bluuebunny/crossref_metadata_2025 huggingface dataset:
Perceptions and attitudes of bicyclists towards self-driving cars: a mixed methods approach
Authors: Luger-Bazinger Claudia , Hollauf Eva , Atasayar Hatun , Zankl Cornelia , Hornung-Prähauser Veronika
Published: August 2023

Efforts to advance Autonomous Vehicles (AVs) have taken on a central role in research and development in recent years and will have a significant influence on road traffic in the future. Research on AVs has mainly focused on the technology itself and the direct users of AVs and their acceptance. However, the role of bicyclists, interacting with AVs in traffic, is not yet researched as thoroughly. Using a mixed methods approach, we combine quantitative results from a survey among bicyclists (N = 889) and qualitative results from a focus group (N = 19) to give insights into bicyclists’ attitudes and expectations towards self-driving cars. The results showed that bicyclists’ affinity for technology is a significant predictor for both their trust and perceived safety towards self-driving cars, as well as an effect of age and gender on these variables. Both from the quantitative and qualitative results, it is clear that flawless functioning of the technology of AVs is a prerequisite for bicyclists encountering and interacting with AVs in traffic, and that the status of the vehicle (autonomous vs. non-autonomous) is very important as well as easy to understand signals that indicate the next manoeuvres of the AV. For supporting interaction with AVs, we found that bicyclists are open to External Human Machine Interface (eHMI) solutions, as long as these ensure inclusion and support the easily-accessible nature of bicycling. Our findings can inform the design of eHMIs that help shape the interaction between bicyclists and AVs in the future, and provide insights on which factors determine the perception of AVs and, ultimately, the acceptance of AVs as part of road traffic.
Identification and verification of novel immune-related ferroptosis signature with excellent prognostic predictive and clinical guidance value in hepatocellular carcinoma
Authors: Jiang Wenxiu , Wang Lili , Zhang Yajuan , Li Hongliang
Published: August 2023

Background: Immunity and ferroptosis often play a synergistic role in the progression and treatment of hepatocellular carcinoma (HCC). However, few studies have focused on identifying immune-related ferroptosis gene biomarkers.

Methods: We performed weighted gene co-expression network analysis (WGCNA) and random forest to identify prognostic differentially expressed immune-related genes (PR-DE-IRGs) highly related to HCC and characteristic prognostic differentially expressed ferroptosis-related genes (PR-DE-FRGs) respectively to run co-expression analysis for prognostic differentially expressed immune-related ferroptosis characteristic genes (PR-DE-IRFeCGs). Lasso regression finally identified 3 PR-DE-IRFeCGs for us to construct a prognostic predictive model. Differential expression and prognostic analysis based on shared data from multiple sources and experimental means were performed to further verify the 3 modeled genes’ biological value in HCC. We ran various performance testing methods to test the model’s performance and compare it with other similar signatures. Finally, we integrated composite factors to construct a comprehensive quantitative nomogram for accurate prognostic prediction and evaluated its performance.

Results: 17 PR-DE-IRFeCGs were identified based on co-expression analysis between the screened 17 PR-DE-FRGs and 34 PR-DE-IRGs. Multi-source sequencing data, QRT-PCR, immunohistochemical staining and testing methods fully confirmed the upregulation and significant prognostic influence of the three PR-DE-IRFeCGs in HCC. The model performed well in the performance tests of multiple methods based on the 5 cohorts. Furthermore, our model outperformed other related models in various performance tests. The immunotherapy and chemotherapy guiding value of our signature and the comprehensive nomogram’s excellent performance have also stood the test.

Conclusion: We identified a novel PR-DE-IRFeCGs signature with excellent prognostic prediction and clinical guidance value in HCC.
GeNetOntology: identifying affected gene ontology terms via grouping, scoring, and modeling of gene expression data utilizing biological knowledge-based machine learning
Authors: Ersoz Nur Sebnem , Bakir-Gungor Burcu , Yousef Malik
Published: August 2023

Introduction: Identifying significant sets of genes that are up/downregulated under specific conditions is vital to understand disease development mechanisms at the molecular level. Along this line, in order to analyze transcriptomic data, several computational feature selection (i.e., gene selection) methods have been proposed. On the other hand, uncovering the core functions of the selected genes provides a deep understanding of diseases. In order to address this problem, biological domain knowledge-based feature selection methods have been proposed. Unlike computational gene selection approaches, these domain knowledge-based methods take the underlying biology into account and integrate knowledge from external biological resources. Gene Ontology (GO) is one such biological resource that provides ontology terms for defining the molecular function, cellular component, and biological process of the gene product.

Methods: In this study, we developed a tool named GeNetOntology which performs GO-based feature selection for gene expression data analysis. In the proposed approach, the process of Grouping, Scoring, and Modeling (G-S-M) is used to identify significant GO terms. GO information has been used as the grouping information, which has been embedded into a machine learning (ML) algorithm to select informative ontology terms. The genes annotated with the selected ontology terms have been used in the training part to carry out the classification task of the ML model. The output is an important set of ontologies for the two-class classification task applied to gene expression data for a given phenotype.

Results: Our approach has been tested on 11 different gene expression datasets, and the results showed that GeNetOntology successfully identified important disease-related ontology terms to be used in the classification model.

Discussion: GeNetOntology will assist geneticists and scientists to identify a range of disease-related genes and ontologies in transcriptomic data analysis, and it will also help doctors design diagnosis platforms and improve patient treatment plans.
Comparative evaluation and analysis of DNA N4-methylcytosine methylation sites using deep learning
Authors: Ju Hong , Bai Jie , Jiang Jing , Che Yusheng , Chen Xin
Published: August 2023

DNA N4-methylcytosine (4mC) is significantly involved in biological processes, such as DNA expression, repair, and replication. Therefore, accurate prediction methods are urgently needed. Deep learning methods have transformed applications that previously require sequencing expertise into engineering challenges that do not require expertise to solve. Here, we compare a variety of state-of-the-art deep learning models on six benchmark datasets to evaluate their performance in 4mC methylation site detection. We visualize the statistical analysis of the datasets and the performance of different deep-learning models. We conclude that deep learning can greatly expand the potential of methylation site prediction.
Role of ICAM1 in tumor immunity and prognosis of triple-negative breast cancer
Authors: Zhou Qin , Xu Jiawei , Xu Yan , Sun Shaokun , Chen Jian
Published: August 2023

Background

Treating triple-negative breast cancer (TNBC) is a difficult landscape owing to its short survival times and high risk of metastasis and recurrence among patients. Although involved in tumor invasion and metastasis, the mechanism of action of intercellular adhesion molecule 1 (ICAM1), a trans-membrane glycoprotein, in TNBC is ambiguous.

Methods

We examined ICAM1’s role in TNBC, focusing on its expression, cell survival, mutation, and tumor immunity. Then, a risk score model was created utilizing co-expressed genes associated with ICAM1. According to their respective risk scores, we divided patients into high- and low-risk groups. Immune function, drug susceptibility differences, and somatic variants were analyzed in the high-and low-risk groups. And we used the CMap database to predict potential medications. Then, TNBC cells with low expression of ICAM-1 were co-cultured with PMA-treated THP-1 cells and CD8 T cells. In addition, We detected the expression of PD-1 and CTLA4 of low ICAM-1 expressing TNBC cells when they were cocultured with CD8 T cells.

Results

ICAM1 was found to be involved in leukocyte cell adhesion, motility, and immune activation. Patients with low-ICAM1 group had shorter disease-free survival (DFS) than those with high-ICAM1 group. The group with elevated levels of ICAM1 exhibited significantly increased levels of T-cell regulation, quiescence in natural killer (NK) cells, and M1 macrophage. ICAM1 expression was correlated with immune checkpoint drugs. The prognostic ability of the risk score model was found to be superior to that of individual genes. Patients categorized as high-risk exhibited elevated clinical stages, showed higher M1 macrophage numbers, and were able to benefit better from immunotherapy. Individuals belonging to the high-risk group exhibit significantly elevated mutation rates in TP53, TTN, and SYNE1 genes, along with increased TMB and PD-L1 levels and decreased TIDE scores. These findings suggest that immunotherapy may be advantageous for the high-risk group. Furthermore, low expression of ICAM1 was found to promote polarization to M2 macrophages along with T-cell exhaustion.

Conclusion

In conclusion, Low ICAM1 expression may be related to immune escape, leading to poor treatment response and a worse prognosis.
Innate adaptive immune cell dynamics in tonsillar tissues during chronic SIV infection
Authors: Shukla Rajni Kant , Gunasena Manuja , Reinhold-Larsson Nicole , Duncan Michael , Hatharasinghe Amila , Cray Samuel , Weragalaarachchi Krishanthi , Kasturiratna Dhanuja , Demberg Thorsten , Liyanage Namal P. M.
Published: August 2023

HIV-infected patients are at higher risk of developing oral mucosal infection and Epstein–Barr virus (EBV)-associated B cell malignancies. However, the potential role of oral immunity in the pathogenesis of oral lesions is unknown. Tonsils are oral-pharyngeal mucosal-associated lymphoid tissues that play an important role in oral mucosal immunity. In this study, we investigated the changes of innate and adaptive immune cells in macaque tonsils during chronic SIV infection. We found significantly higher frequencies of classical monocytes, CD3+CD56+ (NKT-like) cells, CD3+CD4+CD8+ (DP), and CD161+ CD4 T cells in tonsils from chronic infected compared to naïve animals. On the contrary, intermediate monocytes and CD3+CD4-CD8- (DN) cells were lower in chronic SIV-infected macaques. We further confirmed a recently described small B-cell subset, NKB cells, were higher during chronic infection. Furthermore, both adaptive and innate cells showed significantly higher TNF-α and cytotoxic marker CD107a, while IL-22 production was significantly reduced in innate and adaptive immune cells in chronic SIV-infected animals. A dramatic reduction of IFN-γ production by innate immune cells might indicate enhanced susceptibility to EBV infection and potential transformation of B cells in the tonsils. In summary, our observation shows that the SIV-associated immune responses are distinct in the tonsils compared to other mucosal tissues. Our data extends our understanding of the oral innate immune system during SIV infection and could aid future studies in evaluating the role of tonsillar immune cells during HIV-associated oral mucosal infections.
TPST2-mediated receptor tyrosine sulfation enhances leukocidin cytotoxicity and S. aureus infection
Authors: He Jie , Yang Xianggui , Yang Kai , Xu Honglin , Chen Cheng , Wang Junxiong , Zeng Jun
Published: August 2023

Background

An essential fact underlying the severity of Staphylococcus aureus (S. aureus) infection is the bicomponent leukocidins released by the pathogen to target and lyse host phagocytes through specific binding cell membrane receptors. However, little is known about the impact of post-transcriptional modification of receptors on the leukocidin binding.

Method

In this study, we used small interfering RNA library (Horizon/Dharmacon) to screen potential genes that affect leukocidin binding on receptors. The cell permeability was investigated through flow cytometry measuring the internalization of 4′,6-diamidino-2-phenylindole. Expression of C5a anaphylatoxin chemotactic receptor 1 (C5aR1), sulfated C5aR1 in, and binding of 6x-His–tagged Hemolysin C (HlgC) and Panton-Valentine leukocidin (PVL) slow-component to THP-1 cell lines was detected and analyzed via flow cytometry. Bacterial burden and Survival analysis experiment was conducted in WT and myeloid TPST-cko C57BL/6N mice.

Results

After short hairpin RNA (shRNA) knockdown of TPST2 gene in THP-1, HL-60, and RAW264.7, the cytotoxicity of HlgAB, HlgCB, and Panton–Valentine leukocidin on THP-1 or HL-60 cells was decreased significantly, and the cytotoxicity of HlgAB on RAW264.7 cells was also decreased significantly. Knockdown of TPST2 did not affect the C5aR1 expression but downregulated cell surface C5aR1 tyrosine sulfation on THP-1. In addition, we found that the binding of HlgC and LukS-PV on cell surface receptor C5aR1 was impaired in C5aR1+TPST2− and C5aR1−TPST2− cells. Phagocyte knockout of TPST2 protects mice from S. aureus infection and improves the survival of mice infected with S. aureus.

Conclusion

These results indicate that phagocyte TPST2 mediates the bicomponent leukocidin cytotoxicity by promoting cell membrane receptor sulfation modification that facilitates its binding to leukocidin S component.
Strategies for enhancing CAR T cell expansion and persistence in HIV infection
Authors: Rothemejer Frederik Holm , Lauritsen Nanna Pi , Søgaard Ole Schmeltz , Tolstrup Martin
Published: August 2023

Chimeric Antigen Receptor (CAR) T cell therapies are tremendously successful in hematological malignancies and show great promise as treatment and curative strategy for HIV. A major determinant for effective CAR T cell therapy is the persistence of CAR T cells. Particularly, antigen density and target cell abundance are crucial for the engagement, engraftment, and persistence of CAR T cells. The success of HIV-specific CAR T cells is challenged by limited antigen due to low cell surface expression of viral proteins and the scarcity of chronically infected cells during antiretroviral therapy. Several strategies have been explored to increase the efficacy of CAR T cells by enhancing expansion and persistence of the engineered cells. This review highlights the challenges of designing CAR T cells against HIV and other chronic viral infections. We also discuss potential strategies to enhance CAR T cell expansion and persistence in the setting of low antigen exposure.
Combining passive and active restoration to rehabilitate a historically polluted marine site
Authors: Bianchelli Silvia , Martini Francesco , Lo Martire Marco , Danovaro Roberto , Corinaldesi Cinzia
Published: August 2023

Introduction

Passive and active restoration approaches have been often considered as different alternatives to achieve the ecological restoration of a degraded site. This false dichotomy has been overcome in terrestrial ecosystems, for which a range of restoration approaches have often been applied within the same restoration project, creating a continuum of interventions. In the marine environment, the combined approach based on passive and active restoration is less studied.

Methods

Here, we tested the possibility of actively restoring a macroalgal population in a historically polluted industrial site, subjected to decadal passive restoration (i.e., unassisted, or spontaneous recovery following cessation of industrial activity), in the Mediterranean Sea. Recently, it has been demonstrated that in the site under scrutiny, there is no longer any sign of the historical contamination or impact on benthic fauna therefore the environmental conditions are indistinguishable from surrounding non-impacted areas. We used artificial breakwater barriers already present in the site to restore a population of the brown algae Gongolaria barbata. The intervention was conducted by applying an in situ recruitment approach and a complementary action using cages to exclude the herbivores. The G. barbata recruits were transplanted on the artificial reefs and after they reached the maximum growth inside the cages, one cage was opened and another one was completely removed to also test the grazing pressure. The associated benthic assemblages were also analysed in terms of meio- and macrofaunal abundance, the richness of taxa, and taxonomic composition.

Results and discussion

Our results indicate that, at least over a relatively short period (i.e., 6 months), the use of the cages represents a useful tool to let the macroalgae grow enough to counterbalance the herbivory pressure. The associated fauna below the macroalgae was characterized by a different taxonomic composition when compared to controls (i.e., artificial reefs without the macroalgae), particularly when considered the rare taxa. In conclusion, the combination of passive and active restoration can be considered a useful approach to restore marine sites degraded by historical industrial activities.
Is it time to switch to bivalirudin for ECMO anticoagulation?
Authors: Navaei Amir , Kostousov Vadim , Teruya Jun
Published: August 2023

For decades, unfractionated heparin (hereafter, heparin) has been the primary anticoagulant used for extracorporeal membrane oxygenation (ECMO) support. More recently, however, bivalirudin, a direct thrombin inhibitor, has emerged as an alternative. This systematic review based on PRISMA guidelines, aims to summarize 16 comparative studies and 8 meta-analysis and review articles published from January, 2011 till May, 2023 which directly compares ECMO courses using heparin versus bivalirudin as the anticoagulant. While this comparison is complicated by the lack of a standardized definition of major bleeding or thrombosis, our overall findings suggest there is no statistical difference between heparin and bivalirudin in incidence of bleeding and thrombosis. That said, some studies found a statistical significance favoring bivalirudin in reducing major bleeding, thrombosis, and the need for transfusions. We also offer essential guidance for appropriately selecting an anticoagulant and monitoring its effect in ECMO settings.
Bio-protection in oenology by Metschnikowia pulcherrima: from field results to scientific inquiry
Authors: Puyo Maëlys , Simonin Scott , Bach Benoit , Klein Géraldine , Alexandre Hervé , Tourdot-Maréchal Raphaëlle
Published: August 2023

Finding alternatives to the use of chemical inputs to preserve the sanitary and organoleptic quality of food and beverages is essential to meet public health requirements and consumer preferences. In oenology, numerous manufacturers already offer a diverse range of bio-protection yeasts to protect must against microbiological alterations and therefore limit or eliminate sulphites during winemaking. Bio-protection involves selecting non-Saccharomyces yeasts belonging to different genera and species to induce negative interactions with indigenous microorganisms, thereby limiting their development and their impact on the matrix. Although the effectiveness of bio-protection in the winemaking industry has been reported in numerous journals, the underlying mechanisms are not yet well understood.

The aim of this review is to examine the current state of the art of field trials and laboratory studies that demonstrate the effects of using yeasts for bio-protection, as well as the interaction mechanisms that may be responsible for these effects. It focuses on the yeast Metschnikowia pulcherrima, particularly recommended for the bio-protection of grape musts.
Positive effects of lignocellulose on the formation and stability of aerobic granular sludge
Authors: Xu Jie , Gao Yuan , Bi Xuejun , Li Lin , Xiang Wenjuan , Liu Shichang
Published: August 2023

Introduction

Lignocellulose is one of the major components of particulate organic matter in sewage, which has a significant influence on biological wastewater treatment process. However, the effect of lignocellulose on aerobic granular sludge (AGS) system is still unknown.

Methods

In this study, two reactors were operated over 5 months to investigate the effect of lignocellulose on granulation process, structure stability and pollutants removal of AGS.

Results and discussion

The results indicated that lignocellulose not only promoted the secretion of tightly bound polysaccharide in extracellular polymeric substances, but also acted as skeletons within granules, thereby facilitating AGS formation, and enhancing structural strength. Lignocellulose imposed little effect on the removal efficiency of pollutants, with more than 95, 99, and 92% of COD, NH4+-N, and PO43−-P were removed in both reactors. However, it did exhibit a noticeable influence on pollutants conversion processes. This might be due to that the presence of lignocellulose promoted the enrichment of functional microorganisms, including Candidatus_Accumulibacter, Candidatus_Competibacter, Nitrosomonas, and Nitrospira, etc. These findings might provide valuable insights into the control strategy of lignocellulose in practical AGS systems.
Toward personalized circuit-based closed-loop brain-interventions in psychiatry: using symptom provocation to extract EEG-markers of brain circuit activity
Authors: Zrenner Brigitte , Zrenner Christoph , Balderston Nicholas , Blumberger Daniel M. , Kloiber Stefan , Laposa Judith M. , Tadayonnejad Reza , Trevizol Alisson Paulino , Zai Gwyneth , Feusner Jamie D.
Published: August 2023

Symptom provocation is a well-established component of psychiatric research and therapy. It is hypothesized that specific activation of those brain circuits involved in the symptomatic expression of a brain pathology makes the relevant neural substrate accessible as a target for therapeutic interventions. For example, in the treatment of obsessive-compulsive disorder (OCD), symptom provocation is an important part of psychotherapy and is also performed prior to therapeutic brain stimulation with transcranial magnetic stimulation (TMS). Here, we discuss the potential of symptom provocation to isolate neurophysiological biomarkers reflecting the fluctuating activity of relevant brain networks with the goal of subsequently using these markers as targets to guide therapy. We put forward a general experimental framework based on the rapid switching between psychiatric symptom states. This enable neurophysiological measures to be derived from EEG and/or TMS-evoked EEG measures of brain activity during both states. By subtracting the data recorded during the baseline state from that recorded during the provoked state, the resulting contrast would ideally isolate the specific neural circuits differentially activated during the expression of symptoms. A similar approach enables the design of effective classifiers of brain activity from EEG data in Brain-Computer Interfaces (BCI). To obtain reliable contrast data, psychiatric state switching needs to be achieved multiple times during a continuous recording so that slow changes of brain activity affect both conditions equally. This is achieved easily for conditions that can be controlled intentionally, such as motor imagery, attention, or memory retention. With regard to psychiatric symptoms, an increase can often be provoked effectively relatively easily, however, it can be difficult to reliably and rapidly return to a baseline state. Here, we review different approaches to return from a provoked state to a baseline state and how these may be applied to different symptoms occurring in different psychiatric disorders.
Case report: Delayed quadriplegia from traumatic carotid cavernous fistula: a rare case with perimedullary venous drainage
Authors: Ma Yu-Hu , Shang Rui , Lin Sen , Li Si-Hao , Wang Ting , Zhang Chang-Wei
Published: August 2023

Background

Carotid cavernous fistula (CCF) refers to the abnormal arteriovenous communication between the carotid system at the skull base and the sphenoid cavernous sinus, which is caused by trauma in almost 75% of cases. The drainage of venous blood to the spinal cord represents a distinctive mechanism, which is commonly observed in dural arteriovenous fistula (DAVF), and typically manifests clinically as progressive myelopathy. However, it is a rare occurrence in clinical practice that traumatic carotid cavernous fistula (TCCF) causes delayed quadriplegia through perimedullary venous drainage.

Case presentation

We report the case of a 29-year-old male patient who was admitted to the hospital with a sudden onset of headache and quadriplegia. The patient had previously lost his right eye in a traffic accident 5 years ago. Cerebral angiography showed a high-flow direct CCF on the right side, accompanied by obvious drainage of cerebellar and perimedullary veins. We successfully performed coil embolization for the CCF, and the symptoms of the patient gradually improved after the operation. During follow-up at sixth-months, the patient regained the ability to walk independently.

Conclusion

We experienced a rare case of TCCF with quadriplegia. Utilizing coil embolization, we achieved successful improvement in the patient’s condition. However, the mechanism and the best treatment of CCF drainage through the perimedullary vein are still unclear. We need to further explore the pathophysiological information of CCF venous drainage.
Abnormal static and dynamic functional network connectivity of the whole-brain in children with generalized tonic-clonic seizures
Authors: Li Yongxin , Ran Yun , Chen Qian
Published: August 2023

Introduction

Generalized tonic-clonic seizures (GTCS) are a subtype of generalized seizures exhibiting bursts of bilaterally synchronous generalized spike-wave discharges. Numerous neuroimaging studies have reported aberrant functional activity and topological organization of brain network in epilepsy patients with GTCS, but most studies have focused on adults. However, the effect of GTCS on the spatial and temporal properties of brain function in children remains unclear. The present study aimed to explore whole-brain static (sFC) and dynamic functional connectivity (dFC) in children with GTCS.

Methods

Twenty-three children with GTCS and 32 matched healthy controls (HCs) were recruited for the present study. Resting-state functional magnetic resonance imaging (MRI) data were collected for each subject. The group independent component analysis method was used to obtain independent components (ICs). Then, sFC and dFC methods were applied and the differences in functional connectivity (FC) were compared between the children with GTCS and the HCs. Additionally, we investigated the correlations between the dFC indicators and epilepsy duration.

Results

Compared to HCs, GTCS patients exhibited a significant decrease in sFC strengths among most networks. The K-means clustering method was implemented for dFC analysis, and the optimal number of clusters was estimated: two discrete connectivity configurations, State 1 (strong connection) and State 2 (weak connection). The decreased dFC mainly occurred in State 1, especially the dFC between the visual network (VIS) and somatomotor network (SMN); but the increased dFC mainly occurred in State 2 among most networks in GTCS children. In addition, GTCS children showed significantly shorter mean dwell time and lower fractional windows in stronger connected State 1, while GTCS children showed significantly longer mean dwell time in weaker connected State 2. In addition, the dFC properties, including mean dwell time and fractional windows, were significantly correlated with epilepsy duration.

Conclusion

Our results indicated that GTCS epilepsy not only alters the connectivity strength but also changes the temporal properties of connectivity in networks in the whole brain. These findings also emphasized the differences in sFC and dFC in children with GTCS. Combining sFC and dFC methods may provide more comprehensive understanding of the abnormal changes in brain architecture in children with GTCS.
Cytological DNA methylation for cervical cancer screening: a validation set
Authors: Kong Linghua , Wang Linhai , Wang Ziyun , Xiao Xiaoping , You Yan , Wu Huanwen , Wu Ming , Liu Pei , Li Lei
Published: August 2023

Background

In a previous training set with a case-controlled design, cutoff values for host EPB41L3 and JAM3 gene methylation were obtained for the detection of cervical intraepithelial neoplasia (CIN) 2 or more severe lesions (CIN2+). This validation trial was conducted to evaluate the role of DNA methylation in screening for CIN2+ by cervical cytology among unselected participants.

Methods

From June 1, 2019, to September 1, 2019, in our study center, we collected liquid-based samples from cervical swabs for methylation assays and hrHPV testing in eligible patients. The primary endpoint was the diagnostic accuracy of DNA methylation and hrHPV genotyping for CIN2+ according to confirmed histology results.

Results

Among 307 participants, compared with hrHPV testing, the methylation assay for CIN2+ had lower sensitivity (68.7% versus 86.1%, p=0.002) but higher specificity (96.7% versus 0.696, p<0.001). The methylation assay also had favorable sensitivity and specificity in patients with negative hrHPV testing (56.3% and 96.9%) and in patients with cervical adenocarcinoma (73.7% and 92.7%). DNA methylation had higher specificity than the hrHPV assay (100.0% versus 44.4%, p<0.001) for identifying residual CIN2+ in patients without residual lesions. Positive cervical DNA methylation was associated with a diagnostic probability of endometrial carcinoma (odds ratio 15.5 [95% confidence interval 4.1-58.6]) but not of ovarian epithelial carcinoma (1.4 [0.3-6.5]).

Conclusions

The host EPB41L3 and JAM3 gene methylation assay in cervical cytology had favorable diagnostic accuracy for CIN2+ and was highly specific for residual CIN2+ lesions The methylation assay is a promising triage tool in hrHPV+ women, or even an independent tool for cervical cancer screening. The methylation status in cervical cytology could also serve as a prognostic biomarker. Its role in detecting endometrial carcinomas is worthy of further exploration.
Recent advances progress in radiotherapy for breast cancer after breast-conserving surgery: a review
Authors: Wang Yun , Shen Jingjing , Gu Peihua , Wang Zhongming
Published: August 2023

Adjuvant radiotherapy after breast-conserving surgery has become an integral part of the treatment of breast cancer. In recent years, the development of radiotherapy technology has made great progress in this field, including the comparison of the curative effects of various radiotherapy techniques and the performance of the segmentation times. The choice of radiotherapy technology needs to be co-determined by clinical evidence practice and evaluated for each individual patient to achieve precision radiotherapy. This article discusses the treatment effects of different radiotherapy, techniques, the risk of second cancers and short-range radiation therapy techniques after breast-conserving surgery such as hypo fractionated whole breast irradiation and accelerated partial breast irradiation. The choice of radiotherapy regimen needs to be based on the individual condition of the patient, and the general principle is to focus on the target area and reduce the irradiation of the normal tissues and organs. Short-range radiotherapy and hypofractionated are superior to conventional radiotherapy and are expected to become the mainstream treatment after breast-conserving surgery.
The molecular profile in patients with polycythemia vera and essential thrombocythemia is dynamic and correlates with disease’s phenotype
Authors: Sobieralski Patryk , Wasąg Bartosz , Leszczyńska Aleksandra , Żuk Monika , Bieniaszewska Maria
Published: August 2023

Introduction

Polycythemia vera (PV) and essential thrombocythemia (ET) are diseases driven by canonical mutations in JAK2, CALR, or MPL gene. Previous studies revealed that in addition to driver mutations, patients with PV and ET can harbor other mutations in various genes, with no established impact on disease phenotype. We hypothesized that the molecular profile of patients with PV and ET is dynamic throughout the disease.

Methods

In this study, we performed a 37-gene targeted next-generation sequencing panel on the DNA samples collected from 49 study participants in two-time points, separated by 78-141 months. We identified 78 variants across 37 analyzed genes in the study population.

Results

By analyzing the change in variant allele frequencies and revealing the acquisition of new mutations during the disease, we confirmed the dynamic nature of the molecular profile of patients with PV and ET. We found connections between specific variants with the development of secondary myelofibrosis, thrombotic events, and response to treatment. We confronted our results with existing conventional and mutation-enhanced prognostic systems, showing the limited utility of available prognostic tools.

Discussion

The results of this study underline the significance of repeated molecular testing in patients with PV and ET and indicate the need for further research within this field to better understand the disease and improve available prognostic tools.
Upregulated FADD is associated with poor prognosis, immune exhaustion, tumor malignancy, and immunotherapy resistance in patients with lung adenocarcinoma
Authors: He Miao , He Yingying , Xu Jian , Zhang Youcai , Cao Xiaoyu , Wang Li , Luo Feng
Published: August 2023

Background

FAS-associated death structural domain (FADD) proteins are important proteins that regulate apoptosis and are also involved in many nonapoptotic pathways in tumors. However, how dysregulated FADD affects the development of lung adenocarcinoma (LUAD) remains unknown.

Method

Transcriptome profiles and corresponding clinical information of LUAD patients were convened from different databases, and the results were validated by qRT−PCR and cell counting kit-8 using LUAD cell lines. Potential associations between FADD and tumor malignancy, the immune microenvironment, genomic stability, and treatment sensitivity in LUAD patients were revealed by systematic bioinformatics analysis.

Results

FADD was significantly overexpressed in LUAD, and patients with higher expression levels of FADD had a worse prognosis and more advanced tumor stage. Functional analysis revealed that elevated expression of FADD was associated with cell cycle dysregulation, angiogenesis, and metabolic disturbances. In addition, overexpression of FADD was associated with a higher infiltration of suppressive immune cells. From a single-cell perspective, cells with lower FADD expression are more active in immune-related pathways. FADD was associated with more genomic mutations, especially TP53. Patients with high FADD expression are more likely to benefit from conventional chemotherapy, while those with low FADD expression are more suitable for immunotherapy.

Conclusions

Upregulated FADD is associated with worse prognosis, immune exhaustion, and tumor malignancy in LUAD patients. In addition, FADD can be an efficient indicator for assessing sensitivity to chemotherapy and immunotherapy. Therefore, FADD has the potential to serve as a new target for precision medicine and targeted therapy for LUAD.
Knowledge structure and hotspots research of glioma immunotherapy: a bibliometric analysis
Authors: Yuan Yexin , Su Yue , Wu Yingxi , Xue Yafei , Zhang Yunze , Zhang Yangyang , Zheng Min , Chang Ting , Qu Yan , Zhao Tianzhi
Published: August 2023

Background

Glioma is the most common primary brain tumor. Traditional treatments for glioma include surgical resection, radiotherapy, chemotherapy, and bevacizumab therapy, but their efficacies are limited. Immunotherapy provides a new direction for glioma treatment. This study aimed to summarize the knowledge structure and research hotspots of glioma immunotherapy through a bibliometric analysis.

Method

Publications pertaining to glioma immunotherapy published during the period from 1st January 1990 to 27th March 2023 were downloaded from the Web of Science Core Collection (WoSCC). Bibliometric analysis and visualization were performed using the CiteSpace, VOSviewer, Online Analysis Platform of Literature Metrology, and R software. The hotspots and prospects of glioma immunotherapy research were illustrated via analyzing the countries, institutions, journals, authors, citations and keywords of eligible publications.

Results

A total of 1,929 publications pertaining to glioma immunotherapy in 502 journals were identified as of 27th March 2023, involving 9,505 authors from 1,988 institutions in 62 countries. Among them were 1,285 articles and 644 reviews. Most of publications were produced by the United States. JOURNAL OF NEURO-ONCOLOGY published the majority of publications pertaining to glioma immunotherapy. Among the authors, Lim M contributed the largest number of publications. Through analyzing keyword bursts and co-cited references, immune-checkpoint inhibitors (ICIs) were identified as the research focus and hotspot.

Conclusion

Using a bibliometric analysis, this study provided the knowledge structure and research hotspots in glioma immunotherapy research during the past 33 years, with ICIs staying in the current and future hotspot. Our findings may direct the research of glioma immunotherapy in the future.
The efficacy and safety of condoliase for lumbar disc herniation: a systematic review and meta-analysis
Authors: Huang Zeling , Xu Bo , Liu Yujiang , Chen Hua , Cai Xuefeng , Zhang Long , Shen Xiaofeng , Li Yuwei
Published: August 2023

Background: Chemonucleolysis is a minimally invasive treatment of lumbar disc herniation (LDH). However, the low specificity of the enzyme and the existence of serious adverse events limit the application of chemonucleolysis. Clinical studies in recent years have shown that Chondroitin sulfate ABC endolyase (condoliase) is a potential therapeutic enzyme for LDH. Aim. A meta-analysis was conducted to determine the efficacy and safety of condoliase in LDH treatment.

Methods: We searched Web of Science, Embase, PubMed, and Cochrane Library databases. Two reviewers independently screened articles, extracted data, and assessed the risk of bias. The outcomes were the total effective rate, Oswestry Disability Index (ODI) score change, the proportion of lumbar surgery after condoliase treatment, herniated mass volume change, Pfirrmann grade change, and adverse events. Review Manager 5.3 and Stata 12.0 were used for meta-, sensitivity, and bias analysis.

Results: Ten studies were included. A single-arm meta-analysis showed that the total effective rate was 78% [95% confidence interval (CI) 75%–81%], the proportion of surgery was 9% (95% CI 7%–12%), the proportion of Pfirrmann grade change was 43% (95%CI 38%–47%), and the adverse events were 4% (95% CI 2%–6%) after condoliase treatment. The two-arm meta-analysis showed that the ODI score change [standardized mean difference (SMD) −2.46, 95% CI −3.30 to −1.63] and the herniated mass volume change (SMD −16.97, 95% CI −23.92 to −10.03) of the condoliase treatment group were greater than those of the placebo control group, and there was no difference in adverse events between the two groups (OR 1.52, 95% CI 0.60–3.85). The results of sensitivity and publication bias analyses showed that the results were robust.

Conclusion: Condoliase intradiscal injection has excellent eutherapeutic and safety for LDH, thus, has considerable potential as a treatment option besides conservative treatment and surgical intervention for LDH.

Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022375492, PROSPERO (CRD42022375492).
Optimization of degradable temporary plugging material and experimental study on stability of temporary plugging layer
Authors: Chen Zhengrong , Wu Guangai , Zhou Jun , Ai Chuanzhi , Zhang Anshun , Xie Xin , Wu Jianshu , Kong Xiangwei , Li Song
Published: August 2023

Temporary plugging technology is an important drilling technique for maintaining wellbore stability and resolving lost circulation problems. The key to its success lies in the use of materials that can form a tight and stable “temporary plugging layer” with certain pressure bearing capacity and a permeability close to zero in the loss channel near the wellbore. Experimental studies have been conducted to develop adhesion formulations for optimal temporary plugging materials, as the matching relationship between particle size and fracture width is critical [(0.5−1)/1]. By measuring the permeability of the temporary plugging layer under varying confining pressure with a soap foam flowmeter, researchers have been able to evaluate the effectiveness, degradation, and dosages of temporary plugging agents. It has been shown that a single-particle material, such as a walnut shell, has a smaller permeability than a hyperfine CaCO3 coated temporary plug layer. The latter, however, is less capable of bearing pressure. By combining different materials, such as walnut shells and hyperfine CaCO3 particles, the researchers were able to create a temporary plug layer that had the lowest permeability and did not change much at variable confining pressures. Its pressure-bearing capacity is strong and the temporary plug works well. Experiments have shown that a ratio of 2:1–3:1 of hyperfine CaCO3 and walnut shell particles work well for plugging a fracture system with particles of size 2–3 times the fracture width. It developed an evaluation method for temporary plugging agents, studied their plugging capability and degradation performance for reservoir conversion, and evaluated degradation performance after successful temporary plugging. The temporary plugging rate of the temporary plugging agent increased from 98.10% to 99.81%, and the maximum temporary plugging pressure is 50.39 MPa, which can be completely reduced at 150°C for 4 h, meeting the technical requirements of “dense temporary plugging, two-way pressure bearing” to some extent.
Physical model of end-diastolic and end-systolic pressure-volume relationships of a heart
Authors: Zhang Yunxiao , Kalhöfer-Köchling Moritz , Bodenschatz Eberhard , Wang Yong
Published: August 2023

Left ventricular stiffness and contractility, characterized by the end-diastolic pressure-volume relationship (EDPVR) and the end-systolic pressure-volume relationship (ESPVR), are two important indicators of the performance of the human heart. Although much research has been conducted on EDPVR and ESPVR, no model with physically interpretable parameters combining both relationships has been presented, thereby impairing the understanding of cardiac physiology and pathology. Here, we present a model that evaluates both EDPVR and ESPVR with physical interpretations of the parameters in a unified framework. Our physics-based model fits the available experimental data and in silico results very well and outperforms existing models. With prescribed parameters, the new model is used to predict the pressure-volume relationships of the left ventricle. Our model provides a deeper understanding of cardiac mechanics and thus will have applications in cardiac research and clinical medicine.
Unravelling the diversity in water usage among wild banana species in response to vapour pressure deficit
Authors: Eyland David , Gambart Clara , Swennen Rony , Carpentier Sebastien
Published: August 2023

The rise in global temperature is not only affecting plant functioning directly, but is also increasing air vapour pressure deficit (VPD). The yield of banana is heavily affected by water deficit but so far breeding programs have never addressed the issue of water deficit caused by high VPD. A reduction in transpiration at high VPD has been suggested as a key drought tolerance breeding trait to avoid excessive water loss, hydraulic failure and to increase water use efficiency. In this study, stomatal and transpiration responses under increasing VPD at the leaf and whole-plant level of 8 wild banana (sub)species were evaluated, displaying significant differences in stomatal reactivity. Three different phenotypic groups were identified under increasing VPD. While (sub)species of group III maintained high transpiration rates under increasing VPD, M. acuminata ssp. errans (group I), M. acuminata ssp. zebrina (group II) and M. balbisiana (group II) showed the highest transpiration rate limitations to increasing VPD. In contrast to group I, group II only showed strong reductions at high VPD levels, limiting the cost of reduced photosynthesis and strongly increasing their water use efficiency. M. acuminata ssp. zebrina and M. balbisiana thus show the most favourable responses. This study provides a basis for the identification of potential parent material in gene banks for breeding future-proof bananas that cope better with lack of water.
Phenomic selection in slash pine multi-temporally using UAV-multispectral imagery
Authors: Li Yanjie , Yang Xinyu , Tong Long , Wang Lingling , Xue Liang , Luan Qifu , Jiang Jingmin
Published: August 2023

Genomic selection (GS) is an option for plant domestication that offers high efficiency in improving genetics. However, GS is often not feasible for long-lived tree species with large and complex genomes. In this paper, we investigated UAV multispectral imagery in time series to evaluate genetic variation in tree growth and developed a new predictive approach that is independent of sequencing or pedigrees based on multispectral imagery plus vegetation indices (VIs) for slash pine. Results show that temporal factors have a strong influence on the h2 of tree growth traits. High genetic correlations were found in most months, and genetic gain also showed a slight influence on the time series. Using a consistent ranking of family breeding values, optimal slash pine families were selected, obtaining a promising and reliable predictive ability based on multispectral+VIs (MV) alone or on the combination of pedigree and MV. The highest predictive value, ranging from 0.52 to 0.56, was found in July. The methods described in this paper provide new approaches for phenotypic selection (PS) using high-throughput multispectral unmanned aerial vehicle (UAV) technology, which could potentially be used to reduce the generation time for conifer species and increase the genetic granularity independent of sequencing or pedigrees.
Trichoderma spp.-mediated mitigation of heat, drought, and their combination on the Arabidopsis thaliana holobiont: a metabolomics and metabarcoding approach
Authors: Senizza Biancamaria , Araniti Fabrizio , Lewin Simon , Wende Sonja , Kolb Steffen , Lucini Luigi
Published: August 2023

Introduction

The use of substances to increase productivity and resource use efficiency is now essential to face the challenge of feeding the rising global population with the less environmental impact on the ecosystems. Trichoderma-based products have been used as biopesticides, to inhibit pathogenic microorganisms, and as biostimulants for crop growth, nutrient uptake promotion, and resistance to abiotic stresses.

Methods

In this work, plant metabolomics combined with roots and rhizosphere bacterial metabarcoding were exploited to inspect the performance of Trichoderma spp. biostimulants on Arabidopsis thaliana under drought, heat and their combination and its impact on plant holobiont.

Results and discussion

An overall modulation of N-containing compounds, phenylpropanoids, terpenes and hormones could be pointed out by metabolomics. Moreover, metabarcoding outlined an impact on alpha and beta-diversity with an abundance of Proteobacteria, Pseudomonadales, Burkholderiales, Enterobacteriales and Azospirillales. A holobiont approach was applied as an integrated analytical strategy to resolve the coordinated and complex dynamic interactions between the plant and its rhizosphere bacteria using Arabidopsis thaliana as a model host species.