bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuronal Cells Display Distinct Stability Controls of Alternative Polyadenylation mRNA Isoforms, Long Non-Coding RNAs, and Mitochondrial RNAs
Authors: Guvenek Aysegul , Shin Jihae , De Filippis Lidia , Zheng Dinghai , Wang Wei , Pang Zhiping P. , Tian Bin 
Published: May 2022

RNA stability plays an important role in gene expression. Here, using 3′ end sequencing of newly made and pre-existing poly(A)+ RNAs, we compare transcript stability in multiple human cell lines, including HEK293T, HepG2, and SH-SY5Y. We show that while mRNA stability is generally conserved across the cell lines, specific transcripts having a high GC content and possibly more stable secondary RNA structures are relatively more stable in SH-SY5Y cells compared to the other 2 cell lines. These features also differentiate stability levels of alternative polyadenylation (APA) 3′UTR isoforms in a cell type-specific manner. Using differentiation of a neural stem cell line as a model, we show that mRNA stability difference could contribute to gene expression changes in neurogenesis and confirm the neuronal identity of SH-SY5Y cells at both gene expression and APA levels. In addition, compared to transcripts using 3′-most exon cleavage/polyadenylation sites (PASs), those using intronic PASs are generally less stable, especially when the PAS-containing intron is large and has a strong 5′ splice site, suggesting that intronic polyadenylation mostly plays a negative role in gene expression. Interestingly, the differential mRNA stability among APA isoforms appears to buffer PAS choice in these cell lines. Moreover, we found that several other poly(A)+ RNA species, including promoter-associated long noncoding RNAs and transcripts encoded by the mitochondrial genome, are more stable in SH-SY5Y cells than the other 2 cell lines, further highlighting distinct RNA metabolism in neuronal cells. Together, our results indicate that distinct RNA stability control in neuronal cells may contribute to the gene expression and APA programs that define their cell identity.
Identification of mRNA Signature for Predicting Prognosis Risk of Rectal Adenocarcinoma
Authors: Jiang Linlin , Wang Peng , Su Mu , Yang Lili , Wang Qingbo 
Published: May 2022

Background: The immune system plays a crucial role in rectal adenocarcinoma (READ). Immune-related genes may help predict READ prognoses.Methods: The Cancer Genome Atlas dataset and GSE56699 were used as the training and validation datasets, respectively, and differentially expressed genes (DEGs) were identified. The optimal DEG combination was determined, and the prognostic risk model was constructed. The correlation between optimal DEGs and immune infiltrating cells was evaluated.Results: Nine DEGs were selected for analysis. Moreover, ADAMDEC1 showed a positive correlation with six immune infiltrates, most notably with B cells and dendritic cells. F13A1 was also positively correlated with six immune infiltrates, particularly macrophage and dendritic cells, whereas LGALS9C was negatively correlated with all immune infiltrates except B cells. Additionally, the prognostic risk model was strongly correlated with the actual situation. We retained only three prognosis risk factors: age, pathologic stage, and prognostic risk model. The stratified analysis revealed that lower ages and pathologic stages have a better prognosis with READ. Age and mRNA prognostic factors were the most important factors in determining the possibility of 3- and 5-year survival.Conclusion: In summary, we identified a nine-gene prognosis risk model that is applicable to the treatment of READ. Altogether, characteristics such as the gene signature and age have a strong predictive value for prognosis risk.
Experimental Investigation on Isothermal Sections at 1273 and 1473 K in the Co–Ti–W System
Authors: Shi Yu , Guo Cuiping , Li Changrong , Du Zhenmin , Hu Die 
Published: May 2022

The microstructures of 25 annealed alloys and XRD patterns of partial critical alloys in the Co–Ti–W system were investigated by using scanning electron microscopy (SEM) with energy dispersive spectrometer (EDS) and X-ray diffraction (XRD) methods. The isothermal sections at 1273 and 1473 K of the Co–Ti–W system were established. Five three-phase regions and five two-phase regions at 1273 K and eight three-phase regions and two two-phase regions at 1473 K were experimentally determined. The maximum solubilities of W in Co3Ti, αCo2Ti, βCo2Ti and CoTi were determined to be ∼7.9 at%, ∼1.5 at.%, ∼5.9 at.% and ∼1.8 at.% at 1273 K, respectively. The maximum solubilities of Ti in Co7W6 and Co3W were determined to be ∼11.9 at.% and ∼15.2 at.% at 1273 K, respectively. The compound Co3Ti with L12 crystal structure was found to be stable at 1473 K in the Co–Ti–W system owing to the addition of W element, which confirmed that W can improve the stability of γ′ with L12 crystal structure in the Co-based superalloys. The composition range of W in Co3Ti was measured to be ∼7.4–10.4 at.% at 1473 K. In addition, the maximum solubilities of Ti in Co7W6 and W in βCo2Ti and CoTi were ∼15.4 at.%, ∼7.6 at.% and ∼3.1 at.% at 1473 K, respectively. No ternary compounds were found in the Co–Ti–W system at 1273 and 1473 K.
Differentiating Slowly Progressive Subtype of Lower Limb Onset ALS From Typical ALS Depends on the Time of Disease Progression and Phenotype
Authors: Zhang Huagang , Chen Lu , Tian Jinzhou , Fan Dongsheng 
Published: May 2022

BackgroundFlail leg syndrome (FLS) is a regional variant of amyotrophic lateral sclerosis (ALS) with the characteristics of slow progression and the symptoms confined to the lumbosacral region for extended periods. However, FLS may not be easily differentiated from typical ALS.ObjectiveThe objective of the study was to determine a cutoff time of disease progression that could differentiate FLS from the typical lower limb onset ALS.MethodsA cutoff point analysis was performed with maximally selected log–rank statistics in patients with lower limb onset ALS registered from 2009 to 2013. Based on the cutoff duration from the lower limb onset to second region significantly involved (SRSI), all patients were divided into the slowly progressive subtype of lower limb onset ALS group and the typical lower limb-onset ALS group. Patients with the slowly progressive subtype of the lower limb onset ALS, who had the flail leg phenotype, were classified as patients with FLS. Differences between groups were analyzed.ResultsAmong the 196 patients recruited, 157 patients with a duration &lt;14 months from lower limb onset to SRSI were classified as having typical lower limb onset ALS. Twenty-nine patients with a duration more than or equal to 14 months and the flail leg phenotype were classified as having FLS. Patients with FLS exhibited a median diagnostic delay of 25 months, a median duration of 24 months from lower limb onset to SRSI, a forced vital capacity abnormity rate of 12.5% at the first visit to our department, and a median survival time of 80 months, which were significantly different from those of patients with typical lower limb onset ALS (p &lt; 0.001, p &lt; 0.001, p = 0.024, p &lt; 0.001). The 5-year survival rate of the FLS group (79.3%) was much higher than that of the other group (1.9%).ConclusionsA crucial feature in differentiating FLS from typical lower limb onset ALS in Chinese patients may be symptoms confined to the lumbosacral region for at least 14 months, which may be better than 12 or 24 months used in the previous studies. The FLS was characterized by slower progression, less and later respiratory dysfunction, and a more benign prognosis than the typical lower limb onset ALS.
Intestinal Barrier Dysfunction in the Absence of Systemic Inflammation Fails to Exacerbate Motor Dysfunction and Brain Pathology in a Mouse Model of Parkinson's Disease
Authors: Jackson Aeja , Engen Phillip A. , Forsyth Christopher B. , Shaikh Maliha , Naqib Ankur , Wilber Sherry , Frausto Dulce M. , Raeisi Shohreh , Green Stefan J. , Bradaric Brinda Desai , Persons Amanda L. , Voigt Robin M. , Keshavarzian Ali 
Published: May 2022

IntroductionParkinson's disease (PD) is the second most common neurodegenerative disease associated with aging. PD patients have systemic and neuroinflammation which is hypothesized to contribute to neurodegeneration. Recent studies highlight the importance of the gut-brain axis in PD pathogenesis and suggest that gut-derived inflammation can trigger and/or promote neuroinflammation and neurodegeneration in PD. However, it is not clear whether microbiota dysbiosis, intestinal barrier dysfunction, or intestinal inflammation (common features in PD patients) are primary drivers of disrupted gut-brain axis in PD that promote neuroinflammation and neurodegeneration.ObjectiveTo determine the role of microbiota dysbiosis, intestinal barrier dysfunction, and colonic inflammation in neuroinflammation and neurodegeneration in a genetic rodent model of PD [α-synuclein overexpressing (ASO) mice].MethodsTo distinguish the role of intestinal barrier dysfunction separate from inflammation, low dose (1%) dextran sodium sulfate (DSS) was administered in cycles for 52 days to ASO and control mice. The outcomes assessed included intestinal barrier integrity, intestinal inflammation, stool microbiome community, systemic inflammation, motor function, microglial activation, and dopaminergic neurons.ResultsLow dose DSS treatment caused intestinal barrier dysfunction (sugar test, histological analysis), intestinal microbiota dysbiosis, mild intestinal inflammation (colon shortening, elevated MPO), but it did not increase systemic inflammation (serum cytokines). However, DSS did not exacerbate motor dysfunction, neuroinflammation (microglial activation), or dopaminergic neuron loss in ASO mice.ConclusionDisruption of the intestinal barrier without overt intestinal inflammation is not associated with worsening of PD-like behavior and pathology in ASO mice.
Prognostic Significance of the Stage at Which an MRD-Negative Status Is Achieved for Patients With Multiple Myeloma Who Received ASCT
Authors: Sun Qian , Li Xiaozhe , Gu Jingli , Huang Beihui , Liu Junru , Chen Meilan , Li Juan 
Published: May 2022

ObjectiveTo explore the prognostic significance of the stage at which a minimal residual disease (MRD)-negative status is achieved for patients with newly diagnosed multiple myeloma (NDMM) who received autologous hematopoietic stem cell transplantation (ASCT).Cases and MethodsA retrospective analysis of 186 NDMM patients who received “induction therapy-ASCT-maintenance therapy” in our center and achieved an MRD-negative status was performed. Patients were divided into three groups, A (induction therapy), B (3 months after ASCT), and C (maintenance therapy), according to the stage at which an MRD-negative status was achieved.ResultsThe median time to progression (TTP) of 186 patients was not reached; the median overall survival (OS) was 113.8 months. The median TTP of the patients in three groups was not reached (P=0.013), and the median OS of the patients in three groups was not reached, not reached, and 71.2 months, respectively (P=0.026). Among patients with standard-risk cytogenetics, the median TTP of those in all three groups was not reached (P=0.121), and the median OS of the patients in three groups was not reached, not reached, and 99.6 months, respectively (P=0.091). Among patients with high-risk cytogenetics, the median TTP of those in three groups was not reached, 53.9 months, and 35.8 months (P=0.060), and the median OS was not reached, 71.2 months, and 60.2 months, respectively (P=0.625). Among patients with R-ISS stage I-II, the median TTP of those in three groups was not reached (P=0.174), and the median OS of the patients in three groups was not reached, not reached, and 99.6 months, respectively (P=0.186). Among the 29 patients with R-ISS stage III, the median TTP of those in the 3 groups were unreached, unreached, and 35.1 months (P&lt;0.001), and the median OS was unreached, unreached, and 48.5 months, respectively (P=0.020). In all enrolled patients, the stage of reaching MRD-negative was an independent prognostic factor for TTP, rather than a prognostic factor for OS. The stage of reaching MRD-negative in patients with R-ISS III was an independent prognostic factor for OS.ConclusionFor the same patients who are MRD-negative, the prognoses of those who achieve an MRD-negative status at different groups are different. The stage at which an MRD-negative status is achieved can predict the prognosis of patients with R-ISS stage III.
Prospective Medicinal Plants and Their Phytochemicals Shielding Autoimmune and Cancer Patients Against the SARS-CoV-2 Pandemic: A Special Focus on Matcha
Authors: Kiriacos Caroline Joseph , Khedr Monika Rafik , Tadros Miray , Youness Rana A. 
Published: May 2022

BackgroundBeing “positive” has been one of the most frustrating words anyone could hear since the end of 2019. This word had been overused globally due to the high infectious nature of SARS-CoV-2. All citizens are at risk of being infected with SARS-CoV-2, but a red warning sign has been directed towards cancer and immune-compromised patients in particular. These groups of patients are not only more prone to catch the virus but also more predisposed to its deadly consequences, something that urged the research community to seek other effective and safe solutions that could be used as a protective measurement for cancer and autoimmune patients during the pandemic.AimThe authors aimed to turn the spotlight on specific herbal remedies that showed potential anticancer activity, immuno-modulatory roles, and promising anti-SARS-CoV-2 actions.MethodologyTo attain the purpose of the review, the research was conducted at the States National Library of Medicine (PubMed). To search databases, the descriptors used were as follows: “COVID-19”/”SARS-CoV-2”, “Herbal Drugs”, “Autoimmune diseases”, “Rheumatoid Arthritis”, “Asthma”, “Multiple Sclerosis”, “Systemic Lupus Erythematosus” “Nutraceuticals”, “Matcha”, “EGCG”, “Quercetin”, “Cancer”, and key molecular pathways.ResultsThis manuscript reviewed most of the herbal drugs that showed a triple action concerning anticancer, immunomodulation, and anti-SARS-CoV-2 activities. Special attention was directed towards “matcha” as a novel potential protective and therapeutic agent for cancer and immunocompromised patients during the SARS-CoV-2 pandemic.ConclusionThis review sheds light on the pivotal role of “matcha” as a tri-acting herbal tea having a potent antitumorigenic effect, immunomodulatory role, and proven anti-SARS-CoV-2 activity, thus providing a powerful shield for high-risk patients such as cancer and autoimmune patients during the pandemic.
Deep Learning for Per-Fraction Automatic Segmentation of Gross Tumor Volume (GTV) and Organs at Risk (OARs) in Adaptive Radiotherapy of Cervical Cancer
Authors: Breto Adrian L. , Spieler Benjamin , Zavala-Romero Olmo , Alhusseini Mohammad , Patel Nirav V. , Asher David A. , Xu Isaac R. , Baikovitz Jacqueline B. , Mellon Eric A. , Ford John C. , Stoyanova Radka , Portelance Lorraine 
Published: May 2022

Background/HypothesisMRI-guided online adaptive radiotherapy (MRI-g-OART) improves target coverage and organs-at-risk (OARs) sparing in radiation therapy (RT). For patients with locally advanced cervical cancer (LACC) undergoing RT, changes in bladder and rectal filling contribute to large inter-fraction target volume motion. We hypothesized that deep learning (DL) convolutional neural networks (CNN) can be trained to accurately segment gross tumor volume (GTV) and OARs both in planning and daily fractions’ MRI scans.Materials/MethodsWe utilized planning and daily treatment fraction setup (RT-Fr) MRIs from LACC patients, treated with stereotactic body RT to a dose of 45-54 Gy in 25 fractions. Nine structures were manually contoured. MASK R-CNN network was trained and tested under three scenarios: (i) Leave-one-out (LOO), using the planning images of N- 1 patients for training; (ii) the same network, tested on the RT-Fr MRIs of the “left-out” patient, (iii) including the planning MRI of the “left-out” patient as an additional training sample, and tested on RT-Fr MRIs. The network performance was evaluated using the Dice Similarity Coefficient (DSC) and Hausdorff distances. The association between the structures’ volume and corresponding DSCs was investigated using Pearson’s Correlation Coefficient, r.ResultsMRIs from fifteen LACC patients were analyzed. In the LOO scenario the DSC for Rectum, Femur, and Bladder was &gt;0.8, followed by the GTV, Uterus, Mesorectum and Parametrium (0.6-0.7). The results for Vagina and Sigmoid were suboptimal. The performance of the network was similar for most organs when tested on RT-Fr MRI. Including the planning MRI in the training did not improve the segmentation of the RT-Fr MRI. There was a significant correlation between the average organ volume and the corresponding DSC (r = 0.759, p = 0.018).ConclusionWe have established a robust workflow for training MASK R-CNN to automatically segment GTV and OARs in MRI-g-OART of LACC. Albeit the small number of patients in this pilot project, the network was trained to successfully identify several structures while challenges remain, especially in relatively small organs. With the increase of the LACC cases, the performance of the network will improve. A robust auto-contouring tool would improve workflow efficiency and patient tolerance of the OART process.
Solasonine Causes Redox Imbalance and Mitochondrial Oxidative Stress of Ferroptosis in Lung Adenocarcinoma
Authors: Zeng Yao-Ying , Luo Ying-Bin , Ju Xu-Dong , Zhang Bo , Cui Ya-Jing , Pan Yan-Bin , Tian Jian-Hui , Teng Wen-Jing , Wu Jianchun , Li Yan 
Published: May 2022

Ferroptosis, a type of iron-dependent oxidative cell death caused by excessive lipid peroxidation, is emerging as a promising cancer therapeutic strategy. Solasonine has been reported as a potential compound in tumor suppression, which is closely linked to ferroptosis. However, ferroptosis caused by solasonine is insufficiently identified and elaborated in lung adenocarcinoma, a fatal disease with high morbidity and mortality rates. First, the biochemical and morphological changes in Calu-1 and A549 cells exposed to solasonine are observed using a cell death assay and a microscope. The cell viability assay is performed after determining the executive concentration of solasonine to assess the effects of solasonine on tumor growth in Calu-1 and A549 cells. The ferroptosis is then identified by using ferroptosis-related reagents on CCK-8, lipid peroxidation assessment, Fe2+, and ROS detection. Furthermore, the antioxidant system, which includes GSH, Cys, GPx4, SLC7A11, and mitochondrial function, is measured to identify the potential pathways. According to the results, solasonine precisely exerts antitumor ability in lung adenocarcinoma cells. Ferroptosis is involved in the solasonine-induced cell death, as well as the accumulation of lipid peroxide, Fe2+, and ROS. Moreover, the failures of antioxidant defense and mitochondrial damage are considered to make a significant contribution to the occurrence of ferroptosis caused by solasonine. The study describes the potential process of ferroptosis caused by solasonine when dealing with lung adenocarcinoma. This encouraging evidence suggests that solasonine may be useful in the treatment of lung cancer.
Development of a Chemoresistant Risk Scoring Model for Prechemotherapy Osteosarcoma Using Single-Cell Sequencing
Authors: Zeng Ziliang , Li Wenpeng , Zhang Di , Zhang Chi , Jiang Xu , Guo Rui , Wang Zheyu , Yang Canchun , Yan Haolin , Zhang Zhilei , Wang Qiwei , Huang Renyuan , Zhao Qiancheng , Li Bo , Hu Xumin , Gao Liangbin 
Published: May 2022

BackgroundChemoresistance is one of the leading causes that severely limits the success of osteosarcoma treatment. Evaluating chemoresistance before chemotherapy poses a new challenge for researchers. We established an effective chemoresistance risk scoring model for prechemotherapy osteosarcoma using single-cell sequencing.MethodsWe comprehensively analyzed osteosarcoma data from the bulk mRNA sequencing dataset TARGET-OS and the single-cell RNA sequencing (scRNA-seq) dataset GSE162454. Chemoresistant tumor clusters were identified using enrichment analysis and AUCell scoring. Its differentiated trajectory was achieved with inferCNV and pseudotime analysis. Ligand–receptor interactions were annotated with iTALK. Furthermore, we established a chemoresistance risk scoring model using LASSO regression based on scRNA-seq-based markers of chemoresistant tumor clusters. The TARGET-OS dataset was used as the training group, and the bulk mRNA array dataset GSE33382 was used as the validation group. Finally, the performance was verified for its discriminatory ability and calibration.ResultsUsing bulk RNA data, we found that osteogenic expression was upregulated in chemoresistant osteosarcoma as compared to chemosensitive osteosarcoma. Then, we transferred the bulk RNA findings to scRNA-seq and noticed osteosarcoma tumor clusters C14 and C25 showing osteogenic cancer stem cell expression patterns, which fit chemoresistant characteristics. C14 and C25 possessed bridge roles in interactions with other clusters. On the one hand, they received various growth factor stimulators and could potentially transform into a proliferative state. On the other hand, they promote local tumor angiogenesis, bone remodeling and immunosuppression. Next, we identified a ten-gene signature from the C14 and C25 markers and constructed a chemoresistant risk scoring model using LASSO regression model. Finally, we found that chemoresistant osteosarcoma had higher chemoresistance risk score and that the model showed good discriminatory ability and calibration in both the training and validation groups (AUCtrain = 0.82; AUCvalid = 0.84). Compared with that of the classic bulk RNA-based model, it showed more robust performance in validation environment (AUCvalid-scRNA = 0.84; AUCvalid-bulk DEGs = 0.54).ConclusionsOur work provides insights into understanding chemoresistant osteosarcoma tumor cells and using single-cell sequencing to establish a chemoresistance risk scoring model. The model showed good discriminatory ability and calibration and provided us with a feasible way to evaluate chemoresistance in prechemotherapy osteosarcoma.