Establishing a Berry Sensory Evaluation Model Based on Machine Learning.

In recent years, people's quality of life has increased, and the requirements for fruits have also become higher; blueberries are particularly popular because of their rich nutrients. In the blueberry industry chain, sensory evaluation is an important link in determining the quality of blueberries. Therefore, to make a more objective scientific evaluation of blueberry quality and reduce the influence of human factors, on the basis of traditional sensory evaluation methods, machine learning is introduced to establish a support vector regression prediction model optimized by the particle swarm algorithm. Ten physical and chemical flavor indices of blueberries (such as catalase, flavonoids, and soluble solids) were used as input data, and sensory evaluation scores were used as output data. Three different predictive models were applied and compared: a particle swarm optimization support vector machine, a convolutional neural network, and a long short-term memory network model. To ensure reliability, the experiments with each of the three models were repeated 20 times, and the mean of each index was calculated. The experimental results showed that the root mean square error and mean absolute error of the particle swarm optimization support vector machine were 0.45 and 0.40, respectively; these values were lower than those of the convolutional neural network (0.96 and 0.78, respectively) and the long short-term memory network (1.22 and 0.97, respectively). Hence, these results highlighted the superiority of the proposed model when sample data are limited.

Molecular Dynamics Simulation of Polymer Nanocomposites with Supramolecular Network Constructed via Functionalized Polymer End-Grafted Nanoparticles.

Since the proposal of self-healing materials, numerous researchers have focused on exploring their potential applications in flexible sensors, bionic robots, satellites, etc. However, there have been few studies on the relationship between the morphology of the dynamic crosslink network and the comprehensive properties of self-healing polymer nanocomposites (PNCs). In this study, we designed a series of modified nanoparticles with different sphericity (η) to establish a supramolecular network, which provide the self-healing ability to PNCs. We analyzed the relationship between the morphology of the supramolecular network and the mechanical performance and self-healing behavior. We observed that as η increased, the distribution of the supramolecular network became more uniform in most cases. Examination of the segment dynamics of polymer chains showed that the completeness of the supramolecular network significantly hindered the mobility of polymer matrix chains. The mechanical performance and self-healing behavior of the PNCs showed that the supramolecular network mainly contributed to the mechanical performance, while the self-healing efficiency was dominated by the variation of η. We observed that appropriate grafting density is the proper way to effectively enhance the mechanical and self-healing performance of PNCs. This study provides a unique guideline for designing and fabricating self-healing PNCs with modified Nanoparticles (NPs).

Molecular dynamics simulation insight into topological structure dependence of self-healing polymer nanocomposites.

Polymer nanocomposites (PNCs), which exhibit excellent mechanical properties through the incorporation of fillers into polymers, have been extensively studied to achieve enhanced self-healing capability for their next-generation development. However, there is still a lack of investigation into the influence of the topological structures of nanoparticles (NPs) on the self-healing capability of PNCs. In this study, we utilized coarse-grained molecular dynamics simulations (CGMDs) to construct a series of PNC systems composed of NPs with different topological structures, including Linear, Ring, and Cross topologies. We employed non-bonding interaction potentials to examine the interactions between the polymer and NPs, and varied the parameters to simulate different functional groups. Our results indicate that the stress-strain curves and the rate of performance loss validate that the Linear structure is the optimal topology for mechanical reinforcement and self-healing properties. By analyzing the stress heat map during stretching, we observed that the Linear structure NPs experience significant stress, allowing the matrix chains to dominate in small recoverable deformations during stretching. It can be speculated that NPs oriented in the direction of extrusion are more effective than others in enhancing performance. Overall, this work provides valuable theoretical guidance and a novel strategy for designing and manipulating high-performance, self-healing PNCs.

Fertility considerations in transgender patients.

PURPOSE OF REVIEW: An update on the latest advances in fertility preservation for transgender women, with an emphasis on the attitudes, access, and techniques. RECENT FINDINGS: With recent warming in perception toward transgendered individuals, fertility preservation services are becoming increasingly available. Although new multidisciplinary transgender clinics are appearing in North America, a 2018 report shows a referral rate for fertility preservation of only 13.5%. Despite interest in child rearing, uptake of fertility preservation is still low as patients are transitioning at increasingly younger ages. Sperm cryopreservation, ideally prior to hormonal therapy, continues to be the mainstay of fertility preservation in transwomen. It is used in conjunction with other assisted reproductive technologies such as intrauterine insemination or in-vitro fertilization with intracytoplasmic sperm injection depending on the quantity of sperm available. Recent research reporting successful autologous grafting of cryopreserved prepubertal testis leading to sperm production and offspring in macaques show great promise in the context of fertility preservation in prepubertal patients. SUMMARY: Despite the increasing accessibility of fertility preservation, referral rates and usage continue to be low, suggesting that barriers are still in place for these individuals. Clinicians must continue to counsel patients regarding the process of fertility preservation and advocate for reduction of financial and infrastructural barriers.

Erratum: Tertiary Lymphoid Structures Associate with Tumour Stage in Urothelial Bladder Cancer.

[This corrects the article DOI: 10.3233/BLC-170120.].

Tertiary Lymphoid Structures Associate with Tumour Stage in Urothelial Bladder Cancer.

BACKGROUND: Urothelial bladder cancer (UBC) is a highly prevalent disease in North America, however its optimal management remains elusive. The contribution of B cell associated responses is poorly understood in bladder cancer. Lymphoid neogenesis is a hallmark of an active immune response at tumor sites that sometimes leads to formation of tertiary lymphoid structures (TLS) that resemble germinal centers formed in secondary lymphoid organs. OBJECTIVE: This study was conducted with an aim to investigate the presence and characteristics of TLS in UBC with a focus to compare and contrast the TLS formation in treatment naive low grade non-muscle invasive (NMIBC) and muscle invasive bladder cancers (MIBC). METHODS: The study cohort consisted of transurethral bladder resection tumour (TURBT) specimens from 28 patients. Sections showing lymphoid aggregates in hematoxylin and eosin (H&E) stained TURBT specimens were further subjected to multi-color immunohistochemistry using immune cell markers specific to CD20+ B cells, CD3+ and CD8+ T cells, PNAd+ high endothelial venules, CD208+ mature dendritic cells, CD21+ follicular dendritic cells to confirm the hallmarks of classical germinal centers. RESULTS: Our pilot study investigating the presence of TLS in bladder cancer patients is the first to demonstrate that well-formed TLS are more common in aggressive high grade MIBC tumors compared to low grade NIMBC. CONCLUSIONS: These novel findings suggest B cell mediated anti-tumour humoral immune responses in bladder cancer progression.

Comprehensive immune transcriptomic analysis in bladder cancer reveals subtype specific immune gene expression patterns of prognostic relevance.

Recent efforts on genome wide profiling of muscle invasive bladder cancer (MIBC) have led to its classification into distinct genomic and transcriptomic molecular subtypes that exhibit variability in prognosis. Evolving evidence from recent immunotherapy trials has demonstrated the significance of pre-existing tumour immune profiles that could guide treatment decisions. To identify immune gene expression patterns associated with the molecular subtypes, we performed a comprehensive in silico immune transcriptomic profiling, utilizing transcriptomic data from 347 MIBC cases from The Cancer Genome Atlas (TCGA). To investigate subtype-associated immune gene expression patterns, we assembled 924 immune response genes and specifically those involved in T-cell cytotoxicity and the Type I/II interferon pathways. A set of 157 ranked genes was able to distinguish the four subtypes in an unsupervised analysis in an original training cohort (n=122) and an expanded, validation cohort (n=225). The most common overrepresented pathways distinguishing the four molecular subtypes, included JAK/STAT signaling, Toll-like receptor signaling, interleukin signaling, and T-cell activation. Some of the most enriched biological processes were responses to IFN-γ, antigen processing and presentation, cytokine mediated signaling, hemopoeisis, cell proliferation and cellular defense response in the TCGA cluster IV. Our novel findings provide further insights into the association between genomic subtypes and immune activation in MIBC and may open novel opportunities for their exploitation towards precise treatment with immunotherapy.

CXCL10 alters the tumour immune microenvironment and disease progression in a syngeneic murine model of high-grade serous ovarian cancer.

OBJECTIVE: We recently established that high STAT1 expression and associated T helper type I tumour immune microenvironment (TME) are prognostic and chemotherapy response predictive biomarkers in high-grade serous ovarian cancer (HGSC). STAT1 induced chemokine CXCL10 is key to the recruitment of lymphocytes in the TME and is significantly highly expressed in the tumours from patients with longer survival. In the current study we therefore aimed to elucidate the role CXCL10 in disease progression and tumour immune transcriptomic alterations using the ID8 syngeneic murine model of HGSC. METHODS: ID8 ovarian cancer cells were engineered for stable knockdown (KD) and overexpression (OX) of CXCL10. The OX and KD cell line derivatives, along with their respective vector controls, were implanted in immunocompetent C57BL/6 mice via intra-peritoneal injections. At end point, immune transcriptomic profiling of tumour tissues and multiplex cytokine profiling of ascites, was performed. Effect of CXCL10 expression on the tumour vasculature and tumour cell proliferation was evaluated by CD31 and Ki67 immunostaining, respectively. RESULTS: Increased CXCL10 expression led to decreased tumour burden and malignant ascites accumulation in the ID8 syngeneic murine model of HGSC. The ascites levels of IL-6 and VEGF were significantly reduced in OX mice compared to the vector controls. The OX tumours also showed reduced vasculature (CD31) and proliferative index (Ki67) compared to the control tumours. Significantly higher expression of genes associated with antigen processing, apoptosis and T cell function was observed in OX tumours compared to the controls. Reduced CXCL10 expression in tumours from KD mice led to increased ascites accumulation and disease progression compared to the controls. CONCLUSION: CXCL10 is a positive determinant of anti-tumour immune responses in HGSC TME and disease progression. These findings are foundational for future translational studies aimed at improving treatment response and survival in HGSC patients, via exploiting the TME.

STAT1-associated intratumoural TH1 immunity predicts chemotherapy resistance in high-grade serous ovarian cancer.

High-grade serous ovarian carcinoma (HGSC) accounts for 70% of all epithelial ovarian cancers but clinical management is challenged by a lack of accurate prognostic and predictive biomarkers of chemotherapy response. This study evaluated the role of Signal Transducer and Activator of Transcription 1 (STAT1) as an independent prognostic and predictive biomarker and its correlation with intratumoural CD8+ T cells in a second independent biomarker validation study. Tumour STAT1 expression and intratumoural CD8+ T cell infiltration were assessed by immunohistochemistry as a multicentre validation study conducted on 734 chemotherapy-naïve HGSCs. NanoString-based profiling was performed to correlate expression of STAT1 target genes CXCL9, CXCL10 and CXCL11 with CD8A transcript expression in 143 primary tumours. Multiplexed cytokine analysis of pre-treatment plasma from resistant and sensitive patients was performed to assess systemic levels of STAT1-induced cytokines. STAT1 was validated as a prognostic and predictive biomarker in both univariate and multivariate models and its expression correlated significantly with intra-epithelial CD8+ T cell infiltration in HGSC. STAT1 levels increased the prognostic and predictive value of intratumoural CD8+ T cells, confirming their synergistic role as biomarkers in HGSC. In addition, expression of STAT1 target genes (CXCL9, CXCL10 and CXCL11) correlated significantly with levels of, and CD8A transcripts from intratumoural CD8+ T cells within the resistant and sensitive tumours. Our findings provide compelling evidence that high levels of STAT1, STAT1-induced chemokines and CD8+ T cells correlate with improved chemotherapy response in HGSC. These results identify STAT1 and its target genes as novel biomarkers of chemosensitivity in HGSC. These findings provide new translational opportunities for patient stratification for immunotherapies based on emerging biomarkers of inflammation in HGSC. An improved understanding of the role of interferon-inducible genes will be foundational for developing immunomodulatory therapies in ovarian cancer.