bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine Learning-Based Radiological Features and Diagnostic Predictive Model of Xanthogranulomatous Cholecystitis
Authors: Zhou Qiao-Mei , Liu Chuan-Xian , Zhou Jia-Ping , Yu Jie-Ni , Wang You , Wang Xiao-Jie , Xu Jian-Xia , Yu Ri-Sheng
Published: February 2022

Background

Xanthogranulomatous cholecystitis (XGC) is a rare benign chronic inflammatory disease of the gallbladder that is sometimes indistinguishable from gallbladder cancer (GBC), thereby affecting the decision of the choice of treatment. Thus, this study aimed to analyse the radiological characteristics of XGC and GBC to establish a diagnostic prediction model for differential diagnosis and clinical decision-making.

Methods

We investigated radiological characteristics confirmed by the RandomForest and Logistic regression to establish computed tomography (CT), magnetic resonance imaging (MRI), CT/MRI models and diagnostic prediction model, and performed receiver operating characteristic curve (ROC) analysis to prove the effectiveness of the diagnostic prediction model.

Results

Based on the optimal features confirmed by the RandomForest method, the mean area under the curve (AUC) of the ROC of the CT and MRI models was 0.817 (mean accuracy = 0.837) and 0.839 (mean accuracy = 0.842), respectively, whereas the CT/MRI model had a considerable predictive performance with the mean AUC of 0.897 (mean accuracy = 0.906). The diagnostic prediction model established for the convenience of clinical application was similar to the CT/MRI model with the mean AUC and accuracy of 0.888 and 0.898, respectively, indicating a preferable diagnostic efficiency in distinguishing XGC from GBC.

Conclusions

The diagnostic prediction model showed good diagnostic accuracy for the preoperative discrimination of XGC and GBC, which might aid in clinical decision-making.
Second Primary Lung Adenocarcinoma After Intensity-Modulated Radiotherapy for Nasopharyngeal Carcinoma
Authors: Xue Fen , Niu Xiaoshuang , Hu Chaosu , He Xiayun
Published: February 2022

Objective

The improvement of the efficacy of intensity-modulated radiotherapy (IMRT) for nasopharyngeal cancer (NPC) has prolonged the survival of patients, and the incidence of the second tumor has gradually increased. Among them, second primary lung adenocarcinoma (SPLAC) attributes the highest incidence. This study aimed to determine the long-term risk of SPLAC in NPC patients after IMRT.

Methods

From May 2005 to May 2018, a total of 1,102 non-metastatic NPC patients who received IMRT in our hospital were enrolled, and the incidence and efficacy of SPLAC were followed up in the long term.

Results

Over a median follow-up period of 66 months, a total of 22 cases of SPLAC were observed, with an incidence of 2.0%. The 1-, 2-, 3-, 4-, and 5-year cumulative risks of SPLAC were 0.4%, 0.7%, 0.8%, 1.1%, and 1.7%, respectively. During follow-up, 90.9% (20/22) of the SPLAC detected was in early stage, and the recurrence rate of surgery alone was 5.3% (1/19).

Conclusion

In NPC patients, the proportion of SPLAC after IMRT was similar to that of the normal population, and most of them were found in early stage during follow-up, with good surgical efficacy.
A Deep Learning Model for Preoperative Differentiation of Glioblastoma, Brain Metastasis and Primary Central Nervous System Lymphoma: A Pilot Study
Authors: Tariciotti Leonardo , Caccavella Valerio M. , Fiore Giorgio , Schisano Luigi , Carrabba Giorgio , Borsa Stefano , Giordano Martina , Palmisciano Paolo , Remoli Giulia , Remore Luigi Gianmaria , Pluderi Mauro , Caroli Manuela , Conte Giorgio , Triulzi Fabio , Locatelli Marco , Bertani Giulio
Published: February 2022

Background

Neuroimaging differentiation of glioblastoma, primary central nervous system lymphoma (PCNSL) and solitary brain metastasis (BM) remains challenging in specific cases showing similar appearances or atypical features. Overall, advanced MRI protocols have high diagnostic reliability, but their limited worldwide availability, coupled with the overlapping of specific neuroimaging features among tumor subgroups, represent significant drawbacks and entail disparities in the planning and management of these oncological patients.

Objective

To evaluate the classification performance metrics of a deep learning algorithm trained on T1-weighted gadolinium-enhanced (T1Gd) MRI scans of glioblastomas, atypical PCNSLs and BMs.

Materials and Methods

We enrolled 121 patients (glioblastoma: n=47; PCNSL: n=37; BM: n=37) who had undergone preoperative T1Gd-MRI and histopathological confirmation. Each lesion was segmented, and all ROIs were exported in a DICOM dataset. The patient cohort was then split in a training and hold-out test sets following a 70/30 ratio. A Resnet101 model, a deep neural network (DNN), was trained on the training set and validated on the hold-out test set to differentiate glioblastomas, PCNSLs and BMs on T1Gd-MRI scans.

Results

The DNN achieved optimal classification performance in distinguishing PCNSLs (AUC: 0.98; 95%CI: 0.95 - 1.00) and glioblastomas (AUC: 0.90; 95%CI: 0.81 - 0.97) and moderate ability in differentiating BMs (AUC: 0.81; 95%CI: 0.70 - 0.95). This performance may allow clinicians to correctly identify patients eligible for lesion biopsy or surgical resection.

Conclusion

We trained and internally validated a deep learning model able to reliably differentiate ambiguous cases of PCNSLs, glioblastoma and BMs by means of T1Gd-MRI. The proposed predictive model may provide a low-cost, easily-accessible and high-speed decision-making support for eligibility to diagnostic brain biopsy or maximal tumor resection in atypical cases.
Identification of circRNA–miRNA–Immune-Related mRNA Regulatory Network in Gastric Cancer
Authors: Wu Zhenhai , Liu Pengyuan , Zhang Ganlu
Published: February 2022

The pathogenesis of gastric cancer (GC) is still not fully understood. We aimed to find the potential regulatory network for ceRNA (circRNA–miRNA–immune-related mRNA) to uncover the pathological molecular mechanisms of GC. The expression profiles of circRNA, miRNA, and mRNA in gastric tissue from GC patients were downloaded from the Gene Expression Omnibus (GEO) datasets. Differentially expressed circRNAs, miRNAs, and immune-related mRNAs were filtered, followed by the construction of the ceRNA (circRNA–miRNA–immune-related mRNA) network. Functional annotation and protein–protein interaction (PPI) analysis of immune-related mRNAs in the network were performed. Expression validation of circRNAs and immune-related mRNAs was performed in the new GEO and TCGA datasets and in-vitro experiment. A total of 144 differentially expressed circRNAs, 216 differentially expressed miRNAs, and 2,392 differentially expressed mRNAs were identified in GC. Some regulatory pairs of circRNA–miRNA–immune-related mRNA were obtained, including hsa_circ_0050102–hsa-miR-4537–NRAS–Tgd cells, hsa_circ_0001013–hsa-miR-485-3p–MAP2K1–Tgd cells, hsa_circ_0003763–hsa-miR-145-5p–FGF10–StromaScore, hsa_circ_0001789–hsa-miR-1269b–MET–adipocytes, hsa_circ_0040573–hsa-miR-3686–RAC1–Tgd cells, and hsa_circ_0006089–hsa-miR-5584-3p–LYN–neurons. Interestingly, FGF10, MET, NRAS, RAC1, MAP2K1, and LYN had potential diagnostic value for GC patients. In the KEGG analysis, some signaling pathways were identified, such as Rap1 and Ras signaling pathways (involved NRAS and FGF10), Fc gamma R-mediated phagocytosis and cAMP signaling pathway (involved RAC1), proteoglycans in cancer (involved MET), T-cell receptor signaling pathway (involved MAP2K1), and chemokine signaling pathway (involved LYN). The expression validation of hsa_circ_0003763, hsa_circ_0004928, hsa_circ_0040573, FGF10, MET, NRAS, RAC1, MAP2K1, and LYN was consistent with the integrated analysis. In conclusion, the identified ceRNA (circRNA–miRNA–immune-related mRNA) regulatory network may be associated with the development of GC.
Multimodal MRI Image Decision Fusion-Based Network for Glioma Classification
Authors: Guo Shunchao , Wang Lihui , Chen Qijian , Wang Li , Zhang Jian , Zhu Yuemin
Published: February 2022

Purpose

Glioma is the most common primary brain tumor, with varying degrees of aggressiveness and prognosis. Accurate glioma classification is very important for treatment planning and prognosis prediction. The main purpose of this study is to design a novel effective algorithm for further improving the performance of glioma subtype classification using multimodal MRI images.

Method

MRI images of four modalities for 221 glioma patients were collected from Computational Precision Medicine: Radiology-Pathology 2020 challenge, including T1, T2, T1ce, and fluid-attenuated inversion recovery (FLAIR) MRI images, to classify astrocytoma, oligodendroglioma, and glioblastoma. We proposed a multimodal MRI image decision fusion-based network for improving the glioma classification accuracy. First, the MRI images of each modality were input into a pre-trained tumor segmentation model to delineate the regions of tumor lesions. Then, the whole tumor regions were centrally clipped from original MRI images followed by max–min normalization. Subsequently, a deep learning-based network was designed based on a unified DenseNet structure, which extracts features through a series of dense blocks. After that, two fully connected layers were used to map the features into three glioma subtypes. During the training stage, we used the images of each modality after tumor segmentation to train the network to obtain its best accuracy on our testing set. During the inferring stage, a linear weighted module based on a decision fusion strategy was applied to assemble the predicted probabilities of the pre-trained models obtained in the training stage. Finally, the performance of our method was evaluated in terms of accuracy, area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), etc.

Results

The proposed method achieved an accuracy of 0.878, an AUC of 0.902, a sensitivity of 0.772, a specificity of 0.930, a PPV of 0.862, an NPV of 0.949, and a Cohen’s Kappa of 0.773, which showed a significantly higher performance than existing state-of-the-art methods.

Conclusion

Compared with current studies, this study demonstrated the effectiveness and superiority in the overall performance of our proposed multimodal MRI image decision fusion-based network method for glioma subtype classification, which would be of enormous potential value in clinical practice.
Predictive Factors for Recurrence of Papillary Thyroid Carcinoma in Children and Adolescents
Authors: Gui Yan , Huang Dongmei , Hou Yun , Wei Xudong , Zhang Jinming , Wang Junyi
Published: February 2022

Background

The incidence of papillary thyroid carcinoma (PTC) in children and adolescents has increased, but the data on long-term outcomes are limited. There are few literatures on the clinicopathological characteristics and prognosis of PTC in children and adolescents in China. Therefore, it is necessary to identify clinicopathological features to precisely predict clinical prognosis and to help choose the optimal method and perform the best therapeutic regimen.

Methods

This study was a retrospective analysis of patients undergoing thyroidectomy at Tianjin Medical University Cancer Institute and Hospital. We analyzed the factors related to the clinicopathological features and prognosis of PTC in children and adolescents.

Results

A total of 95 juvenile PTC patients who underwent thyroidectomy were enrolled. Our research found that patients with younger age (<14 years) were predominantly multifocal and have positive preoperative thyroglobulin (Tg) and higher recurrence rate, and their number of lymph node metastases (LNMs) was more than that of the older group (14–18 years). Maximal tumor size >2 cm, T stage, and multifocality were the risk factors for LNM and the number of LNM (p < 0.05). Multivariate analysis displayed the number of central LNM as the independent risk factor for lateral LNM, and multifocality was the independent risk factor for the number of central and lateral LNM. Younger age at diagnosis, positive preoperative thyroid-stimulating hormone (TSH), maximal tumor size >2 cm, lateral LNM, number of LNM, N staging, and American Thyroid Association (ATA) pediatric risk were related to poor prognosis in PTC patients (p < 0.05). Cox regression analysis found that younger age at diagnosis and positive preoperative TSH were independent risk factors for recurrence of PTC in children and adolescents.

Conclusions

Our study showed that the clinicopathological characteristics of younger age compared with older age were as follows: highly aggressive, prone to metastases, and higher recurrence rate. In our opinion, patients with characteristics such as younger age at diagnosis, positive preoperative TSH, maximal tumor size >2 cm, lateral LNM, and number of LNM >5 may be considered for prophylactic or therapeutic dissection of additional metastatic LNs by high-volume surgeons to prevent and reduce the recurrence rate of patients during long-term follow-up.
A Novel Copper(II) Indenoisoquinoline Complex Inhibits Topoisomerase I, Induces G2 Phase Arrest, and Autophagy in Three Adenocarcinomas
Authors: Molinaro Caroline , Wambang Nathalie , Bousquet Till , Vercoutter-Edouart Anne-Sophie , Pélinski Lydie , Cailliau Katia , Martoriati Alain
Published: February 2022

Topoisomerases, targets of inhibitors used in chemotherapy, induce DNA breaks accumulation leading to cancer cell death. A newly synthesized copper(II) indenoisoquinoline complex WN197 exhibits a cytotoxic effect below 0.5 µM, on MDA-MB-231, HeLa, and HT-29 cells. At low doses, WN197 inhibits topoisomerase I. At higher doses, it inhibits topoisomerase IIα and IIβ, and displays DNA intercalation properties. DNA damage is detected by the presence of γH2AX. The activation of the DNA Damage Response (DDR) occurs through the phosphorylation of ATM/ATR, Chk1/2 kinases, and the increase of p21, a p53 target. WN197 induces a G2 phase arrest characterized by the unphosphorylated form of histone H3, the accumulation of phosphorylated Cdk1, and an association of Cdc25C with 14.3.3. Cancer cells die by autophagy with Beclin-1 accumulation, LC3-II formation, p62 degradation, and RAPTOR phosphorylation in the mTOR complex. Finally, WN197 by inhibiting topoisomerase I at low concentration with high efficiency is a promising agent for the development of future DNA damaging chemotherapies.
Comprehensive Analysis Identified ASF1B as an Independent Prognostic Factor for HBV-Infected Hepatocellular Carcinoma
Authors: Wang Xianmo , Yi Huawei , Tu Jiancheng , Fan Wen , Wu Jiahao , Wang Li , Li Xiang , Yan Jinrong , Huang Huali , Huang Rong
Published: February 2022

Purpose

Hepatitis B (HBV)-infected hepatocellular carcinoma is one of the most common cancers, and it has high incidence and mortality rates worldwide. The incidence of hepatocellular carcinoma has been increasing in recent years, and existing treatment modalities do not significantly improve prognosis. Therefore, it is important to find a biomarker that can accurately predict prognosis.

Methods

This study was analyzed using the The Cancer Genome Atlas (TCGA) database and validated by the International Cancer Genome Consortium (ICGC) database. The STRING database was used to construct a gene co-expression network and visualize its functional clustering using Cytoscape. A prognostic signature model was constructed to observe high and low risk with prognosis, and independent prognostic factors for HBV-infected hepatocellular carcinoma were identified by Cox regression analysis. The independent prognostic factors were then analyzed for expression and survival, and their pathway enrichment was analyzed using gene set enrichment analysis (GSEA).

Results

805 differentially expressed genes (DEGs) were obtained by differential analysis. Protein–protein interaction (PPI) showed that DEGs were mostly clustered in functional modules, such as cellular matrix response, cell differentiation, and tissue development. Prognostic characterization models showed that the high-risk group was associated with poor prognosis, while Cox regression analysis identified ASF1B as the only independent prognostic factor. As verified by expression and prognosis, ASF1B was highly expressed in HBV-infected hepatocellular carcinoma and led to a poor prognosis. GSEA showed that high ASF1B expression was involved in cell cycle-related signaling pathways.

Conclusion

Bioinformatic analysis identified ASF1B as an independent prognostic factor in HBV-infected hepatocellular carcinoma, and its high expression led to a poor prognosis. Furthermore, it may promote hepatocellular carcinoma progression by affecting cell cycle-related signaling pathways.
ABCC6 Knockdown Fuels Cell Proliferation by Regulating PPARα in Hepatocellular Carcinoma
Authors: Zhao Zhicong , Zhao Zhenjun , Wang Jianye , Zhang He , Xi Zhifeng , Xia Qiang
Published: February 2022

The ATP binding cassette (ABC) transporter family is ubiquitous in eukaryotes, specifically in vertebrates, and plays a crucial role in energy homeostasis, cell signaling, and drug resistance. Accumulating evidence indicates that some ABC transporters contribute to cancer cell proliferation and tumor progression; however, relatively little is known about the behavior of the ABC transporter family in hepatocellular carcinoma (HCC). By analyzing two public transcriptomic databases, we evaluated the effect of genes in the ABC transporter family on HCC prognostic prediction; ABCC6 was selected for further study. Notably, ABCC6 was found to be downregulated in HCC tissues and correlated with favorable outcomes in patients with HCC. Moreover, ABCC6 knockdown not only significantly promoted cell proliferation in vitro and in vivo, but also inhibited cell cycle arrest and cell apoptosis. Transcriptome analysis revealed that ABCC6 depletion enhanced the “mitotic cell cycle” and “DNA replication” pathways, and suppressed the “PPAR signaling pathway”. Further investigation demonstrated that PPARα, one of the key regulators in peroxisome metabolism, is located downstream of ABCC6. In summary, our study provides profound insights into the behavior of ABC transporter family genes in various HCC cohorts, identifies ABCC6 as a biomarker for early-stage HCC diagnosis, and offers experimental basis for further investigations of targeting ABCC6 in the treatment of patients with HCC.
Utility of Clinical–Radiomic Model to Identify Clinically Significant Prostate Cancer in Biparametric MRI PI-RADS V2.1 Category 3 Lesions
Authors: Jin Pengfei , Yang Liqin , Qiao Xiaomeng , Hu Chunhong , Hu Chenhan , Wang Ximing , Bao Jie
Published: February 2022

Purpose

To determine the predictive performance of the integrated model based on clinical factors and radiomic features for the accurate identification of clinically significant prostate cancer (csPCa) among Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions.

Materials and Methods

A retrospective study of 103 patients with PI-RADS 3 lesions who underwent pre-operative 3.0-T MRI was performed. Patients were randomly divided into the training set and the testing set at a ratio of 7:3. Radiomic features were extracted from axial T2WI, diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC) images of each patient. The minimum redundancy maximum relevance (mRMR) and least absolute shrinkage and selection operator (LASSO) feature selection methods were used to identify the radiomic features and construct a radiomic model for csPCa identification. Moreover, multivariable logistic regression analysis was used to integrate the clinical factors with radiomic feature model to further improve the accuracy of csPCa identification, and the two are presented in the form of normogram. The performance of the integrated model was compared with radiomic model and clinical model on testing set.

Results

A total of four radiomic features were selected and used for radiomic model construction producing a radiomic score (Radscore). Radscore was significantly different between the csPCa and the non-csPCa patients (training set: p < 0.001; testing set: p = 0.035). Multivariable logistic regression analysis showed that age and PSA could be used as independent predictors for csPCa identification. The clinical–radiomic model produced the receiver operating characteristic (ROC) curve (AUC) in the testing set was 0.88 (95%CI, 0.75–1.00), which was similar to clinical model (AUC = 0.85; 95%CI, 0.52–0.90) (p = 0.048) and higher than the radiomic model (AUC = 0.71; 95%CI, 0.68–1.00) (p < 0.001). The decision curve analysis implies that the clinical–radiomic model could be beneficial in identifying csPCa among PI-RADS 3 lesions.

Conclusion

The clinical–radiomic model could effectively identify csPCa among biparametric PI-RADS 3 lesions and thus could help avoid unnecessary biopsy and improve the life quality of patients.
Sesquiterpene Lactones Attenuate Paclitaxel Resistance Via Inhibiting MALAT1/STAT3/ FUT4 Axis and P-Glycoprotein Transporters in Lung Cancer Cells
Authors: Ding Yaming , Zhen Zhang , Nisar Muhammad Azhar , Ali Farman , Din Riaz Ud , Khan Muhammad , Mughal Tafail Akbar , Alam Gulzar , Liu Linlin , Saleem Muhammad Zubair
Published: February 2022

Paclitaxel resistance is a challenging factor in chemotherapy resulting in poor prognosis and cancer recurrence. Signal transducer and activator of transcription factor 3 (STAT3), a key transcription factor, performs a critical role in cancer development, cell survival and chemoresistance, while its inactivation overwhelms drug resistance in numerous cancer types including lung cancer. Additionally, the fucosyltransferase 4 (FUT4) is a crucial enzyme in post-translational modification of cell-surface proteins involved in various pathological conditions such as tumor multidrug resistance (MDR). The P-glycoprotein (P-GP) is the well-known ABC transporter member that imparts drug resistance in different cancer types, most notably paclitaxel resistance in lung cancer cells. LncRNA-MALAT1 exerts a functional role in the cancer development as well as the drug resistance and is linked with STAT3 activation and activity of FUT4. Moreover, STAT3-mediated induction of P-GP is well-documented. Natural compounds of Sesquiterpene Lactone (SL) family are well-known for their anticancer properties with particular emphasis over STAT3 inhibitory capabilities. In this study, we explored the positive correlation of MALAT1 with STAT3 and FUT4 activity in paclitaxel resistant A549 (A549/T) lung cancer cells. Additionally, we investigated the anticancer activity of two well-known members of SLs, alantolactone (ALT) and Brevilin A (Brv-A), in A549/T lung cancer cells. ALT and Brv-A induced apoptosis in A549/T cells. Furthermore, these two natural SLs suppressed MALAT1 expression, STAT3 activation, and FUT4 and P-GP expression which are the hallmarks for paclitaxel resistance in A549 lung cancer cells. The inhibition of MALAT1 enhanced the competence of these SLs members significantly, which accounted for the growth inhibition as well as anti-migratory and anti-invasive effects of ALT and Brv-A. These findings suggest SLs to be the promising agents for overcoming paclitaxel resistance in A549 lung cancer cells.
Induction of Heme Oxygenase-1 Modifies the Systemic Immunity and Reduces Atherosclerotic Lesion Development in ApoE Deficient Mice
Authors: Yao Leyi , Hao Yali , Wen Guanmei , Xiao Qingzhong , Wu Penglong , Wang Jinheng , Liu Jinbao
Published: February 2022

Heme oxygenase-1 (HO-1) has been reported to protect against oxidation and inflammation in atherosclerosis. It remains unclear how the immune system participates in the cytoprotective function of HO-1 in the context of atherosclerosis. In this study, we attempted to investigate the potential effect of a HO-1 inducer, hemin, and a HO-1 inhibitor, Tin-protoporphyrin IX (SnPP), on the progression of atherosclerosis in ApoE deficient mice. Using mass cytometry, 15 immune cell populations and 29 T cell sub-clusters in spleen and peripheral blood were thoroughly analyzed after hemin or SnPP treatment. SnPP elevated risk factors of atherosclerosis, whereas hemin reduced them. In-depth analysis showed that hemin significantly modified the immune system in both spleen and peripheral blood. Hemin increased dendritic (DC) and myeloid-derived suppressor cells (MDSCs), but decreased natural killer (NK) cells. An opposite effect was observed with SnPP treatment in terms of NK cells. NK cells and MDSCs were positively and negatively correlated with total cholesterol and low-density lipoprotein, respectively. Moreover, the T cell profiles were significantly reshaped by hemin, whereas only minor changes were observed with SnPP. Several hemin-modulated T cell clusters associated with atherosclerosis were also identified. In summary, we have unraveled an important regulatory role for HO-1 pathway in immune cell regulation and atherosclerosis. Our finding suggests that modulating HO-1 signaling represents a potential therapeutic strategy against atherosclerosis.
Transcriptomic Analysis Reveal the Molecular Mechanisms of Seed Coat Development in Cucurbita pepo L.
Authors: Xue Yingyu , Shen Zhiyan , Tao Fei , Zhou Jingjiang , Xu Bingliang
Published: February 2022

Cucurbita pepo is one of the earliest cultivated crops. It is native to Central and South America and is now widely cultivated all over the world for its rich nutrition, short growth period, and high yield, which make it suitable for intercropping. Hull-less C. pepo L. (HLCP) is a rare variant in nature that is easier to consume. Its seed has a seed kernel but lacks a seed coat. The molecular mechanism underlying the lack of seed coat development in the HLCP variety is not clear yet. The BGISEQ-500 sequencing platform was used to sequence 18 cDNA libraries of seed coats from hulled C. pepo (CP) and HLCP at three developmental stages (8, 18, and 28 days) post-pollination. We found that lignin accumulation in the seed coat of the HLCP variety was much lower than that of the CP variety. A total of 2,099 DEGs were identified in the CP variety, which were enriched mainly in the phenylpropanoid biosynthesis pathway, amino sugar, and nucleotide sugar metabolism pathways. A total of 1,831 DEGs were identified in the HLCP variety and found to be enriched mainly in the phenylpropanoid biosynthesis and metabolism pathways of starch and sucrose. Among the DEGs, hub proteins (FusA), protein kinases (IRAK4), and several transcription factors related to seed coat development (MYB, bHLH, NAC, AP2/EREBP, WRKY) were upregulated in the CP variety. The relative expression levels of 12 randomly selected DEGs were determined using quantitative real-time PCR analysis and found to be consistent with those obtained using RNA-Seq, with a correlation coefficient of 0.9474. We found that IRAK4 protein kinases, AP2/EREBP, MYB, bHLH, and NAC transcription factors may play important roles in seed coat development, leading to the formation of HLCP.
Analysis of Morphological Traits, Cannabinoid Profiles, THCAS Gene Sequences, and Photosynthesis in Wide and Narrow Leaflet High-Cannabidiol Breeding Populations of Medical Cannabis
Authors: Murovec Jana , Eržen Jan Jurij , Flajšman Marko , Vodnik Dominik
Published: February 2022

Cannabis sativa L. is one of the oldest cultivated crops, used in medicine for millennia due to therapeutic characteristics of the phytocannabinoids it contains. Its medicinal properties are highly influenced by the chemotype, that is, the ratio of the two main cannabinoids cannabidiol (CBD) and Δ-9-tetrahydrocannabinol (THC). Based on published data, the chemotype should correlate with plant morphology, genetics, and photosynthetic properties. In this work, we investigated leaf morphology, plant growth characteristics, cannabinoid profiles, THCAS gene sequences, and plant photosynthetic traits in two breeding populations of medical cannabis (MX-CBD-11 and MX-CBD-707). The populations differed significantly in morphological traits. The MX-CBD-11 plants were taller, less branched, and their leaves had narrower leaflets than the bushier, wideleaved MX-CBD-707 plants, and there were significant differences between populations in the dry biomass of different plant parts. Based on these morphological differences, MX-CBD-11 was designated as a narrow leaflet drug type or vernacular “Sativa” type, while MX-CBD-707 was classified as wide leaflet drug type or “Indica” type. Chemical characterisation revealed a discrepancy between the expected chemotypes based on plant morphology; although both populations have high CBD, within each Type II (CBD/THC intermediate) and Type III (CBD dominant) plants were detected. The THCAS gene sequence analysis clustered the plants based on their chemotypes and showed high similarity to the THCAS sequences deposited in NCBI. In silico complementary analysis, using published molecular markers for chemotype determination, showed their low discrimination power in our two populations, demonstrating the genotype dependence of the molecular markers. Basic photosynthetic traits derived from light and CO2 response curves were similar in the populations. However, measurements of gas exchange under chamber conditions revealed higher stomatal conductivity and photosynthesis in MX-CBD-707 plants, which were also characterised by higher day respiration. The results of this study showed that based on visual appearance and some morphological measurements, it is not possible to determine a plant’s chemotype. Visually homogenous plants had different cannabinoid profiles and, vice versa, morphologically distinct plants contained similar CBD and THC content. The two chemotypes identified in our experimental plants therefore did not correlate with plant visual appearance, leaf morphometry, and photosynthetic properties of the populations studied. Correlation was only demonstrated with the respect to THCAS sequences, which showed great discrimination power between the chemotypes.
Genome-Wide Association and Genomic Prediction for Stripe Rust Resistance in Synthetic-Derived Wheats
Authors: Mahmood Zahid , Ali Mohsin , Mirza Javed Iqbal , Fayyaz Muhammad , Majeed Khawar , Naeem Muhammad Kashif , Aziz Abdul , Trethowan Richard , Ogbonnaya Francis Chuks , Poland Jesse , Quraishi Umar Masood , Hickey Lee Thomas , Rasheed Awais , He Zhonghu
Published: February 2022

Stripe rust caused by Puccnina striiformis (Pst) is an economically important disease attacking wheat all over the world. Identifying and deploying new genes for Pst resistance is an economical and long-term strategy for controlling Pst. A genome-wide association study (GWAS) using single nucleotide polymorphisms (SNPs) and functional haplotypes were used to identify loci associated with stripe rust resistance in synthetic-derived (SYN-DER) wheats in four environments. In total, 92 quantitative trait nucleotides (QTNs) distributed over 65 different loci were associated with resistance to Pst at seedling and adult plant stages. Nine additional loci were discovered by the linkage disequilibrium-based haplotype-GWAS approach. The durable rust-resistant gene Lr34/Yr18 provided resistance in all four environments, and against all the five Pst races used in this study. The analysis identified several SYN-DER accessions that carried major genes: either Yr24/Yr26 or Yr32. New loci were also identified on chr2B, chr5B, and chr7D, and 14 QTNs and three haplotypes identified on the D-genome possibly carry new alleles of the known genes contributed by the Ae. tauschii founders. We also evaluated eleven different models for genomic prediction of Pst resistance, and a prediction accuracy up to 0.85 was achieved for an adult plant resistance, however, genomic prediction for seedling resistance remained very low. A meta-analysis based on a large number of existing GWAS would enhance the identification of new genes and loci for stripe rust resistance in wheat. The genetic framework elucidated here for stripe rust resistance in SYN-DER identified the novel loci for resistance to Pst assembled in adapted genetic backgrounds.
Transcriptomic Analysis Revealed Reactive Oxygen Species Scavenging Mechanisms Associated With Ferrous Iron Toxicity in Aromatic Keteki Joha Rice
Authors: Regon Preetom , Dey Sangita , Rehman Mehzabin , Pradhan Amit Kumar , Chowra Umakanta , Tanti Bhaben , Talukdar Anupam Das , Panda Sanjib Kumar
Published: February 2022

Lowland acidic soils with water-logged regions are often affected by ferrous iron (Fe2+) toxicity, a major yield-limiting factor of rice production. Under severe Fe2+ toxicity, reactive oxygen species (ROS) are crucial, although molecular mechanisms and associated ROS homeostasis genes are still unknown. In this study, a comparative RNA-Seq based transcriptome analysis was conducted to understand the Fe2+ toxicity tolerance mechanism in aromatic Keteki Joha. About 69 Fe homeostasis related genes and their homologs were identified, where most of the genes were downregulated. Under severe Fe2+ toxicity, the biosynthesis of amino acids, RNA degradation, and glutathione metabolism were induced, whereas phenylpropanoid biosynthesis, photosynthesis, and fatty acid elongation were inhibited. The mitochondrial iron transporter (OsMIT), vacuolar iron transporter 2 (OsVIT2), ferritin (OsFER), vacuolar mugineic acid transporter (OsVMT), phenolic efflux zero1 (OsPEZ1), root meander curling (OsRMC), and nicotianamine synthase (OsNAS3) were upregulated in different tissues, suggesting the importance of Fe retention and sequestration for detoxification. However, several antioxidants, ROS scavenging genes and abiotic stress-responsive transcription factors indicate ROS homeostasis as one of the most important defense mechanisms under severe Fe2+ toxicity. Catalase (CAT), glutathione (GSH), ascorbate peroxidase (APX), monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), and glutathione reductase (GR) were upregulated. Moreover, abiotic stress-responsive transcription factors, no apical meristem (NAC), myeloblastosis (MYB), auxin response factor (ARF), basic helix-loop-helix (bZIP), WRKY, and C2H2-zinc finger protein (C2H2-ZFP) were also upregulated. Accordingly, ROS homeostasis has been proposed as an essential defense mechanism under such conditions. Thus, the current study may enrich the understanding of Fe-homeostasis in rice.
Transcriptional Landscape of Cotton Fiber Development and Its Alliance With Fiber-Associated Traits
Authors: Prasad Priti , Khatoon Uzma , Verma Rishi Kumar , Aalam Shahre , Kumar Ajay , Mohapatra Debashish , Bhattacharya Parthasarthi , Bag Sumit K. , Sawant Samir V.
Published: February 2022

Cotton fiber development is still an intriguing question to understand fiber commitment and development. At different fiber developmental stages, many genes change their expression pattern and have a pivotal role in fiber quality and yield. Recently, numerous studies have been conducted for transcriptional regulation of fiber, and raw data were deposited to the public repository for comprehensive integrative analysis. Here, we remapped > 380 cotton RNAseq data with uniform mapping strategies that span ∼400 fold coverage to the genome. We identified stage-specific features related to fiber cell commitment, initiation, elongation, and Secondary Cell Wall (SCW) synthesis and their putative cis-regulatory elements for the specific regulation in fiber development. We also mined Exclusively Expressed Transcripts (EETs) that were positively selected during cotton fiber evolution and domestication. Furthermore, the expression of EETs was validated in 100 cotton genotypes through the nCounter assay and correlated with different fiber-related traits. Thus, our data mining study reveals several important features related to cotton fiber development and improvement, which were consolidated in the “CottonExpress-omics” database.
Landscape Genomics in Tree Conservation Under a Changing Environment
Authors: Feng Li , Du Fang K.
Published: February 2022

Understanding the genetic basis of how species respond to changing environments is essential to the conservation of species. However, the molecular mechanisms of adaptation remain largely unknown for long-lived tree species which always have large population sizes, long generation time, and extensive gene flow. Recent advances in landscape genomics can reveal the signals of adaptive selection linking genetic variations and landscape characteristics and therefore have created novel insights into tree conservation strategies. In this review article, we first summarized the methods of landscape genomics used in tree conservation and elucidated the advantages and disadvantages of these methods. We then highlighted the newly developed method “Risk of Non-adaptedness,” which can predict the genetic offset or genomic vulnerability of species via allele frequency change under multiple scenarios of climate change. Finally, we provided prospects concerning how our introduced approaches of landscape genomics can assist policymaking and improve the existing conservation strategies for tree species under the ongoing global changes.
Rehydration Compensation of Winter Wheat Is Mediated by Hormone Metabolism and De-Peroxidative Activities Under Field Conditions
Authors: Liu Xuejing , Wang Xiaodong , Liu Pan , Bao Xiaoyuan , Hou Xiaoyang , Yang Mingming , Zhen Wenchao
Published: February 2022

Water deficit and rehydration frequently occur during wheat cultivation. Previous investigations focused on the water deficit and many drought-responsive genes have been identified in winter wheat. However, the hormone-related metabolic responses and de-peroxidative activities associated with rehydration are largely unknown. In this study, leaves of two winter wheat cultivars, “Hengguan35” (HG, drought-tolerant cultivar) and “Shinong086” (SN, drought-sensitive cultivar), were used to investigate water deficit and the post-rehydration process. Rehydration significantly promoted wheat growth and postponed spike development. Quantifications of antioxidant enzymes, osmotic stress-related substances, and phytohormones revealed that rehydration alleviated the peroxidation and osmotic stress caused by water deficit in both cultivars. The wheat cultivar HG showed a better rehydration-compensation phenotype than SN. Phytohormones, including abscisic acid, gibberellin (GA), jasmonic acid (JA), and salicylic acid (SA), were detected using high-performance liquid chromatography and shown to be responsible for the rehydration process. A transcriptome analysis showed that differentially expressed genes related to rehydration were enriched in hormone metabolism- and de-peroxidative stress-related pathways. Suppression of genes associated with abscisic acid signaling transduction were much stronger in HG than in SN upon rehydration treatment. HG also kept a more balanced expression of genes involved in reactive oxygen species pathway than SN. In conclusion, we clarified the hormonal changes and transcriptional profiles of drought-resistant and -sensitive winter wheat cultivars in response to drought and rehydration, and we provided insights into the molecular processes involved in rehydration compensation.
Comprehensive Time-Course Transcriptome and Co-expression Network Analyses Identify Salt Stress Responding Mechanisms in Chlamydomonas reinhardtii Strain GY-D55
Authors: Zhang Luo-Yan , Xing Zhao-Tian , Chen Li-Qian , Zhang Xue-Jie , Fan Shou-Jin
Published: February 2022

It is highly necessary to understand the molecular mechanism underlying the salt stress response in green algae, which may contribute to finding the evolutionary cues of abiotic stress response in plants. Here, we reported a comprehensive temporal investigation of transcriptomes using data at eight different time points, from an early stage (2 h) to a late stage (up to 96 h) in Chlamydomonas reinhardtii GY-D55 cells. The principal component analysis (PCA) of transcriptome profiles showed that the samples of the early and late stages were well separated. A total of 12,445 genes were detected as differentially expressed genes. There were 1,861/2,270 common upregulated/downregulated genes for each time point compared with control samples. Samples treated with salt for 2, 8, and 24 h had a relatively large number of characteristic upregulated/downregulated genes. The functional enrichment analysis highlighted the timing of candidate regulatory mechanisms for salt stress responses in GY-D55 cells. Short time exposure to salt stress impaired oxidation-reduction, protein synthesis and modification, and photosynthesis. The algal cells promoted transcriptional regulation and protein folding to deal with protein synthesis/modification impairments and rapidly accumulated glycerol in the early stage (2–4 h) to cope with osmotic stress. At 12 and 24 h, GY-D55 cells showed increased expressions of signaling and photosynthetic genes to deal with the damage of photosynthesis. The co-expression module blue was predicted to regulate endoplasmic reticulum (ER) stress at early time points. In addition, we identified a total of 113 transcription factors (TFs) and predicted the potential roles of Alfin, C2C2, and the MYB family TFs in algal salt stress response.
High-Throughput Sequencing-Based Analysis of Rhizosphere and Diazotrophic Bacterial Diversity Among Wild Progenitor and Closely Related Species of Sugarcane (Saccharum spp. Inter-Specific Hybrids)
Authors: Malviya Mukesh Kumar , Li Chang-Ning , Lakshmanan Prakash , Solanki Manoj Kumar , Wang Zhen , Solanki Anjali Chandrol , Nong Qian , Verma Krishan K. , Singh Rajesh Kumar , Singh Pratiksha , Sharma Anjney , Guo Dao-Jun , Dessoky Eldessoky S. , Song Xiu-Peng , Li Yang-Rui
Published: February 2022

Considering the significant role of genetic background in plant-microbe interactions and that most crop rhizospheric microbial research was focused on cultivars, understanding the diversity of root-associated microbiomes in wild progenitors and closely related crossable species may help to breed better cultivars. This study is aimed to fill a critical knowledge gap on rhizosphere and diazotroph bacterial diversity in the wild progenitors of sugarcane, the essential sugar and the second largest bioenergy crop globally. Using a high-throughput sequencing (HTS) platform, we studied the rhizosphere and diazotroph bacterial community ofSaccharum officinarumL. cv. Badila (BRS),Saccharum barberi(S.barberi) Jesw. cv Pansahi (PRS),Saccharum robustum[S. robustum;(RRS),Saccharum spontaneum(S. spontaneum); SRS], andSaccharum sinense(S. sinense) Roxb. cv Uba (URS) by sequencing their 16S rRNA andnifHgenes. HTS results revealed that a total of 6,202 bacteria-specific operational taxonomic units (OTUs) were identified, that were distributed as 107 bacterial groups. Out of that, 31 rhizobacterial families are commonly spread in all five species. With respect tonifHgene,S.barberiandS. spontaneumrecorded the highest and lowest number of OTUs, respectively. These results were validated by quantitative PCR analysis of both genes. A total of 1,099 OTUs were identified for diazotrophs with a core microbiome of 9 families distributed among all the sugarcane species. The core microbiomes were spread across 20 genera. The increased microbial diversity in the rhizosphere was mainly due to soil physiochemical properties. Most of the genera of rhizobacteria and diazotrophs showed a positive correlation, and few genera negatively correlated with the soil properties. The results showed that sizeable rhizospheric diversity exists across progenitors and close relatives. Still, incidentally, the rhizosphere microbial abundance of progenitors of modern sugarcane was at the lower end of the spectrum, indicating the prospect ofSaccharumspecies introgression breeding may further improve nutrient use and disease and stress tolerance of commercial sugarcane. The considerable variation for rhizosphere microbiome seen inSaccharumspecies also provides a knowledge base and an experimental system for studying the evolution of rhizobacteria-host plant association during crop domestication.
An Evaluation of Nuclei Preparation of the Dormant Axillary Bud of Grapevine for Cell Cycle Analysis by Flow Cytometry
Authors: Hermawaty Dina , Considine John A. , Considine Michael J.
Published: February 2022

Whether the division of cells of a dormant meristem may be arrested, e.g., in the G1 phase, has proven to be an extremely difficult hypothesis to test. This is particularly so for woody perennial buds, where dormant and quiescent states are diffuse, and the organ may remain visibly unchanged for 6–9 months of the year. Flow cytometry (FCM) has been widely applied in plant studies to determine the genome size and endopolyploidy. In this study, we present the application of FCM to measure the cell cycle status in mature dormant buds of grapevine (Vitis vinifera cv. Cabernet Sauvignon), which represent a technically recalcitrant structure. This protocol illustrates the optimisation and validation of FCM data analysis to calculate the cell cycle status, or mitotic index, of dormant grapevine buds. We have shown how contamination with debris can be experimentally managed and give reference to the more malleable tomato leaves. We have also given a clear illustration of the primary pitfalls of data analysis to avoid artefacts or false results. Data acquisition and analysis strategies are detailed and can be readily applied to analyse FCM data from other recalcitrant plant samples.
Self-Report Measures of Procrastination Exhibit Inconsistent Concurrent Validity, Predictive Validity, and Psychometric Properties
Authors: Vangsness Lisa , Voss Nathaniel M. , Maddox Noelle , Devereaux Victoria , Martin Emma
Published: February 2022

Procrastination is a chronic and widespread problem; however, emerging work raises questions regarding the strength of the relationship between self-reported procrastination and behavioral measures of task engagement. This study assessed the internal reliability, concurrent validity, predictive validity, and psychometric properties of 10 self-report procrastination assessments using responses collected from 242 students. Participants’ scores on each self-report instrument were compared to each other using correlations and cluster analysis. Lasso estimation was used to test the self-report scores’ ability to predict two behavioral measures of delay (days to study completion; pacing style). The self-report instruments exhibited strong internal reliability and moderate levels of concurrent validity. Some self-report measures were predictive of days to study completion. No self-report measures were predictive of deadline action pacing, the pacing style most commonly associated with procrastination. Many of the self-report measures of procrastination exhibited poor fit. These results suggest that researchers should exercise caution in selecting self-report measures and that further study is necessary to determine the factors that drive misalignment between self-reports and behavioral measures of delay.
More Thumbs Than Rules: Is Rationality an Exaptation?
Authors: Mastrogiorgio Antonio , Felin Teppo , Kauffman Stuart , Mastrogiorgio Mariano
Published: February 2022

The literatures on bounded and ecological rationality are built on adaptationism—and its associated modular, cognitivist and computational paradigm—that does not address or explain the evolutionary origins of rationality. We argue that the adaptive mechanisms of evolution are not sufficient for explaining human rationality, and we posit that human rationality presents exaptive origins, where exaptations are traits evolved for other functions or no function at all, and later co-opted for new uses. We propose an embodied reconceptualization of rationality—embodied rationality—based on the reuse of the perception-action system, where many neural processes involved in the control of the sensory-motor system, salient in ancestral environments have been later co-opted to create—by tinkering—high-level reasoning processes, employed in civilized niches.