bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Intracellular Drug Disposition in the Response of Acute Myeloid Leukemia to Cytarabine and Idarubicin Induction Chemotherapy
Authors: Rodríguez-Macías Gabriela , Briz Oscar , Cives-Losada Candela , Chillón María C. , Martínez-Laperche Carolina , Martínez-Arranz Ibon , Buño Ismael , González-Díaz Marcos , Díez-Martín José L. , Marin Jose J. G. , Macias Rocio I. R.
Published: June 2023

Despite its often low efficacy and high toxicity, the standard treatment for acute myeloid leukemia (AML) is induction chemotherapy with cytarabine and idarubicin. Here, we have investigated the role of transporters and drug-metabolizing enzymes in this poor outcome. The expression levels (RT-qPCR) of potentially responsible genes in blasts collected at diagnosis were related to the subsequent response to two-cycle induction chemotherapy. The high expression of uptake carriers (ENT2), export ATP-binding cassette (ABC) pumps (MDR1), and enzymes (DCK, 5-NT, and CDA) in the blasts was associated with a lower response. Moreover, the sensitivity to cytarabine in AML cell lines was associated with ENT2 expression, whereas the expression of ABC pumps and enzymes was reduced. No ability of any AML cell line to export idarubicin through the ABC pumps, MDR1 and MRP, was found. The exposure of AML cells to cytarabine or idarubicin upregulated the detoxifying enzymes (5-NT and DCK). In AML patients, 5-NT and DCK expression was associated with the lack of response to induction chemotherapy (high sensitivity and specificity). In conclusion, in the blasts of AML patients, the reduction of the intracellular concentration of the active metabolite of cytarabine, mainly due to the increased expression of inactivating enzymes, can determine the response to induction chemotherapy.
Editorial for the Special Issue on High-Risk Localized and Locally Advanced Prostate Cancer
Authors: Izumi Kouji
Published: June 2023

The recent development of imaging modalities, such as diffusion-weighted whole-body imaging with background suppression (DWIBS) and positron emission tomography of prostate-specific membrane antigen (PSMA-PET) with a radioactive diagnostic agent, has enabled the detection of minute metastases in patients diagnosed with high-risk localized and locally advanced prostate cancer by conventional modalities [...]
Apathy in Parkinson’s Disease: Clinical Patterns and Neurobiological Basis
Authors: Béreau Matthieu , Van Waes Vincent , Servant Mathieu , Magnin Eloi , Tatu Laurent , Anheim Mathieu
Published: June 2023

Apathy is commonly defined as a loss of motivation leading to a reduction in goal-directed behaviors. This multidimensional syndrome, which includes cognitive, emotional and behavioral components, is one of the most prevalent neuropsychiatric features of Parkinson’s disease (PD). It has been established that the prevalence of apathy increases as PD progresses. However, the pathophysiology and anatomic substrate of this syndrome remain unclear. Apathy seems to be underpinned by impaired anatomical structures that link the prefrontal cortex with the limbic system. It can be encountered in the prodromal stage of the disease and in fluctuating PD patients receiving bilateral chronic subthalamic nucleus stimulation. In these stages, apathy may be considered as a disorder of motivation that embodies amotivational behavioral syndrome, is underpinned by combined dopaminergic and serotonergic denervation and is dopa-responsive. In contrast, in advanced PD patients, apathy may be considered as cognitive apathy that announces cognitive decline and PD dementia, is underpinned by diffuse neurotransmitter system dysfunction and Lewy pathology spreading and is no longer dopa-responsive. In this review, we discuss the clinical patterns of apathy and their treatment, the neurobiological basis of apathy, the potential role of the anatomical structures involved and the pathways in motivational and cognitive apathy.
Fabrication of Zn2+-Loaded Polydopamine Coatings on Magnesium Alloy Surfaces to Enhance Corrosion Resistance and Biocompatibility
Authors: Meng Lingjie , Liu Xuhui , Hong Qingxiang , Ji Yan , Wang Lingtao , Zhang Qiuyang , Chen Jie , Pan Changjiang
Published: June 2023

In this study, inspired by the adhesion protein of mussels, a Zn2+-loaded polydopamine (PDA/Zn2+) coating was prepared on an alkali–heat-treated magnesium alloy surface, through the chelating effect of PDA with metal ions, to improve anticorrosion and biocompatibility. The results of water contact angles show that the PDA/Zn2+ coatings with different Zn2+ contents had excellent wettability, which contributed to the selective promotion of the albumin adsorption. The corrosion degradation behaviors of the modified magnesium alloys were characterized using potentiodynamic scanning polarization curves, electrochemical impedance spectroscopy (EIS), and an immersion test, the results indicate that anticorrosion was significantly improved with the increase of Zn2+ content in the coating. Meanwhile, the PDA/Zn2+ coatings with different Zn2+ concentrations demonstrated improved hemocompatibility, confirmed by assays of the hemolysis rate and platelet adhesion behaviors. In addition, the results regarding the growth behaviors of endothelial cells (ECs) suggest that, due to the sustained release of Zn2+ from the coatings, the modified magnesium alloys could enhance the adhesion, proliferation, and upregulated expression of vascular endothelial growth factor (VEGF) and nitric oxide (NO) in endothelial cells, and that better cytocompatibility to ECs could be achieved as the Zn2+ concentration increased. Therefore, the PDA/Zn2+ coatings developed in this study could be utilized to modify magnesium alloy surfaces, to simultaneously impart better anticorrosion, hemocompatibility, and endothelialization.
Synthesis of Porous MgF2 Coating by a Sol–Gel Method Accompanied by Phase Separation
Authors: Lin Yu , Wang Rui , Xu Yang , Li Dongyun , Ge Hongliang
Published: June 2023

Surfaces with translucent and wear-resistant effects have a wide range of applications, especially as protective layers. In this work, a simple and convenient method for the preparation of porous magnesium fluoride (MgF2) coatings was proposed. Nano-porous MgF2 powder was prepared with sol–gel and phase separation methods by optimizing the polymer amount and used for the preparation of thick layers onto PVC substrates. The automated surface area and porosity analyzer (BET) and scanning electron microscopy (SEM) confirmed that the layers containing 0.028‰ PEO presented a 3D structure with pore sizes in the range of 16 nm. The layer reached 93% transmittance in the visible region, a Vickers hardness value of 2889.1 kg/mm2, and a friction coefficient of 0.2 in the wear test.
Active Control Topological Valley Modes in Metamaterial Plates
Authors: Zhou Jingxuan , Zhang Jie , Chang Jiahui , Li Zheng-Yang , Yan Dongjia
Published: June 2023

Phononic crystals and metamaterials have a unique band structure that allows for the existence of topologically protected surface states. The topologically protected edge states can guide elastic waves without significant scattering or loss of energy. One of the most promising applications of topological insulators in wave guiding is in the field of acoustics, where they can be used to design highly efficient and robust acoustic wave guides. However, the high efficiency, precision, reconfigurability, and robustness of elastic waves remains challenging. The topological insulators provide a feasible method to design high-efficiency, robust, and low-backscattering waveguides. In this work, a novel design of hexagonal metamaterial plates composed of a base plate and piezoelectric patches is proposed. The hexagonal metamaterial plate can generate robust topologically protected edge waves via active control. The paths of the topologically protected edge waves can be tuned by adjusting the control parameters. The robustness and efficiency of the proposed hexagonal metamaterial plate are testified to by the numerical examples. These findings provide systematic theoretical guidelines for designing reconfigurable wave guides, elastic wave splitters, and novel elastic wave devices and hold great promise for the development of high-performance and versatile wave guide technologies with potential applications in a wide range of fields.
RETRACTED: The Effect of Treatment Temperature on Microstructure and Mechanical Behavior of a Fine-Grained YSZ–NiO(Ni) Anode Material
Authors: Vasyliv Bogdan , Kulyk Volodymyr , Duriagina Zoia , Kovbasiuk Taras
Published: June 2023

Reduction–oxidation (redox) cycling of a solid oxide fuel cell (SOFC) due to leakage of a fuel or standby and shutdown cycling is an issue that has attracted the attention of many research groups for a long time. The researchers mainly note the harmful effects of redox cycling on the microstructure of SOFC constituents and search for ways to mitigate or diminish them. The purpose of this study was to use reduction and oxidation stages in an appropriate mode as a positive preconditioning to improve redox cycling stability of Ni-containing SOFC anode materials. The redox treatment was applied to YSZ–NiO(Ni) anode substrate specimens at 600 °C and 800 °C. The mechanical tests (flexural strength, microhardness, and fracture toughness) were performed on these specimens and the results were compared to those for as-sintered and one-time reduced specimens. Microstructure and fracture surface morphology of material in corresponding modes were analyzed. The main findings were summarized as follows: (i) Redox treatment at 600 °C provides an increase in flexural strength and electrical conductivity of YSZ–NiO(Ni) anode cermets; (ii) the treatment at 800 °C causes formation of a gradient microstructure with lateral cracks that result in a significant decrease in flexural strength; (iii) the mode of redox treatment at 600 °C for 4 h in Ar–5% H2/air atmosphere provides an increase in flexural strength of YSZ–NiO(Ni) anode cermets (up to 127 ± 4 MPa), while electrical conductivity was provided at a comparatively high level (7 × 105 S/m).
On the Evolutionary History of Philometridae (Nematoda: Dracunculoidea): Integrative Taxonomy Reveals Evidence of Character Diversification and Host–Parasite Cophylogenetic Patterns
Authors: Ailán-Choke Lorena Gisela , Paschoal Fabiano , Couto João Victor , Pereira Felipe Bisaggio
Published: June 2023

(1) Background: Integrative taxonomy has been important in the comprehension of relationships among nematode parasites. Philometridae is a highly diverse family of these organisms, but poorly-known regarding genetic characterization and evolution. An integrative taxonomic analysis was performed to improve the knowledge of the evolutionary history of Philometridae. (2) Methods: Phylogenies were reconstructed based on genetic sequences alone and integrated with morphological/life history traits, which were phylogenetically mapped. The host–parasite cophylogeny was evaluated. (3) Results: Previously unpublished 28S rDNA sequences are given for some species. The phylogeny from this marker, although limited by data scarcity, showed similar patterns as that from 18S rDNA. Clades shared common features related to the structure of the esophagus and of the tail in males (especially the gubernaculum), site of infection, habitat, host taxa and geographic origin; most of these features were phylogenetically informative. The integrative phylogeny was better resolved. A cophylogenetic signal was present mainly in clades of freshwater species. (4) Conclusions: The speciation process in Philometridae is not unique or uniform; host capture, host–parasite co-evolution and allopatric (especially in freshwater) events may be occurring simultaneously in different lineages, places and times. Cases of plesiomorphy retention probably occur. Evolutionary convergence of poorly-informative characters is suggested, even though they are important for species diagnosis.
Functional PET Neuroimaging in Consciousness Evaluation: Study Protocol
Authors: Paunet Tom , Mariano-Goulart Denis , Deverdun Jeremy , Le Bars Emmanuelle Le , Fourcade Marjolaine , Kucharczak Florentin
Published: June 2023

Ensuring a robust and reliable evaluation of coma deepness and prognostication of neurological outcome is challenging. We propose to develop PET neuroimaging as a new diagnostic and prognosis tool for comatose patients using a recently published methodology to perform functional PET (fPET). This exam permits the quantification of task-specific changes in neuronal metabolism in a single session. The aim of this protocol is to determine whether task-specific changes in glucose metabolism during the acute phase of coma are able to predict recovery at 18 months. Participation will be proposed for all patients coming for a standard PET-CT in our center in order to evaluate global cerebral metabolism during the comatose state. Legally appointed representative consent will be obtained to slightly modify the exam protocol: (1) [18]F-fluorodeoxyglucose ([18]F-FDG) bolus plus continuous infusion instead of a simple bolus and (2) more time under camera to perform dynamic acquisition. Participants will undergo a 55-min fPET session with a 20% bolus + 80% infusion protocol. Two occurrences of three block (5-min rest, 10-min auditory stimulation and 10-min emotional auditory stimulation) will be performed after reaching equilibrium of FDG arterial concentration. We will compare the regional brain metabolism at rest and during the sessions of auditory and emotional auditory stimulation to search for a determinant of coma recovery (18 months of follow-up after the exam). Emotional auditory stimulation should induce an activation of: the auditory cortex, the consciousness areas and the neural circuitry for emotion (function to coma deepness). An activation analysis will be carried out to highlight regional brain activation using dedicated custom-made software based on Python statistical and image processing toolboxes. The association between activation levels and the Coma Recovery Scale-Revisited (CRS-R) will be assessed using multivariate analysis. If successful, the results from this study will help improve coma prognosis evaluation based on the pattern of neuronal metabolism at the onset of the pathology. The study protocol, rationale and methods are described in this paper.
Comparative Transcriptome Analysis Reveals Key Genes and Pathways Associated with Phosphate-Sensitive Behaviors in Cunninghamia lanceolata (Lamb.) Hook.
Authors: Wei Ruping , Hu Dehuo , Chen Jinhui , Zheng Huiquan , Shi Jisen
Published: June 2023

Cunninghamia lanceolate (Lamb.) Hook. (Chinese fir) is one of the most important wood-producing species, supplying ~20% of commercial timber by plantations in China. However, the genetic potential of the bred variety is limited by soil degrading in the long term and requiring continuous replanting, and especially the shortage and supply of active and efficient phosphorus. Recently, great attention has been paid to the genotypic variation in phosphorus conversion and utilization efficiency by tree breeders. In this study, the morphological characteristics were used to evaluate the Chinese fir clonal Pi-efficiency stress. A Pi-tolerant clone and a Pi-sensitive clone were selected for RNA sequencing, respectively. In addition, gene function annotation and weighted correlation network analysis (WGCNA) were performed. A total of 60 hub genes were selected, combining phosphate accumulation under Pi-deficiency stress. We also used RNA-seq data to analyze the differences in the response of Pi-sensitive clones and Pi-tolerant clones to Pi-deficiency stress, and real-time quantitative polymerase chain reaction (RT-PCR) analyses were used to test the validity of transcriptome data. The present study provided new insights into the molecular mechanisms of Pi-efficient utilization in Chinese fir clones.
Heavy Logging Machinery Impacts Soil Physical Properties More than Nematode Communities
Authors: Gibson Kara S. , Neher Deborah A. , Johnson Nancy C. , Parmenter Robert R. , Antoninka Anita J.
Published: June 2023

Mechanized logging equipment causes considerable soil disturbance, but little information is available regarding thresholds for impacts on soil nematodes—critical members of soil foodwebs which perform important ecological functions. We examined responses of nematode communities and soil physical characteristics to the increasing number of passes (one, three, or nine) by a tracked feller buncher during thinning of a xeric mixed conifer forest in New Mexico, USA. Within and between the harvester tracks, we measured soil surface penetration resistance and shear strength, quantified bulk density at four depth increments up to a maximum depth of 27 cm, and characterized nematode assemblages in the upper 10 cm. Eight months after treatment, nematode communities were less impacted than soil physical properties by harvester passes. Total nematode abundance was unaffected by any level of feller buncher disturbance, and sensitive K-selected nematode groups were reduced only at nine passes. Conversely, soil compaction occurred with a single pass and extended deep into the soil profile to at least 23–27 cm. The first pass also decreased surface penetration resistance and shear strength, indicating disruption of soil surface structural integrity. Additional passes did not further increase bulk density or decrease surface structural integrity. Our results indicate that low levels of logging machinery traffic may have negligible effects on nematode communities, but nevertheless emphasize the importance of minimizing areas subjected to disturbance because of impacts on soil physical properties.
Keystone Soil Microbial Modules Associated with Priming Effect under Nitrogen- and Glucose-Addition Treatments
Authors: Xu Min , Zeng Quanxin , Liu Yuanyuan , Liu Chengchung , Zhang Qiufang , Mei Kongcan , Yuan Xiaochun , Zhang Xiaoqing , Chen Yuehmin
Published: June 2023

The priming effect (PE) is important for understanding the decomposition of soil organic matter (SOM) and forecasting C-climate feedback. However, there are limited studies on microbial community-level properties and the keystone taxa involved in the process. In this study, we collected soil from a subtropical Phyllostachys edulis forest undergoing long-term N-addition and conducted an incubation experiment to evaluate the effects of single and repeated addition of 13C-labeled glucose. Our results demonstrated that previously N-fertilized soil had a smaller cumulative PE compared with that of the control (11% average decrease). This could be primarily explained (26%) by the lower abundance of bacterial r-strategy group members (B_mod#2, constituting Proteobacteria, Firmicutes, and Actinobacteria phyla) under N-addition treatments. A single C-addition induced a greater PE than that of repeated C-additions (2.66- to 3.11-fold). Single C addition led to greater C to N ratios of microbial biomass and fungi to bacteria, positively impacting cumulative PE, indicating that the shifts in fungal/bacterial dominance play an important role in regulating PE. Moreover, a saprophytic taxa group (F_Mod#3, primarily composed of the phyla Ascomycota) explained 62% of the differences in cumulative PE between single and repeated C-additions. Compared with repeated C-additions, a greater abundance of B_Mod#2 and F_Mod#3, as well as C-related hydrolase activity, was observed under single C-addition, inducing greater cumulative PE. Therefore, sufficient C may facilitate the proliferation of r-strategy bacterial taxa and saprophytic fungal taxa, thereby increasing SOM decomposition. Our findings provide novel insights into the relationship between microbial community-level properties and PE.
Use of GIS in Selecting Suitable Tree Crop Cultivation Sites in Mountainous Less Favoured Areas: An Example from Greece
Authors: Tsiaras Stefanos , Domakinis Christos
Published: June 2023

The aim of this paper is the selection of suitable tree crop cultivation sites in mountainous less favoured areas, as a forest policy measure under the scope of sustainable development. Ten different crop types were proposed as being most suitable in the study area, Pierion Municipal Unit, which is located in the Municipality of Katerini, in the Pieria Prefecture of Greece. In order to determine the most suitable sites for cultivation, data layers that involved the factors of topography, climate, pedology and geology were derived from existing maps and free-of-charge datasets, so that they could be consequently processed with the aid of Geographic Information Systems (GIS). The data processing was performed by following criteria, which were established in accordance with the current literature and were translated into Boolean algebra expressions. The latter helped to identify locations where the values of the factors that were employed were most favourable for the cultivation of walnut trees (Juglans sp.), olive trees (Olea sp.), cherry trees (Prunus sp.), apple (Malus sp.), dogwood trees (Cornus sp.), pomegranate trees (Punica sp.), chestnut trees (Castanea sp.) and other crop types. Moreover, the resulting map indicated that the majority of the suitable sites for cultivation were considered favourable for growing walnut trees (24.9%), followed by cherry trees (19.6%) and olive trees (12.1%). Proposing the most suitable cultivations within the study area contributes to forest policy planning and promotes the sustainable development of mountainous less favoured areas, leading to a more rational management of natural resources, a raised awareness of environmental protection, the maintenance of the local population and income enhancement through the production of high quality crops and sustainable yields.
Semi-Supervised Tree Species Classification for Multi-Source Remote Sensing Images Based on a Graph Convolutional Neural Network
Authors: Wang Xueliang , Wang Jian , Lian Zuozheng , Yang Nan
Published: June 2023

As a current research hotspot, graph convolution networks (GCNs) have provided new opportunities for tree species classification in multi-source remote sensing images. To solve the challenge of limited label information, a new tree species classification model was proposed by using the semi-supervised graph convolution fusion method for hyperspectral images (HSIs) and multispectral images (MSIs). In the model, the graph-based attribute features and pixel-based features are fused to deepen the correlation of multi-source images to improve accuracy. Firstly, the model employs the canonical correlation analysis (CCA) method to maximize the correlation of multi-source images, which explores the relationship between information from various sources further and offers more valuable insights. Secondly, convolution calculations were made to extract features and then map graph node fusion, which not only reduces redundancy features but also enhances compelling features. Finally, the relationship between representative descriptors is captured through the use of hyperedge convolution in the training process, and the dominant features on the graph are fully mined. The tree species are classified through two fusion feature operations, leading to improved classification performance compared to state-of-the-art methods. The fusion strategy can produce a complete classification map of the study areas.
Thin Cell Layer Tissue Culture Technology with Emphasis on Tree Species
Authors: Sharma Vikas , Magotra Tanvi , Chourasia Ananya , Mittal Divye , Prathap Singh Ujjwal , Sharma Saksham , Sharma Shivika , García Ramírez Yudith , Dobránszki Judit , Martinez-Montero Marcos Edel
Published: June 2023

An increased dependency on plant-based resources for food, shelter, and medicinal usage has increased their sustainable and unsustainable exploitation. To use this resource sustainably, plant tissue culture (PTC) is one important technology. Among different PTC techniques, thin cell layer (TCL) technology is a relatively simple and easily adaptable technique for in vitro cultures of plants. This technique uses small explants about 0.5–2 mm in thickness excised from different plant organs. It has been successfully used in the large-scale propagation of vegetables, legumes, and plants with medicinal benefits. TCL technology has proven to be effective in stimulating various organogenic responses when combined with various new methods such as nanotechnology or microtome-based explantation, especially in tree species. It is considered an important tool in plant biotechnology. Although the morphogenetic response per explant is usually higher in conventional explants, the appropriate use of plant growth regulators and geometric factors in TCL has the potential to make it more efficient and beneficial. This article provides an overview of the concept of TCL as applied to different plant species, particularly trees, since there are few, if any, summaries of TCL technology, especially in trees. This review will certainly revitalize this important technology so that it can be used effectively for successful mass propagation in the field of plant tissue culture.
Top-Leader Growth in Nordmann Fir (Abies nordmanniana)
Authors: Veierskov Bjarke
Published: June 2023

The growth of the top-leader in Abies nordmanniana was measured over a 6-year period, and showed a consistent growth pattern, with an initial growth phase reaching a maximum growth rate that varied between 12.0 and 22.5 mm per day, and which could be correlated with the temperature in July of the previous year. The daily growth rate always peaked in the last week of June. In late-bud-breaking plants, the top-leader became short because of a low growth rate in this first phase of growth. In the second growth phase, the daily growth rate slowly declined, but was similar in all plants, regardless of the size of the top-leader when this phase began, and the timing of the bud break. The growth in the second growth phase was correlated with the precipitation in the period. Growth cessation occurred in the basal part of the top-leader soon after bud break, and progressed slowly apically, whereby the upper 25% of a young top-leader contributed to 50% of the final length, as growth in this section continued throughout the major part of the growth season.
Comparative Mitochondrial Genomes between the Genera Amiota and Phortica (Diptera: Drosophilidae) with Evolutionary Insights into D-Loop Sequence Variability
Authors: Zhang Caihong , Wang Yalian , Chen Hongwei , Huang Jia
Published: June 2023

To address the limited number of mitochondrial genomes (mitogenomes) in the subfamily Steganinae (Diptera: Drosophilidae), we assembled 12 complete mitogenomes for six representative species in the genus Amiota and six representative species in the genus Phortica. We performed a series of comparative and phylogenetic analyses for these 12 Steganinae mitogenomes, paying special attention to the commonalities and differences in the D-loop sequences. Primarily determined by the lengths of the D-loop regions, the sizes of the Amiota and Phortica mitogenomes ranged from 16,143–16,803 bp and 15,933–16,290 bp, respectively. Our results indicated that the sizes of genes and intergenic nucleotides (IGNs), codon usage and amino acid usage, compositional skewness levels, evolutionary rates of protein-coding genes (PCGs), and D-loop sequence variability all showed unambiguous genus-specific characteristics and provided novel insights into the evolutionary implications between and within Amiota and Phortica. Most of the consensus motifs were found downstream of the D-loop regions, and some of them showed distinct genus-specific patterns. In addition, the D-loop sequences were phylogenetically informative as the data sets of PCGs and/or rRNAs, especially within the genus Phortica.
Molecular Modeling Analysis Provides Genotype–Phenotype Correlation Insights in a Patient with Ankyloblepharon-Ectodermal Dysplasia-Clefting Syndrome
Authors: Douka Anna , Goutzanis Lambros , Vlachakis Dimitrios , Chrousos George P. , Yapijakis Christos
Published: June 2023

Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome is a rare autosomal dominant disorder. AEC is caused by mutations in the TP63 gene that encodes the tumor suppressor p63 protein, itself involved in the regulation of epidermal proliferation, development, and differentiation. We present here a typical AEC case of a four-year-old girl with extensive skin erosions and erythroderma of the scalp and the trunk, and to a lesser extent of the limbs, nail dystrophy on the fingers and toes, xerophthalmia, a high-arched palate, oligodontia, and hypohidrosis. Mutation analysis of the TP63 gene detected a de novo missense mutation in exon 14 (c.1799G>T; p.Gly600Val). We discuss the phenotype–genotype correlation by presenting the clinical features of AEC in the patient, and the effect of the detected mutation in p63 structure and function using protein structural modeling, in view of similar cases in the literature. We performed a molecular modeling study in order to link the effect on the protein structure level of the missense mutation G600V. We noted that the introduction of the bulkier Valine residue in place of the slim Glycine residue caused a significantly altered 3D conformational arrangement of that protein region, pushing away the adjacent antiparallel α helix. We propose that the introduced locally altered structure of the G600V mutant p63 has a significant functional effect on specific protein–protein interactions, thus affecting the clinical phenotype.
Genome-Wide Identification of B-Box Gene Family and Expression Analysis Suggest Its Roles in Responses to Cercospora Leaf Spot in Sugar Beet (Beta Vulgaris L.)
Authors: Song He , Ding Guangzhou , Zhao Chunlei , Li Yanli
Published: June 2023

The B-box (BBX) protein, which is a zinc-finger protein containing one or two B-box domains, plays a crucial role in the growth and development of plants. Plant B-box genes are generally involved in morphogenesis, the growth of floral organs, and various life activities in response to stress. In this study, the sugar beet B-box genes (hereafter referred to as BvBBXs) were identified by searching the homologous sequences of the Arabidopsis thaliana B-box gene family. The gene structure, protein physicochemical properties, and phylogenetic analysis of these genes were systematically analyzed. In this study, 17 B-box gene family members were identified from the sugar beet genome. A B-box domain can be found in all sugar beet BBX proteins. BvBBXs encode 135 to 517 amino acids with a theoretical isoelectric point of 4.12 to 6.70. Chromosome localization studies revealed that BvBBXs were dispersed across nine sugar beet chromosomes except chromosomes 5 and 7. The sugar beet BBX gene family was divided into five subfamilies using phylogenetic analysis. The gene architectures of subfamily members on the same evolutionary tree branch are quite similar. Light, hormonal, and stress-related cis-acting elements can be found in the promoter region of BvBBXs. The BvBBX gene family was differently expressed in sugar beet following Cercospora leaf spot infection, according to RT-qPCR data. It is shown that the BvBBX gene family may influence how the plant reacts to a pathogen infection.
Properties of INDETERMINATE DOMAIN Proteins from Physcomitrium patens: DNA-Binding, Interaction with GRAS Proteins, and Transcriptional Activity
Authors: Khan Saiful Islam , Yamada Ren , Shiroma Ryoichi , Abe Tatsuki , Kozaki Akiko
Published: June 2023

INDETERMINATE DOMAIN (IDD) proteins are plant-specific transcription factors that interact with GRAS proteins, such as DELLA and SHORT ROOT (SHR), to regulate target genes. The combination of IDD and DELLA proteins regulates genes involved in gibberellic acid (GA) synthesis and GA signaling, whereas the combination of IDD with the complex of SHR and SCARECROW, another GRAS protein, regulates genes involved in root tissue formation. Previous bioinformatic research identified seven IDDs, two DELLA, and two SHR genes in Physcomitrium patens, a model organism for non-vascular plants (bryophytes), which lack a GA signaling pathway and roots. In this study, DNA-binding properties and protein–protein interaction of IDDs from P. patens (PpIDD) were analyzed. Our results showed that the DNA-binding properties of PpIDDs were largely conserved between moss and seed plants. Four PpIDDs showed interaction with Arabidopsis DELLA (AtDELLA) proteins but not with PpDELLAs, and one PpIDD showed interaction with PpSHR but not with AtSHR. Moreover, AtIDD10 (JACKDAW) interacted with PpSHR but not with PpDELLAs. Our results indicate that DELLA proteins have modified their structure to interact with IDD proteins during evolution from moss lineage to seed plants, whereas the interaction of IDD and SHR was already present in moss lineage.
Physical Therapy Assessment Tool Threshold Values to Identify Sarcopenia and Locomotive Syndrome in the Elderly
Authors: Kim Hae-In , Kim Myung-Chul
Published: June 2023

This study aimed to evaluate sarcopenia and locomotive syndrome in Korean elderly patients, analyze the closely related factors, and determine the threshold for distinguishing participants with sarcopenia, locomotive syndrome, and non-disease. To this end, we enrolled 210 subjects aged 65 years or more and classified them into the sarcopenia (n = 36) and locomotive syndrome (n = 164) groups; a control group was also included (n = 10). We evaluated the characteristics of these patients using the Timed Up and Go (TUG) test and Berg Balance Scale (BBS) and performed statistical analysis. Our findings showed statistically significant differences between the groups, leading to the derivation of a significant threshold value. The threshold value of the TUG test between the control and locomotive syndrome groups was 9.47 s; the threshold value of the BBS was 54 points, respectively. The threshold value of the TUG test between the locomotive syndrome and sarcopenia groups was 10.27 s, and the threshold value of the BBS was 50 points, respectively. These findings suggest that sarcopenia is closely related to locomotive syndrome, and that sarcopenia and locomotive syndrome can be identified using a physical therapy diagnostic evaluation tool.
Adolescent Pregnancy in South Asia: A Pooled Analysis of Demographic and Health Surveys
Authors: Poudel Samikshya , Dobbins Timothy , Razee Husna , Akombi-Inyang Blessing
Published: June 2023

Adolescent pregnancy has important health and social implications. Despite the availability of nationally representative household survey data, there are limited studies that analyze factors associated with adolescent pregnancy across countries of South Asia. This study aimed to identify factors associated with adolescent pregnancy across South Asia. This study used the most recent Demographic and Health Survey (DHS) data from six countries in South Asia: Afghanistan, Bangladesh, India, the Maldives, Nepal, and Pakistan. Pooled individual record data from 20,828 ever-married women aged 15–19 years were used for the analysis. Multivariable logistic regression analysis, informed by the World Health Organization framework on social determinants of health, was performed to examine factors associated with adolescent pregnancy. Adolescent pregnancy was highest in Afghanistan compared to Bangladesh, Nepal, Pakistan, India, and the Maldives. Multivariable analyses confirmed that being from a poor household or male-headed household, increasing maternal age, having no access to newspapers, and having no knowledge of family planning were significantly associated with adolescent pregnancy. The use or intention to use contraceptives was protective against adolescent pregnancy. To reduce adolescent pregnancy in South Asia, interventions targeting adolescents from poor households with limited access to mass media should be considered, especially those from households with an existing patriarchal structure.
The Factors Associated with the Development of COVID-19 Symptoms among Employees in a U.S. Healthcare Institution
Authors: Abu-Alhaija Dania M. , Matibiri Paidamoyo , Brittingham Kyle , Wulsin Victoria , Davis Kermit G. , Huston Thomas , Gillespie Gordon
Published: June 2023

Healthcare workers have experienced increased occupational health risks caused by COVID-19 disease. The purpose of this project was to examine the relationships between reporting COVID-19 symptoms by employees in a healthcare institution in the United States and employees’ demographics, vaccination status, co-morbid conditions, and body mass index (BMI). This project employed a cross-sectional design. It involved the analysis of data on COVID-19 exposure and infection incidents among employees in the healthcare institution. The dataset contained more than 20,000 entries. The results indicate that being female, African American, between 20 and 30 years old, diagnosed with diabetes, diagnosed with chronic obstructive pulmonary disease (COPD), or on immunosuppressive medicines is associated with greater reporting of COVID-19 symptoms by the employees. Furthermore, BMI is associated with reporting COVID-19 symptoms; the higher the BMI, the greater the likelihood of reporting a symptomatic infection. Moreover, having COPD, being 20–30 years old, being 40–50 years old, BMI, and vaccination status were significantly associated with employees reporting symptoms while controlling for other variables associated with reporting the symptoms among the employees. These findings may be applicable to other infectious disease outbreaks or pandemics.
Anti-Islet Autoantibodies in Type 1 Diabetes
Authors: Kawasaki Eiji
Published: June 2023

Anti-islet autoantibodies serve as key markers in immune-mediated type 1 diabetes (T1D) and slowly progressive T1D (SPIDDM), also known as latent autoimmune diabetes in adults (LADA). Autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA), tyrosine phosphatase-like protein IA-2 (IA-2A), and zinc transporter 8 (ZnT8A) are currently employed in the diagnosis, pathological analysis, and prediction of T1D. GADA can also be detected in non-diabetic patients with autoimmune diseases other than T1D and may not necessarily reflect insulitis. Conversely, IA-2A and ZnT8A serve as surrogate markers of pancreatic β-cell destruction. A combinatorial analysis of these four anti-islet autoantibodies demonstrated that 93–96% of acute-onset T1D and SPIDDM cases were diagnosed as immune-mediated T1D, while the majority of fulminant T1D cases were autoantibody-negative. Evaluating the epitopes and immunoglobulin subclasses of anti-islet autoantibodies help distinguish between diabetes-associated and non-diabetes-associated autoantibodies and is valuable for predicting future insulin deficiency in SPIDDM (LADA) patients. Additionally, GADA in T1D patients with autoimmune thyroid disease reveals the polyclonal expansion of autoantibody epitopes and immunoglobulin subclasses. Recent advancements in anti-islet autoantibody assays include nonradioactive fluid-phase assays and the simultaneous determination of multiple biochemically defined autoantibodies. Developing a high-throughput assay for detecting epitope-specific or immunoglobulin isotype-specific autoantibodies will facilitate a more accurate diagnosis and prediction of autoimmune disorders. The aim of this review is to summarize what is known about the clinical significance of anti-islet autoantibodies in the pathogenesis and diagnosis of T1D.
Sarcopenic Obesity in People with Alcoholic Use Disorder: Relation with Inflammation, Vascular Risk Factors and Serum Vitamin D Levels
Authors: Martín-González Candelaria , Fernández-Alonso Paula , Pérez-Hernández Onán , Abreu-González Pedro , Espelosín-Ortega Elisa , Fernández-Rodríguez Camino María , Martín-Ponce Esther , González-Reimers Emilio
Published: June 2023

In recent years, the terms sarcopenia, sarcopenic obesity, and osteosarcopenic obesity (OSO) were coined to define a situation in elderly people strongly associated with frailty and increased mortality. Possibly, a complex interplay of several hormones and cytokines are involved in its development. Ongoing research detected that OSO may occur at any age and in several conditions. The prevalence of OSO in alcoholism was poorly analyzed. The aim of this study was to analyze the prevalence of OSO in alcoholism and its relationship with proinflammatory cytokines and/or common complications of alcoholism, such as cirrhosis, cancer, or vascular disease. We included 115 patients with alcoholic use disorder. Body composition analysis was performed by double X-ray absorptiometry. Handgrip strength was recorded using a dynamometer. We assessed liver function according to Child’s classification, and determined serum levels of proinflammatory cytokines (TNF-α, IL-6, IL-8), routine laboratory variables, and vitamin D. People with alcoholic use disorder showed a high prevalence of OSO, especially regarding OSO obesity (60%), OSO osteopenia (55.65%), and OSO lean mass (60.17%). OSO handgrip was closely, independently, related to the presence of vascular calcification (χ2 = 17.00; p < 0.001). OSO handgrip was related to several proinflammatory cytokines and vitamin D. Vitamin D deficiency kept a close correlation with OSO handgrip (rho = −0.54, p < 0.001). Therefore, among people with alcohol use disorder, OSO prevalence was high. OSO handgrip is related to serum proinflammatory cytokine levels supporting the possible pathogenetic role of these cytokines on OSO development. Vitamin D deficiency is related to OSO handgrip suggesting its pathogenetic involvement in sarcopenia in patients with alcohol use disorder. The close association between OSO handgrip and vascular calcification is clinically relevant and suggests that OSO handgrip may constitute a prognostic tool in these patients.
A Pilot Study to Detect Viable Salmonella spp. in Diarrheal Stool Using Viability Real-Time PCR as a Culture-Independent Diagnostic Tool in a Clinical Setting
Authors: Thilakarathna Surangi H. , Chui Linda
Published: June 2023

Frontline laboratories are adopting culture-independent diagnostic testing (CIDT) such as nucleic acid amplification tests (NAATs) due to numerous advantages over culture-based testing methods. Paradoxically, the viability of pathogens, a crucial factor determining active infections, cannot be confirmed with current NAATs alone. A recent development of viability PCR (vPCR) was introduced to mitigate this limitation associated with real-time PCR (qPCR) by using a DNA-intercalating dye to remove residual and dead cell DNA. This study assessed the applicability of the vPCR assay on diarrheal stools. Eighty-five diarrheal stools confirmed for Salmonellosis were tested via qPCR and vPCR using in-house primers and probe targeting the invA gene. vPCR-negative stools (Ct cut off > 31) were enriched in mannitol selenite broth (MSB) to verify low bacterial loads. vPCR assay showed ~89% sensitivity (qPCR- and vPCR-positive stools: 76/85). vPCR-negative stools (9/85; qPCR-positive: 5; qPCR-negative: 4) were qPCR- and culture-positive post-MSB-enrichment and confirmed the presence of low viable bacterial loads. Random sampling error, low bacterial loads, and receiving stools in batches could contribute to false negatives. This is a pilot study and further investigations are warranted to explore vPCR to assess pathogen viability in a clinical setting, especially when culture-based testing is unavailable.
The Role of Cocaine- and Amphetamine-Regulated Transcript (CART) in Cancer: A Systematic Review
Authors: Owe-Larsson Maja , Pawłasek Jan , Piecha Tomasz , Sztokfisz-Ignasiak Alicja , Pater Mikołaj , Janiuk Izabela R.
Published: June 2023

The functions of cocaine- and amphetamine-regulated transcript (CART) neuropeptide encoded by the CARTPT gene vary from modifying behavior and pain sensitivity to being an antioxidant. Putative CART peptide receptor GPR160 was implicated recently in the pathogenesis of cancer. However, the exact role of CART protein in the development of neoplasms remains unclear. This systematic review includes articles retrieved from the Scopus, PubMed, Web of Science and Medline Complete databases. Nineteen publications that met the inclusion criteria and describe the association of CART and cancer were analyzed. CART is expressed in various types of cancer, e.g., in breast cancer and neuroendocrine tumors (NETs). The role of CART as a potential biomarker in breast cancer, stomach adenocarcinoma, glioma and some types of NETs was suggested. In various cancer cell lines, CARTPT acts an oncogene, enhancing cellular survival by the activation of the ERK pathway, the stimulation of other pro-survival molecules, the inhibition of apoptosis or the increase in cyclin D1 levels. In breast cancer, CART was reported to protect tumor cells from tamoxifen-mediated death. Taken together, these data support the role of CART activity in the pathogenesis of cancer, thus opening new diagnostic and therapeutic approaches in neoplastic disorders.
Investigation of the Role of a Zinc Uptake Regulator (Zur) in the Virulence of Pectobacterium odoriferum
Authors: Chen Changlong , Cui Shuang , Guan Jiantao , Su Yanyan , Liang Xucong , Tian Yu , Xie Hua
Published: June 2023

Pectobacterium spp. infect many horticultural crops worldwide and lead to serious crop losses. Zinc-uptake-regulator (Zur) proteins are present widely in prokaryotes and play an important role in pathogenicity. To uncover the role of Zur in P. odoriferum, we constructed mutant (ΔZur) and overexpression [Po (Zur)] strains of a Zur, and a virulence assay showed that the Po (Zur) was of significantly lower virulence, while the ΔZur displayed significantly increased virulence on Chinese cabbage compared to their respective control strains, wild-type P. odoriferum (Po WT) and P. odoriferum harboring an empty vector (Po (EV)) (p < 0.05). The growth curves of the ΔZur and Po (Zur) showed no obvious differences from those of the control strains. Comparative transcriptome analysis showed that Zur overexpression in P. odoriferum induced differentially expressed genes (DEGs) related to flagellum and cell motility, while mutating Zur resulted in DEGs mainly corresponding to divalent-metal-ion transport and membrane transport. Phenotypic experiments on the Po (Zur) showed that flagellum numbers and cell motility were reduced in comparison with the control, while those of the ΔZur did not change. Collectively, these results show that the Zur negatively regulates the virulence of P. odoriferum and might function via a dual mechanism dependent on dose.
In Vitro and In Vivo Efficacy of a Stroma-Targeted, Tumor Microenvironment Responsive Oncolytic Adenovirus in Different Preclinical Models of Cancer
Authors: Alfano Ana , Cafferata Eduardo G. A. , Gangemi Mariela , Nicola Candia Alejandro , Malnero Cristian M. , Bermudez Ismael , Lopez Mauricio Vargas , Ríos Gregorio David , Rotondaro Cecilia , Cuneo Nicasio , Curiel David T. , Podhajcer Osvaldo L. , Lopez Maria Veronica
Published: June 2023

More than one million women are diagnosed annually worldwide with a gynecological cancer. Most gynecological cancers are diagnosed at a late stage, either because a lack of symptoms, such as in ovarian cancer or limited accessibility to primary prevention in low-resource countries, such as in cervical cancer. Here, we extend the studies of AR2011, a stroma-targeted and tumor microenvironment responsive oncolytic adenovirus (OAdV), whose replication is driven by a triple hybrid promoter. We show that AR2011 was able to replicate and lyse in vitro fresh explants obtained from human ovarian cancer, uterine cancer, and cervical cancer. AR2011 was also able to strongly inhibit the in vitro growth of ovarian malignant cells obtained from human ascites fluid. The virus could synergize in vitro with cisplatin even on ascites-derived cells obtained from patients heavily pretreated with neoadjuvant chemotherapy. AR2011(h404), a dual transcriptionally targeted derived virus armed with hCD40L and h41BBL under the regulation of the hTERT promoter, showed a strong efficacy in vivo both on subcutaneous and intraperitoneally established human ovarian cancer in nude mice. Preliminary studies in an immunocompetent murine tumor model showed that AR2011(m404) expressing the murine cytokines was able to induce an abscopal effect. The present studies suggest that AR2011(h404) is a likely candidate as a novel medicine for intraperitoneal disseminated ovarian cancer.