bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deciphering intratumoral heterogeneity of hepatocellular carcinoma with microvascular invasion with radiogenomic analysis
Authors: Wang Yi , Zhu Gui-Qi , Yang Rui , Wang Cheng , Qu Wei-Feng , Chu Tian-Hao , Tang Zheng , Yang Chun , Yang Li , Zhou Chang-Wu , Miao Geng-Yun , Liu Wei-Ren , Shi Ying-Hong , Zeng Meng-Su 
Published: October 2023

Abstract
Background and aims
The recurrence and metastasis of hepatocellular carcinoma (HCC) are mainly caused by microvascular invasion (MVI). Our study aimed to uncover the cellular atlas of MVI+ HCC and investigate the underlying immune infiltration patterns with radiomics features.

Methods
Three MVI positive HCC and three MVI negative HCC samples were collected for single-cell RNA-seq analysis. 26 MVI positive HCC and 30 MVI negative HCC tissues were underwent bulk RNA-seq analysis. For radiomics analysis, radiomics features score (Radscore) were built using preoperative contrast MRI for MVI prediction and overall survival prediction. We deciphered the metabolism profiles of MVI+ HCC using scMetabolism and scFEA. The correlation of Radscore with the level of APOE+ macrophages and iCAFs was identified. Whole Exome Sequencing (WES) was applied to distinguish intrahepatic metastasis (IM) and multicentric occurrence (MO). Transcriptome profiles were compared between IM and MO.

Results
Elevated levels of APOE+ macrophages and iCAFs were detected in MVI+ HCC. There was a strong correlation between the infiltration of APOE+ macrophages and iCAFs, as confirmed by immunofluorescent staining. MVI positive tumors exhibited increased lipid metabolism, which was attributed to the increased presence of APOE+ macrophages. APOE+ macrophages and iCAFs were also found in high levels in IM, as opposed to MO. The difference of infiltration level and Radscore between two nodules in IM was relatively small. Furthermore, we developed Radscore for predicting MVI and HCC prognostication that were also able to predict the level of infiltration of APOE+ macrophages and iCAFs.

Conclusion
This study demonstrated the interactions of cell subpopulations and distinct metabolism profiles in MVI+ HCC. Besides, MVI prediction Radscore and MVI prognostic Radscore were highly correlated with the infiltration of APOE+ macrophages and iCAFs, which helped to understand the biological significance of radiomics and optimize treatment strategy for MVI+ HCC.
BRAF D594A mutation defines a unique biological and immuno-modulatory subgroup associated with functional CD8+ T cell infiltration in colorectal cancer
Authors: Li Wenjing , Zhao Chenyi , Li Wenhui , Gong Yang , Ma Kaili , Lu Yujie , Liu Xiaowei , Zhang Lianjun , Guo Feng 
Published: October 2023

Abstract
Background
BRAF non-V600 mutation occupies a relatively small but critical subset in colorectal cancer (CRC). However, little is known about the biological functions and impacts of BRAF class III mutation in CRC. Here, we aim to explore how D594A mutation impacts on biological behaviors and immune related signatures in murine CRC cells.

Methods
BRAF V600E (class I), G469V (class II) and D594A (class III) mutant cell lines were established based on MC38 cells. The biological behaviors of cells were evaluated in respect of cell growth, cell proliferation, cell apoptosis, cell migration and invasion by the methods of colony-forming assay, CCK-8 assay, Annexin V/PI staining and transwell assay. The concentrations of soluble cytokines were detected by ELISA. The membrane expression of immuno-modulatory molecules and the pattern of tumor infiltrating lymphocyte were evaluated by flow cytometry. The molecular mechanism was explored by RNA sequencing. Immunohistochemistry (IHC) staining was used for the detection of CD8α in tumor tissues. qRT-PCR and western blot were performed to assess the mRNA and protein expression. Anti-PD-L1 treatment and cytokines neutralization experiments were conducted in in vivo models.

Results
D594A mutant cells displayed lower grade malignancy characteristics than V600E (class I) and G469V (class II) mutant cells. Meanwhile, D594A mutation led to evident immuno-modulatory features including upregulation of MHC Class I and PD-L1. In vivo experiments displayed that the frequency of infiltrated CD8+ T cells was significantly high within D594A mutant tumors, which may provide potential response to anti-PD-L1 therapy. RNA sequencing analysis showed that D594A mutation led to enhanced expression of ATF3 and THBS1, which thus facilitated CXCL9 and CXCL10 production upon IFN-γ treatment. In addition, CXCL9 or CXCL10 neutralization reduced the infiltration of CD8+ T cells into THBS1-overexpressing tumors.

Conclusions
D594A mutant CRC exhibited lower aggressiveness and immune-activated phenotype. ATF3-THBS1-CXCL9/CXCL10 axis mediated functional CD8+ T cells infiltration into the microenvironment of D594A mutant CRC. Our present study is helpful to define this mutation in CRC and provide important insights in designing effective immunotherapeutic strategies in clinic.
RIZ2 at the crossroad of the EGF/EGFR signaling in colorectal cancer
Authors: Di Donato Marzia , Di Zazzo Erika , Salvati Annamaria , Sorrentino Carmela , Giurato Giorgio , Fiore Donatella , Proto Maria Chiara , Rienzo Monica , Casamassimi Amelia , Gazzerro Patrizia , Bifulco Maurizio , Castoria Gabriella , Weisz Alessandro , Nassa Giovanni , Abbondanza Ciro 
Published: October 2023

Abstract
Background
Colorectal cancer (CRC) is the third most deadly and fourth most diagnosed cancer worldwide. Despite the progress in early diagnosis and advanced therapeutic options, CRC shows a poor prognosis with a 5 year survival rate of ~ 45%. PRDM2/RIZ, a member of PR/SET domain family (PRDM), expresses two main molecular variants, the PR-plus isoform (RIZ1) and the PR-minus (RIZ2). The imbalance in their expression levels in favor of RIZ2 is observed in many cancer types. The full length RIZ1 has been extensively investigated in several cancers where it acts as a tumor suppressor, whereas few studies have explored the RIZ2 oncogenic properties. PRDM2 is often target of frameshift mutations and aberrant DNA methylation in CRC. However, little is known about its role in CRC.

Methods
We combined in-silico investigation of The Cancer Genome Atlas (TCGA) CRC datasets, cellular and molecular assays, transcriptome sequencing and functional annotation analysis to assess the role of RIZ2 in human CRC.

Results
Our in-silico analysis on TCGA datasets confirmed that PRDM2 gene is frequently mutated and transcriptionally deregulated in CRC and revealed that a RIZ2 increase is highly correlated with a significant RIZ1 downregulation. Then, we assayed several CRC cell lines by qRT-PCR analysis for the main PRDM2 transcripts and selected DLD1 cell line, which showed the lowest RIZ2 levels. Therefore, we overexpressed RIZ2 in these cells to mimic TCGA datasets analysis results and consequently to assess the PRDM2/RIZ2 role in CRC. Data from RNA-seq disclosed that RIZ2 overexpression induced profound changes in CRC cell transcriptome via EGF pathway deregulation, suggesting that RIZ2 is involved in the EGF autocrine regulation of DLD1 cell behavior. Noteworthy, the forced RIZ2 expression increased cell viability, growth, colony formation, migration and organoid formation. These effects could be mediated by the release of high EGF levels by RIZ2 overexpressing DLD1 cells.

Conclusions
Our findings add novel insights on the putative RIZ2 tumor-promoting functions in CRC, although additional efforts are warranted to define the underlying molecular mechanism.
Motor-cognitive functions required for driving in post-stroke individuals identified via machine-learning analysis
Authors: Tabuchi Genta , Furui Akira , Hama Seiji , Yanagawa Akiko , Shimonaga Koji , Xu Ziqiang , Soh Zu , Hirano Harutoyo , Tsuji Toshio 
Published: October 2023

Abstract
Background
People who were previously hospitalised with stroke may have difficulty operating a motor vehicle, and their driving aptitude needs to be evaluated to prevent traffic accidents in today’s car-based society. Although the association between motor-cognitive functions and driving aptitude has been extensively studied, motor-cognitive functions required for driving have not been elucidated.

Methods
In this paper, we propose a machine-learning algorithm that introduces sparse regularization to automatically select driving aptitude-related indices from 65 input indices obtained from 10 tests of motor-cognitive function conducted on 55 participants with stroke. Indices related to driving aptitude and their required tests can be identified based on the output probability of the presence or absence of driving aptitude to provide evidence for identifying subjects who must undergo the on-road driving test. We also analyzed the importance of the indices of motor-cognitive function tests in evaluating driving aptitude to further clarify the relationship between motor-cognitive function and driving aptitude.

Results
The experimental results showed that the proposed method achieved predictive evaluation of the presence or absence of driving aptitude with high accuracy (area under curve 0.946) and identified a group of indices of motor-cognitive function tests that are strongly related to driving aptitude.

Conclusions
The proposed method is able to effectively and accurately unravel driving-related motor-cognitive functions from a panoply of test results, allowing for autonomous evaluation of driving aptitude in post-stroke individuals. This has the potential to reduce the number of screening tests required and the corresponding clinical workload, further improving personal and public safety and the quality of life of individuals with stroke.
Dysregulation of intracellular redox homeostasis by the SARS-CoV-2 ORF6 protein
Authors: De Angelis Marta , Anichini Gabriele , Palamara Anna Teresa , Nencioni Lucia , Gori Savellini Gianni 
Published: October 2023

AbstractSARS-CoV-2 has evolved several strategies to overcome host cell defenses by inducing cell injury to favour its replication. Many viruses have been reported to modulate the intracellular redox balance, affecting the Nuclear factor erythroid 2-Related Factor 2 (NRF2) signaling pathway. Although antioxidant modulation by SARS-CoV-2 infection has already been described, the viral factors involved in modulating the NRF2 pathway are still elusive. Given the antagonistic activity of ORF6 on several cellular pathways, we investigated the role of the viral protein towards NRF2-mediated antioxidant response. The ectopic expression of the wt-ORF6 protein negatively impacts redox cell homeostasis, leading to an increase in ROS production, along with a decrease in NRF2 protein and its downstream controlled genes. Moreover, when investigating the Δ61 mutant, previously described as an inactive nucleopore proteins binding mutant, we prove that the oxidative stress induced by ORF6 is substantially related to its C-terminal domain, speculating that ORF6 mechanism of action is associated with the inhibition of nuclear mRNA export processes. In addition, activation by phosphorylation of the serine residue at position 40 of NRF2 is increased in the cytoplasm of wt-ORF6-expressing cells, supporting the presence of an altered redox state, although NRF2 nuclear translocation is hindered by the viral protein to fully antagonize the cell response. Furthermore, wt-ORF6 leads to phosphorylation of a stress-activated serine/threonine protein kinase, p38 MAPK, suggesting a role of the viral protein in regulating p38 activation. These findings strengthen the important role of oxidative stress in the pathogenesis of SARS-CoV-2 and identify ORF6 as an important viral accessory protein hypothetically involved in modulating the antioxidant response during viral infection.
Traditional medical practices for children in five islands from the Society archipelago (French Polynesia)
Authors: Chassagne François , Butaud Jean-François , Ho Raimana , Conte Eric , Hnawia Édouard , Raharivelomanana Phila 
Published: October 2023

Abstract
Background
Traditional Polynesian medicine for children has been poorly documented, and few data are available on their efficacy and safety. In this context, the aim of this study was to identify traditional practices used for treating children and then assess the efficacy and safety of the most cited remedies by reviewing the literature.

Methods
In 2022, a semi-structured survey was carried out on five islands from the Society archipelago (Bora Bora, Huahine, Moorea, Raiatea, and Tahiti). A total of 86 participants were interviewed including 19 experts in herbalism. A thorough literature review was performed on the most cited plant species to gather the relevant ethnobotanical, pharmacological, and clinical data of each remedy.

Results
Participants mentioned using 469 remedies to treat 69 health disorders. The most represented health categories were digestive system, skin disorders, infectious diseases, and respiratory system. A total of 67 plant species (representing 731 use-reports) were mentioned and Annona muricata, Gardenia taitensis, and Hibiscus rosa-sinensis were the main plants reported. Regarding the safety of cited remedies, one plant (Microsorum grossum) showed high risk of toxicity, and its use should be avoided in infants and children.

Conclusion
Our survey confirms the importance of traditional medical practices for children in the Society Islands. A lack of data in children for most cited remedies demonstrate the need for more pharmacological and toxicological research on Polynesian medicinal plants. Finally, the potential risk of toxicity for some cited plant species reported calls for a better information of traditional medicine users and healers.
Avian Plasmodium spp. and Haemoproteus spp. parasites in mosquitoes in Germany
Authors: Köchling Katharina , Schaub Günter A. , Werner Doreen , Kampen Helge 
Published: October 2023

Abstract
Background
Although haemosporidian parasites may cause considerable health and economic problems in aviaries, there is limited understanding of the vectors transmitting them. Mosquito-borne Plasmodium species are responsible for the deaths of numerous exotic (= immunologically naïve) birds in zoos every year, while native birds are adapted to the parasites and largely protected by an effective immune response.

Methods
Mosquitoes were collected in bird/animal parks, wetlands and private gardens in various regions of Germany from 2020 to 2022. Females were pooled with up to 10 specimens according to taxon, location and date. Extracted DNA was screened for avian Haemosporida-specific mitochondrial rDNA using real-time polymerase chain reaction (PCR). Positive samples were amplified by a Plasmodium/Haemoproteus-specific nested PCR targeting the partial cytochrome b gene, followed by sequencing of the PCR product for species identification. Sequences were checked against GenBank and MalAvi databases.

Results
PCR of 2633 pools with 8834 female mosquitoes signalled infection with Plasmodium in 46 pools and with Haemoproteus in one pool. Further amplification and sequencing demonstrated the occurrence of Haemoproteus majoris lineage PARUS1 (n = 1) as well as several Plasmodium species and lineages, including Plasmodium relictum SGS1 (n = 16) and GRW11 (n = 1), P. matutinum LINN1 (n = 13), P. vaughani SYAT05 (n = 10), P. circumflexum TURDUS01 (n = 3), P. cathemerium PADOM02 (n = 1) and Plasmodium sp. SYBOR02 (n = 1) and PLOPRI01 (n = 1). The infections were detected in Culex pipiens sensu lato (n = 40), Culiseta morsitans/fumipennis (n = 6) and Aedes cinereus/geminus (n = 1).

Conclusions
Although the overall Plasmodium minimum infection rate (5.2) appears to be low, the results demonstrated not only the ongoing circulation of Plasmodium parasites in the German mosquito population, but also the occurrence of eight distinct Plasmodium lineages, with three of them (PADOM02, SYBOR02, PLOPRI01) being detected in Germany for the first time. This study highlights the importance of conducting mosquito-borne pathogen surveillance studies simultaneously targeting vectors and vertebrate hosts, as certain species may be detected more readily in their vectors than in their vertebrate hosts, and vice versa.

Graphical Abstract
An epigenetic hypothesis for ovarian cancer prevention by oral contraceptive pill use
Authors: Avramenko Anna S. , Flanagan James M. 
Published: October 2023

Abstract
Background
Ovarian cancer is the second most common gynecological cancer type after uterine cancers. In 2020, according to worldwide statistics, there were more than 313,000 new cases of ovarian cancer. Most concerning with ovarian cancer is the poor overall survival, with only 30% of patients surviving for longer than 5 years after diagnosis. The reason for this poor outcome includes late diagnosis due to non-specific symptoms and a lack of any highly effective biomarkers of the early stages of ovarian carcinogenesis. However, it is important to note that some modifiable lifestyle factors can be preventative [pregnancy, breastfeeding and combined oral contraceptives pill (COCP) use].

Results
There is now increasing data reporting the role of epigenetic changes, which are detectable in ovarian cancer tumors, suggesting the possibility that epigenetics may also play a key role in the mechanism of long-term effective prevention of ovarian cancer. To our knowledge, there is a lack of high-quality data on the molecular mechanisms of ovarian cancer prevention, although several hypotheses have been proposed.

Conclusions
This review focusses on the evidence for a proposed novel hypothesis—that COCPs act as a chemoprevention through the impact on the epigenome of the cells of origin of ovarian cancer—fallopian tubes epithelium.
A systematic review of mechanistic models used to study avian influenza virus transmission and control
Authors: Lambert Sébastien , Bauzile Billy , Mugnier Amélie , Durand Benoit , Vergne Timothée , Paul Mathilde C. 
Published: October 2023

AbstractThe global spread of avian influenza A viruses in domestic birds is causing increasing socioeconomic devastation. Various mechanistic models have been developed to better understand avian influenza transmission and evaluate the effectiveness of control measures in mitigating the socioeconomic losses caused by these viruses. However, the results of models of avian influenza transmission and control have not yet been subject to a comprehensive review. Such a review could help inform policy makers and guide future modeling work. To help fill this gap, we conducted a systematic review of the mechanistic models that have been applied to field outbreaks. Our three objectives were to: (1) describe the type of models and their epidemiological context, (2) list estimates of commonly used parameters of low pathogenicity and highly pathogenic avian influenza transmission, and (3) review the characteristics of avian influenza transmission and the efficacy of control strategies according to the mechanistic models. We reviewed a total of 46 articles. Of these, 26 articles estimated parameters by fitting the model to data, one evaluated the effectiveness of control strategies, and 19 did both. Values of the between-individual reproduction number ranged widely: from 2.18 to 86 for highly pathogenic avian influenza viruses, and from 4.7 to 45.9 for low pathogenicity avian influenza viruses, depending on epidemiological settings, virus subtypes and host species. Other parameters, such as the durations of the latent and infectious periods, were often taken from the literature, limiting the models’ potential insights. Concerning control strategies, many models evaluated culling (n = 15), while vaccination received less attention (n = 6). According to the articles reviewed, optimal control strategies varied between virus subtypes and local conditions, and depended on the overall objective of the intervention. For instance, vaccination was optimal when the objective was to limit the overall number of culled flocks. In contrast, pre-emptive culling was preferred for reducing the size and duration of an epidemic. Early implementation consistently improved the overall efficacy of interventions, highlighting the need for effective surveillance and epidemic preparedness.
Unmapped short reads from whole-genome sequencing indicate potential infectious pathogens in German Black Pied cattle
Authors: Neumann Guilherme B. , Korkuć Paula , Reißmann Monika , Wolf Manuel J. , May Katharina , König Sven , Brockmann Gudrun A. 
Published: October 2023

AbstractWhen resequencing animal genomes, some short reads cannot be mapped to the reference genome and are usually discarded. In this study, unmapped reads from 302 German Black Pied cattle were analyzed to identify potential pathogenic DNA. These unmapped reads were assembled and blasted against NCBI’s database to identify bacterial and viral sequences. The results provided evidence for the presence of pathogens. We found sequences of Bovine parvovirus 3 and Mycoplasma species. These findings emphasize the information content of unmapped reads for gaining insight into bacterial and viral infections, which is important for veterinarians and epidemiologists.
Relationship between psychological detachment from work and depressive symptoms: indirect role of emotional exhaustion and moderating role of self-compassion
Authors: Wu Qinglu , Qi Tengfei , Wei Jun , Shaw Amy 
Published: October 2023

AbstractThe importance of psychological detachment during nonwork time has been emphasized, and its effect on depressive symptoms has been identified. However, the mechanism underlying this association remains to be elucidated. This study was conducted to identify the indirect role of emotional exhaustion in the association between psychological detachment and depressive symptoms and the moderating role of self-compassion in the relationship between emotional exhaustion and depressive symptoms on the basis of the recovery–engagement–exhaustion model and emotion regulation theory. Through an online survey, relevant data were collected from 727 university teachers (mean age, 37.65 ± 7.77 years; 38.5% men). Indirect and moderation effect were analyzed through structural equation modeling (Mplus). Psychological detachment was found to be associated with depressive symptoms through emotional exhaustion. Self-compassion moderated the association between emotional exhaustion and depressive symptoms. The association between emotional exhaustion and depressive symptoms was weaker among university teachers with high levels of self-compassion than among those with low levels of self-compassion. This study improves our understanding of the association between psychological detachment and depressive symptoms by identifying the emotional pathway and protective function of self-compassion. Interventions for improving mental health in work context should be designed considering psychological detachment and self-compassion to deal with work-induced emotional strain.