bluuebunny/crossref_metadata_2025 huggingface dataset:
Intravascular lithotripsy (IVL) enabled the percutaneous closure of a severely calcified paravalvular leak regurgitation following implantation of a self-expandable transcatheter aortic valve: a case report
Authors: Evola Salvatore , D’Agostino Alessandro , Adorno Daniele , Triolo Oreste Fabio , Giarratana Gioacchino , Castrovinci Sebastiano , Argano Vincenzo , Onorato Eustaquio Maria
Published: February 2024

Background

Closure of paravalvular leak (PVL) regurgitation after self-expandable (SE) transcatheter aortic valve implantation (TAVI) may be more challenging than after balloon-expandable (BE) valve implantation.

Case summary

An 85-year-old woman suffering from long-standing atrial fibrillation and severe symptomatic aortic stenosis underwent SE TAVI (26 mm Evolut™ R®, Medtronic Inc., MN, USA). A total of eighteen months after TAVI she was admitted for congestive heart failure and two-dimensional (2D) transesophageal echocardiography (TEE) color Doppler showed moderate-severe PVL regurgitation due to a long and heavily calcified leak located below the left coronary sinus. The patient was deemed to be at prohibitive surgical risk and a catheter-based PVL closure procedure was planned. A first attempt to cross the PVL from the femoral artery was unsuccessful due to an inappropriate angle between the catheter and the entry site of this hard-to-approach calcified leak. A Terumo hydrophilic guidewire 0.35 inch-260 cm from the right radial artery was then successfully advanced across the leak to the left ventricle (LV); however, of most of the catheters used, only a Glidecath 4-Fr could cross the leak over the hydrophilic wire. The hydrophilic guidewire was replaced with a stiffer guidewire that, after creating a loop in the LV, was advanced across the self-expandable valve into the descending aorta where it was snared and externalized through the left femoral artery, thus creating an arterio-arterial (AA) loop. A 6-Fr Multipurpose guiding catheter was advanced over the exchange wire and the leak was crossed with an additional 0.0014 coronary guidewire (PILOT, Abbott Vascular), predilated with two non-compliant balloon dilatation catheters, and finally, the PVL was engaged with a 3.0 mm × 12 mm Shockwave balloon (Shockwave Medical Inc, Santa Clara, California, USA). Intravascular lithotripsy (IVL) application to this highly calcified leak and the increased support provided by the stiff guidewire finally allowed the progression of the 6-Fr dedicated delivery sheath (ODS III) into the LV. A 5 mm square twist (ST) device (PLD, Occlutech, Helsingborg, Sweden) was successfully deployed within the leak and the final echocardiographic and angiographic control confirmed the effective PVL closure.

Discussion

In patients at high surgical risk with moderate to severe regurgitation after SE TAVI due to a hard-to-approach calcified long tract, an extra AA support loop is mandatory during percutaneous PVL closure. Furthermore, IVL application greatly facilitates the progression of the delivery sheath and occluder which is key to a successful procedure.
The influence of anthropomorphism on children's learning and attitudes toward snakes
Authors: Reider Lori Beth , LoBue Vanessa
Published: February 2024

Introduction

Previous research suggests that negative input contributes to children's fear development, while more positive input can reduce children's fear. The current study examined whether using anthropomorphic input can alter children's learning and attitudes toward snakes in ways that may promote more positive attitudes toward a commonly feared animal.

Methods

Children from the United States (N = 89; Mage = 5.43 years; 47 females, 42 males) reported their baseline knowledge and fear of snakes. Children then heard a story about a snake that did (n = 44) or did not (n = 45) contain anthropomorphic information. Following the story, children answered questions about their fear of snakes, knowledge acquired from the story, willingness to attribute anthropomorphic qualities to snakes, and willingness to help snakes.

Results and discussion

After hearing either story, children reported less fear of snakes. Further, while children in the anthropomorphic condition were more likely to attribute anthropomorphic qualities to snakes, there were no differences in the amount of information children learned. Most importantly, children in the anthropomorphic condition prioritized helping snakes more than children in the neutral condition. These findings demonstrate the impact of anthropomorphic information on children's attitudes and learning, and highlight the ways in which altering the input children receive may impact their learning and attitudes toward living creatures.
Soil degradation in andean watersheds: a case study using remote sensing
Authors: Oñate-Valdivieso Fernando , Oñate-Paladines Arianna , Díaz Ricardo
Published: February 2024

Soil degradation is one of the greatest challenges faced by arid and semi-arid zones, as it causes a progressive loss of the capacity of soils to sustain life and human activities. In the present study, five spectral indices, individually associated with erosion, desertification, salinity, and soil sealing, were evaluated in a semi-arid region of the Ecuadorian Andes to study of soil degradation. The results were validated through field observations and samples processed in the laboratory. The spectral indices presented correlation coefficients between 0.5278 and 0.8809 with field observations. These indices provided useful information to understand the current state of the soils and their potential deterioration. The study area showed greater vulnerability to erosion caused by the combination of scarce vegetation, irregular topography, and significant seasonal rainfall. The advance of urbanization, mechanized agriculture, and overgrazing had a high impact by impermeabilizing considerable surfaces, while the advance of desertification and soil salinization showed little incidence in the study area. The systematic application of these indices would become a valuable means for monitoring soil degradation in Andean watersheds.
Could a playful approach to teaching be a path to resonant connections? Experiences from teacher education in Denmark
Authors: Skovbjerg Helle Marie , Jensen Julie Borup
Published: February 2024

Creative and playful approaches to teaching in teacher education emerge these years. Due to the increasing focus on performance, pace, visible goals, and efficiency in the educational systems within the Western societies, there seem to be a search for new answers when organising teaching within teacher education—also for the future. Based on empirical material created in a large research project in teacher education in Denmark, this paper analyses how playful approaches can contribute to improving conditions for a holistic approach to education, and how these approaches must be linked to concrete pedagogical actions. By applying a theoretical framework of playful approaches to learning in teacher education based on Rosa, Lennon and Skovbjerg, the main contribution of the paper is to point to both pedagogical directions and clarifications when working with playful approaches in teacher education.
Socioeconomic disparities and regional environment are associated with cervical lymph node metastases in children and adolescents with differentiated thyroid cancer: developing a web-based predictive model
Authors: Mao Yaqian , Wang Jinwen , Luo Yinghua , Lin Wei , Yao Jin , Wen Junping , Chen Gang
Published: February 2024

Purpose

To establish an online predictive model for the prediction of cervical lymph node metastasis (CLNM) in children and adolescents with differentiated thyroid cancer (caDTC). And analyze the impact between socioeconomic disparities, regional environment and CLNM.

Methods

We retrospectively analyzed clinicopathological and sociodemographic data of caDTC from the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2019. Risk factors for CLNM in caDTC were analyzed using univariate and multivariate logistic regression (LR). And use the extreme gradient boosting (XGBoost) algorithm and other commonly used ML algorithms to build CLNM prediction models. Model performance assessment and visualization were performed using the area under the receiver operating characteristic (AUROC) curve and SHapley Additive exPlanations (SHAP).

Results

In addition to common risk factors, our study found that median household income and living regional were strongly associated with CLNM. Whether in the training set or the validation set, among the ML models constructed based on these variables, the XGBoost model has the best predictive performance. After 10-fold cross-validation, the prediction performance of the model can reach the best, and its best AUROC value is 0.766 (95%CI: 0.745-0.786) in the training set, 0.736 (95%CI: 0.670-0.802) in the validation set, and 0.733 (95%CI: 0.683-0.783) in the test set. Based on this XGBoost model combined with SHAP method, we constructed a web-base predictive system.

Conclusion

The online prediction model based on the XGBoost algorithm can dynamically estimate the risk probability of CLNM in caDTC, so as to provide patients with personalized treatment advice.
Effect of the time interval between denudation and ICSI on fresh embryo transfer reproductive outcomes: a retrospective study
Authors: Xiao Li , Xue Luqi , Zhang Ju , Fan Wei , Zhu Huili , Huang Wei
Published: February 2024

Purpose

This study aims to determine if the incubation after oocyte denudation before Intra-cytoplasmic sperm injection (ICSI) affects the clinical pregnancy rate.

Methods

This was a retrospective, consecutive data analysis of 1370 patients who underwent ICSI cycles at the Department of Reproductive Medicine of West China Second University of Sichuan University (Chengdu, Sichuan) between January 2020 and July 2022. The primary outcome was the clinical pregnancy rate. The second outcome included fertilization rate, biochemical pregnancy rate, and miscarriage rates.

Results

A total of 1370 continuous fresh transferred ICSI cycles were analyzed. Multivariate linear regression and logistic regression analysis of factors related to clinical pregnancy rates revealed that clinical pregnancy rates were significantly associated with denudation (DEN)-ICSI time interval. Long DEN-ICSI intervals are associated with a higher clinical pregnancy rate during fresh embryo transfer.

Conclusion

The DEN-ICSI time interval is an independent factor for clinical outcomes in fresh ICSI transfer cycles.
Nitrous oxide and nitric oxide fluxes differ from tea plantation and tropical forest soils after nitrogen addition
Authors: Toteva Galina Y. , Reay David , Jones Matthew R. , Cowan Nicholas , Deshpande Ajinkya , Weerakoon Buddhika , Nissanka Sarath , Drewer Julia
Published: February 2024

South Asia is experiencing a rapid increase in nitrogen (N) pollution which is predicted to continue in the future. One of the possible implications is an increase in gaseous reactive N losses from soil, notably in the form of nitrous oxide (N2O) and nitric oxide (NO). Current knowledge of N2O and NO dynamics in forest ecosystems is not sufficient to understand and mitigate the impacts on climate and air quality. In order to improve the understanding of emissions from two major land uses in Sri Lanka, we investigated the emission potential for N2O and NO fluxes measured by absorption spectroscopy and chemiluminescence, respectively, in response to three different N addition levels (the equivalent of 0, 40 and 100 kg N ha−1 yr.−1 deposition in the form of NH4+) from soils of two typical land uses in Sri Lanka: a secondary montane tropical forest and a tea plantation using soil laboratory incubations of repacked soil cores. We observed an increase in NO fluxes which was directly proportional to the amount of N applied in line with initial expectations (maximum flux ranging from 6–8 ng NO-N g−1 d−1 and from 16–68 ng NO-N g−1 d−1 in forest and tea plantation soils, respectively). However, fluxes of N2O did not show a clear response to N addition, the highest treatment (100 N) did not result in the highest fluxes. Moreover, fluxes of N2O were higher following the addition of a source of carbon (in the form of glucose) across treatment levels and both land uses (maximum flux of 2–34 ng N2O-N g−1 d−1 in forest and 808–3,939 ng N2O-N g−1 d−1 in tea plantation soils). Both N2O and NO fluxes were higher from tea plantation soils compared to forest soils irrespective of treatment level, thus highlighting the importance of land use and land management for gaseous reactive N fluxes and therefore N dynamics.
Settling down with anthropomorphic clay figurines in eastern North America
Authors: Miller G. Logan
Published: February 2024

Indigenous peoples have occupied eastern North America for over 10,000 years; yet the earliest anthropomorphic figurines were only manufactured in the past several thousand years. This emergence of human figurine traditions in eastern North America is correlated with increased settlement permanence, and community size related to key demographic thresholds. In this study, I present an overview of two previously unreported figurine assemblages from the Middle Woodland period in Illinois and use these assemblages as a jumping-off point to examine the emergence of early human figurines in eastern North America. To illustrate the importance of the correlation between anthropomorphic figurines and settling down, I focus on what figurines do that encouraged the emergence of widespread traditions of figurine manufacture and use as the size of affiliative communities increased. This study involves examining early figurines and their broader context through the lens of a model of the socioeconomic dynamics of settling down in conjunction with an examination of the materiality of miniature 3-D anthropomorphic figurines. Key to this latter perspective is understanding not what figurines represent but what they do.
The integrated bioinformatic analysis identifies immune microenvironment-related potential biomarkers for patients with gestational diabetes mellitus
Authors: Chen Jie-ling , Dai Hui-fang , Kan Xin-chen , Wu Jie , Chen Hong-Wu
Published: February 2024

Background

Gestational diabetes mellitus (GDM), a transient disease, may lead to short- or long-term adverse influences on maternal and fetal health. Therefore, its potential functions, mechanisms and related molecular biomarkers must be comprehended for the control, diagnosis and treatment of GDM.

Methods

The differentially expressed genes (DEGs) were identified using GSE49524 and GSE87295 associated with GDM from the Gene Expression Omnibus database, followed by function enrichment analysis, protein-protein interactions network construction, hub DEGs mining, diagnostic value evaluation and immune infiltration analysis. Finally, hub DEGs, the strongest related to immune infiltration, were screened as immune-related biomarkers.

Results

A hundred and seven DEGs were identified between patients with GDM and healthy individuals. Six hub genes with high diagnostic values, including ALDH1A1, BMP4, EFNB2, MME, PLAUR and SLIT2, were identified. Among these, two immune-related genes (PLAUR and SLIT2) with the highest absolute correlation coefficient were considered immune-related biomarkers in GDM.

Conclusion

Our study provides a comprehensive analysis of GDM, which would provide a foundation for the development of diagnosis and treatment of GDM.
Diet-derived circulating antioxidants and risk of inflammatory bowel disease: a Mendelian randomization study and meta-analysis
Authors: Zou Menglong , Liang Qiaoli , Zhang Wei , Liang Junyao , Zhu Ying , Xu Yin
Published: February 2024

Background

Previous studies have shown conflicting results regarding the impact of circulating antioxidants on the risk of inflammatory bowel disease (IBD). In this study, our intent was to investigate the causal relationship between circulating antioxidants and IBD using Mendelian randomization (MR).

Methods

Instrumental variables for absolute circulating antioxidants (ascorbate, retinol, lycopene, and β-carotene) and circulating antioxidant metabolites (α-tocopherol, γ-tocopherol, ascorbate, and retinol) were screened from published studies. We obtained outcome data from two genome-wide association study (GWAS) databases, including the international inflammatory bowel disease genetics consortium (IIBDGC, 14,927 controls and 5,956 cases for Crohn’s disease (CD), 20,464 controls and 6,968 cases for ulcerative colitis (UC), and 21,770 controls and 12,882 cases for IBD) and the FinnGen study (375,445 controls and 1,665 cases for CD, 371,530 controls and 5,034 cases for UC, and 369,652 controls and 7,625 cases for IBD). MR analysis was performed in each of the two databases and those results were pooled using meta-analysis to assess the overall effect of exposure on each phenotype. In order to confirm the strength of the findings, we additionally conducted a replication analysis using the UK Biobank.

Results

In the meta-analysis of the IIBDGC and FinnGen, we found that each unit increase in absolute circulating level of retinol was associated with a 72% reduction in the risk of UC (OR: 0.28, 95% CI: 0.10 to 0.78, P=0.015). The UC GWAS data from the UK Biobank also confirmed this causal relationship (OR: 0.99, 95% CI: 0.97 to 1.00, P=0.016). In addition, there was suggestive evidence that absolute retinol level was negatively associated with IBD (OR: 0.41, 95% CI: 0.18 to 0.92, P=0.031). No other causal relationship was found.

Conclusion

Our results provide strong evidence that the absolute circulating level of retinol is associated with a reduction in the risk of UC. Further MR studies with more instrumental variables on circulating antioxidants, especially absolute circulating antioxidants, are needed to confirm our results.
Reprogramming of regulatory T cells in inflammatory tumor microenvironment: can it become immunotherapy turning point?
Authors: Liu Jinming , Zhang Biao , Zhang Guolin , Shang Dong
Published: February 2024

Overcoming the immunosuppressive tumor microenvironment and identifying widely used immunosuppressants with minimal side effects are two major challenges currently hampering cancer immunotherapy. Regulatory T cells (Tregs) are present in almost all cancer tissues and play an important role in preserving autoimmune tolerance and tissue homeostasis. The tumor inflammatory microenvironment causes the reprogramming of Tregs, resulting in the conversion of Tregs to immunosuppressive phenotypes. This process ultimately facilitates tumor immune escape or tumor progression. However, current systemic Treg depletion therapies may lead to severe autoimmune toxicity. Therefore, it is crucial to understand the mechanism of Treg reprogramming and develop immunotherapies that selectively target Tregs within tumors. This article provides a comprehensive review of the potential mechanisms involved in Treg cell reprogramming and explores the application of Treg cell immunotherapy. The interference with reprogramming pathways has shown promise in reducing the number of tumor-associated Tregs or impairing their function during immunotherapy, thereby improving anti-tumor immune responses. Furthermore, a deeper understanding of the mechanisms that drive Treg cell reprogramming could reveal new molecular targets for future treatments.
Research on the impact mechanism of scientific and technological innovation on the high-quality development of the marine economy
Authors: Feng Min , Guan Hongjun , Wang Yichuan , Liu Yilin
Published: February 2024

Promoting the high-quality development of the marine economy is an inevitable choice for building a maritime power, and technological innovation can provide strong impetus for the high-quality development of the marine economy. Therefore, it is urgent to clarify the impact mechanism of technological innovation on the high-quality development of the marine economy, and promote the high-quality development of the marine economy. This study employs panel data from 11 coastal provinces and municipalities (autonomous regions) in China, spanning the years 2006 to 2020. The objective is to empirically evaluate the mechanism through which scientific and technical innovation impacts the high-quality development of the marine economy. This is achieved by utilizing the PVAR model and the mediation effect model. The research findings indicate that there is a noteworthy impact of enhancing scientific and technological innovation on the marine economy of China. Moreover, there exists a significant reciprocal relationship between scientific and technological innovation and the pursuit of high-quality development in the marine economy. It is observed that scientific and technological innovation not only has a positive influence on the high-quality development of the marine economy by enhancing green total factor productivity and optimizing the industrial structure, but it also facilitates the advancement of the marine economy through the chain mediation path of “improving green total factor productivity and optimizing industrial structure”.
How to report and make sense of a new HIV-1 circulating recombinant form?
Authors: Wan Zhenzhou , Zhang Chiyu
Published: February 2024

Co-circulation of multiple HIV-1 subtypes in the same high-risk groups leads to the on-going generation of various inter-subtype recombinants, including unique (URFs) and circulating (CRFs) recombinant forms, which brings a new challenge for the prevention and eradication of HIV/AIDS. Identification and prompt reporting of new CRFs will provide not only new insights into the understanding of genetic diversity and evolution of HIV-1, but also an early warning of potential prevalence of these variants. Currently, 140 HIV-1 CRFs have been described; however, their prevalence and clinical importance are less concerned. Apart from the mosaic genomic maps, less other valuable information, including the clinical and demographic data, genomic sequence characteristics, origin and evolutionary dynamics, as well as representative genomic fragments for determining the variants, are available for most of these CRFs. Accompanied with the growing increase of HIV-1 full-length genomic sequences, more and more CRFs will be identified in the near future due to the high recombination potential of HIV-1. Here, we discuss the prevalence and clinical importance of various HIV-1 CRFs and propose how to report and make sense of a new HIV-1 CRF.
Gut microbiota affects obesity susceptibility in mice through gut metabolites
Authors: Wen Yuhang , Luo Yadan , Qiu Hao , Chen Baoting , Huang Jingrong , Lv Shuya , Wang Yan , Li Jiabi , Tao Lingling , Yang Bailin , Li Ke , He Lvqin , He Manli , Yang Qian , Yu Zehui , Xiao Wudian , Zhao Mingde , Zou Xiaoxia , Lu Ruilin , Gu Congwei
Published: February 2024

Introduction

It is well-known that different populations and animals, even experimental animals with the same rearing conditions, differ in their susceptibility to obesity. The disparity in gut microbiota could potentially account for the variation in susceptibility to obesity. However, the precise impact of gut microbiota on gut metabolites and its subsequent influence on susceptibility to obesity remains uncertain.

Methods

In this study, we established obesity-prone (OP) and obesity-resistant (OR) mouse models by High Fat Diet (HFD). Fecal contents of cecum were examined using 16S rDNA sequencing and untargeted metabolomics. Correlation analysis and MIMOSA2 analysis were used to explore the association between gut microbiota and intestinal metabolites.

Results

After a HFD, gut microbiota and gut metabolic profiles were significantly different between OP and OR mice. Gut microbiota after a HFD may lead to changes in eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), a variety of branched fatty acid esters of hydroxy fatty acids (FAHFAs) and a variety of phospholipids to promote obesity. The bacteria g_Akkermansia (Greengene ID: 175696) may contribute to the difference in obesity susceptibility through the synthesis of glycerophosphoryl diester phosphodiesterase (glpQ) to promote choline production and the synthesis of valyl-tRNA synthetase (VARS) which promotes L-Valine degradation. In addition, gut microbiota may affect obesity and obesity susceptibility through histidine metabolism, linoleic acid metabolism and protein digestion and absorption pathways.
Genome-wide identification of resistance genes and response mechanism analysis of key gene knockout strain to catechol in Saccharomyces cerevisiae
Authors: Liao Hong , Li Qian , Chen Yulei , Tang Jiaye , Mou Borui , Lu Fujia , Feng Peng , Li Wei , Li Jialian , Fu Chun , Long Wencong , Xiao Ximeng , Han Xuebing , Xin Wenli , Yang Fengxuan , Ma Menggen , Liu Beidong , Yang Yaojun , Wang Hanyu
Published: February 2024

Engineering Saccharomyces cerevisiae for biodegradation and transformation of industrial toxic substances such as catechol (CA) has received widespread attention, but the low tolerance of S. cerevisiae to CA has limited its development. The exploration and modification of genes or pathways related to CA tolerance in S. cerevisiae is an effective way to further improve the utilization efficiency of CA. This study identified 36 genes associated with CA tolerance in S. cerevisiae through genome-wide identification and bioinformatics analysis and the ERG6 knockout strain (ERG6Δ) is the most sensitive to CA. Based on the omics analysis of ERG6Δ under CA stress, it was found that ERG6 knockout affects pathways such as intrinsic component of membrane and pentose phosphate pathway. In addition, the study revealed that 29 genes related to the cell wall-membrane system were up-regulated by more than twice, NADPH and NADP+ were increased by 2.48 and 4.41 times respectively, and spermidine and spermine were increased by 2.85 and 2.14 times, respectively, in ERG6Δ. Overall, the response of cell wall-membrane system, the accumulation of spermidine and NADPH, as well as the increased levels of metabolites in pentose phosphate pathway are important findings in improving the CA resistance. This study provides a theoretical basis for improving the tolerance of strains to CA and reducing the damage caused by CA to the ecological environment and human health.
DNA-based doping and fabrication of PN diodes
Authors: Bai Ruobing , Liu Yihan , Zhang Bomin , Chen Beishan , Xiong Feng , Liu Haitao
Published: February 2024

This paper reports the fabrication of silicon PN diode by using DNA nanostructure as the etching template for SiO2 and also as the n-dopant of Si. DNA nanotubes were deposited onto p-type silicon wafer that has a thermal SiO2 layer. The DNA nanotubes catalyze the etching of SiO2 by HF vapor to expose the underlying Si. The phosphate groups in the DNA nanotube were used as the doping source to locally n-dope the Si wafer to form vertical P-N junctions. Prototype PN diodes were fabricated and exhibited expected blockage behavior with a knee voltage of ca. 0.7 V. Our work highlights the potential of DNA nanotechnology in future fabrication of nanoelectronics.
TUBA4A downregulation as observed in ALS post-mortem motor cortex causes ALS-related abnormalities in zebrafish
Authors: Van Schoor Evelien , Strubbe Dufie , Braems Elke , Weishaupt Jochen , Ludolph Albert C. , Van Damme Philip , Thal Dietmar Rudolf , Bercier Valérie , Van Den Bosch Ludo
Published: February 2024

Disease-associated variants of TUBA4A (alpha-tubulin 4A) have recently been identified in familial ALS. Interestingly, a downregulation of TUBA4A protein expression was observed in familial as well as sporadic ALS brain tissue. To investigate whether a decreased TUBA4A expression could be a driving factor in ALS pathogenesis, we assessed whether TUBA4A knockdown in zebrafish could recapitulate an ALS-like phenotype. For this, we injected an antisense oligonucleotide morpholino in zebrafish embryos targeting the zebrafish TUBA4A orthologue. An antibody against synaptic vesicle 2 was used to visualize motor axons in the spinal cord, allowing the analysis of embryonic ventral root projections. Motor behavior was assessed using the touch-evoked escape response. In post-mortem ALS motor cortex, we observed reduced TUBA4A levels. The knockdown of the zebrafish TUBA4A orthologue induced a motor axonopathy and a significantly disturbed motor behavior. Both phenotypes were dose-dependent and could be rescued by the addition of human wild-type TUBA4A mRNA. Thus, TUBA4A downregulation as observed in ALS post-mortem motor cortex could be modeled in zebrafish and induced a motor axonopathy and motor behavior defects reflecting a motor neuron disease phenotype, as previously described in embryonic zebrafish models of ALS. The rescue with human wild-type TUBA4A mRNA suggests functional conservation and strengthens the causal relation between TUBA4A protein levels and phenotype severity. Furthermore, the loss of TUBA4A induces significant changes in post-translational modifications of tubulin, such as acetylation, detyrosination and polyglutamylation. Our data unveil an important role for TUBA4A in ALS pathogenesis, and extend the relevance of TUBA4A to the majority of ALS patients, in addition to cases bearing TUBA4A mutations.
Deplete and repeat: microglial CSF1R inhibition and traumatic brain injury
Authors: Boland Rebecca , Kokiko-Cochran Olga N.
Published: February 2024

Traumatic brain injury (TBI) is a public health burden affecting millions of people. Sustained neuroinflammation after TBI is often associated with poor outcome. As a result, increased attention has been placed on the role of immune cells in post-injury recovery. Microglia are highly dynamic after TBI and play a key role in the post-injury neuroinflammatory response. Therefore, microglia represent a malleable post-injury target that could substantially influence long-term outcome after TBI. This review highlights the cell specific role of microglia in TBI pathophysiology. Microglia have been manipulated via genetic deletion, drug inhibition, and pharmacological depletion in various pre-clinical TBI models. Notably, colony stimulating factor 1 (CSF1) and its receptor (CSF1R) have gained much traction in recent years as a pharmacological target on microglia. CSF1R is a transmembrane tyrosine kinase receptor that is essential for microglia proliferation, differentiation, and survival. Small molecule inhibitors targeting CSF1R result in a swift and effective depletion of microglia in rodents. Moreover, discontinuation of the inhibitors is sufficient for microglia repopulation. Attention is placed on summarizing studies that incorporate CSF1R inhibition of microglia. Indeed, microglia depletion affects multiple aspects of TBI pathophysiology, including neuroinflammation, oxidative stress, and functional recovery with measurable influence on astrocytes, peripheral immune cells, and neurons. Taken together, the data highlight an important role for microglia in sustaining neuroinflammation and increasing risk of oxidative stress, which lends to neuronal damage and behavioral deficits chronically after TBI. Ultimately, the insights gained from CSF1R depletion of microglia are critical for understanding the temporospatial role that microglia develop in mediating TBI pathophysiology and recovery.
Ecological decoding of visual aesthetic preference with oscillatory electroencephalogram features—A mini-review
Authors: Welter Marc , Lotte Fabien
Published: February 2024

In today's digital information age, human exposure to visual artifacts has reached an unprecedented quasi-omnipresence. Some of these cultural artifacts are elevated to the status of artworks which indicates a special appreciation of these objects. For many persons, the perception of such artworks coincides with aesthetic experiences (AE) that can positively affect health and wellbeing. AEs are composed of complex cognitive and affective mental and physiological states. More profound scientific understanding of the neural dynamics behind AEs would allow the development of passive Brain-Computer-Interfaces (BCI) that offer personalized art presentation to improve AE without the necessity of explicit user feedback. However, previous empirical research in visual neuroaesthetics predominantly investigated functional Magnetic Resonance Imaging and Event-Related-Potentials correlates of AE in unnaturalistic laboratory conditions which might not be the best features for practical neuroaesthetic BCIs. Furthermore, AE has, until recently, largely been framed as the experience of beauty or pleasantness. Yet, these concepts do not encompass all types of AE. Thus, the scope of these concepts is too narrow to allow personalized and optimal art experience across individuals and cultures. This narrative mini-review summarizes the state-of-the-art in oscillatory Electroencephalography (EEG) based visual neuroaesthetics and paints a road map toward the development of ecologically valid neuroaesthetic passive BCI systems that could optimize AEs, as well as their beneficial consequences. We detail reported oscillatory EEG correlates of AEs, as well as machine learning approaches to classify AE. We also highlight current limitations in neuroaesthetics and suggest future directions to improve EEG decoding of AE.
The effects of ultrasonic processing on the antioxidant activity of Geotrichum candidum LG-8 and its cell wall extracts
Authors: Jiao Fengping , Cui Xianping , Gong Xiaodi , Jiang Guozheng , Wang Jinbiao , Meng Ling
Published: February 2024

Introduction

Extraction techniques that influence cell wall polysaccharides (EPS) is crucial for maximizing their bioactivity. This study evaluates ultrasound technology for extracting antioxidant polysaccharides from Geotrichum candidum LG-8, assessing its impacton antioxidant activity.

Methods

Ultrasound extraction of EPS from G. candidum LG-8 was optimized (18 min, pH 7.0, 40 W/cm2, 0.75 M NaCl). ABTS scavenging efficiency and monosaccharide composition of LG-EPS1 and LG-EPS3 were analyzed using Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM).

Results

The Results showed that ultrasonic treatment markedly increased the ABTS radical scavenging efficiency of LG-8 cells by 47%. At a concentration of 1 mg/mL, the ultrasonically extracted LG-EPS1 and LG-EPS3 polysaccharides exhibited significant ABTS radical scavenging efficiencies of 26% and 51%, respectively. Monosaccharide composition analysis identified mannose and glucose in LG-EPS1, while LG-EPS3 was primarily composed of mannose. FTIR spectra verified the polysaccharides' presence, and SEM provided visual confirmation of the nanoparticle structures characteristic of LG-EPS1 and LG-EPS3.

Discussion

This research not only underscores the technological merits of ultrasound in polysaccharide extraction but also highlights the potential of G. candidum LG-8 derived polysaccharides as valuable bioactive compounds for antioxidant utilization.
LINC01134: a pivotal oncogene with promising predictive maker and therapeutic target in hepatocellular carcinoma
Authors: Yu Yutian , Wang Jialing , Guo Qingfa , Luo Hongliang
Published: February 2024

Hepatocellular carcinoma (HCC) represents a leading and fatal malignancy within the gastrointestinal tract. Recent advancements highlight the pivotal role of long non-coding RNAs (lncRNAs) in diverse biological pathways and pathologies, particularly in tumorigenesis. LINC01134, a particular lncRNA, has attracted considerable attention due to its oncogenic potential in hepatoma. Current research underscores LINC01134’s potential in augmenting the onset and progression of HCC, with notable implications in drug resistance. This review comprehensively explores the molecular functions and regulatory mechanisms of LINC01134 in HCC, offering a fresh perspective for therapeutic interventions. By delving into LINC01134’s multifaceted roles, we aim to foster novel strategies in HCC management.
Exploring the application and future outlook of Artificial intelligence in pancreatic cancer
Authors: Zhao Guohua , Chen Xi , Zhu Mengying , Liu Yang , Wang Yue
Published: February 2024

Pancreatic cancer, an exceptionally malignant tumor of the digestive system, presents a challenge due to its lack of typical early symptoms and highly invasive nature. The majority of pancreatic cancer patients are diagnosed when curative surgical resection is no longer possible, resulting in a poor overall prognosis. In recent years, the rapid progress of Artificial intelligence (AI) in the medical field has led to the extensive utilization of machine learning and deep learning as the prevailing approaches. Various models based on AI technology have been employed in the early screening, diagnosis, treatment, and prognostic prediction of pancreatic cancer patients. Furthermore, the development and application of three-dimensional visualization and augmented reality navigation techniques have also found their way into pancreatic cancer surgery. This article provides a concise summary of the current state of AI technology in pancreatic cancer and offers a promising outlook for its future applications.
Bioinformatics characterization of variants of uncertain significance in pediatric sensorineural hearing loss
Authors: Clay Sloane , Evans Adele , Zambrano Regina , Otohinoyi David , Hicks Chindo , Tsien Fern
Published: February 2024

Introduction

Rapid advancements in Next Generation Sequencing (NGS) and bioinformatics tools have allowed physicians to obtain genetic testing results in a more rapid, cost-effective, and comprehensive manner than ever before. Around 50% of pediatric sensorineural hearing loss (SNHL) cases are due to a genetic etiology, thus physicians regularly utilize targeted sequencing panels that identify variants in genes related to SNHL. These panels allow for early detection of pathogenic variants which allows physicians to provide anticipatory guidance to families. Molecular testing does not always reveal a clear etiology due to the presence of multigenic variants with varying classifications, including the presence of Variants of Uncertain Significance (VUS). This study aims to perform a preliminary bioinformatics characterization of patients with variants associated with Type II Usher Syndrome in the presence of other multigenic variants. We also provide an interpretation algorithm for physicians reviewing molecular results with medical geneticists.

Methods

Review of records for multigenic and/or VUS results identified several potential subjects of interest. For the purposes of this study, two ADGRV1 compound heterozygotes met inclusion criteria. Sequencing, data processing, and variant calling (the process by which variants are identified from sequence data) was performed at Invitae (San Francisco CA). The preliminary analysis followed the recommendations outlined by the American College of Medical Genetics and Association for Molecular Pathology (ACMG-AMP) in 2015 and 2019. The present study utilizes computational analysis, predictive data, and population data as well as clinical information from chart review and publicly available information in the ClinVar database.

Results

Two subjects were identified as compound heterozygotes for variants in the gene ADGRV1. Subject 1's variants were predicted as deleterious, while Subject 2's variants were predicted as non-deleterious. These results were based on known information of the variants from ClinVar, multiple lines of computational data, population databases, as well as the clinical presentation.

Discussion

Early molecular diagnosis through NGS is ideal, as families are then able to access a wide range of resources that will ultimately support the child as their condition progresses. We recommend that physicians build strong relationships with medical geneticists and carefully review their interpretation before making recommendations to families, particularly when addressing the VUS. Reclassification efforts of VUS are supported by studies like ours that provide evidence of pathogenic or benign effects of variants.
The dual effect of endoplasmic reticulum stress in digestive system tumors and intervention of Chinese botanical drug extracts: a review
Authors: Zhang Jinlong , Chen Yanyu , Chen Bo , Sun Dajuan , Sun Zhen , Liang Junwei , Liang Jing , Xiong Xin , Yan Hua
Published: February 2024

Endoplasmic reticulum (ER) homeostasis is essential for maintaining human health, and once imbalanced, it will trigger endoplasmic reticulum stress (ERS), which participates in the development of digestive system tumors and other diseases. ERS has dual effect on tumor cells, activating adaptive responses to promote survival or inducing apoptotic pathways to accelerate cell death of the tumor. Recent studies have demonstrated that Chinese botanical drug extracts can affect the tumor process of the digestive system by regulating ERS and exert anticancer effects. This article summarizes the dual effect of ERS in the process of digestive system tumors and the intervention of Chinese botanical drug extracts in recent years, as reference for the combined treatment of digestive system tumors with Chinese and modern medicine.
AgTC and AgETL: open-source tools to enhance data collection and management for plant science research
Authors: Vargas-Rojas Luis , Ting To-Chia , Rainey Katherine M. , Reynolds Matthew , Wang Diane R.
Published: February 2024

Advancements in phenotyping technology have enabled plant science researchers to gather large volumes of information from their experiments, especially those that evaluate multiple genotypes. To fully leverage these complex and often heterogeneous data sets (i.e. those that differ in format and structure), scientists must invest considerable time in data processing, and data management has emerged as a considerable barrier for downstream application. Here, we propose a pipeline to enhance data collection, processing, and management from plant science studies comprising of two newly developed open-source programs. The first, called AgTC, is a series of programming functions that generates comma-separated values file templates to collect data in a standard format using either a lab-based computer or a mobile device. The second series of functions, AgETL, executes steps for an Extract-Transform-Load (ETL) data integration process where data are extracted from heterogeneously formatted files, transformed to meet standard criteria, and loaded into a database. There, data are stored and can be accessed for data analysis-related processes, including dynamic data visualization through web-based tools. Both AgTC and AgETL are flexible for application across plant science experiments without programming knowledge on the part of the domain scientist, and their functions are executed on Jupyter Notebook, a browser-based interactive development environment. Additionally, all parameters are easily customized from central configuration files written in the human-readable YAML format. Using three experiments from research laboratories in university and non-government organization (NGO) settings as test cases, we demonstrate the utility of AgTC and AgETL to streamline critical steps from data collection to analysis in the plant sciences.
Target enrichment sequencing coupled with GWAS identifies MdPRX10 as a candidate gene in the control of budbreak in apple
Authors: Watson Amy E. , Guitton Baptiste , Soriano Alexandre , Rivallan Ronan , Vignes Hélène , Farrera Isabelle , Huettel Bruno , Arnaiz Catalina , Falavigna Vítor da Silveira , Coupel-Ledru Aude , Segura Vincent , Sarah Gautier , Dufayard Jean-François , Sidibe-Bocs Stéphanie , Costes Evelyne , Andrés Fernando
Published: February 2024

The timing of floral budbreak in apple has a significant effect on fruit production and quality. Budbreak occurs as a result of a complex molecular mechanism that relies on accurate integration of external environmental cues, principally temperature. In the pursuit of understanding this mechanism, especially with respect to aiding adaptation to climate change, a QTL at the top of linkage group (LG) 9 has been identified by many studies on budbreak, but the genes underlying it remain elusive. Here, together with a dessert apple core collection of 239 cultivars, we used a targeted capture sequencing approach to increase SNP resolution in apple orthologues of known or suspected A. thaliana flowering time-related genes, as well as approximately 200 genes within the LG9 QTL interval. This increased the 275 223 SNP Axiom® Apple 480 K array dataset by an additional 40 857 markers. Robust GWAS analyses identified MdPRX10, a peroxidase superfamily gene, as a strong candidate that demonstrated a dormancy-related expression pattern and down-regulation in response to chilling. In-silico analyses also predicted the residue change resulting from the SNP allele associated with late budbreak could alter protein conformation and likely function. Late budbreak cultivars homozygous for this SNP allele also showed significantly up-regulated expression of C-REPEAT BINDING FACTOR (CBF) genes, which are involved in cold tolerance and perception, compared to reference cultivars, such as Gala. Taken together, these results indicate a role for MdPRX10 in budbreak, potentially via redox-mediated signaling and CBF gene regulation. Moving forward, this provides a focus for developing our understanding of the effects of temperature on flowering time and how redox processes may influence integration of external cues in dormancy pathways.
The ambivalence of the implementation of the US arctic policy: integrating and disintegration factors of the allies
Authors: Dauylbayev Aidarkhan , Yelmurzayeva Raushan , Kamaljanova Takhira , Ibragimova Gulnara
Published: February 2024

The Arctic region is gaining increasing strategic importance due to its economic potential, resource richness, and shifting geopolitical landscape. The United States has recognized this significance and has established alliances and partnerships with various countries in the region to enhance its positions and interests. However, concerns exist regarding the limited understanding of the complex dynamics and evolving relationships among the US Arctic allies. The lack of comprehensive analysis and up-to-date information hinders the understanding of their strategic documents, military exercises, and interactions with global players like China and Russia. To address these concerns, our objective was to identify, analyze, and assess the factors that strengthen or weaken the interaction between US allies and partners in the Arctic region. We conducted an analysis of national Arctic strategies, reports, publications, and expert opinions from Western Arctic Council countries such as the USA, Canada, Denmark, Iceland, Norway, Sweden, and Finland. We also examined the reports and structures of the US defense services, interstate organizations like the North Atlantic Treaty Organization (NATO) and the North American Aerospace Defense Command (NORAD), as well as insights from leading experts on Arctic affairs in allied countries. The study revealed several factors that contribute to the strengthening of the US allies in the Arctic. These include active military cooperation within the North Atlantic Alliance, joint exercises, intelligence sharing, and the development of Arctic infrastructure to enhance regional security and defense capabilities. However, we also identified factors that weaken engagement among the US allies. These include differences in strategic goals, competing territorial claims, domestic political considerations, and varying relationships with other Arctic stakeholders like Russia and China. These factors can lead to tensions and challenges, which undermine collective action and impede the achievement of common goals.