bluuebunny/crossref_metadata_2025 huggingface dataset:
Thickness Dependence of Cu-layer-based Transparent Heaters
Authors: Choi Dooho
Published: June 2022

In this study, ultrathin (4-40 nm) Cu-layer-based transparent heaters prepared on glass substrates were investigated for cost-effective applications. The Cu heaters were embedded between ZnO layers serving as anti-reflection and anti-corrosion layers. The Cu layer thicknesses varied in the range of 4-40 nm, and the corresponding structural, electrical, optical and thermal properties were evaluated. Cu was found to follow the Volmer-Weber 3D growth mode in the early deposition stage, where isolated islands grow and coalesce to form a continuous layer at ~12 nm. In the thickness regime of discontinuous Cu layers, a significant increase in sheet resistance was observed due to the reduced current paths and the high severity of electron scattering at the Cu/ZnO interfaces. Because of light absorption associated with the localized surface plasmon resonance (LSPR) in the presence of pores in the films, visible transparency peaks near the thickness of the complete film-closure, beyond which stronger light absorption decreases transparency. The sheet resistance of the transparent heaters was modulated in the range of 0.8-96.2 Ω/sq. The heating characteristics well follow Joule’s law which predicts a higher temperature for a lower-resistance heater at a given voltage. The measured temperature-power relation is linear, from which the important heater parameter of convective heat transfer coefficient is extracted.
Determination of Shelf Life of Rainbow Trout (Oncorhynchus mykiss) Fillets Cooked at Different Combinations of Temperatures Using the Sous Vide Technique
Authors: ÇALIŞIR ERÜMİT Pakize , OĞUZHAN YILDIZ Pinar
Published: June 2022

This study aimed to determine the shelf life of rainbow trout (Oncorhynchus mykiss) fillets, which were applied sous vide technique at different temperatures (55, 65 and 70°C) and stored at 4±1°C for 18 days. The fillets were subjected to chemical (total volatile basic nitrogen, thiobarbituric acid reacting substances and pH), microbiological (total aerobic mesophilic, psychrophilic bacteria and yeast-mold) and sensory analyzes (appearance, texture, odor and color). The results showed that the total number of mesophilic aerobic and psychrophilic bacteria did not exceed the limit values during the storage period in the groups treated with sous vide. In addition, temperature and storage time had a statistically significant (p<0.01) effect on all bacterial groups. The control group samples had higher TVB-N, TBARS and pH values during the storage period compared to the samples with the sous vide technique. When the sensory analysis results were examined, it was found that the most liked group among all groups, except for the odor parameter, was the group that was cooked at 55°C during storage time. As a result of the analysis, it was determined that the sous vide technique applied to the fish had a positive effect on the shelf life, and the most suitable cooking temperature and time were 15 minutes at 70°C.
Ghale Gaon: A Study in Contribution of Promoting Rural Tourism Development of Nepal.
Authors: Krishna Chandra Jha , Rijal Nimananda
Published: June 2022

Abstract. The Ghale Gaon, a village situated on a ridge of the mountain, the ridge of the mountain is approximately 2100 Meter height from the sea level in the Lamjung district of Kwolasothar rural Municipality. Ghale Gaon is approximately 205km northwest of Kathmandu and 125 km northeast of Pokhara the scenic village of the district. Homestay started in 2001, this was declared one of the best villages for homestay tourism development in the SAARC Region of the country. The iconic tower of the village gives a feeling of sitting on the lap of the gigantic Himalayas of Annapurna and Lamjung Himal and 90 percent of visitors are satisfied and like the village, they have also suggested improving the living condition also and feeling water shortage to some extent. The government also needs to support preparing infrastructure also. Key Words: Rural Tourism, Ghale Gaon, Contribution, Scenic views
Reconstruction in Jordanian Arabic Relative Clauses: An
Experimentally-Based Syntactic Account
Authors: Al-Aqarbeh Rania
Published: June 2022

This study aims at experimentally exploring whether reconstruction can actually
be taken as a diagnostic of movement in JA. Three experiments were conducted. Experiment
1, an acceptability judgment task, investigated the availability of gap and resumption
strategies in JA relative clause and wh-interrogative. Experiment 2, combining both forced-choice and acceptability judgment tasks, tested the availability of reconstruction effects in
JA relative clauses regarding the type of the binding principles (A, C, and BVA), resumptive
pronouns (Weak and Strong RPs), and islands (strong and weak islands). Adopting the same
design of Experiment 2, Experiment 3 tested the availability of reconstruction effects in JA
wh-interrogatives. The findings reveal that only resumption strategy is available in JA
relative clauses. Furthermore, JA relative clauses do not exhibit sensitivity to islands; JA
wh-interrogatives do. Reconstruction effects are available in JA relative clauses
irrespective of the type of the binding principle, the type of the RP, and the type of the island,
whereas the presence of strong islands blocks the availability of reconstruction effects in
JA wh-interrogatives. The theoretical implications of these findings unravel that relative
clauses in JA are derived via base-generation rather than A’-movement whereby the
referentiality of the RP is achieved by binding..
Book Review of Ringrow and Pihlaja’s Contemporary Media Stylistics
Authors: Adil Jaafar Eman
Published: June 2022

Contemporary Media Stylistics permits readers to explore a variety of
methodological applications to data analysis. Recent developments in technology and media
communication provide linguists and stylisticians with authentic data for analysis based on
real-life communication. .
Green Self-identity as a Mediating Variable of Green Knowledge and Green Purchase Behavior
Authors: Silintowe Yunita Budi Rahayu , Sukresna I Made
Published: June 2022

Future environmental sustainability is a shared concern of ours. Many of the problems that arise as a result of environmental issues remain unresolved, but they can be solved with community support in the form of public purchase behavior on environmentally friendly products. This study aims to explore the effect of green knowledge on green purchase behavior with green self-identity as a mediating variable. The data was collected through the use of a questionnaire and a self-administered survey, which generated 271 valid responses. To develop a research model and evaluate hypotheses, the PLS-SEM approach with SmartPLS Version 3.0 was employed. Findings. The results showed that there is a direct influence between green knowledge on green purchase behavior, green knowledge on green self-identity, green self-identity on green purchase behavior, and green self-identity mediate between green knowledge and green purchase behavior. The applied implication for producers is that it is necessary for business actors to provide knowledge to consumers regarding environmental conservation efforts through environmentally friendly products produced by pro-environmental producers.
Comparison of the 3D-Microstructure Between Alveolar and Iliac Bone for Enhanced Bioinspired Bone Graft Substitutes
Authors: Rothweiler Rene , Gross Christian , Bortel Emely , Früh Sarah , Gerber Javier , Boller Elodie , Wüster Jonas , Stricker Andres , Fretwurst Tobias , Iglhaut Gerhard , Nahles Susanne , Schmelzeisen Rainer , Hesse Bernhard , Nelson Katja
Published: June 2022

In oral- and maxillofacial bone augmentation surgery, non-vascularized grafts from the iliac crest demonstrate better clinical performance than alveolar bone grafts. The underlying mechanisms are not fully understood but are essential for the enhancement of bone regeneration scaffolds. Synchrotron Radiation µ-CT at a pixel size of 2.3 μm was used to characterize the gross morphology and the vascular and osteocyte lacuna porosity of patient-matched iliac crest/alveolar bone samples. The results suggest a difference in the spatial distribution of the vascular pore system. Fluid simulations reveal the permeability tensor to be more homogeneous in the iliac crest, indicating a more unidirectional fluid flow in alveolar bone. The average distance between bone mineral and the closest vessel pore boundary was found to be higher in alveolar bone. At the same time, osteocyte lacunae density is higher in alveolar bone, potentially compensating for the longer average distance between the bone mineral and vessel pores. The present study comprehensively quantified and compared the 3D microarchitecture of intraindividual human alveolar and iliac bone. The identified difference in pore network architecture may allow a bone graft from the iliac crest to exhibit higher regeneration potential due to an increased capacity to connect with the surrounding pore network of the residual bone. The results may contribute to understanding the difference in clinical performance when used as bone grafts and are essential for optimization of future scaffold materials.
Bone Marrow Derived Mesenchymal Stromal Cells Promote Vascularization and Ciliation in Airway Mucosa Tri-Culture Models in Vitro
Authors: Luengen Anja E. , Cheremkhina Maria , Gonzalez-Rubio Julian , Weckauf Jan , Kniebs Caroline , Uebner Hendrik , Buhl E. Miriam , Taube Christian , Cornelissen Christian G. , Schmitz-Rode Thomas , Jockenhoevel Stefan , Thiebes Anja Lena
Published: June 2022

Patients suffering from irresectable tracheal stenosis often face limited treatment options associated with low quality of life. To date, an optimal tracheal replacement strategy does not exist. A tissue-engineered tracheal substitute promises to overcome limitations such as implant vascularization, functional mucociliary clearance and mechanical stability. In order to advance a tracheal mucosa model recently developed by our group, we examined different supporting cell types in fibrin-based tri-culture with primary human umbilical vein endothelial cells (HUVEC) and primary human respiratory epithelial cells (HRE). Bone marrow-derived mesenchymal stromal cells (BM-MSC), adipose-derived mesenchymal stromal cells (ASC) and human nasal fibroblasts (HNF) were compared regarding their ability to promote mucociliary differentiation and vascularization in vitro. Three-dimensional co-cultures of the supporting cell types with either HRE or HUVEC were used as controls. Mucociliary differentiation and formation of vascular-like structures were analyzed by scanning electron microscopy (SEM), periodic acid Schiff’s reaction (PAS reaction), two-photon laser scanning microscopy (TPLSM) and immunohistochemistry. Cytokine levels of vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), interleukin-6 (IL6), interleukin-8 (IL8), angiopoietin 1, angiopoietin 2, fibroblast growth factor basic (FGF-b) and placenta growth factor (PIGF) in media supernatant were investigated using LEGENDplex™ bead-based immunoassay. Epithelial morphology of tri-cultures with BM-MSC most closely resembled native respiratory epithelium with respect to ciliation, mucus production as well as expression and localization of epithelial cell markers pan-cytokeratin, claudin-1, α-tubulin and mucin5AC. This was followed by tri-cultures with HNF, while ASC-supported tri-cultures lacked mucociliary differentiation. For all supporting cell types, a reduced ciliation was observed in tri-cultures compared to the corresponding co-cultures. Although formation of vascular-like structures was confirmed in all cultures, vascular networks in BM-MSC-tri-cultures were found to be more branched and extended. Concentrations of pro-angiogenic and inflammatory cytokines, in particular VEGF and angiopoietin 2, revealed to be reduced in tri-cultures compared to co-cultures. With these results, our study provides an important step towards a vascularized and ciliated tissue-engineered tracheal replacement. Additionally, our tri-culture model may in the future contribute to an improved understanding of cell-cell interactions in diseases associated with impaired mucosal function.
A Robot Platform for Highly Efficient Pollutant Purification
Authors: Wang Haocheng , Yu Shimin , Liao Junjie , Qing Xudong , Sun Daxing , Ji Fengtong , Song Wenping , Wang Lin , Li Tianlong
Published: June 2022

In this study, we propose a highly efficient robot platform for pollutant adsorption. This robot system consists of a flapping-wing micro aircraft (FWMA) for long-distance transportation and delivery and cost-effective multifunctional Janus microrobots for pollutant purification. The flapping-wing micro air vehicle can hover for 11.3 km with a flapping frequency of approximately 15 Hz, fly forward up to 31.6 km/h, and drop microrobots to a targeted destination. The Janus microrobot, which is composed of a silica microsphere, nickel layer, and hydrophobic layer, is used to absorb the oil and process organic pollutants. These Janus microrobots can be propelled fast up to 9.6 body lengths per second, and on-demand speed regulation and remote navigation are manageable. These Janus microrobots can continuously carry oil droplets in aqueous environments under the control of a uniform rotating magnetic field. Because of the fluid dynamics induced by the Janus microrobots, a highly efficient removal of Rhodamine B is accomplished. This smart robot system may open a door for pollutant purification.
Effects of Triiodothyronine on Human Osteoblast-Like Cells: Novel Insights From a Global Transcriptome Analysis
Authors: Rodrigues Bruna Moretto , Mathias Lucas Solla , Deprá Igor de Carvalho , Cury Sarah Santiloni , de Oliveira Miriane , Olimpio Regiane Marques Castro , De Sibio Maria Teresa , Gonçalves Bianca Mariani , Nogueira Célia Regina
Published: June 2022

Background: Thyroid hormones play a significant role in bone development and maintenance, with triiodothyronine (T3) particularly being an important modulator of osteoblast differentiation, proliferation, and maintenance. However, details of the biological processes (BPs) and molecular pathways affected by T3 in osteoblasts remain unclear.

Methods: To address this issue, primary cultures of human adipose-derived mesenchymal stem cells were subjected to our previously established osteoinduction protocol, and the resultant osteoblast-like cells were treated with 1 nm or 10 nm T3 for 72 h. RNA sequencing (RNA-Seq) was performed using the Illumina platform, and differentially expressed genes (DEGs) were identified from the raw data using Kallisto and DESeq2. Enrichment analysis of DEGs was performed against the Gene Ontology Consortium database for BP terms using the R package clusterProfiler and protein network analysis by STRING.

Results: Approximately 16,300 genes were analyzed by RNA-Seq, with 343 DEGs regulated in the 1 nm T3 group and 467 upregulated in the 10 nm T3 group. Several independent BP terms related to bone metabolism were significantly enriched, with a number of genes shared among them (FGFR2, WNT5A, WNT3, ROR2, VEGFA, FBLN1, S1PR1, PRKCZ, TGFB3, and OSR1 for 1nM T3; and FZD1, SMAD6, NOG, NEO1, and ENG for 10 nm T3). An osteoblast-related search in the literature regarding this set of genes suggests that both T3 doses are unfavorable for osteoblast development, mainly hindering BMP and canonical and non-canonical WNT signaling.

Conclusions: Therefore, this study provides new directions toward the elucidation of the mechanisms of T3 action on osteoblast metabolism, with potential future implications for the treatment of endocrine-related bone pathologies.
Crosstalk Between the Gut and Brain: Importance of the Fecal Microbiota in Patient With Brain Tumors
Authors: Li Yuping , Jiang Haixiao , Wang Xiaolin , Liu Xiaoguang , Huang Yujia , Wang Zhiyao , Ma Qiang , Dong Lun , Qi Yajie , Zhang Hengzhu , Lu Guangyu
Published: June 2022

Background

Variations in the gut microbiota may affect the metabolism, inflammation and immune response of the host. Microbiota dysbiosis has been extensively investigated in neurological disorders and diseases of the central nervous system (CNS). However, the alterations of the gut microbiota in patients suffering from brain tumors and the associations of the gut microbiota with these diseases remain unknown. Herein, we investigate the alterations of the gut microbiota community in patients with brain tumors and the associations between the two and further explore microbial markers used for the diagnosis of brain tumors.

Methods

In our study, we recruited 158 participants, consisting of 101 brain tumor patients (65 benign and 36 malignant cases) and 57 age- and sex-matched healthy controls (HCs). We characterized the gut microbial community by using 16S rRNA gene amplicon sequencing and investigated its correlations with clinical features.

Results

The results showed remarkably less microbial ecosystem richness and evenness in patients with brain tumors than in HCs. The gut microbiota community structure underwent profound changes in the brain tumor group, including an increase in the abundances of pathogenic bacteria, such as Fusobacteriota and Proteobacteria and a reduction in the abundances of probiotic bacteria, such as Bifidobacterium or Lachnospira. Moreover, our study indicated more significant correlations and clustering of pathogens in the malignant brain tumor group. Furthermore, a biomarker panel was used to discriminate the brain tumor patients from the healthy controls (AUC: 0.77). Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation revealed an accumulation of harmful metabolites and disorders of the basic physiological pathways in the brain tumor group.

Conclusions

Our study revealed that brain tumor patients may possess divergent host-microbe interactions from those of healthy controls, especially in malignant brain tumor patients. In addition, the intestinal flora may be involved in immune responses and metabolism in the microenvironment of brain tumors. All evidence, including the biomarker panel, suggests that the intestinal flora may be a useful diagnostic and predictive tool and an important preventive target for brain tumors.
An Update of Mobile Colistin Resistance in Non-Fermentative Gram-Negative Bacilli
Authors: Khuntayaporn Piyatip , Thirapanmethee Krit , Chomnawang Mullika Traidej
Published: June 2022

Colistin, the last resort for multidrug and extensively drug-resistant bacterial infection treatment, was reintroduced after being avoided in clinical settings from the 1970s to the 1990s because of its high toxicity. Colistin is considered a crucial treatment option for Acinetobacter baumannii and Pseudomonas aeruginosa, which are listed as critical priority pathogens for new antibiotics by the World Health Organization. The resistance mechanisms of colistin are considered to be chromosomally encoded, and no horizontal transfer has been reported. Nevertheless, in November 2015, a transmissible resistance mechanism of colistin, called mobile colistin resistance (MCR), was discovered. Up to ten families with MCR and more than 100 variants of Gram-negative bacteria have been reported worldwide. Even though few have been reported from Acinetobacter spp. and Pseudomonas spp., it is important to closely monitor the epidemiology of mcr genes in these pathogens. Therefore, this review focuses on the most recent update on colistin resistance and the epidemiology of mcr genes among non-fermentative Gram-negative bacilli, especially Acinetobacter spp. and P. aeruginosa.
Short- and Long-Term Effects of High-Intensity Interval Training vs. Moderate-Intensity Continuous Training on Left Ventricular Remodeling in Patients Early After ST-Segment Elevation Myocardial Infarction—The HIIT-EARLY Randomized Controlled Trial
Authors: Eser Prisca , Trachsel Lukas D. , Marcin Thimo , Herzig David , Freiburghaus Irina , De Marchi Stefano , Zimmermann Andreas J. , Schmid Jean-Paul , Wilhelm Matthias
Published: June 2022

Aim

Due to insufficient evidence on the safety and effectiveness of high-intensity interval training (HIIT) in patients early after ST-segment elevation myocardial infarction (STEMI), we aimed to compare short- and long-term effects of randomized HIIT or moderate-intensity continuous training (MICT) on markers of left ventricular (LV) remodeling in STEMI patients receiving optimal guideline-directed medical therapy (GDMT).

Materials and Methods

Patients after STEMI (<4 weeks) enrolled in a 12-week cardiac rehabilitation (CR) program were recruited for this randomized controlled trial (NCT02627586). During a 3-week run-in period with three weekly MICT sessions, GDMT was up-titrated. Then, the patients were randomized to HIIT or isocaloric MICT for 9 weeks. Echocardiography and cardiopulmonary exercise tests were performed after run-in (3 weeks), end of CR (12 weeks), and at 1-year follow-up. The primary outcome was LV end-diastolic volume index (LVEDVi) at the end of CR. Secondary outcomes were LV global longitudinal strain (GLS) and cardiopulmonary fitness.

Results

Seventy-three male patients were included, with the time between STEMI and start of CR and randomization being 12.5 ± 6.3 and 45.8 ± 10.8 days, respectively. Mixed models revealed no significant group × time interaction for LVEDVi at the end of CR (p = 0.557). However, there was a significantly smaller improvement in GLS at 1-year follow-up in the HIIT compared to the MICT group (p = 0.031 for group × time interaction). Cardiorespiratory fitness improved significantly from a median value of 26.5 (1st quartile 24.4; 3rd quartile 1.1) ml/kg/min at randomization in the HIIT and 27.7 (23.9; 31.6) ml/kg/min in the MICT group to 29.6 (25.3; 32.2) and 29.9 (26.1; 34.9) ml/kg/min at the end of CR and to 29.0 (26.6; 33.3) and 30.6 (26.0; 33.8) ml/kg/min at 1 year follow-up in HIIT and MICT patients, respectively, with no significant group × time interactions (p = 0.138 and 0.317).

Conclusion

In optimally treated patients early after STEMI, HIIT was not different from isocaloric MICT with regard to short-term effects on LVEDVi and cardiorespiratory fitness. The worsening in GLS at 1 year in the HIIT group deserves further investigation, as early HIIT may offset the beneficial effects of GDMT on LV remodeling in the long term.
Application of Postoperative Remote Follow-Up of CIED Based on the 5G Cloud Technology Support Platform in Areas With Underdeveloped Medical Resources
Authors: Tong Lin , Long Yu , Xiong Shiqiang , Li Jin , Huang Wenchao , Liu Hanxiong , Cai Lin
Published: June 2022

Postoperative follow-up is crucial for the clinical management of patients carrying cardiovascular implantable electronic devices (CIED). However, in a plethora of underdeveloped areas of China, due to limited medical resources and associated economic costs, geographical restrictions, the outbreak of the COVID-19 pandemic, and various other reasons, the medical system is unable to meet the ever-increasing demand for long-term clinical follow-up and telemedicine services. Based on these challenges, postoperative remote follow-up of CIED based on the 5G-cloud technology support platform (5G-CTP) may have the potential to optimize the allocation of medical resources and provide patients with high-quality CIED follow-up services locally. These unique characteristics of CIED follow-up utilizing 5G-CTP are qualified to protect the safety of the patients in terms of both clinical safety and cyber security. Furthermore, during the COVID-19 pandemic, remote follow-up of CIED significantly reduces the risk of viral exposure to patients and medical staff while having the potential to improve the current situation of CIED postoperative follow-up.
Sensitivity of Tropical Cyclone Intensity Variability to Different Stochastic Parameterization Methods
Authors: Patra Mahashweta , Fan Wai-Tong , Kieu Chanh
Published: June 2022

Proper representations of stochastic processes in tropical cyclone (TC) models are critical for capturing TC intensity variability in real-time applications. In this study, three different stochastic parameterization methods, namely, random initial conditions, random parameters, and random forcing, are used to examine TC intensity variation and uncertainties. It is shown that random forcing produces the largest variability of TC intensity at the maximum intensity equilibrium and the fastest intensity error growth during TC rapid intensification using a fidelity-reduced dynamical model and a cloud-resolving model (CM1). In contrast, the random initial condition tends to be more effective during the early stage of TC development but becomes less significant at the mature stage. For the random parameter method, it is found that this approach depends sensitively on how the model parameters are randomized. Specifically, randomizing model parameters at the initial time appears to produce much larger effects on TC intensity variability and error growth compared to randomizing model parameters every model time step, regardless of how large the random noise amplitude is. These results highlight the importance of choosing a random representation scheme to capture proper TC intensity variability in practical applications.
Influence of Clay Content on Crack Evolution of Clay–Sand Mixture
Authors: Jiang Xiangang , Huang Qin , Zhang Zongliang , Vallejo Luis E. , Chen Xiaoqing , Zhao Wanyu , Deng Hongyan , Liu Xingrong , Song Danqing , Chen Zhuo
Published: June 2022

Clay particles have an important influence on the cracking of clay–sand mixture, but the quantitative relationships between the clay content and crack evolution of the clay–sand mixture are still not clear. In order to explore the crack evolution process of the clay–sand mixture under different clay content conditions, we prepared nine groups of saturated clay–sand mixture samples with different clay contents and carried out drying experiments and Brazilian tests. The geometric dimensions and development forms of soil cracking were quantitatively analyzed by taking pictures of the sample cracks, image processing, and weighing the variation of the soil mass at the corresponding time during the drying process. The results showed that when the clay content was greater than 50%, the development process of the clay–sand mixture cracks can be divided into three stages: the formation stage of main cracks, the generation stage of the autonomously derived secondary fractures, and the stage of cracks widening. When it was less than 50%, the cracks in the development process of clay–sand mixture cracks had the characteristics of short length, dense crack spacing, no main cracks, and no obvious stage. The clay could add the tensile strength of the mixture and restrain crack development. The clay content had a significant effect on the shrinkage cracking and crack development process of soil, which shows that with the increase in the clay content, the tensile strength increases and restrains the crack development; the crack rate increases continuously and the width of cracks become larger; the lower the clay content, the lower is the crack rate and the smaller is the average crack width. The water content of samples with different clay soil contents all nonlinearly decreased with the increase in drying time, and the corresponding residual water content increased with the increase in the clay soil content at the same time. The water content of initial cracking, stable crack length, stable crack width, and stable block of the clay–sand mixture increased with the increase in the clay content, and the water content of the stable crack length was the same as that of the stable block number.
Learn to Machine Learn via Games in the Classroom
Authors: Zammit Marvin , Voulgari Iro , Liapis Antonios , Yannakakis Georgios N.
Published: June 2022

Artificial Intelligence (AI) and Machine Learning (ML) algorithms are increasingly being adopted to create and filter online digital content viewed by audiences from diverse demographics. From an early age, children grow into habitual use of online services but are usually unaware of how such algorithms operate, or even of their presence. Design decisions and biases inherent in the ML algorithms or in the datasets they are trained on shape the everyday digital lives of present and future generations. It is therefore important to disseminate a general understanding of AI and ML, and the ethical concerns associated with their use. As a response, the digital game ArtBot was designed and developed to teach fundamental principles about AI and ML, and to promote critical thinking about their functionality and shortcomings in everyday digital life. The game is intended as a learning tool in primary and secondary school classrooms. To assess the effectiveness of the ArtBot game as a learning experience we collected data from over 2,000 players across different platforms focusing on the degree of usage, interface efficiency, learners' performance and user experience. The quantitative usage data collected within the game was complemented by over 160 survey responses from teachers and students during early pilots of ArtBot. The evaluation analysis performed in this paper gauges the usability and usefulness of the game, and identifies areas of the game design which need improvement.
Altered Caffeine Metabolism Is Associated With Recurrent Hypoglycemia in Type 2 Diabetes Mellitus: A UPLC–MS-Based Untargeted Metabolomics Study
Authors: Lijing Wang , Sujie Ke , Linxi Wang , Lishan Huang , Liqin Qi , Zhidong Zhan , Kejun Wu , Mengjun Zhang , Xiaoying Liu , Xiaohong Liu , Libin Liu
Published: June 2022

Background

Recurrent hypoglycemia (RH) is well known to impair awareness of hypoglycemia and increase the risk of severe hypoglycemia; the underlying mechanism requires further understanding. We aimed to investigate the metabolic characteristic profile for RH in type 2 diabetes mellitus (T2DM) patients and explore the potential metabolic mechanism and prevention strategies.

Methods

We screened 553 community-based T2DM patients. T2DM with RH (DH group, n=40) and T2DM without hypoglycemia (DC group, n=40) were assigned in the case-control study, matched by propensity score matching. Non-targeted, global metabolite profiling was conducted using ultra-high performance liquid chromatography-mass spectrometry. Principal component analysis and supervised projections to latent structures-discriminant analysis were constructed to evaluate the potential biomarkers. Metabolites with a fold change of >2.0 or <0.5, a t-test q-value <0.05, and variable importance in projection value of >1 were identified as significantly differential metabolites. MetaboAnalyst was performed to analyze the related metabolic pathways.

Results

We identified 12 significantly distinct metabolites as potential biomarkers of RH, which were enriched in five pathways; the caffeine metabolic pathway was the most dominant related one. Caffeine and its main downstream metabolites (theophylline and paraxanthine, all q <0.05) were significantly lower during RH. The combination of these metabolites can serve as a reliable predictor biomarker for RH (area under the curve = 0.88). Regarding lipid metabolism, triglyceride was upregulated (P=0.003) and the O-Acylcarnitine was downregulated (q < 0.001). Besides, RH was accompanied by lower phenylalanine (q=0.003) and higher cortisone (q=0.005) levels.

Conclusions

RH in T2DM is accompanied by caffeine, lipolysis, phenylalanine, and cortisone metabolism abnormalities. Caffeine might be a reliable candidate biomarker and potential prevention strategy for RH, but further validation studies are needed.

Clinical Trial Registry

Chi CTR 1900026361, 2019-10-3.
Prognostic and Predictive Value of CCND1/Cyclin D1 Amplification in Breast Cancer With a Focus on Postmenopausal Patients: A Systematic Review and Meta-Analysis
Authors: Jeffreys Sarah A. , Becker Therese M. , Khan Sarah , Soon Patsy , Neubauer Hans , de Souza Paul , Powter Branka
Published: June 2022

Background

Up to 80% of breast cancers (BCa) are estrogen receptor positive and current treatments target the estrogen receptor (endocrine therapies) and/or CDK4/6 (CDK4/6 inhibitors). CCND1 encodes the protein cyclin D1, responsible for regulation of G1 to S phase transition in the cell cycle. CCND1 amplification is common in BCa and contributes to increased cyclin D1 expression. As there are signalling interactions between cyclin D1 and the estrogen receptor, understanding the impact of CCND1 amplification on estrogen receptor positive patients’ disease outcomes, is vital. This review aims to evaluate CCND1 amplification as a prognostic and predictive biomarker in BCa.

Materials and Methods

Publications were retrieved from the databases: PubMed, MEDLINE, Embase and Cochrane library. Exclusion criteria were duplication, publication type, non-English language, in vitro and animal studies, not BCa, male BCa, premenopausal BCa, cohort size <35, CCND1 amplification not reported. Publications with cohort duplication, and inadequate recurrence free survival (RFS) and overall survival (OS) data, were also excluded. Included publications were assessed for Risk of Bias (RoB) using the Quality In Prognosis Studies tool. Statistical analyses (Inverse Variance and Mantel-Haenszel) were performed in Review Manager. The PROSPERO registration number is [CRD42020208179].

Results

CCND1 amplification was significantly associated with positive estrogen receptor status (OR:1.70, 95% CI:1.19-2.43, p = 0.004) and cyclin D1 overexpression (OR: 5.64, 95% CI: 2.32-13.74, p=0.0001). CCND1 amplification was significantly associated with shorter RFS (OR: 1.64, 95% CI: 1.13-2.38, p = 0.009), and OS (OR: 1.51, 95% CI: 1.19-1.92, p = 0.0008) after removal of studies with a high RoB. In endocrine therapy treated patients specifically, CCND1 amplification predicted shorter RFS (HR: 2.59, 95% CI: 1.96-3.41, p < 0.00001) and OS (HR: 1.59, 95% CI: 1.00-2.49, p = 0.05) also after removal of studies with a high RoB.

Conclusion

While a lack of standardised approach for the detection of CCND1 amplification is to be considered as a limitation, CCND1 amplification was found to be prognostic of shorter RFS and OS in BCa. CCND1 amplification is also predictive of reduced RFS and OS in endocrine therapy treated patients specifically. With standardised methods and cut offs for the detection of CCND1 amplification, CCND1 amplification would have potential as a predictive biomarker in breast cancer patients.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42020208179.
Validating and Comparing C-TIRADS, K-TIRADS and ACR-TIRADS in Stratifying the Malignancy Risk of Thyroid Nodules
Authors: Chen Qingfang , Lin Mingnan , Wu Size
Published: June 2022

The thyroid imaging reporting and data system (TIRADS) was proposed by experts for optimal ultrasound evaluation of malignancy risk of thyroid focal lesions. There are several versions of TIRADS, some of them have been validated sufficiently, and the others have not been well assessed. In this study, a recently launched Chinese version of TIRADS (C-TIRADS) for malignancy risk stratification of thyroid nodules was validated, and the performance was compared to that of the Korean TIRADS (K-TIRADS) and American College of Radiology(ACR) TIRADS (ACR-TIRADS). Archives of 2177 patients who had undergone thyroid ultrasound examination, coarse needle tissue biopsy and/or surgery were reviewed, and 1978 patients with 1982 thyroid nodules were assessed according to the three TIRADSs. The histopathology was taken as the golden standard. The results showed the 1982 thyroid nodules were consisted of 1306 benign nodules and 676 malignant nodules. The malignancy risk accounted for 1.09%, 2.14%, 10.34%, 49.28%, 88.19% and 85.29% of the total nodules that were categorised as C-TIRADS 2, 3, 4A, 4B, 4C and 5, respectively; 0.00%, 1.64%, 2.87%,18.71% and 82.22% of the total nodules that were categorised as ACR-TIRADS 1, 2, 3, 4 and 5, respectively; 0.85%, 3.27%, 24.27% and 80.96% of the total nodules that were categorised as K-TIRADS 2, 3, 4 and 5, respectively. The correlation between the category of TIRADS and percentile of malignancy was 0.94 in the C-TIRADS, 1.00 in the ACR-TIRADS, and 1.00 in the K-TIRADS, respectively. The highest values of accuracy(AUC) of ROC curves of C-TIRADS 4B, K-TIRADS 5 and ACR-TIRADS 5 were taken as the cut-off values for risk stratification, respectively. The sensitivity, specificity, positive and negative predictive values and AUC by C-TIRADS 4B, K-TIRADS 5 and ACR-TIRADS 5 for malignancy risk stratification of thyroid nodules were 90.83%, 84.23%, 74.88% and 94.66% and 0.88, respectively; 83.58%, 89.82%, 80.95%, 91.36% and 0.87, respectively; and 85.50%, 90.35%, 82.10%, 92.33% and 0.88, respectively (P>0.05 for all). We concluded that the C-TIRADS has excellent performance in the malignancy risk stratification of thyroid nodules by the optimized cut-off value, which is comparable to that in K-TIRADS and ACR-TIRADS.
Why Are Households Willing to Pay for Renewable Energy? Lessons From Romania
Authors: Maxim Alexandru , Jijie Dumitru-Tudor , Roman Teodora
Published: June 2022

Renewable energy is seen as a key tool in addressing the dual issue of increasing energy demand and climate change mitigation. In the current geopolitical climate, it may also play a key long-term role in increasing energy security. In order to reach the ambitious green energy targets set for each European Union member state public support for fiscal and other support mechanisms is required. The purpose of this paper is to determine to what extent the population in the North-East region of Romania is willing to make financial sacrifices for further development of renewable energy. We also explore what lifestyle and socio-demographic factors influence willingness to pay. We applied a discrete choice experiment on a sample of 602 households from the populous North-East region of Romania. Our results show that the creation of new jobs and the increase of the national energy independence, followed by the reduction of pollution are societal benefits that would convince households to pay a premium in order to support renewable energy development. Increased local budgets for rural communities resulting from the taxation of new energy companies is not one of the desired outcomes of green energy development. The study is useful in the design of adequate fiscal and renewable support policies and serves companies by identifying willingness to pay influence factors, as well as by demonstrating a market segmentation procedure.
Improving China’s Global Lithium Resource Development Capacity
Authors: Li Hanshi , Zhu Ting , Chen Xiangshun , Liu Hanbin , He Guangsheng
Published: June 2022

Flourishing sales of new electric vehicles have led to a considerable surge in demand for the vital, upstream raw material, lithium (Li). As an essential energy metal and raw material for the production of batteries, lithium has become indispensable to the electric vehicle industry. It has been identified as a strategic, emerging industrial mineral in China. Based on a literature review and qualitative analysis of the imbalance between the supply and demand of lithium raw materials in China, this paper analyzes the current challenges of China’s lithium supply chain, especially mining, pricing and recycling, that are obstructing the realization of China’s carbon neutrality. On this basis, relevant policy suggestions are proposed from three perspectives: strengthening lithium resource development and reserve capacity, promoting international cooperation for lithium supply, and properly regulating the circular economy of domestic lithium resources.
Genetic Characterization and Population Connectedness of North American and European Dairy Goats
Authors: Teissier Marc , Brito Luiz F. , Schenkel Flavio S. , Bruni Guido , Fresi Pancrazio , Bapst Beat , Robert-Granie Christèle , Larroque Hélène
Published: June 2022

Genomic prediction of breeding values is routinely performed in several livestock breeding programs around the world, but the size of the training populations and the genetic structure of populations evaluated have, in many instances, limited the increase in the accuracy of genomic estimated breeding values. Combining phenotypic, pedigree, and genomic data from genetically related populations can be a feasible strategy to overcome this limitation. However, the success of across-population genetic evaluations depends on the pedigree connectedness and genetic relationship among individuals from different populations. In this context, this study aimed to evaluate the genetic connectedness and population structure of Alpine and Saanen dairy goats from four countries involved in the European project SMARTER (SMAll RuminanTs Breeding for Efficiency and Resilience), including Canada, France, Italy, and Switzerland. These analyses are paramount for assessing the potential feasibility of an across-country genomic evaluation in dairy goats. Approximately, 9,855 genotyped individuals (with 51% French genotyped animals) and 6,435,189 animals included in the pedigree files were available across all four populations. The pedigree analyses indicated that the exchange of breeding animals was mainly unilateral with flows from France to the other three countries. Italy has also imported breeding animals from Switzerland. Principal component analyses (PCAs), genetic admixture analysis, and consistency of the gametic phase revealed that French and Italian populations are more genetically related than the other dairy goat population pairs. Canadian dairy goats showed the largest within-breed heterogeneity and genetic differences with the European populations. The genetic diversity and population connectedness between the studied populations indicated that an international genomic evaluation may be more feasible, especially for French and Italian goats. Further studies will investigate the accuracy of genomic breeding values when combining the datasets from these four populations.
Bursts of Genomic Instability Potentiate Phenotypic and Genomic Diversification in Saccharomyces cerevisiae
Authors: Heasley Lydia R. , Argueso Juan Lucas
Published: June 2022

How microbial cells leverage their phenotypic potential to survive in a changing environment is a complex biological problem, with important implications for pathogenesis and species evolution. Stochastic phenotype switching, a particularly fascinating adaptive approach observed in numerous species across the tree of life, introduces phenotypic diversity into a population through mechanisms which have remained difficult to define. Here we describe our investigations into the mechanistic basis of colony morphology phenotype switching which occurs in populations of a pathogenic isolate of Saccharomyces cerevisiae, YJM311. We observed that clonal populations of YJM311 cells produce variant colonies that display altered morphologies and, using whole genome sequence analysis, discovered that these variant clones harbored an exceptional collection of karyotypes newly altered by de novo structural genomic variations (SVs). Overall, our analyses indicate that copy number alterations, more often than changes in allelic identity, provide the causative basis of this phenotypic variation. Individual variants carried between 1 and 16 de novo copy number variations, most of which were whole chromosomal aneuploidies. Notably, we found that the inherent stability of the diploid YJM311 genome is comparable to that of domesticated laboratory strains, indicating that the collections of SVs harbored by variant clones did not arise by a chronic chromosomal instability (CIN) mechanism. Rather, our data indicate that these variant clones acquired such complex karyotypic configurations simultaneously, during stochastic and transient episodes of punctuated systemic genomic instability (PSGI). Surprisingly, we found that the majority of these highly altered variant karyotypes were propagated with perfect fidelity in long-term passaging experiments, demonstrating that high aneuploidy burdens can often be conducive with prolonged genomic integrity. Together, our results demonstrate that colony morphology switching in YJM311 is driven by a stochastic process in which genome stability and plasticity are integrally coupled to phenotypic heterogeneity. Consequently, this system simultaneously introduces both phenotypic and genomic variation into a population of cells, which can, in turn perpetuate population diversity for many generations thereafter.
Review: Sustainable Clinical Development of CAR-T Cells – Switching From Viral Transduction Towards CRISPR-Cas Gene Editing
Authors: Wagner Dimitrios L. , Koehl Ulrike , Chmielewski Markus , Scheid Christoph , Stripecke Renata
Published: June 2022

T cells modified for expression of Chimeric Antigen Receptors (CARs) were the first gene-modified cell products approved for use in cancer immunotherapy. CAR-T cells engineered with gammaretroviral or lentiviral vectors (RVs/LVs) targeting B-cell lymphomas and leukemias have shown excellent clinical efficacy and no malignant transformation due to insertional mutagenesis to date. Large-scale production of RVs/LVs under good-manufacturing practices for CAR-T cell manufacturing has soared in recent years. However, manufacturing of RVs/LVs remains complex and costly, representing a logistical bottleneck for CAR-T cell production. Emerging gene-editing technologies are fostering a new paradigm in synthetic biology for the engineering and production of CAR-T cells. Firstly, the generation of the modular reagents utilized for gene editing with the CRISPR-Cas systems can be scaled-up with high precision under good manufacturing practices, are interchangeable and can be more sustainable in the long-run through the lower material costs. Secondly, gene editing exploits the precise insertion of CARs into defined genomic loci and allows combinatorial gene knock-ins and knock-outs with exciting and dynamic perspectives for T cell engineering to improve their therapeutic efficacy. Thirdly, allogeneic edited CAR-effector cells could eventually become available as “off-the-shelf” products. This review addresses important points to consider regarding the status quo, pending needs and perspectives for the forthright evolution from the viral towards gene editing developments for CAR-T cells.
Phenotypic and Immunometabolic Aspects on Stem Cell Memory and Resident Memory CD8+ T Cells
Authors: La Manna Marco Pio , Shekarkar Azgomi Mojtaba , Tamburini Bartolo , Badami Giusto Davide , Mohammadnezhad Leila , Dieli Francesco , Caccamo Nadia
Published: June 2022

The immune system, smartly and surprisingly, saves the exposure of a particular pathogen in its memory and reacts to the pathogen very rapidly, preventing serious diseases.

Immunologists have long been fascinated by understanding the ability to recall and respond faster and more vigorously to a pathogen, known as “memory”.

T-cell populations can be better described by using more sophisticated techniques to define phenotype, transcriptional and epigenetic signatures and metabolic pathways (single-cell resolution), which uncovered the heterogeneity of the memory T-compartment. Phenotype, effector functions, maintenance, and metabolic pathways help identify these different subsets. Here, we examine recent developments in the characterization of the heterogeneity of the memory T cell compartment. In particular, we focus on the emerging role of CD8+TRMand TSCMcells, providing evidence on how their immunometabolism or modulation can play a vital role in their generation and maintenance in chronic conditions such as infections or autoimmune diseases.