Preoperative platelet distribution width predicts bone metastasis in patients with breast cancer.

PURPOSE: Bone metastases occur in 50-70% of patients with breast cancer (BC) and result in high mortality. Platelet distribution width (PDW), a commonly used parameter of activated platelets, has been associated with a poor prognosis in BC. We aim to investigate the prognostic role of PDW for bone metastasis in BC patients. METHODS: 515 patients who received BC surgery in the Harbin Medical University Cancer Hospital from July 1, 2016, to December 31, 2017, were reviewed. Patients' characteristics and platelet indices upon enrollment in this study were collected. The Kaplan-Meier method was used to estimate the 5-year bone metastasis incidence. The univariate and multivariate Cox regression analyses were utilized to identify risk factors associated with bone metastasis. RESULTS: The patients with bone metastases exhibited lower PDW levels than the patients without bone metastases. Moreover, decreased PDW was significantly correlated with histologic type, multifocal disease, and lymph node status. In addition, the patients with reduced PDW levels were more likely to develop bone metastasis. Multivariate analysis showed that PDW was an independent predictor for bone metastasis. CONCLUSION: PDW is an independent predictor of bone metastasis in BC. Further research is warranted.

Topology Optimization Driven Bone-Remodeling Simulation for Lumbar Interbody Fusion.

This study proposes a numerical approach for simulating bone remodeling in lumbar interbody fusion (LIF). It employs a topology optimization method to drive the remodeling process and uses a pixel function to describe the structural topology and bone density distribution. Unlike traditional approaches based on strain energy density or compliance, this study adopts von Mises stress to guide the remodeling of LIF. A novel pixel interpolation scheme associated with stress criteria is applied to the physical properties of the bone, directly addressing the stress shielding effect caused by the implanted cage, which significantly influences the bone remodeling outcome in LIF. Additionally, a boundary inverse approach is utilized to reconstruct a simplified analysis model. To reduce computational cost while maintaining high structural resolution and accuracy, the scaled boundary finite element method (SBFEM) is introduced. The proposed numerical approach successfully generates results that closely resemble human lumbar interbody fusion.

Evolution of fermented grain yeast communities in strong-flavored baijiu and functional validation of yeasts that produce superior-flavored substances.

BACKGROUND: Baijiu is a well-known alcoholic beverage in China and the quality is determined by various microorganisms during the fermentation process. Yeast is one of the most important microorganisms in the fermentation of baijiu. It has a strong esterification capacity and also affects the aroma. RESULTS: High-throughput sequencing results showed that the fermented grains (jiupei) during baijiu production were mainly composed of eight highly abundant yeast species. The species and abundance of yeasts changed significantly with the fermentation process. The flavor of 30 yeast strains in the jiupei was determined by a sniffing test and gas chromatography-mass spectrometry (GC-MS). The strain with the highest flavor substance content (2.34 mg L-1), named YX3205, was identified as Clavispora lusitaniae. Tolerance results showed that C. lusitaniae YX3205 can tolerate up to 15% (v v-1) ethanol. In a solid-state simulated fermentation experiment, the content of 24 flavor substances was significantly increased in the fortified group, and the total ester content reached 4240.73 µg kg-1, which was 2.8 times higher than that of the control group. CONCLUSION: The present study demonstrated the potential of C. lusitaniae YX3205 to enhance the flavor of baijiu, thereby serving as a valuable strain for the improvement of the flavor quality of baijiu. © 2024 Society of Chemical Industry.

Ionic Liquids-Driven Cluster-to-Cluster Conversion of Polyhydrido Copper(I) Clusters Cu7H5 to Cu8H6 and Cu12H9.

Although ionic liquids (ILs) are of prime interest for the synthesis of various nanomaterials, they are scarcely utilized for the polyhydrido copper(I) [Cu(I)H] clusters. Herein, two air-stable Cu(I)H clusters, [Cu8H6(dppy)6](NTf2)2 (Cu8H6) and {Cu12H9(dppy)6[N(CN)2]3} (Cu12H9), are synthesized in high yields for the first time from the ILs-driven conversion of an unprecedented cluster [Cu7H5(dppy)6](ClO4)2 (Cu7H5) by a facile three-layers diffusion crystal (TLDC) method, strategically introducing IL-NTf2 and IL-N(CN)2 as two types of unusual interfacial crystallized templates, respectively. Their structures are fully characterized by various spectroscopic methods and X-ray crystallography, which shows that the anion of IL plays an important role as an anion template and an anion ligand in controlling the structural conversion of Cu(I)H clusters. Their photophysical properties are also investigated, and it is found that all reported clusters exhibit red luminescence with λem ranging from 600 to 690 nm.

Exposing Cu(100) Surface via Ion-Implantation-Induced Oxidization and Etching for Promoting Hydrogen Evolution Reaction.

Metallic materials with unique surface structure have attracted much attention due to their unique physical and chemical properties. However, it is hard to prepare bulk metallic materials with special crystal faces, especially at the nanoscale. Herein, we report an efficient method to adjust the surface structure of a Cu plate which combines ion implantation technology with the oxidation-etching process. The large number of vacancies generated by ion implantation induced the electrochemical oxidation of several atomic layers in depth; after chemical etching, the Cu(100) planes were exposed on the surface of the Cu plate. As a catalyst for acid hydrogen evolution reaction, the Cu plate with (100) planes merely needs 273 mV to deliver a current density of 10 mA/cm2 because the high-energy (100) surface has moderate hydrogen adsorption and desorption capability. This work provides an appealing strategy to engineer the surface structure of bulk metallic materials and improve their catalytic properties.

Transition-metal-free radical difluorobenzylation/cyclization of unactivated alkenes: access to ArCF2-substituted ring-fused quinazolinones.

A mild and efficient transition-metal-free radical difluorobenzylation/cyclization of unactivated alkenes toward the synthesis of difluorobenzylated polycyclic quinazolinone derivatives with easily accessible α,α-difluoroarylacetic acids has been developed. This transformation has the advantages of wide functional group compatibility, a broad substrate scope, and operational simplicity. This methodology provided a highly attractive access to pharmaceutically valuable ArCF2-containing polycyclic quinazolinones.

Tetrandrine alleviates silicosis by inhibiting canonical and non-canonical NLRP3 inflammasome activation in lung macrophages.

Silicosis caused by inhalation of silica particles leads to more than ten thousand new occupational exposure-related deaths yearly. Exacerbating this issue, there are currently few drugs reported to effectively treat silicosis. Tetrandrine is the only drug approved for silicosis treatment in China, and despite more than decades of use, its efficacy and mechanisms of action remain largely unknown. Here, in this study, we established silicosis mouse models to investigate the effectiveness of tetrandrine of early and late therapeutic administration. To this end, we used multiple cardiopulmonary function test, as well as markers for inflammation and fibrosis. Moreover, using single cell RNA sequencing and transcriptomics of lung tissue and quantitative microarray analysis of serum from silicosis and control mice, our results provide a novel description of the target pathways for tetrandrine. Specifically, we found that tetrandrine attenuated silicosis by inhibiting both the canonical and non-canonical NLRP3 inflammasome pathways in lung macrophages. Taken together, our work showed that tetrandrine yielded promising results against silicosis-associated inflammation and fibrosis and further lied the groundwork for understanding its molecular targets. Our results also facilitated the wider adoption and development of tetrandirne, potentially accelerating a globally accepted therapeutic strategy for silicosis.

Pirfenidone ameliorates silica-induced lung inflammation and fibrosis in mice by inhibiting the secretion of interleukin-17A.

Silicosis is a global occupational disease characterized by lung dysfunction, pulmonary inflammation, and fibrosis, for which there is a lack of effective drugs. Pirfenidone has been shown to exert anti-inflammatory and anti-fibrotic properties in the lung. However, whether and how pirfenidone is effective against silicosis remains unknown. Here, we evaluated the efficacy of pirfenidone in the treatment of early and advanced silicosis in an experimental mouse model and explored its potential pharmacological mechanisms. We found that pirfenidone alleviated silica-induced lung dysfunction, secretion of inflammatory cytokines (TNF-α, IL-1ß, IL-6) and deposition of fibrotic proteins (collagen I and fibronectin) in both early and advanced silicosis models. Moreover, we observed that both 100 and 200 mg/kg pirfenidone can effectively treat early-stage silicosis, while 400 mg/kg was recommended for advanced silicosis. Mechanistically, antibody array and bioinformatic analysis showed that the pathways related to IL-17 secretion, including JAK-STAT pathway, Th17 differentiation, and IL-17 pathway, might be involved in the treatment of silicosis by pirfenidone. Further in vivo experiments confirmed that pirfenidone reduced the production of IL-17A induced by silica exposure via inhibiting STAT3 phosphorylation. Neutralizing IL-17A by anti-IL-17A antibody improved lung function and reduced pulmonary inflammation and fibrosis in silicosis animals. Collectively, our study has demonstrated that pirfenidone effectively ameliorated silica-induced lung dysfunction, pulmonary inflammation and fibrosis in mouse models by inhibiting the secretion of IL-17A.

A Statistical Framework for Mapping Risk Genes from De Novo Mutations in Whole-Genome-Sequencing Studies.

Analysis of de novo mutations (DNMs) from sequencing data of nuclear families has identified risk genes for many complex diseases, including multiple neurodevelopmental and psychiatric disorders. Most of these efforts have focused on mutations in protein-coding sequences. Evidence from genome-wide association studies (GWASs) strongly suggests that variants important to human diseases often lie in non-coding regions. Extending DNM-based approaches to non-coding sequences is challenging, however, because the functional significance of non-coding mutations is difficult to predict. We propose a statistical framework for analyzing DNMs from whole-genome sequencing (WGS) data. This method, TADA-Annotations (TADA-A), is a major advance of the TADA method we developed earlier for DNM analysis in coding regions. TADA-A is able to incorporate many functional annotations such as conservation and enhancer marks, to learn from data which annotations are informative of pathogenic mutations, and to combine both coding and non-coding mutations at the gene level to detect risk genes. It also supports meta-analysis of multiple DNM studies, while adjusting for study-specific technical effects. We applied TADA-A to WGS data of ∼300 autism-affected family trios across five studies and discovered several autism risk genes. The software is freely available for all research uses.

[Relationship between dietary behavior and malnutrition of children aged 3-5 years in five cities of China].

OBJECTIVE: To explore the status of malnutrition and dietary behavior characteristics of children aged 3-5 in Tonghua, Nanchang, Changsha, Kunming and Weinan, and to analyze the relationship between them. METHODS: Data was from National Nutrition and Health Systematic Survey for 0-18 Years Old Children in China. A total of 1741 children were randomly selected from five cities by multi-stage stratified cluster sampling, and their physical fitness was measured and investigated by questionnaire. Chi-square test and multivariate binomial Logistic regression analysis were used to assess the relationship between nutritional deficiency and diet and feeding behavior. RESULTS: Among the investigated children, the underweight rate, stunting rate and wasting rate were 0.52%, 1.09% and 1.03%, respectively. Dietary behavior restriction was the risk factor for stunting(OR=4.72, 95% CI 1.41-15.84), poor eating habits were the risk factor for wasting(OR=3.64, 95% CI 1.01-13.34). No statistical association was found between underweight and diet and feeding behavior. CONCLUSION: The incidence of malnutrition among children aged 3-5 years in five urban areas of China is low. There is a correlation between malnutrition and poor diet and feeding behavior. Measures should be taken to correct the poor eating habits of children and the feeding behavior of caregivers, so as to improve the nutritional status of children.

Erratum: Mei, Y., et al. Mechanics Based Tomography: A Preliminary Feasibility Study. Sensors 2017, 17, 1075.

The authors wish to correct Figures 12 and 14 in their paper published in Sensors [1], doi:10.3390/s17051075, http://www.mdpi.com/1424-8220/17/5/1075[...].

Mechanics Based Tomography: A Preliminary Feasibility Study.

We present a non-destructive approach to sense inclusion objects embedded in a solid medium remotely from force sensors applied to the medium and boundary displacements that could be measured via a digital image correlation system using a set of cameras. We provide a rationale and strategy to uniquely identify the heterogeneous sample composition based on stiffness (here, shear modulus) maps. The feasibility of this inversion scheme is tested with simulated experiments that could have clinical relevance in diagnostic imaging (e.g., tumor detection) or could be applied to engineering materials. No assumptions are made on the shape or stiffness quantity of the inclusions. We observe that the novel inversion method using solely boundary displacements and force measurements performs well in recovering the heterogeneous material/tissue composition that consists of one and two stiff inclusions embedded in a softer background material. Furthermore, the target shear modulus value for the stiffer inclusion region is underestimated and the inclusion size is overestimated when incomplete boundary displacements on some part of the boundary are utilized. For displacements measured on the entire boundary, the shear modulus reconstruction improves significantly. Additionally, we observe that with increasing number of displacement data sets utilized in solving the inverse problem, the quality of the mapped shear moduli improves. We also analyze the sensitivity of the shear modulus maps on the noise level varied between 0.1% and 5% white Gaussian noise in the boundary displacements, force and corresponding displacement indentation. Finally, a sensitivity analysis of the recovered shear moduli to the depth, stiffness and the shape of the stiff inclusion is performed. We conclude that this approach has potential as a novel imaging modality and refer to it as Mechanics Based Tomography (MBT).

A new naphthalenepropanoic acid analog from the marine-derived actinomycetes Micromonospora sp. HS-HM-036.

A new naphthalenepropanoic acid analog (1) was isolated from the broth of the actinomycetes Micromonospora sp. HS-HM-036. The structure of compound 1 was determined based on MS and extensive NMR analysis. A preliminary investigation of the biological activity of compound 1 was also described.

Pre-treatment neutrophil-to-lymphocyte ratio predicts prognosis in patients with locoregionally advanced laryngeal carcinoma treated with chemoradiotherapy.

OBJECTIVE: The aim of this study was to investigate the effect of neutrophil-to-lymphocyte ratio on the prognosis of patients with locoregionally advanced laryngeal carcinoma treated with chemoradiotherapy. METHODS: One hundred and twenty-five patients with locoregionally advanced laryngeal carcinoma (cT3-4 N0-3M0) treated with chemoradiotherapy were reviewed retrospectively. Chemoradiotherapy comprised external beam radiotherapy to the larynx (70 Gy) with three cycles of cisplatin at 3 week intervals. The survival rate was calculated using the Kaplan-Meier method, and a multivariate analysis was used to identify significant factors associated with prognosis, using a Cox proportional hazards model. RESULTS: During the median (range) follow-up of 45 months, the median neutrophil-to-lymphocyte ratio was 3.02. The high neutrophil-to-lymphocyte ratio group (neutrophil-to-lymphocyte ratio > 3.0) contained 69 patients and the low neutrophil-to-lymphocyte ratio group (neutrophil-to-lymphocyte ratio < 3.0) contained 46 patients. The low neutrophil-to-lymphocyte ratio group patients had a significantly higher chemoradiotherapeutic disease control rate (86.96 vs. 69.57%, P = 0.031). Forty-six patients had a low neutrophil-to-lymphocyte ratio (<3.0) before chemoradiotherapy and their progression-free survival and 75% overall survival were significantly better than that of the high neutrophil-to-lymphocyte ratio patients (P = 0.015, P = 0.045). Multivariate analysis showed that neutrophil-to-lymphocyte ratio and N stage were independent prognostic indicators for progression-free survival (with a hazard ratio of 1.79, P = 0.003 and a hazard ratio of 1.28, P = 0.034) and overall survival (with a hazard ratio of 1.51, P = 0.029 and a hazard ratio of 1.21, P = 0.043), respectively. CONCLUSION: Pre-treatment neutrophil-to-lymphocyte ratio is a useful prognostic marker in patients with locoregionally advanced laryngeal carcinoma treated with chemoradiotherapy.

Sestrin2 protects the myocardium against radiation-induced damage.

The purpose of this study was to investigate the role of Sestrin2 in response to radiation-induced injury to the heart and on the cardiomyopathy development in the mouse. Mice with genetic deletion of the Sestrin2 (Sestrin2 knockout mice [Sestrin2 KO]) and treatment with irradiation (22 or 15 Gy) were used as independent approaches to determine the role of Sestrin2. Echocardiography (before and after isoproterenol challenge) and left ventricular (LV) catheterization were performed to evaluate changes in LV dimensions and function. Masson's trichrome was used to assess myocardial fibrosis. Immunohistochemistry and Western blot were used to detect the capillary density. After 22 or 15 Gy irradiation, the LV ejection fraction (EF) was impaired in wt mice at 1 week and 4 months after irradiation when compared with sham irradiation. Compared to wt mice, Sestrin2 KO mice had significant reduction in reduced LVEF at 1 week and 4 months after irradiation. A significant increase in LV end-diastolic pressure and myocardial fibrosis and a significant decrease in capillary density were observed in irradiation-wt mice, as well as in irradiation-Sestrin2 KO mice. Sestrin2 involved in the regulation of cardiomyopathy (such as myocardial fibrosis) after irradiation. Overexpression of Sestrin2 might be useful in limiting radiation-induced myocardial injury.

Serum ferritin predicted prognosis in patients with locally advanced pancreatic cancer.

AIM: The present study evaluated the value of serum ferritin (SF) level for the prognosis of patients with locally advanced pancreatic cancer (LAPC). PATIENTS & METHODS: A total of 79 patients with LAPC treated by chemoradiotherapy were reviewed retrospectively. Pretreatment and post-treatment levels of SF were obtained. RESULTS: Median progression-free survival (PFS) was 11.8 months; median overall survival was 18.3 months. A total of 36 patients with elevated SF level showed significantly worse overall survival and PFS than patients with low SF level (p = 0.002 and p = 0.004, respectively). In total, 17 patients showed normal SF level after chemoradiotherapy, and their median PFS was 3.2 months longer than that of patients whose SF levels were not restored after chemoradiotherapy. CONCLUSION: SF may serve as a valuable tool to assess prognosis and monitor chemoradiotherapy response in patients with LAPC.

Standardized uptake value on positron emission tomography/computed tomography predicts prognosis in patients with locally advanced pancreatic cancer.

BACKGROUND: The aim of the present study was to investigate the use and value of maximum standardized uptake value (SUV max) on positron emission tomography/computed tomography (PET/CT) images as a prognostic marker for patients with locally advanced pancreatic cancer (LAPC). MATERIALS AND METHODS: The medical records of all consecutive patients who underwent PET/CT examination in our institution were retrospectively reviewed. Inclusion criteria were histologically or cytologically proven LAPC. Patients with distant metastasis were excluded. For statistical analysis, the SUV max of primary pancreatic cancer was measured. Survival rates were calculated using the Kaplan-Meier method, and multivariable analysis was performed to determine the association of SUV max with overall survival (OS) and progression-free survival (PFS) using a Cox proportional hazards model. RESULTS: Between July 2006 and June 2013, 69 patients were enrolled in the present study. OS and PFS were 14.9 months [95% confidence interval (CI) 13.1-16.7] and 8.3 months (95% CI 7.1-9.5), respectively. A high SUV max (>5.5) was observed in 35 patients, who had significantly worse OS and PFS than the remaining patients with a low SUV max (P = 0.025 and P = 0.003). Univariate analysis showed that SUV max and tumor size were prognostic factors for OS, with a hazard ratio of 1.90 and 1.81, respectively. A high SUV max was an independent prognostic factor, with a hazard ratio of 1.89 (95% CI 1.015-3.519, P = 0.045). CONCLUSION: The present study suggests that increased SUV max is a predictor of poor prognosis in patients with LAPC.

Diagnosis of Forme Fruste Keratoconus Using Corvis ST Sequences with Digital Image Correlation and Machine Learning.

PURPOSE: This study aimed to employ the incremental digital image correlation (DIC) method to obtain displacement and strain field data of the cornea from Corvis ST (CVS) sequences and access the performance of embedding these biomechanical data with machine learning models to distinguish forme fruste keratoconus (FFKC) from normal corneas. METHODS: 100 subjects were categorized into normal (N = 50) and FFKC (N = 50) groups. Image sequences depicting the horizontal cross-section of the human cornea under air puff were captured using the Corvis ST tonometer. The high-speed evolution of full-field corneal displacement, strain, velocity, and strain rate was reconstructed utilizing the incremental DIC approach. Maximum (max-) and average (ave-) values of full-field displacement V, shear strain γxy, velocity VR, and shear strain rate γxyR were determined over time, generating eight evolution curves denoting max-V, max-γxy, max-VR, max-γxyR, ave-V, ave-γxy, ave-VR, and ave-γxyR, respectively. These evolution data were inputted into two machine learning (ML) models, specifically Naïve Bayes (NB) and Random Forest (RF) models, which were subsequently employed to construct a voting classifier. The performance of the models in diagnosing FFKC from normal corneas was compared to existing CVS parameters. RESULTS: The Normal group and the FFKC group each included 50 eyes. The FFKC group did not differ from healthy controls for age (p = 0.26) and gender (p = 0.36) at baseline, but they had significantly lower bIOP (p < 0.001) and thinner central cornea thickness (CCT) (p < 0.001). The results demonstrated that the proposed voting ensemble model yielded the highest performance with an AUC of 1.00, followed by the RF model with an AUC of 0.99. Radius and A2 Time emerged as the best-performing CVS parameters with AUC values of 0.948 and 0.938, respectively. Nonetheless, no existing Corvis ST parameters outperformed the ML models. A progressive enhancement in performance of the ML models was observed with incremental time points during the corneal deformation. CONCLUSION: This study represents the first instance where displacement and strain data following incremental DIC analysis of Corvis ST images were integrated with machine learning models to effectively differentiate FFKC corneas from normal ones, achieving superior accuracy compared to existing CVS parameters. Considering biomechanical responses of the inner cornea and their temporal pattern changes may significantly improve the early detection of keratoconus.

Effectiveness of school-based physical activity programs in enhancing attention, academic performance, and social relationships among children with intellectual disabilities: evidence from Pakistani schools.

Physical activity (PA) offers extensive benefits for all children, including those with intellectual disabilities (ID), who face significant challenges in behavioral management and psycho-social well-being. This study investigates the effects of school-based PA on attention, academic performance, and relationships with teachers and parents in children with ID. A 12-week single-blind randomized controlled trial was conducted with 102 children with ID, aged 6 to 12 years (71 boys and 31 girls) from grades 1 to 5. Participants were divided into three groups: MVPA (moderate to vigorous PA), MPA (mild PA), and NPA (no PA). Each group engaged in PA three times a week for 45 min per session, with activities planned by a fitness trainer and supervised by the researcher. Outcome measures were assessed using SNAP-IV, STRS, CPRS, and APRS scales before and after the intervention. The results indicated that MVPA had a more significant positive impact on all outcomes compared to MPA and NPA. MPA also produced notable improvements relative to NPA. These findings underscore the importance of integrating PA into educational settings as a comprehensive strategy to enhance attention, academic performance, and social interactions for children with ID. This research highlights PA as a vital tool for addressing behavioral challenges and fostering better developmental outcomes in this population.

Corrigendum to "Crystal structure of RNA helicase from Saint Louis encephalitis virus and discovery of its inhibitors" [Genes Dis 10 (2023) 389-392].

[This corrects the article DOI: 10.1016/j.gendis.2022.07.001.].