bluuebunny/crossref_metadata_2025 huggingface dataset:
Exceptional response to the ALK and ROS1 inhibitor lorlatinib and subsequent mechanism of resistance in relapsed ALK F1174L-mutated neuroblastoma
Authors: Liu Tingting , Merguerian Matthew D. , Rowe Steven P. , Pratilas Christine A. , Chen Allen R. , Ladle Brian H.
Published: July 2021

Treatment of high-risk neuroblastoma typically incorporates multiagent chemotherapy, surgery, radiation therapy, autologous stem cell transplantation, immunotherapy, and differentiation therapy. The discovery of activating mutations in ALK receptor tyrosine kinase (ALK) in ∼8% of neuroblastomas opens the possibility of further improving outcomes for this subset of patients with the addition of ALK inhibitors. ALK inhibitors have shown efficacy in tumors such as non-small-cell lung cancer and anaplastic large cell lymphoma in which wild-type ALK overexpression is driven by translocation events. In contrast, ALK mutations driving neuroblastomas are missense mutations in the tyrosine kinase domain yielding constitutive activation and differing sensitivity to available ALK inhibitors. We describe a case of a patient with relapsed, refractory, metastatic ALK F1174L-mutated neuroblastoma who showed no response to the first-generation ALK inhibitor crizotinib but had a subsequent complete response to the ALK/ROS1 inhibitor lorlatinib. The patient's disease relapsed after 13 mo of treatment. Sequencing of cell-free DNA at the time of relapse pointed toward a potential mechanism of acquired lorlatinib resistance: amplification of CDK4 and FGFR1 and a NRAS Q61K mutation. We review the literature regarding differing sensitivity of ALK mutations found in neuroblastoma to current FDA-approved ALK inhibitors and known pathways of acquired resistance. Our report adds to the literature of important correlations between neuroblastoma ALK mutation status and clinical responsiveness to ALK inhibitors. It also highlights the importance of understanding acquired mechanisms of resistance.
Telework amidst the COVID-19 pandemic: effects on work style reform in Japan
Authors: Hosoda Masahiro
Published: July 2021

Purpose

This study aims to examine how the COVID-19 pandemic affected telework initiatives in Japanese companies and investigate the factors that affect telework based on the technology, organization and environment (TOE) model, through the analysis of published documents.

Design/methodology/approach

Document analysis was adopted. Documents were collected from English news articles in the Nikkei Asian Review and Nikkei Asia which cover Japan's economy, industries and markets. The results of surveys by the Persol Research Institute and Tokyo Chamber of Commerce and Industry were also provided to discuss factors promoting and hindering telework. Content analysis was adopted to analyse the documents.

Findings

COVID-19 had an unavoidable impact on the implementation of telework that the government had previously failed to instigate. Japanese listed companies tend to implement telework, whereas small- and medium-sized companies are struggling. The ratio of telework has been low even after the declaration of the state of emergency because there exist organizational, technological and environmental barriers to telework in Japan.

Originality/value

This study contributes to discussions on work style reform by focusing on the impacts of the COVID-19 pandemic on telework. This research also gives new insight into operationalization of telework in organizations not only in Japan but also in other countries known for low rates of telework and inflexible work styles such as Korea.
The regulation of multilateral development banks: is it needed? A preliminary analysis
Authors: Gianfagna Laura , Crimaldi Irene , Gallan Davide
Published: July 2021

Purpose

A difference is noted by comparing the net loans to the non-financial sector in the two sets of institutions. The post-global financial crisis (GFC), literature agrees on a reduced lending pace by financial institutions (FIs) as a result of stricter capital regulations. At the same time, an increasing volume of outstanding loans, directed even to advanced countries, characterize the balance sheet of several multilateral development banks (MDBs).

Design/methodology/approach

This paper observes how a different degree of banking regulation might have shaped the economic response to the GFC by FIs and MDBs.

Findings

The authors indicate that MDBs’ financing, with a coherent objective of countercyclical support to the economies hit by the GFC, seems to have filled a market gap caused by the FIs’ pro-cyclical lending reduction.

Originality/value

While a controversial issue is whether Basel standards should be imposed on MDBs, a harmonization amongst MDBs of their transparency and reporting standards might be beneficial: some preliminary consideration has been portrayed.
How social media advertising features influence consumption and sharing intentions: the mediation of customer engagement
Authors: Ji Chunli , Mieiro Susana , Huang Guihai
Published: July 2021

Purpose

Social media advertising (SMA) has become overly critical in the interactive marketing research field. This paper aimed to construct a research architecture model and to investigate the mediating effect of customer engagement between SMA and consumer behavioral intention in the context of Macao's casino integrated resorts.

Design/methodology/approach

The authors collected data from 300 Chinese-speaking visitors of Macao's casino integrated resorts through a face-to-face survey. The hypotheses derived from the conceptual model were tested through two-stage structural equation modeling. The authors considered age and gender as control variables.

Findings

This study found that entertainment and promotional rewards had significant direct effects on consumption intention. Social media dependency did affect directly not only consumption intention but also sharing intention. Customer engagement on SMA mediated the effects of two SMA features (entertainment and promotional rewards) and one feature of SMA viewers (social media dependency) on consumption intention. As to extraneous variables, neither age nor gender significantly influenced consumer behavioral intention.

Practical implications

The casino integrated resort managers should enhance the entertainment elements and provide reasonable promotional rewards to increase SMA's effectiveness. Managers should also consider the social media usage habits of the targeted customers. Further academic research on casino integrated resorts in other regions may use this study as a basis for investigating the mediation of customer engagement on SMA.

Originality/value

This study contributed to understanding the mediating mechanism of customer engagement on SMA by conceptualizing customer engagement on SMA as a unique idea and provided a conceptual framework for further theoretical and empirical research in the interactive marketing research field.
CEO behavior and sustainability performance: the moderating role of corporate governance
Authors: Kouaib Amel , Bouzouitina Asma , Jarboui Anis
Published: July 2021

Purpose

This paper explores how the tension between a firm's CEO overconfidence feature and externally observable hubris attribute may determine the level of corporate sustainability performance. This work also contemplates the impact of the moderator “corporate governance practices.”

Design/methodology/approach

This study uses a sample of 658 firm-year-observations using a sample of European real estate firms indexed on Stoxx Europe 600 Index from 2006 to 2019. To test the developed hypotheses, feasible generalized least square (FGLS) regression is applied.

Findings

Findings suggest that a good corporate governance score strengthens the positive effect of the psychological bias (CEO overconfidence) on corporate sustainability performance while it fails to attenuate the negative effect of the cognitive bias (CEO hubris).

Research limitations/implications

The research provides an overview of the impact of CEO personality traits on the corporate sustainability performance level in the European real estate sup-sector. As corporate governance can have a major impact to control these traits, the authors recommend European real estate companies to improve their corporate governance practices.

Originality/value

This study contributes to the existent literature this gap with two empirical novelties: (1) providing a novel insight into sustainability involvement using a sample of European real estate sup-sector and (2) investigating the moderating effect on the link between CEO psychological and cognitive biases and sustainability performance. This study provides empirical evidence that entrenchment problems arising from CEO hubris would not be mitigated by a good corporate governance practice.
Infill parameters influence over the natural frequencies of ABS specimens obtained by extrusion-based 3D printing
Authors: Parpala Radu Constantin , Popescu Diana , Pupaza Cristina
Published: July 2021

Purpose

The mechanical performances of 3D-printed parts are influenced by the manufacturing variables. Many studies experimentally evaluate the impact of the process parameters on specimens’ static and dynamic behavior with the aim of tailoring the mechanical response of the prints. However, this experimental approach is hampered by the very large number of parameters, 3D printers and materials, the development of computer simulation models being thus required. In the context, this study aims to fill a gap by experimentally investigating the influence of infill related parameters over the vibrations of 3D-printed specimens, as well as to propose and validate a parametric finite element (FE) model for the prediction of eigenfrequencies.

Design/methodology/approach

A generally applicable FE model is not yet available for the 3D printing technology based on the material extrusion process due to the large number of parameters settings that determine a large variability of outcomes. Hence, the idea of developing numerical simulation models that address sets of parameters and assess their impact on a certain mechanical property. For the natural frequency, the influence of the infill density and infill line width is studied in this paper. An FE script that automates the generation of the model geometry by using the considered set of parameters is developed and run. The results of the modal analysis are compared to the experimental values for validating the script.

Findings

Based on the experimental results, a linear regression between the weight of the part and the first natural frequency is established. The response surfaces indicate that the infill density is the most significant parameter of influence. The weight-frequency function is then used for the prediction of the natural frequency of specimens manufactured with other infill parameters and values, including different infill patterns.

Practical implications

As the malfunctions or mechanical damages can be caused by the resonant vibration of parts during use, this research develops a FE-parameterized model that evaluates and predicts the eigenfrequencies of 2D printed parts to prevent these undesirable events. The targeted functional applications are those in which 3D-printed polymer parts are used, such as drone arms or drone propellers.

Originality/value

This research studies the influence of process parameters on the natural frequency of 3D-printed polylactic acid specimens, a topic scarcely addressed in literature. It also proposes a new approach for the development of parameterized FE models for sets of parameters, instead of a general model, to reduce the time and resources allocated to the experimental tests. Such a model is provided in this paper for evaluating the influence of infill parameters on 3D prints eigenfrequency. The numerical model is validated for other infill settings.
Birds of different morphs use slightly different strategies to achieve similar reproductive performance following heatwave exposure
Authors: Fragueira Rita , Helfenstein Fabrice , Fischer Klaus , Beaulieu Michaël
Published: July 2021

Responses to extreme climatic events may differ between individuals of distinct morphs which differ in life‐history strategies, resulting in climate change ‘winners’ and ‘losers’ within species.

We examined the reproductive performance and carry‐over effects on offspring of black‐ and red‐headed Gouldian finches Erythrura gouldiae after exposure to simulated heatwaves of moderate or severe intensity. We expected black‐headed pairs' reproductive performance to decline after the severe heatwave because only the condition of black‐headed females deteriorates during such a heatwave.

Supporting the fact that Gouldian finches of different morphs use alternative reproductive strategies, we found that black‐headed females initiated egg‐laying a month earlier than red‐headed females after experiencing a severe heatwave. We also found that this severe heatwave resulted in shorter spermatozoa in males irrespective of their morph. Despite these effects associated with heatwave intensity, the overall reproductive performance of both morphs was not affected by this factor, which was possibly due to an increased nestling provisioning rate by parents after exposure to the severe heatwave. However, offspring still bore the cost of parental exposure to the severe heatwave, as they showed a reduced condition (lower plasma antioxidant capacity and transient lower breathing rate) and higher oxidative damage (at least in fledglings with black‐headed parents).

These results suggest that inter‐morph phenotypic variability in the Gouldian finch does not result in clear differences in reproductive performance following heatwave exposure, despite basal phenotypic differences between morphs.

Whether animals using alternative reproductive strategies are, in the end, differently affected by climate changes will likely depend on the capacity of their offspring to recover from altered developmental conditions.
Phylogenetically closely related pseudomonads isolated from arthropods exhibit differential insect‐killing abilities and genetic variations in insecticidal factors
Authors: Vesga Pilar , Augustiny Eva , Keel Christoph , Maurhofer Monika , Vacheron Jordan
Published: July 2021

Strains belonging to the Pseudomonas protegens and Pseudomonas chlororaphis species are able to control soilborne plant pathogens and to kill pest insects by producing virulence factors such as toxins, chitinases, antimicrobials or two‐partner secretion systems. Most insecticidal Pseudomonas described so far were isolated from roots or soil. It is unknown whether these bacteria naturally occur in arthropods and how they interact with them. Therefore, we isolated P. protegens and P. chlororaphis from various healthy insects and myriapods, roots and soil collected in an agricultural field and a neighbouring grassland. The isolates were compared for insect killing, pathogen suppression and host colonization abilities. Our results indicate that neither the origin of isolation nor the phylogenetic position mirror the degree of insecticidal activity. Pseudomonas protegens strains appeared homogeneous regarding phylogeny, biocontrol and insecticidal capabilities, whereas P. chlororaphis strains were phylogenetically and phenotypically more heterogenous. A phenotypic and genomic analysis of five closely related P. chlororaphis isolates displaying varying levels of insecticidal activity revealed variations in genes encoding insecticidal factors that may account for the reduced insecticidal activity of certain isolates. Our findings point towards an adaption to insects within closely related pseudomonads and contribute to understand the ecology of insecticidal Pseudomonas.
Metagenomic insights into soil microbial communities involved in carbon cycling along an elevation climosequences
Authors: Dai Zhongmin , Zang Huadong , Chen Jie , Fu Yingyi , Wang Xuehua , Liu Huaiting , Shen Congcong , Wang Jianjun , Kuzyakov Yakov , Becker Joscha N. , Hemp Andreas , Barberán Albert , Gunina Anna , Chen Huaihai , Luo Yu , Xu Jianming
Published: July 2021

Diversity and community composition of soil microorganisms along the elevation climosequences have been widely studied, while the microbial metabolic potential, particularly in regard to carbon (C) cycling, remains unclear. Here, a metagenomic analysis of C related genes along five elevations ranging from 767 to 4190 m at Mount Kilimanjaro was analysed to evaluate the microbial organic C transformation capacities in various ecosystems. The highest gene abundances for decomposition of moderate mineralizable compounds, i.e. carbohydrate esters, chitin and pectin were found at the mid‐elevations with hump‐shaped pattern, where the genes for decompositions of recalcitrant C (i.e. lignin) and easily mineralizable C (i.e. starch) showed the opposite trend (i.e. U‐shaped pattern), due to high soil pH and seasonality in both low and high elevations. Notably, the gene abundances for the decompositions of starch, carbohydrate esters, chitin and lignin had positive relationships with corresponding C compounds, indicating the consistent responses of microbial functional profiles and metabolites to elevation climosequences. Understanding of adaptation of microbial communities, potential function and metabolites to elevation climosequences and their influencing factors provided a new insight for the regulation of terrestrial C storage.
Lactate metabolism in strictly anaerobic microorganisms with a soluble NAD+‐dependent l‐lactate dehydrogenase
Authors: Rosenbaum Florian P. , Poehlein Anja , Egelkamp Richard , Daniel Rolf , Harder Sönke , Schlüter Hartmut , Schoelmerich Marie Charlotte
Published: July 2021

Lactate is a universal metabolite and energy source, yet the mode of lactate metabolism in many strictly anaerobic microorganisms is still enigmatic. This sparked us to investigate the biochemistry and bioenergetics of lactate metabolism in the model acetogenic bacterium Moorella thermoacetica. Growth and metabolism were dependent on CO2 and the chemiosmotic gradient. We discovered a l‐lactate:NAD+ oxidoreductase (LDH) in cell‐free extracts, exhibiting an average specific activity of 362.8 ± 22.9 mU mg−1. The enzyme was reversible, most active at 65°C and pH 9, with Km values of 23.1 ± 3.7 mM for l‐lactate and 273.3 ± 39.1 μM for NAD+. In‐gel activity assays and mass spectrometric proteomics revealed that the ldh gene encoded the characterized LDH. Transcriptomic and genomic analyses showed that ldh expression was induced by lactate and there was a single nucleotide polymorphism near the predicted NAD+ binding site. Genes encoding central redox and energy metabolism complexes, such as, the energetic coupling site Ech2, menaquinone, and the electron bifurcating EtfABCX and MTHFR were also upregulated in cells grown on lactate. These findings ultimately lead to a redox‐balanced metabolic model that shows how growth on lactate can proceed in a microorganism that only has a conventional NAD+‐reducing LDH.
‘It's scientific!’ Play, parody, and the para‐ethnographic in Southwest China
Authors: Swancutt Katherine
Published: July 2021

Play and games encourage persons to hold the world at a distance, while occasionally challenging its norms through parody, mimicry, and clowning, too. In this article, I offer new ethnography on drinking games among the Nuosu of Southwest China, who distribute penalty shots by injecting them directly into glasses with a syringe. While this revelry may evoke the recent Nuosu history of heroin (ab)use and HIV/AIDS, syringes are used in drinking games to parody the scientific writ large, which encompasses China's modern nation‐building approach, rationality, technological progress, biomedicine, hygiene, urban life, industry, precise standardized measurements, and even the human sciences, including anthropology, ethnology, and ethno‐history. Offering two case studies in which Nuosu ethno‐historians gesture to the scientific and the para‐ethnographic during drinking games, I show that – like ethnography – their play is meant to encourage everyone to stretch the bounds of the occasion by adopting a reflexive stance towards it.
A comparative study of amino acid, mineral and vitamin profiles of milk from Turkish Saanen, Hair and Maltese goat breeds throughout lactation
Authors: Günay Emine , Güneşer Onur , Karagül Yüceer Yonca
Published: July 2021

This study aimed to evaluate the changes in nutritional compounds such as amino acids, minerals, and vitamins in the milk of Turkish Saanen, Hair and Maltese goat breeds. The Turkish Saanen goat breed had lower dry matter, fat, nitrogen, and vitamins A, E and B2than Maltese and Hair goat breeds throughout lactation period. High levels of proline, leucine, glutamic acid, and glutamine were found in all breeds. Except for tyrosine, all other amino acids were higher in Hair goat milk than those in other breed milk. The calcium content of the samples ranged from 1164.79 to 1214.16 mg/L.
Unravelling the fruit microbiome: The key for developing effective biological control strategies for postharvest diseases
Authors: Zhang Hongyin , Serwah Boateng Nana Adwoa , Ngolong Ngea Guillaume Legrand , Shi Yu , Lin Hetong , Yang Qiya , Wang Kaili , Zhang Xiaoyun , Zhao Lina , Droby Samir
Published: July 2021

Fruit‐based diets are recognized for their benefits to human health. The safety of fruit is a global concern for scientists. Fruit microbiome represents the whole microorganisms that are associated with a fruit. These microbes are either found on the surfaces (epiphytes) or in the tissues of the fruit (endophytes). The recent knowledge gained from these microbial communities is considered relevant to the field of biological control in prevention of postharvest fruit pathology. In this study, the importance of the microbiome of certain fruits and how it holds promise for solving the problems inherent in biocontrol and postharvest crop protection are summarized. Research needs on the fruit microbiome are highlighted. Data from DNA sequencing and “meta‐omics” technologies very recently applied to the study of microbial communities of fruits in the postharvest context are also discussed. Various fruit parameters, management practices, and environmental conditions are the main determinants of the microbiome. Microbial communities can be classified according to their structure and function in fruit tissues. A critical mechanism of microbial biological control agents is to reshape and interact with the microbiome of the fruit. The ability to control the microbiome of any fruit is a great potential in postharvest management of fruits. Research on the fruit microbiome offers important opportunities to develop postharvest biocontrol strategies and products, as well as the health profile of the fruit.
Practical in‐storage interventions to control foodborne pathogens on fresh produce
Authors: Sheng Lina , Zhu Mei‐Jun
Published: July 2021

Although tremendous efforts have been made to ensure fresh produce safety, various foodborne outbreaks and recalls occur annually. Most of the current intervention strategies are evaluated within a short timeframe (less than 1 h), leaving the behavior of the remaining pathogens unknown during subsequent storages. This review summarized outbreak and recall surveillance data from 2009 to 2018 obtained from government agencies in the United States to identify major safety concerns associated with fresh produce, discussed the postharvest handling of fresh produce and the limitations of current antimicrobial interventions, and reviewed the intervention strategies that have the potential to be applied in each storage stage at the commercial scale. One long‐term (up to 12 months) prepacking storage (apples, pears, citrus among others) and three short‐term (up to 3 months) postpacking storages were identified. During the prepacking storage, continuous application of gaseous ozone at low doses (≤1 ppm) is a feasible option. Proper concentration, adequate circulation, as well as excess gas destruction and ventilation systems are essential to commercial application. At the postpacking storage stages, continuous inhibition can be achieved through controlled release of gaseous chlorine dioxide in packaging, antimicrobial edible coatings, and biocontrol agents. During commercialization, factors that need to be taken into consideration include physicochemical properties of antimicrobials, impacts on fresh produce quality and sensory attributes, recontamination and cross‐contamination, cost, and feasibility of large‐scale production. To improve fresh produce safety and quality during storage, the collaboration between researchers and the fresh produce industry needs to be improved.
Potential impacts of 3D modeling and 3D printing in firearm toolmark examinations
Authors: Li Sun Yi , Turner Jennifer , Golightly Scott , Zelbst Pamela , Yu Jorn
Published: July 2021

In this work, two gun barrels were 3D‐printed using a metal alloy material from the same 3D digital model created in silico. After assembling the barrels in a reference Colt 45 Auto semi‐automatic pistol, a total of 100 rounds of ammunition were successfully test‐fired through each barrel. Heavy and gross striations were observed on all fired bullets. The striations on bullets discharged from the corresponding 3D‐printed gun barrel were found to be identifiable. Moreover, bullets fired from one 3D‐printed gun barrel were easily excluded from those fired from the other 3D‐printed gun barrel by visual examination under a comparison microscope. The resulting unconventional striations that were observed were apparent to an experienced firearm and toolmark examiner. These features could provide valuable investigative leads related to the 3D printing process. Since 3D printing has become an option for firearm manufacturing, the forensic science community should establish a knowledge base associated with the toolmark features generated by the 3D‐printed products.
Strategic malting barley improvement for craft brewers through consumer sensory evaluation of malt and beer
Authors: Craine Evan B. , Bramwell Stephen , Ross Carolyn F. , Fisk Scott , Murphy Kevin M.
Published: July 2021

American craft brewers are targeting barley malt as a novel source of flavor and as a means of differentiation. However, fundamental tools have only recently emerged to aid barley breeders in supporting this effort, such as the hot steep malt sensory method, a wort preparation method recently approved by the American Society of Brewing Chemists for evaluation of extractable malt flavor. The primary objective of this study was to determine if insights into beer liking and sensory attributes can be gained through hot steep malt sensory using an untrained panel of craft beer consumers (n = 95). We evaluated consumer acceptance of hot steep and beer samples of different barley genotypes using a 9‐point hedonic scale, check‐all‐that‐apply (CATA), and open comment during separate sensory panels. Beers brewed with Washington State University breeding lines (n = 4), selected for all‐malt craft brewing, generally had higher consumer acceptance than the industry‐standard control variety (CDC Copeland). Genotype had a significant influence on the consumer acceptance of beer aroma, appearance, taste/flavor, sweetness, and overall liking but only on hot steep appearance. Significant differences between genotypes were found for 18% (fruity and other) and 46% (chemical, citrus, earthy, fruity, stale, and sweet aromatic) of CATA attributes for the hot steep and beer panels, respectively. Hot steep and beer liking and sensory attributes had low correlation coefficients. For example, beer overall liking was negatively correlated with chemical (r = −0.338, p < 0.0001) and positively correlated with fruity (r = 0.265, p < 0.0001). This study demonstrates that untrained craft beer consumers can better differentiate among genotypes using beers than hot steep samples.

Practical Application

In general, Washington State University barley breeding lines had higher consumer acceptance than the control variety, CDC Copeland. Each genotype had a distinctive beer flavor profile, such as 12WA_120.14 (fruity and sweet aromatic), which had the highest consumer acceptance ratings, and 10WA_107.43 (citrus), which has been released as the variety “Palmer.” The results illustrate that the use of different barley genotypes presents varied sensory properties in the final beer and that particular malt and beer sensory attributes may influence consumer acceptance.
Enteromorpha prolifera polysaccharide prevents high‐ fat diet‐induced obesity in hamsters: A NMR‐based metabolomic evaluation
Authors: Guo Fuchuan , Han Mengyuan , Lin Song , Ye Hui , Chen Jiedong , Zhu Hongni , Lin Wenting
Published: July 2021

Enteromorpha prolifera polysaccharide (EP) has been shown to exhibit hypolipidemic and hypoglycemic activities in various experimental models. Here, an 1H‐NMR‐based metabolomic study was conducted to explore the regulatory effects of EP on serum metabolic changes in obese hamsters. High‐fat diet (HFD)‐fed hamsters were orally administrated with EP (300, 450, or 600 mg/kg) once daily for 12 weeks. Compared with HFD‐fed hamsters, EP treatment (450 and 600 mg/kg) significantly decreased the body weight (by 8.69 and 8.24%), liver weight (by 7.87 and 8.25%), epididymal white adipose tissue (by 19.54 and 17.26%), perirenal white adipose tissue (by 28.09 and 28.94%), serum total cholesterol (by 24.31 and 18.61%), triglyceride (by 30.64 and 31.38%), and low‐density lipoprotein cholesterol (by 38.26 and 36.30%), respectively. In addition, EP intervention also significantly decreased hepatic cholesterol (by 23.20, 38.16, and 34.57%) and triglyceride content (by 17.78, 41.47, and 35.50%) as well as serum levels of alanine aminotransferase (ALT) and ALT/aspartate aminotransferase (AST) ratio. The serum samples of normal diet (ND) group, HFD group and HFD + EP 450 mg/kg (HFD + MEP) group were further analyzed by 1H‐NMR spectroscopy. Compared with ND group, 17 and 2 metabolites were significantly upregulated and downregulated in HFD group, respectively. Interestingly, EP treatment significantly downregulated nine metabolites and upregulated one metabolite when compared to those in HFD group. Our results indicated that EP intervention partially ameliorated HFD‐induced metabolic dysfunction, and the most prominent metabolic pathways included citrate cycle, synthesis and degradation of ketone bodies, pyruvate metabolism, valine, leucine and isoleucine degradation, and arginine biosynthesis.

Practical Application

Enteromorpha prolifera polysaccharide (EP), the main active component of Enteromorpha prolifera, is reported to have many biological activities. However, the antiobesity effect of EP and its corresponding metabolic mechanism have not been reported so far. The results of this study confirmed the antiobesity effect of EP on HFD‐induced obese hamsters and elucidated its possible metabolic mechanism. Our study highlighted that EP might be used in weight‐loss functional foods.
Genome analysis of Streptomyces sp. UH6 revealed the presence of potential chitinolytic machinery crucial for chitosan production
Authors: Duhsaki Lal , Mukherjee Saumashish , Rani Tirupaati Swaroopa , Madhuprakash Jogi
Published: July 2021

Chitosan and its derivatives have numerous applications in wastewater treatment as bio‐coagulants, flocculants and bio‐adsorbents against both particulate and dissolved pollutants. Chitinolytic bacteria secrete an array of enzymes, which play crucial role in chitin to chitosan conversion. Consequently, there is a growing demand for identification and characterization of novel bacterial isolates with potential implications in chitosan production. We describe genomic features of the new isolate Streptomyces sp. UH6. Analysis of the 6.51 Mb genome revealed the GC content as 71.95% and presence of 6990 coding sequences of which 63% were functionally annotated. Further, we identified two possible chitin‐utilization pathways, which employ secreted enzymes like lytic polysaccharide monooxygenases and family‐18 glycoside hydrolases (GHs). More importantly, the genome has six family‐4 polysaccharide deacetylases with probable role in chitin to chitosan conversion, as well as two chitosanases belonging to GH46 and GH75 families. In addition, the gene clusters, dasABC and ngcEFG coding for transporters, which mediate the uptake of N,N′‐diacetylchitobiose and N‐acetyl‐d‐glucosamine were identified. Several genes responsible for hydrolysis of other polysaccharides and fermentation of sugars were also identified. Taken together, the phylogenetic and genomic analyses suggest that the isolate Streptomyces sp. UH6 secretes potential chitin‐active enzymes responsible for chitin to chitosan conversion.
Understanding total energy expenditure in people with dementia: A systematic review with directions for future research
Authors: Porter Judi , Thompson Hannah , Tjahyo Alvin Surya
Published: July 2021

Objective

Weight loss is a primary manifestation of dementia. This review aimed to systematically synthesise the literature on total energy expenditure (TEE) in people with dementia.

Methods

The protocol, registered with PROSPERO, was reported against PRISMA guidelines. Eligible studies investigated TEE in people with dementia. Six electronic databases and a supplementary Internet search identified relevant publications. Results were synthesised narratively.

Results

The final library considered the TEE of 358 participants. Two studies used the gold standard method of doubly labelled water (DLW); other studies used TEE measures validated against DLW. TEE varied considerably, from 6095 ± 1353 kJ to 9765 ± 2066 kJ. The TEE of community‐dwelling people with dementia (range 8430 ± 2250 kJ‐9765 ± 2066 kJ) was higher than in institutionalised groups (range 6095 ± 1353 kJ‐7619 ± 1827 kJ).

Conclusion

New technologies will enable future research in this patient population to be less burdensome than those reliant on DLW measures. In planning future research, avoidance of selection bias and considering disease stage and movement are important considerations.
Chinese breast cancer patients with CYP2D6*10 mutant genotypes have a better prognosis with toremifene than with tamoxifen
Authors: Wang Hongyue , Ma Xinchi , Zhang Bin , Zhang Yaotian , Han Ning , Wei Linlin , Sun Chaonan , Sun Shichen , Zeng Xue , Guo Hong , Li Yubing , Zhang Yanyu , Zhao Jiaming , Qin Zilan , Liu Zhuang , Zhang Na
Published: July 2021

Purpose

To evaluate the prognosis of estrogen receptor‐positive breast cancer patients with CYP2D6*10 mutant genotypes under tamoxifen or toremifen therapy.

Methods

Estrogen receptor‐positive breast cancer patients were selected and CYP2D6*10 genotypes (C/C, C/T, and T/T) were determined by Sanger sequencing. Patients were divided into tamoxifen, toremifene, or tamoxifen + toremifene groups according to prior therapy. The correlation between CYP2D6*10 genotype and disease‐free survival was analyzed.

Results

In total, 293 estrogen receptor‐positive breast cancer patients treated with tamoxifen or toremifene between 2008 and 2017 were studied. Median follow‐up was 39 months (10–141). Of these, 107 (36.52%), 112 (38.23%), and 74 (25.26%) patients had C/C, C/T, and T/T genotypes, respectively. Genotype was significantly associated with disease‐free survival in tamoxifen patients. Patients with C/T and T/T genotypes showed worse disease‐free survival than patients with a C/C genotype. Genotype and disease‐free survival in toremifene and tamoxifen+toremifene patients were not correlated. Of patients with a C/T genotype, toremifene or tamoxifen+toremifene groups showed better disease‐free survival than tamoxifen patients. Although disease‐free survival of patients with a T/T genotype in the three groups was not statistically different, tamoxifen patients showed worse disease‐free survival. There was no correlation between different treatments and disease‐free survival in patients with a C/C genotype. Cox proportional hazard analysis revealed toremifene patients had a better prognosis than tamoxifen patients; toremifene was an independent protective factoremifene for disease‐free survival.

Conclusions

Tamoxifen was less effective in patients with CYP2D6*10 C/T and T/T genotypes. Estrogen receptor‐positive breast cancer patients with a CYP2D6*10 mutation genotype have a better prognosis with toremifen than tamoxifen.
Immune status of decidual macrophages is dependent on the CCL2/CCR2/JAK2 pathway during early pregnancy
Authors: Wei Chun‐Yan , Li Ming‐Qing , Zhu Xiao‐Yong , Li Da‐Jin
Published: July 2021

Problem

Decidual macrophages (dMφ) play an important role in the formation of maternal–fetal immune tolerance. However, factors that influence the immune status of dMφ and the related potential mechanisms have not been elucidated to date.

Method of study

The gene transcription in dMφ, decidual stromal cells (DSCs), extravillous trophoblasts (EVTs), and peripheral monocytes (pMo) from human samples were measured using real‐time polymerase chain reaction (PCR). Monocyte‐DSC co‐culture was established to explore whether DSCs influenced dMφ polarization via C‐C motif ligand 2 (CCL2)‐C‐C chemokine receptor (CCR2) binding using flow cytometry. In vivo, changes in dMφ percentage and M1 and M2 marker expression after treatment with CCR2 or Janus kinase 2 (JAK2) inhibitor were detected with flow cytometry. Embryo resorption percentages in the above groups were also analyzed.

Results

We found that dMφ were an M1/M2 mixed status at the maternal–fetal interface during early pregnancy. CCL2 influenced the immune status of dMφ in an autocrine and paracrine manner. As a downstream regulator of CCR2 and triggers the Stat3 pathway, JAK2 was found to be essential for dMφ homeostasis in vivo. JAK2 inhibitor decreased the dMφ proportion and attenuated Ki67, CD36, CD86, CD206, TNF, and IL‐10 expression in dMφ at E8.5 d. Moreover, CCR2‐JAK2 pathway inhibition decreased the width of the placental labyrinth layer, further influencing the pregnancy outcome.

Conclusion

The M1/M2 mixed immune status of dMφ was regulated by DSCs via CCR2, and the CCL2/CCR2/JAK2 pathway was essential for the immune status of dMφ and the outcome of early pregnancy.
Factors associated with mortality in patients with COVID‐19 admitted to intensive care: a systematic review and meta‐analysis
Authors: Taylor E. H. , Marson E. J. , Elhadi M. , Macleod K. D. M. , Yu Y. C. , Davids R. , Boden R. , Overmeyer R. C. , Ramakrishnan R. , Thomson D. A. , Coetzee J. , Biccard B. M.
Published: July 2021

Identification of high‐risk patients admitted to intensive care with COVID‐19 may inform management strategies. The objective of this meta‐analysis was to determine factors associated with mortality among adults with COVID‐19 admitted to intensive care by searching databases for studies published between 1 January 2020 and 6 December 2020. Observational studies of COVID‐19 adults admitted to critical care were included. Studies of mixed cohorts and intensive care cohorts restricted to a specific patient sub‐group were excluded. Dichotomous variables were reported with pooled OR and 95%CI, and continuous variables with pooled standardised mean difference (SMD) and 95%CI. Fifty‐eight studies (44,305 patients) were included in the review. Increasing age (SMD 0.65, 95%CI 0.53–0.77); smoking (OR 1.40, 95%CI 1.03–1.90); hypertension (OR 1.54, 95%CI 1.29–1.85); diabetes (OR 1.41, 95%CI 1.22–1.63); cardiovascular disease (OR 1.91, 95%CI 1.52–2.38); respiratory disease (OR 1.75, 95%CI 1.33–2.31); renal disease (OR 2.39, 95%CI 1.68–3.40); and malignancy (OR 1.81, 95%CI 1.30–2.52) were associated with mortality. A higher sequential organ failure assessment score (SMD 0.86, 95%CI 0.63–1.10) and acute physiology and chronic health evaluation‐2 score (SMD 0.89, 95%CI 0.65–1.13); a lower PaO2:FIO2 (SMD −0.44, 95%CI −0.62 to −0.26) and the need for mechanical ventilation at admission (OR 2.53, 95%CI 1.90–3.37) were associated with mortality. Higher white cell counts (SMD 0.37, 95%CI 0.22–0.51); neutrophils (SMD 0.42, 95%CI 0.19–0.64); D‐dimers (SMD 0.56, 95%CI 0.43–0.69); ferritin (SMD 0.32, 95%CI 0.19–0.45); lower platelet (SMD −0.22, 95%CI −0.35 to −0.10); and lymphocyte counts (SMD −0.37, 95%CI −0.54 to −0.19) were all associated with mortality. In conclusion, increasing age, pre‐existing comorbidities, severity of illness based on validated scoring systems, and the host response to the disease were associated with mortality; while male sex and increasing BMI were not. These factors have prognostic relevance for patients admitted to intensive care with COVID‐19.
Asylum Seeking, Border Security, Hope
Authors: Hodge Paul , Hodge Steven
Published: July 2021

Asylum seeking galvanises brutal state responses. The challenge of confronting the brutality of border security is understanding the elusive interlocking of knowledge and power that normalises technologies of securitisation, detention, and defiance of international conventions. In this paper we employ Marxist philosopher Ernest Bloch to interrogate the temporal horizon of border security discourse revealing the act of asylum seeking as a form of activism threatening breakthrough to an alternative future. In this analysis we expose discourses, such as Australia’s Operation Sovereign Borders, as formations marked by temporal closure as much as by a specific imbrication of knowledge and power. Drawing on nine vignettes, we discern opposing versions of hope as people seeking asylum, politicians, activists, practitioners, and Australian citizens are enrolled into the diffuse and multifaceted global response to asylum seeking. We demonstrate differing temporalities distinguishing and advocating the overwhelming vision of hope in the act of asylum seeking itself.
Clinical features and treatment of Langerhans cell histiocytosis
Authors: Rodriguez‐Galindo Carlos
Published: July 2021

Langerhans cell histiocytosis (LCH) is caused by the expansion of CD1a+/CD207+ cells and is characterised by a wide spectrum of organ involvement and dysfunction, affecting all ages. While almost all organs and systems can be affected, only the involvement and dysfunction of liver, spleen, and haematopoietic system influence survival. The LCH pathogenic cells are defined by universal activation of the mitogen‐activated protein kinase (MAPK) signalling pathway. The most common alteration is a somatic BRAFV600E mutation, which is present in approximately two‐thirds of the cases, followed by MAP2K1 mutations. Treatment of LCH is risk‐adapted; patients with single lesions may respond well to local treatment, whereas patients with multi‐system disease require systemic chemotherapy. While survival for patients without organ dysfunction is excellent, mortality rates for patients with organ dysfunction may reach 20%. Despite progress made in the treatment of LCH, disease reactivation rates remain above 30%, and standard second‐line treatment has yet to be established. Long‐term effects, including neuroendocrine dysfunction and neurodegeneration, represent a major challenge for survivors. Treatment with BRAF or MEK inhibitors results in immediate responses, but reactivations are very common after discontinuation. Their role as single agents and in combination with chemotherapy is being explored.
Work and home boundary violations during the COVID‐19 pandemic: The role of segmentation preferences and unfinished tasks
Authors: Kerman Katja , Korunka Christian , Tement Sara
Published: July 2021

During the COVID‐19 pandemic, an unprecedented number of employees faced the challenges of telework. However, the current literature has a limited understanding of the implications of employees' obligated home‐based telework and their satisfaction with the work and home domains. We use boundary theory to examine work and home boundary violations in relation to satisfaction with domain investment in two daily diary studies, examining both domain‐specific and cross‐domain effects. In addition, we examine the moderating role of segmentation preferences in both studies and investigate the mediating role of work‐ and home‐related unfinished tasks in Study 2. Both studies provide empirical evidence of the domain‐specific relationship between boundary violations and domain satisfaction and provide limited support for cross‐domain effects. Neither study finds support for the notion that segmentation preferences moderate the relationship between boundary violations and domain satisfaction. Finally, the results of Study 2 highlight the importance of unfinished tasks in the relationship between boundary violations and domain satisfaction. Specifically, work and home boundary violations relate to an increase in unfinished tasks in both domains. Finally, the indirect effects suggest that home‐related unfinished tasks may be detrimental to satisfaction in both domains, while work‐related unfinished tasks may be detrimental for work‐related, but not home‐related, satisfaction.
Mental health and coping strategies during the COVID‐19 pandemic: A qualitative study of unemployed and employed people in Nigeria
Authors: Ogueji Ifeanyichukwu Anthony , Agberotimi Samson Femi , Adesanya Bolaji Johnson , Gidado Taiwo Nurudeen
Published: July 2021

The coronavirus disease 2019 (COVID‐19) significantly disrupted human activities all over the world. Despite this, little or nothing is known about mental health and coping strategies during the COVID‐19 pandemic among the unemployed and employed people in Nigeria. Therefore, this study was an effort towards bridging this knowledge gap. We employed a qualitative design with 66 participants (age range = 18–62 years) who described how the COVID‐19 pandemic affected their mental health and how they coped during the COVID‐19 pandemic. The data were analyzed using thematic analysis. Our findings revealed distressing impacts (e.g., depressive and anxious impacts, stress, loss of job, financial challenges, loneliness, etc.) for the unemployed and employed groups. Further, the unemployed group utilized more positive coping strategies (e.g., engaging in activities, hope, relaxation, connecting with others, etc.) than the employed group; whereas, only the employed group utilized a maladaptive coping strategy (alcohol consumption). These data have practical implications for protecting mental health and fostering positive coping in these groups during and beyond the COVID‐19 pandemic.
Deletion or inhibition of prolyl oligopeptidase blocks lithium‐induced phosphorylation of GSK3b and Akt by activation of protein phosphatase 2A
Authors: Myöhänen Timo T. , Mertens Freke , Norrbacka Susanna , Cui Hengjing
Published: July 2021

Alterations in prolyl oligopeptidase (PREP) activity have been connected, for example, with bipolar and major depressive disorder, and several studies have reported that lack or inhibition of PREP blocks the effects of lithium on inositol 1,4,5‐triphosphate (IP3) levels. However, the impact of PREP modulation on other intracellular targets of lithium, such as glycogen synthase kinase 3 beta (GSK3b) or protein kinase B (Akt), has not been studied. We recently found that PREP regulates protein phosphatase 2A (PP2A), and because GSK3b and Akt are PP2A substrates, we studied if PREP‐related lithium insensitivity is dependent on PP2A. To assess this, HEK‐293 and SH‐SY5Y cells with PREP deletion or PREP inhibition (KYP‐2047) were exposed to lithium, and thereafter, the phosphorylation levels of GSK3b and Akt were measured by Western blot. As expected, PREP deletion and inhibition blocked the lithium‐induced phosphorylation on GSK3b and Akt in both cell lines. When lithium exposure was combined with okadaic acid, a PP2A inhibitor, KYP‐2047 did not have effect on lithium‐induced GSK3b and Akt phosphorylation. Therefore, we conclude that PREP deletion or inhibition blocks the intracellular effects of lithium on GSK3b and Akt via PP2A activation.