bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adaptive gamification in E‐learning: A literature review and future challenges
Authors: Bennani Souha , Maalel Ahmed , Ben Ghezala Henda 
Published: December 2021

AbstractThe trend of gamification in online education has grown as technological advancements allow for more digitized learning environments to create interactive and engaging learning experiences. Learners are motivated in various ways, which necessitates an understanding of gamification mechanics and dynamics that produce enjoyment to adapt them to a variety of factors such as personality, needs, values, and motivations of each learner. Furthermore, exploration and advancement in the field of artificial intelligence (AI) allow us to provide an intelligent adaptive gamification environment. The aim of this study is to review the existing literature on adaptive gamification in e‐learning, as well as to highlight the scoops and future challenges of adaptive gamification applications. The present research followed the literature review method. For the data collected in this study, we used a qualitative approach. This paper presents in the first part a literature review of studies and a synthesis of the literature on the application of adaptive gamification in online education. The second part deals with the use of AI with adaptive gamification in online education and proposes its different techniques and future adaptation.
Augmentation of antitumor function of tumor‐infiltrating lymphocytes against triple‐negative breast cancer by PD‐1 blockade
Authors: Song Hongming , Wang Haibo , Gong Mingkai , Wu Li , Liu Xiangping , Cao Weihong , Gao Xueqiang , Dou Rongrong , Chen Qiaoyu , Hu Haiyan 
Published: December 2021

AbstractT‐cell‐based immunotherapy and immune checkpoint blockade have been successfully used to treat several human solid cancers. The present study attempted to investigate the feasibility and efficacy of the antitumor effect of adoptive cell therapy along with programmed cell death protein 1 (PD‐1) inhibitor on triple‐negative breast cancer (TNBC). Tumor infiltration lymphocytes (TILs) from TNBC mouse tumor tissues were isolated and expanded, and TILs for adoptive cell therapy (TILs‐ACT) were applied in combination with a PD‐1 inhibitor to the TNBC mouse model. The pre‐ and post‐therapy antitumor efficacy, cytokine secretion, and pathological changes were assessed both in vitro and in vivo. We found that TILs exhibited higher IFN‐γ and TNF‐α secretion than conventional T cells. The TILs‐ACT combined with PD‐1 inhibitor promoted active T‐cell infiltration into the tumor tissue and exerted a strong antitumor effect in an in vivo model. Additionally, the strategy could downregulate the expression of inhibitory marker PD‐1 on TILs. In conclusion, PD‐1 blockade regulated T‐cell exhaustion that synergized with adoptive TIL transfer immunotherapy, leading to eradication of established TNBC tumors. These findings might be useful in developing a feasible and effective therapeutic approach for TNBC.
Porcine oviductal extracellular vesicles facilitate early embryonic development via relief of endoplasmic reticulum stress
Authors: Fu Bo , Ma Hong , Zhang Dong‐jie , Wang Liang , Li Zhong‐qiu , Guo Zhen‐hua , Liu Zi‐guang , Wu Sai‐hui , Meng Xiang‐ren , Wang Fang , Chen Wen‐gui , Liu Di 
Published: December 2021

AbstractThe key to successful in vitro embryo production (IVEP) is to mimic the natural in vivo oviductal microenvironment. Although the chemically defined media in extensive use for the in vitro culture of mammalian embryos is based on the composition of oviductal fluid, the IVEP systems in current use must still bypass the oviduct to produce embryos in vitro. Extracellular vesicles (EVs) in the oviduct are versatile intercellular delivery vehicles for maternal–embryo communication, and a lack of them can be associated with failed early embryonic development under in vitro culture conditions. Herein, we isolated EVs from porcine oviduct fluid and confirmed that oviductal EV supplementation improves the embryonic development of parthenogenetically activated (PA) embryos in terms of blastocyst formation rates and total cell numbers. Our experiments also revealed that a beneficial effect of oviductal EVs on PA embryos was achievable, at least in part, by relieving endoplasmic reticulum stress. These results suggest that the maternal–embryo communication mediated by oviductal EVs benefits early embryonic development. Given the contribution of oviductal EVs to early embryonic development, these findings offer novel insights for the optimization of current IVEP systems.
The unique Akt inhibitor SC66 suppressed AMPK activity and abolished autophagy through the EGFR‐p62 pathway
Authors: Hou Bolin , Li Erwei , Liang Jingnan , Liu Shuchun , Yang Huaiyi , Liu Ling , Jiang Xuejun 
Published: December 2021

AbstractAkt is usually considered to be a negative regulator of both autophagy and adenosine 5′‐monophosphate (AMP)‐activated protein kinase (AMPK) signaling. In the present study, we found that SC66, a pyridine‐based allosteric Akt inhibitor, suppressed basal and H2O2‐induced autophagy concurrent with decreased phosphorylation and activity of AMPK. SC66 treatment led to the formation of a high molecular weight (HMW) form of SQSTM1/p62 (p62), which is an autophagic substrate and is essential for selective autophagy. Moreover, we observed that SC66 inhibited the binding of p62 and microtubule‐associated protein light chain 3 (LC3). The immunoprecipitation results revealed the interaction between p62 and epidermal growth factor receptor (EGFR), and knockdown of EGFR reversed SC66‐mediated autophagy inhibition without affecting the phosphorylation of acetyl‐CoA carboxylase (ACC), a well‐known substrate of AMPK. SC66 increased the interaction between EGFR and Beclin 1 and markedly decreased the association of EGFR with VPS34, a critical protein for autophagy induction. Collectively, the data presented here indicate that EGFR‐p62 pathway plays a critical role in Akt‐mediated positive regulation of autophagy.
Solution Phase Reactivity of Dibenzo[c,e][1,2]azaborinine: Activation and Insertion into Si‐E Single Bonds (E=H, OSi(CH3)3, F, Cl) by a BN‐Aryne
Authors: Keck Constanze , Hahn Jennifer , Gupta Divanshu , Bettinger Holger F. 
Published: December 2021

AbstractThe boron‐nitrogen analogue of ortho‐benzyne, 1,2‐azaborinine, is a reactive intermediate that features a formal boron‐nitrogen triple bond. We here show by combining experimental and computational techniques that the Lewis acidity of the boron center of dibenzo[c,e][1,2]azaborinine allows interaction with the silicon containing single bonds Si−E through the silicon bonding partner E (E=F, Cl, OR, H). The binding to boron activates the Si−E bonds for subsequent insertion reaction. This shows that the BN‐aryne is a ferocious species that even can activate and insert into the very strong Si−F bond.
Exploring the Influence of Intermolecular Interactions in Prebiotic Chemistry Using Laser Spectroscopy and Calculations
Authors: Camiruaga Ander , Usabiaga Imanol , Calabrese Camilla , Lamas Iker , Basterretxea Francisco J. , Fernández José A. 
Published: December 2021

AbstractOne of the most fascinating questions in chemistry is why nature chose CGAT as the alphabet of life. Very likely, such selection was the result of multiple factors and a long period of refinement. Here, we explore how the intermolecular interactions influenced such process, by characterizing the formation of dimers between adenine, theobromine and 4‐aminopyrimidine. Using a combination of mass‐resolved excitation spectroscopy and DFT calculations, we determined the structure of adenine‐theobromine and 4‐aminopyrimidine‐theobromine dimers. The binding energy of these dimers is very close to the canonical adenine‐thymine nucleobases. Likewise, the dimers are able to adopt Watson‐Crick conformations. These findings seem to indicate that there were many options available to build the first versions of the informational polymers, which also had to compete with other molecules, such as 4‐aminopyrimidine, which does not have a valid attaching point for a saccharide. For some reason, nature did not select the most strongly‐bonded partners or if it did, such proto‐bases were later replaced by the nowadays canonical CGAT.
Bioinspired Transformations Using Strictosidine Aglycones: Divergent Total Syntheses of Monoterpenoid Indole Alkaloids in the Early Stage of Biosynthesis
Authors: Sakamoto Jukiya , Ishikawa Hayato 
Published: December 2021

AbstractA series of bioinspired transformations that are applied to convert strictosidine aglycones into monoterpenoid indole alkaloids is reported. The highly reactive key intermediates, strictosidine aglycones, were prepared in situ by simple removal of a silyl protecting group from the silyl ether derivatives, and converted selectively via bioinspired transformations under substrate control into heteroyohimbine‐ and corynantheine‐type, and akagerine and naucleaoral related alkaloids. Thus, concise, divergent total syntheses of 13 monoterpenoid indole alkaloids, (−)‐cathenamine, (−)‐tetrahydroalstonine, (+)‐dihydrocorynantheine, (−)‐corynantheidine, (−)‐akagerine, (−)‐dihydrocycloakagerine, (−)‐naucleaoral B, (+)‐naucleidinal, (−)‐naucleofficines D and III, (−)‐nauclefiline, and (−)‐naucleamides A and E, were accomplished in fewer than 13 steps.
Bimodal Fluorescence/Magnetic Resonance Molecular Probes with Extended Spin Lifetimes
Authors: Yang Shengjun , Saul Philip , Mamone Salvatore , Kaltschnee Lukas , Glöggler Stefan 
Published: December 2021

AbstractBimodal molecular probes combining nuclear magnetic resonance (NMR) and fluorescence have been widely studied in basic science, as well as clinical research. The investigation of spin phenomena holds promise to broaden the scope of available probes allowing deeper insights into physiological processes. Herein, a class of molecules with a bimodal character with respect to fluorescence and nuclear spin singlet states is introduced. Singlet states are NMR silent but can be probed indirectly. Symmetric, perdeuterated molecules, in which the singlet states can be populated by vanishingly small electron‐mediated couplings (below 1 Hz) are reported. The lifetimes of these states are an order of magnitude longer than the longitudinal relaxation times and up to four minutes at 7 T. Moreover, these molecules show either aggregation induced emission (AIE) or aggregation caused quenching (ACQ) with respect to their fluorescence. In the latter case, the existence of excited dimers, which are proposed to use in a switchable manner in combination with the quenching of nuclear spin singlet states, is observed
To minimize foraging time, use high‐efficiency, energy‐expensive search and capture methods when food is abundant but low‐efficiency, low‐cost methods during food shortages
Authors: Norberg R. Åke 
Published: December 2021

AbstractBased on a mathematical model, I show that the amount of food in the habitat determines which among alternative methods for search of prey, respectively, for pursuit‐and‐capture give the shortest daily foraging time. The higher the locomotor activity, the higher the rate of energy expenditure and the larger the habitat space a predator can search for prey per time unit. Therefore, I assume that the more efficient a foraging method is, the higher its rate of energy expenditure. Survival selectionfavors individuals that use foraging methods that cover their energy needs in the shortest possible time. Therefore, I take the optimization criterion to be minimization of the daily foraging time or, equivalently, maximization of the rate of net energy gain. When time is limiting and food is in short supply, as during food bottleneck periods, low‐efficiency, low‐cost foraging methods give shorter daily foraging times than high‐efficiency, energy‐expensive foraging methods. When time is limiting, food is abundant and energy needs are large, as during reproduction, high‐efficiency high‐cost foraging methods give shorter daily foraging times than low‐efficiency low‐cost foraging methods. When time is not limiting, food is abundant, and energy needs are small, the choice of foraging method is not critical. Small animals have lower rates of energy expenditure for locomotion than large animals. At a given food density and with similar diet, small animals are therefore more likely than large ones to minimize foraging time by using high‐efficiency energy‐expansive foraging methods and to exploit patches and sites that require energy‐demanding locomotion modes.Survival selectiontakes place at food shortages, while low‐efficiency low‐cost foraging methods are used, whereasreproduction selectionoccurs when food is abundant and high‐efficiency energy‐expensive foraging methods do better. In seasonal environments, selection therefore acts on different foraging methods at different times. Morphological adaptation to one method may oppose adaptation to another. Such conflicts select against foraging and morphological specialization and tend to give species‐poor communities of year‐round resident generalists. But a stable year‐round food supply favors specialization, niche narrowing, and dense species packing.
Phylogenetic diversity and community assembly in a naturally fragmented system
Authors: Peterson Katie , Ruffley Megan , Parent Christine E. 
Published: December 2021

AbstractWe sought to assess effects of fragmentation and quantify the contribution of ecological processes to community assembly by measuring species richness, phylogenetic, and phenotypic diversity of species found in local and regional plant communities. Specifically, our fragmented system is Craters of the Moon National Monument and Preserve, Idaho, USA. CRMO is characterized by vegetated islands, kipukas, that are isolated in a matrix of lava. We used floristic surveys of vascular plants in 19 kipukas to create a local species list to compare traditional dispersion metrics, mean pairwise distance, and mean nearest taxon distance (MPD and MNTD), to a regional species list with phenotypic and phylogenetic data. We combined phylogenetic and functional trait data in a novel machine‐learning model selection approach, Community Assembly Model Inference (CAMI), to infer probability associated with different models of community assembly given the data. Finally, we used linear regression to explore whether the geography of kipukas explained estimated support for community assembly models. Using traditional metrics of MPD and MNTD neutral processes received the most support when comparing kipuka species to regional species. Individually no kipukas showed significant support for overdispersion. Rather, five kipukas showed significant support for phylogenetic clustering using MPD and two kipukas using MNTD. Using CAMI, we inferred neutral and filtering models structured the kipuka plant community for our trait of interest. Finally, we found as species richness in kipukas increases, model support for competition decreases and lower elevation kipukas show more support for habitat filtering models. While traditional phylogenetic community approaches suggest neutral assembly dynamics, recently developed approaches utilizing machine learning and model choice revealed joint influences of assembly processes to form the kipuka plant communities. Understanding ecological processes at play in naturally fragmented systems will aid in guiding our understanding of how fragmentation impacts future changes in landscapes.
Gobbling across landscapes: Eastern wild turkey distribution and occupancy–habitat associations
Authors: Pollentier Christopher D. , Hardy Michael A. , Lutz R. Scott , Hull Scott D. , Zuckerberg Benjamin 
Published: December 2021

AbstractExtensive restoration and translocation efforts beginning in the mid‐20th century helped to reestablish eastern wild turkeys (Meleagris gallopavo silvestris) throughout their ancestral range. The adaptability of wild turkeys resulted in further population expansion in regions that were considered unfavorable during initial reintroductions across the northern United States. Identification and understanding of species distributions and contemporary habitat associations are important for guiding effective conservation and management strategies across different ecological landscapes. To investigate differences in wild turkey distribution across two contrasting regions, heavily forested northern Wisconsin, USA, and predominately agricultural southeast Wisconsin, we conducted 3050 gobbling call‐count surveys from March to May of 2014–2018 and used multiseason correlated‐replicate occupancy models to evaluate occupancy–habitat associations and distributions of wild turkeys in each study region. Detection probabilities varied widely and were influenced by sampling period, time of day, and wind speed. Spatial autocorrelation between successive stations was prevalent along survey routes but was stronger in our northern study area. In heavily forested northern Wisconsin, turkeys were more likely to occupy areas characterized by moderate availability of open land cover. Conversely, large agricultural fields decreased the likelihood of turkey occupancy in southeast Wisconsin, but occupancy probability increased as upland hardwood forest cover became more aggregated on the landscape. Turkeys in northern Wisconsin were more likely to occupy landscapes with less snow cover and a higher percentage of row crops planted in corn. However, we were unable to find supporting evidence in either study area that the abandonment of turkeys from survey routes was associated with snow depth or with the percentage of agricultural cover. Spatially, model‐predicted estimates of patch‐specific occupancy indicated turkey distribution was nonuniform across northern and southeast Wisconsin. Our findings demonstrated that the environmental constraints of turkey occupancy varied across the latitudinal gradient of the state with open cover, snow, and row crops being influential in the north, and agricultural areas and hardwood forest cover important in the southeast. These forces contribute to nonstationarity in wild turkey–environment relationships. Key habitat–occupancy associations identified in our results can be used to prioritize and strategically target management efforts and resources in areas that are more likely to harbor sustainable turkey populations.
Tackling societal challenges together: Co‐creation strategies and social innovation in EU policy and funded projects
Authors: Meister Broekema Peter , Horlings Lummina G. , Bulder Elles 
Published: December 2021

AbstractThe last decade we saw an increasing academic, policy, and professional interest in the use of co‐creation to tackle societal challenges. Most research focused on qualitative analysis of case studies. This led to an understanding that co‐creation is essential for social innovation. We started this paper by analyzing co‐creation strategies ex ante to understand how EU‐funded consortia intend to tackle societal challenges. By quantitatively analyzing 300 EU projects and qualitatively analyzing the Horizon2020 “co‐creation for growth and inclusion” call, our research revealed four different types of consortia. We characterized these types by the coordinators and dubbed them, respectively, as research led, government led, enterprise led, and other led. These consortia were quite different in terms of diversity and preferred partners. We also distinguished three distinct co‐creation strategies that are focused on inclusion of stakeholders, the outcome, or tool development. We discovered that these strategies are not linked to types of consortia or projects, but only to the call text. We therefore conclude that the policy design of Horizon2020 led to a program that aims to stimulate innovation, but has become too rigid to be able to do so.
Sphingosine‐1‐phosphate promotes tumor development and liver fibrosis in mouse model of congestive hepatopathy
Authors: Kawai Hironari , Osawa Yosuke , Matsuda Michitaka , Tsunoda Tomoyuki , Yanagida Keisuke , Hishikawa Daisuke , Okawara Miku , Sakamoto Yuzuru , Shimagaki Tomonari , Tsutsui Yuriko , Yoshida Yuichi , Yoshikawa Shiori , Hashi Kana , Doi Hiroyoshi , Mori Taizo , Yamazoe Taiji , Yoshio Sachiyo , Sugiyama Masaya , Okuzaki Daisuke , Komatsu Haruki , Inui Ayano , Tamura‐Nakano Miwa , Oyama Chinatsu , Shindou Hideo , Kusano Hironori , Kage Masayoshi , Ikegami Toru , Yanaga Katsuhiko , Kanto Tatsuya 
Published: December 2021

Abstract

Background and Aims
Chronic liver congestion reflecting right‐sided heart failure (RHF), Budd‐Chiari syndrome, or Fontan‐associated liver disease (FALD) is involved in liver fibrosis and HCC. However, molecular mechanisms of fibrosis and HCC in chronic liver congestion remain poorly understood.

Approach and Results
Here, we first demonstrated that chronic liver congestion promoted HCC and metastatic liver tumor growth using murine model of chronic liver congestion by partial inferior vena cava ligation (pIVCL). As the initial step triggering HCC promotion and fibrosis, gut‐derived lipopolysaccharide (LPS) appeared to induce LSECs capillarization in mice and in vitro. LSEC capillarization was also confirmed in patients with FALD. Mitogenic factor, sphingosine‐1‐phosphate (S1P), was increased in congestive liver and expression of sphingosine kinase 1, a major synthetase of S1P, was increased in capillarized LSECs after pIVCL. Inhibition of S1P receptor (S1PR) 1 (Ex26) and S1PR2 (JTE013) mitigated HCC development and liver fibrosis, respectively. Antimicrobial treatment lowered portal blood LPS concentration, LSEC capillarization, and liver S1P concentration accompanied by reduction of HCC development and fibrosis in the congestive liver.

Conclusions
In conclusion, chronic liver congestion promotes HCC development and liver fibrosis by S1P production from LPS‐induced capillarized LSECs. Careful treatment of both RHF and liver cancer might be necessary for patients with RHF with primary or metastatic liver cancer.
Vapour source and spatiotemporal variation of precipitation isotopes in Southwest Spain
Authors: Kohfahl Claus , Fonseca Rodríguez Rolf , Ruiz Bermudo Fernando , Vadillo Iñaki 
Published: December 2021

AbstractThe δ2H and δ18O composition of 77 precipitation samples collected between January 2014 and April 2019 from two sites across the Guadalquivir Basin, SW Spain, were analysed. The first site is located in an urban area of Seville at 100 km distance to the Atlantic coast and the second site is located in a dune area of the Doñana National Park a few kilometres from the coast. Sampling was performed within intervals of at least 14 days if rain occurred but frequently intervals were longer according to the rainfall incidence. Samples from both sites are available for the period February 2016 to June 2018 with six samples containing identical rain events at both locations. Precipitation weighted averages and local meteoric water lines produced by weighting and non‐weighting regression methods are presented for its use in hydrological applications. Results show a remarkably high variability in δ2H and δ18O values and precipitation weighted average d‐excess values of 11.8‰ and 13‰ at the sites Plaza de España and Doñana, respectively. Temperature and amount effects were found to be weak. A significant influence of secondary evaporation for single rainfall events during summer was identified by enriched isotopic signatures with reduced d‐excess values plotting close or below the global meteoric water line. Backward trajectory analysis of 115 days with daily rainfall above 3 mm yield a predominant Atlantic Ocean vapour source with negligible Mediterranean influence and therefore, d‐excess variability is attributed to the different ocean surface conditions of relative humidity and sea surface temperature. Parallel sampling indicate very similar isotopic signatures at both sites and point to the existence of thermal effects of the Plaza de España site in Seville city during the summer season.