Pediatric intestinal development is immature, vulnerable to external influences and produce a variety of intestinal diseases. At present, breakthroughs have been made in the treatment of pediatric intestinal diseases, but there are still many challenges, such as toxic side effects, drug resistance, and the lack of more effective treatments and specific drugs. In recent years, dietary polyphenols derived from plants have become a research hotspot in the treatment of pediatric intestinal diseases due to their outstanding pharmacological activities such, as anti-inflammatory, antibacterial, antioxidant and regulation of intestinal flora. This article reviewed the mechanism of action and clinical evidence of dietary polyphenols in the treatment of pediatric intestinal diseases, and discussed the influence of physiological characteristics of children on the efficacy of polyphenols, and finally prospected the new dosage forms of polyphenols in pediatrics.
Correlations of fluctuations are essential to understanding many-body systems and key information for advancing quantum technologies. To fully describe the dynamics of a physical system, all time-ordered correlations (TOCs), i.e., the dynamics-complete set of correlations are needed. The current measurement techniques can only access a limited set of TOCs, and there has been no systematic and feasible solution for extracting the dynamic-complete set of correlations hitherto. Here we propose a platform-universal protocol to selectively detect arbitrary types of TOCs via quantum channels. In our method, the quantum channels are synthesized with various controls, and engineer the evolution of a sensor-target system along a specific path that corresponds to a desired correlation. Using nuclear magnetic resonance, we experimentally demonstrate this protocol by detecting a specific type of fourth-order TOC that has never been accessed previously. We also show that the knowledge of the TOCs can be used to significantly improve the precision of quantum optimal control. Our method provides a new toolbox for characterizing the quantum many-body states and quantum noise, and hence for advancing the fields of quantum sensing and quantum computing.
Inherently chiral calix[4]arenes are an excellent structural scaffold for asymmetric synthesis, chiral recognition, sensing, and circularly polarized luminescence. However, their catalytic asymmetric synthesis remains challenging. Herein, we report an efficient synthesis of inherently chiral calix[4]arene derivatives via cascade asymmetric cyclization and oxidation reactions. The three-component reaction features a broad substrate scope (33 examples), high efficiency (up to 90% yield), and excellent enantioselectivity (>95% ee on average). The potential applications of calix[4]arene derivatives are highlighted by their synthetic transformation and a detailed investigation of their photophysical and chiroptical properties.
Synaptic plasticity is a key cellular model for learning, memory and chronic pain. Most previous studies were carried out in rats and mice, and less is known about synaptic plasticity in non-human primates. In the present study, we used integrative experimental approaches to study long-term potentiation (LTP) in the anterior cingulate cortex (ACC) of adult tree shrews. We found that glutamate is the major excitatory transmitter and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionicacid (AMPA) receptors mediate postsynaptic responses. LTP in tree shrews was greater than that in adult mice and lasted for at least 5 h. N-methyl-d-aspartic acid (NMDA) receptors, Ca2+ influx and adenylyl cyclase 1 (AC1) contributed to tree shrew LTP. Our results suggest that LTP is a major form of synaptic plasticity in the ACC of primate-like animals. This article is part of a discussion meeting issue 'Long-term potentiation: 50 years on'.
Gyrus Cinguli , Long-Term Potentiation , Receptors, AMPA , Receptors, N-Methyl-D-Aspartate , Tupaiidae , Animals , Long-Term Potentiation/physiology , Gyrus Cinguli/physiology , Tupaiidae/physiology , Mice , Receptors, N-Methyl-D-Aspartate/metabolism , Receptors, AMPA/metabolism , Adenylyl Cyclases/metabolism , Glutamic Acid/metabolism , Male
The design of bioelectronics capable of stably tracking brain-wide, single-cell, and millisecond-resolved neural activities in the developing brain is critical to the study of neuroscience and neurodevelopmental disorders. During development, the three-dimensional (3D) structure of the vertebrate brain arises from a 2D neural plate 1,2 . These large morphological changes previously posed a challenge for implantable bioelectronics to track neural activity throughout brain development 3-9 . Here, we present a tissue-level-soft, sub-micrometer-thick, stretchable mesh microelectrode array capable of integrating into the embryonic neural plate of vertebrates by leveraging the 2D-to-3D reconfiguration process of the tissue itself. Driven by the expansion and folding processes of organogenesis, the stretchable mesh electrode array deforms, stretches, and distributes throughout the entire brain, fully integrating into the 3D tissue structure. Immunostaining, gene expression analysis, and behavioral testing show no discernible impact on brain development or function. The embedded electrode array enables long-term, stable, brain-wide, single-unit-single-spike-resolved electrical mapping throughout brain development, illustrating how neural electrical activities and population dynamics emerge and evolve during brain development.
Given the heterogeneity of tumors, there is an urgent need for accurate prognostic parameters in prostate cancer (PCa) patients. Lipid metabolism (LM) reprogramming and oxidative stress (OS) play a vital role in the progression of PCa. In this work, we identified five LM-OS-related genes (including ACOX2, PPRAGC1A, PTGS1, PTGS2, and HAO1) associated with the biochemical recurrence (BCR) of PCa. Subsequently, a prognostic signature was established based on these five genes. Kaplan-Meier survival estimates, receiver operating characteristic curves, and relationship analysis between risk score and clinical characters were applied to measure the robustness of the signature in an external cohort. A nomogram of risk score combined with clinical characteristics was constructed for clinical application. Functional enrichment analysis suggested that the underlying mechanism related to the signature included the calcium signaling, lipid transport, and cell cycle signaling pathways. Furthermore, WEE1 inhibitor was identified as a potential agent related to the cell cycle for high-risk patients. The mRNA expression and the prognostic value of the five genes were determined, and ACOX2 was identified as the key gene related to the prognostic signature. The protein expression of ACOX2 was measured in a prostate tissue microarray through an immunohistochemistry assay, confirming the bioinformatics results. By constructing the ACOX2-overexpressing PCa cell lines PC-3 and 22Rv1, the biological function of PCa cells was investigated. The cell viability, colony formation, migration, and invasion ability of PCa cell lines overexpressing ACOX2 were hindered. Decreased cellular lipid content and elevated cellular ROS content were observed in ACOX2-overexpressing PCa cell lines with reduced G2/M phases. In conclusion, this work presents the first prognostic signature specifically focused on LM-OS for PCa. ACOX2 could serve as a favorable indicator for the BCR in PCa. Further experiments are required to identify the potential underlying mechanism.
Background: Evidence of the relationship between platelet count and 30-day in-hospital mortality in ICU stroke patients is still scarce. Therefore, the purpose of this study was to explore the relationship between platelet count and 30-day in-hospital mortality among ICU stroke patients. Methods: We conducted a multicenter retrospective cohort study using data from 8,029 ICU stroke patients in the US eICU-CRD v2.0 database from 2014 to 2015. Utilizing binary logistic regression, smooth curve fitting, and subgroup analyses, we examined the link between platelet count and 30-day in-hospital mortality. Results: The 30-day in-hospital mortality prevalence was 14.02%, and the mean platelet count of 223 × 109/L. Adjusting for covariates, our findings revealed an inverse association between platelet count and 30-day in-hospital mortality (OR = 0.975, 95% CI: 0.966, 0.984). Subgroup analyses supported the robustness of these results. Moreover, a nonlinear relationship was observed between platelet count and 30-day in-hospital mortality, with the inflection point at 163 × 109/L. On the left side of the inflection point, the effect size (OR) was 0.92 (0.89, 0.95), while on the right side, the relationship was not statistically significant. Conclusion: This study establishes an independent negative association between platelet count and 30-day in-hospital mortality in ICU stroke patients. Furthermore, a nonlinear relationship with a saturation effect was identified, suggesting that maintaining the platelet count around 163 × 109/L can reduce 30-day in-hospital mortality in these patients.
BACKGROUND: Nitrogen (N) is essential for plant growth and development. In Lithocarpus polystachyus Rehd., a species known for its medicinal and food value, phlorizin is the major bioactive compound with pharmacological activity. Research has revealed a positive correlation between plant nitrogen (N) content and phlorizin synthesis in this species. However, no study has analyzed the effect of N fertilization on phlorizin content and elucidated the molecular mechanisms underlying phlorizin synthesis in L. polystachyus. RESULTS: A comparison of the L. polystachyus plants grown without (0 mg/plant) and with N fertilization (25, 75, 125, 175, 225, and 275 mg/plant) revealed that 75 mg N/plant fertilization resulted in the greatest seedling height, ground diameter, crown width, and total phlorizin content. Subsequent analysis of the leaves using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) detected 150 metabolites, including 42 flavonoids, that were differentially accumulated between the plants grown without and with 75 mg/plant N fertilization. Transcriptomic analysis of the L. polystachyus plants via RNA sequencing revealed 162 genes involved in flavonoid biosynthesis, among which 53 significantly differed between the N-treated and untreated plants. Fertilization (75 mg N/plant) specifically upregulated the expression of the genes phenylalanine ammonia-lyase (PAL), 4-coumarate-CoA ligase (4CL), and phlorizin synthase (PGT1) but downregulated the expression of trans-cinnamate 4-monooxygenase (C4H), shikimate O-hydroxycinnamoyltransferase (HCT), and chalcone isomerase (CHI), which are related to phlorizin synthesis. Finally, an integrated analysis of the transcriptome and metabolome revealed that the increase in phlorizin after N fertilization was consistent with the upregulation of phlorizin biosynthetic genes. Quantitative real-time PCR (qRTâPCR) was used to validate the RNA sequencing data. Thus, our results indicated that N fertilization increased phlorizin metabolism in L. polystachyus by regulating the expression levels of the PAL, PGT1, 5-O-(4-coumaroyl)-D-quinate 3'-monooxygenase (C3'H), C4H, and HCT genes. CONCLUSIONS: Our results demonstrated that the addition of 75 mg/plant N to L. polystachyus significantly promoted the accumulation of flavonoids, including phlorizin, and the expression of flavonoid synthesis-related genes. Under these conditions, the genes PAL, 4CL, and PGT1 were positively correlated with phlorizin accumulation, while C4H, CHI, and HCT were negatively correlated with phlorizin accumulation. Therefore, we speculate that PAL, 4CL, and PGT1 participate in the phlorizin pathway under an optimal N environment, regulating phlorizin biosynthesis. These findings provide a basis for improving plant bioactive constituents and serve as a reference for further pharmacological studies.
Fertilizers , Metabolome , Nitrogen , Phlorhizin , Transcriptome , Nitrogen/metabolism , Metabolome/drug effects , Gene Expression Regulation, Plant/drug effects , Gene Expression Profiling , Tandem Mass Spectrometry , Plant Proteins/genetics , Plant Proteins/metabolism
Owing to their lack of outer skin, Chinese bayberries are highly susceptible to mechanical damage during picking, which accelerates bacterial invasion and rotting, shortening their shelf life. In this study, montmorillonite (MMT) was used to absorb an aqueous sodium chlorite solution embedded in a carboxymethyl cellulose sodium hydrogel after freeze drying, and the hydrogel was crosslinked by Al3+ ions. Al3+ hydrolyzed to produce H+, creating an acidic environment within the hydrogel and reacting with NaClO2 to slowly release ClO2. We prepared a ClO2 slow-release hydrogel gasket with 0.5 wt% MMT-NaClO2 and investigated its storage effect on postharvest Chinese bayberries. Its inhibition rates against Escherichia coli and Listeria monocytogenes were 98.84% and 98.96%, respectively. The results showed that the gasket preserved the appearance and nutritional properties of the berries. The antibacterial hydrogel reduced hardness loss by 26.57% and ascorbic acid loss by 46.36%. This new storage method could also be applicable to other fruits and vegetables.
Osteoporosis is a complex endocrine disease characterized by a decline in bone mass and microstructural integrity. It constitutes a major global health problem. Recent progress in the field of artificial intelligence (AI) has opened new avenues for the effective diagnosis of osteoporosis via radiographs. This review investigates the application of AI classification of osteoporosis in radiographs. A comprehensive exploration of electronic repositories (ClinicalTrials.gov, Web of Science, PubMed, MEDLINE) was carried out in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement (PRISMA). A collection of 31 articles was extracted from these repositories and their significant outcomes were consolidated and outlined. This encompassed insights into anatomical regions, the specific machine learning methods employed, the effectiveness in predicting BMD, and categorizing osteoporosis. Through analyzing the respective studies, we evaluated the effectiveness and limitations of AI osteoporosis classification in radiographs. The pooled reported accuracy, sensitivity, and specificity of osteoporosis classification ranges from 66.1% to 97.9%, 67.4% to 100.0%, and 60.0% to 97.5% respectively. This review underscores the potential of AI osteoporosis classification and offers valuable insights for future research endeavors, which should focus on addressing the challenges in technical and clinical integration to facilitate practical implementation of this technology.
Objectives: Hypertension and hypertensive disorders of pregnancy (HDP) are common diseases in women at different stages, which affect women's physical and mental health, and the impact of the latter on the offspring cannot not be ignored. Observational studies have investigated the correlation between uterine leiomyoma (UL) and the above conditions, but the relationship remains unclear. In this study, we employed two-sample Mendelian randomization (MR) analysis to assess the association between UL and hypertension, HDP, as well as blood pressure. Methods: We collected genetic association data of UL (35,474 cases), hypertension (129,909 cases), HDP (gestational hypertension with 8,502 cases, pre-eclampsia with 6,663 cases and eclampsia with 452cases), systolic blood pressure (SBP) and diastolic blood pressure (DBP) (both 757,601 participants) from published available genome-wide association studies (GWAS). The single nucleotide polymorphisms (SNPs) associated with UL phenotype were used as instrumental variables, and hypertension, three sub-types of HDP, SBP and DBP were used as outcomes. The inverse-variance weighted (IVW) method was employed as the primary method of causal inference. Heterogeneity was assessed using Cochran's Q test, and sensitivity analyses were conducted using MR-Egger regression and MR pleiotropy residual sum and outlier (MR-PRESSO) tests to evaluate the pleiotropy of instrumental variables. PhenoScanner search was used to remove confounding SNP. Robustness and reliability of the results were assessed using methods such as the weighted median and weighted mode. Results: The IVW analysis revealed a positive correlation between genetically predicted UL and SBP [odds ratio (OR)= 1.67, 95% confidence interval (CI):1.24~2.25, P = 0.0007], and no statistical association was found between UL and hypertension, HDP, or DBP. The MR-Egger regression suggested that the above causal relationships were not affected by horizontal pleiotropy. The weighted median method and weighted model produced similar results to the IVW. Conclusion: Based on large-scale population GWAS data, our MR analysis suggested a causal relationship between UL and SBP. Therefore, women with UL, especially pregnant women, should pay attention to monitoring their blood pressure levels. For patients with hypertension who already have UL, interventions for UL may serve as potential therapeutic methods for managing blood pressure.
Blood Pressure , Genome-Wide Association Study , Hypertension , Leiomyoma , Mendelian Randomization Analysis , Polymorphism, Single Nucleotide , Uterine Neoplasms , Humans , Female , Leiomyoma/genetics , Uterine Neoplasms/genetics , Blood Pressure/genetics , Pregnancy , Hypertension/genetics , Hypertension/epidemiology , Hypertension, Pregnancy-Induced/genetics
Artificial intelligence (AI) edge devices prefer employing high-capacity nonvolatile compute-in-memory (CIM) to achieve high energy efficiency and rapid wakeup-to-response with sufficient accuracy. Most previous works are based on either memristor-based CIMs, which suffer from accuracy loss and do not support training as a result of limited endurance, or digital static random-access memory (SRAM)-based CIMs, which suffer from large area requirements and volatile storage. We report an AI edge processor that uses a memristor-SRAM CIM-fusion scheme to simultaneously exploit the high accuracy of the digital SRAM CIM and the high energy-efficiency and storage density of the resistive random-access memory memristor CIM. This also enables adaptive local training to accommodate personalized characterization and user environment. The fusion processor achieved high CIM capacity, short wakeup-to-response latency (392 microseconds), high peak energy efficiency (77.64 teraoperations per second per watt), and robust accuracy (<0.5% accuracy loss). This work demonstrates that memristor technology has moved beyond in-lab development stages and now has manufacturability for AI edge processors.
Developing facile and direct synthesis routes for enantioselective construction of cyclic π-conjugated molecules is crucial. However, originate chirality from the distorted structure around heptagon-containing polyarenes is largely overlooked, the enantioselective construction of all-carbon heptagon-containing polyarenes remains a challenge. Herein, we present a highly enantioselective synthesis route for fabricating all carbon heptagon-containing polyarenes via palladium-catalyzed carbene-based cross-coupling of benzyl bromides and N-arylsulfonylhydrazones. A wide range of nonplanar, saddle-shaped tribenzocycloheptene derivatives are efficiently prepared in high yields with excellent enantioselectivities using this approach. In addition, stereochemical stability experiments show that these saddle-shaped tribenzocycloheptene derivatives have high inversion barriers.
AIMS: The vascular aging process accelerated by type 2 diabetes mellitus (T2DM) is responsible for the elevated risk of associated cardiovascular diseases (CVDs). Metabolic disorder-induced immune senescence has been implicated in multi-organ/tissue damage. Herein, we sought to determine the role of immunosenescence in diabetic vascular aging and to investigate the underlying mechanisms. METHODS AND RESULTS: Aging hallmarks of the immune system appear prior to the vasculature in streptozotocin (STZ)/high-fat diet (HFD)-induced T2DM mice or db/db mice. Transplantation of aged splenocytes or diabetic splenocytes into young mice triggered vascular senescence and injury compared to normal control splenocyte transfer. RNA-seq profile and validation in immune tissues revealed that the Toll-like receptor 4 (TLR4)- Nuclear factor-kappa B (NF-κB) -NLRP3 axis might be the mediator of diabetic premature immunosenescence. The absence of Nlrp3 attenuated immune senescence and vascular aging during T2DM. Importantly, senescent immune cells, particularly T cells, provoked perivascular adipose tissue (PVAT) dysfunction and alternations in its secretome, which in turn impair vascular biology. In addition, senescent immune cells may uniquely affect vasoconstriction via influencing PVAT. Lastly, rapamycin alleviated diabetic immune senescence and vascular aging, which may be partly due to NLRP3 signaling inhibition. CONCLUSION: These results indicated that NLRP3 inflammasome-mediated immunosenescence precedes and drives diabetic vascular aging. The contribution of senescent immune cells to vascular aging is a combined effect of their direct effects and induction of PVAT dysfunction, the latter of which can uniquely affect vasoconstriction. We further demonstrated that infiltration of senescent T cells in PVAT was increased and associated with PVAT secretome alterations. Our findings suggest that blocking the NLRP3 pathway may prevent early immunosenescence and thus mitigate diabetic vascular aging and damage, and targeting senescent T cells or PVAT might also be the potential therapeutic approach.
Flexible electronics implanted during tissue formation enable chronic studies of tissue-wide electrophysiology. Here, we integrate tissue-like stretchable electronics during organogenesis of human stem cell-derived pancreatic islets, stably tracing single-cell extracellular spike bursting dynamics over months of functional maturation. Adapting spike sorting methods from neural studies reveals maturation-dependent electrical patterns of α and ß-like (SC-α and ß) cells, and their stimulus-coupled dynamics. We identified two major electrical states for both SC-α and ß cells, distinguished by their glucose threshold for action potential firing. We find that improved hormone stimulation capacity during extended culture reflects increasing numbers of SC-α/ß cells in low basal firing states, linked to energy and hormone metabolism gene upregulation. Continuous recording during further maturation by entrainment to daily feeding cycles reveals that circadian islet-level hormone secretion rhythms reflect sustained and coordinate oscillation of cell-level SC-α and ß electrical activities. We find that this correlates with cell-cell communication and exocytic network induction, indicating a role for circadian rhythms in coordinating system-level stimulus-coupled responses. Cyborg islets thus reveal principles of electrical maturation that will be useful to build fully functional in vitro islets for research and therapeutic applications.
Nickel-catalyzed transannulation reactions triggered by the extrusion of small gaseous molecules have emerged as a powerful strategy for the efficient construction of heterocyclic compounds. However, their use in asymmetric synthesis remains challenging because of the difficulty in controlling stereo- and regioselectivity. Herein, we report the first nickel-catalyzed asymmetric synthesis of N-N atropisomers by the denitrogenative transannulation of benzotriazones with alkynes. A broad range of N-N atropisomers was obtained with excellent regio- and enantioselectivity under mild conditions. Moreover, density functional theory (DFT) calculations provided insights into the nickel-catalyzed reaction mechanism and enantioselectivity control.
The large abundance of termites is partially achieved by their defensive abilities. Stylotermitidae represented by a single extant genus, Stylotermes, is a member of a termite group Neoisoptera that encompasses 83% of termite species and 94% of termite genera and is characterized by the presence of the frontal gland. Within Neoisoptera, Stylotermitidae represents a species-poor sister lineage of all other groups. We studied the structure of the frontal, labral and labial glands in soldiers and workers of Stylotermes faveolus, and the composition of the frontal gland secretion in S. faveolus and Stylotermes halumicus. We show that the frontal gland is a small active secretory organ in soldiers and workers. It produces a cocktail of monoterpenes in soldiers, and some of these monoterpenes and unidentified proteins in workers. The labral and labial glands are developed similarly to other termite species and contribute to defensive activities (labral in both castes, labial in soldiers) or to the production of digestive enzymes (labial in workers). Our results support the importance of the frontal gland in the evolution of Neoisoptera. Toxic, irritating and detectable monoterpenes play defensive and pheromonal functions and are likely critical novelties contributing to the ecological success of these termites.
Cockroaches , Isoptera , Animals , Pheromones/metabolism , Monoterpenes/metabolism
The accumulation of oleic acid (OA) in the meibum from patients with meibomian gland dysfunction (MGD) suggests that it may contribute to meibomian gland (MG) functional disorder, as it is a potent stimulator of acne-related lipogenesis and inflammation in sebaceous gland. Therefore, we investigate whether OA induces lipogenesis and inflammasome activation in organotypic cultured mouse MG and human meibomian gland epithelial cells (HMGECs). Organotypic cultured mouse MG and HMGECs were exposed to OA or combinations with specific AMPK agonists 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR). Lipogenic status, ductal keratinization, squamous metaplasia, NLRP3/ASC/Caspase-1 inflammasome activation, proinflammatory cytokine IL-1ß production, and AMPK pathway phosphorylation in MG were subsequently examined by lipid staining, immunofluorescence staining, immunohistochemical staining, ELISA assay, and Western blot analyses. We found that OA significantly induced lipid accumulation, ductal keratinization, and squamous metaplasia in organotypic cultured MG, as evidenced by increased lipids deposition within acini and duct, upregulated expression of lipogenic proteins (SREBP-1 and HMGCR), and elevation of K10/Sprr1b. Additionally, OA induced NLRP3/ASC/Caspase-1 inflammasome activation, cleavage of Caspase-1, and production of downstream proinflammatory cytokine IL-1ß. The findings of lipogenesis and NLRP3-related proinflammatory response in OA-stimulated HMGECs were consistent with those in organotypic cultured MG. OA exposure downregulated phospho-AMPK in two models, while AICAR treatment alleviated lipogenesis by improving AMPK/ACC phosphorylation and SREBP-1/HMGCR expression. Furthermore, AMPK amelioration inhibited activation of the NLRP3/ASC/Caspase-1 axis and secretion of IL-1ß, thereby relieving the OA-induced proinflammatory response. These results demonstrated that OA induced lipogenic disorder and NLRP3 inflammasome activation in organotypic cultured mouse MG and HMGECs by suppressing the AMPK signaling pathway, indicating OA may play an etiological role in MGD.
Carcinoma, Squamous Cell , Inflammasomes , Humans , Mice , Animals , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Sterol Regulatory Element Binding Protein 1/metabolism , Oleic Acid/pharmacology , Oleic Acid/metabolism , Meibomian Glands/metabolism , AMP-Activated Protein Kinases/metabolism , Lipogenesis , Epithelial Cells/metabolism , Caspase 1/metabolism , Cytokines/metabolism , Metaplasia/metabolism , Carcinoma, Squamous Cell/metabolism , Interleukin-1beta/metabolism
Cell line development (CLD) represents a complex but highly critical process during the development of a biological drug. To shed light on this crucial workflow, a team of BioPhorum members (authors) has developed and executed surveys focused on the activities and effort involved in a typical CLD campaign. An average of 27 members from different companies that participate in the BioPhorum CLD working group answered surveys covering three distinguishable stages of a standard CLD process: (1) Pre-transfection, including vector design and construction; (2) Transfection, spanning the initial introduction of vector into cells and subsequent selection and analysis of the pools; and (3) Single Cell Cloning and Lead Clone Selection, comprising methods of isolating single cells and confirming clonal origin, subsequent expansion and screening processes, and methods for identifying and banking lead clones. The surveys were very extensive, including a total of 341 questions split between antibody and complex molecule CLD processes. In this survey review, the authors interpret and highlight responses for antibody development and, where relevant, contrast complex molecule development challenges to provide a comprehensive industry perspective on the typical time and effort required to develop a CHO production cell line.
BACKGROUND: Breast cancer (BC) metastasis is the common cause of high mortality. Conventional prognostic criteria cannot accurately predict the BC metastasis risk. The machine learning technologies can overcome the disadvantage of conventional models. AIM: We developed a model to predict BC metastasis using the random survival forest (RSF) method. METHODS: Based on demographic data and routine clinical data, we used RSF-recursive feature elimination to identify the predictive variables and developed a model to predict metastasis using RSF method. The area under the receiver operating characteristic curve (AUROC) and Kaplan-Meier survival (KM) analyses were plotted to validate the predictive effect when C-index was plotted to assess the discrimination and Brier scores was plotted to assess the calibration of the predictive model. RESULTS: We developed a metastasis prediction model comprising three variables (pathological stage, aspartate aminotransferase, and neutrophil count) selected by RSF-recursive feature elimination. The model was reliable and stable when assessed by the AUROC (0.932 in training set and 0.905 in validation set) and KM survival analyses (p < .0001). The C-indexes (0.959) and Brier score (0.097) also validated the good predictive ability of this model. CONCLUSIONS: This model relies on routine data and examination indicators in real-time clinical practice and exhibits an accurate prediction performance without increasing the cost for patients. Using this model, clinicians can facilitate risk communication and provide precise and efficient individualized therapy to patients with breast cancer.
Breast Neoplasms , Neoplasms, Second Primary , Humans , Female , Breast Neoplasms/diagnosis , Breast Neoplasms/therapy , Area Under Curve , Communication , Leukocyte Count , Machine Learning
