bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-Additive and Asymmetric Allelic Expression of p38 mapk in Hybrid Tilapia (Oreochromis niloticus ♀ × O. aureus ♂)
Authors: Liu Zihui , Chen Binglin , Zou Zhiying , Li Dayu , Zhu Jinglin , Yu Jie , Xiao Wei , Yang Hong
Published: January 2024

Hybridization is a widely used breeding technique in fish species that enhances desirable traits in cultured species through heterosis. However, the mechanism by which hybrids alter gene expression to form heterosis remains unclear. In this study, a group of hybrid tilapia was used to elucidate heterosis through interspecies crossing. Specifically, p38 was analyzed to describe the regulation of gene expression variation in hybrid tilapia. Transcripts from the Nile tilapia allele were found to be significantly higher than those from the blue tilapia allele in hybrid individuals, indicating that the expression of p38 was dominated by Nile tilapia sub-genomic alleles. The study also found a compensatory interaction of cis- and trans-acting elements of the Nile tilapia and blue tilapia sub-genomes, inducing a non-additive expression of p38 in hybrids. Eight specific SNPs were identified in the p38 promoter regions of Nile tilapia and blue tilapia, and were found to be promoter differences leading to differences in gene expression efficiencies between parental alleles using a dual-luciferase reporter system. This study provides insights into the non-additive expression patterns of key functional genes in fish hybrids related to growth and immunity response.
Ligilactobacillus animalis 506 Protects the Intestinal Barrier from the Damaging Effects of Enteric Pathogens and Deoxynivalenol
Authors: Boll Erik Juncker , Winther Katrine Damgaard , Knudsen Tine Thorup Møller , Copani Giuseppe , Cappellozza Bruno Ieda
Published: January 2024

This study investigated the impact of L. animalis 506 on gut barrier integrity and regulation of inflammation in vitro using intestinal epithelial cell lines. Caco-2 or HT29 cell monolayers were challenged with enterotoxigenic E. coli (ETEC) or a ruminant isolate of Salmonella Heidelberg in the presence or absence of one of six probiotic Lactobacillus spp. strains. Among these, L. animalis 506 excelled at exerting protective effects by significantly mitigating the decreased transepithelial electrical resistance (TEER) as assessed using area under the curve (AUC) (p < 0.0001) and increased apical-to-basolateral fluorescein isothiocyanate (FITC) dextran translocation (p < 0.0001) across Caco-2 cell monolayers caused by S. Heidelberg or ETEC, respectively. Similarly, L. animalis 506 and other probiotic strains significantly attenuated the S. Heidelberg- and ETEC-induced increase in IL-8 from HT29 cells (p < 0.0001). Moreover, L. animalis 506 significantly counteracted the TEER decrease (p < 0.0001) and FITC dextran translocation (p < 0.0001) upon challenge with Clostridium perfringens. Finally, L. animalis 506 significantly attenuated DON-induced TEER decrease (p < 0.01) and FITC dextran translocation (p < 0.05) and mitigated occludin and zona occludens (ZO)-1 redistribution in Caco-2 cells caused by the mycotoxin. Collectively, these results demonstrate the ability of L. animalis 506 to confer protective effects on the intestinal epithelium in vitro upon challenge with enteric pathogens and DON known to be of particular concern in farm animals.
Low Genetic Variability of the Tundra Vole in Lithuania
Authors: Prakas Petras , Butkauskas Dalius , Balčiauskienė Laima , Balčiauskas Linas
Published: January 2024

The distribution and spread of the tundra vole (Alexandromys oeconomus) in Lithuania have been documented over the last 70 years, but the genetic diversity of the species has not been studied. In this study, we examined A. oeconomus trapped in three sites in northern and western Lithuania using mtDNA sequence analysis of the cytb and control region. The western and northern sites are separated by anthropogenic landscape barriers. The western site is subject to regular spring flooding. Phylogenetic analyses of the studied individuals placed them in the Central European phylogroup, suggesting that Lithuanian A. oeconomus originated from northeastern Poland. In Lithuania, the genetic diversity of A. oeconomus at both mtDNA loci was relatively low (Hd < 0.6, π < 0.002) compared to that found in other European samples (Hd = 0.833–0.958; π = 0.00402–0.01552). Individuals analyzed in Lithuania were genetically different from samples collected in Poland and Northern Europe (ΦST > 0.15, p < 0.05). The genetic divergence between the western and northern samples of A. oeconomus in Lithuania, together with the low genetic variability among the voles studied, provides new insights into the phylogeography of the species and the influence of barriers on the colonization of the country.
Establishment of an Indirect ELISA Method for the Detection of the Bovine Rotavirus VP6 Protein
Authors: Niu Xiaoxia , Liu Qiang , Wang Pu , Zhang Gang , Jiang Lingling , Zhang Sinong , Zeng Jin , Yu Yongtao , Wang Yujiong , Li Yong
Published: January 2024

The objective of this study was to develop an indirect ELISA utilizing a polyclonal antibody against bovine rotavirus (BRV) VP6 protein. To achieve this, pcDNA3.1-VP6, a recombinant eukaryotic expression plasmid, was constructed based on the sequence of the conserved BRV gene VP6 and was transfected into CHO-K1 cells using the transient transfection method. The VP6 protein was purified as the coating antigen using nickel ion affinity chromatography, and an indirect ELISA was subsequently established. The study found that the optimal concentration of coating for the VP6 protein was 1 μg/mL. The optimal blocking solution was 3% skim milk, and the blocking time was 120 min. The secondary antibody was diluted to 1:4000, and the incubation time for the secondary antibody was 30 min. A positive result was indicated when the serum OD450 was greater than or equal to 0.357. The coefficients of variation were less than 10% both within and between batches, indicating the good reproducibility of the method. The study found that the test result was positive when the serum dilution was 217, indicating the high sensitivity of the method. A total of 24 positive sera and 40 negative sera were tested using the well-established ELISA. The study also established an indirect ELISA assay with good specificity and sensitivity for the detection of antibodies to bovine rotavirus. Overall, the results suggest that the indirect ELISA method developed in this study is an effective test for detecting such antibodies.
EEG Emotion Classification Based on Graph Convolutional Network
Authors: Fan Zhiqiang , Chen Fangyue , Xia Xiaokai , Liu Yu
Published: January 2024

EEG-based emotion recognition is a task that uses scalp-EEG data to classify the emotion states of humans. The study of EEG-based emotion recognition can contribute to a large spectrum of application fields including healthcare and human–computer interaction. Recent studies in neuroscience reveal that the brain regions and their interactions play an essential role in the processing of different stimuli and the generation of corresponding emotional states. Nevertheless, such regional interactions, which have been proven to be critical in recognizing emotions in neuroscience, are largely overlooked in existing machine learning or deep learning models, which focus on individual channels in brain signals. Motivated by this, in this paper, we present RGNet, a model that is designed to learn the regional level representation of EEG signal for accurate emotion recognition. Specifically, after applying preprocessing and feature extraction techniques on raw signals, RGNet adopts a novel region-wise encoder to extract the features of channels located within each region as input to compute the regional level features, enabling the model to effectively explore the regional functionality. A graph is then constructed by considering each region as a node and connections between regions as edges, upon which a graph convolutional network is designed with spectral filtering and learned adjacency matrix. Instead of focusing on only the spatial proximity, it allows the model to capture more complex functional relationships. We conducted experiments from the perspective of region division strategies, region encoders and input feature types. Our model has achieved 98.64% and 99.33% for Deap and Dreamer datasets, respectively. The comparison studies show that RGNet outperforms the majority of the existing models for emotion recognition from EEG signals.
Aspect-Level Sentiment Analysis Based on Syntax-Aware and Graph Convolutional Networks
Authors: Gu Qun , Wang Zhidong , Zhang Hai , Sui Siyi , Wang Rui
Published: January 2024

Aspect-level sentiment analysis is a task of identifying and understanding the sentiment polarity of specific aspects of a sentence. In recent years, significant progress has been made in aspect-level sentiment analysis models based on graph convolutional neural networks. However, existing models still have some shortcomings, such as aspect-level sentiment analysis models based on graph convolutional networks not making full use of the information of specific aspects in a sentence and ignoring the enhancement of the model by external general knowledge of sentiment. In order to solve these problems, this paper proposes a sentiment analysis model based on the Syntax-Aware and Graph Convolutional Network (SAGCN). The model first integrates aspect-specific features into contextual information, and second incorporates external sentiment knowledge to enhance the model’s ability to perceive sentiment information. Finally, a multi-head self-attention mechanism and Point-wise Convolutional Transformer (PCT) are applied to capture the semantic information of the sentence. The semantic and syntactic information of the sentences are considered together. Experimental results on three benchmark datasets show that the SAGCN model is able to achieve superior performance compared to the benchmark methods.
A Radar Echo Extrapolation Model Based on a Dual-Branch Encoder–Decoder and Spatiotemporal GRU
Authors: Cheng Yong , Qu Haifeng , Wang Jun , Qian Kun , Li Wei , Yang Ling , Han Xiaodong , Liu Min
Published: January 2024

Precipitation forecasting is an immensely significant aspect of meteorological prediction. Accurate weather predictions facilitate services in sectors such as transportation, agriculture, and tourism. In recent years, deep learning-based radar echo extrapolation techniques have found effective applications in precipitation forecasting. However, the ability of existing methods to extract and characterize complex spatiotemporal features from radar echo images remains insufficient, resulting in suboptimal forecasting accuracy. This paper proposes a novel extrapolation algorithm based on a dual-branch encoder–decoder and spatiotemporal Gated Recurrent Unit. In this model, the dual-branch encoder–decoder structure independently encodes radar echo images in the temporal and spatial domains, thereby avoiding interference between spatiotemporal information. Additionally, we introduce a Multi-Scale Channel Attention Module (MSCAM) to learn global and local feature information from each encoder layer, thereby enhancing focus on radar image details. Furthermore, we propose a Spatiotemporal Attention Gated Recurrent Unit (STAGRU) that integrates attention mechanisms to handle temporal evolution and spatial relationships within radar data, enabling the extraction of spatiotemporal information from a broader receptive field. Experimental results demonstrate the model’s ability to accurately predict morphological changes and motion trajectories of radar images on real radar datasets, exhibiting superior performance compared to existing models in terms of various evaluation metrics. This study effectively improves the accuracy of precipitation forecasting in radar echo images, provides technical support for the short-range forecasting of precipitation, and has good application prospects.
Nanotechnology Innovations in Pediatric Cardiology and Cardiovascular Medicine: A Comprehensive Review
Authors: Moisa Stefana Maria , Burlacu Alexandru , Butnariu Lacramioara Ionela , Vasile Corina Maria , Brinza Crischentian , Spoiala Elena Lia , Maștaleru Alexandra , Leon Maria Magdalena , Rosu Solange Tamara , Vatasescu Radu , Cinteză Eliza Elena
Published: January 2024

(1) Background: Nanomedicine, incorporating various nanoparticles and nanomaterials, offers significant potential in medical practice. Its clinical adoption, however, faces challenges like safety concerns, regulatory hurdles, and biocompatibility issues. Despite these, recent advancements have led to the approval of many nanotechnology-based products, including those for pediatric use. (2) Methods: Our approach included reviewing clinical, preclinical, and animal studies, as well as literature reviews from the past two decades and ongoing trials. (3) Results: Nanotechnology has introduced innovative solutions in cardiovascular care, particularly in managing myocardial ischemia. Key developments include drug-eluting stents, nitric oxide-releasing coatings, and the use of magnetic nanoparticles in cardiomyocyte transplantation. These advancements are pivotal for early detection and treatment. In cardiovascular imaging, nanotechnology enables noninvasive assessments. In pediatric cardiology, it holds promise in assisting the development of biological conduits, synthetic valves, and bioartificial grafts for congenital heart defects, and offers new treatments for conditions like dilated cardiomyopathy and pulmonary hypertension. (4) Conclusions: Nanomedicine presents groundbreaking solutions for cardiovascular diseases in both adults and children. It has the potential to transform cardiac care, from enhancing myocardial ischemia treatment and imaging techniques to addressing congenital heart issues. Further research and guideline development are crucial for optimizing its clinical application and revolutionizing patient care.
Gram-Positive Bacterial Membrane-Based Biosensor for Multimodal Investigation of Membrane–Antibiotic Interactions
Authors: Bint-E-Naser Samavi Farnush , Mohamed Zeinab Jushkun , Chao Zhongmou , Bali Karan , Owens Róisín M. , Daniel Susan
Published: January 2024

As membrane-mediated antibiotic resistance continues to evolve in Gram-positive bacteria, the development of new approaches to elucidate the membrane properties involved in antibiotic resistance has become critical. Membrane vesicles (MVs) secreted by the cytoplasmic membrane of Gram-positive bacteria contain native components, preserving lipid and protein diversity, nucleic acids, and sometimes virulence factors. Thus, MV-derived membrane platforms present a great model for Gram-positive bacterial membranes. In this work, we report the development of a planar bacterial cytoplasmic membrane-based biosensor using MVs isolated from the Bacillus subtilis WT strain that can be coated on multiple surface types such as glass, quartz crystals, and polymeric electrodes, fostering the multimodal assessment of drug–membrane interactions. Retention of native membrane components such as lipoteichoic acids, lipids, and proteins is verified. This biosensor replicates known interaction patterns of the antimicrobial compound, daptomycin, with the Gram-positive bacterial membrane, establishing the applicability of this platform for carrying out biophysical characterization of the interactions of membrane-acting antibiotic compounds with the bacterial cytoplasmic membrane. We report changes in membrane viscoelasticity and permeability that correspond to partial membrane disruption when calcium ions are present with daptomycin but not when these ions are absent. This biomembrane-based biosensing platform enables an assessment of membrane biophysical characteristics during exposure to antibiotic drug candidates to aid in identifying compounds that target membrane disruption as a mechanism of action.
Minimal Clinically Important Difference of Scales Reported in Stroke Trials: A Review
Authors: Mishra Biswamohan , Sudheer Pachipala , Agarwal Ayush , Nilima Nilima , Srivastava Madakasira Vasantha Padma , Vishnu Venugopalan Y.
Published: January 2024

There is a growing awareness of the significance of using minimum clinically important differences (MCIDs) in stroke research. An MCID is the smallest change in an outcome measure that is considered clinically meaningful. This review is the first to provide a comprehensive summary of various scales and patient-reported outcome measures (PROMs) used in stroke research and their MCID values reported in the literature, including a concise overview of the concept of and methods for determining MCIDs in stroke research. Despite the controversies and limitations surrounding the estimation of MCIDs, their importance in modern clinical trials cannot be overstated. Anchor-based and distribution-based methods are recommended for estimating MCIDs, with patient self-evaluation being a crucial component in capturing the patient’s perspective on their health. A combination of methods can provide a more comprehensive understanding of the clinical relevance of treatment effects, and incorporating the patient’s perspective can enhance the care of stroke patients.
Calm Contact Technique Based on the Endocrinological Mechanism of Hypnosis—A Theoretical Proposal
Authors: Varga Katalin , Nagy Zita S.
Published: January 2024

This paper proposes the “calm contact” technique: an imaginative scenario where someone is in gentle contact with a loved one where the essence of the experience is to enjoy safety and calmness in peaceful social contact. The theoretical background is outlined by combining the brain mechanisms of stress reactions and hypnosis. In addition to the ancient stress responses (flight or fight or freeze), there are oxytocin-based options at the human level: tend and befriend behavior and the state of calm and connection, which is not a stress reaction but a resting reaction. These social-based reactions could prevent the organism from the primitive freezing response. Some studies proved that “hypnosis” as a setting reduces cortisol levels and could raise oxytocin levels. The beneficial mechanisms of the “calm contact” technique are analyzed in relation to “social support” and the psychoaffective effects of central oxytocin. The subjective effects of the proposed technique are outlined based on reports of healthy volunteers. The “calm contact” technique could be an alternative or adjunct to the “safe place” technique, applying the recent findings of endocrinological brain mechanisms of hypnosis. Clinical implications and limitations are briefly summarized.
Determinants of Quality of Life (QoL) in Female Caregivers in Elderly Care Facilities in Korea
Authors: Kim Hee-Kyung , Oh Hye-Suk
Published: January 2024

Background: The purpose of this study was to analyze the effects of general characteristics, fatigue, depression, self-efficacy, job stress and interpersonal relationships on the quality of life (QoL) of caregivers in nursing hospitals and use them as basic data for intervention programs to improve the quality of life of caregivers. Methods: The participants in the study were 137 caregivers, aged 52–76, who were actively working in nursing hospitals. Data were collected from caregivers by visiting 9 hospitals in 6 cities, with a questionnaire of fatigue, depression, self-efficacy, job stress, interpersonal relationship, quality of life. Results: Age, marriage, marital satisfaction, education, education experience of QoL, monthly income, perceived economic status, hobby or leisure activity, and number of disease showed differences in the degree of QoL at a statistically significant level. In stage 1, economic status (β = −0.18, p = 0.033) and hobby or leisure activity (β = 0.19, p = 0.025) were influencing factors (F = 4.58, p < 0.001). In stage 2, monthly income (β = −0.19, p = 0.034) and perceived economic status (β = −0.18, p = 0.035) were influencing factors. In stage 3, age (β = −2.80, p = 0.006), perceived economic status (β = −2.41, p = 0.017), self-efficacy (β = 3.19, p = 0.002) and interpersonal relationship (β = 7.12, p < 0.001) were influencing factors which showed 61.5% explanatory power (F = 12.88, p < 0.001). Since the subject’s fatigue, depression, and stress did not affect the quality of life, further research is needed. Conclusions: In order to improve the quality of life of caregivers, it would be necessary to develop interventions for raising their self-efficacy and interpersonal relationship by considering their degree of economic status, hobby or leisure activity, monthly income, and age.
A Predictive Model for the Growth Diameter of Mold under Different Temperatures and Relative Humidities in Indoor Environments
Authors: Wang Chenyang , Mei Yong , Wang Heqi , Guo Xinzhu , Yang Ting , Du Chenqiu , Yu Wei
Published: January 2024

A substantial body of evidence suggests that indoor mold exposure is a cause of allergic and respiratory diseases in humans. While models exist for assessing the risk of mold growth on building materials, few study the characteristics of mold growth after germination. This study conducted mold growth experiments in a constant temperature chamber, using four temperature settings of 15, 20, 25 and 30 °C, and three relative humidities of 56 to 61%, 75 to 76% and 83 to 86%. A mold growth prediction model was established using temperature and relative humidity. The accuracy of the model was verified by comparing the sampling and the predicted values in a laboratory environment. The results indicated that reducing the environmental temperature and relative humidity could significantly inhibit the growth of mold, although the inhibitory effects varied. Temperature might play a more critical role. At higher temperatures (25 °C and 30 °C), the growth rate and lag time of mold tended to be consistent and there were differences in the maximum diameter. In the predictive model, the polynomial secondary model for the maximum growth rate and lag time and the Arrhenius–Davey secondary model for the maximum diameter (A) had good predictive effects (Adj.R2 > 0.850). It is speculated that temperature is the key factor affecting the maximum growth diameter of mold. The mold growth prediction model could better predict the growth of mold in actual environments without wind Adj.R2 > 0.800), but the accuracy of the model decreased under windy conditions (wind velocity < 1 m/s). The mold growth predictive model we established could be used to predict the growth characteristics of mold in windless environments. It also provides control suggestions for the regulation of temperature and relative humidity in indoor environments, supporting indoor thermal environment management and pollutant control, and ensuring indoor human health.
Structural Behavior of a Fixed-End Arched Cellular Steel Beam without Lateral Support
Authors: Ning Qiujun , Lu Jiawei , Li Shaojuan , Lu Xiaosong
Published: January 2024

The arched cellular beam has the advantages of both the solid-web arch and the straight beam with web opening, and has become increasingly admired by architects in recent years. In this paper, four arched cellular beam specimens are designed using an orthogonal test method (OTM) with a three-factor and two-level approach. Firstly, the static loading test is carried out to analyze the mechanical response of the arched cellular beam under concentrated load. Then, a numerical analysis based on ABAQUS finite element (FE) software is carried out. The results show that the simulation results agree well with the test results, which indicates the accuracy of the simulation analysis method. Finally, the buckling load of the arched cellular beam under three different loads is calculated using the variable parameter FE analysis. Combined with the range analysis in the OTM, the influence of the target factor on the buckling load of the arched cellular beam is determined. The results show that the order of the factors affecting the out-of-plane elastic buckling is rise–span ratio > web height–thickness ratio > diameter–depth ratio.
Study on Inverse Analysis Technique Considering Influence of Construction Procedure on Performance of Large-Span Steel Latticed Arch
Authors: Wang Yimin , Dai Kangxi , Ju Jinsan
Published: January 2024

In this paper, the influence of the construction process of large-span steel latticed arch on the geometric configuration and bearing capacity performance of the large-span steel latticed arch is calculated and analyzed by using the inverse analysis technique. By comparing the calculation results of single pre-deformation adjustment of the node co-ordinates in zero state of the whole structure and the dynamic adjustment of the node co-ordinates of the unconstructed part of the structure, it is found that the inverse analysis method of dynamic node co-ordinate adjustment is used to achieve the unification of the geometric configuration of the final structure and the bearing capacity performance of the structure. The results show that the inverse analysis method of dynamic node co-ordinate adjustment proposed in this paper can simulate and track the dynamic changes of structural geometry and stable bearing capacity performance in the actual construction process, which can not only consider the influence of the installed part of the structure on the co-ordinate adjustment value of the uninstalled part of the structure but also consider the deformation influence of the subsequent uninstalled structure on the installed structure and can realize the optimal approximation of the final state structure to the geometric configuration of the zero state structure and the accurate calculation of the bearing capacity performance with the progress of the construction process.
Serum Anti-Zta and Anti-LMP1 Antibodies in Oropharyngeal Cancer Related to Epstein–Barr Virus—Diagnostic Usefulness
Authors: Polz Anna , Morshed Kamal , Drop Bartłomiej , Drop Andrzej , Polz-Dacewicz Małgorzata
Published: January 2024

Background: The role of the Epstein–Barr virus (EBV), the first known human oncogenic virus, in the development of nasopharyngeal cancer (NPC) is already well documented. There are few studies in the available scientific literature on oropharyngeal cancer associated with EBV infection. Due to the lack of an effective vaccine against EBV, it is necessary to search for new markers for the early diagnosis and prognosis of this disease. The aim of current study was to determine the usefulness of anti-Zta and anti-LMP1 antibodies as diagnostic and prognostic markers in EBV positive OPSCC patients. Methods: For this purpose, experiments were carried out to determine both the prevalence and level of EBVCA, EBNA1, EA, Zta, and LMP1 antibodies in serum patients depending on histological differentiation-grading and TNM classification (ELISA assay). Results: Based on the obtained results, we showed that OPSCC EBV positive patients are characterized by a higher level of anti-Zta antibodies than in the EBV negative group. Their level depended on the clinical stage. Moreover, a ROC analysis confirmed the diagnostic accuracy of anti-Zta antibodies. Conclusions: Anti-Zta and anti-LMP1 antibodies may be useful in the diagnosis of OPSCC. It seems that combined antibody testing should be performed to increase diagnostic accuracy.
TCGAnalyzeR: An Online Pan-Cancer Tool for Integrative Visualization of Molecular and Clinical Data of Cancer Patients for Cohort and Associated Gene Discovery
Authors: Zengin Talip , Masud Başak Abak , Önal-Süzek Tuğba
Published: January 2024

For humans, the parallel processing capability of visual recognition allows for faster comprehension of complex scenes and patterns. This is essential, especially for clinicians interpreting big data for whom the visualization tools play an even more vital role in transforming raw big data into clinical decision making by managing the inherent complexity and monitoring patterns interactively in real time. The Cancer Genome Atlas (TCGA) database’s size and data variety challenge the effective utilization of this valuable resource by clinicians and biologists. We re-analyzed the five molecular data types, i.e., mutation, transcriptome profile, copy number variation, miRNA, and methylation data, of ~11,000 cancer patients with all 33 cancer types and integrated the existing TCGA patient cohorts from the literature into a free and efficient web application: TCGAnalyzeR. TCGAnalyzeR provides an integrative visualization of pre-analyzed TCGA data with several novel modules: (i) simple nucleotide variations with driver prediction; (ii) recurrent copy number alterations; (iii) differential expression in tumor versus normal, with pathway and the survival analysis; (iv) TCGA clinical data including metastasis and survival analysis; (v) external subcohorts from the literature, curatedTCGAData, and BiocOncoTK R packages; (vi) internal patient clusters determined using an iClusterPlus R package or signature-based expression analysis of five molecular data types. TCGAnalyzeR integrated the multi-omics, pan-cancer TCGA with ~120 subcohorts from the literature along with clipboard panels, thus allowing users to create their own subcohorts, compare against existing external subcohorts (MSI, Immune, PAM50, Triple Negative, IDH1, miRNA, metastasis, etc.) along with our internal patient clusters, and visualize cohort-centric or gene-centric results interactively using TCGAnalyzeR.
Expanding Our Knowledge of DICER1 Gene Alterations and Their Role in Thyroid Diseases
Authors: Riascos Maria Cristina , Huynh Anh , Faquin William C. , Nosé Vania
Published: January 2024

Mutations in DICER1, a gene involved in RNA interference, have been associated with a wide range of multi-organ neoplastic and non-neoplastic conditions. Historically known for its association with pleuropulmonary blastoma, DICER1 syndrome has received more attention due to the association with newly discovered diseases and tumors. Recent studies evaluating DICER1 mutations and DICER1-driven thyroid disease in both pediatric and adult thyroid nodules revealed thyroid disease as the most common manifestation of DICER1 mutations. This study undertakes a comprehensive investigation into DICER1 mutations, focusing on their role in thyroid diseases. Specific attention was given to thyroid follicular nodular disease and differentiated thyroid carcinomas in infancy as highly indicative of germline DICER1 mutation or DICER1 syndrome. Additionally, poorly differentiated thyroid carcinoma and thyroblastoma were identified as potential indicators of somatic DICER1 mutations. Recognizing these manifestations should prompt clinicians to expedite genetic evaluation for this neoplastic syndrome and classify these patients as high risk for additional multi-organ malignancies. This study comprehensively synthesizes the current knowledge surrounding this genetically associated entity, providing intricate details on histologic findings to facilitate its diagnosis.
A Comprehensive Bioinformatic Analysis of RNA-seq Datasets Reveals a Differential and Variable Expression of Wildtype and Variant UGT1A Transcripts in Human Tissues and Their Deregulation in Cancers
Authors: Hu Dong Gui , Marri Shashikanth , Hulin Julie-Ann , McKinnon Ross A. , Mackenzie Peter I. , Meech Robyn
Published: January 2024

The UGT1A locus generates over 60 different alternatively spliced transcripts and 30 circular RNAs. To date, v2 and v3 transcripts are the only variant UGT1A transcripts that have been functionally characterized. Both v2 and v3 transcripts encode the same inactive variant UGT1A proteins (i2s) that can negatively regulate glucuronidation activity and influence cancer cell metabolism. However, the abundance and interindividual variability in the expression of v2 and v3 transcripts in human tissues and their potential deregulation in cancers have not been comprehensively assessed. To address this knowledge gap, we quantified the expression levels of v1, v2, and v3 transcripts using RNA-seq datasets with large cohorts of normal tissues and paired normal and tumor tissues from patients with six different cancer types (liver, kidney, colon, stomach, esophagus, and bladder cancer). We found that v2 and v3 abundance varied significantly between different tissue types, and that interindividual variation was also high within the same tissue type. Moreover, the ratio of v2 to v3 variants varied between tissues, implying their differential regulation. Our results showed higher v2 abundance in gastrointestinal tissues than liver and kidney tissues, suggesting a more significant negative regulation of glucuronidation by i2 proteins in gastrointestinal tissues than in liver and kidney tissues. We further showed differential deregulation of wildtype (v1) and variant transcripts (v2, v3) in cancers that generally increased the v2/v1 and/or v3/v1 expression ratios in tumors compared to normal tissues, indicating a more significant role of the variants in tumors. Finally, we report ten novel UGT1A transcripts with novel 3′ terminal exons, most of which encode variant proteins with a similar structure to UGT1A_i2 proteins. These findings further emphasize the diversity of the UGT1A transcriptome and proteome.
Advanced Hyperpolarized 13C Metabolic Imaging Protocol for Patients with Gliomas: A Comprehensive Multimodal MRI Approach
Authors: Autry Adam W. , Vaziri Sana , Gordon Jeremy W. , Chen Hsin-Yu , Kim Yaewon , Dang Duy , LaFontaine Marisa , Noeske Ralph , Bok Robert , Villanueva-Meyer Javier E. , Clarke Jennifer L. , Oberheim Bush Nancy Ann , Chang Susan M. , Xu Duan , Lupo Janine M. , Larson Peder E. Z. , Vigneron Daniel B. , Li Yan
Published: January 2024

This study aimed to implement a multimodal 1H/HP-13C imaging protocol to augment the serial monitoring of patients with glioma, while simultaneously pursuing methods for improving the robustness of HP-13C metabolic data. A total of 100 1H/HP [1-13C]-pyruvate MR examinations (104 HP-13C datasets) were acquired from 42 patients according to the comprehensive multimodal glioma imaging protocol. Serial data coverage, accuracy of frequency reference, and acquisition delay were evaluated using a mixed-effects model to account for multiple exams per patient. Serial atlas-based HP-13C MRI demonstrated consistency in volumetric coverage measured by inter-exam dice coefficients (0.977 ± 0.008, mean ± SD; four patients/11 exams). The atlas-derived prescription provided significantly improved data quality compared to manually prescribed acquisitions (n = 26/78; p = 0.04). The water-based method for referencing [1-13C]-pyruvate center frequency significantly reduced off-resonance excitation relative to the coil-embedded [13C]-urea phantom (4.1 ± 3.7 Hz vs. 9.9 ± 10.7 Hz; p = 0.0007). Significantly improved capture of tracer inflow was achieved with the 2-s versus 5-s HP-13C MRI acquisition delay (p = 0.007). This study demonstrated the implementation of a comprehensive multimodal 1H/HP-13C MR protocol emphasizing the monitoring of steady-state/dynamic metabolism in patients with glioma.
Methylene Blue Metabolic Therapy Restrains In Vivo Ovarian Tumor Growth
Authors: da Veiga Moreira Jorgelindo , Nleme Nancy , Schwartz Laurent , Leclerc-Desaulniers Kim , Carmona Euridice , Mes-Masson Anne-Marie , Jolicoeur Mario
Published: January 2024

Ovarian cancer remains a significant challenge, especially in platinum-resistant cases where treatment options are limited. In this study, we investigated the potential of methylene blue (MB) as a metabolic therapy and complementary treatment approach for ovarian cancer. Our findings demonstrated a significant in vivo reduction in the proliferation of TOV112D-based ovarian-cell-line xenografts. In this preclinical study, which used a carboplatin-resistant ovarian cancer tumor model implanted into mice, MB-mediated metabolic therapy exhibited superior tumor slowdown compared to carboplatin treatment alone. This indicates, for the first time, MB’s potential as an alternative or adjuvant treatment, especially for resistant cases. Our in vitro study on TOV112D and ARPE-19 sheds light on the impact of such an MB-based metabolic therapy on mitochondrial energetics (respiration and membrane potential). MB showed a modulatory role in the oxygen consumption rate and the mitochondrial membrane potential. These results revealed, for the first time, that MB specifically targets TOV112D mitochondria and probably induces cell apoptosis. The differential response of normal (ARPE-19) and cancer (TOV112D) cells to the MB treatment suggests potential alterations in cancer cell mitochondria, opening avenues for therapeutic approaches that target the mitochondria. Overall, our findings suggest the efficacy of MB as a possible treatment for ovarian cancer and provide valuable insights into the mechanisms underlying the efficacy of methylene blue metabolic therapy in ovarian cancer treatment.
Evaluation of Zonulin Expression and Its Potential Clinical Significance in Glioblastoma
Authors: Repossi Roberta , Martín-Ramírez Rita , Gómez-Bernal Fuensanta , Medina Lilian , Fariña-Jerónimo Helga , González-Fernández Rebeca , Martín-Vasallo Pablo , Plata-Bello Julio
Published: January 2024

Glioblastoma, the deadliest adult brain tumor, poses a significant therapeutic challenge with a dismal prognosis despite current treatments. Zonulin, a protein influencing tight junctions and barrier functions, has gained attention for its diverse roles in various diseases. This study aimed to preliminarily analyze the circulating and tumor zonulin levels, evaluating their impact on disease prognosis and clinical–radiological factors. Additionally, we investigated in vitro zonulin expression in different glioblastoma cell lines under two different conditions. The study comprised 34 newly diagnosed glioblastoma patients, with blood samples collected before treatment for zonulin and haptoglobin analysis. Tumor tissue samples from 21 patients were obtained for zonulin expression. Clinical, molecular, and radiological data were collected, and zonulin protein levels were assessed using ELISA and Western blot techniques. Furthermore, zonulin expression was analyzed in vitro in three glioblastoma cell lines cultured under standard and glioma-stem-cell (GSC)-specific conditions. High zonulin expression in glioblastoma tumors correlated with larger preoperative contrast enhancement and edema volumes. Patients with high zonulin levels showed a poorer prognosis (progression-free survival [PFS]). Similarly, elevated serum levels of zonulin were associated with a trend of shorter PFS. Higher haptoglobin levels correlated with MGMT methylation and longer PFS. In vitro, glioblastoma cell lines expressed zonulin under standard cell culture conditions, with increased expression in tumorsphere-specific conditions. Elevated zonulin levels in both the tumor and serum of glioblastoma patients were linked to a poorer prognosis and radiological signs of increased disruption of the blood–brain barrier. In vitro, zonulin expression exhibited a significant increase in tumorspheres.
Tumor Response on Diagnostic Imaging after Proton Beam Therapy for Hepatocellular Carcinoma
Authors: Niitsu Hikaru , Mizumoto Masashi , Li Yinuo , Nakamura Masatoshi , Ishida Toshiki , Iizumi Takashi , Saito Takashi , Numajiri Haruko , Makishima Hirokazu , Nakai Kei , Oshiro Yoshiko , Maruo Kazushi , Sakurai Hideyuki
Published: January 2024

Background: Follow-up after treatment for hepatocellular carcinoma (HCC) can be mostly performed using dynamic CT or MRI, but there is no common evaluation method after radiation therapy. The purpose of this study is to examine factors involved in tumor reduction and local recurrence in patients with HCC treated with proton beam therapy (PBT) and to evaluate HCC shrinkage after PBT. Methods: Cases with only one irradiated lesion or those with two lesions irradiated simultaneously were included in this study. Pre- and post-treatment lesions were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) by measuring the largest diameter. Results: The 6-, 12-, and 24-month CR + PR rates after PBT were 33.1%, 57.5%, and 76.9%, respectively, and the reduction rates were 25.1% in the first 6 months, 23.3% at 6–12 months, and 14.5% at 13–24 months. Cases that reached CR/PR at 6 and 12 months had improved OS compared to non-CR/non-PR cases. Conclusions: It is possible that a lesion that reached SD may subsequently transition to PR; it is reasonable to monitor progress with periodic imaging evaluations even after 1 year of treatment.
Obesity Is Associated with Distal Migration of Pancreatic Adenocarcinoma to Body and Tail: A Multi-Center Study
Authors: Sbeit Wisam , Gershovitz Gil , Shahin Amir , Shhadeh Shhady , Salman Mahmoud , Basheer Maamoun , Khoury Tawfik
Published: January 2024

(1) Background: Pancreatic adenocarcinoma (PAC) is one of the most lethal types of cancer. Most cases of PAC occur in the head of the pancreas. Given the proximity of the pancreatic head to the bile duct, most patients present clinically during early stages of the disease, while distally located PAC could have delayed clinical presentation. (2) Aims: To assess predictors of non-head PAC. (3) Methods: A retrospective multicenter study was conducted, including all patients who had endoscopic ultrasound (EUS) for pancreatic masses and who had histologic confirmation of PAC. (4) Results: Of the 151 patients included, 92 (60.9%) had pancreatic head cancer, and 59 (39.1%) had distal pancreatic cancer. PAC at body was the most common location in the distal PAC group (31 patients (52.5%)). Logistic regression analysis demonstrated a significant association of obesity with distal migration of PAC (OR 4.44, 95% CI 1.15–17.19, p = 0.03), while none of the other assessed parameters showed a significant association. Notably, abdominal pain was more significantly associated with distal PAC vs. head location (OR 2.85, 95% CI 1.32–6.16, p = 0.008). (5) Conclusions: Obesity shows a significant association as a clinical predictor of distal PAC. Further studies are needed to better explore this association.
Harnessing the Systemic Biology of Functional Decline and Cachexia to Inform more Holistic Therapies for Incurable Cancers
Authors: Willbanks Amber , Seals Mina , Karmali Reem , Roy Ishan
Published: January 2024

Options for treatment of incurable cancer remain scarce and are largely focused on limited therapeutic mechanisms. A new approach specific to advanced cancers is needed to identify new and effective treatments. Morbidity in advanced cancer is driven by functional decline and a number of systemic conditions, including cachexia and fatigue. This review will focus on these clinical concepts, describe our current understanding of their underlying biology, and then propose how future therapeutic strategies, including pharmaceuticals, exercise, and rehabilitation, could target these mechanisms as an alternative route to addressing incurable cancer.
Prevention of Post-Hepatectomy Liver Failure in Cirrhotic Patients Undergoing Minimally Invasive Liver Surgery for HCC: Has the Round Ligament to Be Preserved?
Authors: Vivarelli Marco , Mocchegiani Federico , Wakabayashi Taiga , Gaudenzi Federico , Nicolini Daniele , Al-Omari Malek A. , Conte Grazia , Borgheresi Alessandra , Agostini Andrea , Rossi Roberta , Fujiyama Yoshiki , Giovagnoni Andrea , Wakabayashi Go , Benedetti Cacciaguerra Andrea
Published: January 2024

Post-hepatectomy liver failure (PHLF) represents a major cause of morbidity and mortality after liver resection. The factors related to PHLF are represented not only by the volume and function of the future liver remnant but also by the severity of portal hypertension. The aim of this study was to assess whether the preservation of the round ligament (RL) may mitigate portal hypertension, thus decreasing the risk of PHLF and ascites in cirrhotic patients while undergoing minimally invasive liver surgery (MILS). All the cirrhotic patients who underwent MILS for HCC from 2016 to 2021 in two international tertiary referral centers were retrospectively analyzed, comparing cases with the RL preserved vs. those with the RL divided. Only patients with cirrhosis ≥ Child A6, portal hypertension, and ICG-R15 > 10% were included. Main postoperative outcomes were compared, and the risk factors for postoperative ascites (severe PHLF, grade B/C) were investigated through a logistic regression. After the application of the selection criteria, a total of 130 MILS patients were identified, with 86 patients with the RL preserved and 44 with the RL divided. The RL-preserved group showed lower incidences of severe PHLF (7.0% vs. 20.5%, p = 0.023) and ascites (5.8% vs. 18.2%, p = 0.026) in comparison with the RL-divided group. After uni/multivariate analysis, the risk factors related to postoperative ascites were RL division and platelets < 92 × 103/µL, calculated with ROC analysis. The preservation of the round ligament during MILS may mitigate portal hypertension, preventing PHLF and ascites in cirrhotic patients with borderline liver function.
Metabolic Imaging Biomarkers of Response to Signaling Inhibition Therapy in Melanoma
Authors: Gupta Pradeep Kumar , Orlovskiy Stepan , Arias-Mendoza Fernando , Nelson David S. , Osborne Aria , Pickup Stephen , Glickson Jerry D. , Nath Kavindra
Published: January 2024

Dabrafenib therapy for metastatic melanoma focuses on blocking growth-promoting signals produced by a hyperactive BRAF protein. We report the metabolic differences of four human melanoma cell lines with diverse responses to dabrafenib therapy (30 mg/kg; oral): WM3918 < WM9838BR < WM983B < DB-1. Our goal was to determine if metabolic changes produced by the altered signaling pathway due to BRAF mutations differ in the melanoma models and whether these differences correlate with response to treatment. We assessed metabolic changes in isolated cells using high-resolution proton magnetic resonance spectroscopy (1H MRS) and supplementary biochemical assays. We also noninvasively studied mouse xenografts using proton and phosphorus (1H/31P) MRS. We found consistent changes in lactate and alanine, either in isolated cells or mouse xenografts, correlating with their relative dabrafenib responsiveness. In xenografts, we also observed that a more significant response to dabrafenib correlated with higher bioenergetics (i.e., increased βNTP/Pi). Notably, our noninvasive assessment of the metabolic status of the human melanoma xenografts by 1H/31P MRS demonstrated early metabolite changes preceding therapy response (i.e., tumor shrinkage). Therefore, this noninvasive methodology could be translated to assess in vivo predictive metabolic biomarkers of response in melanoma patients under dabrafenib and probably other signaling inhibition therapies.
Promising Diagnostic and Therapeutic Approaches Based on VHHs for Cancer Management
Authors: Cong Ying , Devoogdt Nick , Lambin Philippe , Dubois Ludwig J. , Yaromina Ala
Published: January 2024

The discovery of the distinctive structure of heavy chain-only antibodies in species belonging to the Camelidae family has elicited significant interest in their variable antigen binding domain (VHH) and gained attention for various applications, such as cancer diagnosis and treatment. This article presents an overview of the characteristics, advantages, and disadvantages of VHHs as compared to conventional antibodies, and their usage in diverse applications. The singular properties of VHHs are explained, and several strategies that can augment their utility are outlined. The preclinical studies illustrating the diagnostic and therapeutic efficacy of distinct VHHs in diverse formats against solid cancers are summarized, and an overview of the clinical trials assessing VHH-based agents in oncology is provided. These investigations demonstrate the enormous potential of VHHs for medical research and healthcare.