bluuebunny/crossref_metadata_2025_split huggingface dataset:
Necropotosis-Induciable Nanoliposomes for Enhanced Cancer Sonoimmunotherapy in Vitro
Authors: Li Meng-meng , Zhu Ya , Yang Mi , Cao Yang , Ran Haitao , Zhang Wei 
Published: June 2021

Abstract
Background: Necroptosis has emerged as a therapeutic target for stimulating antitumor immune responses in dying tumor cells. However, its suppressed expression of receptor-interacting protein kinase 3 (RIPK3), a key enzyme in necrosis in most cancer cells, limits the clinical translation to exploiting necroptosis.Design: We fabricated a multifunctional phase-transition nanoparticles platform by constructing Lip-ICG-PFP-cRGD, utilizing liposome and indocyanine green (ICG) as the shell and perfluoropentane (PFP) as the core. The platform system represented the combination of sonodynamic therapy (SDT) and immunotherapy for cancer treatment by inducing necroptosis and disrupting the cell membrane through the acoustic cavitation effect mediated by ultrasound. In addition to their inherent contrasting ability under photoacoustic imaging, our liposomes may also be used as an ultrasound imaging probe after being irradiated with low-intensity focused ultrasound (LIFU).Results: We demonstrate that nanoparticles can trigger necroptosis in ovarian cancer cells, which ruptures cell membrane by acoustic cavitation effect. When exposed to LIFU, the nanoparticles effectively facilitate the release of damage-associated molecular patterns by inducing burst-mediated cell-membrane decomposition. Moreover, the PFP phase change caused RIPK3/MLKL-independent necroptosis by acoustic cavitation effect, resulting in the release of biologically active DAMPs (CRT and HMGB1) to facilitate antitumor immunity. Therefore, necroptosis-inducible nanoparticles remarkably enhance antitumor immunity by activating CD8+ cytotoxic T cells and maturing dendritic cells in vitro. Conclusion: We have successfully synthesized Lip-ICG-PFP-cRGD nanoparticles, which can achieve SDT and provoke necroptosis by bubble-mediated cell membrane rupture. The innovative nanoparticle causes immunogenic cell death in cancer cells via RIPK3-independent necroptosis, which is a promising enhancer for cancer immunotherapy.
Recurrent Events Analysis with Piece-wise exponential Additive Mixed Models
Authors: Ramjith Jordache , Bender Andreas , Roes Kit C. B. , Jonker Marianne A. 
Published: June 2021

Abstract
Background: Recurrent events analysis plays an important role in many applications, including the study of chronic diseases or recurrence of infections. Historically, most models for the analysis of time-to-event data, including recurrent events, have been based on Cox proportional hazards regression. Recently, however, the Piece-wise exponential Additive Mixed Model (PAMM) has gained popularity as a flexible framework for survival analysis. While many papers and tutorials have been presented in the literature on the application of Cox based models, few papers have provided detailed instructions for the application of PAMMs and to our knowledge, none exist for recurrent events analysis. Methods: The PAMM is introduced as a framework for recurrent events analysis. We describe the application of the model to unstratified and stratified shared frailty models for recurrent events. We illustrate how penalized splines can be used to estimate non-linear and time-varying covariate effects without a priori assumptions about their functional shape. The model is motivated for both, analysis on the gap timescale ("clock-reset") and calendar timescale ("clock-forward"). The data augmentation necessary for the application to recurrent events is described and explained in detail. Results: Simulations confirmed that the model provides unbiased estimates of covariate effects and the frailty variance, as well as equivalence to the Cox model when proportional hazards are assumed. Applications to recurrence of staphylococcus aureus and malaria in children illustrates the estimation of seasonality, bivariate non-linear effects, multiple timescales and relaxation of the proportional hazards assumption via time-varying effects. The R package pammtools has been extended to facilitate estimation, visualization and interpretation of PAMMs for recurrent events analysis. Conclusion: PAMMs provide a flexible framework for the analysis of time-to-event and recurrent events data. The estimation of PAMMs is based on Generalized Additive Mixed Models and thus extends the researcher’s toolbox for recurrent events analysis.
A Cooperative Mobile Robot and Manipulator System (Co-MRMS) for Transport and Lay-up of Fibre Plies in Modern Composite Material Manufacture
Authors: Yang Manman , Yu Leijian , Wong Cuebong , Mineo Carmelo , Yang Erfu , Bomphray Iain , Huang Ruoyu 
Published: June 2021

Abstract
Composite materials are widely used in industry due to their light weight and specific performance. Currently, composite manufacturing mainly relies on manual labour and individual skills, especially in transport and lay-up processes, which are time-consuming and prone to errors. As part of a preliminary investigation into the feasibility of deploying autonomous robotics for composite manufacturing, this paper investigates a cooperative mobile robot and manipulator system (Co-MRMS) for material transport and composite lay-up, which mainly comprises a mobile robot, a fixed-base manipulator and a machine vision sub-system. In the proposed system, marker-based and Fourier transform-based machine vision approaches are used to achieve high accuracy capability in localisation and fibre orientation detection respectively. Moreover, a particle based approach is adopted to model material deformation during manipulation within robotic simulations. As a case study, a vacuum suction based end-effector model is developed to deal with sagging effects and to quickly evaluate different gripper designs, comprising of an array of multiple suction cups. Comprehensive simulations and physical experiments, conducted with a 6-DOF serial manipulator and a two-wheeled differential drive mobile robot, demonstrate the efficient interaction and high performance of the Co-MRMS for autonomous material transportation, material localisation, fibre orientation detection and grasping of deformable material. Additionally, the experimental results verify that the presented machine vision approach achieves high accuracy in localisation (the root mean square error is 4.04 mm) and fibre orientation detection (the root mean square error is 1.84°).
Association of Waist Circumference With Blood Pressure and Familial Dietary Habits in Preschool Children: A Cross-Sectional Study in Northeastern China.
Authors: Tang Xiao , Liu Yang , Hu Jiajin , Zhai Lingling , Jia Lihong , Ding Ning , Ma Yanan , Wen Deliang 
Published: June 2021

Abstract
BackgroundChildhood obesity increases the risk of elevated blood pressure (BP) in children. However, which obesity indicator is most closely associated with BP remains debatable. Moreover, the familial dietary environments play important roles on obesity, but which dietary factors are strong and independent ones for childhood obesity is unclear. Our study aimed to determine the superior indices associated with BP among body mass index (BMI), waist circumference (WC) and waist-to-height ratio (WHtR). Then, determine the independent familial dietary factors for those superior indices.Method605 children aged 2 to 6, as well as their parents were involved in this study. The children’s weights, heights, WC and BP were measured. Information on familial environments was obtained by asking the parents to complete questionnaires. BMI, WC and WHtR were standardized into their standardized z-score values and categorical variables of these three obesity indices were defined as BMI Category, WC Category and WHtR Category. Logistic regression was used to analyze the associations between standardized z-score of BMI, WC, WHtR and elevated BP. Multivariate stepwise linear regression and multivariate stepwise logistic regression were used to determine the independent factors for obesity indicators that were closely with BP.ResultsNumerical obesity indices associated with BP were, in order of decreasing association: WC, BMI and WHtR. The categorical variable that most closely associated with BP was WC Category. Parental BMI, birth weight of children, eating wheat as staple food, appetite, eating speed, snacking while watching TV, parental encouragement to eat a diverse assortment of foods and drinking milk were independent factors for WC in males or females. The risk of abdominal obesity would increase 1.375 times in males and 1.631 times in females if appetite increased one level. If eating speed increased one level, the risk of abdominal obesity would increase 1.165 times in males and 0.905 times in females. Children who drank milk greater than 6 times per week had a 0.546 times lower risk of abdominal obesity than those did not.ConclusionWC had the closest association with BP. Besides genetics, familial diet were independent factors for WC and abdominal obesity in preschool children.
Distributed Compressed Sensing Based Channel Parameter Estimation for MIMO-FBMC Communications
Authors: Wang Han , Wang Xianpeng 
Published: June 2021

Abstract
For the sparse correlation between channels in multiple input multiple output filter bank multicarrier with offset quadrature amplitude modulation (MIMO-FBMC/OQAM) systems, the distributed compressed sensing (DCS)-based channel estimation approach is studied. A sparse adaptive distributed sparse channel estimation method based on weak selection threshold is proposed. Firstly, the correlation between MIMO channels is utilized to represent a joint sparse model, and channel estimation is transformed into a joint sparse signal reconstruction problem. Then, the number of correlation atoms for inner product operation is optimized by weak selection threshold, and sparse signal reconstruction is realized by sparse adaptation. The experiment results show that proposed DCS-based method not only estimates the multipath channel components accurately but also achieves higher channel estimation performance than classical orthogonal matching pursuit (OMP) method and other traditional DCS methods in the time-frequency dual selective channels.
DoE Directed Optimization, Development and Characterization of Resveratrol Loaded Nlc System for the Nose to Brain Delivery in the Management of Glioblastoma Multiforme
Authors: Kumar Nitish , Gupta Ghanshyam Das , Arora Daisy 
Published: June 2021

Abstract
Nose to brain delivery of resveratrol can be a very useful method to overcome the limitations possessed by conventional delivery approaches namely, hepatic metabolism, low bioavailability and half-life of resveratrol, and presence of blood-brain barrier (BBB). The objective of this research work was to develop and optimize the resveratrol-loaded NLCs and coating these carriers with chitosan to increase the residence time of the formulation into the nasal cavity and enhanced permeation across the nasal mucosa. Three CQAs (Particle size, Entrapment efficiency, and PDI), and CMAs (Solid: total lipid concentration, surfactant concentration, and bioactive amount) were selected and the formulation was optimized using the Box-Behnken design (BBD) approach. The optimized batch was evaluated for physicochemical characteristics such as particle size (168.24 ± 8.24 nm), PDI (0.151 ± 0.003), and entrapment efficiency (77.42 ± 3.76 %). This optimized batch was coated with chitosan, which produced coated NLCs with a particle size of 317.7 ± 15.9 nm, and PDI was 0.089 ± 0.009. The morphological study using TEM confirmed the spherical shape, size, and surface coating of the NLCs. Furthermore, both the uncoated and coated particles were analyzed for in vitro resveratrol release, ex vivo diffusion study, and antioxidant assay. NLCs was founded to show sustained in vitro release characteristic, and enhanced bioactive diffusion across the nasal mucosa compared to the bioactive solution of resveratrol. The antioxidant assay revealed that the antioxidant property of resveratrol was intact in the formulation, and a slight increase in antioxidant activity of the formulation was also observed which may be due to the presence of sesame oil in the formulation. These results indicated that the chitosan-coated NLCs can be used to deliver therapeutic moieties more efficiently via the nose to brain drug delivery.
Baseline Viral Load Predicts Antiretroviral Therapy Outcomes Among HIV-Infected Patients: An Observational Cohort Study
Authors: Zhou Chao , Zhang Wei , Lu Rong-Rong , Ouyang Lin , Xing Hui , Shao Yi-Ming , Wu Guo-Hui , Ruan Yu-Hua 
Published: June 2021

Abstract
Background

Many factors are associated with human immunodeficiency virus (HIV) antiretroviral therapy (ART) outcomes. Viral load (VL) is a strong predictor of disease progression among HIV-infected patients. The aim of this study was to evaluate the influence of baseline VL on treatment-related mortality and virologic failure.
Methods

This retrospective study observed HIV-infected patients who were initiated on ART between 2012 and 2018 in Chongqing, China. Mortality assessment included the early mortality rate (deaths within the first 12 months) and the overall mortality rate (deaths during entire observation period). Virologic failure was defined as VL ≥ 200 copies/mL at 12 (range 9–15) months after treatment initiation. Cox proportional hazards regression and logistic regression models were used to evaluate the effects of baseline VL on mortality and virologic failure.
Results

The cohort included 9791 HIV patients; 50.1% of patients had baseline VL test at ART initiation, and only 18.4% had a baseline VL level of < 10,000 copies/mL. ART initiation at higher VL was significantly associated with the early mortality (10,000–99,999 copies/mL: AHR = 2.4; ≥100,000 copies/mL: AHR = 3.4) and the overall mortality (≥ 100,000 copies/mL: AHR = 1.7). Patients with VL ≥ 100,000 copies/mL and without baseline VL at ART initiation had higher virologic failure rate (AOR = 3.5 and AOR = 3.2, respectively).
Conclusions

ART initiation with higher VL was significantly associated with a greater risk of mortality and virologic failure, especially in the early stage of treatment. Baseline VL is essential for medical staff as it allows monitoring of treatment effect and allows for interventions to reduce HIV transmission. Continued efforts are needed to enhance the coverage of baseline VL testing.
Cardiovascular Outcomes of Type 2 Diabetic Patients Treated With DPP‑4 Inhibitors Versus Sulphonylureas As Add-on to Metformin in Clinical Practice
Authors: Bazo-Alvarez Juan Carlos , Pal Kingshuk , Pham Tra My , Nazareth Irwin , Petersen Irene , Sharma Manuj 
Published: June 2021

Abstract
Background: DPP-4 inhibitors (DPP-4i) and sulphonylureas remain the most widely prescribed add-on treatments after metformin. However, there is limited evidence from clinical practice comparing major adverse cardiovascular events (MACE) in patients prescribed these treatments, particularly among those without prior history of MACE and from vulnerable population.Methods: Using electronic health records from the UK primary care, we undertook a retrospective cohort study with people diagnosed type-2 diabetes mellitus, comparing incidence of MACE (myocardial infarction, stroke, major cardiovascular surgery, unstable angina) and all-cause mortality among those prescribed DPP-4i versus sulphonylureas as add-on to metformin. We stratified analysis by history of MACE, age, social deprivation and comorbidities and adjusted for HbA1c, weight, smoking-status, comorbidities and medications.Results: We identified 17,570 patients prescribed sulphonylureas and 6,267 prescribed DPP-4i between 2008-2017. Of these, 16.3% had pre-existing MACE. Primary incidence of MACE was similar in patients prescribed DPP-4i and sulphonylureas (10.3 vs 8.5 events per 1000 person-years; adjusted Hazard Ratio (adjHR): 0.94; 95%CI 0.80–1.14). For those with pre-existing MACE, rates for recurrence were higher, but similar between the two groups (21.8 vs 17.2 events per 1000 person-years; adjHR: 0.93; 95%CI 0.69–1.24). For those aged over 75 and with BMI less than 25kg/m2 there was a protective effect for DPP-I, warranting further investigation.Conclusions: Patients initiating a DPP-4i had similar risk of cardiovascular outcomes to those initiating a sulphonylurea. This indicates the choice should be based on safety and cost, not cardiovascular prognosis, when deciding between a DPP-4i or sulphonylurea as add-on to metformin.
Theoretical Study of the Effect of Water Clusters on the Enol Content of Acetone as a Model for Understanding the Effect of Water on Enolization Reaction
Authors: Nafe Zahra Tohidi , Arshadi Nematollah 
Published: June 2021

Abstract
The enolization of simple carbonyl compounds is a key reaction for many chemical and biochemical processes. Numerous theoretical and experimental studies have been done to probe aspects of the mechanism of this reaction. In this work, the effect of small water clusters, (H2O)n: n=1-9, on the enol content of acetone is investigated by using density functional theory calculations at the M06 level of theory in the gas and solution phases. The calculations indicated that the formation of hydrogen-bonded assemblies between water clusters and both tautomers of acetone affect the enolization reaction. Among them, the trimeric water cluster has the highest binding energy difference (DEb) in the solution phase and greatly shift the equilibrium in the favor of the enol form. The results also shown that under this condition, the enol content of acetone increased by decreasing the polarity of the solvent. The practical conclusion of this study is that the enol content of carbonyl compounds can be maximized only by addition a defined amount of water.
Physicochemical Property and Pharmacological Activity of Exopolysaccharide From Endophytic Bacterium Bacillus Sp. B3 Isolated From Polygonatum Sibiricum
Authors: Zhang Xunlian , Song Yingjuan , Li Kun , Liu Xiaoyu , Liu Zhaoxi , Rong Yongheng , Mao Weian , Zhang Houcheng , Kong Yun , Chen Min 
Published: June 2021

Abstract
Polygonatum sibiricum is a widely used traditional Chinese medicine with various functions. In this study, Bacillus sp. B3 as its endophytic bacterium, which produced the maximum amount of exopolysaccharide (EPS), was isolated. The EPS-B3 produced by Bacillus sp. B3 was purified and identified. As suggested by the analysis of monosaccharide composition, EPS-B3 with an average molecular weight of 1.863×104 Da, was composed of three main monosaccharides, including galactose, glucose and mannose with a molecular ratio of 15: 3: 1. The monosaccharide component of EPS-B3 was different from P. sibiricum polysaccharide (PSP), but they exhibited similar antioxidant and antitumor activity. It is worth to point out that, EPS-B3 exhibited higher Ferric reducing power than PSP. As suggested by the results, the EPS produced by endophytic bacterium from the medicinal plants might have the potential to serve as an alternative of the medicinal herbs.
Prevalence, Virulence Genes and Antimicrobial Profiles of Escherichia Coli O157:H7 Isolated from Healthy Cattle
Authors: Tayh Ghassan , Boubaker Salma Mariem , Khedher Rym Ben , Jbeli Mounir , Chehida Faten Ben , Mamlouk Aymen , Dâaloul-Jedidi Monia , Messadi Lilia 
Published: June 2021

Abstract
Background: Shiga toxin-producing Escherichia coli (STEC) O157:H7 is associated with intestinal infection in human and considered a main cause of food-borne diseases. It was isolated from animals, human and food. The aim of the study was to assess the incidence of E. coli O157:H7 in fecal samples of healthy cattle collected in slaughterhouses (n=160) and from farms (n=100).Methods: E. coli isolates were detected on MacConkey agar. A total of 236 E. coli isolates were recovered from fecal samples of healthy cattle. We used sorbitol MacConkey to detect non-sorbitol fermenting colonies that were examined for the presence of O157 antigen by latex agglutination, and positive bacteria were screened for the existence of stx1, stx2, eaeA and ehxA by PCR as well as rfbEO157 and fliCH7 genes specific for serotype O157. All isolates were examined for the susceptibility against 21antibiotics discs.Results: Of the 236 E. coli isolates, 4.2% (10/236) were positive for STEC O157:H7. Shiga toxin gene (stx2) was present in 70% of isolates, stx1 and ehxA were confirmed in 60% of the isolates, whereas eae was identified in two isolates. Other virulence factors screened (fimH, sfa/focDE, cdt3, traT, iutA and hly) were present among the 10 isolates. All E. coli O157:H7 isolates were sensitive to amoxicillin/clavulanic acid, cefotaxime, cefepime, aztreonam, colistin and sulfamethoxazole/trimethoprim. All isolates belong to the phylo-group E.Conclusion: This is the first study of the incidence of E. coli O157:H7 in cattle in Tunisia. Our finding proves the existence of STEC O157:H7 in healthy animals producing food for human consumption which could be a source of human contamination.
Driver Genes of Locally Advanced Well-differentiated Thyroid Cancer: Genetic Landscape Based on the TCGA Database
Authors: Jung Ah Ra , Jang Dong Hyuk , Choi Jung Ho , Lee Yoon Se 
Published: June 2021

Abstract
Background: Despite the usually favorable prognosis of well-differentiated thyroid cancer (WDTC) following appropriate treatment, advanced T-staged WDTCs are associated with poor prognosis. This study focused on identifying the driver genes of locally advanced WDTC by analyzing the TCGA cohort.Methods: We analyzed data on 501 patients with WDTC from the TCGA cohort. Patients were classified into two subgroups of pathological T4 stage or T1-3 stage (Cluster1 and Cluster2, respectively). The mRNA expression differences between subgroups were compared for several genes in the TCGA cohorts.Results: Cluster1 included 23 patients with pathological T4 classification (Papillary=21/Follicular=2) and Cluster2 included 478 patients (Papillary=371/Follicular=100/Others=7). The Cluster1 subgroup showed worse overall survival than the Cluster2 subgroup (p < 0.05). The two subgroups were analyzed for 34 genes reported in previous studies. Known genetic thyroid cancer alterations, including BRAF, RAS, RET, and ALK, were not different in the two subgroups. In Cluster1, MET, SERPINA1, TIMP1, PROS1, FN1, CDKN2A, and CDKN2B were significantly elevated, while TG, DNAH9, TFF3, CRABP1, TPO, JAK2, KIT, KDR, and NFE2L2 were significantly lower compared with the Cluster2 (all, p < 0.05). A TERT, EIF1AX, and ATM showed significantly frequent somatic mutations in Cluster1 compared to Cluster2. We also identified seven pathways related to the 16 genetic markers.Conclusions: Locally advanced WDTC presented 16 genetic alterations compared to less aggressive thyroid cancers. Somatic mutations associated with local invasion transformation were identified. Genetic profiles associated with locally advanced WDTC have prognostic significance, but these findings must be validated to further understand the pathway.
Mathematical model for recovering discrete parts of a text message
Authors: Malashina Anastasia 
Published: June 2021

Abstract
The paper studies the procedure for restoring discreet segments of an unknown source message based on information about possible variants of each sign. An algorithm is proposed based on compiling dictionaries of appropriate lengths, searching for text sections with a total number of character variants that do not exceed a given boundary, and then iterating through and eliminating false variants of dictionary values. Statistical properties of short-length text dictionaries are investigated, and extrapolation estimates are made for long-length texts. The main mathematical properties of this algorithm are described. Theoretical studies of the effectiveness of the procedure under consideration are carried out within the framework of a certain probability-theoretical model.