bluuebunny/crossref_metadata_2025 huggingface dataset:
Benefit‐Risk Assessment of Off‐Label Drug Use in Children: The Bravo Framework
Authors: van der Zanden Tjitske M. , Mooij Miriam G. , Vet Nienke J. , Neubert Antje , Rascher Wolfgang , Lagler Florian B. , Male Christoph , Grytli Helene , Halvorsen Thomas , de Hoog Matthijs , de Wildt Saskia N.
Published: June 2021

A drug is granted a license for use after a thorough assessment of risks and benefits based on high‐quality scientific proof of its efficacy and safety. Many drugs that are relevant to children are not licensed for use in this population implying that a thorough assessment of risks and benefits in the pediatric population has not been made at all, implying a negative risk‐benefit balance in children, or implying insufficient information to establish the risk‐benefit balance. Use of drugs without positive assessment of risks and benefits exposes children to potential lack of efficacy, unknown toxicity, and harm. To aid guideline committees and individual prescribers, we here present a tutorial of the Benefit and Risk Assessment for Off‐label use (BRAvO) decision framework. This pragmatic framework offers a structured assessment of benefits and risks of off‐label drug use, including a clinical pharmacological based approach to age‐appropriate dose selection. As proof of concept and to illustrate the practical use, we have applied the framework to assess benefits and risks of off‐label use of ondansetron for gastroenteritis‐induced nausea and vomiting. The framework could also guide decisions on off‐label use in other special populations (e.g., pregnant women, elderly, obese, or critically ill patients) where off‐label drug use is frequent, thereby contributing to effective and safe pharmacotherapy.
Immunopharmacogenomics: Mechanisms of HLA‐Associated Drug Reactions
Authors: Deshpande Pooja , Hertzman Rebecca J. , Palubinsky Amy M. , Giles Jason B. , Karnes Jason H. , Gibson Andrew , Phillips Elizabeth J.
Published: June 2021

The human leukocyte antigen (HLA) system is the most polymorphic in the human genome that has been associated with protection and predisposition to a broad array of infectious, autoimmune, and malignant diseases. More recently over the last two decades, HLA class I alleles have been strongly associated with T‐cell‐mediated drug hypersensitivity reactions. In the case of abacavir hypersensitivity and HLA‐B*57:01, the 100% negative predictive value and low number needed to test to prevent a single case has led to a durable and effective global preprescription screening strategy. However, HLA associations are still undefined for most drugs clinically associated with different delayed drug hypersensitivity phenotypes, and an HLA association relevant to one population is not generalizable across ethnicities. Furthermore, while a specific risk HLA allele is necessary for drug‐induced T‐cell activation, it is not sufficient. The low and incomplete positive predictive value has hindered efforts at clinical implementation for many drugs but has provided the impetus to understand the mechanisms of HLA class I restricted T‐cell‐mediated drug hypersensitivity reactions. Current research has focused on defining the contribution of additional elements of the adaptive immune response and other genetic and ecologic risk factors that contribute to drug hypersensitivity risk. In this review we focus on new insights into immunological, pharmacological, and genetic mechanisms underpinning HLA‐associated drug reactions and the implications for future translation into clinical care.
Molecularly Functionalized Electrodes for Efficient Electrochemical Water Remediation
Authors: He Xiang , Eberhart Michael S. , Martinson Alex B. F. , Tiede David M. , Mulfort Karen L.
Published: June 2021

The development and investigation of materials that leverage unique interfacial effects on electronic structure and redox chemistry are likely to play an outstanding role in advanced technologies for wastewater treatment. Here, the use of surface functionalization of metal oxides with a RuIIpoly(pyridyl) complex was reported as a way to create hybrid assemblies with optimized electrochemical performance for water remediation, superior to those that could be achieved with the molecular catalyst or metal‐oxide electrodes used individually. Mechanistic analysis demonstrated that the molecularly functionalized electrodes could suppress the formation of hydroxyl radicals (i. e., the dominant remediation pathway for bare metal‐oxide electrodes), allowing the water remediation to proceed through the highly oxidizing Ru3+ ions in the surface‐bound complexes. Furthermore, the underlying metal‐oxide substrates played a crucial role in altering the electronic structure and electrochemical properties of the surface‐bound catalyst, such that the competing side reaction (i. e., water splitting) was largely inhibited.
Repetitive Synthesis of High‐Molecular‐Weight Hyaluronic Acid with Immobilized Enzyme Cascades
Authors: Gottschalk Johannes , Aßmann Miriam , Kuballa Jürgen , Elling Lothar
Published: June 2021

Industrial hyaluronic acid (HA) production comprises either fermentation with Streptococcus strains or extraction from rooster combs. The hard‐to‐control product quality is an obstacle to these processes. Enzymatic syntheses of HA were developed to produce high‐molecular‐weight HA with low dispersity. To facilitate enzyme recovery and biocatalyst re‐use, here the immobilization of cascade enzymes onto magnetic beads was used for the synthesis of uridine‐5’‐diphosphate‐α‐d‐N‐acetyl‐glucosamine (UDP‐GlcNAc), UDP‐glucuronic acid (UDP‐GlcA), and HA. The combination of six enzymes in the UDP‐sugar cascades with integrated adenosine‐5'‐triphosphate‐regeneration reached yields between 60 and 100 % for 5 repetitive batches, proving the productivity. Immobilized HA synthase from Pasteurella multocida produced HA in repetitive batches for three days. Combining all seven immobilized enzymes in a one‐pot synthesis, HA production was demonstrated for three days with a HA concentration of up to 0.37 g L−1, an average MW of 2.7–3.6 MDa, and a dispersity of 1.02–1.03.
Adopt framework that promotes collaboration for providing disability services
Authors: Hope Joan
Published: June 2021

Meeting the needs of students with disabilities requires disability services providers to work with other stakeholders to be effective. And while the traditional model requires students to reach out to disability services providers, faculty members, and others for the support they need, many students don't realize what services are available and don't understand who does what on campus.
Consistent declines in aquatic biodiversity across diverse domains of life in rivers impacted by surface coal mining
Authors: Simonin Marie , Rocca Jennifer D. , Gerson Jacqueline R. , Moore Eric , Brooks Alexander C. , Czaplicki Lauren , Ross Matthew R. V. , Fierer Noah , Craine Joseph M. , Bernhardt Emily S.
Published: June 2021

The rivers of Appalachia (United States) are among the most biologically diverse freshwater ecosystems in the temperate zone and are home to numerous endemic aquatic organisms. Throughout the Central Appalachian ecoregion, extensive surface coal mines generate alkaline mine drainage that raises the pH, salinity, and trace element concentrations in downstream waters. Previous regional assessments have found significant declines in stream macroinvertebrate and fish communities after draining these mined areas. Here, we expand these assessments with a more comprehensive evaluation across a broad range of organisms (bacteria, algae, macroinvertebrates, all eukaryotes, and fish) using high‐throughput amplicon sequencing of environmental DNA (eDNA). We collected water samples from 93 streams in Central Appalachia (West Virginia, United States) spanning a gradient of mountaintop coal mining intensity and legacy to assess how this land use alters downstream water chemistry and affects aquatic biodiversity. For each group of organisms, we identified the sensitive and tolerant taxa along the gradient and calculated stream specific conductivity thresholds in which large synchronous declines in diversity were observed. Streams below mining operations had steep declines in diversity (−18 to −41%) and substantial shifts in community composition that were consistent across multiple taxonomic groups. Overall, large synchronous declines in bacterial, algal, and macroinvertebrate communities occurred even at low levels of mining impact at stream specific conductivity thresholds of 150–200 µS/cm that are substantially below the current U.S. Environmental Protection Agency aquatic life benchmark of 300 µS/cm for Central Appalachian streams. We show that extensive coal surface mining activities led to the extirpation of 40% of biodiversity from impacted rivers throughout the region and that current water quality criteria are likely not protective for many groups of aquatic organisms.
Extensive historical and contemporary hybridization suggests premating isolation in Vermivora warblers is not strong: A reply to Confer et al.
Authors: Toews David P. L. , Baiz Marcella D. , Kramer Gunnar R. , Lovette Irby J. , Streby Henry M. , Taylor Scott A.
Published: June 2021

We present comments on an article published by Confer et al. (Ecology and Evolution, 10, 2020). Confer et al. (2020) aggregate data from multiple studies of social pairing between Vermivora chrysoptera and V. cyanoptera, two wood warblers in the family Parulidae that hybridize extensively where they co‐occur. From analysis of these data, they conclude there is near‐complete reproductive isolation between these two species. In our reply, we show that this finding is not supported by other lines of evidence, and significant drawbacks of their study design preclude such strong conclusions. In our critique, we show that (a) coarse‐scale plumage classifications cannot be used to accurately estimate hybrid ancestry in Vermivora; (b) extra‐pair paternity is very high in Vermivora and is likely facilitating hybridization, yet was not considered by Confer et al. (2020), and we suggest this will have a substantial influence on the interpretation of reproductive isolation in the system; and (c) the central finding of strong total reproductive isolation is not compatible with the results of other long‐term studies, which demonstrate low isolation and high gene flow. We conclude with a more comprehensive interpretation of hybridization and reproductive isolation in Vermivora warblers.
The impacts of flowering phenology on the reproductive success of the narrow endemic Nouelia insignis Franch. (Asteraceae)
Authors: Liu FangYan , Gao ChengJie , Chen Min , Tang GuoYong , Sun Yongyu , Li Kun
Published: June 2021

Nouelia insignis Franch. (Asteraceae) is a short, narrow endemic and endangered tree, growing with a natural population in the dry and hot valley of the Jinsha River in the southwest area of China. In this work, flowering phenology (time and duration), floral biology, visit frequency and behavior of pollinators, and pollination characteristics were studied based on investigation in the field and analysis in the laboratory with the help of a stereomicroscope, and the relationship between seed setting rate and reproductive traits, as well as the relationship between flowering time and rainfall before flowering, was tested using the method of general linear regression model. The results showed that natural population of N. insignis exhibited high flowering synchrony with relatively stable flowering duration, and the flowering time fluctuated greatly depending on the rainfall 5 months before flowering. The pollination of N. insignis required pollinators, and insect activities played a very important role in the pollination process. However, lack of the pollinators was not a limitation for reproductive fitness in N. insignis, although the number of pollinators was small and the frequency of visits was low. In addition, no pollen limitation was found during pollination. The average seed setting rate of N. insignis in the natural condition was only 1.52%–3.73%, and it was generally affected by changes in flowering phenology between years and had a higher seed set in early flowering year. The annual variation of seed set might be related to the annual variations of stamen and pistil functions, such as changes of pollen viability and stigma receptivity, which were closely related to flowering time. The results of this study are of value for further conservation actions on natural population of this threatened endemic plant.
Levosimendan in venoarterial ECMO weaning. Rational and design of a randomized double blind multicentre trial
Authors: Ellouze Omar , Soudry Faure Agnès , Radhouani Mohamed , Abou‐Arab Osama , Besnier Emmanuel , Moussa Mouhamed , Cransac Amélie , Ksiazek Elea , Fischer Marc‐Olivier , Mertes Paul Michel , Bouhemad Belaid , Guinot Pierre Grégoire
Published: June 2021

Aims

Venoarterial extracorporeal membrane oxygenation (VA‐ECMO) is increasingly being used in circulatory failure. The main indications are cardiogenic shock, post‐cardiotomy cardiac failure, and refractory cardiac arrest. However, VA‐ECMO weaning is particularly challenging, and weaning failure is reported to be as high as 50%, with increased related mortality. Levosimendan is a novel long acting effect inodilator used in cardiogenic shock and terminal heart failure decompensation. Levosimendan use in VA‐ECMO patients seems to reduce weaning failure regardless of the initial aetiology and to reduce mortality when administrated early after VA‐ECMO initiation. However, studies are limited to retrospective analyses and reported case series. The aim of the WEANILEVO trial is to evaluate whether administration of levosimendan before VA‐ECMO weaning is associated with a reduced rates of weaning failure and recourse to other temporary circulatory support.

Methods and results

WEANILEVO is a randomized, prospective, multicentre, double‐blind, parallel‐group, controlled trial. One hundred eighty patients will be enrolled if they had acute circulatory heart failure treated with VA‐ECMO and for whom weaning is expected within 48 h. The study drugs are either levosimendan (0.2 μg/kg/min for 24 h) or a placebo. The primary endpoint of the trial is the absence of VA‐ECMO weaning, recourse to another VA‐ECMO, or other temporary circulatory assistance or death within 7 days of VA‐ECMO weaning.

Conclusions

Levosimendan use in VA‐ECMO appears to be beneficial for reducing weaning failure and mortality. The results of WEANILEVO should significantly influence decisions regarding the use of levosimendan for VA‐ECMO weaning.
Comparison of in‐hospital outcomes of patients with vs. without ischaemic cardiomyopathy undergoing veno‐arterial‐extracorporeal membrane oxygenation
Authors: Seong Seok‐Woo , Jin Guiyue , Kim Mijoo , Ahn Kye Taek , Yang Jeong Hoon , Gwon Hyeon‐Cheol , Ko Young‐Guk , Yu Cheol Woong , Chun Woo Jung , Jang Woo Jin , Kim Hyun‐Joong , Bae Jang‐Whan , Kwon Sung Uk , Lee Hyun‐Jong , Lee Wang Soo , Park Sang‐Don , Cho Sung Soo , Ahn Joong Hyun , Song Pil Sang , Jeong Jin‐Ok
Published: June 2021

Aims

This study aimed to investigate differences in baseline and treatment characteristics, and in‐hospital mortality according to the aetiologies of cardiogenic shock in patients undergoing veno‐arterial‐extracorporeal membrane oxygenation (VA‐ECMO).

Methods and results

The RESCUE registry is a multicentre, observational cohort that includes 1247 patients with cardiogenic shock from 12 centres. A total of 496 patients requiring VA‐ECMO were finally selected, and the study population was stratified by cardiogenic shock aetiology [ischaemic cardiomyopathy (ICM, n = 342) and non‐ICM (NICM, n = 154)]. The primary outcome of interest was in‐hospital mortality. Sensitivity analyses including propensity‐score matching adjustments were performed. Mean age of the entire population was 61.8 ± 14.2, and 30.8% were women. There were significant differences in baseline characteristics; notable differences included the older age of patients with ICM (65.1 ± 13.7 vs. 58.2 ± 13.8, P < 0.001), preponderance of males [258 (75.4%) vs. 85 (55.2%), P < 0.001], and higher prevalence of diabetes mellitus [140 (40.9%) vs. 39 (25.3%), P = 0.001] compared with patients in the NICM aetiology group. Patients with ischaemic cardiogenic shock were more likely to have longer shock duration before VA‐ECMO implantation (518.7 ± 941.4 min vs. 292.4 ± 707.8 min, P = 0.003) and were less likely to undergo distal limb perfusion than those with NICM [108 (31.6%) vs. 79 (51.3%), P < 0.001]. In‐hospital mortality in the overall cohort was 52.2%; patients with ICM had a higher unadjusted risk of in‐hospital mortality [203 (59.4%) vs. 56 (36.4%); unadjusted hazard ratio, 2.295; 95% confidence interval, 1.698–3.100; P < 0.001]. There were no significant differences in the primary outcome between the two aetiologies following propensity‐score matching multiple adjustments (adjusted hazard ratio, 1.265; 95% confidence interval, 0.840–1.906; P = 0.260).

Conclusions

Results of the current study indicated among patients with cardiogenic shock undergoing VA‐ECMO, ischaemic aetiology does not seem to impact in‐hospital mortality. These findings underline that early initiation and appropriate treatment strategies of VA‐ECMO for patients with ICM shock are required.
Mixed Multimetallic tris(2‐pyridylmethyl)amine Based Complexes: Synthesis and Chiroptical Properties
Authors: Carmo dos Santos Nadia Alessandra , Badetti Elena , Begato Federico , Wurst Klaus , Licini Giulia , Zonta Cristiano
Published: June 2021

Continuous intensification of reaction screening methodologies has required the development of novel high‐throughput analytical technologies. This urge involves also chirality related fields where nowadays novel methods for reliable, fast and effective analysis are developed. Within this field, chiroptical spectroscopies have emerged as promising techniques, in particular when they are combined with stereodynamic probes for optical signal amplification. We report here the synthesis and characterisation of a series of molecular architectures based on a modified tris(2‐pyridylmethyl)amine (TPMA) complex which are able to amplify the electronic CD signal of phenylalanine. The study reports the synthesis of six novel TPMA based supramolecular architectures characterised by the presence of two different metals within the same molecule. Besides the synthesis, the study highlights how mixing metals influences the chiroptical properties of the formed compounds.
Automated Synthesis of Heavily Phosphorylated Peptides
Authors: Grunhaus Dana , Friedler Assaf , Hurevich Mattan
Published: June 2021

Multi phosphorylated peptides are key tools in understanding the biological roles of protein phosphorylation patterns. In this work, we focused on multi phosphorylated peptides with over four, clustered, phosphorylation sites that are termed herein heavily phosphorylated peptides (HPPs). The synthesis of heavily phosphorylated peptides is extremely difficult and requires the use of a wide temperature range. Standard peptide synthesizers are incapable of both cooling and heating, which impedes the automated synthesis of those peptides. Herein, we used the oligosaccharide synthesizer Glyconeer 2.1 to develop a protocol for the automated synthesis of heavily phosphorylated peptides. The Glyconeer 2.1 is able to both cool and heat, which enabled the development of highly controlled coupling and deprotection conditions that were used for the automated synthesis of four different heavily phosphorylated peptides with five or more, clustered, phosphorylation sites. Our approach paves the way for an easy automated synthesis of a variety of heavily phosphorylated peptides.
The national divide: A social representations approach to US political identity
Authors: Hanson Kristin , O'Dwyer Emma , Lyons Evanthia
Published: June 2021

Extending research on US ideological identity as a social identity, this study employs a social representations approach to capture identity meaning as a form of national attachment. Across two studies (n = 723), we demonstrate that two novel organizing principles of US ideological identity—national reverence(veneration of the nation in the abstract, its symbols, sacred texts, and founding fathers) andindividual support(a focus on the progress of individuals and the change required to bring about equality)—significantly predicted ideological self‐categorization, 2016 presidential voting, and affective political polarization over and above right‐wing authoritarianism and social dominance orientation. The results suggest an integration of national and conservative identities that places US national identity in opposition to liberal identity and to progress and equality, pointing to the divisive employment of national identity in the current political environment.
Moralization and moral trade‐offs explain (in)tolerance of Muslim minority behaviours
Authors: Adelman Levi , Verkuyten Maykel , Yogeeswaran Kumar
Published: June 2021

How do people decide whether specific minority behaviours should or should not be tolerated in society? The current research investigates the role of moralization in tolerance of Muslim minority behaviours that differ in their level of perceived normative dissent with four national samples of majority group members in the Netherlands and Germany (N = 3628). Study 1 revealed that behaviours perceived as more normatively dissenting were increasingly moralized and tolerated less. In Studies 2 and 3, we found that more normatively dissenting behaviours prompted people to prioritize the moral value of social cohesion over freedom and become less tolerant. Finally, Study 4 shows that priming the moral value of religious freedom decreases intolerance of a highly dissenting Muslim minority practice. Taken together, these studies reveal that moralization and value prioritizing can be associated with either intolerance or tolerance of minority behaviours depending on the perceived normative dissenting nature of these behaviours.
Understanding a liminal condition: Comparing emerging representations of the “vegetative state”
Authors: Zulato Edoardo , Montali Lorenzo , Bauer Martin W.
Published: June 2021

Our research explored the social representations of the ‘vegetative state’ across different cultural (India, Italy, and the UK) and social milieus (left‐leaning, right‐leaning, and religious/tabloid newspapers). The aim was to discover how public discourse engages liminality between life and death. Qualitative and quantitative text analyses were conducted on news headlines and full‐texts from British (n = 300), Indian (n = 300), and Italian (n = 300) newspapers published between January 1990 and June 2019. Our study shows three results: (a) the vegetative state is a potentially global issue that remains discussed with local timing and characteristics; (b) it is commonly represented in eight frames of different resonance across cultural milieus; (c) the news flows are organised on different dimensions (quality, political, and ideological). Results shed light on how liminality is discursively managed by the interplay of cultural resources and social positionings. In particular, this suggests a hitherto unrecognised function of the objectification process: personification as position‐taking.
Investigation of exergetic and exergo‐sustainability metrics for high by‐pass turbofan engine at different power settings
Authors: Aygun Hakan
Published: June 2021

This paper investigates influences of several throttle settings on several exergetic and exergo‐sustainability parameters by employing thermodynamic principles for high by‐pass turbofan engine as named PW4000 engine. First, energy efficiency of the PW4000 is found to vary between 9.77% and 37.69% due to rising from 5544 RPM to 9169 RPM. Considering exergetic results on component basis, rising power setting leads to increase exergy efficiency of the components. Also, the combustor of PW4000 belongs to lowest exergy efficiency throughout 19 RPMs. Namely, exergy efficiency of the combustor increases from 69.14% to 86.31% whereas that of LPT raises from 92.01% to 93.25% owing to the increase in RPM. Considering sustainability parameters for whole engine, exergy efficiency of PW4000 varies from 9.13% to 35.26% whereas its exergetic sustainability index increases from 0.276 to 1.238 throughout RPM values. Furthermore, environmental effect factor of PW4000 decreases from 3.26 to 0.807 due to rising RPM value. According to these results, it is revealed that there are generally nonlinear relationship between thermodynamic parameters and power settings. To measure exergetic metrics of turbofan engines for different running points can allow researchers to find optimum RPM value of the engine in terms of thermodynamic sustainability.
A comparative study on two different configurations of hybrid photovoltaic thermal collector with experimental validation and uncertainty analysis
Authors: Boumaaraf Houria , Boumaaraf Billel , Slimani Mohamed El‐Amine , Ait‐Cheikh Mohamed Salah , Touafek Khaled
Published: June 2021

In addition to the electricity produced by photovoltaic cells, the use of a hybrid photovoltaic thermal collector (PV/T) can simultaneously produce thermal energy and reduce the energy loss from the photovoltaic module. There are many types of hybrid PV/T collector depending on the number of additional glasses, the configuration of the exchanger used, the nature of the heat transfer fluid, and so forth. In this article, we will study a polycrystalline photovoltaic module with a diode and a hybrid PV/T collector with glazed and unglazed configurations, a comparison of electrical and thermal studies is presented between these three systems under the climatic conditions of Ghardaïa city (semiarid region). To this end, a numerical model have been developed and evaluated by means of a simulation in the MATLAB environment. In addition, it has been validated experimentally. The experimental results are in good agreement with those of simulation, the useful energy efficiency values are 6.78, 68, and 67.86% for the photovoltaic generator (GPV), unglazed hybrid collector (PV/T‐I), and glazed hybrid collector (PV/T‐II), respectively; otherwise, the energy losses for the same systems reach 93.22, 32, and 32.14%, respectively; therefore, the hybrid collector has the best overall performance compared to the GPV. The results also show the effect of additional glass on the useful energy of the hybrid collector under semiarid area climatic conditions.
Improved fast pyrolysis bio‐oils from straw and miscanthus by fractionated condensation
Authors: Conrad Stefan , Blajin Cristina , Schulzke Tim , Deerberg Goerge
Published: June 2021

Fast pyrolysis is one of the most promising conversion processes for producing advanced biofuels, which can be used as substitute for fuel oils or chemicals. Herbaceous biomass due to its comparatively high amount of cellulose and catalytically active inorganic content results in pyrolysis oil with high water content even if the original biomass was dry. Such bio‐oil separates into two phases: an upper aqueous phase and a bottom tarry phase. The phase separation by decantation is not an efficient method to reduce the water content and total acid number because a part of valuable components will be lost to the aqueous phase. To improve the quality of bio‐oils producing single‐phase liquids by staged condensation seems to be the better method. The minimum condensation temperature which leads to single‐phase liquid bio‐oils was determined to be around 66°C for wheat/barley straw and 62°C for miscanthus. A further increase in temperature will result in bio‐oils with lower water content and total acid number, but goes along with higher losses of organics to the second condensation stage.
Engineering geomorphology: A novel professional profile to face applied challenges in earth surface dynamics in mid‐Europe
Authors: Laimer Hans Jörg
Published: June 2021

Engineering geomorphology is concerned with the assessment of surface processes, sediment dynamics, landform changes and geomorphological hazards, which are related to civil engineering and construction. As an important planning component, it contributes significantly to the solution of societal problems on a dynamic earth surface. Unlike in the UK and other countries where it has become an independent sector within geotechnical engineering, the discipline has found little attention up to now in mid‐European applied geosciences. This ESEX commentary discusses the under‐representation and proposes an advancement of professional engineering geomorphology within the German‐speaking countries. The relation to neighbouring disciplines and the history of the field are illustrated from the academic and practical perspectives. A brief outline of potential fields of activity, recent professional practice and requirements for academic training are presented to provide aspiring practitioners with an idea of their future prospects as engineering geomorphologists. As part of their qualification, teamwork with geologists and engineers must be considered a key aspect, involving mutual knowledge of methods, techniques and interfaces for the propagation of uncertainty. The discussion demonstrates ways engineering geomorphology could be implemented as an established profession/academic discipline in mid‐Europe as part of physical geography, geosciences and neighbouring engineering disciplines.
Microencapsulation: An overview on concepts, methods, properties and applications in foods
Authors: Choudhury Nitamani , Meghwal Murlidhar , Das Kalyan
Published: June 2021

Microencapsulation is an advanced food processing technology, using which any compound can be encapsulated inside a particular material, making a tiny sphere of diameter ranging from 1 μm to several 100 μm. Microencapsulation is done for protecting the sensitive compounds and, hence, ensuring their safe delivery. The compound or active material which is encapsulated is called the core and the material which is used for encapsulating is called the encapsulant. Encapsulants can be either polymeric or nonpolymeric materials like cellulose, ethylene glycol, and gelatin. There are several techniques used for microencapsulation. Fluidized bed coating, spray cooling, spray drying, extrusion, and coacervation are few to be named. The selection of a particular technique depends upon the properties of the core material, encapsulant, and different properties and morphology of the capsules desired. The characterization and optimization of efficient and successful encapsulation can be done by studying the encapsulation efficiency and various properties of the capsules like morphology, size, hydrophobicity, hygroscopicity, solubility, surface tension, thermal behavior, and mechanical properties. Microencapsulation is a technology that is extensively used in foods, whether as a fortifying tool or as a mode for the development of a functional food. Based on the fundamental understanding of encapsulation and latest research and findings from literature, this review critically analyses and brings together the utilization of this particular technique in foods, different methods used for encapsulation, different properties of the capsules which result from the different techniques adopted for microencapsulation and different release mechanisms used for delivering the compounds.
Therapeutic effects of vitamin D and cancer: An overview
Authors: Varghese Jisha Elsa , Balasubramanian Balamuralikrishnan , Velayuthaprabhu Shanmugam , Thirunavukkarasu Velusamy , Rengarajan Rengasamy Lakshminarayanan , Murugesh Easwaran , Manikandan Pappusamy , Arun Meyyazhagan , Anand Arumugam Vijaya
Published: June 2021

Since vitamin D's discovery, strenuous efforts to investigate its physiological exploit and deficiency on human health were done. Our body synthesizes fat‐soluble vitamin D when get exposed to sunlight. In recent years, experimental data indicate that sunlight exposure and an adequate level of circulating vitamin D can reduce the incidence of cancer. Several in vitro and in vivo studies also suggest vitamin D as a potentially valuable supplement for cancer treatment and prevention. Nevertheless, there need to be adequate clinical studies performed to substantiate the suppressive ability of vitamin D concerning cancer incidence. Thus, understanding the cellular mechanisms of vitamin D can be advantageous for preventing several chronic diseases. Consequently, this review concentrates on different studies that have been conducted to characterize the outcome of vitamin D in reducing cancer incidence and its medication by cellular progression mechanism.
Risks and Benefits of Discontinuation of Nucleos(t)ide Analogue Treatment: A Treatment Concept for Patients With HBeAg‐Negative Chronic Hepatitis B
Authors: van Bömmel Florian , Berg Thomas
Published: June 2021

Systematic discontinuation of long‐term treatment with nucleos(t)ide analogues (NAs) is one strategy to increase functional cure rates in patients with chronic hepatitis B e antigen (HBeAg)–negative hepatitis B. Currently, available study results are heterogeneous; however, long‐term hepatitis B surface antigen (HBsAg) loss rates of up to 20% have been reported in prospective trials. This review proposes criteria that can be used when considering NA discontinuation in patients with chronic hepatitis B virus (HBV). Discontinuing NA treatment frequently results in a virologic and biochemical relapse that runs through different phases: the lag phase, reactivation phase, and consolidation phase. The HBV‐DNA flares observed during the reactivation phase are often transient and most likely represent a trigger for inducing a long‐term immune control by specific CD8+ T cells, and therefore do not need immediate interventions but close follow‐up evaluation. Low HBsAg levels at the time of treatment cessation predict a positive long‐term response to NA discontinuation associated with a higher likelihood of HBsAg clearance. Other host and viral biomarkers are currently under evaluation that may prove to be helpful to further characterize the population that may benefit most from the finite NA treatment concept. Potential harmful biochemical flares during the reactivation phase need to be identified early and can be effectively terminated by reintroducing NA treatment. Hepatic decompensation represents a risk to patients with cirrhosis undergoing NA discontinuation. Therefore, the finite NA approach should only be considered after excluding advanced fibrosis and cirrhosis and if a close follow‐up of the patient and supervision by an experienced physician can be guaranteed. Conclusion: For selected patients, NA discontinuation has become a powerful tool to achieve control over HBeAg‐negative HBV infections. Its significant effect represents a challenge to novel treatment approaches, but it may also serve as their enhancer.
Association of Genetic Risk Score With NAFLD in An Ethnically Diverse Cohort
Authors: Wang Jun , Conti David V. , Bogumil David , Sheng Xin , Noureddin Mazen , Wilkens Lynne R. , Le Marchand Loic , Rosen Hugo R. , Haiman Christopher A. , Setiawan Veronica Wendy
Published: June 2021

Most genetic studies of nonalcoholic fatty liver disease (NAFLD) have been conducted in Whites. In this large and ethnically diverse cohort, we assessed the transportability of previously identified genetic variants for NAFLD, built a genetic risk score (GRS), and examined its association with NAFLD risk in multiple ethnic groups. Thirty previously identified genome‐wide association studies (GWAS) variants (P < 5 × 10−8) and 17 other variants associated with NAFLD were examined in a nested case‐control study of NAFLD (1,448 cases/8,444 controls) in this multi‐ethnic cohort study. We then built a GRS using 11 independent single‐nucleotide polymorphisms from these prior studies and examined its association with NAFLD by cirrhosis status across multiple ethnic groups. Of the 30 GWAS SNPs, 20 (67%) were replicated (P < 0.05) in the pooled multi‐ethnic population. The highest percentage of replication was seen in Latinos (43%), followed by Japanese Americans (37%), Whites (17%), and Native Hawaiians and African Americans (≤10%). Several genetic variants, including those in PNPLA3 (patatin‐like phospholipase domain containing 3), HSD17B13 (hydroxysteroid 17‐beta dehydrogenase 13), TM6SF2 (transmembrane 6 superfamily member 2), GATAD2A (GATA zinc finger domain containing 2A), GCKR (glucokinase regulator), SUGP1 (SURP and G‐patch domain containing 1), MBOAT7 (membrane bound O‐acyltransferase domain containing 7), TRIB1 (tribbles pseudokinase 1), SAMM50 (sorting and assembly machinery component), and ERLIN1 (ER lipid raft associated 1)–CHUK (component of inhibitor of nuclear factor kappa B kinase complex)–CWF19L1 (CWF19 like cell cycle control factor 1) gene cluster, were replicated in at least two ethnic groups. An 11‐SNP weighted GRS was associated with NAFLD risk in the multi‐ethnic population (odds ratio [OR] per SD increase = 1.41; 95% confidence interval [CI] = 1.32‐1.50), as well as in each ethnic group (OR ranged from 1.30 in African Americans to 1.52 in Latinos). The GRS–NAFLD association was stronger for NAFLD with cirrhosis (OR = 1.67; 95% CI = 1.46‐1.92) compared to NAFLD without cirrhosis (OR = 1.37; 95% CI = 1.28‐1.46) (P
heterogeneity = 0.003). Conclusion: In this ethnically diverse cohort, we replicated several key genetic variants for NAFLD and showed the utility of GRS based on the risk alleles for NAFLD risk stratification in multiple ethnic groups.
Can edible oils, as practical phase change materials, be used for body cooling after physical work in a hot–humid environment?
Authors: Wijayanto Titis , Herliansyah Muhammad Kusumawan , Ayu Ajeng Sekar , Sudarman Puspitaningrum Adi
Published: June 2021

This study investigated whether wearing phase change material (PCM) packs made of edible oils, such as coconut oil (CO) and palm oil (PO), after engaging in physical activities can alleviate heat strain in a hot and humid environment. Eleven healthy young males performed a treadmill exercise for 30 min. After the physical activity, the participants underwent resting recovery for 30 min with or without a cooling vest made of either CO‐ or PO‐based PCM packs. Results showed that wearing PCM packs made of edible oils as a personal cooling device significantly reduced tympanic temperature, mean skin temperature, and heart rate during the recovery period. The CO‐ and PO‐based PCM packs also improved perceptual thermal strain during recovery. Hence, PCMs made of edible oils can be used as a cooling device to reduce heat strain and improve comfort after physical work in a hot and humid environment. From the aspects of ergonomics and human factors, the use of CO‐ and PO‐based PCM packs for personal cooling is a viable option for preventing heat‐related disorders and maintaining productivity and workers' well‐being.
Long‐Term Effects of Sglt2 Deletion on Bone and Mineral Metabolism in Mice
Authors: Gerber Claire , Wang Xueyan , David Valentin , Quaggin Susan E. , Isakova Tamara , Martin Aline
Published: June 2021

Sodium‐glucose cotransporter 2 (SGLT2) inhibitors improve kidney and cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM). However, bone fragility has emerged as a side effect in some but not in all human studies. Because use of SGLT2 inhibitors in humans affects mineral metabolism, we investigated the long‐term effects of genetic loss of Sglt2 function on bone and mineral metabolism in mice. Slc5a2 nonsense mutation in Sweet Pee (SP) mice results in total loss of Sglt2 function. We collected urine, serum, and bone samples from 15‐week‐old and 25‐week‐old wild‐type (WT) and SP mice fasted from food overnight. We measured parameters of renal function and mineral metabolism and we assessed bone growth, microarchitecture, and mineralization. As expected, 15‐week‐old and 25‐week‐old SP mice showed increased glucosuria, and normal kidney function compared to age‐matched WT mice. At 15 weeks, SP mice did not show alterations in mineral metabolism parameters. At 25 weeks, SP mice showed reduced fasting 24‐hour urinary calcium excretion and increased fractional excretion of phosphate, but normal serum calcium and phosphate, parathyroid hormone (PTH), vitamin D (1,25(OH)2D), and fibroblast growth factor (FGF23) levels. At 25 weeks, but not at 15 weeks, SP mice showed reduced body weight compared to WT. This was associated with reduced femur length at 25 weeks, suggesting impaired skeletal growth. SP mice did not show trabecular or cortical bone microarchitectural modifications but showed reduced cortical bone mineral density compared to WT mice at 25 weeks. These results suggest that loss of Sglt2 function in mice in the absence of T2DM does not alter regulatory hormones FGF23, PTH, and 1,25(OH)2D, but may contribute to bone fragility over the long term. Future studies are required to determine how loss of Sglt2 function impacts bone fragility in T2DM. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Cytokines: Application in recurrence appraisal for differentiated thyroid carcinoma and their relation with radioiodine ablation
Authors: Yang Mengdie , Yin Yuzhen , Zhang Jiajia , Yi Wanwan , Liu Jin , Chen Duo , Zhang Han , Fan Xin , Zhang Yu , Zhu Mengqin , Qin Shanshan , Lv Zhongwei , Yu Fei
Published: June 2021

The limitations in discriminating preablation disease‐active status of differentiated thyroid carcinoma (DTC) still represent a major challenge to radioiodine dose management. Cytokines, the small protein signaling molecules that constitute the thyroid tumor microenvironment, play significant roles in the facilitation of intercellular communication and the control of tumorigenesis. Also, more attention should be paid to the molecular events within the innate and adaptive immune systems that occur after the organism being exposed to ionizing radiation. Therefore, we implemented a study of 260 patients with DTC in thyroid hormone withdrawal status who were treated with total thyroidectomy to explore the relationship between cytokines and recurrence/active disease status. Besides, we made a cross‐sectional study to analyze pre‐ and post‐ablation serum concentration of cytokines of 86 patients with DTC. There was a relationship between clinicohistopathological characteristics of patients with DTC and the presence of cytokines. It is noteworthy that patients with recurrence/active disease were at a higher serum interleukin‐2 receptor (IL‐2R) level than the disease‐free patients (213.59 ± 75.43 pg/ml vs. 186.80 ± 77.40 pg/ml, P = 0.005). Positive correlation was observed between serum IL‐2R and thyroglobulin (Tg) (P = 0.003). We also found significant changes in the cytokine profile after radioiodine ablation, including the decrease of tumor necrosis factor‐α and IL‐8 (P < 0.001, P < 0.001, respectively), and increase of IL‐2R (P < 0.001). Thus, we suggest that serum IL‐2R may assist in evaluating the disease status during the post‐thyroidectomy follow‐up and radioiodine therapy has an immunoregulatory effect on serum cytokines.
Novelty as Opportunity and Risk: A Situated Cognition Analysis of Psychological Control and Novelty Seeking
Authors: Min Bora , Schwarz Norbert
Published: June 2021

Novel products present unknown opportunities as well as unknown risks. Past research suggested that low psychological control highlights risks and reduces the adoption of novel products. Consistent with a situated cognition perspective, we show that this depends on the specifics of low control. Across five studies, novelty seeking was lower after consumers thought about instances of low (vs. high) personal influence, but higher after consumers thought about instances of low (vs. high) predictability of the world. Thinking about a lack of personal influence increased the perceived importance of personal capability and in turn impaired the exploration of novel options, whereas thinking about an unpredictable world increased the perceived importance of preparedness for an unknown future and in turn the exploration of novel options. Throughout, perceiving low personal influence benefited familiar products, whereas seeing the world as unpredictable benefited novel products. This highlights that understanding consumers' responses to a lack of control requires joint consideration of the specifics of threat and task, consistent with situated cognition principles.
Artificial intelligence‐based analysis of body composition in Marfan: skeletal muscle density and psoas muscle index predict aortic enlargement
Authors: Beetz Nick Lasse , Maier Christoph , Shnayien Seyd , Trippel Tobias Daniel , Gehle Petra , Fehrenbach Uli , Geisel Dominik
Published: June 2021

Background

Patients with Marfan syndrome are at risk for aortic enlargement and are routinely monitored by computed tomography (CT) imaging. The purpose of this study is to analyse body composition using artificial intelligence (AI)‐based tissue segmentation in patients with Marfan syndrome in order to identify possible predictors of progressive aortic enlargement.

Methods

In this study, the body composition of 25 patients aged ≤50 years with Marfan syndrome and no prior aortic repair was analysed at the third lumbar vertebra (L3) level from a retrospective dataset using an AI‐based software tool (Visage Imaging). All patients underwent electrocardiography‐triggered CT of the aorta twice within 2 years for suspected progression of aortic disease, suspected dissection, and/or pre‐operative evaluation. Progression of aortic enlargement was defined as an increase in diameter at the aortic sinus or the ascending aorta of at least 2 mm. Patients meeting this definition were assigned to the ‘progressive aortic enlargement’ group (proAE group) and patients with stable diameters to the ‘stable aortic enlargement’ group (staAE group). Statistical analysis was performed using the Mann–Whitney U test. Two possible body composition predictors of aortic enlargement—skeletal muscle density (SMD) and psoas muscle index (PMI)—were analysed further using multivariant logistic regression analysis. Aortic enlargement was defined as the dependent variant, whereas PMI, SMD, age, sex, body mass index (BMI), beta blocker medication, and time interval between CT scans were defined as independent variants.

Results

There were 13 patients in the proAE group and 12 patients in the staAE group. AI‐based automated analysis of body composition at L3 revealed a significantly increased SMD measured in Hounsfield units (HUs) in patients with aortic enlargement (proAE group: 50.0 ± 8.6 HU vs. staAE group: 39.0 ± 15.0 HU; P = 0.03). PMI also trended towards higher values in the proAE group (proAE group: 6.8 ± 2.3 vs. staAE group: 5.6 ± 1.3; P = 0.19). Multivariate logistic regression revealed significant prediction of aortic enlargement for SMD (P = 0.05) and PMI (P = 0.04).

Conclusions

Artificial intelligence‐based analysis of body composition at L3 in Marfan patients is feasible and easily available from CT angiography. Analysis of body composition at L3 revealed significantly higher SMD in patients with progressive aortic enlargement. PMI and SMD significantly predicted aortic enlargement in these patients. Using body composition as a predictor of progressive aortic enlargement may contribute information for risk stratification regarding follow‐up intervals and the need for aortic repair.