bluuebunny/crossref_metadata_2025 huggingface dataset:
Resolving isobaric interferences in direct infusion tandem mass spectrometry
Authors: Kaeslin Jérôme , Zenobi Renato
Published: February 2022

Rationale

The co‐fragmentation of precursors in direct infusion (DI) tandem high‐resolution mass spectrometry (HRMS) can complicate the fragment spectra and consequently lead to false hits during compound identification.

Methods

The method herein described, termed IQAROS (incremental quadrupole acquisition to resolve overlapping spectra), modulates the intensities of precursors and fragments by stepwise movement of the quadrupole isolation window over the mass‐to‐charge (m/z) range of the precursors. The modulated signals are then deconvoluted by a linear regression model to reconstruct the fragment spectra with less interference. The hardware to demonstrate the use of IQAROS was an orbitrap with electrospray ionization (ESI) or secondary electrospray ionization (SESI), although the method can also be applied to other ionization techniques or mass analyzers.

Results

Assessing the performance of IQAROS with isobaric standards revealed that the reconstructed fragment spectra match with spectra acquired from the pure standards and that more compounds were correctly identified compared with the classical approach with the quadrupole centered at the m/z value of the precursor of interest. Moreover, the strength of IQAROS is exemplified by the identification of two isobaric biomarkers directly from a breath sample with SESI‐HRMS.

Conclusions

With IQAROS, cleaner fragment spectra of co‐fragmenting isobars during DI‐HRMS analysis can be obtained. IQAROS can easily be set up by the standard graphical user interface of the instrument. Therefore, it facilitates the characterization of features of interest in samples analyzed by DI‐HRMS, for example, in high‐throughput or real‐time metabolomics.
Mosaic loss of the Y chromosome and men's health
Authors: Fukami Maki , Miyado Mami
Published: February 2022

Background

Although Y chromosomal genes are involved in male sex development, spermatogenesis, and height growth, these genes play no role in the survival or mitosis of somatic cells. Therefore, somatic cells lacking the Y chromosome can stay and proliferate in the body.

Methods

Several molecular technologies, including next‐generation sequencing and multiplex PCR‐based assays, are used to detect mosaic loss of the Y chromosome (mLOY) in the blood of men.

Main findings

Accumulating evidence suggests that mLOY represents the most common acquired chromosomal alteration in humans, affecting >40% of men over 70 years of age. Advanced age, tobacco smoking, and some SNPs in cell cycle genes are known to increase the frequency of mLOY. The developmental process of mLOY in elderly men remains to be clarified, but it possibly reflects recurrent mitotic elimination of Y chromosomes or clonal expansion of 45,X cell lineages. In rare cases, mLOY also occurs in young men and fetuses. MLOY has been associated with early death, cancers, and other disorders in elderly men, infertility in reproductive‐aged men, and developmental defects in children.

Conclusion

Y chromosomes in men can be lost at every life stage and Y chromosomal loss is associated with various health problems.
Consensus tracking for singular multi‐agent systems with Lipschitz nonlinear dynamics and external disturbances
Authors: Liu Tianya , Sheng Andong , Ma Cui‐Qin , Qi Guoqing , Li Yinya
Published: February 2022

The consensus tracking control problem for singular multi‐agent systems (SMASs) with Lipschitz nonlinearities and unknown disturbances is investigated. An extended state observer using only the relative output information is introduced and then a distributed consensus protocol is proposed, whose performance is analyzed using matrix analysis, singular system theory and Lyapunov stability theory. Sufficient conditions for ensuring consensus tracking with disturbance rejection of linear and Lipschitz nonlinear SMASs are, respectively, obtained under directed networks. Specifically, an equivalent formulation of achieving consensus tracking for SMASs is established, and the design procedures of gain matrices in the proposed consensus protocols are presented by the linear matrix inequality solver. Finally, simulation examples are provided to illustrate the theoretical results.
Out of the trap: Conversion funnel business model, customer switching costs, and industry profitability
Authors: Abolfathi Niloofar , Fosfuri Andrea , Santamaria Simone
Published: February 2022

Research Summary

Across many industries, firms employ a conversion funnel business model to attract customers with basic and affordable products, generate lock‐in, and then sell them more advanced and expensive products. We argue that this business model, coupled with high customer switching costs, results in a market outcome characterized by aggressive pricing and reduced profits. A sudden reduction in customer switching costs disrupts the conversion funnel and can eventually increase industrywide prices and profitability, an outcome that contradicts conventional wisdom in strategy research. We develop a stylized model to formalize our ideas and provide supportive evidence using a difference‐in‐differences methodology with staggered treatment for a large, global sample of mobile telecommunications operators.

Managerial Summary

Industry changes that lower customer frictions can surprisingly be beneficial for companies. Building on the telecommunications industry, we document how a reduction in customer switching costs following mobile number portability increases the profitability of mobile operators. We explain this finding based on a change in companies' business model. When switching costs are high, companies adopt a funnel business model designed to convert customers from basic to advanced products. While advantageous for a single company, when strategic interactions are accounted for, the diffusion of this business model has a depressive effect on average market prices and profitability. A reduction in customer switching costs breaks the funnel and decouples product pricing decisions that, counterintuitively, can lead to higher industrywide prices and greater profitability.
Quaternized Polysaccharide‐Based Cationic Micelles as a Macromolecular Approach to Eradicate Multidrug‐Resistant Bacterial Infections while Mitigating Antimicrobial Resistance
Authors: Xie Fang , Jiang Lai , Xiao Ximian , Lu Yiwen , Liu Runhui , Jiang Wei , Cai Jie
Published: February 2022

Microbial infections and microbial resistance lead to a high demand for new antimicrobial agents. Quaternized polysaccharides are cationic antimicrobial candidates; however, the limitation of homogeneous synthesis solvents that affect the molecular structure and biological activities, as well as their drug resistance remains unclear. Therefore, the authors homogeneously synthesize a series of quaternized chitin (QC) and quaternized chitosan (QCS) derivatives via a green and effective KOH/urea system and investigate their structure–activity relationship and biological activity in vivo and in vitro. Their study reveals that a proper match of degree of quaternization (DQ) and degree of deacetylation (DD′) of QC or QCS is key to balance antimicrobial property and cytotoxicity. They identify QCS‐2 as the optimized antimicrobial agent with a DQ of 0.46 and DD′ of 82%, which exhibits effective broad‐spectrum antimicrobial properties, good hemocompatibility, excellent cytocompatibility, and effective inhibition of bacterial biofilm formation and eradication of mature bacterial biofilms. Moreover, QCS‐2 exhibits a low propensity for development of drug resistance and significant anti‐infective effects on MRSA in vivo comparable to that of vancomycin, avoiding excessive inflammation and promoting the formation of new blood vessels, hair follicles, and collagen deposition to thus expedite wound healing.
Combination of Photothermal Therapy with Anti‐Inflammation Therapy Attenuates the Inflammation Tumor Microenvironment and Weakens Immunosuppression for Enhancement Antitumor Treatment
Authors: Zhang Di , Yang Jinghong , Ye Sheng , Wang Yutong , Liu Chuang , Zhang Qianbing , Liu Ruiyuan
Published: February 2022

Photothermal therapy has gained widespread attention in cancer treatment, although its efficacy is suppressed due to the inflammatory response and immunosuppression, resulting in a discounted therapeutic effect. In this contribution, a high‐performance NIR absorption organic small chromophore is developed, which is encapsulated into Pluronic F‐127 to fabricate NIR absorption organic nanoparticles (TTM NPs) with excellent photothermal conversion efficiency (51.49%) for photothermal therapy. TTM NPs based photothermal therapy are combined with Aspisol, a kind of nonsteroidal anti‐inflammatory drug, to weaken the inflammation and immunosuppression tumor microenvironment and enhance the antitumor effect. The results prove that the combination therapy realizes effective thermal elimination of primary tumors, inhibition of distant tumors, and suppression of tumor metastasis. The data show that combination therapy can suppress the expression of inflammatory factors, enhance dendritic cell activation and maturation, reverse the immunosuppression, facilitate T cell infiltration, and restore antitumor cytotoxic T lymphocyte activity. This study provides a paradigm to extend the development of photothermal therapy.
Synthesis and Characterization of the Starch‐ZnO Hybrid Nanoparticles: Effect of the Amylose Content
Authors: Cao Yu , Bian Xiaofang , Luo Shunjing , Liu Chengmei , Hu Xiuting
Published: February 2022

In this work, starches with different amylose contents are used as the stabilizer to prepare zinc oxide nanoparticles through the in situ chemical precipitation method. X‐ray diffraction analysis confirms formation of hexagonal ZnO nanoparticles. It is observed that the ZnO nanoparticles are coated by starch when starch is added during preparation of ZnO nanoparticles, which indicates that the nanoparticles are the starch‐ZnO hybrid nanoparticles. Moreover, hybridization with starches reduces the size of ZnO nanoparticles and the size of hybrid particles is in the order of high‐amylose starch‐ZnO nanoparticles < normal starch‐ZnO nanoparticles < waxy starch‐ZnO nanoparticles. In addition, in the presence of waxy corn starch, some starch particles appear around the waxy corn starch‐ZnO nanoparticles. Hybridization with high‐amylose corn starch enhances the UV absorption ability of ZnO nanoparticles. Furthermore, hybridization with starch enhances the antibacterial activity of ZnO nanoparticles. These results suggest that high‐amylose corn starch has the strongest ability to stabilize ZnO nanoparticles and improve their properties.
Single‐Crystal‐to‐Single‐Crystal (SCSC) Transformation of a Binuclear Cadmium (II) Complex to a Discrete Mononuclear Cadmium (II) Complex
Authors: Xiao Li‐Yuan , Zhang Le‐Xi , Kang You‐Ning , Yin Yan‐Yan , Yuan Zi‐Yuan , Ma Teng , Li Lan‐Xun , Luo Cong‐Yuan , Liu Yang , He Yi‐Mei , Bie Li‐Jian
Published: February 2022

A new binuclear complex {[Cd(phen)2(H2O)] ⋅ (TMA)2−}2 has been synthesized through the reaction of o‐phenanthroline (phen), 3‐thiophenemalonic acid (H2TMA), and cadmium acetate in a 1 : 2 (v/v) EtOH‐H2O mixture at room temperature. This complex can undergo single‐crystal‐to‐single‐crystal (SCSC) transformation to a new mononuclear complex [Cd(phen)3] ⋅ 2(HTMA)− ⋅ H2TMA} by a simple in‐situ solvent evaporation method at room temperature without changing the reaction system. In the whole SCSC process, with the solvent water molecules decreasing and the concentration of ligands increasing, the phen ligands replace the coordination water and coordinate with cadmium ions, finally resulting in the crystal structure transformation in the solid state.
New Insights into Alkali Metal Tungstates: The High Temperature Polymorphism of Na2WO4, the New Polymorph Li2WO4‐V and the Redetermined Crystal Structure of Li2W2O7
Authors: Hämmer Matthias , Höppe Henning A.
Published: February 2022

Trimorphous temperature‐dependent polymorphism (I: above 591°C, II: 589‐591°C, III: below 589°C) was confirmed for sodium tungstate Na2WO4 using DSC and temperature‐programmed powder XRD. Na2WO4‐I crystallises in space group Fddd (no. 70, a=650.28(1), b=1285.12(3), c=1105.26(2) pm, 63 rparam., RBragg = 0.008), for Na2WO4‐II a unit cell is suggested. Moreover, the crystal structure of the new triclinic polymorph Li2WO4‐V prepared employing a LiF flux was elucidated in space group P
(no. 2, a=527.45(2), b=777.69(3), c=797.31(3) pm, α=105.835(2), β=103.391(2), γ=90.581(2)°, 1080 irefl., 100 param., wR2=0.063). Finally, the crystal structure of Li2W2O7 crystallising in space group P
(no. 2, a=505.57(1), b=705.00(2), c=829.03(2) pm, α=69.646(1), β=77.868(1), γ=77.868(1)°, 2386 refl., 105 param., wR2=0.025) was redetermined revealing yet unreported lithium disorder yielding new insights into its high ionic conductivity.
Correction to: CRISPR-Cas9-mediated Gene Editing in Human Induced Pluripotent Stem Cells
Authors: in ’t Groen Stijn L. M. , Broeders Mike , Pijnappel W. W. M. Pim
Published: February 2022

In the original version of this book, chapter 16 was published non-open access. It has now been changed to open access under a CC BY 4.0 license and the copyright holder has been updated to “The Author(s).” This book has also been updated with these changes.
Territorialising Circularity
Authors: Furlan Cecilia , Wandl Alexander , Cavalieri Chiara , Unceta Pablo Munoz
Published: February 2022

Nowadays, the circularity concept dominates the debate on resource management in cities and territories. The idea is often used as a vehicle towards a more sustainable socio-ecological transition, based on the circular economy (CE) framework. Unlike other sustainability frameworks, CE originates in ecological and environmental economics and industrial ecology. It focuses on developing an alternative economic and technological model for production and consumption, avoiding natural resource depletion and redesigning processes and cycles of materials (closed-loops). However, when CE is translated to cities and territories, its environmental, economic and design agency is often neglected. On the one hand, it demands to acknowledge the need for a relational understanding of space, place and actors involved and, on the other, to explore the spatial specificity of CE. Therefore, there is a need for a broader theoretical discourse on the CE’s territoriality as the predominant. Research on circular urban and territorial development demands more than merely upscaling industrial ecosystems diagrams and generating circular businesses. Consequently, what is the role of territory in the CE conceptualisation in the urbanism literature? How to interpret territories through the lens of circularity, which tools, methods are needed? Therefore, territory, its role and meaning in the CE contribution to urban regeneration is the key focus of this text.
Circular City: Urban and Territorial Perspectives
Authors: Lucertini Giulia , Musco Francesco
Published: February 2022

The United Nation’s 17 Sustainable development Goals (SDG) can be considered as the lighthouse of the great challenges which humanity will be confronted with. Many of these goals are related to our behaviors and our “take, make, and dispose,” namely, the linear dominant economic model that, in the last centuries, is leading to an ongoing increase of resource consumption and, consequently, a huge generation of waste. In fact, the rate of both natural resource consumption and waste generation are urgent issues, especially in the urban and peri-urban areas that will require proper solutions. The city is and will be even more in the future the most affected and the major drivers of resource consumption since it is expected that by 2050 more than 70% of the population will live in urbanized areas, and cities will grow in number and size. It means that land, water, food, energy, and other natural resource are increasingly necessary, but because resources are limited, it is required to change the linear consumption model in a new circular model of use and consumption where waste is avoided. In the last few years, emerged that waste management practices are improving according to the European Waste Hierarchy guidance, but there is still a wide possibility of improvement. This chapter explores, on one hand, what means the circular city, and on the other hand how to build it suggesting some policy recommendations. Considering urban and peri-urban areas as the space of material and people flows, thus optimizing the space used by flows and improving their interactions, it will be possible to construct another step toward circularity. In that view, the circular city acquires an urban and territorial perspective that can be managed with the urban and territorial tools, measures, policies, and plans, able to link also issues like climate adaptation, resilience, and sustainability. Finally, we argue that important work must be done in the immediate future in order to re-think and re-design urban spaces, urban practices, and infrastructures, thus shift from linear to circular city.
Outsourcing and Safety—An Introduction
Authors: Hayes Jan , Tillement Stéphanie
Published: February 2022

Organisational safety theory and research has not kept pace with changing trends in the way work is organised. Outsourcing has become very common and is known to be problematic for workplace safety. This book aims to extend consideration of the link between safety and outsourcing to system safety.
Implications for Safe Outsourcing
Authors: Tillement Stéphanie , Hayes Jan
Published: February 2022

This chapter describes some of the lessons highlighted by the different authors of the book. By assessing the different contributions, it discusses the main research and managerial challenges related to the nexus between safety and outsourcing practices. Two main issues are considered: (1) the implications of fragmentation and (2) the importance of addressing the temporal dimension and transience.
Inter-organisational Collaboration for the Safety of Railway Vehicles: A Japanese Case
Authors: Hara Takuji
Published: February 2022

Shinkansen, the Japanese bullet train, has been operating for over 55 years without serious system accidents. Rolling stock is designed and manufactured through a collaboration between railway companies and contracted manufacturers. Safety is ensured through interactions among organisational actors, material entities, institutions and structures. Safety of such a large technical system in an inter-organisational setting cannot be built by material entities but also requires institutions for coordination, and the mindfulness and leadership of relevant actors.
Contracting Qualities that Challenge Reliability: A Case of the Utility Sector
Authors: olde Scholtenhuis Léon L.
Published: February 2022

This study uses the utility construction sector as a case to build the argument that specialisation, transience and price competition impede the reliable functioning of supply chains. These three contracting qualities obstruct the establishment of antecedents of mindfulness and the adherence to mindful organising principles. We offer three solution directions to improve contracting practice.
When the Project Ends and Operations Begin: Ensuring Safety During Commissioning Through Boundary Work
Authors: Russel Anne , Tillement Stéphanie
Published: February 2022

Ensuring safe performance in inter-organisational projects involves managing a whole range of organisational, occupational and spatio-temporal boundaries. Regarding future safety, the commissioning phase is crucial. Drawing from the case of the commissioning of a new nuclear installation, we highlight the challenges associated with the transition between the project and operations and show the socio-material and temporal arrangements that support or hinder boundary work.
SMILE - Smart eMaIl Link Domain Extractor
Authors: Mossano Mattia , Berens Benjamin , Heller Philip , Beckmann Christopher , Aldag Lukas , Mayer Peter , Volkamer Melanie
Published: February 2022

Phishing over email continues to be a significant threat, as such messages still end up in users’ inboxes. Several studies showed that users rarely check the URL in the statusbar before clicking a link and that they have difficulties reading URLs. To support users, we propose SMILE (Smart eMaIl Link domain Extractor), a novel approach that provides the relevant information to distinguish between legitimate and phishing emails checking the links in them. Once applied, SMILE modifies all links in an email to contain the domain and top-level-domain of the URL behind them, e.g., “Click here” in an legitimate Amazon email is modified to “Click here [amazon.com]”.
Syndecan-4 affects myogenesis via Rac1-mediated actin remodeling and exhibits copy-number amplification and increased expression in human rhabdomyosarcoma tumors
Authors: Szabo Kitti , Varga Daniel , Vegh Attila Gergely , Liu Ning , Xiao Xue , Xu Lin , Dux Laszlo , Erdelyi Miklos , Rovo Laszlo , Keller-Pinter Aniko
Published: February 2022

Skeletal muscle demonstrates a high degree of regenerative capacity repeating the embryonic myogenic program under strict control. Rhabdomyosarcoma is the most common sarcoma in childhood and is characterized by impaired muscle differentiation. In this study, we observed that silencing the expression of syndecan-4, the ubiquitously expressed transmembrane heparan sulfate proteoglycan, significantly enhanced myoblast differentiation, and fusion. During muscle differentiation, the gradually decreasing expression of syndecan-4 allows the activation of Rac1, thereby mediating myoblast fusion. Single-molecule localized superresolution direct stochastic optical reconstruction microscopy (dSTORM) imaging revealed nanoscale changes in actin cytoskeletal architecture, and atomic force microscopy showed reduced elasticity of syndecan-4-knockdown cells during fusion. Syndecan-4 copy-number amplification was observed in 28% of human fusion-negative rhabdomyosarcoma tumors and was accompanied by increased syndecan-4 expression based on RNA sequencing data. Our study suggests that syndecan-4 can serve as a tumor driver gene in promoting rabdomyosarcoma tumor development. Our results contribute to the understanding of the role of syndecan-4 in skeletal muscle development, regeneration, and tumorigenesis.
The Epidermal Microbiome Within an Aggregation of Leopard Sharks (Triakis semifasciata) Has Taxonomic Flexibility with Gene Functional Stability Across Three Time-points
Authors: Doane Michael P. , Johnson Colton J. , Johri Shaili , Kerr Emma N. , Morris Megan M. , Desantiago Ric , Turnlund Abigail C. , Goodman Asha , Mora Maria , Lima Laís Farias Oliveira , Nosal Andrew P. , Dinsdale Elizabeth A.
Published: February 2022

The epidermis of Chondrichthyan fishes consists of dermal denticles with production of minimal but protein-rich mucus that collectively, influence the attachment and biofilm development of microbes, facilitating a unique epidermal microbiome. Here, we use metagenomics to provide the taxonomic and functional characterization of the epidermal microbiome of the Triakis semifasciata (leopard shark) at three time-points collected across 4 years to identify links between microbial groups and host metabolism. Our aims include (1) describing the variation of microbiome taxa over time and identifying recurrent microbiome members (present across all time-points); (2) investigating the relationship between the recurrent and flexible taxa (those which are not found consistently across time-points); (3) describing the functional compositions of the microbiome which may suggest links with the host metabolism; and (4) identifying whether metabolic processes are shared across microbial genera or are unique to specific taxa. Microbial members of the microbiome showed high similarity between all individuals (Bray–Curtis similarity index = 82.7, where 0 = no overlap, 100 = total overlap) with the relative abundance of those members varying across sampling time-points, suggesting flexibility of taxa in the microbiome. One hundred and eighty-eight genera were identified as recurrent, including Pseudomonas, Erythrobacter, Alcanivorax, Marinobacter, and Sphingopxis being consistently abundant across time-points, while Limnobacter and Xyella exhibited switching patterns with high relative abundance in 2013, Sphingobium and Sphingomona in 2015, and Altermonas, Leeuwenhoekiella, Gramella, and Maribacter in 2017. Of the 188 genera identified as recurrent, the top 19 relatively abundant genera formed three recurrent groups. The microbiome also displayed high functional similarity between individuals (Bray–Curtis similarity index = 97.6) with gene function composition remaining consistent across all time-points. These results show that while the presence of microbial genera exhibits consistency across time-points, their abundances do fluctuate. Microbial functions however remain stable across time-points; thus, we suggest the leopard shark microbiomes exhibit functional redundancy. We show coexistence of microbes hosted in elasmobranch microbiomes that encode genes involved in utilizing nitrogen, but not fixing nitrogen, degrading urea, and resistant to heavy metal.
Time-dependent expression of high-mobility group box-1 and toll-like receptors proteins as potential determinants of skin wound age in rats: Forensic implication
Authors: Abd-Elhakim Yasmina M. , Omran Bothina H. F. , Ezzeldein Shimaa A. , Ahmed Amany I. , El-Sharkawy Nabela I. , Mohamed Amany Abdel-Rahman
Published: February 2022

The skin wound age determination in living subjects is an imperative task for forensic experts. In this study, we investigated the time-dependent expression of high-mobility group box-1 (HMGB1) and toll-like receptors 2 and 4 (TLR2 and 4) in rat skin wounds using real-time PCR and seek their forensic potentials during the skin wound repair process. In addition, the levels of serum pro-inflammatory cytokines (tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6)), as well as nitric oxide (NO) production, were measured. The wound tissue and serum samples were collected after 30 min, 2 h, 6 h, 12 h, 1 day, 3 days, 5 days, and 7 days after incision. As a control (zero time), skin specimens and blood samples were collected without incision. The results reveal that the HMGB1, TLR2, and TLR4 expression levels were increased in a time-dependent manner until the first day where the peak level was achieved for the three tested genes compared with the zero time. On the 7th day, the statistical significance was lost for TLR2 and TLR4 but persisted for HMGB1. The serum TNF-α, IL6, and NO levels peaked within 30 min and 1st and 3rd day after injury, respectively. On the 7th day after incision, no significant differences exist in the TNF-α serum level compared to the control group, but the statistical significance persisted for IL6 and NO. It was apparent that the analyzed genes in the wound tissues showed higher R2 values rather than the serum biochemical indicators. Of note, a strong positive correlation was evident between the HMGB1 and that of TLR2 and TLR4 relative expression as well as IL-6 serum level. Conclusively, based on the observed changes in the analyzed markers in wound tissues and serum and R2 values obtained from mathematical models established to determine the wound age, the relative expression of HMGB1, TLR2, and TLR4 could be a reliable indicator for wound age determination in living subjects. Further investigation of these markers and mathematical models in human tissues is necessary.
J wave syndromes in patients with spinal and bulbar muscular atrophy
Authors: Steinmetz Karoline , Rudic Boris , Borggrefe Martin , Müller Kathrin , Siebert Reiner , Rottbauer Wolfgang , Ludolph Albert , Buckert Dominik , Rosenbohm Angela
Published: February 2022

Background

Males with X-linked recessive spinobulbar muscular atrophy (SBMA) are reported to die suddenly and a Brugada electrocardiography (ECG) pattern may be present. A hallmark of this pattern is the presence of ST segment elevations in right precordial leads associated with an increased risk of sudden cardiac death.

Objective

We aimed to detect subtle myocardial abnormalities using ECG and cardiovascular magnetic resonance imaging (CMR) in patients with SBMA.

Methods

30 SBMA patients (55.7 ± 11.9 years) and 11 healthy male controls underwent 12-lead ECGs were recorded using conventional and modified chest leads. CMR included feature-tracking strain analysis, late gadolinium enhancement and native T1 and T2 mapping.

Results

Testosterone levels were increased in 6/29 patients. Abnormal ECGs were recorded in 70%, consisting of a Brugada ECG pattern, early repolarization or fragmented QRS. Despite normal left ventricular ejection fraction (66 ± 5%), SBMA patients exhibited more often left ventricular hypertrophy as compared to controls (34.5% vs 20%). End-diastolic volumes were smaller in SBMA patients (left ventricular volume index 61.7 ± 14.7 ml/m2 vs. 79.1 ± 15.5 ml/m2; right ventricular volume index 64.4 ± 16.4 ml/m2 vs. 75.3 ± 17.5 ml/m2). Tissue characterization with T1-mapping revealed diffuse myocardial fibrosis in SBMA patients (73.9% vs. 9.1%, device-specific threshold for T1: 1030 ms).

Conclusion

SBMA patients show abnormal ECGs and structural abnormalities, which may explain an increased risk of sudden death. These findings underline the importance of ECG screening, measurement of testosterone levels and potentially CMR imaging to assess cardiac risk factors.
Home-monitoring of vital capacity in people with a motor neuron disease
Authors: Helleman Jochem , Bakers Jaap N. E. , Pirard Evelien , van den Berg Leonard H. , Visser-Meily Johanna M. A. , Beelen Anita
Published: February 2022

Background

Home-monitoring of spirometry has the potential to improve care for patients with a motor neuron disease (MND) by enabling early detection of respiratory dysfunction and reducing travel burden. Our aim was to evaluate the validity and feasibility of home-monitoring vital capacity (VC) in patients with MND.

Methods

We included 33 patients with amyotrophic lateral sclerosis, progressive muscular atrophy or primary lateral sclerosis who completed a 12-week home-monitoring protocol, consisting of 4-weekly unsupervised home assessments of VC and a functional rating scale. At baseline, during a home visit, patients/caregivers were trained in performing a VC test, and the investigator performed a supervised VC test, which was repeated at final follow-up during a second home visit. Validity of the unsupervised VC tests was evaluated by the differences between supervised and unsupervised VC tests, and through Bland–Altman 95% limits-of-agreement. Feasibility was assessed by means of a survey of user-experiences.

Results

The 95% limits-of-agreement were [− 14.3; 11.7] %predicted VC, and 88% of unsupervised VC tests fell within 10%predicted of supervised VC. 88% of patients experienced VC testing as easy and not burdensome, however, 15% patients did not think their VC test was performed as well as in the clinic. 94% of patients would like home-monitoring of VC in MND care.

Discussion

Unsupervised VC testing at home, with prior face-to-face training, is a valid and time-efficient method for the remote monitoring of respiratory function, and well-accepted by patients with MND and their caregivers.
Localised relative scotoma in cuticular drusen
Authors: Charng Jason , Balaratnasingam Chandrakumar , Attia Mary S. , Heath Jeffery Rachael C. , Chen Fred K.
Published: February 2022

Purpose

To investigate retinal sensitivity changes in eyes with pure cuticular drusen.

Methods

Multimodal imaging and microperimetry (37-loci grid) data were examined retrospectively to evaluate functional changes in eyes with pure cuticular drusen. Mean sensitivity in the cuticular drusen cohort was compared to age-matched normals. An age- and loci-specific normative reference was created to analyse localised sensitivity deviation.

Results

The mean number loci with relative scotoma in the cuticular drusen cohort (n = 27, mean [SD] age: 48.5 [12.4] years) referenced to normal eyes (n = 80, 53.5 [14.6] years) was 5.5 (95% confidence interval 3.0 to 8.1). However, mean sensitivity was not statistically different to the age-matched normal cohort (95% CI, − 2.3 to + 3.4 dB). The 37-loci grid was stratified into three rings of the approximately same number of loci, and the percentage of cuticular drusen eyes with pointwise deviation was significantly lower in the inner compared to the middle ring (12.3 [5.3]% vs. 17.3 [5.1]%, p < 0.05).

Conclusions

Eyes with cuticular drusen demonstrated relative scotoma, but mean sensitivity was not affected. Pointwise sensitivity provides a more robust measure of retinal sensitivity than mean sensitivity in cuticular drusen and should be assessed both in the clinic and in future clinical trials.
Incidence and prognostic factors in severe drug-induced interstitial lung disease caused by antineoplastic drug therapy in the real world
Authors: Kaku Sawako , Horinouchi Hidehito , Watanabe Hirokazu , Yonemori Kan , Okusaka Takuji , Boku Narikazu , Yamazaki Naoya , Kawai Akira , Ohe Yuichiro , Kusumoto Masahiko
Published: February 2022

Purpose

Investigate the frequency and prognostic factors of severe drug-induced interstitial lung disease (DILD) caused by antineoplastic drugs regardless of cancer types or type of drugs.

Methods

From 2014 to 2018, we reviewed patients with a history of antineoplastic agents administration in the real-world database of our hospital's electronic medical record and extracted patients who experienced "severe" DILD, requiring hospitalization with treatment or developed during hospitalization and required treatment. We collected patients' backgrounds, clinical and radiological features, laboratory data, treatment, and survival outcomes.

Results

19,132 cancer patients received antineoplastic drug therapy during the study period, and 120 (0.62%) experienced severe DILD. The incidence of severe DILD in patients with thoracic cancer was highest among the patients included in this analysis (2.52% vs. 0.34% other cancers). Diffuse alveolar damage (DAD) pattern on CT was associated with higher mortality in patients with severe DILD compared with non-DAD pattern (hazard ratio [HR], 11.24; 95% CI, 4.82–26.2). Multivariate analysis revealed that the DAD pattern at diagnosis as severe DILD (HR, 3.59; 95% CI, 1.17–11.03), concurrent/previous interstitial lung disease (HR, 3.20; 95% CI, 1.27–8.10), and ECOG performance status of 2–4 (HR, 3.81; 95% CI, 1.10–13.17) were independent risk factors for mortality in patients with severe DILD.

Conclusions

The frequency of severe DILD was highest in patients with thoracic cancer. The DAD pattern was associated with a poor outcome. From the perspective of DILD, special attention should be paid when administering antineoplastic agents to patients with thoracic cancer.
Operator-norm homogenisation estimates for the system of Maxwell equations on periodic singular structures
Authors: Cherednichenko Kirill , D’Onofrio Serena
Published: February 2022

For arbitrarily small values of $$\varepsilon >0,$$

ε
>
0
,

we formulate and analyse the Maxwell system of equations of electromagnetism on $$\varepsilon $$
ε
-periodic sets $$S^\varepsilon \subset {{\mathbb {R}}}^3.$$

S
ε

⊂

R

3

.

Assuming that a family of Borel measures $$\mu ^\varepsilon ,$$

μ
ε

,

such that $$\mathrm{supp}(\mu ^\varepsilon )=S^\varepsilon ,$$

supp

(

μ
ε

)

=

S
ε

,

is obtained by $$\varepsilon $$
ε
-contraction of a fixed 1-periodic measure $$\mu ,$$

μ
,

and for right-hand sides $$f^\varepsilon \in L^2({\mathbb {R}}^3, d\mu ^\varepsilon ),$$

f
ε

∈

L
2

(

R

3

,
d

μ
ε

)

,

we prove order-sharp norm-resolvent convergence estimates for the solutions of the system. Our analysis includes the case of periodic “singular structures”, when $$\mu $$
μ
is supported by lower-dimensional manifolds. The estimates are obtained by combining several new tools we develop for analysing the Floquet decomposition of an elliptic differential operator on functions from Sobolev spaces with respect to a periodic Borel measure. These tools include a generalisation of the classical Helmholtz decomposition for $$L^2$$

L
2

functions, an associated Poincaré-type inequality, uniform with respect to the parameter of the Floquet decomposition, and an appropriate asymptotic expansion inspired by the classical power series. Our technique does not involve any spectral analysis and does not rely on the existing approaches, such as Bloch wave homogenisation or the spectral germ method.
Vulnerable Waters are Essential to Watershed Resilience
Authors: Lane Charles R. , Creed Irena F. , Golden Heather E. , Leibowitz Scott G. , Mushet David M. , Rains Mark C. , Wu Qiusheng , D’Amico Ellen , Alexander Laurie C. , Ali Genevieve A. , Basu Nandita B. , Bennett Micah G. , Christensen Jay R. , Cohen Matthew J. , Covino Tim P. , DeVries Ben , Hill Ryan A. , Jencso Kelsey , Lang Megan W. , McLaughlin Daniel L. , Rosenberry Donald O. , Rover Jennifer , Vanderhoof Melanie K.
Published: February 2022

Watershed resilience is the ability of a watershed to maintain its characteristic system state while concurrently resisting, adapting to, and reorganizing after hydrological (for example, drought, flooding) or biogeochemical (for example, excessive nutrient) disturbances. Vulnerable waters include non-floodplain wetlands and headwater streams, abundant watershed components representing the most distal extent of the freshwater aquatic network. Vulnerable waters are hydrologically dynamic and biogeochemically reactive aquatic systems, storing, processing, and releasing water and entrained (that is, dissolved and particulate) materials along expanding and contracting aquatic networks. The hydrological and biogeochemical functions emerging from these processes affect the magnitude, frequency, timing, duration, storage, and rate of change of material and energy fluxes among watershed components and to downstream waters, thereby maintaining watershed states and imparting watershed resilience. We present here a conceptual framework for understanding how vulnerable waters confer watershed resilience. We demonstrate how individual and cumulative vulnerable-water modifications (for example, reduced extent, altered connectivity) affect watershed-scale hydrological and biogeochemical disturbance response and recovery, which decreases watershed resilience and can trigger transitions across thresholds to alternative watershed states (for example, states conducive to increased flood frequency or nutrient concentrations). We subsequently describe how resilient watersheds require spatial heterogeneity and temporal variability in hydrological and biogeochemical interactions between terrestrial systems and down-gradient waters, which necessitates attention to the conservation and restoration of vulnerable waters and their downstream connectivity gradients. To conclude, we provide actionable principles for resilient watersheds and articulate research needs to further watershed resilience science and vulnerable-water management.
Scalable, password-based and threshold authentication for smart homes
Authors: Huszti Andrea , Kovács Szabolcs , Oláh Norbert
Published: February 2022

Smart homes are a special use-case of the IoT paradigm, which is becoming more and more important in our lives. Although sensors, devices and applications make our daily lives easier, they often collect our sensitive data, which may lead to security problems (e.g., hacked devices, botnets, etc.). In several cases, the appropriate security mechanisms are missing within the devices. Therefore, security measures have become a central topic in the field of IoT. The most essential requirements are secure user–device authentication and confidentiality of transferred sensitive data. Passwords are the most widely used factors in various areas, such as user authentication, key establishment, and also secret sharing. Password-based protocols that are resistant to typical threats, such as offline dictionary, man-in-the-middle and phishing attacks, generate new session keys. The major aim of these solutions is to guarantee high-level security, even if a user applies a single low-entropy human memorable password for all their accounts. We introduce a threshold and password-based, distributed, mutual authenticated key agreement with key confirmation protocol for a smart home environment. The proposed protocol is a scalable and robust scheme, which forces the adversary to corrupt $$l-1$$

l
-
1

smart home devices, where l is the threshold, in order to perform an offline dictionary attack. The protocol is designed to achieve password-only setting, and end-to-end security if the chosen IoT devices are also authenticated besides the user. We also provide a security analysis of the protocol in AVISPA. We apply the on-the-fly model checker and the constraint-logic-based attack searcher to perform protocol verification for bounded numbers of sessions. We show that the proposed protocol provides session key secrecy and mutual authentication of the user and the device manager. Since efficiency is a crucial aspect, we implemented our protocol to measure the computation and communication costs and demonstrate that our solution is appropriate and eligible for smart homes.
Role of liver stiffness measurements in patients who develop hepatocellular carcinoma after clearance of the hepatitis C virus
Authors: Gyotoku Yoshinori , Shirahashi Ryosaku , Suda Toshikuni , Tamano Masaya
Published: February 2022

Purpose

To measure changes in liver stiffness over time due to direct-acting antiviral (DAA) therapy in hepatitis C patients using shear wave elastography (SWE).

Methods

Patients with hepatitis C treated with DAA therapy in a university medical center between July 2015 and April 2020 were evaluated. Shear wave velocity (Vs) of the liver was measured using SWE. Alanine aminotransferase (ALT), platelet count, and α-fetoprotein (AFP) were measured at the same time, and the FIB-4 index was estimated. Absence of hepatocellular carcinoma was confirmed at baseline and end of therapy. Imaging was then performed every 6 months. Patient characteristics were compared between patients who did and did not develop carcinoma.

Results

The mean age of the 229 patients (93 men) was 65.6 years. Eight patients developed carcinoma during follow-up (mean 32.6 ± 19.5 months). Significant differences were found between the groups in terms of AFP, platelet count, and Fib-4 index at baseline; the pre-treatment data had the best relationship with hepatocarcinogenesis. Mean Vs decreased significantly during DAA therapy, and then decreased further. Liver stiffness 6 months after treatment ended had the best relationship with hepatocarcinogenesis.

Conclusion

In patients with a sustained virological response, risk of developing cancer can be predicted by measuring Vs approximately 6 months after treatment.
Characterization and modeling the hygroscopic behavior of cellulose acetate membranes
Authors: Khoshtinat Shiva , Carvelli Valter , Marano Claudia
Published: February 2022

Exploiting materials with the ability to respond to the environmental stimuli is experiencing an enormous research interest. In particular, polymers that are sensitive to the changes of humidity levels attract great attention as self-actuators. The sensitivity of these materials to the level of moisture is expressed by their hygroscopic properties, namely, the coefficient of hygroscopic expansion. In this context, this study details the effect of moisture absorption on cellulose acetate membranes, as potential material for humidity-responsive self-actuators. The aim is two-fold. The first deals with the evaluation of the coefficient of hygroscopic expansion (α) through the determination of the absorbed moisture concentration at saturation (Csat) and the relevant moisture absorption induced strain (εhygro). The second assesses the accuracy of a finite element modeling in describing the coupling of moisture absorption in cellulose acetate membranes and the corresponding dimensional variation, using the material properties experimentally measured. The experimentally measured Csat and εhygro resulted a non-linear dependency on relative humidity. Also the coefficient of hygroscopic expansion (α = Csat /εhygro) resulted to have a non-linear dependency on the relative humidity, as well. By this input, numerical simulations were performed for different relative humidity levels, showing accurate description of experimental data.
ICT infrastructure in firms and online sales
Authors: Hagsten Eva
Published: February 2022

This study investigates whether the underlying information and communication technology (ICT) infrastructure of firms affects the development of online sales, based on a novel micro-aggregated panel dataset encompassing a large group of European countries. The dataset includes continuous measures of online sales activities, as well as of standard production function input variables. Dynamic System GMM estimations show positive and significant associations between the proportion of firms selling online and the ICT infrastructure, measured as the proportion of broadband internet connected employees. The magnitude of the effect is stronger in the group of manufacturing than in the service firms, but in both industries, there is a threshold beyond which the positive effects of the infrastructure diminish. In addition, there is evidence that improvements in the infrastructure lead to a stronger effect on medium-sized and large rather than on small firms.
Narratives of the Future Affect Fertility: Evidence from a Laboratory Experiment
Authors: Vignoli Daniele , Minello Alessandra , Bazzani Giacomo , Matera Camilla , Rapallini Chiara
Published: February 2022

In recent years, fertility rates have declined in most wealthy countries. This phenomenon has largely been explained by focusing on the rise of economic uncertainty. We contribute to this debate by arguing that, under uncertain conditions,narratives of the future—i.e., socially conveyed imagined futures—impact individuals’ decision-making about childbearing. To assess this impact, we conducted (for the first time in fertility intention research) a controlled laboratory experiment in two contrasting settings: Florence (Italy,N = 800) and Oslo (Norway,N = 874). Individuals were randomly exposed to a specific positive or negative future economic scenario (treatments) and were compared with individuals who were not exposed to any scenario (control group). Participants were then asked whether they intended to have a child in the next three years. The results showed a clearcausalimpact of narratives of the future on fertility intentions among the participants. Moreover, when the actual economic condition at the macro- (country context) or micro-level (labor-market status and characteristics) was more favorable,negativenarratives of the future played a more crucial role. Conversely, when the actual economic conditions were less favorable,positivenarratives of the future proved especially important. We conclude that, in the era of global uncertainty, individuals respond to more than their actual situation and constraints; narratives of the future create adistance experiencefrom the daily routine that plays a potent role by inhibiting or facilitating fertility decision-making.