bluuebunny/crossref_metadata_2025 huggingface dataset:
Economic Evaluation of Home Care for Stroke Patients Compared to Hospital Care: A Systematic Review
Authors: Khoramrooz Maryam , Asgharzadeh Asra , Alidoost Saeide , Foroughi Zeynab , Azami Saber , Rezapour Aziz
Published: November 2021

Context: Stroke is one of the main causes of premature death and disability, imposing significant costs on the healthcare system, especially due to expensive hospital care. Home care service is one of the interventions used in the last two decades to reduce the cost of services provided for stroke patients in different countries. Objectives: The present study aimed to systematically review studies related to the economic evaluation of home care compared to hospital care for stroke patients. Data Sources: A search was conducted between January 1990 and January 2021. PubMed, Scopus, Web of Science, and Embase databases were searched systematically. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to select the studies. Data Extraction: To evaluate the quality of studies included in this systematic review, Drummond’s ten-item checklist was used. Results: Five economic evaluation studies were included in this review. The included studies reported different results regarding the effect of home care on improving different indicators and the cost-effectiveness ratio of home care to hospital care. Most previous studies reported that home care is a more cost-effective option for improving many indicators, such as physical function and quality-adjusted life years (QALY), and for reducing mortality and institutionalization, compared to hospital care. Conclusions: Home care is a more cost-effective option than hospital care for stroke patients with regard to some indicators, such as the Barthel index for Activities of Daily Living, Modified Rankin Scale (MRS), quality of life, mortality, and institutionalization. However, there are some exemptions to this conclusion. Due to limitations, such as heterogeneity of interventions in the existing studies, different levels of patients’ disabilities, different perspectives toward economic evaluation, and differences in the healthcare systems of countries, further research is needed according to the context of each country based on clinical trials.
Urban-architectural and symbolic review of the memorial-monumental heritage of Kosovo and Metohija in the works of Svetomir Arsić Basara
Authors: Barać Mirjana
Published: November 2021

The subject of the paper is a spatial, urban-architectural, and symbolic interpretation of the monuments of the National Liberation War in Kosovo and Metohija, by Svetomir Arsić Basara. The Monument to People's Heroes Boris Vukmirović and Ramiz Sadiku and the Monument to the Šar Mountains Partisan Detachment were chosen for the analysis. The aim of this paper is to determine the relations between the sculptural form and man, but also the basic urban-architectural and monumental relations, characteristics, messages, and meanings, through the interpretation of the principles of spatial perception of the monuments. For the purposes of this research, data on the available archival material and the existing condition of the monuments were collected, an interview was conducted with the author of the monuments, Svetomir Arsić Basara, and then an urban-architectural and symbolic interpretation of the monuments was given. The paper provides a historical overview, an overview of social circumstances and relations, as well as authorial processes in urban-architectural designing solutions, therefore, this paper can contribute to the expansion of the current modest knowledge about the urban-architectural characteristics of the monuments, and a better understanding of their memorial symbolism.
Leisure-time physical activity among older adults in Brazil: results from the Brazilian National Health Survey – 2013
Authors: Häfele Vítor , Häfele César Augusto , Jerônimo Jeferson Santos , Ferreira Rodrigo Wiltgen , Maravillo Steve Anthony , Silva Marcelo Cozzensa da
Published: November 2021

Introduction: Health behaviors are fundamental for healthy aging. In this sense, the practice of physical activity is one of the most beneficial factors for the health of individuals. Objective: To describe the prevalence of leisure-time physical activity among the older adults and analyze in terms of sociodemographic characteristics, national regions, Federative Units of Brazil, and types of physical activity practiced. Methods: Study utilizing data from the Brazilian National Health Survey - 2013. Leisure-time physical activity was analyzed with two distinct cutoff points: 1) Some physical activity - 10 or more minutes/week; 2) Meeting recommended 150 minutes/week of physical activity. Results: Nearly 21% of the older adults completed some physical activity, and 13.2% reached the physical activity recommendations. There was no difference in the prevalence of physical activity between men and women. Individuals aged 60-69 years and those with higher income were more active than their peers. As for the national regions, the North had the lowest prevalence of physically active older adults. Among all regions, walking was the most frequent form of physical activity practiced. Conclusion: The prevalence of older adults who practiced some physical activity and reached the physical activity recommendations was low, with walking being the most common form of physical activity. Older adults with higher age, low socioeconomic status and from the Northern Brazilian regions were the least active.
Bruxism in children and adolescents with cerebral palsy
Authors: Silva Sara Maria , Martins Renata Asfor Rocha Carvalho , Ribeiro Thyciana Rodrigues
Published: November 2021

This study aims to summarize the existing evidence from primary studies in order to answer the following question: "are children and adolescents with cerebral palsy (CP) frequently affected by bruxism?". For such, databases Web of Science, Medline (via PubMed), Lilacs, SciELO, Scopus and Wiley Online Library were used, with the keywords “Cerebral Palsy” and “Bruxism” alone and in combination, without the restriction of the publication date. The search included all articles published until May 2020. A total of 229 publications were found, of which 12 were selected, after careful analysis. Retrospective data analyses, cross-sectional studies and observational case-control studies published in English and with samples composed of children and/or adolescents were included. Case reports, literature reviews and studies whose sample consisted of adults-only were excluded. In the evaluated studies, bruxism was present in all samples with cerebral palsy. However, oral signs and symptoms resulting from this parafunction were reported only in three studies, in which the presence of dental wear and pain was evaluated. Therefore, bruxism in children and adolescents with cerebral palsy is a frequent oral condition, however, knowledge about the associated and risk factors for the occurrence of this problem in these patients remains limited.
Assistance strategies for women victims of gender-based violence during the COVID-19 pandemic
Authors: Couto Pablo Luiz Santos , Souza da Costa Pereira Samantha , Vilela Alba Benemérita Alves , França Luiz Carlos Moraes , Silva Dejeane de Oliveira , Gomes Antônio Marcos Tosoli
Published: November 2021

The objective was to analyze the scientific evidence on assistance strategies provided to women, victims of gender violence, in several countries, in the COVID-19 pandemic. It is a narrative review of the literature, by searching PubMed, Scopus and Virtual Health Library databases, using the keywords “COVID-19” and “women” and “violence”. Seventy-six publications were initially found. After the selection, based on the inclusion criteria and the answers to the guiding question, 25 articles were used, submitted to the analysis of semantic content. There were five categories of analysis: Internet accessibility, telehealth and digital exclusion; Emergency telephone lines for reporting violence during the pandemic; Readjustment/expansion of services to combat COVID-19 to assist women victims of violence; Health education and intersectoral actions - interface with media programs; State actions and society responses. It is concluded that the main evidenced actions are anchored in the support and intersectoral actions proposed by the governments. It will help the State to develop strategies, enabling health professionals to rethink their practice, in a contextualized way to the current reality, from welcoming women to notification of suspicion, as well as health education for the empowerment of victims.
EGFR transactivates RON to drive oncogenic crosstalk
Authors: Franco Nitta Carolina , Green Ellen W , Jhamba Elton D , Keth Justine M , Ortiz-Caraveo Iraís , Grattan Rachel M , Schodt David J , Gibson Aubrey C , Rajput Ashwani , Lidke Keith A , Wilson Bridget S , Steinkamp Mara P , Lidke Diane S
Published: November 2021

Crosstalk between different receptor tyrosine kinases (RTKs) is thought to drive oncogenic signaling and allow therapeutic escape. EGFR and RON are two such RTKs from different subfamilies, which engage in crosstalk through unknown mechanisms. We combined high-resolution imaging with biochemical and mutational studies to ask how EGFR and RON communicate. EGF stimulation promotes EGFR-dependent phosphorylation of RON, but ligand stimulation of RON does not trigger EGFR phosphorylation – arguing that crosstalk is unidirectional. Nanoscale imaging reveals association of EGFR and RON in common plasma membrane microdomains. Two-color single particle tracking captured formation of complexes between RON and EGF-bound EGFR. Our results further show that RON is a substrate for EGFR kinase, and that transactivation of RON requires formation of a signaling competent EGFR dimer. These results support a role for direct EGFR/RON interactions in propagating crosstalk, such that EGF-stimulated EGFR phosphorylates RON to activate RON-directed signaling.
A functional topography within the cholinergic basal forebrain for encoding sensory cues and behavioral reinforcement outcomes
Authors: Robert Blaise , Kimchi Eyal Y , Watanabe Yurika , Chakoma Tatenda , Jing Miao , Li Yulong , Polley Daniel B
Published: November 2021

Basal forebrain cholinergic neurons (BFCNs) project throughout the cortex to regulate arousal, stimulus salience, plasticity, and learning. Although often treated as a monolithic structure, the basal forebrain features distinct connectivity along its rostrocaudal axis that could impart regional differences in BFCN processing. Here, we performed simultaneous bulk calcium imaging from rostral and caudal BFCNs over a 1-month period of variable reinforcement learning in mice. BFCNs in both regions showed equivalently weak responses to unconditioned visual stimuli and anticipated rewards. Rostral BFCNs in the horizontal limb of the diagonal band were more responsive to reward omission, more accurately classified behavioral outcomes, and more closely tracked fluctuations in pupil-indexed global brain state. Caudal tail BFCNs in globus pallidus and substantia innominata were more responsive to unconditioned auditory stimuli, orofacial movements, aversive reinforcement, and showed robust associative plasticity for punishment-predicting cues. These results identify a functional topography that diversifies cholinergic modulatory signals broadcast to downstream brain regions.
The alpha/B.1.1.7 SARS-CoV-2 variant exhibits significantly higher affinity for ACE-2 and requires lower inoculation doses to cause disease in K18-hACE2 mice
Authors: Bayarri-Olmos Rafael , Johnsen Laust Bruun , Idorn Manja , Reinert Line S , Rosbjerg Anne , Vang Søren , Hansen Cecilie Bo , Helgstrand Charlotte , Bjelke Jais Rose , Bak-Thomsen Theresa , Paludan Søren R , Garred Peter , Skjoedt Mikkel-Ole
Published: November 2021

The alpha/B.1.1.7 SARS-CoV-2 lineage emerged in autumn 2020 in the United Kingdom and transmitted rapidly until winter 2021 when it was responsible for most new COVID-19 cases in many European countries. The incidence domination was likely due to a fitness advantage that could be driven by the receptor-binding domain (RBD) residue change (N501Y), which also emerged independently in other variants of concern such as the beta/B.1.351 and gamma/P.1 strains. Here, we present a functional characterization of the alpha/B.1.1.7 variant and show an eightfold affinity increase towards human angiotensin-converting enzyme-2 (ACE-2). In accordance with this, transgenic hACE2 mice showed a faster disease progression and severity after infection with a low dose of B.1.1.7, compared to an early 2020 SARS-CoV-2 isolate. When challenged with sera from convalescent individuals or anti-RBD monoclonal antibodies, the N501Y variant showed a minor, but significant elevated evasion potential of ACE-2/RBD antibody neutralization. The data suggest that the single asparagine to tyrosine substitution remarkable rise in affinity may be responsible for the higher transmission rate and severity of the B.1.1.7 variant.
Simulation in vocational education
Authors: Gustavsson Susanne
Published: November 2021

This study addresses the use of driving simulators in vocational education. The aim of the study is to use the experiences of vocational teachers and questions to identify critical aspects of simulator-assisted teaching. The Background section contains a description of studies regarding digitalisation within other educational contexts and teaching with simulators in other contexts as well as teacher competencies and the school’s quality measures. The study’s empirical evidence consists of observations and discussions with vocational teachers. The Results section contains an account of the vocational teacher’s questions in the form of identified problem areas. The Conclusions section of the study highlights simulator-assisted teaching and the importance of substantive aspects, as well as the connection to professional knowledge and competency, the possibility of adapting the teaching based on the needs of the student, and the consequences of the teaching for the professional skills and knowledge acquired by the student. The Discussion section addresses aspects such as teaching-related issues regarding transfer, the work of the vocational programme and the school with regard to the implementation of new technology in the teaching process, and the vocational teacher’s role and situation. In order to further develop knowledge about simulator-supported teaching in vocational education, more practice related studies of students' learning process and how the teaching contributes to the development of vocational skills are required.
Yrkesfaglig vurderingspolicy
Authors: Leonardsen Julie , Fjørtoft Henning
Published: November 2021

Vurdering i yrkesfag er viet forholdsvis lite plass i forskning. Yrkesfaglærere i videregående opplæring skal kvalifisere kompetente fagarbeidere for fremtiden, utdanne demokratiske samfunnsborgere og støtte unge menneskers faglige, sosiale og personlige utvikling. Der er imidlertid utfordrende å tyde hvordan policymakere mener yrkesfaglærere skal håndtere dette komplekse oppdraget. Denne studien bruker tematisk analyse (Clarke & Braun, 2017) for å undersøke hvordan forventninger til yrkesfaglærere i videregående opplæring fremstilles i fem norske utdanningspolitiske dokumenter. For å forstå de dilemmaene som preger yrkesfaglig vurderingspolicy, trekker vi på to kunnskapsgrunnlag: a) forskning på læreres vurderingskompetanse og b) begrepet «wicked problems» (Rittel & Webber, 1973). Studien spør: Hvordan rammer nasjonale retningslinjer forventningene til yrkesfaglæreres vurderinger? Vi identifiserer fem politiske innramminger som fremstiller ulike, og tidvis motstridende forventninger til yrkesfaglæreres vurderer-oppdrag. Policymakere forventer at yrkesfaglærere kan 1) forhandle mellom juridiske krav, 2) utdanne unge mennesker til sosial deltakelse, 3) bruke vurdering for å støtte læring og motivasjon, 4) kvalifisere en arbeidsstyrke for fremtiden, og 5) bli profesjonelle lærere. Vi diskuterer hvordan motstridende forventninger til yrkesfaglærers vurderer-oppdrag fremstilles i policy og undersøker hvilke grep policymakere tyr til for å fremstille slike komplekse, sosiale og økonomiske utfordringer som håndterbare. Videre peker vi på hvilke implikasjoner slike grep kan ha for relevans, kvalitet og validitet i vurdering i yrkesfag.
The tongue of the red panda (Ailurus fulgens fulgens Cuvier, 1825)—a stereoscopy, light microscopy and ultrastructural analysis
Authors: Goździewska-Harłajczuk Karolina , Hamouzová Pavla , Klećkowska-Nawrot Joanna , Čížek Petr
Published: November 2021

In the light of recent molecular studies, there are two phylogenetic species of the red panda (Ailurus fulgens): Ailurus fulgens fulgens and Ailurus fulgens styani. The red panda belongs to the endangered species living in the wild only in Asia and is included in the CITES list. Although the biology and diet of this species has been extensively described, the histological structure of the tongue and lingual glands has not yet been characterized in detail in relation to the lifestyle of this mammal under specific conditions and as a basis for comparative anatomical studies of the biodiversity of endemic species. Study samples were collected from two adult males of Ailurus fulgens f. held in Wrocław Zoological Garden. Both tongues were examined macroscopically; moreover, samples with lingual papillae for light microscopy and scanning electron microscopy (SEM) were collected from the apex, body and root of the tongue. Both tongues of the Ailurus fulgens f. males were approximately 9 cm long. The dorsal lingual surface was covered with mechanical and gustatory lingual papillae. Filiform papillae were observed on the apex and the body of the tongue, while small conical papillae were observed on the root of the tongue. An elongated, 1–1.5 cm long cylinder-shaped lyssa was observed in the ventral part of the apex. Moreover, most numerous and largest round in shape fungiform papillae were observed on the apex and on the border of the body and root of the tongue, located directly rostrally to 12–13 round and oval in shape vallate papillae. The SEM study showed that filiform papillae on the apex had several long secondary processes, while filiform papillae on the body of the tongue were taller and their secondary papillae were shorter than the equivalent structures on the apex of the tongue. The SEM study showed numerous taste pores on the surface of the fungiform papilla, while irregular surface of the vallate papillae, however some of them had smoother surface. Mixed glands (comprised of mucous acini and serous acini) were present within the vallum (within the connective tissue core) of the vallate papilla. Beneath the papillae more serous glands were observed, while the posterior lingual glands in the caudal part of the root of the tongue were mucoserous (mucous units were prevalent). A characteristic feature of the tongue of Ailurus fulgens f. was the presence of lyssa, which is comparable to other representatives of Carnivora, but the number of vallate papillae was individually variable. The lack of strongly developed mechanical conical papillae probably may be related to the type of plant food that is particularly dominant in red panda. Further differences between Ailurus fulgens f. and Ailurus fulgens s. cannot be excluded. The results of these studies may be useful especially for veterinarians specializing in working with exotic animals and people dealing with wildlife conservation.
Children's clarification requests in interviews: Testing the effects of age, question characteristics, and brief intervention strategies
Authors: Rodriguez Steen Lillian A. , Malloy Lindsay C.
Published: November 2021

In some contexts (e.g., legal and medical), it is imperative that children indicate when they do not understand an adult's question. Yet, little research has examined children's clarification requests. We asked 122 4‐ to 9‐year‐olds tricky and simple interview questions to assess how often and how children request clarification in interviews, the factors associated with these requests, and whether brief interventions that supplement standard ground rule instructions increase such requests. Overall, the majority of children requested clarification at least once, and most did so explicitly. Child age and question characteristics appeared to influence such requests. Questions that were tricky, especially those that were inaudible or included complex vocabulary/syntax, elicited more clarification requests than simple questions. Supplementing standard ground rule instructions with additional explanations failed to significantly increase clarification requests, though teaching children a clear method for requesting clarification had limited effects on their responses. Results provide insight into children's cognitive development and have implications for interviewing children.
Enhanced High‐Temperature Strength of a Low‐Density Dispersion‐Strengthened Fe–Mn–Al–C Steel
Authors: Wu Zhiqiang , Hasan Md Nzmul , Zhou Honggang , Hu Jun , Liu Longfei , Lu Liwei , An Xianghai
Published: November 2021

A novel low‐density dispersion‐strengthened Fe–18%Mn–8%Al–0.8%C (wt%) steel exhibiting superior high‐temperature strength at 700–900 °C, is developed. The finely dispersed ferritic grains that form near the grain boundaries of the austenite phase provide significant strengthening by pinning the dislocations and enable high microstructural stability by restricting the dynamic recovery/recrystallization. The high Mn content provides remarkable solid solution strengthening to this steel, while the high aluminum content prominently lowers the density to enhance the specific strength. This newly developed steel with low alloying and manufacturing costs has great potentials for structural applications at elevated temperatures.
Magnetic Artificial Cilia Carpets for Transport, Mixing, and Directional Diffusion
Authors: Miao Jiaqi , Zhang Tieshan , Li Gen , Shang Wanfeng , Shen Yajing
Published: November 2021

Natural cilia undertake various roles, such as sensing, propulsion, and transport, in an extensive range of biological systems, and the development of artificial cilia systems has received great attention nowadays. Herein, a multifunctional magnetic artificial cilia carpet (MACC) via a bottom‐up template‐free approach based on magnetic self‐assembly is reported. The in‐plane and out‐of‐plane motion model of the single cilium is established, and then it is expanded to the asynchronous and synchronous collective motion of MACC. Through the cooperation of multi‐cilia actuated by an external magnetic field, the MACC exhibits different cilia‐inspired collective motion to realize multiple functions, i.e., reverse cargo transport for different‐shape objects, linear/circumferential solid mixing based on the asynchronous/synchronous collective motion, and directional diffusion in the viscosity‐dominated environment. The proposed MACCs and relevant control strategies deepen the knowledge of the collective motion of artificial cilia systems and broaden their applications for small‐scale manipulation and microfluidic devices.
Electrochromic Displays Having Two‐Dimensional CIE Color Space Tunability
Authors: Zhang Wu , Li Haizeng , Elezzabi Abdulhakem Y.
Published: November 2021

Electrochromic devices with a wide color gamut distribution have long been sought after for non‐emissive display technologies. The current state‐of‐the‐art multicolor electrochromic displays utilize a single electrochromic layer, which restricts their color tunability within a linear or curved segment scope in International Commission on Illumination (CIE) color space and thus leads to limited color hues. Herein, it is demonstrated vivid electrochromic displays with broadened color hues via fabricating Zn‐based multicolor electrochromic displays having 2D CIE color space tunability. In addition, it is revealed that a Fabry–Perot nanocavity structure can further tune the color hues via altering the coordinate of the 2D CIE color space. It is known that this is the first demonstration of 2D CIE color space tunability realization from a single transparent or reflective electrochromic device. These findings represent a novel strategy for fabricating multicolor electrochromic displays and are expected to advance the development of electrochromic displays.
Multivalent Noncovalent Interfacing and Cross‐Linking of Supramolecular Tubes
Authors: Xiu Fangyuan , Knežević Anamarija , Kwangmettatam Supaporn , Di Iorio Daniele , Huskens Jurriaan , Kudernac Tibor
Published: November 2021

Natural supramolecular filaments have the ability to cross‐link with each other and to interface with the cellular membrane via biomolecular noncovalent interactions. This behavior allows them to form complex networks within as well as outside the cell, i.e., the cytoskeleton and the extracellular matrix, respectively. The potential of artificial supramolecular polymers to interact through specific noncovalent interactions has so far only seen limited exploration due to the dynamic nature of supramolecular interactions. Here, a system of synthetic supramolecular tubes that cross‐link forming supramolecular networks, and at the same time bind to biomimetic surfaces by the aid of noncovalent streptavidin–biotin linkages, is demonstrated. The architecture of the networks can be engineered by controlling the density of the biotin moiety at the exterior of the tubes as well as by the concentration of the streptavidin. The presented strategy provides a pathway for designing adjustable artificial supramolecular superstructures, which can potentially yield more complex biomimetic adaptive materials.
An NIR Discrete Metallacycle Constructed from Perylene Bisimide and Tetraphenylethylene Fluorophores for Imaging‐Guided Cancer Radio‐Chemotherapy
Authors: Ding Yuan , Tong Zongrui , Jin Lulu , Ye Binglin , Zhou Jiong , Sun Zhongquan , Yang Huang , Hong Liangjie , Huang Feihe , Wang Weilin , Mao Zhengwei
Published: November 2021

To promote the clinical theranostic performances of platinum‐based anticancer drugs, imaging capability is urgently desired, and their chemotherapeutic efficacy needs to be upgraded. Herein, a theranostic metallacycle (M) is developed for imaging‐guided cancer radio‐chemotherapy using perylene bisimide fluorophore (PPy) and tetraphenylethylene‐based di‐Pt(II) organometallic precursor (TPE‐Pt) as building blocks. The formation of this discrete supramolecular coordination complex facilitates the encapsulation of M by a glutathione (GSH)‐responsive amphiphilic block copolymer to prepare M‐loaded nanoparticles (MNPs). TPE‐Pt acts as a chemotherapeutic drug and also an excellent radiosensitizer, thus incorporating radiotherapy into the nanomedicine to accelerate the therapeutic efficacy and overcome drug resistance. The NIR‐emission of PPy is employed to detect the intracellular delivery and tissue distribution of MNPs in real time. In vitro and in vivo investigations demonstrate the excellent anticancer efficacy combining chemotherapy and radiotherapy; the administration of this nanomedicine effectively inhibits the tumor growth and greatly extends the survival rate of cisplatin‐resistant A2780CIS‐tumor‐bearing mice. Guided by in vivo fluorescence imaging, radio‐chemotherapy is precisely carried out, which facilitates boosting of the therapeutic outcomes and minimizing undesired side effects. The success of this theranostic system brings new hope to supramolecular nanomedicines for their potential clinical translations.
Assessing the Photovoltaic Quality of Vacuum‐Thermal Evaporated Organic Semiconductor Blends
Authors: Kaienburg Pascal , Jungbluth Anna , Habib Irfan , Kesava Sameer Vajjala , Nyman Mathias , Riede Moritz K.
Published: November 2021

Vacuum‐thermal evaporation (VTE) is a highly relevant fabrication route for organic solar cells (OSCs), especially on an industrial scale as proven by the commercialization of organic light emitting diode‐based displays. While OSC performance is reported for a range of VTE‐deposited molecules, a comprehensive assessment of donor:acceptor blend properties with respect to their photovoltaic performance is scarce. Here, the organic thin films and solar cells of three select systems are fabricated and ellipsometry, external quantum efficiency with high dynamic range, as well as OTRACE are measured to quantify absorption, voltage losses, and charge carrier mobility. These parameters are key to explain OSC performance and will help to rationalize the performance of other material systems reported in literature as the authors’ methodology is applicable beyond VTE systems. Furthermore, it can help to judge the prospects of new molecules in general. The authors find large differences in the measured values and find that today's VTE OSCs can reach high extinction coefficients, but only moderate mobility and voltage loss compared to their solution‐processed counterparts. What needs to be improved for VTE OSCs is outlined to again catch up with their solution‐processed counterparts in terms of power conversion efficiency.
Genotype by environment analysis on multi‐canopy cropping system in rice: Effects of different types of flag leaves
Authors: Hidayah Ummu Fitrothul , Suwarno Willy Bayuardi , Aswidinnoor Hajrial
Published: November 2021

Breeding rice (Oryza sativa L.) for the multi‐canopy (MC) cropping system is one of the novel ideas for increasing production. This system involves combining rice genotypes with different plant heights to form stratified panicles and flag leaves. This study aimed to elucidate the effects of different characteristics of flag leaves of tall plant genotypes on yield and agronomic traits in MC cultivation. The study was conducted from May 2020 to January 2021 at the IPB University Experimental Station at Babakan, Bogor, West Java, Indonesia. The genetic materials were seven rice inbred lines of F9 from an ongoing breeding program at IPB University, consisting of four tall genotypes with different flag leaf characters, namely IPB187‐F‐90‐1‐1 (ordinary, short flag leaf); IPB189‐F‐19‐2‐1 (V‐shaped, medium‐length flag leaf); IPB187‐F‐40‐1‐2 (V‐shape, narrow, half rolled, and long flag leaf); IPB189‐F‐8‐1‐1 (wide, long flag leaf), and three short genotypes, namely IPB193‐F‐19‐1‐3, IPB187‐F‐69‐2‐3, and IPB189‐F‐13‐1‐1. The experiment was carried out in four environmental conditions, namely: (a) monoculture and (b) MC, 2020 dry season, (c) monoculture, and (d) MC, 2020/2021 wet season, using a randomized complete block design with three replications. The results showed that the genotype × cropping system interaction significantly affected total yield (p < .05). The MC cropping system produced a higher average yield (6.65 t ha–1) than the monoculture (6.01 t ha–1) across the two seasons. The genotype with V‐shape and medium‐length flag leaf gave the highest yield in MC. This study substantiated the potential of breeding rice varieties suitable for the MC system.
Biasing the Hierarchy Motifs of Nanotoroids: from 1D Nanotubes to 2D Porous Networks
Authors: Valera Jorge S. , Arima Hironari , Naranjo Cristina , Saito Takuho , Suda Natsuki , Gómez Rafael , Yagai Shiki , Sánchez Luis
Published: November 2021

Hierarchical organization of self‐assembled structures into superstructures is omnipresent in Nature but has been rarely achieved in synthetic molecular assembly due to the absence of clear structural rules. We herein report on the self‐assembly of scissor‐shaped azobenzene dyads which form discrete nanotoroids that further organize into 2D porous networks. The steric demand of the peripheral aliphatic units diminishes the trend of the azobenzene dyad to constitute stackable nanotoroids in solution, thus affording isolated (unstackable) nanotoroids upon cooling. Upon drying, these nanotoroids organize at graphite surface to form well‐defined 2D porous networks. The photoirradiation with UV and visible light enabled reversible dissociation and reconstruction of nanotoroids through the efficient trans↔cis isomerization of azobenzene moieties in solution.
Dynamic Kinetic Sensitization of β‐Dicarbonyl Compounds—Access to Medium‐Sized Rings by De Mayo‐Type Ring Expansion
Authors: Paulisch Tiffany O. , Mai Lukas A. , Strieth‐Kalthoff Felix , James Michael J. , Henkel Christian , Guldi Dirk M. , Glorius Frank
Published: November 2021

Herein, we present a photocatalyzed two‐carbon ring expansion of β‐dicarbonyl compounds with unactivated olefins that provides facile access to medium‐sized rings. Selective sensitization of the substoichiometric enol tautomer enables reactivity of substrates incompatible with the classical De Mayo reaction conditions. Key to success is the identification of the metal‐based sensitizerfac‐[Ir(CF3‐pmb)3], which can be excited using common near‐visible LEDs, and possesses a high triplet excited state energy of 73.3 kcal mol−1. This exactly falls in the range between the triplet energies of the enol and keto tautomer, thereby enabling a dynamic kinetic sensitization. Demonstrating the applicability offac‐[Ir(CF3‐pmb)3] as a photocatalyst in organic synthesis for the first time, we describe a two‐step photocycloaddition‐ring‐opening cascade with β‐ketoesters, ‐diketones, and ‐ketoamides. The mechanism has been corroborated by time‐resolved spectroscopy, as well as further experimental and computational studies.
One size fits all? Stature estimation from footprints and the effect of substrate and speed on footprint creation
Authors: Wiseman Ashleigh L. A. , De Groote Isabelle
Published: November 2021

Estimation of stature from footprint lengths is a common prediction in forensic cases and in paleoanthropology upon the discovery of fossil footprints. Many studies, which have estimated stature from footprints, generally use a “one‐size‐fits‐all” approach that usually involves applying a known ratio of foot length to total stature to do so, although this method has fallen out of practice in forensic cases in recent years but is still commonly used for fossil trace evidence. Yet, we know that substrate and speed can change the dimensions of a footprint, so why are these “one‐size‐fits‐all” approaches still used today? We tested footprint production across different substrates at a walk, a fast walk, and a jog. We calculated how accurately footprint dimensions were impressed between these different conditions and identified sources of error in footprint lengths, and the percentage changes of how significantly a footprint can change in length between different conditions. We provide a table with different ratios that we encourage practitioners/field scientists to refer to and use when estimating stature from footprints, with respect to the substrate on which the footprint was created and the speed at which it was created. We actively encourage researchers to add the ratios by testing more substrates so that in the future stature can be more accurately estimated, thus aiding the paleoanthropological community, but also forensic investigations by statistically highlighting how different conditions can affect trace dimensions.
A Self‐locked β‐Cyclodextrin‐rhodamine B Spirolactam with Photoswitching Properties
Authors: Panagiotakis Stylianos , Saridakis Emmanuel , Malanga Milo , Mavridis Irene M. , Yannakopoulou Konstantina
Published: November 2021

Supramolecular organization and self‐assembly are the pillars of functionality of many nanosystems. The covalent conjugate (6‐spirolactam rhodamine B‐6‐monodeoxy)‐β‐cyclodextrin (Rho‐βCD) is assembled as a self‐included, rigid nanostructure, identical in the crystal and in aqueous solution, as revealed by detailed X‐ray and NMR analyses. Rho‐βCD self‐assembly is the result of an interesting reaction pathway, which partially de‐aggregates Rho and disturbs the zwitterion↔spirolactone equilibrium. Rho‐βCD is stable at pH 4.6, but displays controllable photoswitching between the colored, fluorescent, zwitterionic and the colorless, non‐fluorescent closed structures, during several iterative cycles. After an initial drop in absorbance, the on‐off process continues without further changes under our irradiation conditions, a consequence of the specific self‐locked arrangement of Rho in the cavity. Rho‐βCD exemplifies a water soluble photoresponsive nanosystem with improved photostability suggesting promising applications in super resolution bioimaging.
Comparison of partial least square, artificial neural network, and support vector regressions for real‐time monitoring of CHO cell culture processes using in situ near‐infrared spectroscopy
Authors: Zavala‐Ortiz Daniel A. , Denner Aurélia , Aguilar‐Uscanga Maria G. , Marc Annie , Ebel Bruno , Guedon Emmanuel
Published: November 2021

The biopharmaceutical industry must guarantee the efficiency and biosafety of biological medicines, which are quite sensitive to cell culture process variability. Real‐time monitoring procedures based on vibrational spectroscopy such as near‐infrared (NIR) spectroscopy, are then emerging to support innovative strategies for retro‐control of key parameters as substrates and by‐product concentration. Whereas monitoring models are mainly constructed using partial least squares regression (PLSR), spectroscopic models based on artificial neural networks (ANNR) and support vector regression (SVR) are emerging with promising results. Unfortunately, analysis of their performance in cell culture monitoring has been limited. This study was then focused to assess their performance and suitability for the cell culture process challenges. PLSR had inferior values of the determination coefficient (R2) for all the monitored parameters (i.e., 0.85, 0.93, and 0.98, respectively for the PLSR, SVR, and ANNR models for glucose). In general, PLSR had a limited performance while models based on ANNR and SVR have been shown superior due to better management of inter‐batch heterogeneity and enhanced specificity. Overall, the use of SVR and ANNR for the generation of calibration models enhanced the potential of NIR spectroscopy as a monitoring tool.
Combined gene and environmental engineering offers a synergetic strategy to enhance r‐protein production in Chinese hamster ovary cells
Authors: Torres Mauro , Dickson Alan J.
Published: November 2021

Environmental growth‐inhibition conditions (GICs) have been used extensively for increasing cell‐specific productivity (qP) of Chinese hamster ovary (CHO) cells, with the most common being temperature downshift and sodium butyrate (NaBu) treatment. B lymphocyte‐induced maturation protein‐1 (BLIMP1) overexpression in CHO cells can also inhibit cell growth and increase product titers and qP. Given the similar responses, this study evaluated the individual and combined effects of BLIMP1 expression, low temperature, and NaBu treatment on culture performance, cell metabolism, and recombinant protein production of CHO cells. As expected, all three interventions decreased cell growth, arrested cells in G1/G0 cell cycle phase, and increased qP. However, CHO cells presented different responses when considering cell viability, recombinant gene expression, and cell metabolism that indicated differences in the molecular loci by which BLIMP1 and GICs generated higher productivities. Combinations of BLIMP1 expression and GICs acted synergistically to inhibit cell growth and maximize r‐protein production, with the BLIMP1/NaBu condition leading to the most significant improvements in product titers and qP. This latter condition also proved to substantially increase product yields (up to 9.8 g immunoglobulin G1 [IgG1]/L and 2.2 g erythropoietin‐Fc [EPO‐Fc]/L) and qP (up to 179 pg/cell/day [pcd] for IgG1 and 30 pcd for EPO‐Fc) in high‐density perfusion cultures. These findings offered mechanistic insights about the productivity‐enhancing effects of BLIMP1 and GICs, as well as their complementarity for generating highly productive processes.
Online estimation of changing metabolic capacities in continuous Corynebacterium glutamicum cultivations growing on a complex sugar mixture
Authors: Sinner Peter , Stiegler Marlene , Goldbeck Oliver , Seibold Gerd M. , Herwig Christoph , Kager Julian
Published: November 2021

Model‐based state estimators enable online monitoring of bioprocesses and, thereby, quantitative process understanding during running operations. During prolonged continuous bioprocesses strain physiology is affected by selection pressure. This can cause time‐variable metabolic capacities that lead to a considerable model‐plant mismatch reducing monitoring performance if model parameters are not adapted accordingly. Variability of metabolic capacities therefore needs to be integrated in the in silico representation of a process using model‐based monitoring approaches. To enable online monitoring of multiple concentrations as well as metabolic capacities during continuous bioprocessing of spent sulfite liquor with Corynebacterium glutamicum, this study presents a particle filtering framework that takes account of parametric variability. Physiological parameters are continuously adapted by Bayesian inference, using noninvasive off‐gas measurements. Additional information on current parameter importance is derived from time‐resolved sensitivity analysis. Experimental results show that the presented framework enables accurate online monitoring of long‐term culture dynamics, whereas state estimation without parameter adaption failed to quantify substrate metabolization and growth capacities under conditions of high selection pressure. Online estimated metabolic capacities are further deployed for multiobjective optimization to identify time‐variable optimal operating points. Thereby, the presented monitoring system forms a basis for adaptive control during continuous bioprocessing of lignocellulosic by‐product streams.
An Update on Natural Antileishmanial Treatment Options from Plants, Fungi and Algae
Authors: Koko Waleed S. , Al Nasr Ibrahim S. , Khan Tariq A. , Schobert Rainer , Biersack Bernhard
Published: November 2021

Efficient drugs for the treatment of leishmaniasis, which is classified as a neglected tropical disease, are sought for. This review covers potential drug candidates from natural plant, fungus and algae sources, which were described over the last six years. The identification of these natural antileishmanials often based on the knowledge of traditional medicines. Crucial insights into the activities of these natural remedies againstLeishmaniaparasites and against infections caused by these parasites in laboratory animals or patients are provided and compared with selected former active examples published more than six years ago. In addition, immuno‐modulatory natural antileishmanials and recent developments on combination therapies including natural products and approved antileishmanials are discussed. The described natural products revealed promising data warranting further efforts on the discovery and development of new antileishmanials based on patterns from nature.
The Application of Biocatalysis in the Preparation and Resolution of Morita‐Baylis‐Hillman Adducts and Their Derivatives
Authors: Juma Wanyama Peter , Nyoni Dubekile , Brady Dean , Bode Moira L.
Published: November 2021

The Morita‐Baylis‐Hillman (MBH) reaction affords highly functionalised allylic alcohols containing a new stereogenic centre. These MBH adducts are very versatile and have been transformed into a large range of products, some of which have medicinal potential. Several examples of asymmetric syntheses of MBH adducts have been reported, although a generally applicable method remains to be developed. Biocatalytic approaches for the synthesis and enzymatic kinetic resolution of MBH adducts have been reported, and are discussed in detail in this review. Enzymes able to catalyse the asymmetric MBH reaction have been identified, but selectivity and efficiency have generally been low. Lipases, esterases and nitrile‐converting enzymes have all been successfully applied in the resolution of MBH adducts, with excellent selectivity being realised in most cases.
Incorporation and Utility of a Responsive Ribonucleoside Analogue in Probing the Conformation of a Viral RNA Motif by Fluorescence and 19F NMR Spectroscopy
Authors: Manna Sudeshna , Sontakke Vyankat A. , Srivatsan Seergazhi G.
Published: November 2021

Development of versatile probes that can enable the study of different conformations and recognition properties of therapeutic nucleic acid motifs by complementing biophysical techniques can greatly aid nucleic acid analysis and therapy. Here, we report the design, synthesis and incorporation of an environment‐sensitive ribonucleoside analogue, which serves as a two‐channel biophysical platform to investigate RNA structure and recognition by fluorescence and 19F NMR spectroscopy techniques. The nucleoside analogue is based on a 5‐fluorobenzofuran‐uracil core and its fluorescence and 19F NMR chemical shifts are highly sensitive to changes in solvent polarity and viscosity. Notably, the modified ribonucleotide and phosphoramidite substrates can be efficiently incorporated into RNA oligonucleotides (ONs) by in vitro transcription and standard solid‐phase ON synthesis protocol, respectively. Fluorescence and 19F readouts of the nucleoside incorporated into model RNA ONs are sensitive to the neighbouring base environment. The responsiveness of the probe was aptly utilized in detecting and quantifying the metal ion‐induced conformational change in an internal ribosome entry site RNA motif of hepatitis C virus, which is an important therapeutic target. Taken together, our probe is a good addition to the nucleic acid analysis toolbox with the advantage that it can be used to study nucleic acid conformation and recognition simultaneously by two biophysical techniques.
PEGylated Poly‐HDACi: A Designer Polyprodrug from Optimized Drug Units**
Authors: Han Jinghua , Wang Da‐Yuan , Wang Qiuyu , Meng Li , Luo Zihan , Li Jing , Kang Yanke , Lv Wenhui , Huang Qingqing , Wang Peng George , Wang Yajie , Shen Jie , Wang Yanming
Published: November 2021

We designed, synthesized, and characterized a tri‐block copolymer. Its hydrophobic part, a chain of histone deacetylase inhibitor (HDACi) prodrug, was symmetrically flanked by two identical PEG blocks, whereas the built‐in HDACi was a linear molecule, terminated with a thiol at one end, and a hydroxyl group at the other. Such a feature facilitated end‐to‐end linkage of prodrugs through alternatively aligned disulfides and carbonates. The disulfides served dual roles: redox sensors of smart nanomedicine, and warheads of masked HDACi drugs. This approach, carefully designed to benefit both control‐release and efficacy, is conceptually novel for optimizing drug units in nanomedicine. Micelles from this designer polyprodrug released only PEG, CO2 and HDACi, and synergized with DOX against HCT116 cells, demonstrating its widespread potential in combination therapy. Our work highlights, for the first time, the unique advantage of thiol‐based drug molecules in nanomedicine design.
Catalytic Reduction of Oximes to Hydroxylamines: Current Methods, Challenges and Opportunities
Authors: Mas‐Roselló Josep , Cramer Nicolai
Published: November 2021

Catalytic reduction of oximes represents a direct efficient approach to synthesize valuable hydroxylamine derivatives. However this transformation presents significant challenges: oximes are hard to reduce and, if reactive, reductive cleavage of the weak N−O bond often leads to primary amine side products. The first suitable systems involved the use of platinum‐based heterogeneous catalysts with hydrogen as reductant and stoichiometric amounts of a strong Brønsted acid. More recently metal‐free and transition‐metal‐based homogeneous catalysts have been developed, which display the highest turnovers (up to 4000). In the asymmetric variants, the E/Z‐geometry of the oxime double bond affects significantly the stereoselectivity, sometimes requiring extra synthetic efforts in substrate preparation. This minireview provides an overview of the advances and limitations in catalytic oxime to hydroxylamine reduction. Emphasis is put on highlighting and comparing the practical aspects of the existing methods, such as their reaction conditions and substrate scope. Additionally, future directions for improving this young research area are suggested.