bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptome and Low-Affinity Sodium Transport Analysis Reveals Salt Tolerance Variations between Two Poplar Trees
Authors: Ma Xuan , Zhang Qiang , Ou Yongbin , Wang Lijun , Gao Yongfeng , Lucas Gutiérrez Rodríguez , Resco de Dios Víctor , Yao Yinan
Published: March 2023

Salinity stress severely hampers plant growth and productivity. How to improve plants’ salt tolerance is an urgent issue. However, the molecular basis of plant resistance to salinity still remains unclear. In this study, we used two poplar species with different salt sensitivities to conduct RNA-sequencing and physiological and pharmacological analyses; the aim is to study the transcriptional profiles and ionic transport characteristics in the roots of the two Populus subjected to salt stress under hydroponic culture conditions. Our results show that numerous genes related to energy metabolism were highly expressed in Populus alba relative to Populus russkii, which activates vigorous metabolic processes and energy reserves for initiating a set of defense responses when suffering from salinity stress. Moreover, we found the capacity of Na+ transportation by the P. alba high-affinity K+ transporter1;2 (HKT1;2) was superior to that of P. russkii under salt stress, which enables P. alba to efficiently recycle xylem-loaded Na+ and to maintain shoot K+/Na+ homeostasis. Furthermore, the genes involved in the synthesis of ethylene and abscisic acid were up-regulated in P. alba but downregulated in P. russkii under salt stress. In P. alba, the gibberellin inactivation and auxin signaling genes with steady high transcriptions, several antioxidant enzymes activities (such as peroxidase [POD], ascorbate peroxidase [APX], and glutathione reductase [GR]), and glycine-betaine content were significantly increased under salt stress. These factors altogether confer P. alba a higher resistance to salinity, achieving a more efficient coordination between growth modulation and defense response. Our research provides significant evidence to improve the salt tolerance of crops or woody plants.
Hepatocyte Nuclear Factor-1α Increases Fibrinogen Gene Expression in Liver and Plasma Fibrinogen Concentration in Rats with Experimental Chronic Renal Failure
Authors: Sucajtys-Szulc Elzbieta , Debska-Slizien Alicja , Rutkowski Boleslaw , Milczarek Ryszard , Szolkiewicz Marek , Swierczynski Julian , Smolenski Ryszard Tomasz
Published: March 2023

Chronic kidney disease (CKD) is associated with elevated plasma fibrinogen concentration. However, the underlying molecular mechanism for elevated plasma fibrinogen concentration in CKD patients has not yet been clarified. We recently found that HNF1α was significantly upregulated in the liver of chronic renal failure (CRF) rats, an experimental model of CKD in patients. Given that the promoter region of the fibrinogen gene possesses potential binding sites for HNF1α, we hypothesized that the upregulation of HNF1α can increase fibrinogen gene expression and consequently plasma fibrinogen concentration in the experimental model of CKD. Here, we found the coordinated upregulation of Aα-chain fibrinogen and Hnfα gene expression in the liver and elevated plasma fibrinogen concentrations in CRF rats, compared with pair-fed and control animals. Liver Aα-chain fibrinogen and HNF1α mRNAs levels correlated positively with (a) liver and plasma fibrinogen levels and (b) liver HNF1α protein levels. The positive correlation between (a) liver Aα-chain fibrinogen mRNA level, (b) liver Aα-chain fibrinogen level, and (c) serum markers of renal function suggest that fibrinogen gene transcription is closely related to the progression of kidney disease. Knockdown of Hnfα in the HepG2 cell line by small interfering RNA (siRNA) led to a decrease in fibrinogen mRNA levels. Clofibrate, an anti-lipidemic drug that reduces plasma fibrinogen concentration in humans, decreased both HNF1α and Aα-chain fibrinogen mRNAs levels in (a) the liver of CRF rats and (b) HepG2 cells. The obtained results suggest that (a) an elevated level of liver HNF1α can play an important role in the upregulation of fibrinogen gene expression in the liver of CRF rats, leading to an elevated concentration of plasma fibrinogen, a protein related to the risk of cardiovascular disease in CKD patients, and (b) fibrates can decrease plasma fibrinogen concentration through inhibition of HNF1α gene expression.
The Genetic Landscape of Myelodysplastic Neoplasm Progression to Acute Myeloid Leukemia
Authors: Bănescu Claudia , Tripon Florin , Muntean Carmen
Published: March 2023

Myelodysplastic neoplasm (MDS) represents a heterogeneous group of myeloid disorders that originate from the hematopoietic stem and progenitor cells that lead to the development of clonal hematopoiesis. MDS was characterized by an increased risk of transformation into acute myeloid leukemia (AML). In recent years, with the aid of next-generation sequencing (NGS), an increasing number of molecular aberrations were discovered, such as recurrent mutations in FLT3, NPM1, DNMT3A, TP53, NRAS, and RUNX1 genes. During MDS progression to leukemia, the order of gene mutation acquisition is not random and is important when considering the prognostic impact. Moreover, the co-occurrence of certain gene mutations is not random; some of the combinations of gene mutations seem to have a high frequency (ASXL1 and U2AF1), while the co-occurrence of mutations in splicing factor genes is rarely observed. Recent progress in the understanding of molecular events has led to MDS transformation into AML and unraveling the genetic signature has paved the way for developing novel targeted and personalized treatments. This article reviews the genetic abnormalities that increase the risk of MDS transformation to AML, and the impact of genetic changes on evolution. Selected therapies for MDS and MDS progression to AML are also discussed.
The Role of the Insular Cortex in Pain
Authors: Labrakakis Charalampos
Published: March 2023

The transition from normal to chronic pain is believed to involve alterations in several brain areas that participate in the perception of pain. These plastic changes are then responsible for aberrant pain perception and comorbidities. The insular cortex is consistently found activated in pain studies of normal and chronic pain patients. Functional changes in the insula contribute to chronic pain; however, the complex mechanisms by which the insula is involved in pain perception under normal and pathological conditions are still not clear. In this review, an overview of the insular function is provided and findings on its role in pain from human studies are summarized. Recent progress on the role of the insula in pain from preclinical experimental models is reviewed, and the connectivity of the insula with other brain regions is examined to shed new light on the neuronal mechanisms of the insular cortex’s contribution to normal and pathological pain sensation. This review underlines the need for further studies on the mechanisms underlying the involvement of the insula in the chronicity of pain and the expression of comorbid disorders.
MicroRNA miR171b Positively Regulates Resistance to Huanglongbing of Citrus
Authors: Lv Yuanda , Zhong Yun , Jiang Bo , Yan Huaxue , Ren Shuang , Cheng Chunzhen
Published: March 2023

Huanglongbing (HLB) is one of the most severe citrus diseases in the world, causing huge economic losses. However, efficient methods of protecting citrus from HLB have not yet been developed. microRNA (miRNA)-mediated regulation of gene expression is a useful tool to control plant diseases, but the miRNAs involved in regulating resistance to HLB have not yet been identified. In this study, we found that miR171b positively regulated resistance to HLB in citrus. Upon infection with HLB bacteria, the bacteria were detected in the second month in the control plants. However, in the miR171b-overexpressing transgenic citrus plants, the bacteria could not be detected until the 24th month. RNA-seq data indicated that multiple pathways, such as photosynthesis, plant–pathogen interaction, the MAPK signaling pathway, etc., might be involved in improving the resistance to HLB in miR171b-overexpressing plants compared with the control. Finally, we determined that miR171b could target SCARECROW-like (SCL) genes to downregulate their expression, which then led to promoted resistance to HLB stress. Collectively, our results demonstrate that miR171b plays a positive regulatory role in resistance to citrus HLB, and provides a new insight into the role of miRNAs in the adaptation of citrus to HLB stress.
Erythrocytes Functionality in SARS-CoV-2 Infection: Potential Link with Alzheimer’s Disease
Authors: Kosenko Elena , Tikhonova Lyudmila , Alilova Gubidat , Montoliu Carmina
Published: March 2023

Coronavirus disease 2019 (COVID-19) is a rapidly spreading acute respiratory infection caused by SARS-CoV-2. The pathogenesis of the disease remains unclear. Recently, several hypotheses have emerged to explain the mechanism of interaction between SARS-CoV-2 and erythrocytes, and its negative effect on the oxygen-transport function that depends on erythrocyte metabolism, which is responsible for hemoglobin-oxygen affinity (Hb-O2 affinity). In clinical settings, the modulators of the Hb-O2 affinity are not currently measured to assess tissue oxygenation, thereby providing inadequate evaluation of erythrocyte dysfunction in the integrated oxygen-transport system. To discover more about hypoxemia/hypoxia in COVID-19 patients, this review highlights the need for further investigation of the relationship between biochemical aberrations in erythrocytes and oxygen-transport efficiency. Furthermore, patients with severe COVID-19 experience symptoms similar to Alzheimer’s, suggesting that their brains have been altered in ways that increase the likelihood of Alzheimer’s. Mindful of the partly assessed role of structural, metabolic abnormalities that underlie erythrocyte dysfunction in the pathophysiology of Alzheimer’s disease (AD), we further summarize the available data showing that COVID-19 neurocognitive impairments most probably share similar patterns with known mechanisms of brain dysfunctions in AD. Identification of parameters responsible for erythrocyte function that vary under SARS-CoV-2 may contribute to the search for additional components of progressive and irreversible failure in the integrated oxygen-transport system leading to tissue hypoperfusion. This is particularly relevant for the older generation who experience age-related disorders of erythrocyte metabolism and are prone to AD, and provide an opportunity for new personalized therapies to control this deadly infection.
Comparison of Efficacy and Inflammatory Response to Thermoconjunctivoplasty Performed with Cautery or Pulsed 1460 nm Laser
Authors: de Souza Rodrigo Guimaraes , Huang David , Prahl Scott , Nakhleh Lauren , Pflugfelder Stephen C.
Published: March 2023

Conjunctivochalasis is a degenerative condition of the conjunctiva that disrupts tear distribution and causes irritation. Thermoreduction of the redundant conjunctiva is required if symptoms are not relieved with medical therapy. Near-infrared laser treatment is a more controlled method to shrink the conjunctiva than thermocautery. This study compared tissue shrinkage, histology, and postoperative inflammation in thermoconjunctivoplasty performed on the mouse conjunctiva using either thermocautery or pulsed 1460 nm near-infrared laser irradiation. Three sets of experiments were performed on female C57BL/6J mice (n = 72, 26 per treatment group and 20 control) to assess conjunctival shrinkage, wound histology, and inflammation 3 and 10 days after treatment. Both treatments effectively shrunk the conjunctiva, but thermocautery caused greater epithelial damage. Thermocautery caused greater infiltration of neutrophils on day 3 and neutrophils and CD11b+ myeloid cells on day 10. The thermocautery group had significantly higher conjunctival expression of IL-1β on day 3. Expression of chemokine CCL2 was higher in the conjunctiva on day 3 and tear concentrations were higher on day 7 in the laser group. These results suggest that pulsed laser treatment causes less tissue damage and postoperative inflammation than thermocautery while effectively addressing conjunctivochalasis.
The Tryptophan and Kynurenine Pathway Involved in the Development of Immune-Related Diseases
Authors: Tsuji Ai , Ikeda Yuka , Yoshikawa Sayuri , Taniguchi Kurumi , Sawamura Haruka , Morikawa Sae , Nakashima Moeka , Asai Tomoko , Matsuda Satoru
Published: March 2023

The tryptophan and kynurenine pathway is well-known to play an important role in nervous, endocrine, and immune systems, as well as in the development of inflammatory diseases. It has been documented that some kynurenine metabolites are considered to have anti-oxidative, anti-inflammatory, and/or neuroprotective properties. Importantly, many of these kynurenine metabolites may possess immune-regulatory properties that could alleviate the inflammation response. The abnormal activation of the tryptophan and kynurenine pathway might be involved in the pathophysiological process of various immune-related diseases, such as inflammatory bowel disease, cardiovascular disease, osteoporosis, and/or polycystic ovary syndrome. Interestingly, kynurenine metabolites may be involved in the brain memory system and/or intricate immunity via the modulation of glial function. In the further deliberation of this concept with engram, the roles of gut microbiota could lead to the development of remarkable treatments for the prevention of and/or the therapeutics for various intractable immune-related diseases.
Proteomic Analysis of Skeletal Muscle and White Adipose Tissue after Aerobic Exercise Training in High Fat Diet Induced Obese Mice
Authors: Chou Tzu-Jung , Lu Chia-Wen , Lin Li-Yu , Hsu Yi-Ju , Huang Chi-Chang , Huang Kuo-Chin
Published: March 2023

Obesity is associated with excessive fat accumulation in adipose tissue and other organs, such as skeletal muscle, whereas aerobic exercise (AE) plays an important role in managing obesity through profound protein regulation. Our study aimed to investigate the impact of AE on proteomic changes in both the skeletal muscle and the epididymal fat pad (EFP) of high-fat-diet-induced obese mice. Bioinformatic analyses were performed on differentially regulated proteins using gene ontology enrichment analysis and ingenuity pathway analysis. Eight weeks of AE significantly reduced body weight, increased the serum FNDC5 level, and improved the homeostatic model assessment of insulin resistance. A high-fat diet caused alterations in a subset of proteins involved in the sirtuin signaling pathway and the production of reactive oxygen species in both skeletal muscle and EFP, leading to insulin resistance, mitochondrial dysfunction, and inflammation. On the other hand, AE upregulated skeletal muscle proteins (NDUFB5, NDUFS2, NDUFS7, ETFD, FRDA, and MKNK1) that enhance mitochondrial function and insulin sensitivity. Additionally, the upregulation of LDHC and PRKACA and the downregulation of CTBP1 in EFP can promote the browning of white adipose tissue with the involvement of FNDC5/irisin in the canonical pathway. Our study provides insights into AE-induced molecular responses and may help further develop exercise-mimicking therapeutic targets.
Induced Coma, Death, and Organ Transplantation: A Physiologic, Genetic, and Theological Perspective
Authors: Coliță Cezar-Ivan , Olaru Denissa-Greta , Coliță Daniela , Hermann Dirk M. , Coliță Eugen , Glavan Daniela , Popa-Wagner Aurel
Published: March 2023

In the clinic, the death certificate is issued if brain electrical activity is no longer detectable. However, recent research has shown that in model organisms and humans, gene activity continues for at least 96 h postmortem. The discovery that many genes are still working up to 48 h after death questions our definition of death and has implications for organ transplants and forensics. If genes can be active up to 48 h after death, is the person technically still alive at that point? We discovered a very interesting parallel between genes that were upregulated in the brain after death and genes upregulated in the brains that were subjected to medically-induced coma, including transcripts involved in neurotransmission, proteasomal degradation, apoptosis, inflammation, and most interestingly, cancer. Since these genes are involved in cellular proliferation, their activation after death could represent the cellular reaction to escape mortality and raises the question of organ viability and genetics used for transplantation after death. One factor limiting the organ availability for transplantation is religious belief. However, more recently, organ donation for the benefit of humans in need has been seen as “posthumous giving of organs and tissues can be a manifestation of love spreading also to the other side of death”.
Gene Expression Profiling as a Novel Diagnostic Tool for Neurodegenerative Disorders
Authors: Martínez-Iglesias Olaia , Naidoo Vinogran , Carril Juan Carlos , Seoane Silvia , Cacabelos Natalia , Cacabelos Ramón
Published: March 2023

There is a lack of effective diagnostic biomarkers for neurodegenerative disorders (NDDs). Here, we established gene expression profiles for diagnosing Alzheimer’s disease (AD), Parkinson’s disease (PD), and vascular (VaD)/mixed dementia. Patients with AD had decreased APOE, PSEN1, and ABCA7 mRNA expression. Subjects with VaD/mixed dementia had 98% higher PICALM mRNA levels, but 75% lower ABCA7 mRNA expression than healthy individuals. Patients with PD and PD-related disorders showed increased SNCA mRNA levels. There were no differences in mRNA expression for OPRK1, NTRK2, and LRRK2 between healthy subjects and NDD patients. APOE mRNA expression had high diagnostic accuracy for AD, and moderate accuracy for PD and VaD/mixed dementia. PSEN1 mRNA expression showed promising accuracy for AD. PICALM mRNA expression was less accurate as a biomarker for AD. ABCA7 and SNCA mRNA expression showed high-to-excellent diagnostic accuracy for AD and PD, and moderate-to-high accuracy for VaD/mixed dementia. The APOE E4 allele reduced APOE expression in patients with different APOE genotypes. There was no association between PSEN1, PICALM, ABCA7, and SNCA gene polymorphisms and expression. Our study suggests that gene expression analysis has diagnostic value for NDDs and provides a liquid biopsy alternative to current diagnostic methods.
The Emerging Importance of Cirsimaritin in Type 2 Diabetes Treatment
Authors: Alqudah Abdelrahim , Athamneh Rabaa Y. , Qnais Esam , Gammoh Omar , Oqal Muna , AbuDalo Rawan , Alshaikh Hanan Abu , AL-Hashimi Nabil , Alqudah Mohammad
Published: March 2023

Cirsimaritin is a dimethoxy flavon that has different biological activities such as antiproliferative, antimicrobial, and antioxidant activities. This study aims to investigate the anti-diabetic effects of cirsimaritin in a high-fat diet and streptozotocin-(HFD/STZ)-induced rat model of type 2 diabetes mellitus (T2D). Rats were fed HFD, followed by a single low dose of STZ (40 mg/kg). HFD/STZ diabetic rats were treated orally with cirsimaritin (50 mg/kg) or metformin (200 mg/kg) for 10 days before terminating the experiment and collecting plasma, soleus muscle, adipose tissue, and liver for further downstream analysis. Cirsimaritin reduced the elevated levels of serum glucose in diabetic rats compared to the vehicle control group (p < 0.001). Cirsimaritin abrogated the increase in serum insulin in the treated diabetic group compared to the vehicle control rats (p < 0.01). The homeostasis model assessment of insulin resistance (HOMA-IR) was decreased in the diabetic rats treated with cirsimaritin compared to the vehicle controls. The skeletal muscle and adipose tissue protein contents of GLUT4 (p < 0.01 and p < 0.05, respectively) and pAMPK-α1 (p < 0.05) were upregulated following treatment with cirsimaritin. Cirsimaritin was able to upregulate GLUT2 and AMPK protein expression in the liver (p < 0.01, <0.05, respectively). LDL, triglyceride, and cholesterol were reduced in diabetic rats treated with cirsimaritin compared to the vehicle controls (p < 0.001). Cirsimaritin reduced MDA, and IL-6 levels (p < 0.001), increased GSH levels (p < 0.001), and reduced GSSG levels (p < 0.001) in diabetic rats compared to the vehicle control. Cirsimaritin could represent a promising therapeutic agent to treat T2D.
Modulation of Visual Responses and Ocular Dominance by Contralateral Inhibitory Activation in the Mouse Visual Cortex
Authors: Wu Wei , Li Lei , Liu Yueqin , Kang Luwei , Guo Hui , Ma Chenchen , Yang Yupeng
Published: March 2023

Both hemispheres connect with each other by excitatory callosal projections, and whether inhibitory interneurons, usually believed to have local innervation, engage in transcallosal activity modulation is unknown. Here, we used optogenetics in combination with cell-type-specific channelrhodopsin-2 expression to activate different inhibitory neuron subpopulations in the visual cortex and recorded the response of the entire visual cortex using intrinsic signal optical imaging. We found that optogenetic stimulation of inhibitory neurons reduced spontaneous activity (increase in the reflection of illumination) in the binocular area of the contralateral hemisphere, although these stimulations had different local effects ipsilaterally. The activation of contralateral interneurons differentially affected both eye responses to visual stimuli and, thus, changed ocular dominance. Optogenetic silencing of excitatory neurons affects the ipsilateral eye response and ocular dominance in the contralateral cortex to a lesser extent. Our results revealed a transcallosal effect of interneuron activation in the mouse visual cortex.
Non-Coding RNAs as Biomarkers for Embryo Quality and Pregnancy Outcomes: A Systematic Review and Meta-Analysis
Authors: Huang Wen , Chen Andy Chun Hang , Ng Ernest Hung Yu , Yeung William Shu Biu , Lee Yin Lau
Published: March 2023

Despite advances in in vitro fertilization (IVF), there is still a lack of non-invasive and reliable biomarkers for selecting embryos with the highest developmental and implantation potential. Recently, small non-coding RNAs (sncRNAs) have been identified in biological fluids, and extracellular sncRNAs are explored as diagnostic biomarkers in the prediction of IVF outcomes. To determine the predictive role of sncRNAs in embryo quality and IVF outcomes, a systematic review and meta-analysis was performed. Articles were retrieved from PubMed, EMBASE, and Web of Science from 1990 to 31 July 2022. Eighteen studies that met the selection criteria were analyzed. In total, 22 and 47 different sncRNAs were found to be dysregulated in follicular fluid (FF) and embryo spent culture medium (SCM), respectively. MiR-663b, miR-454 and miR-320a in FF and miR-20a in SCM showed consistent dysregulation in two different studies. The meta-analysis indicated the potential predictive performance of sncRNAs as non-invasive biomarkers, with a pooled area under curve (AUC) value of 0.81 (95% CI 0.78, 0.844), a sensitivity of 0.79 (95% CI 0.72, 0.85), a specificity of 0.67 (95% CI 0.52, 0.79) and a diagnostic odds ratio (DOR) of 8 (95% CI 5, 12). Significant heterogeneity was identified among studies in sensitivity (I2  =  46.11%) and specificity (I2  =  89.73%). This study demonstrates that sncRNAs may distinguish embryos with higher developmental and implantation potentials. They can be promising non-invasive biomarkers for embryo selection in ART. However, the significant heterogeneity among studies highlights the demand for prospective multicenter studies with optimized methods and adequate sample sizes in the future.
A View on Uterine Leiomyoma Genesis through the Prism of Genetic, Epigenetic and Cellular Heterogeneity
Authors: Koltsova Alla , Efimova Olga , Pendina Anna
Published: March 2023

Uterine leiomyomas (ULs), frequent benign tumours of the female reproductive tract, are associated with a range of symptoms and significant morbidity. Despite extensive research, there is no consensus on essential points of UL initiation and development. The main reason for this is a pronounced inter- and intratumoral heterogeneity resulting from diverse and complicated mechanisms underlying UL pathobiology. In this review, we comprehensively analyse risk and protective factors for UL development, UL cellular composition, hormonal and paracrine signalling, epigenetic regulation and genetic abnormalities. We conclude the need to carefully update the concept of UL genesis in light of the current data. Staying within the framework of the existing hypotheses, we introduce a possible timeline for UL development and the associated key events—from potential prerequisites to the beginning of UL formation and the onset of driver and passenger changes.
Unraveling the Role of Antimicrobial Peptides in Insects
Authors: Stączek Sylwia , Cytryńska Małgorzata , Zdybicka-Barabas Agnieszka
Published: March 2023

Antimicrobial peptides (AMPs) are short, mainly positively charged, amphipathic molecules. AMPs are important effectors of the immune response in insects with a broad spectrum of antibacterial, antifungal, and antiparasitic activity. In addition to these well-known roles, AMPs exhibit many other, often unobvious, functions in the host. They support insects in the elimination of viral infections. AMPs participate in the regulation of brain-controlled processes, e.g., sleep and non-associative learning. By influencing neuronal health, communication, and activity, they can affect the functioning of the insect nervous system. Expansion of the AMP repertoire and loss of their specificity is connected with the aging process and lifespan of insects. Moreover, AMPs take part in maintaining gut homeostasis, regulating the number of endosymbionts as well as reducing the number of foreign microbiota. In turn, the presence of AMPs in insect venom prevents the spread of infection in social insects, where the prey may be a source of pathogens.
A Quick Prototype for Assessing OpenIE Knowledge Graph-Based Question-Answering Systems
Authors: Di Paolo Giuseppina , Rincon-Yanez Diego , Senatore Sabrina
Published: March 2023

Due to the rapid growth of knowledge graphs (KG) as representational learning methods in recent years, question-answering approaches have received increasing attention from academia and industry. Question-answering systems use knowledge graphs to organize, navigate, search and connect knowledge entities. Managing such systems requires a thorough understanding of the underlying graph-oriented structures and, at the same time, an appropriate query language, such as SPARQL, to access relevant data. Natural language interfaces are needed to enable non-technical users to query ever more complex data. The paper proposes a question-answering approach to support end users in querying graph-oriented knowledge bases. The system pipeline is composed of two main modules: one is dedicated to translating a natural language query submitted by the user into a triple of the form , while the second module implements knowledge graph embedding (KGE) models, exploiting the previous module triple and retrieving the answer to the question. Our framework delivers a fast OpenIE-based knowledge extraction system and a graph-based answer prediction model for question-answering tasks. The system was designed by leveraging existing tools to accomplish a simple prototype for fast experimentation, especially across different knowledge domains, with the added benefit of reducing development time and costs. The experimental results confirm the effectiveness of the proposed system, which provides promising performance, as assessed at the module level. In particular, in some cases, the system outperforms the literature. Finally, a use case example shows the KG generated by user questions in a graphical interface provided by an ad-hoc designed web application.
A Systematic Review of Transformer-Based Pre-Trained Language Models through Self-Supervised Learning
Authors: Kotei Evans , Thirunavukarasu Ramkumar
Published: March 2023

Transfer learning is a technique utilized in deep learning applications to transmit learned inference to a different target domain. The approach is mainly to solve the problem of a few training datasets resulting in model overfitting, which affects model performance. The study was carried out on publications retrieved from various digital libraries such as SCOPUS, ScienceDirect, IEEE Xplore, ACM Digital Library, and Google Scholar, which formed the Primary studies. Secondary studies were retrieved from Primary articles using the backward and forward snowballing approach. Based on set inclusion and exclusion parameters, relevant publications were selected for review. The study focused on transfer learning pretrained NLP models based on the deep transformer network. BERT and GPT were the two elite pretrained models trained to classify global and local representations based on larger unlabeled text datasets through self-supervised learning. Pretrained transformer models offer numerous advantages to natural language processing models, such as knowledge transfer to downstream tasks that deal with drawbacks associated with training a model from scratch. This review gives a comprehensive view of transformer architecture, self-supervised learning and pretraining concepts in language models, and their adaptation to downstream tasks. Finally, we present future directions to further improvement in pretrained transformer-based language models.
Ontology-Driven Knowledge Sharing in Alzheimer’s Disease Research
Authors: Lazarova Sophia , Petrova-Antonova Dessislava , Kunchev Todor
Published: March 2023

Alzheimer’s disease is a debilitating neurodegenerative condition which is known to be the most common cause of dementia. Despite its rapidly growing prevalence, medicine still lacks a comprehensive definition of the disease. As a result, Alzheimer’s disease remains neither preventable nor curable. In recent years, broad interdisciplinary collaborations in Alzheimer’s disease research are becoming more common. Furthermore, such collaborations have already demonstrated their superiority in addressing the complexity of the disease in innovative ways. However, establishing effective communication and optimal knowledge distribution between researchers and specialists with different expertise and background is not a straightforward task. To address this challenge, we propose the Alzheimer’s disease Ontology for Diagnosis and Preclinical Classification (AD-DPC) as a tool for effective knowledge sharing in interdisciplinary/multidisciplinary teams working on Alzheimer’s disease. It covers six major conceptual groups, namely Alzheimer’s disease pathology, Alzheimer’s disease spectrum, Diagnostic process, Symptoms, Assessments, and Relevant clinical findings. All concepts were annotated with definitions or elucidations and in some cases enriched with synonyms and additional resources. The potential of AD-DPC to support non-medical experts is demonstrated through an evaluation of its usability, applicability and correctness. The results show that the participants in the evaluation process who lack prior medical knowledge can successfully answer Alzheimer’s disease-related questions by interacting with AD-DPC. Furthermore, their perceived level of knowledge in the field increased leading to effective communication with medical experts.
A Helium Speech Unscrambling Algorithm Based on Deep Learning
Authors: Chen Yonghong , Zhang Shibing
Published: March 2023

Helium speech, the language spoken by divers in the deep sea who breathe a high-pressure helium–oxygen mixture, is almost unintelligible. To accurately unscramble helium speech, a neural network based on deep learning is proposed. First, an isolated helium speech corpus and a continuous helium speech corpus in a normal atmosphere are constructed, and an algorithm to automatically generate label files is proposed. Then, a convolution neural network (CNN), connectionist temporal classification (CTC) and a transformer are combined into a speech recognition network. Finally, an optimization algorithm is proposed to improve the recognition of continuous helium speech, which combines depth-wise separable convolution (DSC), a gated linear unit (GLU) and a feedforward neural network (FNN). The experimental results show that the accuracy of the algorithm, upon combining the CNN, CTC and the transformer, is 91.38%, and the optimization algorithm improves the accuracy of continuous helium speech recognition by 9.26%.
A Survey on Feature Selection Techniques Based on Filtering Methods for Cyber Attack Detection
Authors: Lyu Yang , Feng Yaokai , Sakurai Kouichi
Published: March 2023

Cyber attack detection technology plays a vital role today, since cyber attacks have been causing great harm and loss to organizations and individuals. Feature selection is a necessary step for many cyber-attack detection systems, because it can reduce training costs, improve detection performance, and make the detection system lightweight. Many techniques related to feature selection for cyber attack detection have been proposed, and each technique has advantages and disadvantages. Determining which technology should be selected is a challenging problem for many researchers and system developers, and although there have been several survey papers on feature selection techniques in the field of cyber security, most of them try to be all-encompassing and are too general, making it difficult for readers to grasp the concrete and comprehensive image of the methods. In this paper, we survey the filter-based feature selection technique in detail and comprehensively for the first time. The filter-based technique is one popular kind of feature selection technique and is widely used in both research and application. In addition to general descriptions of this kind of method, we also explain in detail search algorithms and relevance measures, which are two necessary technical elements commonly used in the filter-based technique.
A Review of the Host Plant Location and Recognition Mechanisms of Asian Longhorn Beetle
Authors: Lyu Fei , Hai Xiaoxia , Wang Zhigang
Published: March 2023

The Asian longhorn beetle (ALB), Anoplophora glabripennis Motschulsky, is a polyphagous xylophage with dozens of reported host tree species. However, the mechanisms by which individuals locate and recognize host plants are still unknown. We summarize the current knowledge of the host plant list, host kairomones, odorant-binding proteins (OBPs) and microbial symbionts of this beetle and their practical applications, and finally discuss the host localization and recognition mechanisms. A total of 209 species (or cultivars) were reported as ALB host plants, including 101 species of higher sensitivity; host kairomones were preferentially bound to ALB recombinant OBPs, including cis-3-hexen-1-ol, δ-3-carene, nonanal, linalool, and β-caryophyllene. In addition, microbial symbionts may help ALB degrade their host. Complementarity of tree species with different levels of resistance may reduce damage, but trapping effectiveness for adults was limited using a combination of host kairomones and sex pheromones in the field. Therefore, we discuss host location behavior from a new perspective and show that multiple cues are used by ALB to locate and recognize host plants. Further research into host resistance mechanisms and visual signal recognition, and the interaction of sex pheromone synthesis, symbiont microbiota, and host plants may help reveal the host recognition mechanisms of ALBs.
Safe and Successful Surgical Outcome in Persons with Hemophilia A with and without Inhibitors Treated with Emicizumab: A Large, Single Center, Real-World Experience
Authors: Castaman Giancarlo , Linari Silvia , Pieri Lisa , Carulli Christian , Prosperi Paolo , Tonelli Paolo , Demartis Francesco , Fjerza Rajmonda , Attanasio Monica , Coppo Mirella , Salvianti Francesca
Published: March 2023

Emicizumab is a humanized recombinant bispecific antibody, bridging together activated factor IX (FIXa) and factor X (FX), thus mimicking the activity of FVIII in vivo. Emicizumab is designed for long-term prophylaxis in patients with severe hemophilia A with and without inhibitors. This approach provides constant protection, with significant reduction in bleeding rate and improved quality of life. However, protection provided by emicizumab is not absolute, and clotting factor concentrates (FVIII, rFVIIa, aPCC) may be necessary for post-traumatic bleeding or surgery, with a potential thrombotic risk or difficulty in preventing bleeding. Real world evidence is still scanty, especially for managing major surgery. In this study, 75 surgeries were managed in 28 patients (27 major procedures in 15 patients and 48 minor procedures in 20 patients. In 17 patients without inhibitors, 30 minor surgeries were carried out by using FVIII in 5, with only a bleeding event, which was successfully treated with FVIII concentrate. Six major surgeries were uneventfully performed with FVIII concentrate. Eleven PWHA and high-titer inhibitors underwent 39 surgical procedures (18 minor and 21 major surgeries). Minor surgeries were mostly performed without prophylaxis with rFVIIa, with only a single bleeding complication. All 21 major surgeries were covered with a homogeneous protocol using rFVIIa. In four instances, bleeding complications occurred, treated with rFVIIa. Of them, a single patient only failed to respond and died because of an uncontrollable bleeding from a large ruptured retroperitoneal pseudotumor. Surgery in patients with emicizumab can be safely carried out with the use of appropriate replacement therapy protocols.
Effect of Frozen-Thawed Embryo Transfer on the Metabolism of Children in Early Childhood
Authors: Dong Ze-Han , Wu Ting , Zhang Chen , Su Kai-Zhen , Wu Yan-Ting , Huang He-Feng
Published: March 2023

Background: As a routine procedure in assisted reproductive technology (ART), it is crucial to assess the safety of frozen and thawed embryo transfer (FET). We aimed to investigate the metabolic profile of children conceived through FET in their early childhood. Method: A total of 147 children between the age of 1.5 and 4 years old, conceived through FET or naturally conceived (NC), were recruited. A total of 89 children, 65 in the FET group and 24 in the NC group (matched with the FET group based on children’s BMI) were included in the final statistical analysis of biochemical markers and metabolomics. Results: Children conceived through FET had a lower level of fasting insulin level and HORM-IR and a higher level of fasting glucose and APOE as compared to children naturally conceived. Metabolomics showed that there were 16 small differential metabolites, mainly including amino acids, carnitines, organic acids, butyric, and secondary bile acid between two groups, which enriched in Nitrogen metabolism, Butanoate metabolism, Phenylalanine metabolism, and D-Arginine and D-ornithine metabolism pathways. Conclusion: Although the FET group had a significantly higher level of APOE and fasting glucose, it cannot yet be considered that children in the FET group had an obvious disorder of glucose and lipid metabolism. However, the potentially more active intestinal flora and lower carnitine levels of children in the FET group suggested by metabolomics are worth further exploration.
A Soccer Shot with Lengthy Consequences—Case Report & Current Literature Review of Commotio Cordis
Authors: Spitaler Philipp , Stühlinger Markus , Adukauskaite Agne , Bauer Axel , Dichtl Wolfgang
Published: March 2023

(1) Background: Commotio cordis, caused by objects being directly delivered to the chest, may cause cardiac arrest in young athletes, even without identifiable structural damage to the sternum, ribs or heart itself. Its prevention and management often remain suboptimal, resulting in dismal outcomes. (2) Case summary: A 32-year semi-professional goalkeeper suffered from a non-penetrating blunt thoracic trauma after being struck by a high-velocity shot during a regional league soccer game. He immediately lost consciousness, collapsed, and was successfully resuscitated through early defibrillation of ventricular fibrillation. After an uneventful follow-up for approximately 6 years, recurrent episodes of ventricular tachycardia occurred, which could ultimately only be prevented by epicardial ablation. (3) Conclusion: Very late recurrences of ventricular tachyarrhythmias may occur after ventricular fibrillation due to blunt chest trauma, even in the primary absence of evident structural myocardial damage.
CAR T-Cell Therapy in Children with Solid Tumors
Authors: Kulczycka Marika , Derlatka Kamila , Tasior Justyna , Lejman Monika , Zawitkowska Joanna
Published: March 2023

The limited efficacy of traditional cancer treatments, including chemotherapy, radiotherapy, and surgery, emphasize the significance of employing innovative methods. CAR (Chimeric Antigen Receptor) T-cell therapy remains the most revolutionizing treatment of pediatric hematological malignancies and solid tumors. Patient’s own lymphocytes are modified ex-vivo using gene transfer techniques and programmed to recognize and destroy specific tumor cells regardless of MHC receptor, which probably makes CAR-T the most personalized therapy for the patient. With continued refinement and optimization, CAR-T cell therapy has the potential to significantly improve outcomes and quality of life for children with limited treatment options. It has shown remarkable success in treating hematological malignancies, such as acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL). However, its effectiveness in treating solid tumors is still being investigated and remains an area of active research. In this review we focus on solid tumors and explain the concept of CAR modified T cells, and discuss some novel CAR designs that are being considered to enhance the safety of CAR T-cell therapy in under-mentioned cancers. Furthermore, we summarize the most crucial recent reports concerning the solid tumors treatment in children. In the end we provide a short summary of many challenges that limit the therapeutic efficacy of CAR-T in solid tumors, such as antigen escape, immunosuppressive microenvironment, poor trafficking, and tumor infiltration, on-target off-tumor effects and general toxicity.
Does the Loss of Teeth Have an Impact on Geriatric Patients’ Cognitive Status?
Authors: Budală Dana Gabriela , Balcoș Carina , Armencia Adina , Virvescu Dragoș Ioan , Lupu Costin Iulian , Baciu Elena Raluca , Vasluianu Roxana Ionela , Tatarciuc Monica , Luchian Ionuț
Published: March 2023

Significant changes in the microstructure of the brain cause dementia and other mental declines associated with aging and disease. Although research has established a connection between oral health and dementia, the underlying pathologic mechanisms are still unknown. Aim: Our aim was to evaluate dentures’ impact on the cognitive state of geriatric patients. Material and methods: A total of 108 individuals seeking treatment at the Faculty of Dental Medicine in Iasi, Romania, participated in the study, which ran from May 2022 to October 2022. Cognitive dysfunction was assessed using the Mini-Mental State Examination. The acquired data were analyzed with IBM SPSS 26.0, and the p-value was set at 0.05. Results: The average value of the MMSE score was 21.81 ± 3.872. Differences between groups of wearer/non-wearer subjects were statistically significant for most of the questions in the questionnaire. Linear regression analysis showed that individuals with a high MMSE score have prosthodontic treatment. A decrease in the MMSE score is associated with a decrease in masticatory efficiency (B = 1.513, p = 0.268). Conclusions: This study provides further evidence that tooth loss is associated with worse cognitive performance. It is thus conceivable that the necessary effects can be achieved by increasing the efforts dedicated to preventing tooth loss in the adult population.
Exploratory Study of Associations and Agreement between Prognostic Patient-Registered Factors, Physiotherapists’ Intuitive Synthesis, and Patient-Reported Factors in Whiplash-Associated Disorders
Authors: Oostendorp Rob A. B. , Scholten-Peeters Gwendolyne G. M. , Mulder Jan , Van Trijffel Emiel , Rutten Geert M. , De Kooning Margot , Laekeman Marjan , Roussel Nathalie , Nijs Jo , Elvers J. W. Hans
Published: March 2023

Background: A large proportion of people who sustain a whiplash injury will have persistent pain, disability, and participation problems. Several prognostic factors for functional recovery have been reported in the literature but these factors are often evaluated based on differing implementations in clinical practice. Additionally, physiotherapists also rely on their clinical intuition to estimate the functional prognosis of their patients, but this is seldom measured in experimental research. Furthermore, no study to date has explored the associations between clinical intuition, clinically estimated factors, and objectively measured factors for functional recovery of patients with Whiplash-Associated Disorders (WAD). Aim: The aim of this exploratory study is to evaluate associations between prognostic factors for functional recovery, based on routinely collected data in a specialized primary care physiotherapy practice in a consecutive sample of patients (n = 523) with WAD. Methods: Three sources of prognostic factors were selected: (1) physiotherapists’ synthesis of clinical intuition in terms of high-risk, inconclusive risk, or low-risk for functional recovery, (2) patient-registered factors from history taking, and (3) patient-reported prognostic factors derived from questionnaires. Prognostic factors were selected based on the literature, recommendations in Dutch clinical practice guidelines, and consensus between experts. Spearman’s rank correlation coefficients were calculated to explore the associations between sources of prognostic factors, using a cutoff ≥0.25 for acceptable association. Results: Associations between physiotherapists’ intuitive synthesis and patient-registered variables were substantial (rs = 0.86), between patient-registered variables and patient-reported variables fair (ranging from 0.30 to 0.41) to substantial (ranging from 0.69 to 0.73), and between physiotherapists intuitive synthesis and patient-reported variables fair (ranging from 0.30 to 0.37). Conclusion: When estimating prognosis for functional recovery using clinical reasoning, physiotherapists should integrate patients’ registered experience of their course of recovery, as well as the timeline after an accident, with their own synthesis of clinical intuition regarding prognostic factors in patients with WAD.