design problem of a flyback booster for next-generation space transportation. In optimization involving objective functions to appraise the aero-/structural-dynamic performance with high fidelity, spatial discretization hinders the overall automation. This research has facilitated an efficient optimal design by wholly automating high-fidelity assessments, which designers had to implement manually, and has accomplished optimizations that directly contribute to real-world design problems. Moreover, this study would accumulate design knowledge for space transportation that the market is reviving. The total automated system yielded the embedding of geometric trait lines to ensure the discretization even for large curvature surfaces; the system innovated a robust automatic error-checking mechanism in the system’s preprocess. Consequently, the entirely automatized optimization procured nondominated solution sets for more precise data analyses in a pragmatic execution period. Design informatics, a framework combining optimization and data analysis, functioned usefully in real-world design on flyback-booster geometry by materializing smooth deriving and verifying a design hypothesis; eventually, the research gained a new design principle.
Outcome following mini-open lower limb fasciotomy for chronic exertional compartment syndrome
Authors: Oliver William M. , Rhatigan Dominic , Mackenzie Samuel P. , White Timothy O. , Duckworth Andrew D. , Molyneux Samuel G.
Published: March 2021

Purpose

The aim of this study was to report outcomes following mini-open lower limb fasciotomy (MLLF) in active adults with chronic exertional compartment syndrome (CECS).

Methods

From 2013–2018, 38 consecutive patients (mean age 31 years [16–60], 71% [n = 27/38] male) underwent MLLF. There were 21 unilateral procedures, 10 simultaneous bilateral and 7 staged bilateral. There were 22 anterior fasciotomies, five posterior and 11 four-compartment. Early complications were determined from medical records of 37/38 patients (97%) at a mean of four months (1–19). Patient-reported outcomes (including EuroQol scores [EQ-5D/EQ-VAS], return to sport and satisfaction) were obtained via postal survey from 27/38 respondents (71%) at a mean of 3.7 years (0.3–6.4).

Results

Complications occurred in 16% (n = 6/37): superficial infection (11%, n = 4/37), deep infection (3%, n = 1/37) and wound dehiscence (3%, n = 1/37). Eight per cent (n = 3/37) required revision fasciotomy for recurrent leg pain. At longer-term follow-up, 30% (n = 8/27) were asymptomatic and another 56% (n = 15/27) reported improved symptoms. The mean pain score improved from 6.1 to 2.5 during normal activity and 9.1 to 4.7 during sport (both p < 0.001). The mean EQ-5D was 0.781 (0.130–1) and EQ-VAS 77 (33–95). Of 25 patients playing sport preoperatively, 64% (n = 16/25) returned, 75% (n = 12/16) reporting improved exercise tolerance. Seventy-four per cent (n = 20/27) were satisfied and 81% (n = 22/27) would recommend the procedure.

Conclusion

MLLF is safe and effective for active adults with CECS. The revision rate is low, and although recurrent symptoms are common most achieve symptomatic improvement, with reduced activity-related leg pain and good health-related quality of life. The majority return to sport and are satisfied with their outcome.
Mineral resource dissipation in life cycle inventories
Authors: Beylot Antoine , Ardente Fulvio , Sala Serenella , Zampori Luca
Published: March 2021

Purpose

The assessment of potential environmental impacts associated to mineral resource use in LCA is a highly debated topic. Most current impact assessment methods consider the extraction of resources as the issue of concern, while their dissipation is an emerging concept. This article proposes an approach to account for mineral resource dissipation in life cycle inventories (LCIs), with application to a case study.

Methods

The definition of mineral resources is first discussed considering both current main LCA practice and the context of resource dissipation. Secondly, the approach is described: considering a short-term perspective (25 years), any flow of resources to (i) environment, (ii) final waste disposal facilities, and (iii) products-in-use in the technosphere, with the resources not providing any significant function anymore (including due to non-functional recycling), is suggested to be reported as dissipative at the level of unit processes. This approach first requires to map the flows of mineral resources into and out of the unit processes under study (“resource flow analysis”), before identifying the dissipative flows and reporting them in LCI datasets.

Results and discussion

The approach is applied to analyze the direct dissipation of mineral resources along the primary production of copper, using Ecoinvent (v3.5) datasets. The production of 1 kg of copper cathode generates 0.88 kg of direct dissipative flows of resources (primarily calcium carbonate, copper, and to a lower extent iron), with important contributions of “tailings disposal,” “pyrometallurgy,” and “mining and concentration.” Moreover, this article discusses (i) how the developed approach would change the interpretation of results regarding mineral resources in LCA, (ii) how far some key methodological aspects of this approach (e.g., the temporal perspective) can affect the inventory results (e.g., in the case of the primary production of copper, considering a long-term perspective implies a significant shift in main contributions regarding both unit processes and resource flows), and finally (iii) the issue of new data requirements, in terms of availability and adequacy.

Conclusions

As demonstrated in the case study, existing LCI datasets and supporting documentation contain at least part of the data and information required to consistently compile the dissipative flows of resources at the unit process level, yet with the need for some complementary data and assessments. This approach may be particularly relevant to better support the development of more resource-efficient techniques or product designs. It is still open how to adapt characterization approaches to account for the impact induced by these resource dissipative flows.
TEAMwISE: synchronised immersive environments for exploration and analysis of animal behaviour
Authors: Klein Karsten , Aichem Michael , Zhang Ying , Erk Stefan , Sommer Björn , Schreiber Falk
Published: March 2021

The recent availability of affordable and lightweight tracking sensors allows researchers to collect large and complex movement data sets. To explore and analyse these data, applications are required that are capable of handling the data while providing an environment that enables the analyst(s) to focus on the task of investigating the movement in the context of the geographic environment it occurred in. We present an extensible, open-source framework for collaborative analysis of geospatial–temporal movement data with a use case in collective behaviour analysis. The framework TEAMwISE supports the concurrent usage of several program instances, allowing to have different perspectives on the same data in collocated or remote set-ups. The implementation can be deployed in a variety of immersive environments, for example, on a tiled display wall and mobile VR devices.

Graphic abstract
Explainable recommendation based on knowledge graph and multi-objective optimization
Authors: Xie Lijie , Hu Zhaoming , Cai Xingjuan , Zhang Wensheng , Chen Jinjun
Published: March 2021

Recommendation system is a technology that can mine user's preference for items. Explainable recommendation is to produce recommendations for target users and give reasons at the same time to reveal reasons for recommendations. The explainability of recommendations that can improve the transparency of recommendations and the probability of users choosing the recommended items. The merits about explainability of recommendations are obvious, but it is not enough to focus solely on explainability of recommendations in field of explainable recommendations. Therefore, it is essential to construct an explainable recommendation framework to improve the explainability of recommended items while maintaining accuracy and diversity. An explainable recommendation framework based on knowledge graph and multi-objective optimization is proposed that can optimize the precision, diversity and explainability about recommendations at the same time. Knowledge graph connects users and items through different relationships to obtain an explainable candidate list for target user, and the path between target user and recommended item is used as an explanation basis. The explainable candidate list is optimized through multi-objective optimization algorithm to obtain the final recommendation list. It is concluded from the results about experiments that presented explainable recommendation framework provides high-quality recommendations that contains high accuracy, diversity and explainability.
Editorial
Authors: Barrett Steve
Published: March 2021

Hydrogen refueling stations continue to open at a very encouraging pace, indeed far too many to be able to report on them all in FCB, with our limited page budget.
Gene Expression Profiling of Muscle-Invasive Bladder Cancer With Secondary Variant Histology
Authors: de Jong Joep J , Narayan Vikram M , Cronican Andrea A , Gupta Shilpa , van Leenders Geert J L H , Boormans Joost L , Gibb Ewan A , Konety Badrinath R
Published: March 2021

Objectives

To determine the potential impact of the presence of secondary variant histology on the gene expression profiles of muscle-invasive bladder cancer (MIBC) tumors.

Methods

For six tumors, revised samples were collected from urothelial and secondary variant components (cohort A). The commercial cohort (cohort B) consisted of the anonymized gene expression profiles of 173 patients with MIBC. Samples were obtained from the clinical use of the Decipher Bladder test that were available as part of the Decipher GRID prospective registry (NCT02609269). Secondary variant presence in cohort B was abstracted from institutional pathology reports. For the commercial cohort, only the urothelial carcinoma component was profiled.

Results

Molecular subtyping of both urothelial and variant components found micropapillary and nested cases were classified as a luminal subtype. Conversely, the sarcomatoid and small cell cases were classified as basal/squamous or neuroendocrine-like, respectively. For cohort B, 50 (29%) of 173 cases had reported secondary variant histology. Cases with squamous variant had basal profiles, small cell cases expressed neuronal markers, and micropapillary cases were classified as luminal. Sarcomatoid tumors had robust epithelial-mesenchymal transition marker expression.

Conclusions

Our data suggest that in MIBC with secondary variant, the urothelial component can demonstrate an expression profile that closely resembles the variant component.
The GGC repeat expansion inNOTCH2NLCis associated with oculopharyngodistal myopathy type 3
Authors: Yu Jiaxi , Deng Jianwen , Guo Xueyu , Shan Jingli , Luan Xinghua , Cao Li , Zhao Juan , Yu Meng , Zhang Wei , Lv He , Xie Zhiying , Meng LingChao , Zheng Yiming , Zhao Yawen , Gang Qiang , Wang Qingqing , Liu Jing , Zhu Min , Zhou Binbin , Li Pidong , Liu Yinzhe , Wang Yang , Yan Chuanzhu , Hong Daojun , Yuan Yun , Wang Zhaoxia
Published: March 2021

Oculopharyngodistal myopathy (OPDM) is an adult-onset neuromuscular disease characterized by progressive ocular, facial, pharyngeal and distal limb muscle involvement. Trinucleotide repeat expansions in LRP12 or GIPC1 were recently reported to be associated with OPDM. However, a significant portion of OPDM patients have unknown genetic causes. In this study, long-read whole-genome sequencing and repeat-primed PCR were performed and we identified GGC repeat expansions in the NOTCH2NLC gene in 16.7% (4/24) of a cohort of Chinese OPDM patients, designated as OPDM type 3 (OPDM3). Methylation analysis indicated that methylation levels of the NOTCH2NLC gene were unaltered in OPDM3 patients, but increased significantly in asymptomatic carriers. Quantitative real-time PCR analysis indicated that NOTCH2NLC mRNA levels were increased in muscle but not in blood of OPDM3 patients. Immunofluorescence on OPDM muscle samples and expressing mutant NOTCH2NLC with (GGC)69 repeat expansions in HEK293 cells indicated that mutant NOTCH2NLC-polyglycine protein might be a major component of intranuclear inclusions, and contribute to toxicity in cultured cells. In addition, two RNA-binding proteins, hnRNP A/B and MBNL1, were both co-localized with p62 in intranuclear inclusions in OPDM muscle samples. These results indicated that a toxic protein gain-of-function mechanism and RNA gain-of-function mechanism may both play a vital role in the pathogenic processes of OPDM3. This study extended the spectrum of NOTCH2NLC repeat expansion-related diseases to a predominant myopathy phenotype presenting as OPDM, and provided evidence for possible pathogenesis of these diseases.
Human tauopathy-derived tau strains determine the substrates recruited for templated amplification
Authors: Tarutani Airi , Miyata Haruka , Nonaka Takashi , Hasegawa Kazuko , Yoshida Mari , Saito Yuko , Murayama Shigeo , Robinson Andrew C , Mann David M A , Tomita Taisuke , Hasegawa Masato
Published: March 2021

Tauopathies are a subset of neurodegenerative diseases characterized by abnormal tau inclusions. Specifically, three-repeat tau and four-repeat tau in Alzheimer’s disease, three-repeat tau in Pick’s disease (PiD) and four-repeat tau in progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) form amyloid-like fibrous structures that accumulate in neurons and/or glial cells. Amplification and cell-to-cell transmission of abnormal tau based on the prion hypothesis are believed to explain the onset and progression of tauopathies. Recent studies support not only the self-propagation of abnormal tau, but also the presence of conformationally distinct tau aggregates, namely tau strains. Cryogenic electron microscopy analyses of patient-derived tau filaments have revealed disease-specific ordered tau structures. However, it remains unclear whether the ultrastructural and biochemical properties of tau strains are inherited during the amplification of abnormal tau in the brain. In this study, we investigated template-dependent amplification of tau aggregates using a cellular model of seeded aggregation. Tau strains extracted from human tauopathies caused strain-dependent accumulation of insoluble filamentous tau in SH-SY5Y cells. The seeding activity towards full-length four-repeat tau substrate was highest in CBD-tau seeds, followed by PSP-tau and Alzheimer’s disease (AD)-tau seeds, while AD-tau seeds showed higher seeding activity than PiD-tau seeds towards three-repeat tau substrate. Abnormal tau amplified in cells inherited the ultrastructural and biochemical properties of the original seeds. These results strongly suggest that the structural differences of patient-derived tau strains underlie the diversity of tauopathies, and that seeded aggregation and filament formation mimicking the pathogenesis of sporadic tauopathy can be reproduced in cultured cells. Our results indicate that the disease-specific conformation of tau aggregates determines the tau isoform substrate that is recruited for templated amplification, and also influences the prion-like seeding activity.
Strengthened structure–function relationships of the corticospinal tract by free water correction after stroke
Authors: Guder Stephanie , Pasternak Ofer , Gerloff Christian , Schulz Robert
Published: March 2021

The corticospinal tract is the most intensively investigated tract of the human motor system in stroke rehabilitative research. Diffusion-tensor-imaging gives insights into its microstructure, and transcranial magnetic stimulation assesses its excitability. Previous data on the interrelationship between both measures are contradictory. Correlative or predictive models which associate them with motor outcome are incomplete. Free water correction has been developed to enhance diffusion-tensor-imaging by eliminating partial volume with extracellular water, which could improve capturing stroke-related microstructural alterations, thereby also improving structure-function relationships in clinical cohorts. In the present cross-sectional study, data of 18 chronic stroke patients and 17 healthy controls, taken from a previous study on cortico-cerebellar motor tracts, were re-analysed: The data included diffusion-tensor-imaging data quantifying corticospinal tract microstructure with and without free water correction, transcranial magnetic stimulation data assessing recruitment curve properties of motor evoked potentials and detailed clinical data. Linear regression modelling was used to interrelate corticospinal tract microstructure, recruitment curves properties and clinical scores. The main finding of the present study was that free water correction substantially strengthens structure-function associations in stroke patients: Specifically, our data evidenced a significant association between fractional anisotropy of the ipsilesional corticospinal tract and its excitability (P = 0.001, adj. R2 = 0.54), with free water correction explaining additional 20% in recruitment curve variability. For clinical scores, only free water correction leads to the reliable detection of significant correlations between ipsilesional corticospinal tract fractional anisotropy and residual grip (P = 0.001, adj. R2 = 0.70) and pinch force (P < 0.001, adj. R2 = 0.72). Finally, multimodal models can be improved by free water correction as well. This study evidences that corticospinal tract microstructure directly relates to its excitability in stroke patients. It also shows that unexplained variance in motor outcome is considerably reduced by free water correction arguing that it might serve as a powerful tool to improve existing models of structure-function associations and potentially also outcome prediction after stroke.
Rapid decline of anti-SARS-CoV-2 antibodies in patients on haemodialysis: the COVID-FRIAT study
Authors: Alcázar-Arroyo Roberto , Portolés José , López-Sánchez Paula , Zalamea Felipe , Furaz Karina , Méndez Ángel , Nieto Luis , Sánchez-Hernández Rosa , Pizarro Soledad , García Alicia , Pereira Mónica , Gallego-Valcárcel Eduardo , Llópez-Carratala Rosario , Gadea-Gironés Ignacio , Martín Roberto , Miranda Blanca ,   COVID-FRIAT study group, Cordón Alfredo , Horna Alicia González , Botella Ana , del Real Paula Manso , Hernández Jesús , San Segundo Eva María García , Guerrero José , Acuña Mariano , Rodríguez Elena Guerrero , Ortiz Alberto , Parra Emilio Gonzalez , Juárez Gema Fernández , Gruss Enrique , Barriola Almudena Ortigosa , Rodríguez Laura , Torre Cristina Ledesma , Alexandru Simona , Simón Dolores Piña , Esteras Raquel , González Adriana Iglesias , Marín Darío Janeiro , García Alicia Sánchez , Hernán David , Sánchez Mónica , Portillo Jesús
Published: March 2021

Background

Coronavirus disease 2019 (COVID-19) patients on haemodialysis (HD) have high mortality. We investigated the value of reverse transcription polymerase chain reaction (RT-PCR) and the dynamic changes of antibodies (enzyme-linked immunosorbent assay immunoglobulin M (IgM) + IgA and/or IgG) in a large HD cohort.

Methods

We conducted a prospective observational study in 10 Madrid HD centres. Infection rate, anti-SARS-CoV-2 antibody dynamics and the incidence of asymptomatic SARS-CoV-2 infection (defined by positive RT-PCR, IgM + IgA and/or IgG) were assessed.

Results

From 1 March to 15 April 2020, 136 of 808 (16.8%) HD patients were diagnosed with symptomatic COVID-19 by RT-PCR of nasopharyngeal swabs and 42/136 (31%) died. In the second fortnight of April, RT-PCR and anti-SARS-CoV-2 antibodies were assessed in 763 of the surviving patients. At this point, 69/91 (75.8%) symptomatic COVID-19 patients had anti-SARS-CoV-2 antibodies. Four weeks later, 15.4% (10/65) of initially antibody-positive patients had become negative. Among patients without prior symptomatic COVID-19, 9/672 (1.3%) were RT-PCR positive and 101/672 patients (15.0%) were antibody positive. Four weeks later, 62/86 (72.1%) of initially antibody-positive patients had become negative. Considering only IgG titres, serology remained positive after 4 weeks in 90% (54/60) of patients with symptomatic COVID-19 and in 52.5% (21/40) of asymptomatic patients. The probability of an adequate serologic response (defined as the development of anti-SARS-CoV-2 antibodies that persisted at 4 weeks) was higher in patients who had symptomatic COVID-19 than in asymptomatic SARS-CoV-2 infection {odds ratio [OR) 4.04 [95% confidence interval (CI) 2.04–7.99]} corrected for age, Charlson comorbidity index score and time on HD. Living in a nursing home [OR 5.9 (95% CI 2.3–15.1)] was the main risk factor for SARS-CoV-2 infection.

Conclusions

The anti-SARS-CoV-2 antibody immune response in HD patients depends on clinical presentation. The antibody titres decay earlier than previously reported for the general population. This inadequate immune response raises questions about the efficacy of future vaccines.
Accurate, ultra-low coverage genome reconstruction and association studies in Hybrid Swarm mapping populations
Authors: Weller Cory A , Tilk Susanne , Rajpurohit Subhash , Bergland Alan O
Published: March 2021

Genetic association studies seek to uncover the link between genotype and phenotype, and often utilize inbred reference panels as a replicable source of genetic variation. However, inbred reference panels can differ substantially from wild populations in their genotypic distribution, patterns of linkage-disequilibrium, and nucleotide diversity. As a result, associations discovered using inbred reference panels may not reflect the genetic basis of phenotypic variation in natural populations. To address this problem, we evaluated a mapping population design where dozens to hundreds of inbred lines are outbred for few generations, which we call the Hybrid Swarm. The Hybrid Swarm approach has likely remained underutilized relative to pre-sequenced inbred lines due to the costs of genome-wide genotyping. To reduce sequencing costs and make the Hybrid Swarm approach feasible, we developed a computational pipeline that reconstructs accurate whole genomes from ultra-low-coverage (0.05X) sequence data in Hybrid Swarm populations derived from ancestors with phased haplotypes. We evaluate reconstructions using genetic variation from the Drosophila Genetic Reference Panel as well as variation from neutral simulations. We compared the power and precision of Genome-Wide Association Studies using the Hybrid Swarm, inbred lines, recombinant inbred lines (RILs), and highly outbred populations across a range of allele frequencies, effect sizes, and genetic architectures. Our simulations show that these different mapping panels vary in their power and precision, largely depending on the architecture of the trait. The Hybrid Swam and RILs outperform inbred lines for quantitative traits, but not for monogenic ones. Taken together, our results demonstrate the feasibility of the Hybrid Swarm as a cost-effective method of fine-scale genetic mapping.