bluuebunny/crossref_metadata_2025 huggingface dataset:
Social and environmental aspects of courtyards in Cyprus vernacular architecture
Authors: Philokyprou Maria , Michael Aimilios
Published: July 2021

Central courtyards emerged in many civilizations of the world. Cyprus was no exception as courtyards formed important architectural features throughout the centuries in the residential architecture of the island. The erection of dwellings attached to each other, the need for a private outdoor protected space due to the introverted character of societies, as well as the climatic conditions, i.e. warm Mediterranean climate, led to a widespread use of the courtyard in nearly all traditional residences of the island in the last two centuries. Apart from vernacular architecture, courtyards appeared in earlier historic periods and, in some cases, they were found to be used in the residential architecture of more recent decades. This paper presents an analytical study of the social and environmental aspects of courtyards in the vernacular dwellings of Cyprus. The research underlines the role of the courtyard as an important social gathering area, as well as a microclimate regulator in the residences. Moreover, it highlights its bioclimatic significance in enhancing the integration of nature's elements into the design and overall architectural concept of the dwelling.
Criteria of sustainable reconstruction and acceptance of the historic town squares in Serbia
Authors: Milojević Milica , Petrović Darko
Published: July 2021

The common feature of contemporary approaches to urban reconstruction is sustainability. For a number of years now, there has been considerable research on the ecological, social and economic aspect of sustainability. In addition to these three pillars, the document Rio+20 introduced the crucial role of culture into the establishment and execution of the paradigm of sustainability. Sustainable tourism, cultural and creative industries and urban revitalization of heritage are the key economy sectors that generate successful local development and strengthen creativity. Public spaces, seen through the prism of sustainability, is the public and cultural capital citizens use, transform, enlarge and then transfer on to future generations. With this in mind, the reconstruction and improvement of the historic town squares as representative public space has particular importance, made yet more significant in our country, given that the regulation of first squares in Serbian towns in 19th and 20th century has been the result of state aspiration towards the European cultural milieu and its endeavor to determine national identity within the framework of European values.
Mapping the vernacular environment: Serbian village atlas as a step towards an eco-village network
Authors: Bunjak Ksenija , Pešić Mladen
Published: July 2021

The main research subject is forming optimal local models of the architectural and technological intervention in rural areas of the Republic of Serbia, as a way of climate change adaptation, as well as their feasibility study on the West Pomoravlje area. Each region has its own unique features. Thus, in the territory of the Republic of Serbia can be defined zones with the same local characteristics, using the following criteria of physical and human geography: geo-physiognomic characteristics, climatic characteristics, economic development, and level of urbanity. These criteria are defined as the most important. They are the primary determinants for choosing the architectural and technological interventions within the local model as a way of climate change adaptation. The first part of research deals with the zoning of the Republic of Serbia and defining the zones with the same local characteristics. Atlas of villages, providing their current types and possible future models, will be created. The second part is based on the case study of one of the zones - West Pomoravlje zone. Villages and households within the zone will be analysed and sorted into the types and groups. Further research will be based on the examination of possibilities of transforming the existing villages into the eco-villages, mapping the most appropriate positions for new eco-villages and forming a potential eco-village network.
Influence of amelioration on the productivity of alfalfa on acid soil types vertisols
Authors: Stojiljković Jelena , Rajičić Vera , Terzić Dragan , Radojević Vuk , Đurić Nenad , Ljubičić Nataša , Popović Vera
Published: July 2021

Alfalfa is the most important forage legume in our agroecological conditions for feeding cattle. In the area of Jablanica district, alfalfa occupies a considerable place in the total plant production. The restrictive factor in the establishment and short durability of alfalfa stand is the low pH of arable agricultural soil. Within the three-year field trial on Vertisol soil type (pH in KCl 4.9), from 2016 to 2018, alfalfa plot yield has been analyzed with different fertilization variants. The research results indicate that alfalfa provides a significantly higher yield on the plot where amelioration measures were applied, through the application of limestone and manure, with the addition of mineral fertilizer. A barely lower yield was achieved on the calcified and manured plot, while the lowest yield was on the control plot, where a generous amount of mineral fertilizer was added, which is a common practice of agricultural producers in the area of Jablanica district.
Correlations of grain yields and yield components among mother's and full-sib progenies of soybean
Authors: Srebrić Mirjana , Perić Vesna
Published: July 2021

The F2 population was developed by crossing the adaptive yield variety of soybean with a variety without the Kunitz trypsin inhibitor in the mature grain. From the segregating F2 population 48 plants were taken. Their seeds were used to set up field experiment; part of the seed was saved for full-sib (FS) crosses. After yield testing, three lines marked as L6, L30 and L38 were chosen. Two FS cross combination, using saved seeds, were made (L30 x L38 and L6 x L30). Progenies of soybean full-sibs (FSF1:2) and each mother plant (F3:4) were grown, to make enough seed for testing in the field experiment. Data obtained in this experiment were processed to determine correlations of grain yield and other studied traits between mother's and proper full-sib progenies, using simple correlations and Spearman's rank correlations. A significant correlation into examinated traits between two types of progenies does not found, except for stem height and 1000 grain weight in the FS combination L30 x L38. The lack of correlation of plant characteristics between progenies of full-sibs and their mothers indicated the influence of lines used as fathers component. In both combinations of FS crosses, FSF1:2 progenies with better yield than the adapted parent (one without Kunitz trypsin inhibitor) were identified, which are considered promising for the further process of creating new varieties.
Flexible operation in the digital economy
Authors: Radović-Marković Mirjana , Vučeković Miloš , Marković Dušan
Published: July 2021

With the digitalization of companies and work, the business environment and working conditions have changed. Namely, the progress in ICT changed the ways of work organization and influenced the new work model. Teleworking and mobile work provided workers with the opportunity to adapt their time and place of work to their needs. Accordingly, digitization enables more complex organizational forms and affects an increasing number of tasks. The main goal of our study was to investigate the implications of work flexibility on the worker's health. In other words, are there any risks that this new working arrangement will lead to a shortening of working life? Our research has shown that these types of work arrangements can lead to increased workload and overwork, even where workers have a high level of autonomy. Consequently, workers are exposed to great health risks: stress, anxiety and other health problems related to the new work environment.
New challenges for banking, financial services and insurance
Authors: Radić Nikola
Published: July 2021

The crisis with the COVID-19 pandemic shows investors, policy makers and the general public that natural disasters can cause economic damage on an unprecedented scale. The pandemic has made customer experience even more differentiated, so banks, financial service providers and insurance companies need to optimize their operations and transform existing business models to meet new requirements and withstand competitive pressure. Because the processes are the "veins" of a highly regulated business, they must adapt to unprecedented change. Changing business models, disruptive technologies, and compliance pressures are forcing traditional institutions to reorganize the way they do business. Digital transformation, the macro trend that has defined the past decade, has accelerated at an incredible rate during 2020. Creative new solutions are made out of the need for people to connect despite physical distance. In addition, customer expectations have changed, so many of them want to be provided with ongoing personalized services. But moving from the old service delivery system to modern solutions has never been an easy task.
Opportunities to Learn From (Advanced) Mathematical Coursework: A Teacher Perspective on Observed Classroom Practice
Authors: Wasserman Nicholas H. , McGuffey William
Published: July 2021

This article explores secondary teachers’ opportunities to learn from an innovative real analysis course, as reflected in their actual classroom teaching. The course used cases of teaching as a site for applying mathematics and developing pedagogical mathematical practices. This article explores particular teaching moments in (N= 6) secondary teachers’ classrooms, and the attributions they gave for why they engaged in those teaching practices. Teachers engaged in instructional practices that exemplified course objectives, and their attributions for their actions contribute a teacher perspective on opportunities to learn in teacher education from (advanced) mathematical coursework. Results highlight cases of teaching and modeled instruction as catalysts of change and as opportunities to develop pedagogy from mathematical activity, and vice versa.
Innovation, conformity and other ambivalences in fashion design
Authors: Campos Amanda Queiroz
Published: July 2021

This article problematizes the creation in fashion design. A noticeable majority of companies in the fashion market accompanies trends, which are edited by bureaux de style, disseminated by fashion designers at week runway shows and advertised as successful bets by the fashion media. This investigation results from the development of a research about the agency of fashion designers. The given scope emphasizes the dialectics of creation x adequacy and innovation x security. More specifically, the paper addresses the considerations of three interviewees conducted for the validation of the research’s results. During the dialogues - which consisted of informal telephone conversations aided by a semi-structured script – the professionals reported their reflections on deliberate acts of creation and the business logic of fashion design corporations.
Intimate partner violence and physical health problems in women
Authors: Pate Tanja , Simonič Barbara
Published: July 2021

Numerous findings in scientific literature consistently show the association of intimate partner violence (IPV) and domestic abuse with the risk for and incidence of a series of different physical health conditions and problems. Studies have shown the association of IPV and overall health and wellbeing especially in women. The purpose of the paper is therefore to present an overview of the research in the field of IPV and women’s mental and physical health. Both quantitative and qualitative research studies published from 2012 to 2018 were included in the review. The results show that IPV is associated with several mental health problems in women, such as depression, anxiety and post-traumatic stress disorder, as well as with women’s worse physical health, chronic pain, substance abuse, gynaecological, cardiovascular and gastrointestinal problems and behavioural syndromes associated with physiological disturbances and physical factors. The article reviews current studies and confirms that the experience of IPV in women has long-term consequences for their physical and mental health.
Environmental Issues and Strategic Corporate Social Responsibility for Organizational Competitiveness
Authors: Ahmed Rizwan Raheem , Streimikiene Dalia
Published: July 2021

The objective of this study is to examine a multi-dimensional modified conceptual model based on stakeholder theory & previous literature. The work represents an attempt to evaluate the association of environmental issues and practices of an organization’s corporate social responsibility and the impact of these two factors on overall competitiveness. We have taken four corporate social responsibility (CSR) factors regarding the environment that affect competitive organizational performance. Additionally, we incorporated green innovation as a mediator and social media marketing apps as a moderator to examine the impact on organizational competitiveness. We collected 906 responses from the manufacturing and services sectors from the regional developing Asian countries China, India, Pakistan, Bangladesh, and the UAE for more generalizable and robust results. We developed a modified questionnaire and conceptual framework to empirically test organizational performance & competitiveness. For the analysis, we employed SEM-based multivariate modeling. The study’s findings reveal that all the considered CSR factors of the environment positively and significantly impact organizational performance for competitiveness. The results further show that both green innovation as a mediator and social media marketing apps as moderators significantly impact the relationship of CSR factors of environment and organizational competitiveness. Thus, the modified conceptual model demonstrates that the environmental CSR factors are beneficial for the manufacturing and service sectors of developing economies, which create value for competitive business, society, and environment. The findings provide valuable directions for the senior management in the manufacturing and services sector to devise and implement environmental strategies for competitiveness.
Job Insecurity, Job Instability, and Job Satisfaction in the Context of the COVID-19 Pandemic
Authors: Nemteanu Marcela-Sefora , Dinu Vasile , Dabija Dan-Cristian
Published: July 2021

The COVID-19 pandemic has brought new challenges regarding employee adaptation to change as well as job security, with levels of wellbeing and satisfaction being greatly affected. Based on the literature as well as on Adaptation-level Theory, Stress and Coping Theory, and Motivationhygiene Theory, this paper approaches the link between job insecurity and job instability during the COVID-19 pandemic along with employee job satisfaction in an emerging market. The proposed conceptual model analyses the influence of job instability and job insecurity on individual job satisfaction, including supervisor support and promotion opportunities. The survey-based empirical study was implemented with the aid of a questionnaire taken by 568 employees in Romania. The results determined with the help of a correlation analysis highlight a strong, direct, and positive link between job instability and employee insecurity in increasing employee competitiveness. The impact of job insecurity and instability on the components considered in terms of job satisfaction vary. Job insecurity was shown to manifest a negative correlation only with regard to satisfaction concerning supervisor support and promotion opportunities. Perceived job instability showed a significant negative impact on individual work satisfaction, satisfaction with supervisor support and promotion opportunities. This paper also enhances the human resources literature by demonstrating how organisational competitiveness might be enhanced during a global pandemic by focusing on employees.
The Digital Competitiveness of European Countries: A Multiple-Criteria Approach
Authors: Stankovic Jelena J. , Marjanovic Ivana , Drezgic Sasa , Popovic Zarko
Published: July 2021

High-quality digital infrastructure is the basis of almost every sector of a modern and innovative economy and society. As a part of the overall competitiveness concept, digital competitiveness is a multidimensional structure that encompasses various factors of the process of digital transformation through the ability of learning and application of new technologies, technology factors that enable digital transformation, and digital readiness factors that assess the preparedness of an economy and citizens to assume digital transformation. The paper aims to propose a methodology for measuring digital competitiveness using a composite index approach including a variety of various indicators. To assess the digital competitiveness of European countries, a multi-criteria analysis was applied in a two-stage procedure integrating CRITIC and TOPSIS as weighting and aggregation methods. The sample includes thirty European countries and the research is based on thirteen indicators provided in the database Eurostat Digital Economy and Society. In addition, a ranking of sample countries according to digital competitiveness is presented. Finally, a cluster analysis was conducted to examine relations between digital competitiveness and several economic performances such as GDP pc, labour productivity and employment rates. The results indicate that Nordic countries have achieved the highest digital competitiveness, while most Eastern European countries still lag behind.
The Performance Determinants of Trading Companies: A Stakeholder Perspective
Authors: Tousek Zdenek , Hinke Jana , Malinska Barbora , Prokop Martin
Published: July 2021

This research aims to propose a model adding to the competitiveness of companies by identifying factors that determine the profitability of the selected companies (both publicly traded and unquoted private companies of all sizes). Another aim is to prove a dichotomy between the motivation of equity holders and senior lenders as far as acceptable financial leverage is concerned. The paper is innovative based on its combination of several different factors influencing corporate profitability (i.e. firm-specific effects: current ratio, labor cost ratio, working capital financing ratio, long-term financing ratio, return on sales, age of the firm; industry-specific effects and other macroeconomic effects) and by assessing determinants concerning the interests of shareholders and other stakeholders using a panel regression analysis with fixed effects. The authors prove that the determinants of the operating performance of Czech trading companies differ substantially when the performance is measured by ROA or by ROE. This clearly shows discrepancies between the equity holder interest to maximize their returns on investment and the other stakeholder interests. Specifically, the authors have found that the leverage, both in terms of working capital and long-term financing, negatively impacts returns on assets. On the other hand, it positively impacts returns for equity holders both in the Wholesale and Retail sub-samples. Interestingly, other determinants of operating performance, such as capital intensity, labor cost ratio, historical profitability, and macroeconomic variables, are of comparable significance, impacting both the ROA and ROE analyses.
Efficacy profile of the CYD-TDV dengue vaccine revealed by Bayesian survival analysis of individual-level phase III data
Authors: Laydon Daniel J , Dorigatti Ilaria , Hinsley Wes R , Nedjati-Gilani Gemma , Coudeville Laurent , Ferguson Neil M
Published: July 2021

Background:

Sanofi-Pasteur’s CYD-TDV is the only licensed dengue vaccine. Two phase three trials showed higher efficacy in seropositive than seronegative recipients. Hospital follow-up revealed increased hospitalisation in 2–5- year-old vaccinees, where serostatus and age effects were unresolved.

Methods:

We fit a survival model to individual-level data from both trials, including year 1 of hospital follow-up. We determine efficacy by age, serostatus, serotype and severity, and examine efficacy duration and vaccine action mechanism.

Results:

Our modelling indicates that vaccine-induced immunity is long-lived in seropositive recipients, and therefore that vaccinating seropositives gives higher protection than two natural infections. Long-term increased hospitalisation risk outweighs short-lived immunity in seronegatives. Independently of serostatus, transient immunity increases with age, and is highest against serotype 4. Benefit is higher in seropositives, and risk enhancement is greater in seronegatives, against hospitalised disease than against febrile disease.

Conclusions:

Our results support vaccinating seropositives only. Rapid diagnostic tests would enable viable ‘screen-then-vaccinate’ programs. Since CYD-TDV acts as a silent infection, long-term safety of other vaccine candidates must be closely monitored.

Funding:

Bill & Melinda Gates Foundation, National Institute for Health Research, UK Medical Research Council, Wellcome Trust, Royal Society.

Clinical trial number:

NCT01373281 and NCT01374516.
Two de novo GluN2B mutations affect multiple NMDAR-functions and instigate severe pediatric encephalopathy
Authors: Kellner Shai , Abbasi Abeer , Carmi Ido , Heinrich Ronit , Garin-Shkolnik Tali , Hershkovitz Tova , Giladi Moshe , Haitin Yoni , Johannesen Katrine M , Steensbjerre Møller Rikke , Berlin Shai
Published: July 2021

The N-methyl-D-aspartate receptors (NMDARs; GluNRS) are glutamate receptors, commonly located at excitatory synapses. Mutations affecting receptor function often lead to devastating neurodevelopmental disorders. We have identified two toddlers with different heterozygous missense mutations of the same, and highly conserved, glycine residue located in the ligand-binding-domain of GRIN2B: G689C and G689S. Structure simulations suggest severely impaired glutamate binding, which we confirm by functional analysis. Both variants show three orders of magnitude reductions in glutamate EC50, with G689S exhibiting the largest reductions observed for GRIN2B (~2000-fold). Moreover, variants multimerize with, and upregulate, GluN2Bwt-subunits, thus engendering a strong dominant-negative effect on mixed channels. In neurons, overexpression of the variants instigates suppression of synaptic GluNRs. Lastly, while exploring spermine potentiation as a potential treatment, we discovered that the variants fail to respond due to G689’s novel role in proton-sensing. Together, we describe two unique variants with extreme effects on channel function. We employ protein-stability measures to explain why current (and future) LBD mutations in GluN2B primarily instigate Loss-of-Function.
Kritisk design literacy i grunnskolen
Authors: Lutnæs Eva
Published: July 2021

Menneskene har med sine kreative krefter erstattet natur med kultur i et slikt omfang at en ny geologisk epoke er foreslått, antropocen. Design som disiplin bærer i seg en transformativ agenda – alltid på vei mot noe nytt. Vil utvikling av grunnskoleelevenes designkompetanse bare øke belastningen på naturen? Her er det avgjørende hvilke roller elevene tilbys gjennom utdanning, samt hvordan design forstås og praktiseres. I denne litteraturstudien settes omstilling mot et mer bærekraftig samfunn som premiss når akademiske tekster granskes. Fire narrativ peker seg ut og danner utgangspunkt for en definisjon der målet for designkompetanse på grunnskolenivå er den kritiske og skapende borger som kan nærme seg problemer som komplekse, fremme endring gjennom egne designprosesser og møte designløsninger med spørsmål om hvordan de støtter opp under bærekraftige praksiser.
A survey on modeling dynamic business processes
Authors: Kalibatiene Diana , Vasilecas Olegas
Published: July 2021

Dynamic and flexible systems offer huge advantages for businesses in addressing dynamic uncertain factors and implementing dynamic business processes (DBP). However, DBP remains a challenge from the perspectives of modeling, simulation, and implementation because of a nontrivial understanding of “What is a dynamic business process?” A variety of approaches for DBP modeling and implementation have been proposed over the past years, yet few comprehensive studies analyzing DBP from different particular perspectives (e.g., business process (BP) variability, aspect oriented BP, service compositions, etc.) and research questions that lay the foundation for the development of a meaning of a DBP have been reported. The motivation behind this review is to examine DBP meaning from a global perspective and, consequently, answer the previously presented research question. Therefore, in this paper, we present a systematic literature review (SLR) comprised of 67 papers from five respective digital libraries, which index Computer Science (CS), Information Systems (IS), and Software Engineering (SE) journals and conference proceedings. Two points of view are analyzed in the selected papers. First, we observe the similarities and differences between the proposed approaches to DBP modeling and implementation. From these observations, we define six main requirements for DBP (DBPR). In addition, the comparison of the selected papers according to DBPR shows that most of the approaches analyzed limit BP dynamicity, since they use partially predefined BP models. Secondly, we analyze the papers based on a visualization perspective that shows the less explored areas as follows: more flexible process modeling approach and its implementation in IS should be developed; usage of historic data should be extended; domain knowledge usage, like goal-orientation, multi-criteria optimization, domain knowledge, artificial intelligence, etc., should be included and extended to ensure BP dynamicity. As such, this study makes important contributions and serves as a useful resource for future DBP studies and practice. Moreover, we expect that our results could inspire researchers and practitioners towards further work aimed at bringing forward the field of DBP modeling and implementation.
Repression of ZCT1, ZCT2 and ZCT3 affects expression of terpenoid indole alkaloid biosynthetic and regulatory genes
Authors: Li Chun Yao , Gibson Susan I.
Published: July 2021

Terpenoid indole alkaloids (TIAs) include several valuable pharmaceuticals. As Catharanthus roseus remains the primary source of these TIA pharmaceuticals, several research groups have devoted substantial efforts to increase production of these compounds by C. roseus. Efforts to increase TIA production by overexpressing positive regulators of TIA biosynthetic genes have met with limited success. This limited success might be due to the fact that overexpression of several positive TIA regulators turns on expression of negative regulators of TIA biosynthetic genes. Consequently, a more effective approach for increasing expression of TIA biosynthetic genes might be to decrease expression of negative regulators of TIA biosynthetic genes. Towards this end, an RNAi construct was generated that expresses a hairpin RNA carrying nucleotide fragments from three negative transcriptional regulators of TIA genes, ZCT1, ZCT2 and ZCT3, under the control of a beta-estradiol inducible promoter. Transgenic C. roseus hairy root lines carrying this ZCT RNAi construct exhibit significant reductions in transcript levels of all three ZCT genes. Surprisingly, out of eight TIA biosynthetic genes analyzed, seven (CPR, LAMT, TDC, STR, 16OMT, D4H and DAT) exhibited decreased rather than increased transcript levels in response to reductions in ZCT transcript levels. The lone exception was T19H, which exhibited the expected negative correlation in transcript levels with transcript levels of all three ZCT genes. A possible explanation for the T19H expression pattern being the opposite of the expression patterns of the other TIA biosynthetic genes tested is that T19H shunts metabolites away from vindoline production whereas the products of the other genes tested shunt metabolites towards vindoline metabolism. Consequently, both increased expression of T19H and decreased expression of one or more of the other seven genes tested would be expected to have similar effects on flux through the TIA pathway. As T19H expression is lower in the ZCT RNAi hairy root lines than in the control hairy root line, the ZCTs could act directly to inhibit expression of T19H. In contrast, ZCT regulation of the other seven TIA biosynthetic genes tested is likely to occur indirectly, possibly by the ZCTs turning off expression of a negative transcriptional regulator of some TIA genes. In fact, transcript levels of a negative TIA transcriptional regulator, GBF1, exhibited a strong, and statistically significant, negative correlation with transcript levels of ZCT1, ZCT2 and ZCT3. Together, these findings suggest that the ZCTs repress expression of some TIA biosynthetic genes, but increase expression of other TIA biosynthetic genes, possibly by turning down expression of GBF1.
ASC‐1 transporter‐dependent amino acid uptake is required for the efficient thermogenic response of human adipocytes to adrenergic stimulation
Authors: Arianti Rini , Vinnai Boglárka Ágnes , Tóth Beáta B. , Shaw Abhirup , Csősz Éva , Vámos Attila , Győry Ferenc , Fischer‐Posovszky Pamela , Wabitsch Martin , Kristóf Endre , Fésüs László
Published: July 2021

Brown and beige adipocytes dissipate energy by uncoupling protein 1 (UCP1)‐dependent and UCP1‐independent thermogenesis, which may be utilized to develop treatments against obesity. We have found that mRNA and protein expression of the alanine/serine/cysteine transporter‐1 (ASC‐1) was induced during adipocyte differentiation of human brown‐prone deep neck and beige‐competent subcutaneous neck progenitors, and SGBS preadipocytes. cAMP stimulation of differentiated adipocytes led to elevated uptake of serine, cysteine, and glycine, in parallel with increased oxygen consumption, augmented UCP1‐dependent proton leak, increased creatine‐driven substrate cycle‐coupled respiration, and upregulation of thermogenesis marker genes and several respiratory complex subunits; these outcomes were impeded in the presence of the specific ASC‐1 inhibitor, BMS‐466442. Our data suggest that ASC‐1‐dependent consumption of serine, cysteine, and glycine is required for efficient thermogenic stimulation of human adipocytes.
Associations Between Safety of Certolizumab Pegol, Disease Activity, and Patient Characteristics, Including Corticosteroid Use and Body Mass Index
Authors: Bykerk Vivian P. , Blauvelt Andrew , Curtis Jeffrey R. , Gaujoux‐Viala Cécile , Kvien Tore K. , Winthrop Kevin , Tilt Nicola , Popova Christina , Mariette Xavier , Haraoui Boulos
Published: July 2021

Objective

To investigate the impact of baseline and time‐varying factors on the risk of serious adverse events (SAEs) in patients during long‐term certolizumab pegol (CZP) treatment.

Methods

Safety data were pooled across 34 CZP clinical trials in rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), and plaque psoriasis (PSO). Cox proportional hazards modeling was used to investigate the association of baseline patient characteristics with risk of serious infectious events (SIEs), malignancies, and major adverse cardiac events (MACEs). Cox modeling for recurrent events assessed the impact of time‐varying body mass index (BMI), systemic corticosteroid (CS) use, and disease activity on SIE risk in RA and SAE risk in PSO.

Results

Data were pooled from 8747 CZP‐treated patients across indications. Cox models reported a 44% increase in SIE risk associated with a baseline BMI of 35 kg/m2 or more versus a baseline BMI of 18.5 kg/m2 to less than 25 kg/m2. Baseline systemic CS use, age of 65 years or more, and disease duration of 10 years or longer also increased SIE risk. Older age was the only identified risk factor for malignancies. The risk of MACEs increased 107% for BMI of 35 kg/m2 or more versus BMI of 18.5 kg/m2 to less than 25 kg/m2 and increased 51% for men versus women. Higher disease activity, older age, systemic CS use, BMI of 35 kg/m2 or more, and baseline comorbidities were SIE risk factors in RA. Age and systemic CS use were risk factors for SAEs in PSO.

Conclusion

Age, BMI, systemic CS use, and disease activity were identified as SIE risk factors in CZP‐treated patients. Risk of malignancies was greater in older patients, whereas obesity and male sex were MACE risk factors.
Gaining Insight into the Deformation of Achilles Tendon Entheses in Mice
Authors: Sartori Julian , Köhring Sebastian , Bruns Stefan , Moosmann Julian , Hammel Jörg U.
Published: July 2021

Understanding the biomechanics of tendon entheses is fundamental for surgical repair and tissue engineering but also relevant in biomimetics and paleontology. Examinations into the 3D tissue deformation under load are an important element in this process. However, entheses are difficult objects for microcomputed tomography due to extreme differences in X–ray attenuation. Herein, the ex vivo examination of Achilles tendon entheses from mice using a combination of tensile tests and synchrotron radiation‐based microcomputed tomography is reported. Strains and volume changes are compared between the more proximal free tendon and the distal tendon that wraps around the Tuber calcanei. Tomographic datasets of relaxed and deformed entheses are recorded with propagation‐based phase contrast. The tissue structure is rendered in sufficient detail to enable manual tracking of patterns along the tendon, as well as digital volume correlation in a suitable pair of tomographic datasets. The strains are higher in the distal than in the proximal tendon. These results support the existence of a compliant zone near the insertion. Necessary steps to extend the automatic tracking of tissue displacements to all stages of the deformation experiment are discussed.
Computational Screening of Single Atoms Anchored on Defective Mo2CO2 MXene Nanosheet as Efficient Electrocatalysts for the Synthesis of Ammonia
Authors: Wang Shuo , Li Lei , San Hui Kwan , Bin Feng , Zhou Wei , Fan Xi , Zalnezhad E. , Li Jing , Hui Kwun Nam
Published: July 2021

The electrochemical nitrogen reduction reaction (NRR) over single‐atom catalysts (SACs) anchored on Mo vacancies of Mo2CO2 MXene nanosheets under ambient conditions suffers from poor selectivity, low yield, and low Faradaic efficiency because of their sluggish kinetics and the competing hydrogen evolution reaction. Herein, density functional theory calculations are performed to improve the understanding of the selectivity and yielding of ammonia through NRR over various isolated SACs, that is, from Sc to Au, anchored on the Mo vacancy of the Mo2CO2 MXene nanosheet (denoted as MO2CO2‐MSA). The potential‐determining step of the NRR shows that eight candidates (i.e., Y, Zr, Nb, Hf, Ta, W, Re, and Os) confined on the defective Mo2CO2 layer could promote the electroreduction from N2 to NH3. Among these, Mo2CO2‐YSA presented the lowest reported reaction Presents the lowest reported reaction energy barrier (0.08 eV) through the distal pathway and high selectivity to NRR compared with the previously synthesized Mo2CO2‐RuSA with a relatively high energy barrier (0.65 eV) and poor selectivity. In addition, the formation energy of Mo2CO2‐YSA is more negative than that of the Mo2CO2‐RuSA catalyst, suggesting that the experimental preparation of the Mo2CO2‐YSA catalyst is highly feasible. This work lays a solid foundation for improving the rational design of MXene‐based systems as efficient electrocatalysts for the synthesis of ammonia.
Enhanced Mechanical and Degradation Properties of Hollow Glass Microspheres/Mg Matrix Composites by Incorporating Copper Power for Degradable Downhole Tool Applications
Authors: Liu Lin , Yu Sirong , Liu Enyang , Zhu Guang , Li Quan , Xiong Wei , Wang Bingying , Yang Xizhen
Published: July 2021

In this work, the effects of Cu addition on the microstructure, mechanical properties, and degradation behavior of the hollow glass microspheres/Mg alloy composites (HGM/MA) are investigated. The results indicate that with the Cu content increases from 0 to 2 wt.%, the grain size reduce from 17.89 ± 1.15 to 12.05 ± 0.85 μm, the compressive strength and Brinell hardness increase from 303 ± 5.5 MPa and 87.2 ± 2.5 HB to 381 ± 9.2 MPa and 119.8 ± 3.3 HB, increase by 25.7% and 37.4%, respectively. When the Cu content is less than 1 wt.%, the formed fine and dispersive Al2CuMg phase provides more galvanic‐corrosion sites, and promotes the exfoliation of the corrosion product layer during degradation process, thereby accelerating the degradation rate. While the excessive Cu addition (>1.5 wt.%) results in the formation of net‐like Al2CuMg phase, which can act as a corrosion barrier to hinder the further degradation of the composites. The composites with 3 wt.% Cu exhibits the highest degradation rate of 88.65 mg cm−2 h−1 in 3 wt.% KCl solution at 366 K, with a favorable ultimate compressive strength of 352 MPa, which is thought as an ideal candidate material for the degradable downhole tools.
Neutrophil Delivered Hollow Titania Covered Persistent Luminescent Nanosensitizer for Ultrosound Augmented Chemo/Immuno Glioblastoma Therapy
Authors: Li Yujie , Teng Xucong , Wang Yongji , Yang Chunrong , Yan Xiuping , Li Jinghong
Published: July 2021

Glioblastoma (GBM) is the most malignant brain tumor with unmet therapeutic demand. The blood‐brain‐barrier (BBB) and tumor heterogeneity limit the treatment effectiveness of various interventions. Here, an ultrasound augmented chemo/immuno therapy for GBM using a neutrophil‐delivered nanosensitizer, is developed. The sensitizer is composed of a ZnGa2O4:Cr3+ (ZGO) core for persistent luminescence imaging and a hollow sono‐sensitive TiO2 shell to generate reactive oxygen species (ROS) for controlled drug release. Immune checkpoint inhibitor (Anti‐PD‐1 antibody) is trapped in the interior of the porous ZGO@TiO2 with paclitaxel (PTX) loaded liposome encapsulation to form ZGO@TiO2@ALP. Delivered by neutrophils (NEs), ZGO@TiO2@ALP‐NEs can penetrate through BBB for GBM accumulation. After intravenous injection, ultrasound irradiation at GBM sites initiates ROS generation from ZGO@TiO2@ALP, leading to liposome destruction for PTX and anti‐PD‐1 antibody release to kill tumors and induce local inflammation, which in‐turn attractes more ZGO@TiO2@ALP‐NEs to migrate into tumor sites for augmented and sustained therapy. The treatment enhances the survival rate of the GBM bearing mice from 0% to 40% and endows them with long‐term immuno‐surveillance for tumor recurrence, providing a new approach for precision therapy against GBM and other cancers.
Opportunities from Doping of Non‐Critical Metal Oxides in Last Generation Light‐Conversion Devices
Authors: Gatti Teresa , Lamberti Francesco , Mazzaro Raffaello , Kriegel Ilka , Schlettwein Derck , Enrichi Francesco , Lago Nicolò , Di Maria Eleonora , Meneghesso Gaudenzio , Vomiero Alberto , Gross Silvia
Published: July 2021

The need to develop sustainable energy solutions is an urgent requirement for society, with the additional requirement to limit dependence on critical raw materials, within a virtuous circular economy model. In this framework, it is essential to identify new avenues for light‐conversion into clean energy and fuels exploiting largely available materials and green production methods. Metal oxide semiconductors (MOSs) emerge among other species for their remarkable environmental stability, chemical tunability, and optoelectronic properties. MOSs are often key constituents in next generation energy devices, mainly in the role of charge selective layers. Their use as light harvesters is hitherto rather limited, but progressively emerging. One of the key strategies to boost their properties involves doping, that can improve charge mobility, light absorption and tune band structures to maximize charge separation at heterojunctions. In this review, effective methods to dope MOSs and to exploit the derived benefits in relation to performance enhancement in different types of devices are identified and critically compared. The work is focused specifically on the best opportunities coming from the use of non‐critical raw materials, so as to contribute in defining an economically feasible roadmap for light conversion technologies based on these highly stable and widely available compounds.
Wine's belated globalization, 1845–2025
Authors: Anderson Kym , Pinilla Vicente
Published: July 2021

In the latest wave of globalization, the share of global wine production crossing national borders has trebled since the mid‐1980s, to more than 40%. Prior to then, wine was confined mostly to southern Europe with very little trade outside Europe. Why was wine globalization so belated? Why did it take so long for wine exports to take off even in the New World regions of European settlement? This article addresses these questions and also seeks to explain the bilateral patterns of wine trade. It concludes by speculating briefly on how wine markets might develop in the foreseeable future.
3D‐Printed Pneumatically Controlled Soft Suction Cups for Gripping Fragile, Small, and Rough Objects
Authors: Koivikko Anastasia , Drotlef Dirk-Michael , Dayan Cem Balda , Sariola Veikko , Sitti Metin
Published: July 2021

A 3D‐printed pneumatically actuated soft suction gripper with an elastomer film is proposed. Suction in such gripper is actively controlled by applying a negative pressure behind the film. The elastomeric gripper body is 3D‐printed, making it easy to customize and integrate into future robotic gripping systems. The gripper can pick a wide variety of objects, such as delicate fruits, small parts, and parts with uneven loads, with high pull‐off forces (over 7.4 N with ∅ 20 mm/55 kPa). The achieved pull‐off forces are significantly higher than the previously reported suction cup grippers with films and more comparable with commercial vacuum grippers. The pull‐off forces show no significant differences with surfaces of varying roughness (up to root‐mean‐square roughness of 5.66 μm) and the gripper is able to pick and release target objects repeatedly. The gripper is also compared with a commercial vacuum gripper with comparable dimensions. It outperforms the commercial gripper in the case of fragile objects, objects smaller than the gripper diameter, and objects with uneven loads. It can apply high pull‐off forces while having controllable release, and is suitable for gripping a wide variety of real‐world objects, including heavy, rough, small, thin, and fragile ones.
Catalytic Reduction of N2 to Borylamine at a Molybdenum Complex
Authors: Bennaamane Soukaina , Espada Maria F. , Mulas Andrea , Personeni Théo , Saffon‐Merceron Nathalie , Fustier‐Boutignon Marie , Bucher Christophe , Mézailles Nicolas
Published: July 2021

Catalytic formation of borylamines from atmospheric N2 is achieved for the first time using a series of homogenous (triphosphine)Mo complexes. Stepwise functionalization of the (triphosphine)Mo‐nitrido complex with chloroborane led to the synthesis of the imido complex. Electrochemical characterization of the (PPP)Mo‐nitrido and (PPP)Mo‐borylimido complexes showed that the latter is much more easily reduced.
A water‐stable luminescent sensor based on Cd2+ coordination polymer for detecting nitroimidazole antibiotics in water
Authors: Ji Xiaoxi , Wu Shuangyan , Song Dongxue , Chen Shiyu , Chen Qing , Gao Enjun , Xu Jin , Zhu Xiaopeng , Zhu Mingchang
Published: July 2021

Effective detection of antibiotics is essential for human health and environmental protection. A new type of water‐stable fluorescent sensor was synthesized and characterized. The antibiotics in the water were detected by fluorescence spectroscopy. The complex presents excellent fluorescence quenching effect on nitroimidazole antibiotics with high selectivity and sensitivity and shows lower limits of detection with a wider linear range. The limit of detection (LOD) of the complex are 0.46 nM for ornidazole (ODZ), 0.73 nM for dimetridazole (DTZ), and 0.46 nM for metronidazole (MDZ). The Ksv values are calculated to be 1.11 × 104 M−1 for ODZ, 0.70 × 104 M−1 for DTZ, and 1.10 × 104 M−1 for MDZ. In addition, the sensor is recyclable and is expected to be used in the detection of nitroimidazole antibiotics in water. The luminescence quenching of Cd2+ complex towards nitroimidazole antibiotics ascribed to the combination of electron transfer and energy transfer.
Health profiles of adults with autism spectrum disorder: Differences between women and men
Authors: DaWalt Leann Smith , Taylor Julie Lounds , Movaghar Arezoo , Hong Jinkuk , Kim Bryan , Brilliant Murray , Mailick Marsha R.
Published: July 2021

The purpose of the present study was to investigate the hypothesis that women with autism have poorer health compared with men with autism, and compared with women without autism. Utilizing electronic health records drawn from a single health care system serving over 2 million individuals, 2119 adults with diagnosed autism spectrum disorders were compared with age‐ and sex‐matched controls. When considering health care utilization, we found evidence of multiplicative risk for conditions within some domains (i.e., nutrition conditions, neurologic disease, psychiatric conditions, and sleep disorders) such that women with autism spectrum disorder (ASD) experienced double jeopardy—meaning they had greater rates of health care utilization within a domain than what would separately be expected by virtue of being a woman and having ASD. For other domains (i.e., endocrine disorders, gastrointestinal disorders), the risk was additive such that being a female and having ASD were both associated with higher health care utilization, but there were no significant interaction effects. It was only with respect to one domain (cardiovascular) that rates of health care utilization were reflective of neither ASD diagnosis nor sex. Overall, our findings suggest that women with ASD are a vulnerable subgroup with high levels of health care utilization.

Lay Summary

This study asked whether women with autism have poorer health compared with men with autism, and compared with women without autism. To answer this question, we used data from electronic health records. We found that women with autism spectrum disorder (ASD) were at the greatest risk for health problems such as nutrition conditions, neurologic disease, psychiatric conditions, and sleep disorders. More research on health of women with ASD is needed.
Water Systems as Plaintiffs
Authors: Sansone Kenneth A.
Published: July 2021

Key Takeaways

Over the past two decades, water systems have recovered billions of dollars in verdicts and settlements through lawsuits against polluters and used these recoveries to fund remediation.

In most situations in which defective products are responsible for contaminating drinking water supplies, the supplier will need to bring its own lawsuit against the responsible parties to achieve monetary recovery.

When a manufacturer has information about its products’ risks and fails to act on it in a responsible way, that manufacturer has been negligent and is responsible for any harm that results.

Though concerns about entering into litigation are understandable, many water suppliers have found it well worth the risk to hold polluters accountable.