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Background: The oscillometrically measured ankle-brachial index (omABI), which is determined by the ratio of ankle to brachial systolic blood pressure measured through oscillography, has been demonstrated as a robust predictor of cardiovascular events. However, the reliability of mean arterial pressure measured by oscillography may be higher than that of systolic blood pressure based on the principle of oscillographic oscillation. We aimed to compare the predictive value of oscillometrically measured ankle-tobrachial mean arterial pressure ratio (omMAPR) and omABI for cardiovascular events and all-cause mortality. Methods: The observation cohort consisted of a total of 37 803 employees from the Chinese Kailuan Group who underwent limb blood pressure measurements during their participation in physical examination between 2010 and 2017. Results: After an average follow-up period of 3 years, a total of 589 cardiovascular events and 570 cases of all-cause mortality were observed. The predictive performance of omMAPR was found to be slightly superior to omABI in terms of cardiovascular events (C-statistics: 0.55 vs. 0.51, P < .001) and all-cause mortality (C-statistics: 0.60 vs. 0.55, P < .001). After adjusting for confounders, within a specific range (omMAPR ≤ 1.06 or omABI ≤ 1.12), each 0.1-unit increase in omMAPR was associated with reductions of 14% (HR = 0.86, 95% CI: 0.77-0.96) and 23% (HR = 0.77, 95% CI: 0.70-0.84) in cardiovascular events and allcause mortality, respectively, while each 0.1-unit increase in omABI was associated with reductions of 12% (HR = 0.88, 95% CI: 0.79-0.97) and 22% (HR = 0.78, 95% CI: 0.72-0.85) in cardiovascular events and all-cause mortality, respectively. However, once out of that range (omMAPR > 1.06 or omABI > 1.12), neither omMAPR nor omABI was significantly associated with cardiovascular events or all-cause mortality. Conclusion: Both omMAPR and omABI within specific ranges (omMAPR ≤ 1.06 or omABI ≤ 1.12) were independent predictors for cardiovascular events and all-cause mortality. Moreover, omMAPR exhibited a slightly superior predictive ability compared to omABI in relation to cardiovascular events and all-cause mortality. The trial registration number is ChiCTR-TNRC-11001489. [ABSTRACT FROM AUTHOR]

Background: The mechanism of cognitive impairment in hemodialysis patients is multifactorial. The relationship between cerebral blood flow and the decline of cognitive function is poorly understood. Objective: To investigate the association between cerebral blood flow variation and decline of cognitive function in older patients undergoing hemodialysis. Methods: In this prospective observational cohort study of 121 older patients undergoing hemodialysis, we used transcranial Doppler ultrasound (TCD) to measure cerebral arterial mean flow velocity (MFV) throughout dialysis, assessed cognitive function at baseline and 12-month follow-up, and then analyzed associations between MFV and changes on cognitive scores. Results: TCD recordings demonstrated a significant reduction in MFV throughout dialysis, which were significantly correlated with cumulative ultrafiltration volume (rho 0.356, p < 0.001), ΔSBP (rho 0.251, p = 0.005), and ΔMAP (rho 0.194, p = 0.032). Compared with the baseline assessments, cognitive scores of participants at the 12-month follow-up were significantly worsened in global cognition (MOCA), some tests of memory (CFT-memory), executive function (TMT-B, SCWT-C, and SCWT-T), attention/processing speed (SDMT), and visuospatial function (CFT-copy) (p < 0.05). The worsening scores in global cognition (MOCA) (β = 0.066, 95% CI 0.018-0.113, p = 0.007) and some tests of memory (AVLT5) (β = 0.050, 95% CI 0.004-0.097, p = 0.035) and executive function (TMT-B, SCWT-C, SCWT-T) (β = 1.955, 95% CI 0.457--3.453, p = 0.011; β = 0.298, 95% CI 0.112-0.484, p = 0.002 and β = 1.371, 95% CI 0.429-2.303, p = 0.004, respectively) were significantly associated with the reduction of MFV. Conclusion: Hemodialysis may significantly reduce cerebral blood flow in older patients; Repetitive intradialytic decreases in CBF may be one of the mechanisms underlying the decline of cognitive function. [ABSTRACT FROM AUTHOR]

In this paper, we examine the problems of existence and computation of proper and stable stabilising compensators in the feedback path of a special class of linear time-invariant multivariable systems characterised by a strictly proper transfer function matrix. For the class of systems that are 'square', i.e. have the same number of inputs and outputs and have no zeros in the closed right half complex plane and the class of 'non-square' systems that include a 'square' subsystem that has no zeros in the closed right half complex plane we present a sufficient condition for the existence and computation of proper stabilising (pole placing) compensators which in certain cases that depend on the transfer function matrix of the system can be chosen to be stable. [ABSTRACT FROM AUTHOR]

Neuromorphic computing has the potential to achieve the requirements of the next-generation artificial intelligence (AI) systems, due to its advantages of adaptive learning and parallel computing. Meanwhile, biocomputing has seen ongoing development with the rise of synthetic biology, becoming the driving force for new generation semiconductor synthetic biology (SemiSynBio) technologies. DNA-based biomolecules could potentially perform the functions of Boolean operators as logic gates and be used to construct artificial neural networks (ANNs), providing the possibility of executing neuromorphic computing at the molecular level. Herein, we briefly outline the principles of neuromorphic computing, describe the advances in DNA computing with a focus on synthetic neuromorphic computing, and summarize the major challenges and prospects for synthetic neuromorphic computing. We believe that constructing such synthetic neuromorphic circuits will be an important step toward realizing neuromorphic computing, which would be of widespread use in biocomputing, DNA storage, information security, and national defense. [ABSTRACT FROM AUTHOR]

Objective: Atrial fibrillation (AF), the most common cardiac arrhythmia, presents significant health challenges, and the intricate connection between insomnia and AF has garnered substantial attention. This cohort study aims to investigate the relationship between insomnia and AF recurrences following radiofrequency ablation. Materials and Methods: Data were retrieved from an electronic database of patients who underwent radiofrequency ablation for AF. The primary endpoint was AF recurrence. We utilized a multivariable Cox model, coupled with three propensity score methods, for analysis. Results: Between January 1, 2017, and June 1, 2022, 541 patients who underwent radiofrequency ablation for AF were recorded in the database. After excluding 185 patients, the final cohort comprised 356 patients. Among them, 68 were afflicted by insomnia, while 288 were not. Over a median follow-up of 755 days, one patient died, and 130 (36.5%) experienced AF recurrence. Multivariate Cox regression analysis revealed that the insomnia group had a higher risk of AF recurrence compared to the non-insomnia group (HR: 1.83, 95% CI: 1.16-2.89). Further landmark analysis showed no significant difference in AF recurrence rates during the initial 1-year follow-up. However, beyond 1 year, the insomnia group demonstrated a significantly higher AF recurrence rate. As the number of insomnia symptoms increased, the risk of AF recurrence also rose significantly, indicating a dose-response relationship. Conclusion: This study establishes a significant link between insomnia and long-term AF recurrence following radiofrequency ablation. It underscores the importance of identifying and addressing insomnia in patients with AF undergoing radiofrequency ablation. [ABSTRACT FROM AUTHOR]

The transformation of lung adenocarcinoma to small cell lung cancer (SCLC) is a recognized resistance mechanism and a hindrance to therapies using epidermal growth factor receptor tyrosine kinase inhibitors (TKIs). The paucity of pretranslational/posttranslational clinical samples limits the deeper understanding of resistance mechanisms and the exploration of effective therapeutic strategies. Here, we developed preclinical neuroendocrine (NE) transformation models. Next, we identified a transcriptional reprogramming mechanism that drives resistance to erlotinib in NE transformation cell lines and cell-derived xenograft mice. We observed the enhanced expression of genes involved in the EHMT2 and WNT/ß-catenin pathways. In addition, we demonstrated that EHMT2 increases methylation of the SFRP1 promoter region to reduce SFRP1 expression, followed by activation of the WNT/ß-catenin pathway and TKI-mediated NE transformation. Notably, the similar expression alterations of EHMT2 and SFRP1 were observed in transformed SCLC samples obtained from clinical patients. Importantly, suppression of EHMT2 with selective inhibitors restored the sensitivity of NE transformation cell lines to erlotinib and delayed resistance in cell-derived xenograft mice. We identify a transcriptional reprogramming process in NE transformation and provide a potential therapeutic target for overcoming resistance to erlotinib. [ABSTRACT FROM AUTHOR]

Background: Acute Respiratory Distress Syndrome (ARDS) or its earlier stage Acute lung injury (ALI), is a worldwide health concern that jeopardizes human well-being. Currently, the treatment strategies to mitigate the incidence and mortality of ARDS are severely restricted. This limitation can be attributed, at least in part, to the substantial variations in immunity observed in individuals with this syndrome. Methods: Bulk and single cell RNA sequencing from ALI mice and single cell RNA sequencing from ARDS patients were analyzed. We utilized the Seurat program package in R and cellmarker 2.0 to cluster and annotate the data. The differential, enrichment, protein interaction, and cell-cell communication analysis were conducted. Results: The mice with ALI caused by pulmonary and extrapulmonary factors demonstrated differential expression including Clec4e, Retnlg, S100a9, Coro1a, and Lars2. We have determined that inflammatory factors have a greater significance in extrapulmonary ALI, while multiple pathways collaborate in the development of pulmonary ALI. Clustering analysis revealed significant heterogeneity in the relative abundance of immune cells in different ALI models. The autocrine action of neutrophils plays a crucial role in pulmonary ALI. Additionally, there was a significant increase in signaling intensity between B cells and M1 macrophages, NKT cells and M1 macrophages in extrapulmonary ALI. The CXCL, CSF3 and MIF, TGFβ signaling pathways play a vital role in pulmonary and extrapulmonary ALI, respectively. Moreover, the analysis of human single-cell revealed DCs signaling to monocytes and neutrophils in COVID-19-associated ARDS is stronger compared to sepsis-related ARDS. In sepsis-related ARDS, CD8+ T and Th cells exhibit more prominent signaling to Bcell nucleated DCs. Meanwhile, both MIF and CXCL signaling pathways are specific to sepsis-related ARDS. Conclusion: This study has identified specific gene signatures and signaling pathways in animal models and human samples that facilitate the interaction between immune cells, which could be targeted therapeutically in ARDS patients of various etiologies. [ABSTRACT FROM AUTHOR]

The genus Metarhizium is one of the most significant entomopathogenic fungi with diverse morphological characteristics and host species. Species of Metarhizium have been widely used for pest control as an environmentally safe alternative to chemical pesticides. This study reports a new species of Metarhizium and a new record of M. bibionidarum from China. The taxonomic positions of the two species within Metarhizium were assessed by morphological and multi-gene phylogenetic data. This assessment confirmed that the new species M. dianzhongense on white grubs (Coleoptera) is a sister to M. ellipsoideum on adult leafhoppers (Hemiptera) and represents a distinctive fungus according to the morphological and phylogenetic evidence. The two species, M. dianzhongense and M. bibionidarum, were described and illustrated. Pathogenicity tests by M. bibionidarum and M. dianzhongense were performed on early instar larvae of the significant agricultural pest Spodoptera frugipera (Lepidoptera). The results demonstrated that both M. bibionidarum and M. dianzhongense exhibit significant insecticidal activity against larvae of S. frugipera, providing new fungal resources for the development of an eco-friendly biocontrol agent against this pest. [ABSTRACT FROM AUTHOR]

Silicon nitride (Si3N4) ceramics with initial β-Si3N4 content from3% to 88% were prepared by spark plasma sintering from 1450 to 1700°C. The effect of initial β-Si3N4 content on the phase transition, microstructure evolution, andmechanical properties of the Si3N4 ceramics was studied. The existence of initial β-Si3N4 accelerated the α-β phase transition. When the initial β-Si3N4 content was 12% and 46%, the aspect ratio of the grains was increased. When the initial β-Si3N4 content was 88%, the grains were mainly composed of short rod-like grains. As the initial β-Si3N4 content increased, the densification process was slowed down. The hardness and fracture toughness of samples reached about 18 GPa and 6 MPa•m1/2. It is proposed that the mechanical properties of samples are connected with the densification process and β-Si3N4 content. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to explore the clinical characteristics of male breast cancer (MBC) patients and the factors influencing their prognosis. Methods: We conducted a retrospective case series analysis of 117 MBC cases who were treated at Zhejiang Cancer Hospital from 2009 to 2022. Cox proportional hazard model was used to identify prognostic factors of MBC. Nomogram was constructed based on these factors, which was further evaluated by C-index and calibration curves. Results: A total of 115 MBC cases were finally included in our analyses, with median diagnosis age of 59 years. Of these cases, 80.0% were estrogen receptor (ER) positive, 79.2% were progesterone receptor (PR) positive, 48.7% were human epidermal growth factor receptor 2 (HER2) negative, and 42.6% had Ki67 levels higher than 15%. 108 (93.9%) cases underwent radical mastectomy, while only 3 (2.6%) received breast-conserving surgery. The Logrank test suggested that lymphocyte-to-monocyte ratio (LMR) was negatively associated with both overall survival (OS) and disease-free survival (DFS) of MBC, while platelet-tolymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) were only positively associated with OS (all P-values < 0.05). Multivariate regression analysis showed that age (HR 1.08, 95% CI 1.03-1.13) was significant prognostic factors for OS. Meanwhile, age (HR 1.06, 95% CI 1.02-1.10), histological differentiation grade (poorly differentiated/undifferentiated vs. welldifferentiated: HR 2.55, 95% CI 1.05-6.17), and TNM stage (IV vs. I: HR 31.59, 95% CI 6.01-165.93) were also significant prognostic factors for DFS. Nomograms were developed for DFS, with C-indexes of 0.782, indicating good predictive performance. Conclusion: Increased age, bigger tumor size, higher TNM stage, and lower histological differentiation grade were associated with poor MBC prognosis, and LMR, PLR, and NLR might be potential predictors for MBC prognosis. [ABSTRACT FROM AUTHOR]

Sea cucumber (Apostichopus japonicus) is one of the cultured species with the highest production value to a single species in China’s marine agricultural industry with high nutritional and medicinal value. Body color influences numerous biological functions in sea cucumbers, and it has become a key trait in selective breeding. It is found that a cultivation environment with strong light intensity leads to a lighter body color of A. japonicus compared to dark conditions. However, little research has been conducted on the molecular mechanisms regulating body color in different breeding environments. In this study, we used Illumina sequencing to examine gene expression patterns in green and purple A. japonicus exposed to different culture conditions. Overall, the genes in the body wall of purple individuals were more affected by the environment. We also identified pathways that were potentially influenced by the breeding environment, such as “Drug metabolism - cytochrome P450”, “Porphyrin and chlorophyll metabolism”, “Phosphatidylinositol signaling system”, “TGF-beta signaling”, and “mTOR signaling”. The aim of this study was to determine the light conditions and breeding environment that are more favorable to the requirements of body color in A. japonicus and apply them to the selection of high-quality breeds. The results obtained will support the breeding of A. japonicus with specific traits and the production of seedlings to promote the development of this maricultural industry. [ABSTRACT FROM AUTHOR]

As power information systems play an increasingly critical role in modern society, higher requirements are placed on the performance and reliability of their network infrastructure. In order to cope with the growing data traffic and network attack threats in the power information system, we select the power information system data center network as the research object and design an overall system solution based on software defined network, including the application layer, control layer and infrastructure layer. A typical fat tree network topology is simulated and analyzed. We define the load balancing and network topology dynamic adjustment problem as a Markov decision process, and design a data flow path acquisition method based on breadth-first search to construct the action space of each host. Then, a deep reinforcement learning algorithm based on deep Q-network, priority experience replay and target network is introduced to provide solutions for optimizing the performance of power information systems and responding to network attacks. Simulation results show that the proposed method is better than the traditional equal-cost multi-path algorithm in terms of average bandwidth utilization, average jitter and average packet loss, and can reduce the probability of network nodes being attacked by more than 11%. [ABSTRACT FROM AUTHOR]

Introduction: Glutathione S-transferase (GST) enzymes play a crucial role in detoxification by catalysing the conjugation of many hydrophobic and electrophilic compounds with reduced glutathione. Polymorphisms in GST genes may influence the susceptibility to various cancers, including melanoma. Aim: We reported a systematic review and meta-analysis to evaluate the association between GST polymorphisms and susceptibility to cutaneous melanoma. Material and methods: A comprehensive search of four databases, namely PubMed, Scopus, Cochrane Library, and Web of Science, was conducted to gather pertinent studies up until 24 August 2023. No restrictions were imposed during the search. The analysis included 32 studies and was broken down into subgroups based on ethnicity, control source, control matching, quality score, and sample size. Results: The forest plot analyses on GSTM1, GSTT1, combined GSTM1/GSTT1, and GSTP1 polymorphisms in relation to melanoma risk showed no statistically significant differences between the case and control groups, except for the recessive model of GSTP1 polymorphism. The analysis revealed significant associations between GSTM1 polymorphisms and melanoma risk in Asians and in studies with a sample size of less than 200. For the combined GSTM1/GSTT1 polymorphisms, a significant association was found in hospital-based controls. Conclusions: While this study enhances our understanding of the genetic factors influencing melanoma risk, it also highlights the need for further research. The current evidence is not sufficient to confirm or reject the intervention effect. Future research should consider gene-gene and gene-environment interactions, which could offer a more comprehensive understanding of the complex biology of melanoma. [ABSTRACT FROM AUTHOR]

With the theoretical and technological developments related to cratonic strike-slip faults, the Shuntuoguole Low Uplift in the Tarim Basin has attracted considerable attention recently. Affected by multistage tectonic movements, the strike-slip faults have controlled the distribution of hydrocarbon resources owing to the special fault characteristics and fault-related structures. In contrast, the kinematics and formation mechanism of strike-slip faults in buried sedimentary basins are difficult to investigate, limiting the discussion of these faults and hydrocarbon accumulation. In this study, we identified the characteristics of massive sigmoidal tension gashes (STGs) that formed in the Shunnan area of the Tarim Basin. High-resolution three-dimensional seismic data and attribute analyses were used to investigate their geometric and kinematic characteristics. Then, the stress state of each point of the STGs was calculated using seismic curvature attributes. Finally, the formation mechanism of the STGs and their roles in controlling hydrocarbon migration and accumulation were discussed. The results suggest that: (1) the STGs developed in the Shunnan area have a wide distribution, with a tensile fault arranged in an en échelon pattern, showing an S-shaped bending. These STGs formed in multiple stages, and differential rotation occurred along the direction of strike-slip stress during formation. (2) Near the principal displacement zone of the strike-slip faults, the stress value of the STGs was higher, gradually decreasing at both ends. The shallow layer deformation was greater than the deep layer deformation. (3) STGs are critical for connecting source rocks, migrating oil and gas, sealing horizontally, and developing efficient reservoirs. This study not only provides seismic evidence for the formation and evolution of super large STGs, but also provides certain guidance for oil and gas exploration in this area. [ABSTRACT FROM AUTHOR]

Gestational diabetes (GDM) changes the maternal metabolic and uterine environment, thus increasing the risk of short- and long-term adverse outcomes for both mother and child. Children of mothers who have GDM during their pregnancy are more likely to develop Type 2 Diabetes (T2D), early-onset cardiovascular disease and GDM when they themselves become pregnant, perpetuating a multigenerational increased risk of metabolic disease. The negative effect of GDM is exacerbated by maternal obesity, which induces a greater derangement of fetal adipogenesis and growth. Multiple factors, including genetic, epigenetic and metabolic, which interact with lifestyle factors and the environment, are likely to contribute to the development of GDM. Genetic factors are particularly important, with 30% of women with GDM having at least one parent with T2D. Fetal epigenetic modifications occur in response to maternal GDM, and may mediate both multi- and transgenerational risk. Changes to the maternal metabolome in GDM are primarily related to fatty acid oxidation, inflammation and insulin resistance. These might be effective early biomarkers allowing the identification of women at risk of GDM prior to the development of hyperglycaemia. The impact of the intrauterine environment on the developing fetus, "developmental programming", has a multisystem effect, but its influence on adipogenesis is particularly important as itwill determine baseline insulin sensitivity, and the response to future metabolic challenges. Identifying the critical window of metabolic development and developing effective interventions are key to our ability to improve population metabolic health. [ABSTRACT FROM AUTHOR]

Based on the electromagnetic shaker table, the resonant fatigue testing system and the corresponding conventional fatigue testing system were designed respectively. The fatigue life (S-N) curves of smooth and notched 7050-T7451 aluminum alloy specimens were measured in the range of 105 - 107 cycles, and the notch fatigue property of 7050-T7451 aluminum alloy under bending resonance environment was studied. The results indicate that the fracture mechanism under bending resonant fatigue environment is roughly the same as that under bending conventional fatigue loading. All the S-N curves obtained through resonant and conventional fatigue tests show a continuously downward trend, and there are no obvious fatigue limits. Notch fatigue property under bending resonance environment presents "stage characteristics", which increases first and then decreases with the increase of cycles. There is a critical cycle number Nc at 8×105 cycles, corresponding to the maximum fatigue notch factor Kf-max (or the maximum notch sensitivity factor qmax). There are two critical cycles N1 and N2. When N¹ < N < N2, the notch fatigue property of the material and the corresponding structures under resonance environment requires more consideration than conventional fatigue loading. [ABSTRACT FROM AUTHOR]

A variety of functionalized 2‐pyrrolidinones bearing N‐trifluoromethylphenyl moieties were prepared in moderate to good yields with high diastereoselectivity through copper(II)‐catalyst and base co‐catalyzed formal [4+1] cycloaddition of cinnamaldehyde nitrones with 1‐ethynylnaphthalen‐2‐ols in the presence of m‐CPBA as the oxidant. The triple bond of 1‐ethynylnaphthalen‐2‐ol served as one‐carbon synthon for the pyrrolidinone ring formation. Mechanistic studies revealed that m‐CPBA played an important role to interrupt the intramolecular O‐cyclization to afford the 2‐pyrrolidinones. Moreover, the reaction could be easily performed at gram scales and the obtained products were selectively converted into diverse pyrroline scaffolds. [ABSTRACT FROM AUTHOR]

To investigate the characteristics of respiratory involvement in Chinese paediatric neuromuscular disease (NMD) at early stage and to explore convenient monitoring methods. Children with NMD (age < 18) diagnosed at a multidisciplinary joint NMD clinic at Peking University First Hospital from January 2016 to April 2021 were included. Overnight polysomnography (PSG) and pulmonary function test (PFT) data were analysed, and the characteristics of four groups: congenital muscular dystrophy (CMD), congenital myopathy, spinal muscular atrophy, and Duchenne muscular dystrophy (DMD) were compared. A total of 83 children with NMD were referred for respiratory assessment, of who 80 children underwent PSG; 41 performed spirometry and 38, both. The duration of pulse oxygen saturation (SpO2) <90% over apnoea and hypopnoea index (AHI) was lowest in DMD and significantly different from CMD (p = 0.033). AHI was positively correlated with the oxygen desaturation index (ODI) (r = 0.929, p = 0.000). The peak expiratory flow (PEF) were positively correlated with forced vital capacity (FVC), both as actual values and percent pred, respectively (r = 0.820, 0.719, p = 0.000). ROC derived sensitivity and specificity of prediction of AHI > 15/h or duration of SpO2<90% ≥ 60 min from FVC <51% pred was 75.8% and 85.7%, respectively. AHI and hypoxia burden were independent factors in children with NMD in PSG and attention needed to be paid in both. FVC might be a daytime predictor for significant sleep-disordered breathing or hypoxia. Nocturnal consecutive oximetry with diurnal peak flow measurement may be convenient and effective for home monitoring at early stage of respiratory involvement. [ABSTRACT FROM AUTHOR]

Due to its extremely complex pathogenesis, no effective drugs to prevent, delay progression, or cure Alzheimer's disease (AD) exist at present. The main pathological features of AD are senile plaques composed of ß-amyloid, neurofibrillary tangles formed by hyperphosphorylation of the tau protein, and degeneration or loss of neurons in the brain. Many risk factors associated with the onset of AD, including gene mutations, aging, traumatic brain injury, endocrine and cardiovascular diseases, education level, and obesity. Growing evidence points to chronic stress as one of the major risk factors for AD, as it can promote the onset and development of AD-related pathologies via a mechanism that is not well known. The use of murine stress models, including restraint, social isolation, noise, and unpredictable stress, has contributed to improving our understanding of the relationship between chronic stress and AD. This review summarizes the evidence derived from murine models on the pathological features associated with AD and the related molecular mechanisms induced by chronic stress. These results not only provide a retrospective interpretation for understanding the pathogenesis of AD, but also provide a window of opportunity for more effective preventive and identifying therapeutic strategies for stressinduced AD. [ABSTRACT FROM AUTHOR]

Background: Topical therapy has been shown to induce an immune response in patients with hepatocellular carcinoma (HCC). In this study, a prospective parallel group control experiment was conducted to compare the differences between radiofrequency ablation and microwave ablation in inducing the immune regulation of NK cells. Methods: Sixty patients with clinically and pathologically confirmed hepatitis Bassociated hepatocellular carcinoma (HCC) were selected for thermal ablation. Patients were randomly assigned into the MWA group (n = 30) and the RFA group (n = 30). Patient’s peripheral blood was isolated on days D0, D7, and month M1. NK cell subsets, receptors, and killing function were detected by flow cytometry and LDH. Student t test and rank sum test were used to compare the statistical differences between the RFA (radio frequency) and MWA (microwave) groups. The Kaplan-Meier curve and log-rank test were used to calculate the difference between the two survival curves. Results: Comparison of the frequency of CD3-CD56+ and CD3-CD56+CD16+ in NK cells between the RFA and WMA groups showed that there was no difference in the D0, D7, M1, D7-D0, M1-D0, and M1-D7 groups. The changes of the inhibitory NK cell receptor CD159A were significantly different at D7 (P<0.05). CD107a were compared between the RFA and WMA groups, indicating that CD107a changes induced by NK cells were significantly different at D7-D0 (P<0.05). Comparison of NK cell lysis activity of target K562 cells between the RFA and WMA groups showed that there was no difference at D0, D7, D7-D0. There was no difference in recurrence-free survival (RFS) between the RFA and WMA groups (P=0.11). Conclusions: The difference between MWA and RFA-induced NK cell changes was mainly manifested in the inhibitory receptors CD159a and CD107a 1 week after surgery, with microwave-induced changes being more severe. Comparison of the NK cell lysis activity of the target K562 cells between the RFA and WMA groups showed that there was no difference in D0, D7, D7- D0. Survival analysis showed that these differences did not affect the recurrence-free survival (RFS) in the two groups. [ABSTRACT FROM AUTHOR]

Purpose: Opioid use disorder is a significant global problem. Chronic heroin use is associated with impairment of cognitive function and conscious control ability. The cholinergic system can be disrupted following heroin administration, indicating that activation of the cholinergic system may prevent chronic heroin misuse. Donepezil as an inhibitor of cholinesterase has been reported to clinically improve cognition and attention. In this study, the inhibition of heroin self-administration and heroin-seeking behaviours by donepezil were evaluated in rats. Methods: Rats were trained to self-administer heroin every four hours for 14 consecutive days under a fixed ratio 1 (FR1) reinforcement schedule, then underwent withdrawal for two weeks. A progressive ratio schedule was then used to evaluate the relative motivational value of heroin reinforcement. After withdrawal, a conditioned cue was introduced for the reinstatement of heroin-seeking behaviour. Donepezil (0.3–3 mg/kg, i.p.) was used during both the FR1 heroin self-administration and progressive ratio schedules. Immunohistochemistry was used to investigate the mechanism of action of donepezil in the rat brain. Results: Pretreatment with high dose donepezil (3 mg/kg) but not low doses (0.3–1 mg/kg) significantly inhibited heroin self-administration under the FR1 schedule. Donepezil decreased motivation values under the progressive ratio schedule in a dose-dependent manner. All doses of donepezil (1–3 mg/kg) decreased the reinstatement of heroin seeking induced by cues. Correlation analysis indicated that the inhibition of donepezil on heroin-seeking behaviour was positively correlated with an increased expression of dopamine receptor 1 (D1R) and dopamine receptor 2 (D2R) in the nucleus accumbens (NAc) and increased expression of choline acetyltransferase (ChAT) in the ventral tegmental area (VTA). Conclusions: The present study demonstrated that donepezil could inhibit heroin intake and heroin-seeking behaviour. Further, donepezil could regulate dopamine receptors in the NAc via an increase of acetylcholine. These results suggested that donepezil could be developed as a potential approach for the treatment of heroin misuse. [ABSTRACT FROM AUTHOR]

The study presents an adaptive robust control method for the Pendubot subjects to matched and mismatched uncertainty. First, the control task is formatted as a reduced-dimension equality constraint of the system states. To handle the matched and mismatched uncertainties, an orthogonal decomposition method is employed to make the mismatched part disappear after decomposition. Based on the above, an adaptive robust control law based on constraint-following is devised. By the Lyapunov approach, it is rigorously proven that the proposed approach ensures the uniform boundedness and uniform ultimate boundedness of the closed-loop control system and thus renders approximate constraint-following, regardless of uncertainty. Simulation and experimental results are provided and discussed, demonstrating the good performance of the proposed approach. [ABSTRACT FROM AUTHOR]

Whether the northern margin of the North China Craton (NCC) was a continental arc or in a lithospheric extensional setting during the Carboniferous is the primary divergence among different tectonic models about the terminal evolutionary history of the southeastern Central Asian Orogenic Belt (CAOB). The Alxa block is the western segment of the northern NCC and contiguous to the southeastern CAOB, and therefore the tectonic setting of the Carboniferous magmatic intrusions in this block can shed light on this controversy. In this contribution, new zircon U–Pb ages, elemental geochemistry, and Sr-Nd isotopes are presented for thirteen Late Carboniferous (~318–300 Ma) magmatic intrusions in the southwestern Alxa block. Among them, seven calc-alkaline I-type granites and one aluminous A2-type granite were probably generated by the partial melting and crystallization differentiation of various crustal sources (perhaps including earlier orogenic materials) under different temperature conditions. Four quartz diorites and one hornblende gabbro may be the partial melts of subduction-modified basaltic lower crust sources and sub-continental lithospheric mantle sources, respectively. According to the integration of the new results and regional geological correlations, the Alxa block and the southeastern CAOB were most likely in a uniform tectonic regime during the Carboniferous. At that time, this region was characterized by the lithospheric extension-related magmatic rock associations, the increasing mantle inputs over time, the clockwise P–T paths of high temperature-low pressure metamorphic rocks, and the transgression sedimentary sequences. All these lines of evidence suggest an intra-continental lithospheric extensional setting rather than a continental arc setting for the southeastern CAOB during the Carboniferous. [ABSTRACT FROM AUTHOR]

Late-life depression (LLD) is one of the most common mental disorders among the older adults. Population aging, social stress, and the COVID-19 pandemic have significantly affected the emotional health of older adults, resulting in a worldwide prevalence of LLD. The clinical phenotypes between LLD and adult depression differ in terms of symptoms, comorbid physical diseases, and coexisting cognitive impairments. Many pathological factors such as the imbalance of neurotransmitters, a decrease in neurotrophic factors, an increase in β-amyloid production, dysregulation of the hypothalamic-pituitary-adrenal axis, and changes in the gut microbiota, are allegedly associated with the onset of LLD. However, the exact pathogenic mechanism underlying LLD remains unclear. Traditional selective serotonin reuptake inhibitor therapy results in poor responsiveness and side effects during LLD treatment. Neuromodulation therapies and complementary and integrative therapies have been proven safe and effective for the treatment of LLD. Importantly, during the COVID-19 pandemic, modern digital health intervention technologies, including socially assistive robots and app-based interventions, have proven to be advantageous in providing personal services to patients with LLD. [ABSTRACT FROM AUTHOR]

The weapon transportation support scheduling problem on aircraft carrier deck is the key to restricting the sortie rate and combat capability of carrier-based aircraft. This paper studies the problem and presents a novel solution architecture. Taking the interference of the carrier-based aircraft deck layout on the weapon transportation route and precedence constraint into consideration, a mixed integer formulation is established to minimize the total objective, which is constituted of makespan, load variance and accumulative transfer time of support unit. Solution approach is developed for the model. Firstly, based on modeling the carrier aircraft parked on deck as convex obstacles, the path library of weapon transportation is constructed through visibility graph and Warshall-Floyd methods. We then propose a bi-population immune algorithm in which a population-based forward/backward scheduling technique, local search schemes and a chaotic catastrophe operator are embedded. Besides, the randomkey solution representation and serial scheduling generation scheme are adopted to conveniently obtain a better solution. The Taguchi method is additionally employed to determine key parameters of the algorithm. Finally, on a set of generated realistic instances, we demonstrate that the proposed algorithm outperforms all compared algorithms designed for similar optimization problems and can significantly improve the efficiency, and that the established model and the bi-population immune algorithm can effectively respond to the weapon support requirements of carrier-based aircraft under different sortie missions. [ABSTRACT FROM AUTHOR]

Introduction: The Tujia is the eighth most populous population in China, but its genetic structure has not been fully studied. Methods: In this study, we utilized 57 autosomal Insertion/deletion (InDel) loci to evaluate the genetic polymorphisms and efficiency of forensic applications in the Chinese Hubei Tujia group, and analyzed the genetic structure variances among the studied group and other 26 different reference populations from five continents in 1000 Genomes Project (1KG). Results: The results showed that 57 InDels have no significant deviations from Hardy-Weinberg equilibrium and linkage equilibrium. The combined power of discrimination (CPD) and the combined probability of exclusion (CPE) values for 57 InDels were 0.99999999999999999999999699822 and 0.999975177214539 in the Hubei Tujia group, respectively. In addition, the results of genetic structure analyses indicated that the Hubei Tujia group has close genetic relationships with the Chinese Han population and other East Asian populations. Discussion: These 57 autosomal InDels can be used as reliable tools for forensic individual identification and paternity testing, and are more suitable for East Asian populations. Furthermore, three InDels (rs72085595, rs145941537, and rs34529639) are promising for inferring ancestral information. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 has a huge negative impact on people's health. Traditional Chinese Medicine (TCM) has a good effect on viral pneumonia. It is of great practical significance to study its pharmacology. Methods: The ingredients and targets of each herb in Maxing Shigan Decoction which obtained from Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and the related targets of COVID-19 were screened by GeneCards database based on the network pharmacology. Venn was used to analyze the intersection target between active ingredients and diseases. Cytoscape software was used to construct an active ingredient-disease target network. The protein-protein interaction network was constructed by STRING database and Cytohubba was used to screen out the key targets. Gene Ontology (GO) functional enrichment analysis and KEGG pathway analysis were performed by DAVID database. Results: In this study, a total of 134 active ingredients and 229 related targets, 198 targets of COVID-19 and 48 common targets of drug-disease were chosen. Enrichment items and pathways were obtained through GO and KEGG pathway analysis. The predicted active ingredients were quercetin, kaempferol, luteolin, naringenin, glycyrol, and the key targets involved IL6, MAPK3, MAPK8, CASP3, IL10, etc. The results showed that the active ingredients of Maxing Shigan Decoction acted on multiple targets which played roles in the treatment of COVID-19 by regulating inflammation, immune system and other pathways. Conclusions: The main contribution of this paper is to use data to mine the principles of the treatment of COVID-19 from the pharmacology of these prescriptions, and the results can be provided theoretical reference for medical workers. [ABSTRACT FROM AUTHOR]

Platinum-based chemotherapy is the primary treatment option for advanced non-small cell lung cancer (NSCLC) patients without a driver gene mutation, but its efficacy is still modest. Through a potential synergistic effect, autologous cellular immunotherapy (CIT) composed of cytokine-induced killer (CIK), natural killer (NK), and T cells might enhance it. NK cells exhibited in vitro cytotoxicity toward lung cancer cells (A549 cells) following platinum therapy. Using flow cytometry, the expression of MICA, MICB, DR4, DR5, CD112, and CD155 on lung cancer cells was assessed. In this retrospective cohort study, there were included 102 previously untreated stage IIIB/IV NSCLC patients ineligible for tyrosine kinase inhibitor (TKI) target therapy who received either chemotherapy alone (n=75) or combination therapy (n=27). The cytotoxicity of NK cells for A549 cells was increased obviously and a time-dependent enhancement of this effect was also observed. After platinum therapy, the levels of MICA, MICB, DR4, DR5, CD112, and CD155 on the surface of A549 cells were increased. In the combination group, the median PFS was 8.3 months, compared to 5.5 months in the control group (p=0.042); the median overall survival was 18.00 months, compared to 13.67 months in the combined group (p=0.003). The combination group had no obvious immune-related adverse effects. The combination of NK cells with platinum showed synergistic anticancer effects. Combining the two strategies increased survival with minor adverse effects. Incorporating CIT into conventional chemotherapy regimens may improve NSCLC treatment. However, additional evidence will require multicenter randomized controlled trials. [ABSTRACT FROM AUTHOR]

The return on government debt is lower than that of asset with similar payoffs. We study optimal debt management and taxation when the government cannot directly redistribute towards the agents in need of liquidity but otherwise has access to a complete set of linear tax instruments. Optimal government debt provision calls for gradually closing the wedge between the returns as much as possible, but tax policy may work as a countervailing force: as long as financial frictions bind, it can be optimal to tax capital even if this magnifies the discrepancy in returns. [ABSTRACT FROM AUTHOR]

Deletion/insertion polymorphism (DIP), as a short insertion/deletion sequence polymorphic genetic marker, has attracted the attention of forensic genetic scientist due to its lack of stutter, short amplicon and abundant ancestral information. In this study, based on a self-developed 43 autosomal deletion/insertion polymorphism (A-DIP) loci panel which could meet the forensic application purposes of individual identification, kinship testing and ancestral inference to some extent, we evaluated the forensic efficiencies of the above three forensic objectives in Chinese Yi, Hani and Miao groups of Yunnan province. The cumulative match probability (CPM) and combined probability of exclusion (CPE) of these three groups were 1.11433E-18, 8.24299E-19, 4.21721E-18; 0.999610217, 0.999629285 and 0.999582084, respectively. Average 96.65% full sibling pairs could be identified from unrelated individual pairs (as likelihood ratios > 1) using this DIP panel, whereas the average false positive rate was 3.69% in three target Yunnan groups. With the biogeographical ancestor prediction models constructed by extreme gradient boosting (XGBoost) and support vector machine (SVM) algorithms, 0.8239 (95% CI 0.7984, 0.8474) of the unrelated individuals could be correctly divided according to the continental origins based on the 43 A-DIPs which were large frequency distribution differentiations among different continental populations. The present results of principal component analysis (PCA), multidimensional scaling (MDS), neighbor joining (NJ) and maximum likelihood (ML) phylogenetic trees and STRUCTURE analyses indicated that these three Yunnan groups had relatively close genetic distances with East Asian populations. [ABSTRACT FROM AUTHOR]

Objective: Currently, the prevalence of hypertension is mainly ascertained using a one-visit population survey, which may lead to overestimation. The purpose of this study was to assess the accuracy of hypertension prevalence determined by a one-visit population survey. Methods: For this cross-sectional study, we continuously enrolled 1116 volunteers without a hypertension history in Hebei province from January 2018 to December 2019. The study population included 511 (45.80%) males and 605 (54.20%) females with a mean age of 48 years. The hypertension prevalence was assessed using two methods: onevisit screening and daytime ambulatory blood pressure (BP) monitoring. We directly compared the performances of daytime ambulatory BP monitoring and one-visit screening in the same group of subjects. In addition, we explored possible thresholds to improve the detection of hypertension. Results: During the one-visit survey, the mean BP value was about 8 mmHg higher than that determined by daytime ambulatory BP monitoring. The prevalence of hypertension was 29.84% and 14.07% during the one-visit and daytime multiple visit surveys, respectively. The risk factors for overestimated hypertension were female sex, body mass index<24.00 kg/m2 , and diastolic BP of 100 mmHg. The positive predictive value of the one-visit population survey for diagnosing hypertension was 36.34%. Furthermore, receiver operating characteristic analysis showed that in males, the best diagnostic threshold for hypertension diagnosis was 148/96 mmHg. Conclusion: The hypertension prevalence was likely overestimated by 2-fold in the one-visit survey group compared to the daytime ambulatory BP monitoring group. Thus, the threshold for one-visit BP screening should be raised to 148/96 mmHg to improve the accuracy of hypertension diagnossis. [ABSTRACT FROM AUTHOR]

Background: The QRS fraction is the ratio of the total amplitude of R waves to the total amplitude of QRS complexes (∑R/QRS) on a 12-lead electrocardiogram. Our group has previously proposed calculation of the QRS fraction as a simple method for estimation of left ventricular ejection fraction. In this study, we explored the ability of the QRS fraction to predict cardiovascular death in patients with heart failure. Methods: The study had a prospective, observational design and collected epidemiological and follow-up data for 1715 patients with heart failure who were inpatients in the Department of Cardiology at the Second Hospital of Hebei Medical University between January 2017 and December 2018. The patients were stratified according to quartile of QRS fraction, namely, lower (<43.8%, Q1 group) middle (43.8%--61.0%, Q2 group), and higher (>61.0%, Q3 group). Results: One thousand and fifty-one (61.28%) of the 1715 patients were male and the median follow-up duration was 261 days (interquartile range 39, 502). There were 341 (19.88%) deaths, including 282 (16.44%) with a cardiovascular cause. The Q1, Q2, and Q3 groups comprised 431 (25.13%), 850 (49.56%), and 434 (25.31%) patients, respectively. There were significant differences in cardiovascular mortality among the three QRS fraction subgroups (p < 0.05). Kaplan- Meier survival curves of different QRS fraction levels showed significant difference among patients with heart failure, especially among those with preserved ejection fraction (p = 0.025 and 0.031, log-rank test). Cox regression analysis showed that the QRS fraction was independently associated with the risk of cardiovascular death. The risk of cardiovascular death was lower in the Q2 and Q3 groups than in the Q1 group, with respective hazard ratios of 0.668 (95% confidence interval 0.457--0.974) and 0.538 (95% confidence interval 0.341--0.849). Conclusions: The QRS fraction may serve as a prognostic indicator of the long-term risk of cardiovascular death in patients with heart failure, especially those with preserved ejection fraction. [ABSTRACT FROM AUTHOR]

Hepatoblastoma is a malignant embryonal tumor with multiple differentiation modes and is the clearest liver malignancy in children. However, little is known about genetic and epigenetic events in Hepatoblastoma. Increased research has recently demonstrated, unique genetic and epigenetic events in Hepatoblastoma, providing insights into its origin and precise treatment. Some genetic disorders and congenital factors are associated with the risk of Hepatoblastoma development, such as the Beckwith-Wiedemann syndrome, Familial Adenomatous polyposis, and Hemihypertrophy. Epigenetic modifications such as DNA modifications, histone modifications, and non-coding RNA regulation are also essential in the development of Hepatoblastoma. Herein, we reviewed genetic and epigenetic events in Hepatoblastoma, focusing on the relationship between these events and cancer susceptibility, tumor growth, and prognosis. By deciphering the genetic and epigenetic associations in Hepatoblastoma, tumor pathogenesis can be clarified, and guide the development of new anti-cancer drugs and prevention strategies. [ABSTRACT FROM AUTHOR]

Resistance to tyrosine kinase inhibitor (TKI) is a tough problem in the treatment of chronic myeloid leukemia in blastic phase (CML-BP), which was often associated with acquired mutations in the kinase domain and not eliminating the leukemic stem cells. The efficacy of TKI or combination with chemotherapy in CML-BP remains unsatisfactory. Chimeric antigen receptor T (CAR-T) cell immunotherapy may overcome TKI and chemotherapy resistance. However, lack of ideal targetable antigens is a major obstacle for treating patients with myeloid malignancies. CD38 is known to be expressed on most (acute myeloid leukemia) AML cells, and its lack of expression on hematopoietic stem cells renders it as a potential therapeutic target for myeloid CML-BP. We develop a CD38-directed CAR-T cell therapy for AML, and two patients with myeloid CML-BP were enrolled (NCT04351022). Two patients, harboring E255K and T315I mutation in the ABL kinase domain, respectively, were resistant to multiple TKIs (imatinib, dasatinib, nilotinib, and ponatinib) and intensive chemotherapy. The blasts in the bone marrow of two patients exhibited high expression of CD38. After tumor reduction chemotherapy and lymphodepletion chemotherapy, 1 × 107 CAR-T-38 cells per kilogram of body weight were administered. They achieved minimal residual disease-negative and BCR::ABL1-negative complete remission and experienced grade II cytokine release syndrome manifesting as fever. Our data highlighted that CAR-T-38 cell therapy may overcome TKI and chemotherapy resistance in patients with myeloid CML-BP. [ABSTRACT FROM AUTHOR]

Circadian rhythms regulate various biological processes, such as cell division and metabolism. Circadian rhythm disruption (CRD) is often associated with malignant tumor progression and poor prognosis. However, the effect of CRD on liver cancer prognosis has not been systematically analyzed or fully elucidated. Here, we developed a method to quantify and assess intratumoral CRD in a single-cell transcriptomic analysis of liver cancer and systematically analyzed the role of CRD in tumor progression and prognosis. Furthermore, a LASSO-Cox regression model based on 14 CRD genes was used to predict overall patient survival across multiple datasets. We found that malignant cells with high CRD scores were enriched in specific metabolic pathways, such as fatty acid metabolism and the trichloroacetic acid cycle. Intercellular communication analysis suggested that CRD regulates chemokine-mediated interactions. With the bulk transcriptomic datasets, we determined that LiverCRD scores were significantly correlated with macrophage infiltration levels and could guide targeted immunotherapy and chemotherapy strategies. In addition, LiverCRD is also associated with the mutational landscape—for example, TP53 mutation frequency was higher in high-CRD samples. Finally, the 14-gene-based LASSO-Cox regression model could accurately predict overall patient survival across datasets. In conclusion, Our proposed analysis reflects the relationship between CRD and the immune environment in liver cancer, suggesting that CRD may serve as a potential prognostic indicator. Our results may help guide targeted anti-tumor strategies. [ABSTRACT FROM AUTHOR]

Purpose: Lymph node (LN) involvement is a key factor in ovarian clear cell carcinoma (OCCC) although, there several indicators can be used to define prognosis. This study examines the prognostic performances of each indicator for OCCC patients by comparing the number of lymph nodes examined (TNLE), the number of positive lymph nodes (PLN), lymph node ratio (LNR), and log odds of metastatic lymph nodes (LODDS). Methods: 1,300 OCCC patients who underwent lymphadenectomy between 2004 and 2015 were extracted from the Surveillance Epidemiology and End Results (SEER) database. Primary outcomes were Overall Survival (OS) and the cumulative incidence of Cancer-Specific Survival (CSS). Kaplan–Meier’s and Fine-Gray’s tests were implemented to assess OS and CSS rates. After conducting multivariate analysis, nomograms using OS and CSS were constructed based upon an improved LN system. Each nomograms’ performance was assessed using Receiver Operating Characteristics (ROC) curves, calibration curves, and the C-index which were compared to traditional cancer staging systems. Results: Multivariate Cox’s regression analysis was used to assess prognostic factors for OS, including age, T stage, M stage, SEER stage, and LODDS. To account for the CSS endpoint, a proportional subdistribution hazard model was implemented which suggested that the T stage, M stage, SEER stage, and LNR are all significant. This enabled us to develop a LODDS-based nomogram for OS and a LNR-based nomogram for CSS. C-indexes for both the OS and CSS nomograms were higher than the traditional American Joint Committee on Cancer (AJCC), 8th edition, staging system. Area Under the Curve (AUC) values for predicting 3- and 5-year OS and CSS between nomograms also highlighted an improvement upon the AJCC staging system. Calibration curves also performed with consistency, which was verified using a validation cohort. Conclusions: LODDS and LNR may be better predictors than N stage, TNLE, and PLNs. For OCCC patients, both the LODDS-based and LNR-based nomograms performed better than the AJCC staging system at predicting OS and CSS. However, further large sample, real-world studies are necessary to validate the assertion. [ABSTRACT FROM AUTHOR]

The article presents a study on the use of the multi-level dietary niche theory in examining the food selection and nutrient regulation responses of the wild rhesus macaque to natural resource variation. Topics discussed include the seasonal availability of their keystone resource, and the association between the evolution of macronutrient regulatory strategies and the temporal pattern of resource variability.

Background: Gestational trophoblastic neoplasia (GTN) is a group of clinically rare tumors that develop in the uterus from placental tissue. Currently, its satisfactory curability derives from the timely and accurately classification and refined management for patients. This study aimed to discover biomarkers that could predict the outcomes of GTN patients after first-line chemotherapy. Methods: A total of 65 GTN patients were included in the study. Patients were divided into the good or poor outcome group and the clinical characteristics of the patients in the two groups were compared. Furthermore, the serum peptide profiles of all patients were uncovered by using weak cation exchange magnetic beads and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Feature peaks were identified by three machine learning algorithms and then models were constructed and compared using five machine learning methods. Additionally, liquid chromatography mass spectrometry was used to identify the feature peptides. Results: Multivariate logistic regression analysis showed that the International Federation of Gynecology and Obstetrics (FIGO) risk score was associated with poor outcomes. Eight feature peaks (m/z =1287, 2042, 2862, 2932, 2950, 3240, 3277 and 6626) were selected for model construction and validation by the three algorithms. Based on the panel combining FIGO risk score and peptide serum signatures, the neural network (nnet) model showed promising performance in both the training (AUC=0.9635) and validation (AUC=0.8788) cohorts. Peaks at m/z 2042, 2862, 2932, 3240 were identified as the partial sequences of transthyretin, fibrinogen alpha chain (FGA), beta-globin and FGA, respectively. Conclusion: We combined FIGO risk score and serum peptide signatures using the nnetmethod to construct themodel which can accurately predict outcome of GTN patients after first-line chemotherapy. With thismodel, patients can be further classified and managed, and those with poor predicted outcomes can be given more attention for developing treatment failure. [ABSTRACT FROM AUTHOR]

Breast cancer is a heterogeneous disease whose subtypes represent different histological origins, prognoses, and therapeutic sensitivity. But there remains a strong need for more specific biomarkers and broader alternatives for personalized treatment. Our study classified breast cancer samples from The Cancer Genome Atlas (TCGA) into three groups based on glycosylation-associated genes and then identified differentially expressed genes under different glycosylation patterns to construct a prognostic model. The final prognostic model containing 23 key molecules achieved exciting performance both in the TCGA training set and testing set GSE42568 and GSE58812. The risk score also showed a significant difference in predicting overall clinical survival and immune infiltration analysis. This work helped us to understand the heterogeneity of breast cancer from another perspective and indicated that the identification of risk scores based on glycosylation patterns has potential clinical implications and immune-related value for breast cancer. [ABSTRACT FROM AUTHOR]