bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptomic profiles of poplar (Populus simonii × P. nigra) cuttings during adventitious root formation
Authors: Yu Yue , Meng Nan , Chen Song , Zhang Hongjiao , Liu Zhijie , Wang Yiran , Jing Yanan , Wang Yuting , Chen Su
Published: September 2022

The formation of adventitious roots (ARs) is vital for the vegetative propagation of poplars. However, the relevant mechanisms remain unclear. To reveal the underlying molecular mechanism, we used RNA-seq to investigate the transcriptional alterations of poplar cuttings soaked in water for 0, 2, 4, 6, 8, and 10 d; 3,798 genes were differentially expressed at all the time points, including 2,448 upregulated and 1,350 downregulated genes. Biological processes including “cell cycle,” “photosynthesis,” “regulation of hormone levels,” and “auxin transport” were enriched in the differentially expressed genes (DEGs). KEGG results showed that the common DEGs were most enriched in the pathway of “Carbon fixation in photosynthetic organisms” and “Starch and sucrose metabolism.” We further dissected 38 DEGs related to root and auxin, including two lateral root primordium 1 (LRP1), one root meristem growth factor (RGF9), one auxin-induced in the root (AIR12), three rooting-associated genes (AUR1 and AUR3), eight auxin transcription factors (ARFs and LBDs), 10 auxin respective genes (SAURs and GH3s), nine auxin transporters (PINs, ABCs, LAX2, and AUXs), and four auxin signal genes (IAAs and TIR1). We found that the rooting abilities of poplar cuttings with and without leaves are different. By applying different concentrations of IBA and sucrose to the top of cuttings without leaves, we found that 0.2 mg/ml IBA and 2 mg/ml sucrose had the best effect on promoting AR formation. The transcriptome results indicated photosynthesis may influence AR formation in poplar cuttings with leaves and revealed a potential regulatory mechanism of leafy cuttage from poplar cuttings. In addition, we provided a new perspective to resolve rooting difficulties in recalcitrant species.
Local Immunoglobulin E in nasal polyps: Role and modulation
Authors: Shen Yang , Zhang Nan , Yang Yucheng , Hong Suling , Bachert Claus
Published: September 2022

In the airway, IgE is traditionally regarded as a key mediator in allergic diseases, such as AR and allergic asthma. However, growing evidence demonstrates the importance of local IgE in airway inflammatory diseases, irrespective of the presence of allergy. In this review, we discuss the most recent evidence for IgE in chronic rhinosinusitis with nasal polyps(CRSwNP), including the local IgE’s characteristics, the modulation of its synthesis, and its function. The levels of local IgE are significantly elevated in polyps independently of IgE serum levels and atopic status. Local IgE, which is correlated with type 2 inflammation, is polyclonal and functional. IgE is produced by active B cells and is dependent on the class switch recombination(CSR). In NPs, this process is triggered by not only allergens but also microbial colonization, especially the superantigen-Staphylococcus aureus. The production of local IgE is modulated by lymphocytes(such as Tfh, ILC2s, iTreg), cytokines(such as IL-4, IL-13, IFN-γ, TGF-β, IL-2, IL-21), transcription factors, and B cell-intrinsic factor. Due to the central role of IgE in NPs, it is regarded as an ideal target for therapy and has been proved to be clinically successful. Based on this knowledge, we believe that exploring the trigger and regulatory factors for the activation of local B cells and CSR to IgE will provide more valuable information for us to recognize the pathological mechanisms of local IgE and offer the possible option for new therapeutic targets of nasal polyps.
Adenosinergic axis and immune checkpoint combination therapy in tumor: A new perspective for immunotherapy strategy
Authors: Liu Zhaoyun , Liu Xiaohan , Shen Hongli , Xu Xintong , Zhao Xianghong , Fu Rong
Published: September 2022

There are two figures and one table in this review, the review consists of 5823 words, without the description of figures and table, but including references.

Tumor cells escape anti-tumor immune responses in various ways, including functionally shaping the microenvironment through the secretion of various chemokines and, cytokines. Adenosine is a powerful immunosuppressive metabolite, that is frequently elevated in the extracellular tumor microenvironment (TME). Thus, it has recently been proposed as a novel antitumor immunoassay for targeting adenosine- generating enzymes, such as CD39, CD73, and adenosine receptors. In recent years, the discovery of the immune checkpoints, such as programmed cell death 1(PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4), has also greatly changed treatment methods and ideas for malignant tumors. Malignant tumor immunotherapy has been developed from point-to-point therapy targeting immune checkpoints, combining different points of different pathways to create a therapy based on the macroscopic immune regulatory system network. This article reviews the theoretical basis of the adenosine energy axis and immune checkpoint combined therapy for malignant tumors and the latest advances in malignant tumors.
Serological biomarkers predict immune-related adverse events and clinical benefit in patients with advanced gastrointestinal cancers
Authors: Wang Yanni , Zou Jianling , Li Yun , Jiao Xi , Wang Yujiao , Zhuo Na , Gao Mengting , Gong Jifang , Li Jian , Zhang Xiaotian , Wang Xicheng , Peng Zhi , Qi Changsong , Wang Zhenghang , Li Jie , Li Yan , Shen Lin , Zhang Henghui , Lu Zhihao
Published: September 2022

Background

Immune checkpoint inhibitors (ICIs) have dramatically improved survival in advanced gastrointestinal (GI) cancer patients, but also resulted in immune-related adverse events (irAEs). This study aimed to evaluate serological biomarkers of irAEs and treatment response in GI cancer patients.

Patients and methods

Metastatic GI cancer patients were enrolled between August 1, 2015, and July 31, 2017. Serum samples were collected at baseline, and a panel of 59 serum biomarkers was tested. The occurrence of irAEs was analyzed, and serological biomarker expression was correlated with irAE incidence and prognosis.

Results

Fifty-one patients were enrolled, of whom 47.1% (24/51) were diagnosed with irAEs, including 4 patients (7.8%) with grade 3-5 irAEs. The most common irAE was thyroiditis (9/51, 17.6%), followed by colitis (7/51, 13.7%). The expression of CD28 (P = 0.042), IL-4 (P = 0.033), IL-15 (P = 0.024) and PD-L1 (P = 0.018) was significantly elevated in patients with grade 3-5 irAEs. For organ-specific irAEs, IL-6 levels were higher in patients with thyroiditis and colitis, while IL-22 and SCF levels were higher in patients with colitis. Increased IL-1α, IL-21, LIF, and PIGF-1 levels were significantly associated with myositis incidence, while the serum levels of six cytokines (BTLA, GM-CSF, IL-4, PD-1, PD-L1 and TIM-3) were higher in patients with rash. Prognostic analysis showed that patients with irAEs had better tumor response (P = 0.029), improved PFS (median survival: undefined vs. 2.1 months, P = 0.002), and extended OS (median survival: undefined vs. 4.3 months, P = 0.003). The prognostic value of irAEs was only significant in patients who received anti-PD-1 inhibitors, but not in those who received anti-PD-L1 inhibitors. Besides, elevated BTLA (median OS: not reached vs. 7 months; P = 0.0168) and PD-1 (median OS: not reached vs. 7 months; P = 0.0223) concentrations were associated with longer OS.

Conclusions

Serological proteins are promising markers for predicting immune-related toxicity and prognosis in GI cancer patients. Organ-specific irAEs have various cytokine profiles. Although further validation is needed before clinical application, this study provided a direction for identifying patients at risk for irAEs, and guiding patient selection for ICI therapy.
Neurocysticercosis research in Mexico: A bibliometric analysis of the Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez
Authors: Rubio Carmen , Rodríguez-Quintero Paola , Fleury Agnès , Suástegui-Román Roberto Alfonso , Bowles Brigham , González-Garibay Guillermo , Pacheco-Aispuro Gerónimo , Lee Ángel
Published: September 2022

Neurocysticercosis (NCC) is the most common neglected parasitic disease of the central nervous system and leads to many economic and health issues in endemic and non-endemic countries. A bibliometric analysis would shed light on the evolution and development of research in this field, and this is the first study on NCC research. Our institution in Mexico City, the Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez (INNN), has set some milestones in the management of neurocysticercosis and has a decade-long experience and such an analysis in an endemic country like Mexico will be beneficial. We tracked the scientific output in Scopus, from its foundation to March 2021. The studied variables were article type, number of citations, area (clinical/experimental), chronological profile, and preferred journals. In the period from 1964 to 2021, from a total of 3,166 articles from the institution, 232 papers are related to neurocysticercosis with a total of 7,155 citations. The trending topics in the clinical area are pharmacology and pathology in the experimental papers. The number of articles has steadily increased, but NCC is currently a neglected topic that needs further research to better address the disease burden and allow its eradication.
Malaria vaccine approaches leveraging technologies optimized in the COVID-19 era
Authors: Kanoi Bernard N. , Maina Michael , Likhovole Clement , Kobia Francis M. , Gitaka Jesse
Published: September 2022

Africa bears the greatest burden of malaria with more than 200 million clinical cases and more than 600,000 deaths in 2020 alone. While malaria-associated deaths dropped steadily until 2015, the decline started to falter after 2016, highlighting the need for novel potent tools in the fight against malaria. Currently available tools, such as antimalarial drugs and insecticides are threatened by development of resistance by the parasite and the mosquito. The WHO has recently approved RTS,S as the first malaria vaccine for public health use. However, because the RTS,S vaccine has an efficacy of only 36% in young children, there is need for more efficacious vaccines. Indeed, based on the global goal of licensing a malaria vaccine with at least 75% efficacy by 2030, RTS,S is unlikely to be sufficient alone. However, recent years have seen tremendous progress in vaccine development. Although the COVID-19 pandemic impacted malaria control, the rapid progress in research towards the development of COVID-19 vaccines indicate that harnessing funds and technological advances can remarkably expedite vaccine development. In this review, we highlight and discuss current and prospective trends in global efforts to discover and develop malaria vaccines through leveraging mRNA vaccine platforms and other systems optimized during COVID-19 vaccine studies.
COVID-19 vaccination reduces mortality in patients on maintenance hemodialysis
Authors: Tylicki Leszek , Biedunkiewicz Bogdan , Puchalska-Reglińska Ewelina , Gellert Ryszard , Burnier Michel , Wolf Jacek , Dȩbska-Ślizień Alicja
Published: September 2022

Patients with chronic kidney disease on maintenance hemodialysis (HD) have a very high risk of death in the course of COVID-19. The aim of the study was to assess the effectiveness of COVID-19 vaccination to reduce the incidence of COVID-19 and the fatality rate in HD patients. A retrospective registry-based cohort study was performed in all HD adult patients in the Pomeranian Voivodeship. Vaccinations were carried out from January to April 2021 with mRNA vaccines, either BNT162b2 or mRNA-1273 with two-dose schedule. In the first analysis (2nd pandemic wave), 1,160 unvaccinated patients were included (59.7% males, 25.7% diabetic). In the second analysis (4th pandemic wave), 1,131 (59.4% male, 30.7% diabetic) individuals were included, 1,042 (92.13%) were fully vaccinated. Three hundred and fifteen HD patients (27.2%) were COVID-19 positive during the 2nd wave, and 6.9% (78/1,131) during the 4th wave. Within the fully vaccinated patients of the 4th wave, 60 were COVID-19 positive, 5.8 vs. 20.2% of unvaccinated COVID-19 positive patients in 2nd wave, respectively. COVID-19 incidence rate ratio (IRR) was 0.21 (4th wave-vaccinated vs. 2nd wave-unvaccinated) indicating a 79% reduction. The IRR between vaccinated and unvaccinated patients of the 4th wave was 0.28 in favor of vaccinated patients with 72% reduction. In the 2nd wave, 93 patients died as a result of COVID-19 (fatality rate: 29.5%). The fatality rate of fully vaccinated patients during the 4th wave was 6.7% (p = 0.004), while the fatality rate in the 4th wave within unvaccinated patients accounted for 11.1%. Significant clinical effectiveness of COVID-19 vaccination was demonstrated in a multicenter study in HD patients.
Predictive validity of admission criteria in predicting academic performance of medical students: A retrospective cohort study
Authors: Almarabheh Amer , Shehata Mohamed Hany , Ismaeel Abdulrahman , Atwa Hani , Jaradat Ahmed
Published: September 2022

Introduction

Admission to medical school is one of the most competitive entry points in higher education. Medical school admissions committees need accurate and precise screening tools to select among well-qualified applicants. This study explores data from a cohort of graduated medical students over 6 years to offer a critical perspective on predictive validity in medical school admissions.

Methods

A retrospective cohort study of 160 students was performed to identify the predictive validity of admission criteria for medical students to predict academic performance over 6 years for a cohort of all students enrolled in the medical program during the academic year 2013–2014.

Results

The main results indicated that there was a statistically significant positive correlation between the admission criteria and Students’ performance in Year 1, Year 4, B.Sc. (Bachelor of Medical Science) exam, and Medical Doctor (MD) exam across the 6 years of the medical program, except for the English Test, which showed that there was no significant correlation with average MD exam scores for students who enrolled directly in Year 1. The results related to students who were admitted to the Foundation Program showed that there was no significant correlation between high school Grade Point Average (HSGPA) and their academic performance in Year 1, Year 4, B.Sc. exam, and MD exam. The overall results related to all study samples indicated that all predictor variables correlate significantly with all outcome variables (academic performance), and the results showed that Science test scores demonstrated 27.7, 15.0, 19.7, and 12.6% of variation in Students’ performance in Year 1, Year 4, B.Sc. exam, and MD exam, respectively.

Conclusion

Science test scores were found to be more predictive of academic performance compared to other predictors. Not all the admission criteria used for student selection are good indicators of their achievement in the medical program. It is recommended that other valid and reliable admission tools, such as the multiple mini-interviews and the questionnaire for a candidate’s suitability to follow a problem-based learning curriculum, should be considered.
Periodontitis induced by orthodontic wire ligature drives oral microflora dysbiosis and aggravates alveolar bone loss in an improved murine model
Authors: Ai Rongshuang , Li Dingyi , Shi Luyao , Zhang Xiaonan , Ding Zhiqiang , Zhu Yiting , He Yujuan
Published: September 2022

Aim

To assess the contribution of polymicrobial disruption of host homeostasis to periodontitis progression in orthodontic wire ligation murine model.

Methods

Orthodontic wire rings were inserted between the first and second molars of mice for 18 days for the orthodontic wire ligation mouse model, and Pg injection model and Pg-LPS injection model were used as controls. Alveolar bone loss and periodontal inflammation were analyzed by micro-CT, histological staining and qRT-PCR. Further, pyrosequencing of 16S rRNA gene amplicon was used to analyze the development of oral microorganism dysbiosis in the mice.

Results

Micro-CT, TRAP staining and qRT-PCR showed that orthodontic wire ligation model led to more severe alveolar bone loss than Pg and Pg-LPS models.

H&E staining and qRT-PCR demonstrated that stronger inflammatory response was induced by the orthodontic wire treatment compared to the other models. In addition, pyrosequencing of 16S rRNA gene amplicons revealed that the composition of oral microbiota presented a transition as the disease progressed and significant differences emerged in oral microbiota communities between orthodontic ligature mice and healthy controls. Furthermore, antibiotic treatment decreased both inflammation and alveolar bone loss in response to microbial community dysbiosis. However, no significant difference in bacterial community composition was observed in Pg and Pg-LPS models.

Conclusions

Orthodontic wire ligation drove oral microbial community transitions that mimicked polymicrobial communities characterized by polymicrobial synergy and dysbiosis. Our improved model is suitable for further study of pathogenesis of periodontitis and exploration of corresponding treatment strategies.
Inferring microRNA regulation: A proteome perspective
Authors: Ofer Dan , Linial Michal
Published: September 2022

Post-transcriptional regulation in multicellular organisms is mediated by microRNAs. However, the principles that determine if a gene is regulated by miRNAs are poorly understood. Previous works focused mostly on miRNA seed matches and other features of the 3′-UTR of transcripts. These common approaches rely on knowledge of the miRNA families, and computational approaches still yield poor, inconsistent results, with many false positives. In this work, we present a different paradigm for predicting miRNA-regulated genes based on the encoded proteins. In a novel, automated machine learning framework, we use sequence as well as diverse functional annotations to train models on multiple organisms using experimentally validated data. We present insights from tens of millions of features extracted and ranked from different modalities. We show high predictive performance per organism and in generalization across species. We provide a list of novel predictions including Danio rerio (zebrafish) and Arabidopsis thaliana (mouse-ear cress). We compare genomic models and observe that our protein model outperforms, whereas a unified model improves on both. While most membranous and disease related proteins are regulated by miRNAs, the G-protein coupled receptor (GPCR) family is an exception, being mostly unregulated by miRNAs. We further show that the evolutionary conservation among paralogs does not imply any coherence in miRNA regulation. We conclude that duplicated paralogous genes that often changed their function, also diverse in their tendency to be miRNA regulated. We conclude that protein function is informative across species in predicting post-transcriptional miRNA regulation in living cells.
Overview of methods for characterization and visualization of a protein–protein interaction network in a multi-omics integration context
Authors: Robin Vivian , Bodein Antoine , Scott-Boyer Marie-Pier , Leclercq Mickaël , Périn Olivier , Droit Arnaud
Published: September 2022

At the heart of the cellular machinery through the regulation of cellular functions, protein–protein interactions (PPIs) have a significant role. PPIs can be analyzed with network approaches. Construction of a PPI network requires prediction of the interactions. All PPIs form a network. Different biases such as lack of data, recurrence of information, and false interactions make the network unstable. Integrated strategies allow solving these different challenges. These approaches have shown encouraging results for the understanding of molecular mechanisms, drug action mechanisms, and identification of target genes. In order to give more importance to an interaction, it is evaluated by different confidence scores. These scores allow the filtration of the network and thus facilitate the representation of the network, essential steps to the identification and understanding of molecular mechanisms. In this review, we will discuss the main computational methods for predicting PPI, including ones confirming an interaction as well as the integration of PPIs into a network, and we will discuss visualization of these complex data.
Four decades of mapping and quantifying neuroreceptors at work in vivo by positron emission tomography
Authors: Gjedde Albert , Wong Dean F.
Published: September 2022

Decryption of brain images is the basis for the necessary translation of the findings from imaging to information required to meet the demands of clinical intervention. Tools of brain imaging, therefore, must satisfy the conditions dictated by the needs for interpretation in terms of diagnosis and prognosis. In addition, the applications must serve as fundamental research tools that enable the understanding of new therapeutic drugs, including compounds as diverse as antipsychotics, antidepressants, anxiolytics, and drugs serving the relief of symptoms from neurochemical disorders as unrelated as multiple sclerosis, stroke, and dementia. Here we review and explain the kinetics of methods that enable researchers to describe the brain’s work and functions. We focus on methods invented by neurokineticists and expanded upon by practitioners during decades of experimental work and on the methods that are particularly useful to predict possible future approaches to the treatment of neurochemical disorders. We provide an overall description of the basic elements of kinetics and the underlying quantification methods, as well as the mathematics of modeling the recorded brain dynamics embedded in the images we obtain in vivo. The complex presentation to follow is necessary to justify the contribution of modeling to the development of methods and to support the specifications dictated by the proposed use in clinical settings. The quantification and kinetic modeling processes are equally essential to image reconstruction and labeling of brain regions of structural or functional interest. The procedures presented here are essential tools of scientific approaches to all conventional and novel forms of brain imaging. The foundations of the kinetic and quantitative methods are keys to the satisfaction of clinicians that actively engage in treating the neurochemical disorders of mammalian brains in the fields of neurology, neurosurgery, and neuropsychiatry.
Serious games and eating behaviors: A systematic review of the last 5 years (2018–2022)
Authors: Limone Pierpaolo , Messina Giovanni , Toto Giusi Antonia
Published: September 2022

Background

Serious game intervention has emerged over the years as a popular strategy for solving the problem of unhealthy eating behavior. This has prompted several scholars to explore its significant impact on eating behaviors, identifying its positive effect on nutritional knowledge and eating behaviors. However, since this research field is yet nascent, an update in knowledge is required to further inform the real-world practice as an alternative intervention for instating healthy eating behavior. Therefore, this current research utilized a systematic review method to reveal the latest state of this concept of a serious game and eating behavior, to identify the position of the literature and shed light on under-researched and emerging areas by recommending future investigations.

Method

To achieve the object of this research, four electronic databases- Science Direct, Web of Science (WoS), APA PsyclNFO, and Emerald- were searched using predefined keywords (search string) relating to the review topic. A total of 15,107 results were retrieved from the databases. After title, abstract, and full-text screening, 15 studies were included following inclusion criteria.

Key findings

The result of this research demonstrated that various designs of serious games comprise an effective intervention for changing eating behavior in both children and adults and addressed the risks of childhood obesity and overweight. The findings also show that the design of the games is co-designed by different specialists such as a nutritionist, psychologist and developer, among others, as either single or multiple players. The effectiveness of the games was attributed to behavior techniques (BT), cognitive theories (CT), and socio-cognitive theories (SCT) of behavior change technique (BCT), incorporating an element of implicit learning in serious games. Feedback and reward were the most reported influencing strategies and self-reporting the evaluation approach.

Conclusion

This research contributed significantly to the body of knowledge in the field of serious games as the most recent review of evidence in the research area. Evidence from 93.33% of the included studies confirmed the effectiveness of serious games in addressing eating behavior. This study concludes that serious games are an effective intervention for improving healthy eating behavior and decreasing unhealthy eating behavior and that various elements of behavior change techniques are essential components of implicit nutritional learning through the games. In addition, it is concluded that the risk of childhood obesity and overweight can be reduced or prevented by leveraging the strength of these games. The need for future research in this field was also pointed out by this study.
Simulation and experimental verification of ambient neutron doses in a pencil beam scanning proton therapy room as a function of treatment plan parameters
Authors: Van Hoey Olivier , Stolarczyk Liliana , Lillhök Jan , Eliasson Linda , Mojzeszek Natalia , Liszka Malgorzata , Alkhiat Ali , Mares Vladimir , Trompier François , Trinkl Sebastian , Martínez-Rovira Immaculada , Romero-Expósito Maite , Domingo Carles , Ploc Ondrej , Harrison Roger , Olko Pawel
Published: September 2022

Out-of-field patient doses in proton therapy are dominated by neutrons. Currently, they are not taken into account by treatment planning systems. There is an increasing need to include out-of-field doses in the dose calculation, especially when treating children, pregnant patients, and patients with implants. In response to this demand, this work presents the first steps towards a tool for the prediction of out-of-field neutron doses in pencil beam scanning proton therapy facilities. As a first step, a general Monte Carlo radiation transport model for simulation of out-of-field neutron doses was set up and successfully verified by comparison of simulated and measured ambient neutron dose equivalent and neutron fluence energy spectra around a solid water phantom irradiated with a variation of different treatment plan parameters. Simulations with the verified model enabled a detailed study of the variation of the neutron ambient dose equivalent with field size, range, modulation width, use of a range shifter, and position inside the treatment room. For future work, it is planned to use this verified model to simulate out-of-field neutron doses inside the phantom and to verify the simulation results by comparison with previous in-phantom measurement campaigns. Eventually, these verified simulations will be used to build a library and a corresponding tool to allow assessment of out-of-field neutron doses at pencil beam scanning proton therapy facilities.
Differences in severity of cardiovascular anomalies in children with Noonan syndrome based on the causative gene
Authors: Shehade-Awwad Nagham , Yeshayahu Yonatan , Pinhas-Hamiel Orit , Katz Uriel
Published: September 2022

Background

Noonan syndrome (NS) is a genetic syndrome, characterized by various dysmorphic features, cardiac anomalies, short stature, and developmental delay. NS is a leading cause of cardiovascular anomalies. The syndrome results from dysregulation in the RAS-MAPK pathway and is related to the RASopathy family syndromes. Pathogenic variants in more than 20 related genes have been identified in association with NS, and several genotype-phenotype correlations were suggested. The specific severity of the same cardiovascular anomalies has not been described as linked to a specific causative gene.

Methods

For this retrospective, single-center study, data retrieved from medical charts of a multidisciplinary NS clinic included genetic diagnosis, cardiac malformations, the need for intervention, demographics, and prenatal diagnosis. We analyzed molecular genetics and the severity of cardiac malformations.

Results

The cohort comprised 74 children with NS. Consistent with previous studies, pathogenic variants in PTPN11 were the most common (62%). Cardiovascular anomalies presented in 57%; pulmonary stenosis (PS) was the most common (about 79% of anomalies). In children with pathogenic variants in PTPN11, PS tended to be more severe and required intervention in 53%, compared to 25% of children with PS and a variant in other genes.

Conclusion

This first Israeli cohort of NS showed similar rates of cardiac malformations and genetic breakdown as previously published. Variants in PTPN11 were prone to a higher risk for severe PS that requires intervention. This finding may assist in genetic counseling and cardiac treatment decisions, and stresses the importance of genetic in addition to clinical diagnosis of NS.
From seaside to bedside: Current evidence and future perspectives in the treatment of breast cancer using marine compounds
Authors: De Sanctis Rita , Jacobs Flavia , Benvenuti Chiara , Gaudio Mariangela , Franceschini Raul , Tancredi Richard , Pedrazzoli Paolo , Santoro Armando , Zambelli Alberto
Published: September 2022

To date, only few marine natural compounds have been proved to be active in breast cancer (BC). The main marine-derived drugs that have been studied for the treatment of BC are tubulin-binding agents (eribulin and plocabulin), DNA-targeting agents (cytarabine and minor groove binders—trabectedin and lurbinectedin) and Antibody-Drug Conjugates (ADCs). Notably, eribulin is the only approved cytotoxic drug for the treatment of advanced BC (ABC), while cytarabine has a limited indication in case of leptomeningeal diffusion of the disease. Also plocabulin showed limited activity in ABC but further research is needed to define its ultimate potential role. The available clinical data for both trabectedin and lurbinectedin are of particular interest in the treatment of BRCA-mutated tumours and HR deficient disease, probably due to a possible immune-mediated mechanism of action. One of the most innovative therapeutic options for the treatment of BC, particularly in TNBC and HER2-positive BC, are ADCs. Some of the ADCs were developed using a specific marine-derived cytotoxic molecule as payload called auristatin. Among these, clinical data are available on ladiratuzumab vedotin and glembatumumab vedotin in TNBC, and on disitamab vedotin and ALT-P7 in HER2-positive patients. A deeper knowledge of the mechanism of action and of the potential predictive factors for response to marine-derived drugs is important for their rational and effective use, alone or in combination. In this narrative review, we discuss the role of marine-derived drugs for the treatment of BC, although most of them are not approved, and the opportunities that could arise from the potential treasure trove of the sea for novel BC therapeutics.
Global trends in research on irritable bowel syndrome and the brain–gut axis: Bibliometrics and visualization analysis
Authors: Wu Peng-Ning , Xiong Shuai , Zhong Peng , Yang Wan-Qing , Chen Min , Tang Tai-Chun
Published: September 2022

Irritable bowel syndrome (IBS) is a gastrointestinal disorder with no structural damage, and its pathogenesis remains unclear. Studies have shown that the brain–gut axis is closely related to the occurrence of IBS. However, studies of IBS related to the brain–gut axis have not been systematically analyzed by bibliometrics and visual analysis. This study is based on 631 publications in the Web of Science Core Collection (WoSCC) to analyze hot spots and trends in this field. The collaborations between different authors, institutions, countries, and keywords were bibliometrically analyzed by CiteSpace software. Meanwhile, VOSviewer analyzed the references. The results show that since 2012, the number of publications has been growing rapidly. According to the collaborative network analysis, the United States, the National University of Ireland, Cork, and J.F. Cryan are the countries, institutions, and authors contributing the most, respectively. Through keywords and literature analysis, mechanisms and therapy associated with IBS and the brain–gut axis have still been a research focus in recent years. Furthermore, the physiological and pathological mechanisms of the brain–gut axis influencing IBS (related to gastrointestinal dysfunction, vagus nerve, visceral pain, intestinal flora, serotonin, tryptophan metabolism, stress, brain-derived neurotrophic factor (BDNF), and malonyldialdehyde) are the future research trends, especially the mechanisms related to intestinal flora. This is the first bibliometric and visualization analysis of IBS and brain–gut axis-related literature to explore research hotspots and trends.
Exosomes and exosomal miRNAs: A new therapy for intervertebral disc degeneration
Authors: Li Zhichao , Wu Yan , Tan Guoqing , Xu Zhanwang , Xue Haipeng
Published: September 2022

Low back pain has been found as a major cause of global disease burden and disability. Intervertebral disc degeneration is recognized as the vital factor causing low back pain. Intervertebral disc degeneration has a complex mechanism and cannot be avoided. Traditional strategies for the treatment of intervertebral disc degeneration cannot meet the needs of intervertebral disc regeneration, so novel treatment methods are urgently required. Exosomes refer to extracellular vesicles that can be released by most cells, and play major roles in intercellular material transport and information transmission. MicroRNAs have been identified as essential components in exosomes, which can be selectively ingested by exosomes and delivered to receptor cells for the regulation of the physiological activities and functions of receptor cells. Existing studies have progressively focused on the role of exosomes and exosomal microRNAs in the treatment of intervertebral disc degeneration. The focus on this paper is placed on the changes of microenvironment during intervertebral disc degeneration and the biogenesis and mechanism of action of exosomes and exosomal microRNAs. The research results and deficiencies of exosomes and exosomal microRNAs in the regulation of apoptosis, extracellular matrix homeostasis, inflammatory response, oxidative stress, and angiogenesis in intervertebral disc degeneration are primarily investigated. The aim of this paper is to identify the latest research results, potential applications and challenges of this emerging treatment strategy.
SPIRAL2 Cryomodule Models: A Gateway to Process Control and Machine Learning
Authors: Vassal Adrien , Ghribi Adnan , Millet François , Bonne François , Bonnay Patrick , Bernaudin Pierre-Emmanuel
Published: September 2022

From simple physical systems to full production lines, numerical models could be used to minimize downtime and to optimize performances. In this article, the system of interest is the SPIRAL2 heavy ion accelerator cryogenic system. This article illustrates three different applications based on a SPIRAL2 cryostat model: optimal controller synthesis, virtual sensor synthesis, and anomaly detection. The two first applications have been deployed on the system. Experimental results are used to illustrate the benefits of such applications. The third application is a case study based on data generated from a thermodynamic twin model.
Differences in nitrogen and phosphorus sinks between the harvest and non-harvest of Miscanthus lutarioriparius in the Dongting Lake wetlands
Authors: Peng Zenghui , Du Yuhang , Niu Shiyu , Xi Lianlian , Niu Yandong , Li Youzhi
Published: September 2022

Plant non-harvest changes element circulation and has a marked effect on element sinks in the ecosystem. In this study, a field investigation was conducted on the fixation of nitrogen and phosphorus in Miscanthus lutarioriparius, the most dominant plant species in the Dongting Lake wetlands. Further, to quantitatively compare the difference in nitrogen and phosphorus sinks between harvest and non-harvest, an in situ experiment on the release of the two elements from two types of litters (leaves and stems) was studied. The nitrogen concentrations in the plant had no significant relationship with the environmental parameters. The phosphorus concentrations were positively related to the plot elevation, soil organic matter, and soil total potassium and were negatively related to the soil moisture. The leaves demonstrated a higher decomposition coefficient than that of the stems in the in situ experiment. The half decomposition time was 0.61 years for leaves and 1.12 years for stems, and the complete decomposition time was 2.83 years for leaves and 4.95 years for stems. Except for the nitrogen concentration in the leaves, all the concentrations increased during the flood period. All concentrations unsteadily changed in the backwater period. Similarly, except for the relative release index of nitrogen in the leaves, all the relative release indices decreased in the flood period. At the end of the in situ decomposition experiment, the relative release indices of both the nitrogen and phosphors were greater than zero, indicating that there was a net release of nitrogen and phosphorus. Under the harvest scenario, the aboveground parts of the plant were harvested and moved from the wetlands, thus increasing the nitrogen and phosphorus sinks linearly over time. The fixed nitrogen and phosphorus in the aboveground parts were released under the non-harvest scenario, gradually accumulating the nitrogen and phosphorus sinks from the first year to the fifth year after non-harvest, reaching a maximum value after the fifth year. This study showed that the nitrogen and phosphorus sinks greatly decreased after the non-harvest of M. lutarioriparius compared to that after harvest. It is recommended to continue harvesting the plant for enhancing the capacity of element sinks.
MsTHI1 overexpression improves drought tolerance in transgenic alfalfa (Medicago sativa L.)
Authors: Yin Hang , Wang Zhaoyu , Li Han , Zhang Yu , Yang Mei , Cui Guowen , Zhang Pan
Published: September 2022

In recent years, drought stress caused by global warming has become a major constraint on agriculture. The thiamine thiazole synthase (THI1) is responsible for controlling thiamine production in plants displaying a response to various abiotic stresses. Nonetheless, most of the THI1 activities in plants remain largely unknown. In this study, we extracted MsTHI1 from alfalfa and demonstrated its beneficial impact on improving the resistance of plants to stress conditions. The highest levels of MsTHI1 expression were identified in alfalfa leaves, triggered by exposure to cold, drought, salt, or alkaline conditions. The upregulation of MsTHI1 in drought-stressed transgenic plants resulted in enhanced accumulation of vitamin B1 (VB1), chlorophyll a (Chl a), chlorophyll b (Chl b), soluble protein, higher soil and plant analyzer development (SPAD) value, and the activity of peroxidase (POD), maintained Fv/Fm, and decreased lipid peroxidation. Moreover, overexpression of MsTHI1 upregulated the transcription of THI4, TPK1, RbcX2, Cu/Zn-SOD, CPK13, and CPK32 and downregulated the transcription of TH1 and CPK17 in transgenic alfalfa under drought stress. These results suggested that MsTHI1 enhances drought tolerance by strengthening photosynthesis, regulating the antioxidant defense system, maintaining osmotic homeostasis, and mediating plant signal transduction.
Reducing and deducing the structures of consciousness through meditation
Authors: Katyal Sucharit
Published: September 2022

According to many first-person accounts, consciousness comprises a subject-object structure involving a mental action or attitude starting from the “subjective pole” upon an object of experience. In recent years, many paradigms have been developed to manipulate and empirically investigate the object of consciousness. However, well-controlled investigation of subjective aspects of consciousness has been more challenging. One way, subjective aspects of consciousness are proposed to be studied is using meditation states that alter its subject-object structure. Most work to study consciousness in this way has been done using Buddhist meditation traditions and techniques. There is another meditation tradition that has been around for at least as long as early Buddhist traditions (if not longer) with the central goal of developing a fine-grained first-person understanding of consciousness and its constituents by its manipulation through meditation, namely the Tantric tradition of Yoga. However, due to the heavy reliance of Yogic traditions on the ancient Indian Samkhya philosophical system, their insights about consciousness have been more challenging to translate into contemporary research. Where such translation has been attempted, they have lacked accompanying phenomenological description of the procedures undertaken for making the precise subject-object manipulations as postulated. In this paper, I address these issues by first detailing how Tantric Yoga philosophy can be effectively translated as a systematic phenomenological account of consciousness spanning the entirety of the subject-object space divided into four “structures of consciousness” from subject to object. This follows from the work of the 20th century polymath and founder of the Tantric Yoga school of Ananda Marga, Prabhat Ranjan Sarkar, who expounded on the “cognitivization” of Samkhya philosophy. I then detail stepwise meditation procedures that make theoretical knowledge of these structures of consciousness a practical reality to a Tantric Yoga meditator in the first-person. This is achieved by entering meditative states through stepwise experiential reduction of the structures of consciousness from object to subject, as part of their meditative goal of “self-realization.” I end by briefly discussing the overlap of these putative meditation states with proposed states from other meditation traditions, and how these states could help advance an empirical study of consciousness.
Evaluation of children’s cognitive load in processing and storage of their spatial working memory
Authors: Chen Hsiang-Chun , Kao Chien-Hui , Wang Tzu-Hua , Lai Yen-Ting
Published: September 2022

Working memory performance affects children’s learning. This study examined objective (task performance), subjective (self-report), and physiological (pupil dilation) cognitive load (CL) while children completed a spatial working memory complex span task. Frist, 80 Taiwanese 11-year-olds (40 boys) who participated in Experiment 1 confirmed the suitability of the materials. Then, 72 Taiwanese 11-year-olds (35 boys) were assigned to high and low complexity groups to participate in Experiment 2 to test the study hypothesis. Children had to recall at the end of a dual-task list and answer two questions regarding the difficulty and mental effort involved in processing and storage. Their pupil diameters were recorded using an eye-tracker. Two-way mixed ANOVA found that the processing requirements and memory load reduced storage and aggravated the subjective CL of storage; the subjective CL of processing was higher under highly complex conditions. Stepwise regression analysis indicated that subjective CL of processing predicted memory performance in low CL conditions, and physiological CL of processing predicted it in high CL conditions.
Relationship between mutuality and depression in patients with chronic heart failure and caregivers in China: An actor-partner interdependence model analysis
Authors: Zhou Ting , Qu Jiling , Sun Huiping , Xue Mengxin , Liu Yongbing
Published: September 2022

Background

Patients with chronic heart failure and their family caregivers may experience adverse emotional problems, such as depression. Mutuality, which refers to the relationship between caregivers and those they care for, is an important factor affecting depression in the dyads. The purpose of this study was to investigate the relationship between mutuality and depression in patients with CHF and their caregivers in China.

Methods

In this cross-sectional study, we used the Mutuality Scale and the Self-Rating Depression Scale to measure mutuality and depression of patients and caregivers. We used SPSS version 26.0 and AMOS version 21.0 to analyze the data. An APIM was established to analyze the actor-partner effects of patient-caregiver mutuality and depression.

Results

A total of 250 dyads of patients and caregivers were included in the study. There were statistically significant differences in mutuality and depression between CHF patients and caregivers. The 4 dimensions of patients’ mutuality all have the actor effect on depression. There were 3 partner effects of caregivers’ “pleasurable activities”, “shared values”, and “reciprocity” on depression. Regarding caregiver depression, we only found an actor effect of caregivers’ “shared values” on depression.

Conclusion

The relationship between patients and caregivers should be evaluated in the clinical setting, and it is very important to develop intervention measures to improve the adverse emotional problems affecting both patients and their caregivers.
Impact of globalization on the environment in major CO2-emitting countries: Evidence using bootstrap ARDL with a Fourier function
Authors: Wu Cheng-Feng , Chang Tsangyao , Wu Tsung-Pao , Leng Kai-jun , Lin Meng-Chen , Huang Shian-Chang
Published: September 2022

Alongside sustainable development as a major global aim, the contribution made by globalization to environmental issues has become crucial in recent decades. Prior studies have focused on how trade in globalization influences the environment. However, multiple economic, social, and political factors are also important, the integration of which needs to be considered in sustainable development. Sharp and smooth breaks in time series models are the consequence of real-world structures. Using the bootstrap autoregressive-distributed lag test with a Fourier function, the present study reexamined the nexus between globalization and the environment in China, the United States, and India. The empirical results indicate that in the United States, the nexus between globalization and the environment is cointegrated in the long-term. In the short term, globalization is improving the environment in the United States and India. However, in China, globalization is resulting in environmental degradation. This research will assist policymakers in developing comprehensive strategies for sustainable development.