bluuebunny/crossref_metadata_2025 huggingface dataset:
Measuring the Usability and Quality of Explanations of a Machine Learning Web-Based Tool for Oral Tongue Cancer Prognostication
Authors: Alabi Rasheed Omobolaji , Almangush Alhadi , Elmusrati Mohammed , Leivo Ilmo , Mäkitie Antti
Published: July 2022

Background: Machine learning models have been reported to assist in the proper management of cancer through accurate prognostication. Integrating such models as a web-based prognostic tool or calculator may help to improve cancer care and assist clinicians in making oral cancer management-related decisions. However, none of these models have been recommended in daily practices of oral cancer due to concerns related to machine learning methodologies and clinical implementation challenges. An instance of the concerns inherent to the science of machine learning is explainability. Objectives: This study measures the usability and explainability of a machine learning-based web prognostic tool that was designed for prediction of oral tongue cancer. We used the System Usability Scale (SUS) and System Causability Scale (SCS) to evaluate the explainability of the prognostic tool. In addition, we propose a framework for the evaluation of post hoc explainability of web-based prognostic tools. Methods: A SUS- and SCS-based questionnaire was administered amongst pathologists, radiologists, cancer and machine learning researchers and surgeons (n = 11) to evaluate the quality of explanations offered by the machine learning-based web prognostic tool to address the concern of explainability and usability of these models for cancer management. The examined web-based tool was developed by our group and is freely available online. Results: In terms of the usability of the web-based tool using the SUS, 81.9% (45.5% strongly agreed; 36.4% agreed) agreed that neither the support of a technical assistant nor a need to learn many things were required to use the web-based tool. Furthermore, 81.8% agreed that the evaluated web-based tool was not cumbersome to use (usability). The average score for the SCS (explainability) was 0.74. A total of 91.0% of the participants strongly agreed that the web-based tool can assist in clinical decision-making. These scores indicated that the examined web-based tool offers a significant level of usability and explanations about the outcome of interest. Conclusions: Integrating the trained and internally and externally validated model as a web-based tool or calculator is poised to offer an effective and easy approach towards the usage and acceptance of these models in the future daily practice. This approach has received significant attention in recent years. Thus, it is important that the usability and explainability of these models are measured to achieve such touted benefits. A usable and well-explained web-based tool further brings the use of these web-based tools closer to everyday clinical practices. Thus, the concept of more personalized and precision oncology can be achieved.
Construction and Optimization of an Ecological Security Pattern Based on the MCR Model: A Case Study of the Minjiang River Basin in Eastern China
Authors: Wang Xinke , Xie Xiangqun , Wang Zhenfeng , Lin Hong , Liu Yan , Xie Huili , Liu Xingzhao
Published: July 2022

The Minjiang River Basin is one of the first pilot areas for ecological conservation and the restoration of mountain–river–forest–farmland–lake–grass in China. Taking the Minjiang River Basin as an example, this paper selected the importance of ecosystem service functions and ecological sensitivity to evaluate the ecological environment and identify ecological sources. Furthermore, we constructed an ecological resistance surface using artificial and natural interference factors. Through a minimum cumulative resistance model (MCR), the ecological security pattern (ESP) of “two barriers, one belt, many corridors, and many spots” was constructed. Research shows that: (1) In total, 43 ecological sources were identified, with a total area of 523 km2, accounting for 0.6% of the total land area. These were mainly distributed in the southwest and northwest of the Minjiang River Basin, such as in Zhangping, covered forest land, and cultivated land. (2) The connectivity of the network was low, and the spatial distribution of the ecological pinch points was uneven. A total of 118 ecological corridors and 22 important ecological pinch points were identified. The total length of the ecological corridor is 3,732,051.88 km, which is dense on the left side and sparse on the right side. (3) The ecological restoration area was composed of a low ecological safety area and a lower ecological safety area; the ecological control area was composed of a medium ecological safety area and a higher ecological safety area; and the ecological conservation area was composed of a high ecological safety area, at 6.5%, 27.7%, and 65.8%, respectively. Constructing the ESP of the Minjiang River Basin is important for promoting harmonious socioeconomic development and ecological protection. In addition, it can provide a reference basis for other experimental areas of mountain–river–forest–farmland–lake–grass.
The Nonlinear Influence of Environmental Regulation on the Transformation and Upgrading of Industrial Structure
Authors: Guan Shuai , Liu Jinquan , Liu Yongfu , Du Mingze
Published: July 2022

This paper measures the transformation and upgrading of industrial structure from two aspects of rationalization and upgrading of industrial structure, and empirically analyzes the impact of environmental regulation on industrial structure transformation and upgrading by using data of 29 provinces in China from 2004 to 2015. It was found that there is a significant nonlinear effect between environmental regulation and the transformation and upgrading of industrial structure. Specifically, environmental regulation is not conducive to the rational development of industrial structure, but with the continuous improvement of economic development level and human capital level, the inhibitory effect of environmental regulation on the rationalization of industrial structure is gradually weakened. The influence coefficient of environmental regulation on the rationalization of industrial structure is 0.0619~0.2648. Moreover, environmental regulation effectively drives the upgrading of industrial structure, and when the level of economic development and human capital are higher than the threshold, the role of environmental regulation in promoting the high development of industrial structure is gradually enhanced. The influence coefficient of environmental regulation on the upgrading of industrial structure is 0.0540~0.5626. Therefore, it is of great significance to formulate appropriate environmental regulation policies according to local conditions in the transformation and upgrading of industrial structure.
A Theoretical Perspective on Why Socioeconomic Health Inequalities Are Persistent: Building the Case for an Effective Approach
Authors: Wilderink Lisa , Bakker Ingrid , Schuit Albertine , Seidell Jacob , Pop Ioana , Renders Carry
Published: July 2022

Despite policy intentions and many interventions aimed at reducing socioeconomic health inequalities in recent decades in the Netherlands and other affluent countries, these inequalities have not been reduced. Based on a narrative literature review, this paper aims to increase insight into why socioeconomic health inequalities are so persistent and build a way forward for improved approaches from a theoretical perspective. Firstly, we present relevant theories focusing on individual determinants of health-related behaviors. Thereafter, we present theories that take into account determinants of the individual level and the environmental level. Lastly, we show the complexity of the system of individual determinants, environmental determinants and behavior change for low socioeconomic position (SEP) groups and describe the next steps in developing and evaluating future effective approaches. These steps include systems thinking, a complex whole-system approach and participation of all stakeholders in system change.
STSGAN: Spatial-Temporal Global Semantic Graph Attention Convolution Networks for Urban Flow Prediction
Authors: Zhou Junwei , Qin Xizhong , Yu Kun , Jia Zhenhong , Du Yan
Published: July 2022

Accurate urban traffic flow prediction plays a vital role in Intelligent Transportation System (ITS). The complex long-term and long-range spatiotemporal correlations of traffic flow pose a significant challenge to the prediction task. Most current research methods focus only on spatial correlations in local areas, ignoring global geographic contextual information. It is challenging to capture spatial information from distant nodes using shallow graph neural networks (GNNs) to model long-range spatial correlations. To handle this problem, we design a novel spatiotemporal global semantic graph-attentive convolutional network model (STSGAN), which is a deep-level network to achieve the simultaneous modelling of spatiotemporal correlations. First, we propose a graph-attentive convolutional network (GACN) to extract the importance of different spatial features and learn the spatial correlation of local regions and the global spatial semantic information. The temporal causal convolution structure (TCN) is utilized to capture the causal relationships between long-short times, thus enabling an integrated consideration of local and overall spatiotemporal correlations. Several experiments are conducted on two real-world traffic flow datasets, and the results show that our approach outperforms several state-of-the-art baselines.
Design, Synthesis and Biological Characterization of Histone Deacetylase 8 (HDAC8) Proteolysis Targeting Chimeras (PROTACs) with Anti-Neuroblastoma Activity
Authors: Darwish Salma , Ghazy Ehab , Heimburg Tino , Herp Daniel , Zeyen Patrik , Salem-Altintas Rabia , Ridinger Johannes , Robaa Dina , Schmidtkunz Karin , Erdmann Frank , Schmidt Matthias , Romier Christophe , Jung Manfred , Oehme Ina , Sippl Wolfgang
Published: July 2022

In addition to involvement in epigenetic gene regulation, histone deacetylases (HDACs) regulate multiple cellular processes through mediating the activity of non-histone protein substrates. The knockdown of HDAC8 isozyme is associated with the inhibition of cell proliferation and apoptosis enhancement in several cancer cell lines. As shown in several studies, HDAC8 can be considered a potential target in the treatment of cancer forms such as childhood neuroblastoma. The present work describes the development of proteolysis targeting chimeras (PROTACs) of HDAC8 based on substituted benzhydroxamic acids previously reported as potent and selective HDAC8 inhibitors. Within this study, we investigated the HDAC8-degrading profiles of the synthesized PROTACs and their effect on the proliferation of neuroblastoma cells. The combination of in vitro screening and cellular testing demonstrated selective HDAC8 PROTACs that show anti-neuroblastoma activity in cells.
Role of PsnWRKY70 in Regulatory Network Response to Infection with Alternaria alternata (Fr.) Keissl in Populus
Authors: Wang Wei , Bai Xiang-Dong , Chen Kun , Gu Chen-Rui , Yu Qi-Bin , Jiang Jing , Liu Gui-Feng
Published: July 2022

WRKY is an important complex family of transcription factors involved in plant immune responses. Among them, WRKY70 plays an important role in the process of the plant defense response to the invasion of pathogens. However, the defense mechanism of PsnWRKY70 is not clear in Populus nigra. In this study, we showed that PsnWRKY70-overexpression lines (OE) had fewer leaf blight symptoms than PsnWRKY70-repressing lines (RE). PsnWRKY70 activated MAP kinase cascade genes (PsnM2K4, PsnMPK3, PsnM3K18), calcium channel proteins-related genes (PsnCNG3, PsnCNGC1, PsnCNG4), and calcium-dependent protein kinases genes (PsnCDPKL, PsnCDPKW, PsnCDPKS, PsnCDPKQ). Furthermore, 129 genes of PsnWRKY70 putative genome-wide direct targets (DTGs) were identified by using transcriptome (RNA-seq) and DNA affinity purification sequencing (DAP-seq). PsnWRKY70 directly binds to the promoters of homologous genes and LRR domain proteins to promote the expression of WRKY6, WRKY18, WRKY22, and WRKY22–1, LRR domain proteins LRR8, LRR-RLK, ADR1-like 2, NB-ARC, etc. Our study suggests that PsnWRKY70 enhances the resistance of A. alternata in poplar by activating genes in both pathogen-associated molecular pattern-triggered immunity (PTI) and effector-triggered immunity (ETI).
AtGAP1 Promotes the Resistance to Pseudomonas syringae pv. tomato DC3000 by Regulating Cell-Wall Thickness and Stomatal Aperture in Arabidopsis
Authors: Cheng Sau-Shan , Ku Yee-Shan , Cheung Ming-Yan , Lam Hon-Ming
Published: July 2022

GTP is an important signaling molecule involved in the growth, development, and stress adaptability of plants. The functions are mediated via binding to GTPases which are in turn regulated by GTPase-activating proteins (GAPs). Satellite reports have suggested the positive roles of GAPs in regulating ABA signaling and pathogen resistance in plants. However, the molecular mechanisms that bring forth the pathogen resistance have remained unclear. In this study, we demonstrated that the expression of AtGAP1 was inducible by Pseudomonas syringae pv. tomato DC3000 (Pst DC3000). The overexpression of AtGAP1 in Arabidopsis promoted the expression of PR1 and the resistance to Pst DC3000. Proteomic analyses revealed the enhanced accumulation of cell-wall-modifying proteins as a result of AtGAP1 overexpression. By microscopic analyses, we showed that the overexpression of AtGAP1 resulted in increased thickness of the mesophyll cell wall and reduced stomatal aperture, which are effective strategies for restricting the entry of foliar pathogens. Altogether, we demonstrated that AtGAP1 increases the resistance to Pst DC3000 in Arabidopsis by promoting cellular strategies that restrict the entry of pathogens into the cells. These results point to a future direction for studying the modes of action of GAPs in regulating plant cell structures and disease resistance.
Rag1 and Rag2 Gene Expressions Identify Lymphopoietic Tissues in Larvae of Rice-Field Eel (Monopterus albus)
Authors: Liu Yuchen , Jiang Nan , Liu Wenzhi , Zhou Yong , Xue Mingyang , Zhong Qiwang , Li Zhong , Fan Yuding
Published: July 2022

In immature lymphocytes, recombination activating genes 1 and 2 are necessary for antigen receptor V (D) J recombination, representing immature lymphocyte biomarkers. Herein, we cloned and sequenced rice-field eel rag1 and rag2 genes. Their expressions in the thymus, liver, and kidney were significant from 0 days post hatching (dph) to 45 dph, peaking at 45 dph in these three tissues. In situ hybridization detected high rag1 and rag2 expressions in the liver, kidney, and thymus of rice-field eel from 2 to 45 dph, suggesting that multiple tissues of rice-field eel contain lymphocyte lineage cells and undergo lymphopoiesis. Tissue morphology was used to observe lymphopoiesis development in these three tissues. The thymus primordium began to develop at 2 dph, while the kidney and liver have generated. Our findings verified that the thymus is the primary lymphopoietic tissue and suggested that, in rice-field eel, lymphocyte differentiation also occurs in the liver and kidney.
Bacillus Calmette–Guérin-Induced Human Mast Cell Activation Relies on IL-33 Priming
Authors: Garcia-Rodriguez Karen M. , Goenka Anu , Thomson Darren D. , Bahri Rajia , Tontini Chiara , Salcman Barbora , Hernandez-Pando Rogelio , Bulfone-Paus Silvia
Published: July 2022

Bacillus Calmette–Guérin (BCG) vaccine is an attenuated strain of Mycobacterium bovis that provides weak protection against tuberculosis (TB). Mast cells (MCs) are tissue-resident immune cells strategically that serve as the first line of defence against pathogenic threats. In this study, we investigated the response of human MCs (hMCs) to BCG. We found that naïve hMCs exposed to BCG did not secrete cytokines, degranulate, or support the uptake and intracellular growth of bacteria. Since we could show that in hMCs IL-33 promotes the transcription of host-pathogen interaction, cell adhesion and activation genes, we used IL-33 for cell priming. The treatment of hMCs with IL-33, but not IFN-γ, before BCG stimulation increased IL-8, MCP-1 and IL-13 secretion, and induced an enhanced expression of the mycobacteria-binding receptor CD48. These effects were comparable to those caused by the recombinant Mycobacterium tuberculosis (Mtb) 19-KDa lipoprotein. Finally, stimulation of hMCs with IL-33 incremented MC-BCG interactions. Thus, we propose that IL-33 may improve the immunogenicity of BCG vaccine by sensitising hMCs.
Modelling Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD) Using Mice and Zebrafish
Authors: Dougnon Godfried , Matsui Hideaki
Published: July 2022

Autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD) are two debilitating neurodevelopmental disorders. The former is associated with social impairments whereas the latter is associated with inattentiveness, hyperactivity, and impulsivity. There is recent evidence that both disorders are somehow related and that genes may play a large role in these disorders. Despite mounting human and animal research, the neurological pathways underlying ASD and ADHD are still not well understood. Scientists investigate neurodevelopmental disorders by using animal models that have high similarities in genetics and behaviours with humans. Mice have been utilized in neuroscience research as an excellent animal model for a long time; however, the zebrafish has attracted much attention recently, with an increasingly large number of studies using this model. In this review, we first discuss ASD and ADHD aetiology from a general point of view to their characteristics and treatments. We also compare mice and zebrafish for their similarities and discuss their advantages and limitations in neuroscience. Finally, we summarize the most recent and existing research on zebrafish and mouse models of ASD and ADHD. We believe that this review will serve as a unique document providing interesting information to date about these models, thus facilitating research on ASD and ADHD.
Non-Functionalized Gold Nanoparticles Inhibit Human Papillomavirus (HPV) Infection
Authors: Valencia-Reséndiz Diana Gabriela , Villegas Atenea , Bahena Daniel , Palomino Kenia , Cornejo-Bravo Jose Manuel , Quintanar Liliana , Palomino-Vizcaino Giovanni , Alvarez-Salas Luis Marat
Published: July 2022

The spontaneous interaction between human papillomavirus type 16 (HPV16) L1 virus-like particles (VLPs) and non-functionalized gold nanoparticles (nfGNPs) interferes with the nfGNPs’ salt-induced aggregation, inhibiting the red–blue color shift in the presence of NaCl. Electron microscopy and competition studies showed that color-shift inhibition is a consequence of direct nfGNP–VLP interaction and, thus, may produce a negative impact on the virus entry cell process. Here, an in vitro infection system based on the HPV16 pseudovirus (PsV) was used to stimulate the natural infection process in vitro. PsVs carry a pseudogenome with a reporter gene, resulting in a fluorescent signal when PsVs infect a cell, allowing quantification of the viral infection process. Aggregation assays showed that nfGNP-treated PsVs also inhibit color shift in the presence of NaCl. High-resolution microscopy confirmed nfGNP–PsV complex formation. In addition, PsVs can interact with silver nanoparticles, suggesting a generalized interaction of metallic nanoparticles with HPV16 capsids. The treatment of PsVs with nfGNPs produced viral infection inhibition at a higher level than heparin, the canonical inhibitor of HPV infection. Thus, nfGNPs can efficiently interfere with the HPV16 cell entry process and may represent a potential active component in prophylactic formulations to reduce the risk of HPV infection.
Mitochondrial Dysfunction Affects the Synovium of Patients with Rheumatoid Arthritis and Osteoarthritis Differently
Authors: Jávor Péter , Mácsai Attila , Butt Edina , Baráth Bálint , Jász Dávid Kurszán , Horváth Tamara , Baráth Bence , Csonka Ákos , Török László , Varga Endre , Hartmann Petra
Published: July 2022

There is growing evidence regarding the role of mitochondrial dysfunction in osteoarthritis (OA) and rheumatoid arthritis (RA). However, quantitative comparison of synovial mitochondrial derangements in these main arthritis forms is missing. A prospective clinical study was conducted on adult patients undergoing knee surgery. Patients were allocated into RA and OA groups based on disease-specific clinical scores, while patients without arthritis served as controls. Synovial samples were subjected to high-resolution respirometry to analyze mitochondrial functions. From the total of 814 patients, 109 cases were enrolled into the study (24 RA, 47 OA, and 38 control patients) between 1 September 2019 and 31 December 2021. The decrease in complex I-linked respiration and dyscoupling of mitochondria were characteristics of RA patients, while both arthritis groups displayed reduced OxPhos activity compared to the control group. However, no significant difference was found in complex II-related activity between the OA and RA groups. The cytochrome C release and H2O2 formation were increased in both arthritis groups. Mitochondrial dysfunction was present in both arthritis groups; however, to a different extent. Consequently, mitochondrial protective agents may have major benefits for arthritis patients. Based on our current study, we recommend focusing on respiratory complex I in rheumatoid arthritis research.
The Pro-Inflammatory Deletion Allele of the NF-κB1 Polymorphism Is Characterized by a Depletion of Subunit p50 in Sepsis
Authors: Marko Britta , Heurich Paulina , Thon Patrick , Zimmer Frieda , Bergmann Lars , Nowak Hartmuth , Rump Katharina , Koos Björn , Adamzik Michael , Unterberg Matthias , Rahmel Tim
Published: July 2022

The functionally important NF-κB1 promoter polymorphism (−94ins/delATTG) significantly shapes inflammation and impacts the outcome of sepsis. However, exploratory studies elucidating the molecular link of this genotype-dependent pattern are lacking. Accordingly, we analyzed lipopolysaccharide-stimulated peripheral blood mononuclear cells from both healthy volunteers (n = 20) and septic patients (n = 10). All individuals were genotyped for the −94ins/delATTG NF-κB1 promoter polymorphism. We found a diminished nuclear activity of the NF-κB subunit p50 in ID/DD genotypes after 48 h of lipopolysaccharide stimulation compared to II genotypes (p = 0.025). This was associated with higher TNF-α (p = 0.005) and interleukin 6 concentrations (p = 0.014) and an increased production of mitochondrial radical oxygen species in ID/DD genotypes (p = 0.001). Although ID/DD genotypes showed enhanced activation of mitochondrial biogenesis, they still had a significantly diminished cellular ATP content (p = 0.046) and lower mtDNA copy numbers (p = 0.010) compared to II genotypes. Strikingly, these findings were mirrored in peripheral blood mononuclear cells taken from septic patients. Our results emphasize the crucial aspect of considering NF-κB subunits in sepsis. We showed here that the deletion allele of the NF-κB1 (−94ins/delATTG) polymorphism was associated with the lower nuclear activity of subunit p50, which, in turn, was associated with aggravated inflammation and mitochondrial dysfunction.
The HIV-1 Gag Protein Displays Extensive Functional and Structural Roles in Virus Replication and Infectivity
Authors: Marie Veronna , Gordon Michelle Lucille
Published: July 2022

Once merely thought of as the protein responsible for the overall physical nature of the human immunodeficiency virus type 1 (HIV-1), the Gag polyprotein has since been elucidated to have several roles in viral replication and functionality. Over the years, extensive research into the polyproteins’ structure has revealed that Gag can mediate its own trafficking to the plasma membrane, it can interact with several host factors and can even aid in viral genome packaging. Not surprisingly, Gag has also been associated with HIV-1 drug resistance and even treatment failure. Therefore, this review provides an extensive overview of the structural and functional roles of the HIV-1 Gag domains in virion integrity, functionality and infectivity.
Genetic Background Matters: Population-Based Studies in Model Organisms for Translational Research
Authors: Olguín Valeria , Durán Anyelo , Las Heras Macarena , Rubilar Juan Carlos , Cubillos Francisco A. , Olguín Patricio , Klein Andrés D.
Published: July 2022

We are all similar but a bit different. These differences are partially due to variations in our genomes and are related to the heterogeneity of symptoms and responses to treatments that patients exhibit. Most animal studies are performed in one single strain with one manipulation. However, due to the lack of variability, therapies are not always reproducible when treatments are translated to humans. Panels of already sequenced organisms are valuable tools for mimicking human phenotypic heterogeneities and gene mapping. This review summarizes the current knowledge of mouse, fly, and yeast panels with insightful applications for translational research.
The Role of RNA Modification in HIV-1 Infection
Authors: Wang Shuqi , Li Huanxiang , Lian Zhengxing , Deng Shoulong
Published: July 2022

RNA plays an important role in biology, and more than 170 RNA modifications have been identified so far. Post-transcriptional modification of RNA in cells plays a crucial role in the regulation of its stability, transport, processing, and gene expression. So far, the research on RNA modification and the exact role of its enzymes is becoming more and more comprehensive. Human immunodeficiency virus 1 (HIV-1) is an RNA virus and the causative agent of acquired immunodeficiency syndrome (AIDS), which is one of the most devastating viral pandemics in history. More and more studies have shown that HIV has RNA modifications and regulation of its gene expression during infection and replication. This review focuses on several RNA modifications and their regulatory roles as well as the roles that different RNA modifications play during HIV-1 infection, in order to find new approaches for the development of anti-HIV-1 therapeutics.
Clinically Applicable Assessment of Tisagenlecleucel CAR T Cell Treatment by Digital Droplet PCR for Copy Number Variant Assessment
Authors: Gkazi Soragia Athina , Gravett Emma , Bautista Carla , Bartram Jack , Ghorashian Sara , Adams Stuart Paul
Published: July 2022

Chimeric antigen receptor (CAR) T cell therapy is an innovative immunotherapy for treating cancers in both children and adults with proven utility in numerous clinical trials. Significantly, some CAR T cell therapies have now been approved by relevant national regulatory bodies across numerous countries for clinical therapeutic use outside of clinical trials. One such recently licensed product is tisagenlecleucel, a CAR T therapy approved for the treatment of B-cell acute lymphoblastic leukemia (B-ALL) using autologous T cells from the patient. The genetically engineered T cells target a protein called CD19, common to B cells, through a CAR incorporating a 4-1BB costimulatory domain to improve response. Since tisagenlecleucel is now a standard of care treatment for B-ALL, it is clinically essential to be able to accurately monitor these CAR T cells in patients. Assessment of the copy number variant (CNV) of the CAR T cell products allows this within a clinically acceptable timeframe for optimal patient benefit. However, no standardized method with high reproducibility and efficiency has been described within a routine clinical laboratory setting. Here, we demonstrated a novel digital droplet PCR (ddPCR)-based methodology for the study of CNV (ddPCR-CNV) in 4-1BB CD19-specific CAR T cells with universal applicability across clinical diagnostic laboratories.
Genome-Wide Identification of TaSAUR Gene Family Members in Hexaploid Wheat and Functional Characterization of TaSAUR66-5B in Improving Nitrogen Use Efficiency
Authors: Lv Weizeng , He Xue , Guo Haojuan , Lan Haibin , Jiao Yanqing , Li Le , Lian Yanhao , Wang Zhiqiang , Xin Zeyu , Ren Yongzhe , Lin Tongbao
Published: July 2022

Excessive input of nitrogen fertilizer not only causes a great waste of resources but brings about a series of ecological and environmental problems. Although Small Auxin Up-regulated RNAs (SAURs) participate in diverse biological processes, the function of SAURs in the nitrogen starvation response has not been well-studied. Here, we identified 308 TaSAURs in wheat and divided them into 10 subfamilies. The promoter regions of most TaSAURs contain hormone responsive elements, and their expression levels change under the treatment of different hormones, such as IAA, MeJA, and ABA. Interestingly, overexpression of one of the TaSAUR family members, a nitrogen starvation responsive gene, TaSAUR66-5B, can promote the growth of Arabidopsis and wheat roots. In addition, overexpression of TaSAUR66-5B in Arabidopsis up-regulates the expression levels of auxin biosynthesis related genes, suggesting that overexpression TaSAUR66-5B may promote root growth by increasing the biosynthesis of auxin. Furthermore, overexpression of TaSAUR66-5B in wheat can increase the biomass and grain yields of transgenic plants, as well as the nitrogen concentration and accumulation of both shoots and grains, especially under low nitrogen conditions. This study provides important genomic information of the TaSAUR gene family and lays a foundation for elucidating the functions of TaSAURs in improving nitrogen utilization efficiency in wheat.
Plant Biomechanics—A Natural Transition from Molecular to Organ Scale
Authors: Kwiatkowska Dorota , Burian Agata
Published: July 2022

Plants are multicellular organisms of a unique structure because their tissues consist of two interwoven networks: a network of interconnected protoplasts that is embedded in a network of tightly joined cell walls [...]
A Focal Impact Model of Traumatic Brain Injury in Xenopus Tadpoles Reveals Behavioral Alterations, Neuroinflammation, and an Astroglial Response
Authors: Spruiell Eldridge Sydnee L. , Teetsel Jonathan F. K. , Torres Ray A. , Ulrich Christina H. , Shah Vrutant V. , Singh Devanshi , Zamora Melissa J. , Zamora Steven , Sater Amy K.
Published: July 2022

Traumatic Brain Injury (TBI) is a global driver of disability, and we currently lack effective therapies to promote neural repair and recovery. TBI is characterized by an initial insult, followed by a secondary injury cascade, including inflammation, excitotoxicity, and glial cellular response. This cascade incorporates molecular mechanisms that represent potential targets of therapeutic intervention. In this study, we investigate the response to focal impact injury to the optic tectum of Xenopus laevis tadpoles. This injury disrupts the blood-brain barrier, causing edema, and produces deficits in visually-driven behaviors which are resolved within one week. Within 3 h, injured brains show a dramatic transcriptional activation of inflammatory cytokines, upregulation of genes associated with inflammation, and recruitment of microglia to the injury site and surrounding tissue. Shortly afterward, astrocytes undergo morphological alterations and accumulate near the injury site, and these changes persist for at least 48 h following injury. Genes associated with astrocyte reactivity and neuroprotective functions also show elevated levels of expression following injury. Since our results demonstrate that the response to focal impact injury in Xenopus resembles the cellular alterations observed in rodents and other mammalian models, the Xenopus tadpole offers a new, scalable vertebrate model for TBI.
The Possible Role of Neural Cell Apoptosis in Multiple Sclerosis
Authors: Kennedy Peter G. E. , George Woro , Yu Xiaoli
Published: July 2022

The etiology of multiple sclerosis (MS), a demyelinating disease affecting the central nervous system (CNS), remains obscure. Although apoptosis of oligodendrocytes and neurons has been observed in MS lesions, the contribution of this cell death process to disease pathogenesis remains controversial. It is usually considered that MS-associated demyelination and axonal degeneration result from neuroinflammation and an autoimmune process targeting myelin proteins. However, experimental data indicate that oligodendrocyte and/or neuronal cell death may indeed precede the development of inflammation and autoimmunity. These findings raise the question as to whether neural cell apoptosis is the key event initiating and/or driving the pathological cascade, leading to clinical functional deficits in MS. Similarly, regarding axonal damage, a key pathological feature of MS lesions, the roles of inflammation-independent and cell autonomous neuronal processes need to be further explored. While oligodendrocyte and neuronal loss in MS may not necessarily be mutually exclusive, particular attention should be given to the role of neuronal apoptosis in the development of axonal loss. If proven, MS could be viewed primarily as a neurodegenerative disease accompanied by a secondary neuroinflammatory and autoimmune process.
Development of Injectable Calcium Sulfate and Self-Setting Calcium Phosphate Composite Bone Graft Materials for Minimally Invasive Surgery
Authors: Chiu Yu-Hsun , Chen I-Cheng , Su Chen-Ying , Tsai Hsin-Hua , Young Tai-Horng , Fang Hsu-Wei
Published: July 2022

The demand of bone grafting is increasing as the population ages worldwide. Although bone graft materials have been extensively developed over the decades, only a few injectable bone grafts are clinically available and none of them can be extruded from 18G needles. To overcome the existing treatment limitations, the aim of this study is to develop ideal injectable implants from biomaterials for minimally invasive surgery. An injectable composite bone graft containing calcium sulfate hemihydrate, tetracalcium phosphate, and anhydrous calcium hydrogen phosphate (CSH/CaP paste) was prepared with different CSH/CaP ratios and different concentrations of additives. The setting time, injectability, mechanical properties, and biocompatibility were evaluated. The developed injectable CSH/CaP paste (CSH/CaP 1:1 supplemented with 6% citric acid and 2% HPMC) presented good handling properties, great biocompatibility, and adequate mechanical strength. Furthermore, the paste was demonstrated to be extruded from a syringe equipped with 18G needles and exerted a great potential for minimally invasive surgery. The developed injectable implants with tissue repairing potentials will provide an ideal therapeutic strategy for minimally invasive surgery to apply in the treatment of maxillofacial defects, certain indications in the spine, inferior turbinate for empty nose syndrome (ENS), or reconstructive rhinoplasty.
Sphingolipid Catabolism and Glycerophospholipid Levels Are Altered in Erythrocytes and Plasma from Multiple Sclerosis Patients
Authors: Momchilova Albena , Pankov Roumen , Alexandrov Alexander , Markovska Tania , Pankov Stefan , Krastev Plamen , Staneva Galya , Vassileva Evgenia , Krastev Nikolai , Pinkas Adriana
Published: July 2022

Multiple sclerosis (MS) is an autoimmune, inflammatory, degenerative disease of the central nervous system. Changes in lipid metabolism have been suggested to play important roles in MS pathophysiology and progression. In this work we analyzed the lipid composition and sphingolipid-catabolizing enzymes in erythrocytes and plasma from MS patients and healthy controls. We observed reduction of sphingomyelin (SM) and elevation of its products—ceramide (CER) and shingosine (SPH). These changes were supported by the detected up-regulation of the activity of acid sphingomyelinase (ASM) in MS plasma and alkaline ceramidase (ALCER) in erythrocytes from MS patients. In addition, Western blot analysis showed elevated expression of ASM, but not of ALCER. We also compared the ratios between saturated (SAT), unsaturated (UNSAT) and polyunsaturated fatty acids and suggest, based on the significant differences observed for this ratio, that the UNSAT/SAT values could serve as a marker distinguishing erythrocytes and plasma of MS from controls. In conclusion, the application of lipid analysis in the medical practice would contribute to definition of more precise diagnosis, analysis of disease progression, and evaluation of therapeutic strategies. Based on the molecular changes of blood lipids in neurodegenerative pathologies, including MS, clinical lipidomic analytical approaches could become a promising contemporary tool for personalized medicine.
PcNRAMP1 Enhances Cadmium Uptake and Accumulation in Populus × canescens
Authors: Yu Wenjian , Deng Shurong , Chen Xin , Cheng Yao , Li Zhuorong , Wu Jiangting , Zhu Dongyue , Zhou Jing , Cao Yuan , Fayyaz Payam , Shi Wenguang , Luo Zhibin
Published: July 2022

Poplars are proposed for the phytoremediation of heavy metal (HM) polluted soil. Characterization of genes involved in HM uptake and accumulation in poplars is crucial for improving the phytoremediation efficiency. Here, Natural Resistance-Associated Macrophage Protein 1 (NRAMP1) encoding a transporter involved in cadmium (Cd) uptake and transport was functionally characterized in Populus × canescens. Eight putative PcNRAMPs were identified in the poplar genome and most of them were primarily expressed in the roots. The expression of PcNRAMP1 was induced in Cd-exposed roots and it encoded a plasma membrane-localized protein. PcNRAMP1 showed transport activity for Cd2+ when expressed in yeast. The PcNRAMP1-overexpressed poplars enhanced net Cd2+ influxes by 39–52% in the roots and Cd accumulation by 25–29% in aerial parts compared to the wildtype (WT). However, Cd-induced biomass decreases were similar between the transgenics and WT. Further analysis displayed that the two amino acid residues of PcNRAMP1, i.e., M236 and P405, play pivotal roles in regulating its transport activity for Cd2+. These results suggest that PcNRAMP1 is a plasma membrane-localized transporter involved in Cd uptake and transporting Cd from the roots to aerial tissues, and that the conserved residues in PcNRAMP1 are essential for its Cd transport activity in poplars.
Beneficial Effects of Theaflavins on Metabolic Syndrome: From Molecular Evidence to Gut Microbiome
Authors: Shi Meng , Lu Yuting , Wu Junling , Zheng Zhibing , Lv Chenghao , Ye Jianhui , Qin Si , Zeng Chaoxi
Published: July 2022

In recent years, many natural foods and herbs rich in phytochemicals have been proposed as health supplements for patients with metabolic syndrome (MetS). Theaflavins (TFs) are a polyphenol hydroxyl substance with the structure of diphenol ketone, and they have the potential to prevent and treat a wide range of MetS. However, the stability and bioavailability of TFs are poor. TFs have the marvelous ability to alleviate MetS through antiobesity and lipid-lowering (AMPK-FoxO3A-MnSOD, PPAR, AMPK, PI3K/Akt), hypoglycemic (IRS-1/Akt/GLUT4, Ca2+/CaMKK2-AMPK, SGLT1), and uric-acid-lowering (XO, GLUT9, OAT) effects, and the modulation of the gut microbiota (increasing beneficial gut microbiota such as Akkermansia and Prevotella). This paper summarizes and updates the bioavailability of TFs, and the available signaling pathways and molecular evidence on the functionalities of TFs against metabolic abnormalities in vitro and in vivo, representing a promising opportunity to prevent MetS in the future with the utilization of TFs.
Gray-Scale, Color Doppler, Spectral Doppler, and Contrast-Enhanced Renal Artery Ultrasound: Imaging Techniques and Features
Authors: Park Byung Kwan
Published: July 2022

Renal artery stenosis (RAS) is increasingly being detected in elderly patients as life expectancy increases. RAS induces hypertension or reduces renal function. Computed tomography or magnetic resonance angiography are objective in detecting RAS but may cause iodine-induced nephrotoxicity or nephrogenic systemic fibrosis in patients with RAS. Ultrasound (US) is, by contrast, a noninvasive and real-time imaging modality useful in patients with reduced renal function. Renal US is not as sensitive for detecting RAS because this technique indirectly assesses the renal artery by analyzing intrarenal hemodynamic changes. Although, ideally, US would be used to directly evaluate the renal artery, its current utility for RAS detection remains unclear. The purpose of this review is to introduce how to assess renal artery with US, to describe imaging features of renal artery US, to compare renal artery US and renal US, and to show how to perform work-up in patients in whom RAS is suspected.
Factors Associated with Variability in Pulse Wave Transit Time Using Pulse Oximetry: A Retrospective Study
Authors: Budiman Hilmanda , Wakita Ryo , Ito Takaya , Maeda Shigeru
Published: July 2022

Pulse wave transit time (PWTT) is the time difference between the occurrence of an R-wave on an electrocardiogram and the detection of pulsatile signals on a pulse oximeter, which reflects changes in blood pressure (BP) corresponding to the vessel wall compliance. However, the factors affecting PWTT variability have not been determined. Thus, we investigated the BP changes associated with variations in PWTT and identified the clinical characteristics associated with these variations. Data related to 605 cases of dental procedures performed under intravenous conscious sedation from April 2020 to November 2021 were collected, and 485 cases were enrolled. Heart rate, systolic blood pressure before and after local anesthesia (LA) administration, and crest and trough PWTT waves during LA administration were recorded. Thereafter, PWTT variability was calculated; cases were divided into two groups: large PWTT variability (LPV, n = 357) and small PWTT variability (SPV, n = 128). The index of large PWTT variability could not detect changes in BP. Logistic regression analysis revealed that factors, such as LA use, age, hypertension, and dental treatment phobia were associated with PWTT variability. The use of epinephrine more than 36.25 µg in each LA resulted in PWTT variability of more than 15 ms.
Markers of Schizophrenia—A Critical Narrative Update
Authors: Galińska-Skok Beata , Waszkiewicz Napoleon
Published: July 2022

Schizophrenia is a long-term mental disease, associated with functional impairment. Therefore, it is important to make an accurate diagnosis and implement the proper treatment. Biomarkers may be a potential tool for these purposes. Regarding advances in biomarker studies in psychosis, the current symptom-based criteria seem to be no longer sufficient in clinical settings. This narrative review describes biomarkers of psychosis focusing on the biochemical (peripheral and central), neurophysiological, neuropsychological and neuroimaging findings as well as the multimodal approach related with them. Endophenotype markers (especially neuropsychological and occulomotor disturbances) can be currently used in a clinical settings, whereas neuroimaging glutamate/glutamine and D2/D3 receptor density changes, as well as immunological Th2 and PRL levels, seem to be potential biomarkers that need further accuracy tests. When searching for biochemical/immunological markers in the diagnosis of psychosis, the appropriate time of body fluid collection needs to be considered to minimize the influence of the stress axis on their concentrations. In schizophrenia diagnostics, a multimodal approach seems to be highly recommended.
Left Ventricular Ejection Fraction Can Predict Atrial Thrombosis Even in Non-High-Risk Individuals with Atrial Fibrillation
Authors: Angebrandt Belošević Petra , Šmalcelj Anton , Kos Nikola , Kordić Krešimir , Golubić Karlo
Published: July 2022

Background—Current guidelines do not recommend routine use of transesophageal echocardiography (TOE) in anticoagulated patients with atrial fibrillation (AF). The aim of our study was to identify predictors for left atrial thrombosis (LAT) in patients with AF that would require TOE despite anticoagulation therapy, using clinical, laboratory and echocardiographic data which are usually obtained in those patients in a real-world setting. Methods—We analyzed data from electronic medical records (EMR) of consecutive AF patients referred to two university hospitals between January 2014 and December 2017 for pulmonary vein isolation (PVI) or direct current cardioversion. The primary endpoint was the presence of left atrial thrombus on TOE. Multivariable and univariable logistic regression models were computed using variables that were significantly different between the LAT and the control groups. Results—A total of 838 patients were included, of whom 132 (15.8%) had LAT. After controlling for other variables, only the left ventricle ejection fraction (LVEF) remained statistically significant with an OR of 0.956 (95% CI 0.934–0.979), p < 0.01. Regression models including LVEF had significantly higher areas under the receiver operating characteristic (ROC) curves, including in subgroups with non-high thromboembolic risk (CHA2DS2-Vasc = 0 or 1), with an area under the curve (AUC) of 0.76 (95% CI 0.71–0.81), p < 0.0001. Conclusions—The LVEF is an independent predictor of LAT, and it might improve thromboembolic risk stratification in future models. LVEF significantly increased the predictive value of the CHA2DS2-Vasc model and was able to identify LAT in non-high-risk patients.
Gait Characterization and Analysis of Hereditary Amyloidosis Associated with Transthyretin Patients: A Case Series
Authors: Vilas-Boas Maria do Carmo , Fonseca Pedro Filipe Pereira , Sousa Inês Martins , Cardoso Márcio Neves , Cunha João Paulo Silva , Coelho Teresa
Published: July 2022

Hereditary amyloidosis associated with transthyretin (ATTRv), is a rare autosomal dominant disease characterized by length-dependent symmetric polyneuropathy that has gait impairment as one of its consequences. The gait pattern of V30M ATTRv amyloidosis patients has been described as similar to that of diabetic neuropathy, associated with steppage, but has never been quantitatively characterized. In this study we aim to characterize the gait pattern of patients with V30M ATTRv amyloidosis, thus providing information for a better understanding and potential for supporting diagnosis and disease progression evaluation. We present a case series in which we conducted two gait analyses, 18 months apart, of five V30M ATTRv amyloidosis patients using a 12-camera, marker based, optical system as well as six force platforms. Linear kinematics, ground reaction forces, and angular kinematics results are analyzed for all patients. All patients, except one, showed a delayed toe-off in the second assessment, as well as excessive pelvic rotation, hip extension and external transverse rotation and knee flexion (in stance and swing phases), along with reduced vertical and mediolateral ground reaction forces. The described gait anomalies are not clinically quantified; thus, gait analysis may contribute to the assessment of possible disease progression along with the clinical evaluation.