bluuebunny/crossref_metadata_2025 huggingface dataset:
Virtual Reality for Distraction and Relaxation in a Pediatric Hospital Setting: An Interventional Study With a Mixed-Methods Design
Authors: Bernaerts Sylvie , Bonroy Bert , Daems Jo , Sels Romy , Struyf Dieter , Gies Inge , van de Veerdonk Wessel
Published: May 2022

Accumulating evidence supports the use of virtual reality (VR) as an effective pain and anxiety management tool for pediatric patients during specific medical procedures in dedicated patient groups. However, VR is still not widely adopted in everyday clinical practice. Feasibility and acceptability measures of clinicians' experiences are often missing in studies, thereby omitting an important stakeholder in VR use in a clinical setting. Therefore, the aim of this mixed-methods study was to investigate the feasibility, acceptability, tolerability (primary outcomes), and preliminary effectiveness (secondary outcome) of Relaxation-VR in both pediatric patients aged 4–16 years and clinicians. Relaxation-VR is a VR application prototype aimed to provide distraction and relaxation for a variety of patient populations and procedures and is used to reduce anxiety, stress (tension) and pain for children in hospital. Multiple measures of acceptability, feasibility and tolerability, and pre-to-post changes in measures of pain, anxiety, stress and happiness were assessed in pediatric patients. At the end of the study, acceptability and feasibility of VR use was assessed in clinicians. Results indicate that VR use (in particular, the Relaxation-VR prototype) for both distraction and relaxation is acceptable, feasible and tolerable for a variety of pediatric patients aged 4–16 years, as assessed in both patients and clinicians, and can reduce anxiety, pain and tension (stress), and increase happiness in a hospital setting.
Variation in Luminescence Characteristics and Paramagnetic Defect Centres in Fine-Grained Quartz From a Loess-Palaeosol Sequence in Tajikistan: Implications for Provenance Studies in Aeolian Environments
Authors: Dave Aditi K. , Timar-Gabor Alida , Scardia Giancarlo , Safaraliev Nosir , Fitzsimmons Kathryn E.
Published: May 2022

Trapped charge characteristics in quartz are of increasing interest for their utility as indicators of sediment provenance. These include sensitivity of optically stimulated luminescence (OSL) and thermoluminescence (TL) signal and paramagnetic E1’ defect centre in quartz. Up until now, these methods have largely been used independently in provenance investigations, especially in aeolian systems. Variations in quartz OSL and TL signal sensitivity in loess-palaeosol sequences has been linked to shifts in sediment source corresponding to climatic fluctuations. However, the processes responsible for observed variation in OSL and TL sensitivity in quartz, including its link to the original rock source and/or its sedimentary history, remains a topic of contention. On the other hand, the intensity of E1’ defect centre in quartz is known to reflect the provenance of quartz, and is also routinely utilised as a provenance indicator in aeolian studies. In this study we aim to understand the variations in E1’ intensity and OSL (and TL) sensitivity by direct comparison of these characteristics in fine-grained quartz from a c. 60 m-thick loess-palaeosol sequence in Tajikistan. In doing so, we investigate the natural processes that may have led to variability in trapped-charge characteristics over the c. 500 ky timespan covered by the sequence. Our results suggest that apart from the inherent link to its provenance signature, the observed luminescence sensitivity of quartz especially in loess-palaeosol sequences are largely influenced by depositional and post-depositional processes during soil formation.
Glacial-Interglacial Variations in Organic Carbon Burial in the Northwest Pacific Ocean Over the Last 380 kyr and its Environmental Implications
Authors: Zhang Yuying , Hu Limin , Wu Yonghua , Dong Zhi , Yao Zhengquan , Gong Xun , Liu Yanguang , Ikehara Minoru , Shi Xuefa
Published: May 2022

The carbon cycle on the Earth’s surface is linked to long-term variations in atmospheric CO2 as well as carbon sequestration in various pools. The burial of particulate organic carbon (OC) in marine sediments is also highly sensitive to the global climate over geological time scales, but with little known about OC burial and its regulations over glacial-interglacial cycles. Here, we present a long-term OC record over the past ∼380 kyr, from the Northwest Pacific Ocean, an ideal region for studying OC burial and its environmental implications on glacial-interglacial timescales. We observed a distinct cyclicity of higher OC burial in glacial periods, which was coupled with input from Asian dust and the Kuroshio Current but seemingly decoupled from biogenic element contents, implying a limited effect of marine productivity on OC burial. Moreover, the sedimentary record of OC was synchronous with oceanic redox conditions, especially the redox sensitive elements at the sediment-water interface, indicating a relatively reducing conditions that enhanced OC preservation during glacial periods. The overall glacial-interglacial OC burial regime in the Northwest Pacific Ocean was conceptually constructed. It showed a higher efficiency of OC burial during glacial periods and significant degradation during interglacial periods. The findings of this study highlighted the important contribution of environmental redox conditions on OC burial in the deep Northwest Pacific, demonstrating the sensitivity of the carbon cycle to global climate on an orbital scale.
Contrastive Video Examples in Teacher Education: A Matter of Sequence and Prompts
Authors: Wilkes Theresa , Stark Lisa , Trempler Kati , Stark Robin
Published: May 2022

Everyday teaching requires teachers to deal with a variety of pedagogical issues, such as classroom disruptions. Against the background of on-going calls for an evidence-informed practice, teachers should ground their pedagogical decisions not only on subjective theories or experience-based knowledge but also on educational theories and empirical findings. However, research suggests that pre- and in-service teachers rather refer to experiential knowledge than to educational knowledge when addressing practical, pedagogical issues. One reason for the infrequent use of educational knowledge is that acquired knowledge has remained inert and cannot be applied to complex situations in practice. Therefore, implementing learning with contrastive (i.e., functional and dysfunctional) video examples in teacher education seems promising to promote pre-service teachers’ acquisition of educational knowledge. The 2×2-intervention study (N= 220) investigated the effects of the video sequence (dysfunctional-functional/functional-dysfunctional) and of video analysis prompts (with/without) on learning outcomes (concept knowledge, application knowledge) and on learning processes (written video analyses). Results revealed that the sequence dysfunctional-functional led to higher application knowledge in the post-test. There was no sequencing effect on concept knowledge. Prompted groups showed higher concept knowledge and application knowledge in the post-test. Furthermore, both experimental factors affected learning processes, which resulted in higher learning outcomes. In conclusion, learning with contrastive video examples in teacher education seems to be more effective if the video examples are presented in the sequence dysfunctional-functional and if instructional prompts guide the video analysis. The results substantiate the relevance of instructional guidance in learning with video examples and broaden the scope of validity of the concept of learning from errors.
Mathematical Modeling of Free Thyroxine Concentrations During Methimazole Treatment for Graves’ Disease: Development and Validation of a Computer-Aided Thyroid Treatment Method
Authors: Theiler-Schwetz Verena , Benninger Thomas , Trummer Christian , Pilz Stefan , Reichhartinger Markus
Published: May 2022

Background

Methimazole (MMI) is the first-line treatment for patients with Graves’ disease (GD). While there are empirical recommendations for initial MMI doses, there is no clear guidance for subsequent MMI dose titrations. We aimed to (a) develop a mathematical model capturing the dynamics of free thyroxine (FT4) during MMI treatment (b), validate this model by use of numerical simulation in comparison with real-life patient data (c), develop the software application Digital Thyroid (DigiThy) serving either as a practice tool for treating virtual patients or as a decision support system with dosing recommendations for MMI, and (d) validate this software framework by comparing the efficacy of its MMI dosing recommendations with that from clinical endocrinologists.

Methods

Based on concepts of automatic control and by use of optimization techniques, we developed two first order ordinary differential equations for modeling FT4 dynamics during MMI treatment. Clinical data from patients with GD derived from the outpatient clinic of Endocrinology at the Medical University of Graz, Austria, were used to develop and validate this model. It was subsequently used to create the web-based software application DigiThy as a simulation environment for treating virtual patients and an autonomous computer-aided thyroid treatment (CATT) method providing MMI dosing recommendations.

Results

Based on MMI doses, concentrations of FT4, thyroid-stimulating hormone (TSH), and TSH-receptor antibodies (TRAb), a mathematical model with 8 patient-specific constants was developed. Predicted FT4 concentrations were not significantly different compared to the available consecutively measured FT4 concentrations in 9 patients with GD (52 data pairs, p=0.607). Treatment success of MMI dosing recommendations in 41 virtually generated patients defined by achieved target FT4 concentrations preferably with low required MMI doses was similar between CATT and usual care. Statistically, CATT was significantly superior (p<0.001).

Conclusions

Our mathematical model produced valid FT4 predictions during MMI treatment in GD and provided the basis for the DigiThy application already serving as a training tool for treating virtual patients. Clinical trial data are required to evaluate whether DigiThy can be approved as a decision support system with automatically generated MMI dosing recommendations.
A Stable Condition and Adaptive Diffusion Coefficients for the Coarse-Mesh Finite Difference Method
Authors: Xu Zhitao , Wu Hongchun , Zheng Youqi , Zhang Qian
Published: May 2022

Coarse-mesh finite difference (CMFD) method is a widely used numerical acceleration method. However, the stability of CMFD method is not good for the problems with optically thick regions. In this paper, a stability rule named the “sign preservation rule” in the field of numerical heat transfer is extended to the scheme of CMFD. It is required that the disturbance of neutron current is positively correlated with that of the negative value of flux gradient. A necessary condition for stability of the CMFD method is derived, an adaptive diffusion coefficient equation is proposed to improve the stability of CMFD method, and the corresponding revised CMFD method is called the rCMFD method. With a few modifications of the code, the rCMFD method was implemented in the hexagonal-Z nodal SN (discrete-ordinates) solver in the NECP-SARAX code system. The rCMFD method and other similar acceleration methods were tested by three fast reactor problems which were obtained by modifying the hexagonal pitches of a benchmark problem. The numerical results indicated that the rCMFD method showed better stability than the traditional CMFD method and the artificially diffusive CMFD (adCMFD) method and a better convergence rate than the adCMFD method and the optimally diffusive CMFD (odCMFD) method for these fast reactor problems.
Hydrogen Energy as Future of Sustainable Mobility
Authors: Chakraborty Suprava , Dash Santanu Kumar , Elavarasan Rajvikram Madurai , Kaur Arshdeep , Elangovan Devaraj , Meraj Sheikh Tanzim , Kasinathan Padmanathan , Said Zafar
Published: May 2022

Conventional fuels for vehicular applications generate hazardous pollutants which have an adverse effect on the environment. Therefore, there is a high demand to shift towards environment-friendly vehicles for the present mobility sector. This paper highlights sustainable mobility and specifically sustainable transportation as a solution to reduce GHG emissions. Thus, hydrogen fuel-based vehicular technologies have started blooming and have gained significance following the zero-emission policy, focusing on various types of sustainable motilities and their limitations. Serving an incredible deliverance of energy by hydrogen fuel combustion engines, hydrogen can revolution various transportation sectors. In this study, the aspects of hydrogen as a fuel for sustainable mobility sectors have been investigated. In order to reduce the GHG (Green House Gas) emission from fossil fuel vehicles, researchers have paid their focus for research and development on hydrogen fuel vehicles and proton exchange fuel cells. Also, its development and progress in all mobility sectors in various countries have been scrutinized to measure the feasibility of sustainable mobility as a future. This, paper is an inclusive review of hydrogen-based mobility in various sectors of transportation, in particular fuel cell cars, that provides information on various technologies adapted with time to add more towards perfection. When compared to electric vehicles with a 200-mile range, fuel cell cars have a lower driving cost in all of the 2035 and 2050 scenarios. To stimulate the use of hydrogen as a passenger automobile fuel, the cost of a hydrogen fuel cell vehicle (FCV) must be brought down to at least the same level as an electric vehicle. Compared to gasoline cars, fuel cell vehicles use 43% less energy and generate 40% less CO2.
Measurement of Resistance, Porosity, and Water Contact Angle of Porous Transport Layers for Low-Temperature Electrolysis Technologies
Authors: Ouimet Ryan J. , Young James L. , Schuler Tobias , Bender Guido , Roberts George M. , Ayers Katherine E.
Published: May 2022

The porous transport layer is an important component of low-temperature electrolysis devices, such as proton exchange membrane water electrolyzers or anion exchange membrane water electrolyzers. PTLs have significant influence on the cell performance as their bulk resistance can impact the ohmic resistance, their contact resistance can impact electrode performance, and their structure can impact the liquid flow to the cell, which could cause mass-transport losses. In order to improve cell performance, optimization of the PTL is critical. Standardized protocols should be utilized to adequately compare PTLs being developed from different institutions. This method will detail a standardized protocol for measuring the resistance of the PTL using a four-wire setup and will also detail a process for measuring the porosity and water contact angle of the PTL using capillary flow porometry.
A Method of Power Flow Database Generation Base on Weighted Sample Elimination Algorithm
Authors: Meng Xianbo , Li Yalou , Shi Dongyu , Hu Shanhua , Zhao Fei
Published: May 2022

With the rapid development of urban power grids, distributed renewable energy sources and adjustable loads have increased significantly, resulting in more complex operation conditions, increasing the difficulty of power flow calculations. The usage of artificial intelligence technology to assist in calculating power flows for large-scale urban grids has a wide range of application prospects. It is currently difficult to generate enough grid operation database with controlled distribution for artificial intelligence (AI) method research. Data is one of the important factors affecting the performance of deep learning algorithms, and the lack of research on data distribution characteristics also hinders the performance of deep learning algorithms. The distributional characteristics of data sets in high-dimensional feature spaces are difficult to represent and measure, and the algorithm design process is prone to encounter curse of dimensionality. This paper proposed a novel method for generating databases to improve the solving efficiency of data-driven power flow calculation problems. The proposed method removes samples based on the characteristics of data distribution. It constructs two databases, namely the blue noise distribution database and the variable density boundary enhanced distribution database. Compared with the classical stochastic sampling database, the proposed boundary-enhanced variable density (BEVD) database has significantly improved the judgment accuracy of power flow convergence. Finally, the China Electric Power Research Institute-36 (CEPRI-36) bus system is used to verify the effectiveness of the proposed method. The judgment accuracy was improved by 2.91%–9.5%.
Fiscal Pressure and Air Pollution in Resource-Dependent Cities: Evidence From China
Authors: Hui Changhong , Shen Fei , Tong Lu , Zhang Jingru , Liu Bei
Published: May 2022

Under the dual pressure of central environmental performance appraisal and fiscal pressure, local Chinese governments, especially those in resource-dependent cities, struggle with reprioritizing environmental protection over economic growth while staying under budget. However, the empirical impact of such endeavors on pollution control remains underexplored. Based on 2003–2018 panel data on resource-dependent cities in China, this paper adopts a dynamic panel model to explore the effect of local government fiscal pressure on air pollution. The results show that (1) due to the effect of path dependency on existing economic development patterns, resource-dependent cities suffer from a vicious circle where fiscal pressure aggravates air pollution emissions. (2) As shown by the heterogeneity test, air pollution emissions increase significantly as financial pressure becomes severe; the situation also worsens in mature-type resource-dependent cities. (3) The increase in the number of years in the office of top local government leaders exacerbates the negative effect of fiscal pressure on air pollution; in contrast, the increase in age of these officials mitigates the negative effect. (4) The results of the mechanism test show that financial pressure mainly aggravates environmental degradation by hindering industrial structure upgrading and inhibiting urban green innovation.
Household Food Waste: The Meaning of Product’s Attributes and Food-Related Lifestyle
Authors: Szymkowiak Andrzej , Borusiak Barbara , Pierański Bartłomiej , Kotyza Pavel , Smutka Luboš
Published: May 2022

The increasing volume and value of food waste is a huge threat to achieving sustainable development, food market stability, human population growth, and people’s well-being. Considering that consumers are responsible for a large degree of food waste, the current study looks at the problem of household food waste from the perspective of both food product attributes and consumers’ lifestyles. Specifically: How do people differ in their food disposal inclination based on their food-related lifestyle and products’ quality attributes? The Total Food Quality Model was applied to describe product attributes (taste, health, process, and convenience) whereas food-related lifestyle was measured with: innovativeness/novelty, information about products/health, convenience, price, taste, local/organic food, and social events. The Choice-Based Conjoint Analysis method, based on 753 participants, was used to assess the importance of individual attributes and levels. Clustering was carried out to identify people with similar preferences: through elbow method and Silhouette value maximization, three customer segments were identified. To investigate the distinct characteristics of these clusters related to food waste, one-way multivariate analysis of variance (MANOVA) was conducted. The obtained results confirm that consumers who overlap in their product attribute preferences also share a food-related lifestyle. The main contribution is the identification of consumer groups and the differences that characterize them in terms of the determinants of behaviour related to the importance of the factors of food products influencing the tendency to waste them.
Impact of Urbanization on Meteorology and Air Quality in Chengdu, a Basin City of Southwestern China
Authors: Wang Haofan , Liu Zhihong , Wu Kai , Qiu Jiaxin , Zhang Yang , Ye Bangping , He Min
Published: May 2022

Rapid urbanization has the potential to fundamentally perturb energy budget and alter urban air quality. While it is clear that urban meteorological parameters are sensitive to urbanization-induced changes in landscapes, a gap exists in our knowledge about how changes in land use and land cover affect the dynamics of urban air quality. Herein, we simulated a severe O3 episode (10–16 July 2017) and a highly polluted PM2.5 episode (25–30 December 2017) and assessed the changes of meteorological phenomenon and evolution of air pollutants induced by urbanization. We found that the urban expansion area (i.e., land use transition from natural to urban surfaces between 2000 and 2017, UEA) has a significant increase in nocturnal 2-m temperature (T2) with maximum values reaching 3 and 4°C in summer and winter, respectively. In contrast, UEA experienced cooling in the daytime with stronger reductions of T2 in winter than in summer. The T2 variability is primarily attributed to the intense thermal inertia and high heat capacity of the urban canopy and the shadowing effect caused by urbanization. Owing to increased surface roughness and decreased surface albedo as well as shadowing effects, the ventilation index (VI) of UEA increased up to 1,200 m2/s in winter while decreased up to 950 m2/s in summer. Changes in meteorological phenomenon alter physical and chemical processes associated with variations in PM2.5 and O3 concentrations. Urbanization leads to enhanced vertical advection process and weakened aerosol production, subsequently causing PM2.5 levels to decrease by 33.2 μg/m3 during the day and 4.6 μg/m3 at night, respectively. Meanwhile, O3 levels increased by 61.4 μg/m3 at 20:00 due to the reduction of horizontal advection induced by urbanization, while O3 concentrations changed insignificantly at other times. This work provides valuable insights into the effects of urbanization on urban meteorology and air quality over typical megacities, which support informed decision-making for urban heat and air pollution mitigation.
Nutrient Partitioning and Dynamics in Coriaria nepalensis Wall Dominated Shrublands of Degraded Hills of Kumaun Himalaya
Authors: Awasthi Pankaj , Bargali Kiran , Bargali Surendra Singh , Khatri Kavita , Jhariya Manoj Kumar
Published: May 2022

Coriaria nepalensis is one of the shrubs which have the ability to mitigate the frequency of perilous natural events or natural calamities. This paper elucidates the nutrient dynamics of C. nepalensis shrublands in degraded hills of Kumaun Himalaya. The average nutrient concentration (N, P, and K) in aboveground components of C. nepalensis was in the following order: Foliage > Twigs > Branches > Bole wood, whereas in belowground components the order was: Fine roots > Lateral roots > Stump root. The order of contribution to total nutrient storage in vegetation was: Tree > Herbs > Shrubs. The proportion of nutrients stored in the shrub layer was in the order: N > K > P. The soil stored a maximum proportion of nutrients at each site (79.48–87.54% N, 70.47–87.88% P, 74.33–88.27% K). Maximum nutrient storage in soil and vegetation was recorded for site 3 (Barapatthar) and minimum for site 1 (Pines). The uptake of N, P, and K by vegetation ranged from 428 to 1,353 kg ha–1 yr–1, 32–102 kg ha–1 yr–1, and 109–479 kg ha–1 yr–1, respectively. In the present study, the turnover time was 1.06–1.33 years for N, 1.03–1.15 years for P, and 1.02–1.13 years for K. Compartment models reflect the distribution of nutrients and net annual flux that will help to develop the management plan to maintain the fertility and productiveness of the degraded sites.
Epigenetic Alterations of DNA Methylation and miRNA Contribution to Lung Adenocarcinoma
Authors: Cai Wenhan , Jing Miao , Wen Jiaxin , Guo Hua , Xue Zhiqiang
Published: May 2022

This study focused on the epigenetic alterations of DNA methylation and miRNAs for lung adenocarcinoma (LUAD) diagnosis and treatment using bioinformatics analyses. DNA methylation data and mRNA and miRNA expression microarray data were obtained from The Cancer Genome Atlas (TCGA) database. The differentially methylated genes (DMGs), differentially expressed genes (DEGs), and differentially expressed miRNAs were analyzed by using the limma package. The DAVID database performed GO and KEGG pathway enrichment analyses. Using STRING and Cytoscape, we constructed the protein–protein interaction (PPI) network and achieved visualization. The online analysis tool CMap was used to identify potential small-molecule drugs for LUAD. In LUAD, 607 high miRNA-targeting downregulated genes and 925 low miRNA-targeting upregulated genes, as well as 284 hypermethylated low-expression genes and 315 hypomethylated high-expression genes, were obtained. They were mainly enriched in terms of pathways in cancer, neuroactive ligand–receptor interaction, cAMP signaling pathway, and cytosolic DNA-sensing pathway. In addition, 40 upregulated and 84 downregulated genes were regulated by both aberrant alternations of DNA methylation and miRNAs. Five small-molecule drugs were identified as a potential treatment for LUAD, and five hub genes (SLC2A1,PAX6,LEP,KLF4, andFGF10) were found in PPI, and two of them (SLC2A1andKLF4) may be related to the prognosis of LUAD. In summary, our study identified a series of differentially expressed genes associated with epigenetic alterations of DNA methylation and miRNA in LUAD. Five small-molecule drugs and five hub genes may be promising drugs and targets for LUAD treatment.
Comprehensive Analysis of circRNAs, miRNAs, and mRNAs Expression Profiles and ceRNA Networks in Decidua of Unexplained Recurrent Spontaneous Abortion
Authors: Liu Xiaohua , Wu Jiabao , Nie Hua , Zhu Xiaoli , Song Ge , Han Lu , Qin Weibing
Published: May 2022

The diagnosis and treatment of unexplained recurrent spontaneous abortion (URSA) are subject to debate, because the exact underlying mechanisms remain unclear. To address this issue, we elucidated the expression profiles of dysregulated circRNAs, miRNAs, and mRNAs and constructed circRNA-associated competitive endogenous RNA (ceRNA) networks by comparing the decidua of URSA with that of normal early pregnancy (NEP) using RNA-sequencing. In total, 550 mRNAs, 88 miRNAs, and 139 circRNAs were differentially expressed (DE) in decidua of URSA. Functional annotation revealed that DE mRNAs as well as potential target genes of DE miRNAs and DE circRNAs are mainly involved in immunologic function, such as antigen processing and presentation, allograft rejection, and T cell receptor signaling pathway. In addition, the top hub genes, includingCCL4, DDX58, CXCL10, CXCL9, MX1, CD44, RPS2, SOCS3, RPS3A,andCXCL11, were identified. The mRNAs involved in ceRNA network were enriched in complement and coagulation cascades and protein processing in the endoplasmic reticulum. We found that circRNAs in the ceRNA network, which acted as decoys for hsa-miR-204-5p, were positively correlated withMFGE8expression. Collectively, the results demonstrated that circRNAs, miRNAs, and mRNAs were aberrantly expressed in the decidua of patients with URSA and played a potential role in the development of URSA. Thus, the establishment of the ceRNA network may profoundly affect the diagnosis and therapy of URSA in the future.
StarGazer: A Hybrid Intelligence Platform for Drug Target Prioritization and Digital Drug Repositioning Using Streamlit
Authors: Lee Chiyun , Lin Junxia , Prokop Andrzej , Gopalakrishnan Vancheswaran , Hanna Richard N. , Papa Eliseo , Freeman Adrian , Patel Saleha , Yu Wen , Huhn Monika , Sheikh Abdul-Saboor , Tan Keith , Sellman Bret R. , Cohen Taylor , Mangion Jonathan , Khan Faisal M. , Gusev Yuriy , Shameer Khader
Published: May 2022

Target prioritization is essential for drug discovery and repositioning. Applying computational methods to analyze and process multi-omics data to find new drug targets is a practical approach for achieving this. Despite an increasing number of methods for generating datasets such as genomics, phenomics, and proteomics, attempts to integrate and mine such datasets remain limited in scope. Developing hybrid intelligence solutions that combine human intelligence in the scientific domain and disease biology with the ability to mine multiple databases simultaneously may help augment drug target discovery and identify novel drug-indication associations. We believe that integrating different data sources using a singular numerical scoring system in a hybrid intelligent framework could help to bridge these different omics layers and facilitate rapid drug target prioritization for studies in drug discovery, development or repositioning. Herein, we describe our prototype of the StarGazer pipeline which combines multi-source, multi-omics data with a novel target prioritization scoring system in an interactive Python-based Streamlit dashboard. StarGazer displays target prioritization scores for genes associated with 1844 phenotypic traits, and is available via https://github.com/AstraZeneca/StarGazer.
Comparative Analysis of the Chloroplast Genome for Aconitum Species: Genome Structure and Phylogenetic Relationships
Authors: Xia Conglong , Wang Manjiong , Guan Yunhui , Li Jian
Published: May 2022

Aconitum is an important medicinal group of the Ranunculaceae family and has been used as conventional medicine in Bai, Yi, and other ethnic groups of China. There are about 350 Aconitum species globally and about 170 species in China. It is challenging to identify the species in morphology, and the lack of molecular biology information hinders the identification and rational utilization of the germplasm of this genus. Therefore, it is necessary to increase the molecular data of Aconitum species. This paper acquired the complete chloroplast (CP) genome sequence of ten medicinal plants of Aconitum species from Yunnan by Illumina paired-end (PE) sequencing technology and compared it with other species in the same family and genus. These CP genomes exhibited typical circular quadripartite structure, and their sizes ranged from 155,475 (A. stylosum) to 155,921 bp (A. vilmoinianum), including a large single-copy region (LSC), a small single-copy region (SSC), and two inverted repeat regions (IRs). Their gene content, order, and GC content (38.1%) were similar. Moreover, their number of genes ranged from 129 (A. vilmoinianum) to 132 (A. ramulosum), including 83 to 85 protein-coding genes (PCGs), 37 tRNA genes (tRNAs), eight rRNA genes (rRNAs), and two pseudogenes. In addition, we performed repeated sequence analysis, genomic structure, and comparative analysis using 42 Aconitum chloroplast genomes, including ten Aconitum chloroplast genomes and other sequenced Aconitum species. A total of 48–79 simple sequence repeats (SSRs) and 17 to 77 long repeat sequences were identified. IR regions showed higher variability than the SSC region and LSC region. Seven mutational hotspots were screened out, including trnK-UUU-trnQ-UGG, psbD, ndhJ-ndhK, clpP, psbH-petB, ycf1, and trnA-UGC-trnI-GAU, respectively. The phylogenetic trees of ten Aconitum species and other Aconitum species revealed that the complete CP genome was beneficial in determining the complex phylogenetic relationships among Aconitum species. This study provides a potential molecular marker and genomic resource for phylogeny and species identification of Aconitum species and an important reference and basis for Ranunculaceae species identification and phylogeny.
Expression and Secretion of Circular RNAs in the Parasitic Nematode, Ascaris suum
Authors: Minkler Sarah J. , Loghry-Jansen Hannah J. , Sondjaja Noelle A. , Kimber Michael J.
Published: May 2022

Circular RNAs (circRNAs) are a recently identified RNA species with emerging functional roles as microRNA (miRNA) and protein sponges, regulators of gene transcription and translation, and modulators of fundamental biological processes including immunoregulation. Relevant to this study, circRNAs have recently been described in the parasitic nematode, Haemonchus contortus, suggesting they may have functionally important roles in parasites. Given their involvement in regulating biological processes, a better understanding of their role in parasites could be leveraged for future control efforts. Here, we report the use of next-generation sequencing to identify 1,997 distinct circRNAs expressed in adult female stages of the gastrointestinal parasitic nematode, Ascaris suum. We describe spatial expression in the ovary-enriched and body wall muscle, and also report circRNA presence in extracellular vesicles (EVs) secreted by the parasite into the external environment. Further, we used an in-silico approach to predict that a subset of Ascaris circRNAs bind both endogenous parasite miRNAs as well as human host miRNAs, suggesting they could be functional as both endogenous and exogenous miRNA sponges to alter gene expression. There was not a strong correlation between Ascaris circRNA length and endogenous miRNA interactions, indicating Ascaris circRNAs are enriched for Ascaris miRNA binding sites, but that human miRNAs were predicted form a more thermodynamically stable bond with Ascaris circRNAs. These results suggest that secreted circRNAs could be interacting with host miRNAs at the host-parasite interface and influencing host gene transcription. Lastly, although we have previously found that therapeutically relevant concentrations of the anthelmintic drug ivermectin inhibited EV release from parasitic nematodes, we did not observe a direct effect of ivermectin treatment on Ascaris circRNAs expression or secretion.
IgG Autoantibodies Against IgE from Atopic Dermatitis Can Induce the Release of Cytokines and Proinflammatory Mediators from Basophils and Mast Cells
Authors: Poto Remo , Quinti Isabella , Marone Gianni , Taglialatela Maurizio , de Paulis Amato , Casolaro Vincenzo , Varricchi Gilda
Published: May 2022

IgE-mediated release of proinflammatory mediators and cytokines from basophils and mast cells is a central event in allergic disorders. Several groups of investigators have demonstrated the presence of autoantibodies against IgE and/or FcεRI in patients with chronic spontaneous urticaria. By contrast, the prevalence and functional activity of anti-IgE autoantibodies in atopic dermatitis (AD) are largely unknown. We evaluated the ability of IgG anti-IgE from patients with AD to induce thein vitroIgE-dependent activation of human basophils and skin and lung mast cells. Different preparations of IgG anti-IgE purified from patients with AD and rabbit IgG anti-IgE were compared for their triggering effects on thein vitrorelease of histamine and type 2 cytokines (IL-4, IL-13) from basophils and of histamine and lipid mediators (prostaglandin D2and cysteinyl leukotriene C4) from human skin and lung mast cells. One preparation of human IgG anti-IgE out of six patients with AD induced histamine release from basophils, skin and lung mast cells. This preparation of human IgG anti-IgE induced the secretion of cytokines and eicosanoids from basophils and mast cells, respectively. Human monoclonal IgE was a competitive antagonist of both human and rabbit IgG anti-IgE. Human anti-IgE was more potent than rabbit anti-IgE for IL-4 and IL-13 production by basophils and histamine, prostaglandin D2and leukotriene C4release from mast cells. Functional anti-IgE autoantibodies rarely occur in patients with AD. When present, they induce the release of proinflammatory mediators and cytokines from basophils and mast cells, thereby possibly contributing to sustained IgE-dependent inflammation in at least a subset of patients with this disorder.
Comprehensive Analysis of a Cancer-Immunity Cycle–Based Signature for Predicting Prognosis and Immunotherapy Response in Patients With Colorectal Cancer
Authors: Hou Yufang , Zhang Rixin , Zong Jinbao , Wang Weiqi , Zhou Mingxuan , Yan Zheng , Li Tiegang , Gan Wenqiang , Lv Silin , Zeng Zifan , Yang Min
Published: May 2022

Immune checkpoint blockade (ICB) has been recognized as a promising immunotherapy for colorectal cancer (CRC); however, most patients have little or no clinical benefit. This study aimed to develop a novel cancer-immunity cycle–based signature to stratify prognosis of patients with CRC and predict efficacy of immunotherapy. CRC samples from The Cancer Genome Atlas (TCGA) were used as the training set, while the RNA data from Gene Expression Omnibus (GEO) data sets and real-time quantitative PCR (RT-qPCR) data from paired frozen tissues were used for validation. We built a least absolute shrinkage and selection operator (LASSO)-Cox regression model of the cancer-immunity cycle–related gene signature in CRC. Patients who scored low on the risk scale had a better prognosis than those who scored high. Notably, the signature was an independent prognostic factor in multivariate analyses, and to improve prognostic classification and forecast accuracy for individual patients, a scoring nomogram was created. The comprehensive results revealed that the low-risk patients exhibited a higher degree of immune infiltration, a higher immunoreactivity phenotype, stronger expression of immune checkpoint–associated genes, and a superior response to ICB therapy. Furthermore, the risk model was closely related to the response to multiple chemotherapeutic drugs. Overall, we developed a reliable cancer-immunity cycle–based risk model to predict the prognosis, the molecular and immune status, and the immune benefit from ICB therapy, which may contribute greatly to accurate stratification and precise immunotherapy for patients with CRC.
Overview of Breastfeeding Under COVID-19 Pandemic
Authors: Pang Zehan , Hu Ruolan , Tian Lili , Lou Fuxing , Chen Yangzhen , Wang Shuqi , He Shiting , Zhu Shaozhou , An Xiaoping , Song Lihua , Liu Feitong , Tong Yigang , Fan Huahao
Published: May 2022

During the global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), pregnant and lactating women are at higher risk of infection. The potential of viral intrauterine transmission and vertical transmission by breastfeeding has raised wide concerns. Breastmilk is rich in nutrients that contribute to infant growth and development, and reduce the incidence rate of infant illness and death, as well as inhibit pathogens significantly, and protect infants from infection. Although it is controversial whether mothers infected with COVID-19 should continue to breastfeed, many countries and international organizations have provided recommendations and guidance for breastfeeding. This review presents the risks and benefits of breastfeeding for mothers infected with COVID-19, and the reasons for the absence of SARS-CoV-2 active virus in human milk. In addition, the antiviral mechanisms of nutrients in breastmilk, the levels of SARS-CoV-2 specific antibodies in breastmilk from COVID-19 infected mothers and vaccinated mothers are also summarized and discussed, aiming to provide some support and recommendations for both lactating mothers and infants to better deal with the COVID-19 pandemic.
Combined Effects of Hydrological Drought and Reduced Food Availability on the Decline of the Little Penguins in South Australia
Authors: Colombelli-Négrel Diane , Nur Darfiana , Auricht Hannah C. C. , Clarke Kenneth D. , Mosley Luke M. , Dann Peter
Published: May 2022

Droughts in many regions of the world are increasing in frequency and severity which, coupled with effects from anthropogenic water extraction and diversion, are reducing river discharges. Yet to date, few studies have investigated the impacts of hydrological droughts (i.e., reduced river outflows to the ocean) on seabirds. Here, we examined the consequences of the “Millennium Drought” on the local decline of an iconic Australian seabird, the little penguin (Eudyptula minor). We analysed monthly and annual penguin numbers in relation to river outflow, rainfall, the characteristics of the coastal waters (sea surface temperatures and chlorophyll-a concentrations), and local abundance of key predators and prey species. We found a negative association between monthly penguin numbers and both sea surface temperatures and river outflow. Annual penguin numbers were positively associated with southern garfish numbers (our local indicator of food availability) but negatively associated with annual chlorophyll-a concentrations. Our findings emphasizing the need for further research into the effect of hydrological droughts on seabird populations and for improved river management that account for potential downstream impacts on the coastal environment receiving freshwater from rivers.
Effect of Ecological Recovery on Macrophyte Dominance and Production in the Venice Lagoon
Authors: Sfriso Adriano , Buosi Alessandro , Sciuto Katia , Wolf Marion , Tomio Yari , Juhmani Abdul-Salam , Sfriso Andrea Augusto
Published: May 2022

In the last decade, the Venice Lagoon showed a significant environmental recovery that changed the assemblages of macroalgal and aquatic angiosperm dominant species and significantly increased the primary production. The decreasing of anthropogenic impacts, such as eutrophication and clam harvesting, favored a strong reduction of Ulvaceae, replaced by species with higher ecological value, and the recolonization of aquatic angiosperms. Consequently, hypo-anoxic conditions, once frequently occurring in the lagoon, have been considerably reduced and aquatic angiosperms have recolonized the area, covering 94.8 km2 in comparison to the 55.9 km2 recorded in 2003 (+70%). Cymodocea nodosa, Zostera marina, and Zostera noltei expanded by 37.5%, 44.6%, and 191%, respectively, with a significant increase in biomass and primary production. In late spring 2018, angiosperms showed a standing crop of approximately 372 ktonnes (+77%) and a net primary production of approximately 1189 ktonnes FW (+67%). In the meantime, Ruppia cirrhosa, which since the 1980s had disappeared from the lagoon areas subjected to tidal expansion, but was still present in some fishing valleys, recolonized the bottoms of the northern lagoon with meadows of over 6 km2; this accounted for a standing crop and net primary production of 8.9 and 18.0 ktonnes, respectively. Based on surveys carried out in 2021, ecological conditions are still improving, and this is increasing both the biodiversity and the production of macroalgae and aquatic angiosperms.
SimStack: An Intuitive Workflow Framework
Authors: Rêgo Celso R. C. , Schaarschmidt Jörg , Schlöder Tobias , Penaloza-Amion Montserrat , Bag Saientan , Neumann Tobias , Strunk Timo , Wenzel Wolfgang
Published: May 2022

Establishing a fundamental understanding of the nature of materials via computational simulation approaches requires knowledge from different areas, including physics, materials science, chemistry, mechanical engineering, mathematics, and computer science. Accurate modeling of the characteristics of a particular system usually involves multiple scales and therefore requires the combination of methods from various fields into custom-tailored simulation workflows. The typical approach to developing patch-work solutions on a case-to-case basis requires extensive expertise in scripting, command-line execution, and knowledge of all methods and tools involved for data preparation, data transfer between modules, module execution, and analysis. Therefore multiscale simulations involving state-of-the-art methods suffer from limited scalability, reproducibility, and flexibility. In this work, we present the workflow framework SimStack that enables rapid prototyping of simulation workflows involving modules from various sources. In this platform, multiscale- and multimodule workflows for execution on remote computational resources are crafted via drag and drop, minimizing the required expertise and effort for workflow setup. By hiding the complexity of high-performance computations on remote resources and maximizing reproducibility, SimStack enables users from academia and industry to combine cutting-edge models into custom-tailored, scalable simulation solutions.
Sex Cord-Stromal Tumors of Testis: A Clinicopathologic and Follow-Up Study of 15 Cases in a High-Volume Institute of China
Authors: Huang Yin , Chen Bo , Cao Dehong , Chen Zeyu , Li Jin , Guo Jianbing , Dong Qiang , Wei Qiang , Liu Liangren
Published: May 2022

Objectives

To report the first series of testicular sex cord-stromal tumors (TSCSTs) with detailed clinicopathologic findings and long-term follow-up in the Chinese population.

Patients and Methods

From 2008 to 2018, 15 patients with TSCST were included in our study. The tumors were analyzed for epidemiological parameters, clinical characteristics, tumor markers, therapy, and follow-up data.

Results

The median age of the patients was 28 years (range, 13–80 years). Para-aortic lymph node metastases were detected in 2 patients after radiological evaluation. Orchiectomy was performed in all patients, and the median diameter of the tumor was 1.5 cm (range, 0.5–5.0 cm). Nine Leydig cell tumors (LCTs), 5 Sertoli cell tumors (SCTs), and 1 unclassified type were confirmed after pathologic evaluation. Thirteen patients (86.7%) were categorized as stage I, and 2 patients (13.3%) were categorized as stage II. The median clinical follow-up was 39.0 months (range, 5–97 months), which showed 10 alive patients, such as 1 patient with progression at 40 months after orchiectomy. The 3- and 5-year progression-free survivals were 100 and 90.0%, respectively.

Conclusion

Testicular sex cord-stromal tumor at stages I and II is a rare subtype with benign behavior and a favorable prognosis in the Chinese population. However, lymph node metastases may be the dominant risk factor for patients with TSCST.
Building Efficient CNN Architectures for Histopathology Images Analysis: A Case-Study in Tumor-Infiltrating Lymphocytes Classification
Authors: Meirelles André L. S. , Kurc Tahsin , Kong Jun , Ferreira Renato , Saltz Joel H. , Teodoro George
Published: May 2022

Background

Deep learning methods have demonstrated remarkable performance in pathology image analysis, but they are computationally very demanding. The aim of our study is to reduce their computational cost to enable their use with large tissue image datasets.

Methods

We propose a method called Network Auto-Reduction (NAR) that simplifies a Convolutional Neural Network (CNN) by reducing the network to minimize the computational cost of doing a prediction. NAR performs a compound scaling in which the width, depth, and resolution dimensions of the network are reduced together to maintain a balance among them in the resulting simplified network. We compare our method with a state-of-the-art solution called ResRep. The evaluation is carried out with popular CNN architectures and a real-world application that identifies distributions of tumor-infiltrating lymphocytes in tissue images.

Results

The experimental results show that both ResRep and NAR are able to generate simplified, more efficient versions of ResNet50 V2. The simplified versions by ResRep and NAR require 1.32× and 3.26× fewer floating-point operations (FLOPs), respectively, than the original network without a loss in classification power as measured by the Area under the Curve (AUC) metric. When applied to a deeper and more computationally expensive network, Inception V4, NAR is able to generate a version that requires 4× lower than the original version with the same AUC performance.

Conclusions

NAR is able to achieve substantial reductions in the execution cost of two popular CNN architectures, while resulting in small or no loss in model accuracy. Such cost savings can significantly improve the use of deep learning methods in digital pathology. They can enable studies with larger tissue image datasets and facilitate the use of less expensive and more accessible graphics processing units (GPUs), thus reducing the computing costs of a study.