bluuebunny/crossref_metadata_2025 huggingface dataset:
HERV-W ENV antigenemia and correlation of increased anti-SARS-CoV-2 immunoglobulin levels with post-COVID-19 symptoms
Authors: Giménez-Orenga Karen , Pierquin Justine , Brunel Joanna , Charvet Benjamin , Martín-Martínez Eva , Perron Hervé , Oltra Elisa
Published: October 2022

Due to the wide scope and persistence of COVID-19´s pandemic, post-COVID-19 condition represents a post-viral syndrome of unprecedented dimensions. SARS-CoV-2, in line with other infectious agents, has the capacity to activate dormant human endogenous retroviral sequences ancestrally integrated in human genomes (HERVs). This activation was shown to relate to aggravated COVID-19 patient´s symptom severity. Despite our limited understanding of how HERVs are turned off upon infection clearance, or how HERVs mediate long-term effects when their transcription remains aberrantly on, the participation of these elements in neurologic disease, such as multiple sclerosis, is already settling the basis for effective therapeutic solutions. These observations support an urgent need to identify the mechanisms that lead to HERV expression with SARS-CoV-2 infection, on the one hand, and to answer whether persistent HERV expression exists in post-COVID-19 condition, on the other. The present study shows, for the first time, that the HERV-W ENV protein can still be actively expressed long after SARS-CoV-2 infection is resolved in post-COVID-19 condition patients. Moreover, increased anti-SARS-CoV-2 immunoglobulins in post-COVID-19 condition, particularly high anti-SARS-CoV-2 immunoglobulin levels of the E isotype (IgE), seem to strongly correlate with deteriorated patient physical function (r=-0.8057, p<0.01). These results indicate that HERV-W ENV antigenemia and anti-SARS-CoV-2 IgE serology should be further studied to better characterize post-COVID-19 condition pathogenic drivers potentially differing in subsets of patients with various symptoms. They also point out that such biomarkers may serve to design therapeutic options for precision medicine in post-COVID-19 condition.
Effect of the change in antiviral therapy indication on identifying significant liver injury among chronic hepatitis B virus infections in the grey zone
Authors: Ren Shan , Wang Wenjing , Lu Junfeng , Wang Kefei , Ma Lina , Zheng Yanhong , Zheng Sujun , Chen Xinyue
Published: October 2022

Objective

In clinical practice, a substantial proportion of chronic hepatitis B virus (HBV) infections that do not fit into any of the usual immune states are considered to be in the “grey zone (GZ)”. This study aimed to investigate the effect of the change in antiviral therapy indication on identifying significant hepatic injury among GZ patients.

Methods

Patients with chronic HBV infections and a persistent normal alanine aminotransferase (ALT) level (PNALT) who underwent ultrasonography-guided percutaneous liver biopsy were examined retrospectively. Evidenced hepatic injury (EHI) was defined as an inflammation grade ≥2 (≥G2) and/or fibrosis stage ≥2 (≥F2). Complete clinical data, liver inflammation, and fibrosis grades were collected, and the levels of cytokines were detected by the Luminex technique, all of which were analysed to investigate the immune and histopathology states of the liver.

Results

A total of 347 patients with chronic HBV infections and PNALT were categorized into immune tolerant (IT, n = 108), inactive HBV surface antigen (HBsAg) carrier (IHC, n = 61), GZ-1 (HBeAg positive in GZ, n = 92), and GZ-2 (HBeAg negative in GZ, n = 68) phases. Among them, 51.3% were in the GZ phase, and 50.1% presented with EHI. The IL-6 levels were higher in the EHI group than in the non-EHI group (2.77 vs. 1.53 pg/ml, Z = −13.32, p = 0.028). The monocyte chemoattractant protein 1 (MCP-1) level was positively correlated with HBV DNA (R = 0.64, p < 0.001) and HBeAg (R = 0.5, p < 0.001) but negatively correlated with fibrosis grade (R = −0.26, p = 0.048). The ratio of EHI in the GZ phase was 60.55%, which was significantly higher than that in patients in the IT (39.8%) and IHC phases (37.7%) (χ2 = 10.4, p = 0.006). A total of 46.69% of all patients exceeded the new ALT antiviral treatment threshold (30 U/L for men and 19 U/L for women). The EHI values in the IT and IHC phases below the new ALT threshold were 32.6% and 37.8%, respectively, whereas higher EHI values of 67.4% and 68.4% were seen in GZ-1 and GZ-2 patients, respectively, exceeding the new ALT threshold, and the difference was statistically significant (χ2 = 11.13, p < 0.001; χ2 = 14.22, p = 0.002). The median age in our cohort was 38.91 years, and only 21.03% were less than 30 years old. The EHI values in the IT and IHC patients <30 years old were 32.4% and 35.8%, respectively, while the ratio of EHI increased to 43.2% once patients were older than 30 years but still in the IT and IHC stages.

Conclusion

Setting 30 years old as a cut-off and lowering the ALT threshold could facilitate screening for the presence of significant liver injury, especially for GZ patients. IL-6 was a good indicator of EHI, and MCP-1 was significantly positively correlated with HBV DNA but negatively correlated with liver fibrosis.
Haploidentical donor stem cell transplantation had a lower incidence of bronchiolitis obliterans syndrome compared with HLA-matched sibling donor transplantation in patients with hematologic malignancies: Benefit from ATG?
Authors: Weng Guangyang , Fan Zhiping , Xue Huiwen , Huang Fen , Xu Na , Jin Hua , Yu Sijian , Ye Zhixin , Fan Jingchao , Xuan Li , Liu Qifa
Published: October 2022

Background

Haploidentical donor stem cell transplantation (HID-SCT) based on antithymocyte globulin (ATG) for graft-versus-host disease (GVHD) prophylaxis had achieved a similar incidence of chronic graft-versus-host disease (cGVHD) with human leukocyte antigen (HLA)-matched sibling donor stem cell transplantation (MSD-SCT). However, bronchiolitis obliterans syndrome (BOS), which serves as pulmonary cGVHD, was rarely compared between HID and MSD transplantation.

Methods

One thousand four hundred five patients with hematologic malignancies who underwent allogeneic SCT were enrolled in this retrospective study. Based on donor type, we divided the patients into three groups: HID, MSD, and match unrelated donor (MUD) groups. The cumulative incidences and risk factors of BOS were analyzed.

Results

The 5-year cumulative incidence of BOS was 7.2% in the whole population. HID transplantation had a lower 5-year cumulative incidence of BOS than MSD transplantation (4.1% vs. 10.0%, p < 0.001) and a similar incidence with MUD transplantation (4.1% vs. 6.2%, p = 0.224). The 5-year cumulative incidence of BOS was lower in the ATG group than that in the non-ATG group in both the whole and MSD populations (4.6% vs. 11.2%, p < 0.001, and 4.1% vs. 11.2%, p = 0.042, respectively). The 5-year incidence of BOS in mixed grafts [peripheral blood stem cell (PBSC) plus bone marrow] group was also lower than that in the PBSC group (4.2% vs. 9.1, p = 0.001). Multivariate analysis showed that HID, ATG, and mixed grafts were protective factors for BOS [odds ratio (OR) 0.3, 95% CI 0.2–0.6, p < 0.001; OR 0.3, 95% CI 0.2–0.7, p = 0.001; OR 0.3, 95% CI 0.1–0.8, p = 0.013], and acute graft-versus-host disease (aGVHD) and cGVHD were independent risk factors for BOS (OR 2.1, 95% 1.1–4.3, p = 0.035; OR 10.1, 95% CI 4.0–25.0, p < 0.001).

Conclusions

HID transplantation had a lower incidence of BOS than MSD transplantation, which might be associated with ATG and mixed grafts.
pyTCR: A comprehensive and scalable solution for TCR-Seq data analysis to facilitate reproducibility and rigor of immunogenomics research
Authors: Peng Kerui , Moore Jaden , Vahed Mohammad , Brito Jaqueline , Kao Guoyun , Burkhardt Amanda M. , Alachkar Houda , Mangul Serghei
Published: October 2022

T cell receptor (TCR) studies have grown substantially with the advancement in the sequencing techniques of T cell receptor repertoire sequencing (TCR-Seq). The analysis of the TCR-Seq data requires computational skills to run the computational analysis of TCR repertoire tools. However biomedical researchers with limited computational backgrounds face numerous obstacles to properly and efficiently utilizing bioinformatics tools for analyzing TCR-Seq data. Here we report pyTCR, a computational notebook-based solution for comprehensive and scalable TCR-Seq data analysis. Computational notebooks, which combine code, calculations, and visualization, are able to provide users with a high level of flexibility and transparency for the analysis. Additionally, computational notebooks are demonstrated to be user-friendly and suitable for researchers with limited computational skills. Our tool has a rich set of functionalities including various TCR metrics, statistical analysis, and customizable visualizations. The application of pyTCR on large and diverse TCR-Seq datasets will enable the effective analysis of large-scale TCR-Seq data with flexibility, and eventually facilitate new discoveries.
A novel necroptosis-related gene index for predicting prognosis and a cold tumor immune microenvironment in stomach adenocarcinoma
Authors: Khan Muhammad , Lin Jie , Wang Baiyao , Chen Chengcong , Huang Zhong , Tian Yunhong , Yuan Yawei , Bu Junguo
Published: October 2022

Background

Gastric cancer (GC) represents a major global clinical problem with very limited therapeutic options and poor prognosis. Necroptosis, a recently discovered inflammatory form of cell death, has been implicated in carcinogenesis and inducing necroptosis has also been considered as a therapeutic strategy.

Objective

We aim to evaluate the role of this pathway in gastric cancer development, prognosis and immune aspects of its tumor microenvironment.

Methods and results

In this study, we evaluated the gene expression of 55 necroptosis-related genes (NRGs) that were identified via carrying out a comprehensive review of the medical literature. Necroptosis pathway was deregulated in gastric cancer samples (n=375) as compared to adjacent normal tissues (n=32) obtained from the “The Cancer Genome Atlas (TCGA)”. Based on the expression of these NRGs, two molecular subtypes were obtained through consensus clustering that also showed significant prognostic difference. Differentially expressed genes between these two clusters were retrieved and subjected to prognostic evaluation via univariate cox regression analysis and LASSO cox regression analysis. A 13-gene risk signature, termed as necroptosis-related genes prognostic index (NRGPI), was constructed that comprehensively differentiated the gastric cancer patients into high- and low-risk subgroups. The prognostic significance of NRGPI was validated in the GEO cohort (GSE84437: n=408). The NRGPI-high subgroup was characterized by upregulation of 10 genes (CYTL1, PLCL1, CGB5, CNTN1, GRP, APOD, CST6, GPX3, FCN1, SERPINE1) and downregulation of 3 genes (EFNA3, E2F2, SOX14). Further dissection of these two risk groups by differential gene expression analysis indicated involvement of signaling pathways associated with cancer cell progression and immune suppression such as WNT and TGF-β signaling pathway. Para-inflammation and type-II interferon pathways were activated in NRGPI-high patients with an increased infiltration of Tregs and M2 macrophage indicating an exhausted immune phenotype of the tumor microenvironment. These molecular characteristics were mainly driven by the eight NRGPI oncogenes (CYTL1, PLCL1, CNTN1, GRP, APOD, GPX3, FCN1, SERPINE1) as validated in the gastric cancer cell lines and clinical samples. NRGPI-high patients showed sensitivity to a number of targeted agents, in particular, the tyrosine kinase inhibitors.

Conclusions

Necroptosis appears to play a critical role in the development of gastric cancer, prognosis and shaping of its tumor immune microenvironment. NRGPI can be used as a promising prognostic biomarker to identify gastric cancer patients with a cold tumor immune microenvironment and poor prognosis who may response to selected molecular targeted therapy.
Patch reefs as sources of long and continuous skeletal records of horizontal reef expansion in Dongsha Atoll, South China Sea
Authors: Wei Yi , Shen Chuan-Chou , Soong Keryea
Published: October 2022

Atolls are annular midocean reefs with various topographical features. The reef rim of an atoll encloses a central lagoon and lagoonal patch reefs therein. Two hypotheses explaining the origins of patch reefs in atoll lagoons have been developed: the karst hypothesis and the growth hypothesis, which emphasize the role of uneven erosion and uneven timing of reef accretion (especially horizontal expansion), respectively, in the formation and growth of patch reefs. In this study, we investigated trends in the locations, depths, ages, sizes, and other features of flat-top and pinnacle-top reefs in the Dongsha Atoll in the South China Sea by analyzing bathymetric LiDAR images and performing U-Th dating on samples we collected from various reefs in the atoll. Three of our main findings were consistent with the growth hypothesis: (1) the differences in ages of the centers of different flat-top patch reefs reflected the different times at which each patch reef reached the surface and started to expand horizontally; (2) the top surfaces of individual flat-top patch reefs had old centers and young peripheries, reflecting horizontal growth; and (3) all the pinnacle-top reefs we examined had more live corals on their tips than on the surrounding bases. We observed no positive correlation between the ages of the centers and the diameters of flat-top patch reefs; that is, larger reefs did not necessarily have older centers, indicating that various complex factors affect the expansion and age patterns of patch reefs. Overall, the findings of this study provide support for the growth hypothesis and for the use of flat-top patch reefs as sources of easily accessible long-term coral skeletal records. They may therefore serve as a reference for future studies on asymmetric reef expansion and other relevant topics.
Long-term behavioral effects of prenatal stress in the Fmr1-knock-out mouse model for fragile X syndrome
Authors: Petroni Valeria , Subashi Enejda , Premoli Marika , Memo Maurizio , Lemaire Valerie , Pietropaolo Susanna
Published: October 2022

Fragile X syndrome (FXS) is a major neurodevelopmental disorder and the most common monogenic cause of autism spectrum disorder (ASD). FXS is caused by a mutation in the X-linked FMR1 gene leading to the absence of the FMRP protein, inducing several behavioral deficits, including motor, emotional, cognitive, and social abnormalities. Beside its clear genetic origins, FXS can be modulated by environmental factors, e.g., stress exposure: indeed the behavioral phenotype of FXS, as well as of ASD patients can be exacerbated by the repeated experience of stressful events, especially early in life. Here we investigated the long-term effects of prenatal exposure to unpredictable chronic stress on the behavioral phenotype of the Fmr1-knock-out (KO) mouse model for FXS and ASD. Mice were tested for FXS- and ASD-relevant behaviors first at adulthood (3 months) and then at aging (18 months), in order to assess the persistence and the potential time-related progression of the stress effects. Stress induced the selective emergence of behavioral deficits in Fmr1-KO mice that were evident in spatial memory only at aging. Stress also exerted several age-specific behavioral effects in mice of both genotypes: at adulthood it enhanced anxiety levels and reduced social interaction, while at aging it enhanced locomotor activity and reduced the complexity of ultrasonic calls. Our findings underline the relevance of gene-environment interactions in mouse models of neurodevelopmental syndromes and highlight the long-term behavioral impact of prenatal stress in laboratory mice.
The evolving panorama of vascular access in the 21st century
Authors: Neyra Nilda Roxana , Wazir Shoaib
Published: October 2022

There are three major types of hemodialysis vascular access: hemodialysis catheters, arteriovenous grafts, and arteriovenous fistulas. Arteriovenous fistulas provide the best access due to their reliability and long-term patency. They are recommended by the current Kidney Disease Outcomes Quality Initiatives (K-DOQI) guidelines; however, not all patients benefit from arteriovenous fistulas due to poor maturation or a lack of adequate vasculature. Currently, hemodialysis is initiated via catheters in the majority of patients. Catheters are associated with high morbidity and mortality due to infection, lower quality of dialysis, and the development of central vein stenosis. The varied responses of patients to the different access types exemplify the need to choose the “right access for the right patient” based on scores that can predict death risk and progression of chronic kidney disease. Additionally, vascular access, often referred to as the “Achilles’ heel” of hemodialysis patients, represents a significant percentage of the Medicare budget that continues to increase yearly. The purpose of this paper is to review the current literature on the management of vascular access complications and infection treatment and prevention. The paper also explores emerging research regarding the devices and methods to improve access outcomes such as early cannulation arteriovenous grafts, endovascular arteriovenous fistula creation, and regenerative grafts with resorbable scaffolds, among others. The data were collected through literature searches via PubMed, Athens and web search engines.
Temporal and electroencephalography dynamics of surreal marketing
Authors: Wang Regina W. Y. , Liu I-Ning
Published: October 2022

Event-related spectral perturbation analysis was employed in this study to explore whether surreal image designs containing metaphors could influence product marketing effects, including consumers’ product curiosity, product comprehension, product preference, and purchase intention. A total of 30 healthy participants aged 21–30 years were recruited. Neurophysiological findings revealed that lower gamma, beta, and theta spectral powers were evoked in the right insula (Brodmann Area 13) by surreal marketing images. This was associated, behaviorally, with the manifestation of higher product curiosity and purchase intention. Based on previous research, the brain functions of this area include novelty, puzzle-solving, and cravings for reward caused by cognitive overload.
Post treatment imaging in patients with local advanced cervical carcinoma
Authors: Ciulla S. , Celli V. , Aiello A. A. , Gigli S. , Ninkova R. , Miceli V. , Ercolani G. , Dolciami M. , Ricci P. , Palaia I. , Catalano C. , Manganaro L.
Published: October 2022

Cervical cancer (CC) is the fourth leading cause of death in women worldwide and despite the introduction of screening programs about 30% of patients presents advanced disease at diagnosis and 30-50% of them relapse in the first 5-years after treatment. According to FIGO staging system 2018, stage IB3-IVA are classified as locally advanced cervical cancer (LACC); its correct therapeutic choice remains still controversial and includes neoadjuvant chemo-radiotherapy, external beam radiotherapy, brachytherapy, hysterectomy or a combination of these modalities. In this review we focus on the most appropriated therapeutic options for LACC and imaging protocols used for its correct follow-up. We explore the imaging findings after radiotherapy and surgery and discuss the role of imaging in evaluating the response rate to treatment, selecting patients for salvage surgery and evaluating recurrence of disease. We also introduce and evaluate the advances of the emerging imaging techniques mainly represented by spectroscopy, PET-MRI, and radiomics which have improved diagnostic accuracy and are approaching to future direction.
Superficial vaginal myofibroblastoma with mushroom-like appearance: A case report with colposcopic findings and literature review
Authors: Wang Yibei , Sun Meige , Wang Jiao
Published: October 2022

Superficial myofibroblastoma (SMF) of the lower female genital tract is a relatively rare benign mesenchymal tumor. The diagnosis is usually challenging as it shares several similar clinicopathological features with other tumors. Herein, we present a case of a 71-year-old Chinese female patient with postmenopausal vaginal bleeding. Colposcopy imaging revealed a well-circumscribed mass in the vagina with a wide pedicle, resembling a mushroom. The patient underwent surgery, and the tumor was histologically diagnosed as SMF. To the best of our knowledge, this is the first report of colposcopic imaging of a superficial vaginal myofibroblastoma. In this case study, we review the clinicopathological features of SMF of the lower female genital tract reported in the literature to improve the understanding of the disease.
Accuracy of CCL20 expression level as a liquid biopsy-based diagnostic biomarker for ovarian carcinoma
Authors: Sakares Watchara , Wongkhattiya Wannaporn , Vichayachaipat Ponlawat , Chaiwut Chompunoot , Yodsurang Varalee , Nutthachote Pattiya
Published: October 2022

Objective

The study aimed to investigate the potentiality of chemokines, including MCP-1, CCL15, CCL20, and CXCL14, as biomarkers for differential diagnosis between benign tumors and ovarian cancer (OC).

Methods

A cross-sectional study was conducted in women aged >18 years who had adnexal masses treated with elective surgery at the HRH Maha Chakri Sirindhorn Medical Center, Srinakharinwirot University, between 2020 and 2021. The preoperative MCP-1, CCL15, CCL20, and CXCL14 serum levels were measured using a sandwich enzyme-linked immunosorbent assay. Preoperative diagnosis was defined according to the risk of malignancy index. The histological diagnosis and cancer subtype were confirmed using pathological specimens.

Results

Ninety-eight participants were preoperatively diagnosed with malignant tumors. The pathological diagnosis confirmed OC in 33 patients and disclosed 27 misdiagnosed cases, of which endometriotic cyst was the most common (44.44%). CCL20 and CA125 serum levels were significantly higher in the patients with cancer than in those with benign. In addition, CCL20 level could differentiate between benign and early-stage malignancy. Furthermore, only CCL20 levels could distinguish endometriotic cysts from OC, whereas CA125 levels could not. Concordant with the serum protein level, the increased mRNA level of CCL20 was observed in ovarian cancers comparing with that in benign tissues. We found that CCL20 levels could differentiate between benign tumors and OC with 60.61% sensitivity and 75.44% specificity at the optimal cutoff value of 38.79 pg/ml. Finally, the logistic regression model integrating CCL20, CA125, and menopause status promoted diagnostic accuracy by increasing the specificity to 91.23%.

Conclusions

Our study revealed the potential usefulness of CCL20 level as a biomarker for diagnosing early-stage OC with endometriosis differentiation. We recommend further studies to confirm the accuracy of CCL20 levels with the current diagnosis in a large patient sample.
Development and validation of a scatter-corrected CBCT image-guided method for cervical cancer brachytherapy
Authors: Wu Ailin , Cui Hehe , Jiang Xiao , Yan Bing , Wu Aidong , Liu Yunqin , Zhu Lei
Published: October 2022

Background and purpose

Multiple patient transfers have a nonnegligible impact on the accuracy of dose delivery for cervical cancer brachytherapy. We consider using on-site cone-beam CT (CBCT) to resolve this problem. However, CBCT clinical applications are limited due to inadequate image quality. This paper implements a scatter correction method using planning CT (pCT) prior to obtaining high-quality CBCT images and evaluates the dose calculation accuracy of CBCT-guided brachytherapy for cervical cancer.

Materials and methods

The CBCT of a self-developed female pelvis phantom and five patients was first corrected using empirical uniform scatter correction in the projection domain and further corrected in the image domain. In both phantom and patient studies, the CBCT image quality before and after scatter correction was evaluated with registered pCT (rCT). Model-based dose calculation was performed using the commercial package Acuros®BV. The dose distributions of rCT-based plans and corrected CBCT-based plans in the phantom and patients were compared using 3D local gamma analysis. A statistical analysis of the differences in dosimetric parameters of five patients was also performed.

Results

In both phantom and patient studies, the HU error of selected ROIs was reduced to less than 15 HU. Using the dose distribution of the rCT-based plan as the baseline, the γ pass rate (2%, 2 mm) of the corrected CBCT-based plan in phantom and patients all exceeded 98% and 93%, respectively, with the threshold dose set to 3, 6, 9, and 12 Gy. The average percentage deviation (APD) of D90 of HRCTV and D2cc of OARs was less than 1% between rCT-based and corrected CBCT-based plans.

Conclusion

Scatter correction using a pCT prior can effectively improve the CBCT image quality and CBCT-based cervical brachytherapy dose calculation accuracy, indicating promising prospects in both simplified brachytherapy processes and accurate brachytherapy dose delivery.
Nomograms for predicting the prognosis of patients with penoscrotal extramammary Paget’s disease: A retrospective study in the SEER database and two medical centers
Authors: Song Le-Bin , Zhou Xiang , Luan Jiao-Chen , Wang Hao-Yang , Cao Xue-Chen , Lu Jia-Wei , Zheng Yu-Jie , Wu Xin-Feng , Lu Yan
Published: October 2022

Background

Extramammary Paget’ s disease (EMPD) is a rare cutaneous malignant tumor, and the prognostic factors associated with penoscrotal EMPD remains unclear. The purpose of this study is to investigate prognostic factors and construct nomograms to predict the outcome of patients with EMPD located in the penis or scrotum.

Methods

From the Surveillance, Epidemiology and End Results (SEER) database, we extracted 95 patients with primary EMPD located in the penis or scrotum as the training cohort. Forty-nine penoscrotal EMPD patients were included from two medical centers as the external validation cohort. Univariate and multivariate Cox regression model were applied to investigating risk factors of cancer-specific survival (CSS) and overall survival (OS). Based on the results of multivariate Cox regression analysis, the nomograms were constructed for predicting CSS and OS of patients with penoscrotal EMPD. The concordance index (C-index), receiver operating characteristic (ROC) curves and calibration curves were applied to evaluate the practicability and accuracy of the nomograms.

Results

In the training cohort, multivariate Cox regression analysis showed that marital status and tumor stage were independent factors of CSS, and marital status, tumor stage and surgery are associated with OS independently in patients with penoscrotal EMPD. Based on these results, we developed nomograms to predict CSS and OS respectively. The C-index values were 0.778 for CSS, and 0.668 for OS in the training set, which displayed the good discriminations. In the external validation set, the C-index values were 0.945 for CSS, and 0.703 for OS. The areas under the curve (AUC) values of nomogram predicting 1-, 3-, and 5-year CSS were 0.815, 0.833, and 0.861 respectively, and 0.839, 0.654, and 0.667 for nomogram predicting 1-, 3-, and 5-year OS respectively. In the validation set, the AUC values of nomogram predicting 1-, 3-, and 5-year CSS were 0.944, 0.896, and 0.896 respectively, and 0.777, 0.762 and 0.692 for nomogram predicting 1-, 3-, and 5-year OS respectively. Additionally, the internal calibration curves also proved that our nomograms have good accuracy.

Conclusions

By incorporating marital status, tumor stage and/or surgery, our nomograms can efficiently predict CSS and OS of patients with penoscrotal EMPD.
An exploratory study of CT radiomics using differential network feature selection for WHO/ISUP grading and progression-free survival prediction of clear cell renal cell carcinoma
Authors: Yin Fu , Zhang Haijie , Qi Anqi , Zhu Zexuan , Yang Liyang , Wen Ge , Xie Weixin
Published: October 2022

Objectives

To explore the feasibility of predicting the World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade and progression-free survival (PFS) of clear cell renal cell cancer (ccRCC) using the radiomics features (RFs) based on the differential network feature selection (FS) method using the maximum-entropy probability model (MEPM).

Methods

175 ccRCC patients were divided into a training set (125) and a test set (50). The non-contrast phase (NCP), cortico-medullary phase, nephrographic phase, excretory phase phases, and all-phase WHO/ISUP grade prediction models were constructed based on a new differential network FS method using the MEPM. The diagnostic performance of the best phase model was compared with the other state-of-the-art machine learning models and the clinical models. The RFs of the best phase model were used for survival analysis and visualized using risk scores and nomograms. The performance of the above models was tested in both cross-validated and independent validation and checked by the Hosmer-Lemeshow test.

Results

The NCP RFs model was the best phase model, with an AUC of 0.89 in the test set, and performed superior to other machine learning models and the clinical models (all p <0.05). Kaplan-Meier survival analysis, univariate and multivariate cox regression results, and risk score analyses showed the NCP RFs could predict PFS well (almost all p < 0.05). The nomogram model incorporated the best two RFs and showed good discrimination, a C-index of 0.71 and 0.69 in the training and test set, and good calibration.

Conclusion

The NCP CT-based RFs selected by differential network FS could predict the WHO/ISUP grade and PFS of RCC.
DNA methylation topology differentiates between normal and malignant in cell models, resected human tissues, and exfoliated sputum cells of lung epithelium
Authors: Tajbakhsh Jian , Mortazavi Fariborz , Gupta Nirdesh K.
Published: October 2022

Background

Global DNA hypomethylation is a prominent feature of cancer cells including lung cancer, that has not been widely explored towards cancer diagnosis. In this study we assess the comparative distribution of global DNA methylation in normal cells versus cancer cells in various specimen models.

Methods

We used in situ immunofluorescence labeling of overall 5-methylcytosine (5mC) and covisualization of global DNA (gDNA) by 4’,6-diamidino-2-phenylindole (DAPI), confocal microscopy and 3D image analysis to derive 5mC/DAPI colocalization patterns in human cell lines (BEAS-2B, A549, H157) and upper respiratory epithelial cells derived from various sources (i.e., sputum from healthy and cancer patients, and resected tissues from normal parenchyma and lung tumors).

Results

By introducing 5mC/DAPI colocalization index as a metric we could distinguish between normal epithelial cells and aberrantly hypomethylated cancer cells. Cultured lung cancer cells (H157 and A549) had significantly lower indices compared to normal cells (BEAS-2B). Furthermore, we were able to identify such extensively hypomethylated low-index cells in tumor tissues and the matching sputum from cancer patients. In contrast, the indices of cells derived from sputum of healthy individuals had more similarity to epithelial cells of normal parenchyma and the phenotypically normal BEAS-2B cells.

Conclusions

The results suggest that 5mC topology using high-resolution image cytometry shows potential for identifying hypomethylated cancerous cells in human tissues and amongst normal cells in matching sputum, which may render a valuable surrogate for biopsied tissues. This promising feature deserves further validation in more comprehensive studies.
Exogenous 6-benzylaminopurine enhances waterlogging and shading tolerance after anthesis by improving grain starch accumulation and grain filling
Authors: Zhang Wenjing , Wang Beibei , Zhang Anmin , Zhou Qirui , Li Yang , Li Lingyu , Ma Shangyu , Fan Yonghui , Huang Zhenglai
Published: October 2022

Due to the frequent occurrence of extreme weather events, the area of wheat affected by continuous cloudy rainfall is increasing, with waterlogging becoming a major limiting factor of wheat yield. To alleviate the effect, spraying exogenous plant growth regulators is often used. In this study, two wheat cultivars, waterlogging-tolerant Yangmai 18 and waterlogging-sensitive Sumai 188, were selected for waterlogging and shading (WS) after anthesis for 7, 11, and 15 days respectively. Three concentrations of 6-benzylaminoadenine (6-BA) solution (15, 25, and 35 mg·L−1) were sprayed after WS treatment and water was sprayed as the control. Then, the effect of spraying 6-BA on photosynthetic characteristics, starch content, grain filling characteristics, and yield was explored under artificially stimulated continuous cloudy rainfall during anthesis. Compared with the control, the application of 6-BA caused a significant increase in grain plumpness throughout grain filling, as well as increases in the net photosynthetic rate (Pn), stomatal conductance (Gs), and transpiration rate (Tr), and a significant decrease in the intercellular CO2 concentration (Ci) of the flag leaves, all of which enhanced the photosynthetic capacity. The content of total starch, amylose, and amylopectin in the grains also increased significantly compared with the control. After WS for 15 days, the starch content increased by 3.81%–11.41% compared with the control. Spraying 6-BA also prolonged grain filling, increased the average grain filling rate, and significantly increased the 1000-grain weight and yield. The thousand-grain weight increased by 5.06%–43.28%, and wheat yield increased by 8.93%–64.27% after spraying 25 mg·L−1 of the 6-BA solution. These findings suggest that the application of 6-BA after WS stress could significantly improve the photosynthetic performance, which is propitious to the accumulation and transport of photosynthetic products after anthesis. Besides, spraying 6-BA can also increase the duration and rate of grain filling and starch accumulation content and improve grain weight, thereby alleviating the adverse effects of WS on wheat yield. Overall, spraying 25 mg·L−1 of the 6-BA solution had an optimal effect. These findings provide a theoretical basis for the exploration of cultivation techniques and measures aimed at alleviating damage caused by continuous rainfall during wheat anthesis.
Rabbit manure compost as a peat substitute for compound growing media: Proportioning optimization according to physiochemical characteristics and seedling effects
Authors: Li Rangling , Hao Hongyun , Yang Chengcai , Wang Liangju , Wang Hongying
Published: October 2022

A large amount of rabbit manure is produced with the development of the rabbit industry, which will cause environmental pollution without proper treatment. Rabbit manure compost may be suitable for seedling cultivation, considering its low moisture, low heavy metal, high lignocellulose, and good fertilizer effect. In this study, a pre-proportioning test of growing media was conducted to optimize the ratio of perlite and vermiculite with peat/rabbit manure compost according to their physicochemical properties. Then, based on the results of the first proportioning optimization, the mixing ratio of rabbit manure compost and peat was further optimized using a bioassay. In this bioassay, salt-tolerant calendula (Calendula officinalis L.) and salt-intolerant cucumber (Cucumis sativus L.) were selected as test plants. The seedling effects (e.g., seedling emergence percentage, plant growth parameters, plant biomass, and nutrient effects) were evaluated. It was shown in the results that the rabbit manure compound growing media could be used for the seedlings, and suitable seedling performance was obtained with the increase of the total porosity (5.0%–61.2%), organic matter content (8.3%–39.9%), and nutrient elements from the rabbit manure compost. From the perspective of seedling emergence, there was no significant difference between rabbit manure compound media and peat treatment, in which the highest emergence percentages were >90%. At the same time, the nutrient performance of plant aboveground was significantly increased in rabbit manure compound growing media compared to peat treatment. In particular, the contents of P and Mg were increased by 31%–141.4% and 80.4%–107.8% for calendula and by 82.6%–117.4% and 35.1%–67.6% for cucumber, respectively. It was indicated in the two-step optimization that the rabbit manure compost proportion of 30%–50% (that is, 60%–100% instead of peat) was more suitable. Additionally, the greenhouse gas emission could be reduced by using rabbit manure compost replacing peat, and the greenhouse gas emission reduction potential would be 3.65 × 105–4.06 × 108 kg CO2-equivalent/year in China, which has important ecological significance.
Zinc oxide nanoparticles improve lettuce (Lactuca sativa L.) plant tolerance to cadmium by stimulating antioxidant defense, enhancing lignin content and reducing the metal accumulation and translocation
Authors: Gao Feng , Zhang Xiaodan , Zhang Jing , Li Jing , Niu Tianhang , Tang Chaonan , Wang Cheng , Xie Jianming
Published: October 2022

Cadmium (Cd) contamination is a serious global concern that warrants constant attention. Therefore, a hydroponic study was conducted to evaluate the effect of different concentrations (0, 1, 2.5, 5, 10, 15 mg/l) of zinc oxide nanoparticles (ZnONPs) on the Cd content in lettuce (Lactuca sativa L.) under Cd stress conditions. The results showed that Cd stress triggered a decrease in plant biomass, an increase in relative electrolyte conductivity (REC), a decrease in root activity, accumulation of reactive oxygen species (ROS) accumulation, and nutrient imbalance. The application of ZnONPs reduced the toxicity symptoms of lettuce seedlings under Cd stress, with the most pronounced effect being observed 2.5 mg/l. ZnONPs promoted the growth of lettuce under Cd stress, mainly in terms of increase in biomass, chlorophyll content, antioxidant enzyme activity, and proline content, as well as reduction in Cd content, malondialdehyde, and reactive oxygen species (ROS) in plant tissues. ZnONPs also enhanced the uptake of ions associated with photosynthesis, such as iron, manganese, magnesium, and zinc. In addition, ZnONPs increase the amount of lignin in the roots, which blocks or reduces the entry of Cd into plant tissues.
Norway spruce somatic embryogenesis benefits from proliferation of embryogenic tissues on filter discs and cold storage of cotyledonary embryos
Authors: Välimäki Sakari , Teyssier Caroline , Tikkinen Mikko , Delile Armelle , Boizot Nathalie , Varis Saila , Lelu-Walter Marie-Anne , Aronen Tuija
Published: October 2022

Vegetative propagation opens opportunities for the multiplication of elite tree progeny for forest regeneration material. For conifers such as Norway spruce (Picea abies) the most efficient vegetative propagation method is seed multiplication through somatic embryogenesis. Efficient culture methods are needed for somatic embryogenesis to be commercially viable. Compared to culturing as clumps, filter disc cultures can improve the proliferation of embryogenic tissue (ET) due to more even spread and better developmental synchronization. In this study, ET proliferation on filter discs was compared to proliferation as clumps. The study comprised 28 genotypes in four trials. The benefits of adding a pre-maturation step and the selection of fresh ET for the subculture were evaluated. Pre-maturation on hormone-free media before maturation did not significantly improve embryo yield but improved greenhouse survival from 69% to 80%, although there was high variation between lines. Filter disc cultivation of ET did result in better growth than in clumps but was more dependent on ET selection and the amount of ET than the clump cultivation method. Filter proliferation also favors certain lines. Post-maturation storage can be used to change the storage compound composition of the produced mature embryos. The embryo storage compound profile was analyzed after post-maturation cold storage treatments of 0, 4, 8, 31, and 61 weeks and compared to that of the zygotic embryos. Cold storage made the storage compound profile of somatic embryos closer to that of zygotic embryos, especially regarding the raffinose family oligosaccharides and storage proteins. Sucrose, hexose, and starch content remained higher in somatic embryos even through cold storage. Prolonged storage appeared less beneficial for embryos, some of which then seemed to spontaneously enter the germination process.
Development of chloroplast transformation and gene expression regulation technology in land plants
Authors: An Yaqi , Wang Yue , Wang Xinwei , Xiao Jianwei
Published: October 2022

Chloroplasts in land plants have their own small circular DNA that is presumed to have originated from cyanobacteria-related endosymbionts, and the chloroplast genome is an attractive target to improve photosynthetic ability and crop yield. However, to date, most transgenic or genetic engineering technologies for plants are restricted to manipulations of the nuclear genome. In this review, we provide a comprehensive overview of chloroplast genetic engineering and regulation of gene expression from the perspective of history and biology, focusing on current and latest methods. In addition, we suggest techniques that may regulate the chloroplast gene expression at the transcriptional or post-transcriptional level.
Highly efficient hairy root genetic transformation and applications in citrus
Authors: Ma Haijie , Meng Xinyue , Xu Kai , Li Min , Gmitter Fred G. , Liu Ningge , Gai Yunpeng , Huang Suya , Wang Min , Wang Min , Wang Nian , Xu Hairen , Liu Jinhua , Sun Xuepeng , Duan Shuo
Published: October 2022

Highly efficient genetic transformation technology is greatly beneficial for crop gene function analysis and precision breeding. However, the most commonly used genetic transformation technology for woody plants, mediated by Agrobacterium tumefaciens, is time-consuming and inefficient, which limits its utility for gene function analysis. In this study, a simple, universal, and highly efficient genetic transformation technology mediated by A. rhizogenes K599 is described. This technology can be applied to multiple citrus genotypes, and only 2–8 weeks were required for the entire workflow. Genome-editing experiments were simultaneously conducted using 11 plasmids targeting different genomic positions and all corresponding transformants with the target knocked out were obtained, indicating that A. rhizogenes-mediated genome editing was highly efficient. In addition, the technology is advantageous for investigation of specific genes (such as ACD2) for obtaining “hard-to-get” transgenic root tissue. Furthermore, A. rhizogenes can be used for direct viral vector inoculation on citrus bypassing the requirement for virion enrichment in tobacco, which facilitates virus-induced gene silencing and virus-mediated gene expression. In summary, we established a highly efficient genetic transformation technology bypassing tissue culture in citrus that can be used for genome editing, gene overexpression, and virus-mediated gene function analysis. We anticipate that by reducing the cost, required workload, experimental period, and other technical obstacles, this genetic transformation technology will be a valuable tool for routine investigation of endogenous and exogenous genes in citrus.
Mating pattern and pollen dispersal in an advanced generation seed orchard of Cunninghamia lanceolata (Lamb.) Hook
Authors: Wu Hanbin , Zhao Shirong , Wang Xihan , Duan Aiguo , Zhang Jianguo
Published: October 2022

Seed orchards represent the link between forest breeding and conifer production forests, and their mating patterns determine the genetic quality of seed orchard crops to a large extent. We genotyped the parental clones and their open pollination offspring in the third-generation seed orchard of Chinese fir using microsatellite markers and observed the synchronization of florescence in the seed orchard to understand the genetic diversity and mating structure of the seed orchard population. Genetic coancestry among parental clones was detected in the third generation seed orchard of Chinese fir, and the genetic diversity of the open-pollinated offspring was slightly higher than that of the parental clones. The external pollen contamination rate ranged from 10.1% to 33.7%, 80% of the offspring were produced by 44% of the parental clones in the orchard, and no evidence of selfing was found. We found that 68.1% of the effective pollination occurred within 50 m, and 19.9% of the effective pollination occurred in the nearest neighbors. We also found that successful mating requires about 30% of florescence overlap between males and females, and there was a significant positive correlation between male reproductive energy and male parental contribution. Our results provide a valuable reference for the management and design of advanced generation seed orchards.
The appropriate expression and coordination of glycolate oxidase and catalase are vital to the successful construction of the photorespiratory metabolic pathway
Authors: Yao Zhen , Rao Zelai , Hou ShuWang , Tian Changwei , Liu Chun-Yan , Yang Xiulan , Zhu Guicai
Published: October 2022

Photorespiration has emerged as a hotspot in the evolution of photosynthesis owing to the energy loss during the process. To ensure the physiological functions of photorespiration such as light protection, H2O2 signaling, and stress resistance, separate the photorespiration glycolic acid flow, and minimize photorespiration loss, a balance must be maintained during the construction of photorespiratory metabolic branch. In this study, glycolate oxidase (GLO) and catalase (CAT) were introduced into potato (Solanum tuberosum) chloroplasts through the expression of fusion protein. Through the examination of phenotypic characteristics, photosynthesis, anatomical structure, and enzyme activity, the efficiency of the photorespiration pathway was demonstrated. The results showed that certain transgenic lines plants had shorter plant height and deformed leaves and tubers in addition to the favorable photosynthetic phenotypes of thicker leaves and larger and denser mesophyll cells. By Diaminobenzidine (DAB) staining analysis of the leaves, the intermediate H2O2 could not be decomposed in time to cause biomass decline and malformation, and the excessive glycolate shunt formed by the overexpression of the fusion protein affected other important physiological activities. Hence, the appropriate and coordinated expression of glycolate oxidase and catalase is essential for the establishment of photorespiration pathways in chloroplasts.