bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crosstalk of angiogenesis-related subtypes, establishment of a prognostic signature and immune infiltration characteristics in colorectal adenocarcinoma
Authors: Cui Guoliang , Liu Jinhui , Wang Manli , Shon Kinyu , Wang Can , Wei Fei , Sun Zhiguang 
Published: November 2022

BackgroundColorectal adenocarcinoma (COAD) is one of the most common malignancies and angiogenesis is vital to the development of cancer. Here, we explored the roles of angiogenesis-related genes (ARGs) that affect the prognosis of COAD and constructed risk models to assess patient prognosis, immune characteristics, and treatment outcomes.MethodsWe comprehensively characterized the transcriptional and genetic modifications of 48 ARGs in COAD and evaluated the expression patterns. We identified two ARG subgroups using the consensus clustering algorithm. Based on the differentially expressed genes (DEGs) of two ARG subtypes, we calculated risk score, namely ARG_scores, and calssified COAD patients into different risk groups. To investigate the expression of ARG_score-related genes, qRT-PCR was performed. Subsequently, we mapped the nomogram to visually and accurately describe the value of the application of ARG_score. Finally, the correlation between ARG_score and clinical features, immune infiltration along with drug sensitivity were explored.ResultsWe identified two ARG related subgroups and there were great differences in overall survival (OS) and tumor microenvironment. Then, we created an ARG_score for predicting overall survival based on eight DEGs and confirmed its reliable predictive power in COAD patients, with higher ARG_score associated with worse prognosis. Furthermore, eight ARG_score-related genes expression was investigated by qRT-PCR. To make the ARG_score clinically feasible, we created a highly reliable nomogram. We also found a higher proportion of microsatellite instability-high (MSI-H) and higher tumor mutational burden (TMB) in the high-risk group. In addition, ARG_score was notably correlated with cancer stem cell indices and drug sensitivity.ConclusionThis scoring model has potential clinical application value in the prognosis, immune microenvironment and therapeutic drug sensitivity of COAD, which provides new insights for personalized treatment.
Rcs phosphorelay affects the sensitivity of Escherichia coli to plantaricin BM-1 by regulating biofilm formation
Authors: Bian Zheng , Liu Wenbo , Jin Junhua , Hao Yanling , Jiang Linshu , Xie Yuanhong , Zhang Hongxing 
Published: November 2022

Introduction: Plantaricin BM-1 is a class IIa bacteriocin produced by Lactobacillus plantarum BM-1 that exerts significant antibacterial activity against many foodborne bacteria. Studies have shown that class IIa bacteriocins inhibit Gram-positive bacteria via the mannose phosphotransferase system; however, their mechanism of action against Gram-negative bacteria remains unknown. In this study, we explored the mechanism through which the Rcs phosphorelay affects the sensitivity of Escherichia coli K12 cells to plantaricin BM-1.Methods and Results: The minimum inhibitory concentrations of plantaricin BM-1 against E. coli K12, E. coli JW5917 (rcsC mutant), E. coli JW2204 (rcsD mutant), and E. coli JW2205 (rcsB mutant) were 1.25, 0.59, 1.31, and 1.22 mg/ml, respectively. Growth curves showed that E. coli JW5917 sensitivity to plantaricin BM-1 increased to the same level as that of E. coli K12 after complementation. Meanwhile, scanning electron microscopy and transmission electron microscopy revealed that, under the action of plantaricin BM-1, the appearance of E. coli JW5917 cells did not significantly differ from that of E. coli K12 cells; however, cell contents were significantly reduced and plasmolysis and shrinkage were observed at both ends. Crystal violet staining and laser scanning confocal microscopy showed that biofilm formation was significantly reduced after rcsC mutation, while proteomic analysis identified 382 upregulated and 260 downregulated proteins in E. coli JW5917. In particular, rcsC mutation was found to affect the expression of proteins related to biofilm formation, with growth curve assays showing that the deletion of these proteins increased E. coli sensitivity to plantaricin BM-1.Discussion: Consequently, we speculated that the Rcs phosphorelay may regulate the sensitivity of E. coli to plantaricin BM-1 by affecting biofilm formation. This finding of class IIa bacteriocin against Gram-negative bacteria mechanism provides new insights.
Delivery of intensity-modulated electron therapy by mechanical scanning: An algorithm study
Authors: Ma Pan , Tian Yuan , Li Minghui , Niu Chuanmeng , Song Yuchun , Dai Jianrong 
Published: November 2022

PurposeIn principle, intensity-modulated electron therapy (IMET) can be delivered through mechanical scanning, with a robotic arm mounting a linac.Materials and methodsHere is a scanning algorithm to identify the back-and-forth, top-to-bottom (zigzag) pattern scan sequence. The algorithm includes generating beam positions with a uniform resolution according to the applicator size; adopting discrete energies to achieve the depth of 90% dose by compositing energies; selecting energy by locating the target’s distal edge; and employing the energy-by-energy scan strategy for step-and-shoot discrete scanning. After a zigzag scan sequence is obtained, the delivery order of the scan spots is optimized by fast simulated annealing (FSA) to minimize the path length. For algorithm evaluation, scan sequences were generated using the computed tomography data of 10 patients with pancreatic cancer undergoing intraoperative radiotherapy, and the results were compared between the zigzag path and an optimized path. A simple calculation of the treatment delivery time, which comprises the irradiation time, the total robotic arm moving time, the time for energy switch, and the time to stop and restart the beam, was also made.ResultsIn these clinical cases, FSA optimization shortened the path lengths by 12%–43%. Assuming the prescribed dose was 15 Gy, machine dose rate was 15 Gy/s, energy switch time was 2 s, stop and restart beam time was 20 ms, and robotic arm move speed was 50 mm/s, the average delivery time was 124±38 s. The largest reduction in path length yielded an approximately 10% reduction in the delivery time, which can be further reduced by increasing the machine dose rate and the robotic arm speed, decreasing the time for energy switch, and/or developing more efficient algorithms.ConclusionMechanically scanning IMET is potentially feasible and worthy of further exploration.
Machine learning-based analysis of a semi-automated PI-RADS v2.1 scoring for prostate cancer
Authors: Singh Dharmesh , Kumar Virendra , Das Chandan J. , Singh Anup , Mehndiratta Amit 
Published: November 2022

BackgroundProstate Imaging-Reporting and Data System version 2.1 (PI-RADS v2.1) was developed to standardize the interpretation of multiparametric MRI (mpMRI) for prostate cancer (PCa) detection. However, a significant inter-reader variability among radiologists has been found in the PI-RADS assessment. The purpose of this study was to evaluate the diagnostic performance of an in-house developed semi-automated model for PI-RADS v2.1 scoring using machine learning methods.MethodsThe study cohort included an MRI dataset of 59 patients (PI-RADS v2.1 score 2 = 18, score 3 = 10, score 4 = 16, and score 5 = 15). The proposed semi-automated model involved prostate gland and zonal segmentation, 3D co-registration, lesion region of interest marking, and lesion measurement. PI-RADS v2.1 scores were assessed based on lesion measurements and compared with the radiologist PI-RADS assessment. Machine learning methods were used to evaluate the diagnostic accuracy of the proposed model by classification of PI-RADS v2.1 scores.ResultsThe semi-automated PI-RADS assessment based on the proposed model correctly classified 50 out of 59 patients and showed a significant correlation (r = 0.94, p &lt; 0.05) with the radiologist assessment. The proposed model achieved an accuracy of 88.00% ± 0.98% and an area under the receiver-operating characteristic curve (AUC) of 0.94 for score 2 vs. score 3 vs. score 4 vs. score 5 classification and accuracy of 93.20 ± 2.10% and AUC of 0.99 for low score vs. high score classification using fivefold cross-validation.ConclusionThe proposed semi-automated PI-RADS v2.1 assessment system could minimize the inter-reader variability among radiologists and improve the objectivity of scoring.
Development of restrictive eating disorders in children and adolescents with long-COVID-associated smell and taste dysfunction
Authors: Brasseler Maire , Schönecker Anne , Steindor Mathis , Della Marina Adela , Bruns Nora , Dogan Burcin , Felderhoff-Müser Ursula , Hebebrand Johannes , Dohna-Schwake Christian , Goretzki Sarah C. 
Published: November 2022

BackgroundAbsent or abnormal senses of smell and taste have been frequently reported during both acute and long COVID in adult patients. In contrast, pediatric patients who test positive for SARS-CoV-2 are often asymptomatic and the loss of smell and/or taste has been infrequently reported. After observing several young patients with COVID-associated anosmia and ageusia at our clinic, we decided to investigate the incidence of subsequent eating disorders in these patients and in SARS-CoV-2 positive patients who did not experience anosmia and ageusia during the same period.Material and methodsA single-site retrospective cohort study of 84 pediatric patients with suspected long COVID who were treated in the Pediatric Infectious Diseases Outpatient Clinic at the University Hospital Essen were evaluated for persistent symptoms of COVID-19. Smell and taste dysfunction as well as eating behaviors were among the signs and symptoms analyzed in this study.Results24 out of 84 children and adolescents described smell and taste dysfunction after confirmed or suspected SARS-CoV-2 infections. A large number of these patients (6 out of 24) demonstrated increased fixation on their eating behavior post-COVID and over time these patients developed anorexia nervosa.Discussion/ConclusionIn this study we saw a possible association of long-lasting post-COVID smell and taste dysfunction with subsequent development of eating disorders. This observation is worrisome and merits further investigation by healthcare providers at multiple clinical sites.
Alpiniae oxyphylla fructus extract promotes longevity and stress resistance of C. elegans via DAF-16 and SKN-1
Authors: Xiao Man , Chen Bocen , Niu Kun , Long Ziyu , Yang Fan , Xie Yiqiang 
Published: November 2022

Background:Alpiniae Oxyphylla Fructus (AOF) is Traditional Chinese medicine and a dietary supplements for centuries, which posseses cardiotonic, neuroprotective, antioxidant, warming the kidney and nourish the spleen, these biological fuction is related to potential anti-aging properties. However, little is known about their effects on aging. This work aimed to investigate the effects of extracts of AOF on longevity and stress resistance in Caenorhabditis elegans (C. elegans) and the mechanisms that underlie its effects.Methods: Wild-type (WT) strand of C.elegans (N2)worms were cultured in growth medium with or without AOF. First, we examined the effects of AOF on lifespan, reproduction and healthspan assay, stress resistance and oxidative analysis, lipofuscin levels. Second, The levels of ROS and MDA, the antioxidant enzyme activities were examined to explore the underlying mechanism of AOF. Finally, the expression of the longevity-related genes were investigated to further understand the AOF’s underlying mechanism.Results: The lifespan of C. elegans was prolonged by 23.44% after treatment with high-dose AOF (100 ug/ml). AOF alleviated aging-related declines in C. elegans health and enhanced resistance to heat shock. Furthermore, AOF decreased reactive oxygen species and malondialdehyde, increased the activities of superoxide dismutase and catalase, and reduced accumulation of fat. AOF upregulated the expression of sod-3, gst-4, daf-16, and skn-1 but downregulated the expression of daf-2 and age-1 and accelerated the translocation of DAF-16 into the nucleus. The extended lifespan induced by AOF was reversed in daf-16(mu86) and skn-1(zu135) mutants, indicating that this gene is involved in AOF-regulated longevity.Conclusion: Our findings demonstrated that AOF extends lifespan and healthspan and enhances stress via boosting the activity of the antioxidant enzyme and controlling the expression of genes associated with insulin/IGF signaling and SKN-1 pathways. As a result, this work suggested AOF as a possible candidate to reduce the signs of aging by activating and inhibiting target genes.
Real-world safety of PCSK9 inhibitors: A pharmacovigilance study based on spontaneous reports in FAERS
Authors: Feng Zhen , Li Xiaoye , Tong Wai Kei , He Qingfeng , Zhu Xiao , Xiang Xiaoqiang , Tang Zhijia 
Published: November 2022

Objective: We aimed to evaluate alirocumab- and evolocumab-related adverse events (AEs) in real-world compared with all other drugs, overall and by gender and age subgroups; we also aimed to compare their risks of cognitive impairment, musculoskeletal disorders and diabetes with various statins and ezetimibe.Methods: We retrospectively extracted AE reports from the FDA Adverse Event Reporting System (FAERS) database during July 2015-June 2021. Disproportionality analyses were performed using reporting odds ratios (RORs) to detect AE signals of alirocumab and evolocumab in the overall population and in different age and gender subgroups, respectively.Results: Compared with all other drugs, both alirocumab and evolocumab had a significant signal in “musculoskeletal and connective tissue disorders” (ROR1 = 2.626, 95% CI 2.552–2.702; ROR2 = 2.575, 95% CI 2.538–2.613). The highest ROR value of 2.311 (95% CI 2.272–2.351) was for “injury, poisoning and procedural complications” and was found in patients aged ≥65 years on evolocumab. The most frequent AEs were “general disorders and administration site conditions” and “musculoskeletal and connective tissue disorders” for all subpopulations. At the preferred term level, the most frequent AE signal was myalgia for alirocumab and injection site pain for evolocumab, overall and by subgroups. Compared with statins/ezetimibe, PCSK9 inhibitors exhibited lower ROR values for adverse events associated with SOC “nervous system disorders”, “psychiatric disorders” and “metabolism and nutrition disorders” (all RORs &lt; 1), but mixed results for musculoskeletal disorders. Compared with all other drugs, undocumented AEs, such as acute cardiac event (ROR = 30.0, 95% CI 9.4–95.3) and xanthoma (ROR = 9.3, 95% CI 3.4–25.5), were also reported.Conclusion: Real-world evidence showed that PCSK9 inhibitors were associated with an increased risk of musculoskeletal and connective tissue disorders and general disorders and administration site conditions, overall and by subgroups. Muscle toxicity, injection site reactions, and influenza-like illness were significant AE signals. Compared with various statins and ezetimibe, PCSK9 inhibitors have shown a favorable safety profile in muscle-related events, cognitive impairment and diabetes. Some undocumented AE signals were also reported. Due to the limitations of spontaneous reporting databases, further studies are still needed to establish causality and validate our results.
Adverse drug events in the prevention and treatment of COVID-19: A data mining study on the FDA adverse event reporting system
Authors: Guo Qiang , Duan Shaojun , Liu Yaxi , Yuan Yinxia 
Published: November 2022

Background: In the emergent situation of COVID-19, off-label therapies and newly developed vaccines may bring the patients more adverse drug event (ADE) risks. Data mining based on spontaneous reporting systems (SRSs) is a promising and efficient way to detect potential ADEs to help health professionals and patients get rid of the risk.Objective: This pharmacovigilance study aimed to investigate the ADEs of some attractive drugs (i.e., “hot drugs” in this study) in COVID-19 prevention and treatment based on the data from the US Food and Drug Administration (FDA) adverse event reporting system (FAERS).Methods: The FAERS ADE reports associated with COVID-19 from the 2nd quarter of 2020 to the 2nd quarter of 2022 were retrieved with hot drugs and frequent ADEs were recognized. A combination of support, lower bound of 95% confidence interval (CI) of the proportional reporting ratio (PRR) was applied to detect significant hot drug and ADE signals by the Python programming language on the Jupyter notebook.Results: A total of 66,879 COVID-19 associated cases were retrieved with 22 hot drugs and 1,109 frequent ADEs on the “preferred term” (PT) level. The algorithm finally produced 992 significant ADE signals on the PT level among which unexpected signals such as “hypofibrinogenemia” of tocilizumab and “disease recurrence” of nirmatrelvir\ritonavir stood out. A picture of signals on the “system organ class” (SOC) level was also provided for a comprehensive understanding of these ADEs.Conclusion: Data mining is a promising and efficient way to assist pharmacovigilance work, and the result of this study could help timely recognize ADEs in the prevention and treatment of COVID-19.
Dysfunctional intercellular communication and metabolic signaling pathways in thin endometrium
Authors: Xu Liang , Fan Yingying , Wang Jianjun , Shi Rui 
Published: November 2022

Background: The endometrial thickness is a key factor for successful implantation. Thin endometrium is associated with lower implantation rate and pregnancy rate. Lacking of a better understanding for the cellular and molecular mechanisms of thin endometrium, managing patients with thin endometrium still represents a major challenge for clinicians.Methods: In this study, we combined four single-cell RNA sequencing (scRNA-seq) and one bulk sequencing (bulk-seq) data for thin endometrium to perform an integrated analysis for endometrial cells in proliferating phase. Cell proportion and differentially expressed genes (DEGs) were analyzed to determine the disease-specific cell type and signaling pathways. The cell-cell communication among cell types were inferred by “CellChat” to illustrate the differential intercellular communication under normal and thin endometrium conditions. GSEA and GSVA were applied to identify dysfunctional signals and metabolic pathways before and after thin endometrium.Results: Integration of scRNA-seq identified eight cell types. The proportion of stromal cells showed a significant difference between normal and thin endometrial tissue. The DEGs in diverse cell types revealed enriched pathways in a cell-specific manner. Aberrant cell-cell signaling transduction was found in almost all cell types, especially in immune cells and epithelial cells. Furthermore, dysfunctional metabolic signaling pathways were induced in a cell-type dependent way. The down-regulation of carbohydrate metabolism and nucleotide metabolism was observed and the energy metabolism switch was indicated.Conclusion: Conclusively, we discover dysfunctional signals and metabolic pathways in thin endometrium, providing insight into mechanisms and therapeutic strategies for the atrophic endometrium.
Responses of tree seedlings to understory filtering by the recalcitrant fern layer in a subtropical forest
Authors: Liu Heming , Liang Mengfang , Yang Qingsong , Zhang Jian , Shen Guochun , Zhang Zhenzhen , Wang Xihua 
Published: November 2022

The recalcitrant understory fern layer is an important ecological filter for seedling regeneration, yet how the fern layer influences seedling regeneration dynamics remains unclear. Here we transplanted 576 seedlings of four dominant tree species, Castanopsis fargesii, Lithocarpus glaber, Schima superba and Hovenia acerba, to the treatments of Diplopterygium glaucum retention and removal under an evergreen broad-leaved forest in eastern China. We monitored the survival, growth and biomass data of these seedlings for 28 months, and then used generalized linear mixed models to evaluate the treatment effects on seedling survival, growth, biomass and root-shoot ratio. Our results showed that fern retention significantly inhibited the seedling establishment of all four species. During the seedling development stage, the seedling relative growth rate of L. glaber decreased under fern retention, which was not the case for the other three species. Root-shoot ratio of C. fargesii and L. glaber increased significantly under fern retention. Our findings provide new evidence of the filtering effect of a recalcitrant fern understory. Notably, we observed that the response of tree seedlings to the recalcitrant fern understory was more sensitive in the establishment stage. Finally, our work highlights that the filtering effect of the recalcitrant fern understory changes depending on the regeneration stages, and that shade-tolerant species, C. fargesii and L. glaber were even more affected by fern disturbed habitats, suggesting that effective management should attempt to curb forest fern outbreaks, thus unblocking forest recruitment.
The benefits of role play in the development of drawing in preschool children
Authors: Bonilla-Sánchez María del Rosario , García-Flores Marco Antonio , Méndez-Balbuena Ignacio , Silva-González Jocelyn Guadalupe , Ramírez-Arroyo Ernesto Vladimir 
Published: November 2022

ObjectiveThe purpose of our study was to demonstrate the benefits of role play based on a Historical–Cultural perspective with the implementation of symbolic elements generated by the development of drawing of preschool children from suburban origin in a group of normal Mexican preschool children. We predict that the quality of the drawings will be improved after the preschoolers participate in such a role play program.MethodsA pre-experimental study was carried out, with pre-test and post-test assessments. The drawings were assessed with quantitative (frequencies of the quality of the parameters) and qualitative (characteristics of the children's drawings) methods. The role play program was based on Elkonin's method, activity theory, and P. Ya Galperin's formation by stages of mental actions. The program encouraged the use of graphic signs and symbols, with the intention of representing situations, actions, objects, and/or contents. Twenty-six preschool children participated in our study.ResultsTo know the effect of the role play program with symbolic elements on the drawing of preschool children, we performed a quantitative and qualitative analysis, a Wilcoxon test contrast between the initial and final assessment. Both analyses showed a significant increase in the scores in all the tasks with a medium–large effect size, being the largest “Pictograms” and “Drawing of the route”; and in the analysis of the qualitative parameters, specifically in “Maintains the objective,” a significant increase was found in all the tasks.DiscussionRole play, being the main activity in preschool age, develops all aspects of the child's psychic life. The importance of role play in a preschool child makes it possible to work in the zone of proximal development with the regulatory function of language, with the planning, execution, and control of playful activity and, most importantly, with the use of various materials and perceptual-graphics tools. These findings showed an improvement in the development and complexity of the symbolic function in the drawings.ConclusionRole play, as a work methodology in preschool age, leads to the use of new meaning systems that prepare the child to carry out present and future complex symbolic actions.