bluuebunny/crossref_metadata_2025 huggingface dataset:
Does research‐informed teaching transform academic practice? Revealing a RIT mindset through impact analysis
Authors: Joseph‐Richard Paul , Almpanis Timos , Wu Qi , Jamil Mohammad Golam
Published: March 2021

Integration of research into teaching is a major area of interest in the field of higher education. Considerable work has been done on how staff and students view this integration, how it can be achieved in practice and how it might best be researched by scholars. However, relatively little research has considered how research‐informed teaching (RIT) impacts teachers’ own practice, in multi‐disciplinary contexts. We interviewed a purposive sample of 20 research‐active teachers from a range of disciplines, at an English University. Using the UK Professional Standards Framework (UKPSF), we mapped our findings of a thematic analysis, concluding that RIT impacts academic practice in a range of distinct and complex ways. Because of RIT, lecture design, delivery, assessments and student support activities have become more inquiry‐focused; study spaces have turned into collaborative learning contexts and classroom communications have become more comprehensible. For lecturers, RIT has helped create a professional identity and a closer engagement with continuous professional development. Based on our analysis, we argue that what makes these impacts possible is a set of characteristics—termed here the ‘RIT mindset’—that drives academics to voluntarily engage in pragmatic research‐teaching integrations to liberate students into real learning. We offer evidence for RIT impact and make visible how and why RIT impacts academic practice. We provide a caution that RIT happens only by design, and to make that design a reality, developing the RIT mindset may be critical.
Post‐abyssal ethics in education research in settings of conflict and crisis: Stories from the field
Authors: Cremin Hilary , Aryoubi Hogai , Hajir Basma , Kurian Nomisha , Salem Hiba
Published: March 2021

This article draws heavily on the post‐abyssal philosophy of Boaventura de Sousa Santos in order to theorise new ways of thinking about research ethics in settings affected by armed conflict and crisis, and to put them into practice. Our article explores the dilemmas and tensions faced by four graduate students and a supervisor across diverse international settings. For some of us, these are places we call home, for others these are places that provide refuge to our people: Afghanistan, Jordan, Lebanon and India. We seek to deepen standard understandings of ethics as institutionalised in university forms, arguing that tidy checklists for safety and risk mitigation do not adequately address the complex affective and socio‐political struggles permeating research, and the bodies of researchers, in these settings. Our main focus here is on how we can synthesise our various experiences in order to offer something of value to others who may be about to go into the field in settings affected by armed conflict and crisis. The question that we address, then, is: how can researchers avoid the limitations, obfuscations and silences of traditional institutional ethics in order to adopt a situated, embodied, post‐abyssal research ethic that might open up new spaces for emotion, encounter, and engagement with struggle, risk and voicing? We use an autoethnographic approach that enables congruence with the aims of this article, and that supports our aspirations for enhanced impact through powerful narrative. We end with discussion that contains suggestions for institutions, supervisors, researchers, and for funding and professional bodies.
Elective versus urgent in‐hospital transcatheter aortic valve implantation
Authors: Kabahizi Alex , Sheikh Azeem S. , Williams Timothy , Tanseco Kristoffer , Myat Aung , Trivedi Uday , de Belder Adam , Cockburn James , Hildick‐Smith David
Published: March 2021

Background

Transcatheter aortic valve implantation (TAVI) is maturing as a treatment option and is now often undertaken during an unscheduled index hospital admission. The aim of this study was to look at procedural and mid‐term outcomes of patients undergoing elective versus urgent in‐hospital transcatheter aortic valve implantation.

Methods

We identified a total of 1,157 patients who underwent TAVI between November 2007 and November 2019 at the Sussex Cardiac Centre in the UK. We compared the demographics, procedural outcomes, 30‐day and 1‐year mortality between elective and urgent patients. Emergency and salvage TAVI cases were excluded.

Results

Of the 1,157 patients who underwent the procedure, 975 (84.3%) had elective while 182 (15.7%) had urgent TAVI. Predominant aortic stenosis was more frequent in elective patients (91.7% vs. 77.4%); p < .01), while predominant aortic regurgitation was seen more commonly in the urgent group (11.5% vs. 4.2%; p < .01). Implantation success was similar between the elective (99.1%) and urgent group (99.4%). In‐hospital (1.65% vs. 1.3%: p .11), 30 day (3.5% vs. 3.3%: p .81) and 1 year (10.9% vs. 11%; p .81) mortality rates were similar in the elective and urgent groups, respectively.

Conclusions

In contemporary practice, urgent TAVI undertaken on the index admission can be performed at similar risk to elective outpatient TAVI.
Effect of soaking time and temperature on water absorption capacity and dimensional changes of bulgur
Authors: Sfayhi‐Terras Dorra , Hadjyahia Nesrine , Zarroug Youkabed
Published: March 2021

Background and objectives

Soaking is a processing treatment used in different grain. The objective of the present work is to study the water absorption of bulgur (precooked, dried, and debranned durum wheat), at various temperatures (35, 50, 60 and 65°C) by measuring the moisture content with respect to time. The effect of soaking time and temperature on three dimensions was examined (length: “a (mm)”; crease side width: “b (mm)”; secondary width: “c (mm)”). Weight, volume, sphericity, and density of the precooked, dried, and debranned wheat kernel were also measured.

Findings

The results indicated higher water absorption capacity at higher temperature. Peleg's model was successfully used to evaluate water absorption during soaking. Peleg's model constants were investigated relative to temperature and confirmed a higher absorption capacity of water. Moreover, during soaking, all the dimensions as well as weight and volume percentages increased with time and temperature. The percent change of secondary width “c” was affected by both temperature and time soaked, indicating that it was the most important parameter controlling the deformation and shape of the kernel.

Conclusion

Bulgur kernel had higher water absorption due to the absence of the outer bran layer, which acts as a barrier for water absorption.

Significance and novetly

Modeling the water absorption of bulgur during soaking and measuring its size is important since it help industries to control the soaking operation and further cooking operation and then to optimize industrial process dishes based with bulgur.
T‐cell non‐Hodgkin’s lymphoma of both breasts: An uncommon presentation of a common disease
Authors: Sereke Senai Goitom , Oriekot Anthony , Mboizi Vincent , Bogere Naghib , Bongomin Felix
Published: March 2021

Secondary T‐cell non‐Hodgkin's lymphoma of the breasts is a very rare disease and can be easily missed as inflammatory carcinoma at initial presentation. High index of suspicion and radiological investigations has a big role in identifying the primary lymphoma.
Carbon dioxide narcosis in the terminal stage of hemodialysis therapy: A case report with the possible pathophysiologies and the treatment methods
Authors: Takahashi Akira
Published: March 2021

The cause and treatment of carbon dioxide narcosis in the terminal stage of hemodialysis have not been fully discussed. As we have experienced the case of complete recovery, we report the possible pathophysiologies and the treatment methods.
Effect of fine coke particles on rheological properties of the binder matrix of carbon anodes in aluminium production process
Authors: Mollaabbasi Roozbeh , Hansen Lene Jensberg , Grande Tor , Taghavi Seyed Mohammad , Alamdari Houshang
Published: March 2021

Aluminium production through the Hall‐Héroult process relies on an extensive use of carbon anodes, which are originally made of coal tar pitch and fine and coarse carbon particles. During the forming process of green anodes, the mixture of the fine particles and the coal‐tar pitch (i.e., the binder matrix) moves between the coarse particles and produces a uniform agglomerated paste. The efficiency of the forming process directly affects the final quality of the baked anode and consequently the efficiency of the Hall‐Héroult process. The rheological properties of the binder matrix play a crucial role in the forming process. In this study, rotation and oscillation tests are used to study the effects of the fine particle concentration and temperature on the viscoelastic properties of the binder matrix. The rotation tests demonstrate that the binder matrix is a shear‐thinning material and that the viscosity is reduced by increasing the shear rate and temperature while it is increased by increasing the concentration of the fine particles. Moreover, the proposed model can predict the viscosity of the binder matrix precisely. The oscillation tests confirm that the elastic and viscous properties are reinforced by increasing the concentration of the fine particles and they are reduced by increasing the angular frequency and temperature. The three‐element Maxwell model is shown to predict the elastic and viscous moduli of the binder matrix. Finally, in a case study and based on the rheological results, the permeation velocity of the binder matrix between the coarse particles is calculated.
Fullerene Mechanochemistry: Serendipitous Discovery of Dumb‐Bell‐Shaped C120 and Beyond
Authors: Wang Guan‐Wu
Published: March 2021

The serendipitous discovery of dumb‐bell‐shaped C120 under high‐speed vibration milling conditions is described. The mechanochemical protocol has been employed to synthesize the He‐, H2‐ or H2O‐encapsualted C120, the cross‐dimer C130, trimer C180, bridged C60 dimers as well as products from many other reactions of fullerenes, carbon nanotubes and graphenes. Mechanochemistry extended to various reactions of non‐fullerene molecules is briefly discussed.

What is the most favorite and original chemistry developed in your research group?

Mechanochemistry and fullerene chemistry.

How do you get into this specific field? Could you please share some experiences with our readers?

The poor solubility of fullerenes in common organic solvents prompts scientists to seek alternative protocol for fullerene chemistry. An idea of performing chemical reactions of fullerenes in the absence of any organic solvent was conceived when I was a guest research fellow in Kyoto University. That was how I first got into the mechanochemical reactions of fullerenes, and made the serendipitous discovery of fullerene dimer C120.

How do you supervise your students?

I encourage my graduate students to do scientific research of their own

ideas within the scope of my group's research interests. I usually emphasize scientific rigor and intolerance of research misconduct to the graduate students when they first join my group. I provide them my guidance on how to do each piece of scientific work including detailed discussion of encountered problems, even spectral analysis and ChemDraw drawing, manuscript writing, etc.

What is the most important personality for scientific research?

Curiosity, creativity, and persistence.

What are your hobbies?

Sports, mainly jogging and running nowadays.

How do you keep balance between research and family?

My balance has heavily leaned toward work thanks to the understanding and support from my family.
Uncommon Bis‐quinolizidine Alkaloids from the Hainan Sponge Neopetrosia chaliniformis
Authors: Chen Bao , Huan Xia‐Juan , Miao Ze‐Hong , de Voogd Nicole J. , Gu Yu‐Cheng , Wang Chang‐Yun , Guo Yue‐Wei , Li Xu‐Wen
Published: March 2021

Main observation and conclusion

Two new bis‐quinolizidine alkaloids, neopetrosiasins A (1) and B (2), possessing cis‐ and trans‐quinolizidine nuclei, one known related analogue petrosin (3) and three known xestospongins (4—6), were isolated from the South China Sea sponge Neopetrosia chaliniformis. The structures of new compounds were unambiguously determined by extensive spectroscopic and single‐crystal X‐ray analyses. In bioassay, compounds 4—6 exhibited moderate cytotoxicity against several human cancer cells.
Organofluorine Hydrazone Derivatives as Multifunctional Anti‐Alzheimer's Agents with CK2 Inhibitory and Antioxidant Features
Authors: Baier Andrea , Kokel Anne , Horton William , Gizińska Ewa , Pandey Garima , Szyszka Ryszard , Török Béla , Török Marianna
Published: March 2021

A set of novel hydrazone derivatives were synthesized and analyzed for their biological activities. The compounds were tested for their inhibitory effect on the phosphorylating activity of the protein kinase CK2, and their antioxidant activity was also determined in three commonly used assays. The hydrazones were evaluated for their radical scavenging against the DPPH, ABTS and peroxyl radicals. Several compounds have been identified as good antioxidants as well as potent protein kinase CK2 inhibitors. Most hydrazones containing a 4‐N(CH3)2 residue or perfluorinated phenyl rings showed high activity in the radical‐scavenging assays and possess nanomolar IC50 values in the kinase assays.
Whiteness evaluation: A review and new proposals
Authors: Sève Robert
Published: March 2021

This publication carries out an in‐depth study of whiteness, various numerical evaluation methods that have been developed over the past 75 years, and review their application and deficiencies in the context of a new proposed Commission Internationale de l'Eclairage (CIE) whiteness formula. The publication first introduces the basic principle of whiteness evaluation from the work of Judd and Selling around 1950, then that of Ganz in the 1970s and finally that of the CIE from 1969 to 1986. The defects of the Judd and Selling formulas became apparent with the use of fluorescent whitening agents. The CIE linear formula cannot predict an optimum for the optical whitening process. Hyperbolic formulas published are much too complicated and are unable to predict correctly the best conditions for that optical whitening. We present a new formula derived from that of the CIE, much simpler than the hyperbolic formulas, and able to predict an optimal shade in the optical whitening process. The formula takes into account the limitations of the white domain; when the blue saturation becomes too great, or when a tint deviation toward green or toward red is too noticeable. The formula gives results identical to those of the CIE formula when the materials are far from commercial whiteness limits. In addition, the formula can be very easily adapted to the CIELAB system and so, gives promising results.
Comprehensive analysis of SARS‐CoV‐2 antibody dynamics in New Zealand
Authors: Whitcombe Alana L , McGregor Reuben , Craigie Alyson , James Alex , Charlewood Richard , Lorenz Natalie , Dickson James MJ , Sheen Campbell R , Koch Barbara , Fox‐Lewis Shivani , McAuliffe Gary , Roberts Sally A , Morpeth Susan C , Taylor Susan , Webb Rachel H , Jack Susan , Upton Arlo , Ussher James E , Moreland Nicole J
Published: March 2021

Objectives

Circulating antibodies are important markers of previous infection and immunity. Questions remain with respect to the durability and functionality of SARS‐CoV‐2 antibodies. This study explored antibody responses in recovered COVID‐19 patients in a setting where the probability of re‐exposure is effectively nil, owing to New Zealand's successful elimination strategy.

Methods

A triplex bead‐based assay that detects antibody isotype (IgG, IgM and IgA) and subclass (IgG1, IgG2, IgG3 and IgG4) responses against Nucleocapsid (N) protein, the receptor binding domain (RBD) and Spike (S) protein of SARS‐CoV‐2 was developed. After establishing baseline levels with pre‐pandemic control sera (n = 113), samples from PCR‐confirmed COVID‐19 patients with mild–moderate disease (n = 189) collected up to 8 months post‐infection were examined. The relationship between antigen‐specific antibodies and neutralising antibodies (NAbs) was explored with a surrogate neutralisation assay that quantifies inhibition of the RBD/hACE‐2 interaction.

Results

While most individuals had broad isotype and subclass responses to each antigen shortly after infection, only RBD and S protein IgG, as well as NAbs, were relatively stable over the study period, with 99%, 96% and 90% of samples, respectively, having responses over baseline 4–8 months post‐infection. Anti‐RBD antibodies were strongly correlated with NAbs at all time points (Pearson's r ≥ 0.87), and feasibility of using finger prick sampling to accurately measure anti‐RBD IgG was demonstrated.

Conclusion

Antibodies to SARS‐CoV‐2 persist for up to 8 months following mild‐to‐moderate infection. This robust response can be attributed to the initial exposure without immune boosting given the lack of community transmission in our setting.
Buffering and prioritization in switches for fast processing table‐miss packets in software‐defined networks
Authors: Lai Yuan‐Cheng , Legese Hailemariam Zelalem , Chen Yen‐Hung , Kuo Yi‐Ting
Published: March 2021

In software‐defined networks, the switch forwards incoming packets according to forwarding rules recorded in the flow entries. When a switch receives a table‐miss packet, meaning no match with any flow entry, it sends this packet as a Packet‐In message to the controller for its further processing. Many Packet‐In messages will cause large overhead and long packet delay. This paper proposes a novel method, Packet‐In Buffering and Prioritization (PIBP), which buffers Packet‐In messages and prioritizes these messages to reduce the number of Packet‐In messages and accelerate their processing, respectively. The concept of PIBP is sending only the first table‐miss packet of each flow to the controller. The other table‐miss packets belonging to the same flow are temporarily stored in the switch. Moreover, these messages have a higher priority. That is, after the packet sent from the controller has been forwarded from the switch, the buffered packets belonging to the same flow are also immediately forwarded. We formally analyze the performance of PIBP with queuing theory. The analytical and simulation results show that PIBP can decrease the average delay of table‐miss packets compared with two typical methods, Priority Queue and Mismatched Packets Table.
Implementation and comparative analysis of evolutionary algorithms for energy optimization in wireless sensor networks
Authors: Kundaliya Brijesh , Hadia Sarman K.
Published: March 2021

Wireless sensor networks will be at the epitome of applications in near future. It is going through tremendous positive changes. Although it suffers from some limitations and it sorts out its limitations day by day. The biggest limitation of wireless sensor networks is the limited energy of the nodes. Most of the energy is used during the routing of the data. An optimized way of routing will save the valuable energy of the node and helpful for increasing the network's lifetime. The optimization algorithms are indeed utterly helpful in many applications across the different fields to optimize the resources. In the proposed worked we have applied Adaptive Particle Swarm Optimization (APSO), Ant Colony Optimization (ACO), Genetic Algorithms (GA), and Simulated Annealing (SA) to a Modified Rendezvous Point Selection Scheme and observed the effect on the network lifetime and energy consumption in the network. We have made an exhaustive comparison of all the optimization algorithms with considerable simulations.
Synthesis and characterization of new pyrazole–tetrazole derivatives as new vasorelaxant agents
Authors: Cherfi Mounir , Dib Ikram , Harit Tarik , Ziyyat Abderrahim , Malek Fouad
Published: March 2021

The synthesis of new functionalized tetrazole–pyrazole compounds is reported. They were fully characterized by spectroscopy and spectrometry methods. The vasorelaxant potency of these molecules was also investigated. All compounds showed a good vasorelaxant activity but the Compound 6 “ethyl 1‐((2‐(3‐bromopropyl)‐2H‐tetrazol‐5‐yl)methyl)‐5‐methyl‐1H‐pyrazole‐3‐carboxylate” seems to have the highest effect, which reached 70% at 10−4 M concentration. This effect was partially endothelium‐dependent; also, the vasorelaxant pattern of this compound was quite similar to that of the verapamil.
Eya2 expression during mouse embryonic development revealed by Eya2lacZ knockin reporter and homozygous mice show mild hearing loss
Authors: Zhang Ting , Xu Jinshu , Xu Pin‐Xian
Published: March 2021

Background

Eya2 expression during mouse development has been studied by in situ hybridization and it has been shown to be involved skeletal muscle development and limb formation. Here, we generated Eya2 knockout (Eya2−) and a lacZ knockin reporter (Eya2lacZ) mice and performed a detailed expression analysis for Eya2lacZ at different developmental stages to trace Eya2lacZ‐positive cells in Eya2‐null mice. We describe that Eya2 is not only expressed in cranial sensory and dorsal root ganglia, retina and olfactory epithelium, and somites as previously reported, but also Eya2 is specifically detected in other organs during mouse development.

Results

We found that Eya2 is expressed in ocular and trochlear motor neurons. In the inner ear, Eya2lacZ is specifically expressed in differentiating hair cells in both vestibular and cochlear sensory epithelia of the inner ear and Eya2−/− or Eya2lacZ/lacZ mice displayed mild hearing loss. Furthermore, we detected Eya2 expression during both salivary gland and thymus development and Eya2‐null mice had a smaller thymus.

Conclusions

As Eya2 is coexpressed with other members of the Eya family genes, these results together highlight that Eya2 as a potential regulator may act synergistically with other Eya genes to regulate the differentiation of the inner ear sensory hair cells and the formation of the salivary gland and thymus.
Lessons learned through listening to biology students during a transition to online learning in the wake of the COVID‐19 pandemic
Authors: Humphrey Eve A. , Wiles Jason R.
Published: March 2021

During the Spring Semester of 2020, an outbreak of a novel coronavirus (SARS‐CoV‐2) and the illnesses it caused (COVID‐19) led to widespread cancelling of on‐campus instruction at colleges and universities in the United States and other countries around the world. Response to the pandemic in university settings included a rapid and unexpected shift to online learning for faculty and students. The transition to teaching and learning online posed many challenges, and the experiences of students during this crisis may inform future planning for distance learning experiences during the ongoing pandemic and beyond. Herein, we discuss the experiences of first‐ and second‐year university students enrolled in a biology seminar course as their classes migrated to online environments. Drawing on reported student experiences and prior research and resources, we discuss the ways we will adjust our own teaching for future iterations of the course while offering recommendations for instructors tasked with teaching in online environments.
Food resource partitioning between juvenile and mature weatherfish Misgurnus fossilis
Authors: Pyrzanowski Kacper , Zięba Grzegorz , Leszczyńska Joanna , Adamczuk Małgorzata , Dukowska Małgorzata , Przybylski Mirosław
Published: March 2021

This study represents a description of the diet composition of one of the largest European cobitids, the weatherfish Misgurnus fossilis. Specimens were collected in a drainage canal, representing a typical habitat for weatherfish, and with gut content analysis conducted with regard to individual total length and maturity stage. Overall, the weatherfish diet mainly consisted of Copepoda, Cladocera, Ostracoda, Oligochaeta, Asellus aquaticus, Chironomidae and Coleoptera larvae, Gastropoda, and detritus. To evaluate size‐related patterns of resource use, fish were assigned to two size classes, defined according to size at first maturation. ANOSIM analyses revealed major ontogenetic shifts in feeding strategy, which were related to size and maturity, with a significant ontogenetic shift in feeding pattern, marked by differences in the proportions of the main taxonomic groups of prey consumed. Copepoda and Cladocera dominated in the diet of small and immature individuals, while large weatherfish primarily fed on detritus. Similarly, cluster analysis of diet classified into these food types showed distinct two groups comprising juvenile and mature fish. The weatherfish is a food opportunist using all available resources, but spatially showed a change in feeding sites. Smaller and sexually immature individuals more often use prey caught in the water column and among macrophytes, while larger (sexually mature) individuals occupying the bottom, much more often use detritus as a food base.
Identifying the patterns of changes in α‐ and β‐diversity across Dacrydium pectinatum communities in Hainan Island, China
Authors: Liu Haodong , Liu Hua , Chen Yongfu , Xu Zhiyang , Dai Yunchuan , Chen Qiao , Ma Yongkang
Published: March 2021

Exploring vegetation distribution spatial patterns facilitates understanding how biodiversity addresses the potential threat of future climate variability, especially for highly diverse and threatened tropical plant communities, but few empirical studies have been performed. Dacrydium pectinatum is a constructive and endangered species in the tropical mountain forests of Hainan Island, China. In this study, sixty‐eight 30 m × 30 m permanent plots of D. pectinatum were investigated, and species‐based and phylogenetic‐based methods were used to analyze the α‐ and β‐diversity pattern variation and its key drivers. Our study showed that species and phylogenetic α‐diversity patterns are different on a local scale. However, on a regional scale, the variations in the two α‐diversity patterns tend to converge, and they decrease with increasing elevation. The phylogenetic structure changes from overdispersion to convergence with increasing elevation. Soil (SOM, TP, AP), topography (EL, SL), and stand (CD) factors and α‐diversity showed close correlations. Species and phylogenetic β‐diversity have significant positive correlations with changing environmental distance and geographical distance; however, as a representative form of habitat heterogeneity, elevation distance has a greater impact on β‐diversity changes than geographical distance. In conclusion, the α‐ and β‐diversity patterns of the D. pectinatum community are mainly related to habitat filtering, especially in high‐elevation areas, and the colonization history of various regions also affects the formation of diversity patterns. Species‐based and phylogenetic‐based methods robustly demonstrated the key role of the habitat filtering hypothesis in community assembly. We believe that more plant diversity patterns need to be explored to understand the biodiversity formation mechanisms in tropical forests. We also recommend strengthening the construction and management of nature reserves to help address the biodiversity loss crisis in endangered tropical plant communities.
Improving the True Cycling of Redox Mediators‐assisted Li‐O2 Batteries
Authors: Cao Deqing , Yu Fengjiao , Chen Yuhui , Gao Xiangwen
Published: March 2021

The application of redox mediators has been considered as a promising strategy to boost the performance of aprotic Li‐O2 batteries. However, the issues brought with redox mediators, especially on the Li anode side have been overlooked. Here, we propose a facile approach of preparing a gel polymer membrane that not only allow uniform Li plating/stripping with large current densities over extended cycling but also inhibit the diffusion of redox mediators and avoid redox shuttling, self‐discharge, and internal short‐circuiting. More importantly, the gel polymer membrane prevents the penetration of O2 and superoxide intermediates from the Li anode. Therefore, it ensures the successful application of both lithium anode and redox mediators in Li‐O2 batteries to achieve the desired high capacity and rate performance. Meanwhile, it helps understand the benefit and problems of added redox mediators and reactive oxygen species so that the performance of such Li‐O2 batteries can be truly evaluated.
An online target and rapid screening method for α‐glucosidase inhibitors based on capillary electrophoresis
Authors: Zhang Ying , Zhong Hai‐Yang , Nsanzamahoro Stanislas , Yao Xiao‐Jun , Wang Wei‐Feng , Yang Jun‐Li
Published: March 2021

Screening enzymatic active compounds is one of the important fields in drug research. α‐Glucosidase can hydrolyze carbohydrates to monosaccharides after meals and lead to the rise of blood glucose levels in human body. Thus, the inhibition of α‐glucosidase activity is an effective approach for the diabetes treatment. In this work, we developed a new method to simultaneously screen multiple bioactive compounds within a single CE running. The affect factors on the method performance, including injection, mixing, incubation, separation and detection, were carefully analyzed and discussed. Under the optimum, the mixture consisting of two internal standards (DMSO and 4‐nitrophenol) and five compounds (lyoniresinol, hydroxytyrosol, rutin, kaempferol, and quercetin) was simultaneously screened, and kaempferol and quercetin showed stronger activity and this conclusion was also supported by offline assay. Furthermore, molecular docking was employed for investigating its interaction mechanism. Eventually, the established method has been applied to screen potential α‐glucosidase inhibitors from an extract of Lycium barbarum and the peak area of rutin, taxifolin, quercetin, and chlorogenic acid in L. barbarum samples changed before and after the enzymatic reaction, confirming that these four compounds had potential inhibitory activities, which was consistent with the literature data. The present work provides a promising method for the target and rapid discovery of bioactive compounds from a plant extract or mixture.
Micro‐aerobic production of isobutanol with engineered Pseudomonas putida
Authors: Ankenbauer Andreas , Nitschel Robert , Teleki Attila , Müller Tobias , Favilli Lorenzo , Blombach Bastian , Takors Ralf
Published: March 2021

Pseudomonas putida KT2440 is emerging as a promising microbial host for biotechnological industry due to its broad range of substrate affinity and resilience to physicochemical stresses. Its natural tolerance towards aromatics and solvents qualifies this versatile microbe as promising candidate to produce next generation biofuels such as isobutanol. In this study, we scaled‐up the production of isobutanol with P. putida from shake flask to fed‐batch cultivation in a 30 L bioreactor. The design of a two‐stage bioprocess with separated growth and production resulted in 3.35 gisobutanol L–1. Flux analysis revealed that the NADPH expensive formation of isobutanol exceeded the cellular catabolic supply of NADPH finally causing growth retardation. Concomitantly, the cell counteracted to the redox imbalance by increased formation of 2‐ketogluconic thereby providing electrons for the respiratory ATP generation. Thus, P. putida partially uncoupled ATP formation from the availability of NADH. The quantitative analysis of intracellular pyridine nucleotides NAD(P)+ and NAD(P)H revealed elevated catabolic and anabolic reducing power during aerobic production of isobutanol. Additionally, the installation of micro‐aerobic conditions during production doubled the integral glucose‐to‐isobutanol conversion yield to 60 mgisobutanol gglucose–1 while preventing undesired carbon loss as 2‐ketogluconic acid.
DNA Methylation Signatures Reveal the Diversity of Processes Remodeling Hepatocellular Carcinoma Methylomes
Authors: Meunier Léa , Hirsch Théo Z. , Caruso Stefano , Imbeaud Sandrine , Bayard Quentin , Roehrig Amélie , Couchy Gabrielle , Nault Jean‐Charles , Llovet Josep M. , Blanc Jean‐Frédéric , Calderaro Julien , Zucman‐Rossi Jessica , Letouzé Eric
Published: March 2021

Background and Aims

DNA methylation patterns are highly rearranged in HCCs. However, diverse sources of variation are intermingled in cancer methylomes, precluding the precise characterization of underlying molecular mechanisms. We developed a computational framework (methylation signature analysis with independent component analysis [MethICA]) leveraging independent component analysis to disentangle the diverse processes contributing to DNA methylation changes in tumors.

Approach and Results

Applied to a collection of 738 HCCs, MethICA unraveled 13 stable methylation components preferentially active in specific chromatin states, sequence contexts, and replication timings. These included signatures of general processes associated with sex and age but also signatures related to specific driver events and molecular subgroups. Catenin beta 1 mutations were major modulators of methylation patterns in HCC, characterized by a targeted hypomethylation of transcription factor 7–bound enhancers in the vicinity of Wnt target genes as well as a widespread hypomethylation of late‐replicated partially methylated domains. By contrast, demethylation of early replicated highly methylated domains was a signature of replication stress, leading to an extensive hypomethylator phenotype in cyclin‐activated HCC. Inactivating mutations of the chromatin remodeler AT‐rich interactive domain‐containing protein 1A were associated with epigenetic silencing of differentiation‐promoting transcriptional networks, also detectable in cirrhotic liver. Finally, a hypermethylation signature targeting polycomb‐repressed chromatin domains was identified in the G1 molecular subgroup with progenitor features.

Conclusions

This study elucidates the diversity of processes remodeling HCC methylomes and reveals the epigenetic and transcriptional impact of driver alterations.
Construction and validation of a machine learning‐based nomogram: A tool to predict the risk of getting severe coronavirus disease 2019 (COVID‐19)
Authors: Yao Zhixian , Zheng Xinyi , Zheng Zhong , Wu Ke , Zheng Junhua
Published: March 2021

Background

Identifying patients who may develop severe coronavirus disease 2019 (COVID‐19) will facilitate personalized treatment and optimize the distribution of medical resources.

Methods

In this study, 590 COVID‐19 patients during hospitalization were enrolled (Training set:n = 285; Internal validation set:n = 127; Prospective set:n = 178). After filtered by two machine learning methods in the training set, 5 out of 31 clinical features were selected into the model building to predict the risk of developing severe COVID‐19 disease. Multivariate logistic regression was applied to build the prediction nomogram and validated in two different sets. Receiver operating characteristic (ROC) analysis and decision curve analysis (DCA) were used to evaluate its performance.

Results

From 31 potential predictors in the training set, 5 independent predictive factors were identified and included in the risk score: C‐reactive protein (CRP), lactate dehydrogenase (LDH), Age, Charlson/Deyo comorbidity score (CDCS), and erythrocyte sedimentation rate (ESR). Subsequently, we generated the nomogram based on the above features for predicting severe COVID‐19. In the training cohort, the area under curves (AUCs) were 0.822 (95% CI, 0.765–0.875) and the internal validation cohort was 0.762 (95% CI, 0.768–0.844). Further, we validated it in a prospective cohort with the AUCs of 0.705 (95% CI, 0.627–0.778). The internally bootstrapped calibration curve showed favorable consistency between prediction by nomogram and the actual situation. And DCA analysis also conferred high clinical net benefit.

Conclusion

In this study, our predicting model based on five clinical characteristics of COVID‐19 patients will enable clinicians to predict the potential risk of developing critical illness and thus optimize medical management.
Smart opinion formation maximization to improve political education of undergraduates in Social Information‐Centric Networking
Authors: Liu Wence
Published: March 2021

Social Information‐Centric Networking (SICN) is an integration of Social Network (SN) and ICN, which is a popular paradigm as most of contents in SN depend on the transmission and interaction of ICN. In SICN, the research on opinion formation maximization is very important. Therefore, this paper considers the scenario regarding the political education of undergraduates and proposes a heuristic opinion formation maximization algorithm, including two stages. (a) The opinion formation model is built based on individual intimacy and social influence. (b) In order to make sure the opinion formation maximization, the collaborative evolution model is built. By comparing with three latest researches, the proposed heuristic algorithm can save the required identification time by 0.379 hour, 0.687 hour and 0.889 hour respectively. The experimental results further demonstrate that the research on opinion formation maximization in SICN makes for the improvement on the political education of undergraduates.
Epigenetic targeting of SLC30A3 by HDAC1 is related to the malignant phenotype of glioblastoma
Authors: Zhang Longzhou , Liu Zengjin , Dong Yang , Kong Lingchang
Published: March 2021

The epigenetic abnormality is believed as a major driver for cancer initiation. Histone modification plays a vital role in tumor formation and progression. Particularly, alteration in histone acetylation has been highly associated with gene expression, cell cycle, as well as carcinogenesis. By analyzing glioblastoma (GBM)‐related microarray from the GEO database and conducting chromatin immunoprecipitation‐sequencing (ChIP‐seq), we discovered that solute carrier family 30 member 3 (SLC30A3), a super enhancer (SE)‐regulated factor, was significantly reduced in GBM tissues. Furthermore, histone deacetylase 1 (HDAC1), overexpressed in GBM tissues, could inhibit SLC30A3 expression by promoting histone H3K27ac deacetylation modification of the SE region of SLC30A3. Our functional validation revealed that SLC30A3 can inhibit the growth and metastatic spread of GBM cells in vitro and in vivo, and can activate the MAPK signaling pathway to promote apoptosis of GBM cells. Moreover, overexpression of HDAC1 resulted in a significant increase in DNA replication activity, a significant decline in apoptosis and cell cycle arrest in GBM cells. In a word, these findings indicate that combined epigenetic targeting of SLC30A3 by HDAC1 and SE is potentially therapeutically feasible in GBM.
Netrin‐1 and clusterin: Innovative potential diagnostic biomarkers for early renal damage in β‐thalassemia major children
Authors: Abd El‐Khalik Sarah Ragab , Sharaby Radwa Mahmoud , Nasif Elham , Hamza Mohamed Bassiony , Ibrahim Rowida Raafat
Published: March 2021

Background

Children with β‐thalassemia major (β‐TM) suffer from tubular dysfunction even before the onset of any renal impairment symptoms and/or clinical signs. Therefore, identifying innovative biomarkers allowing early renal damage detection has focused attention.

Aim

This study aims to preliminary assess Netrin‐1(NTN‐1) and clusterin (CLU) in β‐TM children and explore their possible roles as surrogate noninvasive biomarkers of renal tubular dysfunction.

Subjects and methods

In this study, 40 β‐TM children and 30 healthy children were enrolled. Routine serum and urinary biochemical variables were determined. Urinary NTN‐1 and CLU levels were measured using ELISA and their mRNA expression in PBMCs were assayed using real‐time PCR. Serum TNF‐α, MDA levels and GST activity were measured.

Results

Urinary NTN‐1 and CLU concentrations and mRNA relative expression levels in PBMCs were significantly increased in β‐TM children relative to controls. Oxidative stress and inflammatory markers revealed significant elevation in β‐TM children compared to controls. The change in these parameters correlated significantly with other renal parameters. ROC curves analysis showed that urinary NTN‐1 and CLU levels are of promising diagnostic performance.

Conclusion

Our results suggest that NTN‐1 and CLU are qualified as new noninvasive biomarker panels for early detection of renal injury in β‐TM children. Moreover, urinary NTN‐1 is recommended as a precise one during the clinical practices.
Organic solvent‐based tissue clearing techniques and their applications
Authors: Zhan Yanjing , Wu Haoyan , Liu Linfeng , Lin Jie , Zhang Shiwen
Published: March 2021

Revealing the true structure of tissues and organs with tissue slicing technology is difficult since images reconstructed in three dimensions are easily distorted. To address the limitations in tissue slicing technology, tissue clearing has been invented and has recently achieved significant progress in three‐dimensional imaging. Currently, this technology can mainly be divided into two types: aqueous clearing methods and solvent‐based clearing methods. As one of the important parts of this technology, organic solvent‐based tissue clearing techniques have been widely applied because of their efficient clearing speed and high clearing intensity. This review introduces the primary organic solvent‐based tissue clearing techniques and their applications.
Atomic force microscopy nanoindentation kinetics and subsurface visualization of soft inhomogeneous polymer
Authors: Morozov Ilya A.
Published: March 2021

Modern techniques of nanoindentation by atomic force microscopy (AFM) produce maps of topography and physical‐mechanical properties of the material. Analysis of the interaction rate of the AFM tip with the soft surface reveals the surface and subsurface structure and expands standard analysis of the material behavior. Phase‐separated polymer (polyurethane, elastic modulus—6 MPa) is studied. Reversible inelastic changes of the surface at different stages of indentation were established in dependence on peculiarities of velocity and position of the AFM‐tip in the material: uniform soft nanofilm covering the outer surface gradually passes into fibrillar heterogeneous structure of the polymer. The point of stable mechanical contact is defined, and the elastic moduli of soft and hard blocks of the polymer are estimated using certain intervals of the indentation. The presented methods of surface analysis are useful in the study of a wide class of soft heterogeneous materials.
DNA methylation analysis improves the prognostication of acute myeloid leukemia
Authors: Samimi Hanie , Mehta Isha , Docking Thomas Roderick , Zainulabadeen Aamir , Karsan Aly , Zare Habil
Published: March 2021

Integration of orthogonal data could provide new opportunities to pinpoint the underlying molecular mechanisms of hematologic disorders. Using a novel gene network approach, we integrated DNA methylation data from The Cancer Genome Atlas (n = 194 cases) with the corresponding gene expression profile. Our integrated gene network analysis classified AML patients into low‐, intermediate‐, and high‐risk groups. The identified high‐risk group had significantly shorter overall survival compared to the low‐risk group (p‐value ≤). Specifically, our approach identified a particular subgroup of nine high‐risk AML cases that died within 2 years after diagnosis. These high‐risk cases otherwise would be incorrectly classified as intermediate‐risk solely based on cytogenetics, mutation profiles, and common molecular characteristics of AML. We confirmed the prognostic value of our integrative gene network approach using two independent datasets, as well as through comparison with European LeukemiaNet and LSC17 criteria. Our approach could be useful in the prognostication of a subset of borderline AML cases. These cases would not be classified into appropriate risk groups by other approaches that use gene expression, but not DNA methylation data. Our findings highlight the significance of epigenomic data, and they indicate integrating DNA methylation data with gene coexpression networks can have a synergistic effect.
Development of neutralizing antibody responses against SARS‐CoV‐2 in COVID‐19 patients
Authors: Teresa Valenzuela María , Urquidi Cinthya , Rodriguez Nicolás , Castillo Luis , Fernández Jorge , Ramírez Eugenio
Published: March 2021

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and coronavirus disease 2019 (COVID‐19) are new global problems. The understanding of the host immune response in COVID‐19 and its implications in the development of therapeutic agents are new challenges. Here, we evaluated the development of immunoglobulin G (IgG) and neutralizing (Nt) antibodies in symptomatic hospitalized COVID‐19 patients. We followed up 117 COVID‐19 confirmed patients from a reference health center for COVID‐19 during the epidemic in Santiago de Chile. One and two sequential blood samples from 117 to 68 cases were, respectively, obtained to evaluate the immune response. Immunofluorescence and neutralization assays in Vero E6 cells with a Chilean SARS‐CoV‐2 strain were performed. Out of the 68 patients, 44% were women and 56% men, and the most frequent comorbidities were hypertension (47.7%) and diabetes (27.4%). The most frequent symptoms or signs related to COVID‐19 were dyspnea, cough, fever, myalgia, and headache. In all the study population, 76.1% and 60.7% of patients were positive for IgG and Nt antibodies in the first blood sample. All patients except one were positive for IgG and Nt antibodies in the second sample. IgG and Nt antibodies positivity increased significantly according to the disease evolution periods. Higher Nt antibody titers were observed in the first sample in patients under 60 years of age. Obese and diabetic patients had no increase in Nt antibodies, unlike normal weight and diabetes‐free patients. Both hypertensive and normotensive patients showed a significant increase in Nt antibodies. These results show an early and robust immune response against SARS‐CoV‐2 infection during severe COVID‐19.
Control of wakefulness by lateral hypothalamic glutamatergic neurons in male mice
Authors: Wang Ren‐fei , Guo Han , Jiang Shi‐yu , Liu Zi‐long , Qu Wei‐min , Huang Zhi‐li , Wang Lu
Published: March 2021

The lateral hypothalamus (LH) plays a key role in the maintenance of cortical activation and wakefulness. In the LH, the two main neuronal cell populations consist of excitatory glutamatergic neurons and inhibitory GABAergic neurons. Recent studies have shown that inhibitory LH GABAergic neurons are wake‐promoting. However, the mechanism by which excitatory LH glutamatergic neurons contribute to sleep‐wake regulation remains unclear. Using fiber photometry in male mice, we demonstrated that LH glutamatergic neurons exhibited high activities during both wakefulness and rapid eye movement sleep. Chemogenetic activation of LH glutamatergic neurons induced an increase in wakefulness that lasted for 6 hr, whereas suppression of LH glutamatergic neuronal activity caused a reduction in wakefulness. Brief optogenetic activation of LH glutamatergic neurons induced an immediate transition from slow‐wave sleep to wakefulness, and long‐lasting optogenetic stimulation of these neurons maintained wakefulness. Moreover, we found that LH‐locus coeruleus/parabrachial nucleus and LH‐basal forebrain projections mediated the wake‐promoting effects of LH glutamatergic neurons. Taken together, our data indicate that LH glutamatergic neurons are essential for the induction and maintenance of wakefulness. The results presented here may advance our understanding of the role of LH in the control of wakefulness.
Time trends and persistence in European temperature anomalies
Authors: Lenti Jacopo , Gil‐Alana Luis A.
Published: March 2021

This paper looks at the level of persistence in the temperature anomalies series of 114 European cities. Once this level of persistence has been identified, the time trend coefficients are estimated and the results indicate that most of the series examined display positive trends, supporting thus climate warming. Moreover, the results obtained confirm the hypothesis that long‐memory behaviour cannot be neglected in the study of temperature time series, changing, therefore, the estimated effect of global warming.