bluuebunny/crossref_metadata_2025 huggingface dataset:
Sexual Risk Behaviour Among School-going Adolescents in Sierra Leone and Liberia. A Secondary Analysis of the 2017 Global School Health Survey
Authors: James Peter Bai , Osborne Augustus , Bah Abdulai Jawo , Margao Emmanuel Kamanda , Conteh-Barat Mohamed
Published: December 2021

Background: There is very little information on sexual risk behaviour among Sierra Leone and Liberia school-going adolescents. The present study assessed the prevalence and determinants of sexual risk behaviours among school-aged adolescents in Sierra Leone and Liberia. Method: We used publicly available nationally representative cross-sectional datasets of the 2017 Sierra Leone and Liberia Global school health survey. The sample consisted of 2798 and 2744 school-going adolescents from Sierra Leone and Liberia, respectively. Results: The majority of adolescents in the two countries were involved in multiple sexual risk behaviour (80.2%), with higher prevalence observed in Sierra Leone (85.2%) than in Liberia (75.3%), Liberian adolescents showed lesser odds of indulging in multiple sexual risk behaviours than their Sierra Leonean counterparts (AOR=0.572; 95%CI: 0.345-0.946). Male compared to females were more likely to engage in multiple sexual risk behaviour (AOR=2.310;95%CI:1.543-3.458), with a similar pattern observed in both countries. Alcohol use was associated with multiple sexual risk behaviour (AOR=3.064; 95%CI: 2.137-4.392). Also, in Sierra Leone and Liberia, adolescents with one and two or more forms of psychological distress were more likely to have ever had sex than those who do show any form of psychological distress. Missing class/school was associated with multiple sexual risk behaviour (AOR=1.655; 95%CI:1.133-2.418). Peer support was only found to be a protective factor against no condom use among Liberian adolescents (AOR=0.608; 95%CI: 0.435-0.850). Less parental support was only associated with ever had sex more likely to have ever had sex as seen among adolescents in Sierra Leone (AOR=2.027; 95%CI: 1.322-3.107) but not Liberia (1.034(0.650-1.644). Conclusion: Our study found a high sexual risk behaviour among school-going adolescents in Sierra Leone and Liberia. Our finding highlights the need to strengthen sexual and reproductive health education in schools and communities that incorporate mental health promotion activities tailored to this group.
Appropriate Distraction Strength For Metatarsophalangeal Joint Arthroscopy
Authors: Kim Jong-Kil , Kim Do-Yeon , Lee Kwang-Bok
Published: December 2021

This study is to investigate the natural metatasophalangeal joint (MTP) distance, the appropriate degree of distraction and the associated factors including age, gender, body mass index(BMI). Regarding natural MTP joint space size, the MTP-2 joint had the largest joint size (2.39 ± 0.37 mm). The MTP-5 joint had the smallest joint size (1.59 ± 0.34 mm). In MTP joint arthroscopy, traction power of 10 lbs is sufficient for appropriate distraction for all MTP joints while traction power of 5 lbs is an appropriate power for distraction of the MTP-2 joint. Manual traction is generally not appropriate for distraction because it is not consistent or sufficient. Less distraction power is required for males than for females, especially for MTP-1, MTP-3, and MTP-4 joints.
High Precision Half‑Life Measurement of the Extinct Radio‑Lanthanide Dysprosium-154
Authors: Chiera Nadine Mariel , Dressler Rugard , Sprung Peter , Talip Zeynep , Schumann Dorothea
Published: December 2021

Sixty years after the discovery of 154Dy, the half-life of this pure alpha-emitter was re-measured. 154Dy was radiochemically separated from proton-irradiated tantalum samples. Sector field- and multicollector-inductively coupled plasma mass spectrometry were used to determine the amount of 154Dy retrieved. The disintegration rate of the radio-lanthanide was measured by means of α-spectrometry. The half-life value was determined as (1.33 ± 0.07)∙106 y, with an uncertainty reduced by a factor of ~10 compared to the currently adopted value of (3.0 ± 1.5)∙106 y. This precise half-life value is crucial for the correct estimation of p-process nucleosynthetic reactions in the lanthanide region, as well as for the safe disposal of irradiated target material from spallation facilities. As a first application of the half-life value found in this work, the excitation functions for the production of 154Dy in proton-irradiated Ta, Pb, and W targets were re-evaluated, which found to be in agreement with theoretical calculations.
An Automated Auroral Detection System Using Deep Learning: Real-time Operation in Tromsø, Norway
Authors: Nanjo Sota , Nozawa Satonori , Yamamoto Masaki , Kawabata Tetsuya , Johnsen Magnar G. , Tsuda Takuo T. , Hosokawa Keisuke
Published: December 2021

The activity of citizen scientists who capture images of aurora borealis using digital cameras has recently been contributing to research regarding space physics by professional scientists. Auroral images captured using digital cameras not only fascinate us, but may also provide information about the energy of precipitating auroral electrons from space; this ability makes the use of digital cameras more meaningful. To support the application of digital cameras, we have developed artificial intelligence that monitors the auroral appearance in Tromsø, Norway, instead of relying on the human eye, and implemented a web application, “Tromsø AI”, which notifies the scientists of the appearance of auroras in real-time. This “AI” has a double meaning: artificial intelligence and eyes (instead of human eyes). Utilizing the Tromsø AI, we also classified large-scale optical data to derive annual, monthly, and UT variations of the auroral occurrence rate for the first time. The derived occurrence characteristics are fairly consistent with the results obtained using the naked eye, and the evaluation using the validation data also showed a high F1 score of over 93%, indicating that the classifier has a performance comparable to that of the human eye classifying observed images
Mindfulness-Based Online Intervention Increases Well-Being And Decreases Stress After Covid-19 Lockdown
Authors: Bossi Francesco , Zaninotto Francesca , D’Arcangelo Sonia , Lattanzi Nicola , Malizia Andrea P. , Ricciardi Emiliano
Published: December 2021

Mindfulness interventions were shown to be effective in improving well-being and reducing perceived stress in several conditions. These effects were also found in online mindfulness-based training, especially on employees in organizational environments. The aim of this study was to test the effectiveness of online mindfulness intervention on healthy employees especially after the first Italian Covid-19 lockdown.Participants in the intervention group underwent an 8-week mindfulness online training program based on the Mindfulness-Based Stress Reduction (MBSR) protocol compared to a control (no-intervention) group. All participants filled in weekly surveys for the whole intervention duration via online questionnaires to measure their habits, mindfulness (FFMQ-15), emotion regulation (ERQ), positive and negative affect (PANAS), depression, anxiety and stress (DASS-21), resilience (RSA) and insomnia (ISI). 46 participants in the intervention group and 54 in the control group completed at least half of the weekly questionnaires and were considered in the longitudinal analyses. We found significant differences between the intervention and control groups over time in the measures of mindfulness (in particular the nonreactivity subscale), positive affect, depression, and insomnia. Moreover, we found that the frequency of practice and ease perceived in practicing were positively correlated to several indices of well-being (mindfulness, positive affect, cognitive reappraisal) and negatively correlated to several indices of stress (negative affect, depression, anxiety, stress, insomnia, expressive suppression). These results show the importance and effectiveness of online mindfulness training programs to cope with stress among employees, especially after the Covid-19 lockdown.
Cellulose Nanoparticles Prepared by Ionic Liquid-Assisted Method Improve the Properties of Bionanocomposite Films
Authors: Vieira Suellen Rocha , Silva Jânia Betânia Alves da , Druzian Janice Izabel , de Jesus Denilson Assis , Mussage Cassamo Ussemane , Pereira Jorge Fernando Brandão , Santos-Ebinuma Valéria Carvalho , Lemos Paulo Vitor França , Correia Paulo Romano Cruz , Ferreira Ederlan de Souza , Souza Carolina Oliveira
Published: December 2021

Bionanocomposites have garnered wide interest from the packaging industry as a biocompatible alternative to non-biodegradable petroleum-based synthetic materials. This study presents a simple and eco-friendly alternative to produce cellulose nanoparticles using a protic ionic liquid, and the effects of their incorporation in cassava starch and chitosan films are evaluated. Bionanocomposite films are prepared using the solvent casting method and are characterized using X-ray diffraction, Fourier transform infrared spectroscopy, zeta potential, thermogravimetry analysis, and transmission electron microscopy. The achieved yield of cellulose nanoparticles is 27.82%, and the crystalline index is 67.66%. The nanoparticles’ incorporation (concentration from 0.2 to 0.3%) results in a progressive reduction of water vapor permeability up to 49.50% and 26.97% for starch and chitosan bionanocomposite films, respectively. The starch films with 0.1% cellulose nanoparticles exhibit significantly increased flexibility compared to those without any addition. The nanoparticles’ incorporation in chitosan films increases the thermal stability without affecting the mechanical properties. The study demonstrates that the use of cellulose nanoparticles obtained using protic ionic liquid can be a simple, sustainable, and viable method to produce bionanocomposites with tailored properties useful for applications in the packaging industry.
A Fast Markovian Method For Modeling Channel Noise In Neurons
Authors: Ankri Norbert , Debanne Dominique
Published: December 2021

Channel noise results from rapid transitions of protein channels from closed to open state and is generally considered as the most dominant source of electrical noise causing membrane-potential fluctuations even in the absence of synaptic inputs. The simulation of a realistic channel noise remains a source of possible error. Although the Markovian method is considered as the golden standard for appropriate description of channel noise, its computation time increasing exponentially with numbers of channels, it is poorly suitable to simulate realistic features. We describe here a novel algorithm for simulating ion channel noise based on Markov chains (MC). Although this new algorithm refers to a Monte-Carlo process, it only needs few random numbers whatever the number of channels involved. Our fast MC (FMC) model does not exhibit the drawbacks due to approximations based on stochastic differential equations. In fact, we show here, that these drawbacks can be highlighted even for a high number of channels.
An Exceptionally Stable and Widespread Hydrated Amorphous Calcium Carbonate Precipitated By the Dog Vomit Slime Mold Fuligo Septica (Myxogastria)
Authors: Garvie Laurence A.J. , Németh Péter , Trif László
Published: December 2021

Biogenic amorphous calcium carbonate (ACC) is typically metastable and can rapidly transform through aging, dehydration, and/or heating to crystalline calcium carbonate. Gaining insight into its structure and properties is typically hampered by its tendency to crystallize over short time periods once isolated from the host organism, and also by the small quantities that are usually available for study. Here, we describe an exceptionally stable hydrated ACC (HACC) precipitated by the cosmopolitan slime mold, Fuligo septica (L.) F.H. Wigg. (1780). A single slime mold can precipitate up to one gram of HACC over the course of one night. Powder x-ray diffraction (XRD) patterns, transmission electron microscopy (TEM) images, infrared absorption (IR) spectra, and lack of optical birefringence are consistent with an amorphous material. XRD simulations supported by thermogravimetric (TG) and evolved gas analysis (EGA) data suggest an intimate association of organic matter with ~1-nm-sized ACC units that have monohydrocalcite- and calcite-like nano-structural properties. It is postulated that this association imparts the extreme stability of the HACC by preventing loss of H2O and subsequent crystallization. The composition, structure, and thermal behavior of the HACC precipitated by F. septica collected over 8000 km apart, and in markedly different environments, suggests a common structure, as well as similar biochemical and biomineralization mechanisms for the HACC formation.
The Control Concept for Upper Limb Exoskeleton
Authors: Lento Bianca , Aoustin Yannick , Zielinska Teresa
Published: December 2021

Robotic exoskeletons inspired by the animal’s external covering are wearable systems that enhance human power, motor skills, or support the movement. The main difficulty, apart from the mechanical structure design, is the development of an exoskeleton control system, as it should recognize the movement intended by the user and assist in its execution. This work is devoted to the exoskeleton of the upper limbs that supports movement. The method of controlling the exoskeleton by means of electromyograms (EMG) was presented. EMG is a technique for recording and assessing the electrical activity produced by skeletal muscles. The main advantage of EMG based control is the ability to forecast intended motion, even if the user is unable to generate it. This work aims to define strategies for controlling the exoskeleton of the upper limb in children suffering from neuromuscular diseases. Such diseases gradually reduce the mobility of the lower and upper limbs. These children are wheelchair bound, so it was assumed that the upper limb exoskeleton could be attached to a wheelchair. EMG signals are recorded, amplified and filtered. An artificial neural network using fuzzy logic to process EMG was used. This network predicts movement trajectories. Using this forecast and taking into account the feedback information, the control system generates the appropriate drive torques.
Dynamic Microbial Network Structure and Assembly Process in Rhizosphere and Bulk Soils Along a Coniferous Plantation Chronosequence
Authors: Wang Ying , Dong Liguo , Zhang Min , Bai Xiaoxiong , Zhang Jiawen , Yu Xuan
Published: December 2021

Aims: During plantation development, microbial composition and diversity are critical for the establishment of plant diversity and multiple ecosystem functions. Here we aimed to evaluate the impacts of chronosequence and soil compartment on the bacterial and fungal community compositions, species co-occurrence, and assembly processes in forest ecosystem.Methods: Soils were collected in rhizosphere and bulk soils along a Pinus tabulaeformis plantation chronosequence (15, 30 and 60 years old). The bacterial and fungal communities were determined using amplicon sequencing.Results: The effect of stand age on the soil properties and microbial community structures was stronger than the effect of the soil compartment. In all soil samples, the dominant bacterial phyla were Proteobacteria, Acidobacteria, Actinobacteria, and Chloroflexi. Basidiomycota, Ascomycota, and Mortierellomycota were the dominant fungal phyla. Higher turnover rates of soil microbial communities were observed in rhizosphere soil than in bulk soil. Dispersal limitation governed the bacterial and fungal community assembly in all soil samples, and the fungal community was more susceptible to dispersal limitation. The bacterial and fungal keystone species compositions in the rhizosphere had significant positive correlations with the soil total phosphorus and nitrite nitrogen and total nitrogen and total phosphorus, respectively, indicating their importance in soil nitrogen and phosphorus cycling. The complexity of bacterial networks increased along the chronosequence. Fungal network complexity did not show a clear age-related trend but increased from bulk soil to the rhizosphere.Conclusions: During Pinus tabulaeformis plantation development, soil microbial assembly was less environmentally constrained due to an increase in resource availability.
Beneficial Effects of Fixed-Dose Combination of Amlodipine and Atorvastatin in Patients with Concomitant Hypertension and Hypercholesterolemia: A Multi-Institutional Cohort Study
Authors: Lin Chia-Pin , Hsiao Fu-Chih , Wu Chia-Tung , Lin Yu-Sheng , Chen Shao-Wei , Chu Pao-Hsien
Published: December 2021

Background

Blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) are important risk factors for cardiovascular (CV) diseases and treating these factors simultaneously is recommended by current guidelines but only short-term clinical results were available. The objective of this study was to examine the longer-term efficacy and safety of fixed-dose combination (FDC) versus free combination of amlodipine and atorvastatin in patients with concomitant hypertension and hypercholesterolemia.
Methods

Patients with hypertension and hypercholesterolemia were stratified into three groups (FDC of amlodipine 5 mg/atorvastatin 10 mg [Fixed 5/10], FDC of amlodipine 5 mg/atorvastatin 20 mg [Fixed 5/20], and free combination of amlodipine 5 mg/atorvastatin 10 mg [Free 5/10]). After inverse probability of treatment weighting, the composite CV outcome, liver function, BP, LDL-C and glycated hemoglobin (HbA1c) changes were compared.
Results

A total of 1,788 patients were eligible for analysis and the mean follow-up period was 1.7 year. There was no significant difference in the composite CV outcome among the three groups during the 30-month follow-up period (Fixed 5/10 6.1%, Fixed 5/20 6.3% and Free 5/10 6.0%). The LDL-C level was significantly reduced in the Fixed 5/20 group (-35.7 mg/dL) compared to the Fixed 5/10 (-23.6 mg/dL) and Free 5/10 (-10.3 mg/dL) groups (P=0.001 and <0.001, respectively). The changes in HbA1c were similar among the three groups.
Conclusions

FDC of amlodipine and atorvastatin, especially the regimen with higher dosage of statin, significantly reduced the mid-term LDL-C level compared to free combination in patients with concomitant hypertension and hypercholesterolemia. Blood sugar level during the follow-up period was not significantly changed by this aggressive treatment strategy.
The Connection Between the Hadley Circulation and Meridional Structure of Tropical SST during ENSO from 1950 to 1977
Authors: Yu Mingxin , Feng Juan , Li Jianping , An Ran
Published: December 2021

The connection between the meridional structure of tropical sea surface temperature (SST) and the Hadley circulation (HC) under the effect of ENSO (El Niño Southern Oscillation) from 1950 to 1977 is studied. We decompose the HC and zonal mean SST into equatorially symmetric (HES for HC, SES for SST) and asymmetric variations (HEA for HC, SEA for SST) to discuss the modulation of their connection by ENSO. During El Niño events from 1950 to 1977, the HC is less sensitive to the different SST meridional structures and expressed by response ratio. The ratio in La Niña and neutral events is around 4, which is equivalent to the result in the climatology. The reason for the decreased ratio during El Niño events is explored. The interdecadal variation in the linkage between the HC and tropical SST is due to a clear interdecadal shift in the impacts of ENSO on the tropical Indian Ocean (TIO) SST. For the period 1950–1977, when El Niño events occur, larger SST warming amplitude is observed over the northern TIO (0°–15°N, 50°–100°E). However, the southern TIO (15°S–0°, 50°–100°E) shows greater warming amplitude during 1980–2016. The anomalous SST variation over the TIO linked to El Niño events alters the meridional SST distribution, inducing anomalies in the meridional circulation. These results can help us to understand the interdecadal modulation by ENSO of the relationship between tropical SST and the HC.
Clinical Characteristics And Prognosis of Vasovagal Syncope With Sinus Arrest In Children
Authors: Sun Rui , Kang Yingying , Chen Yeshi , Li Xiaohui , Zhang Mingming , Shi Lin
Published: December 2021

The aim of this study was to analyze the clinical characteristics and prognosis of vasovagal syncope(VVS) with sinus arrest in children. From July 2017 to October 2020, cases of VVS with sinus arrest were recruited from patients diagnosed as VVS in our department. The clinical data, the results of the head-up tilt testing (HUTT), and follow-up information were analyzed. 223 patients were diagnosed as VVS during the time, and 10 cases of VVS with sinus arrest were recruited, who had a median age of 9.5 years（interquartile range: 6.8 to 10.4 years), a gender ratio of 1:1, and median sinus arrest time of 7.7s(range: 3.39 to 19s). These patients were given oral rehydration salts and orthostatic training, as well as 2 children treated with metoprolol and 5 children with sertraline hydrochloride. No child was implanted with pacemakers. During a median of 26 months of follow-up (interquartile range: 21 to 33 months), only one of the children had once syncope episode, three children had 1~4 times of prodromal symptoms. Conclusion The present research most crucial finding was that VVS patients with sinus arrest in children were younger than ordinary pediatric VVS patients. Oral rehydration salts(ORS) and autonomic nerve function exercise may improve clinical symptoms in children with VVS accompanied by sinus arrest. Pacemakers for VVS with sinus arrest in children should be cautious.
Clinical and Economic Impact of ‘ROS1-Testing’ Strategy Compared to a ‘No- ROS1-Testing’ Strategy in Advanced NSCLC in Spain
Authors: Rojo Federico , Conde Esther , Torres Héctor , Cabezón-Gutiérrez Luis , Bautista Dolores , Ramos Inmaculada , Carcedo David , Arrabal Natalia , García J. Francisco , Galán Raquel , Nadal Ernest
Published: December 2021

Background: Detection of the ROS1 rearrangement is mandatory in patients with advanced or metastatic non-small cell lung cancer (NSCLC) to allow targeted therapy with specific inhibitors. However, in Spanish clinical practice ROS1 determination is not yet fully widespread. The aim of this study is to determine the clinical and economic impact of sequentially testing ROS1 in addition to EGFR and ALK in Spain.Methods: A joint model (decision-tree and Markov model) was developed to determine the cost-effectiveness of testing ROS1 strategy versus a no-ROS1 testing strategy in Spain. Distribution of ROS1 techniques, rates of testing, positivity, and invalidity of biomarkers included in the analysis (EGFR, ALK, ROS1 and PD-L1) were based on expert opinion and Lungpath real-world database. Treatment allocation depending on the molecular testing results was defined by expert opinion. For each treatment, a 3-states Markov model was developed, where progression free survival (PFS) and overall survival (OS) curves were parameterized using exponential extrapolations to model transition of patients among health states. Only medical direct costs were included (€ 2021). A lifetime horizon was considered and a discount rate of 3% was applied for both costs and effects. Both deterministic and probabilistic sensitivity analyses were performed to address uncertainty.Results: A target population of 8,755 patients with advanced NSCLC (non-squamous or never smokers squamous) entered the model. Over a lifetime horizon, the ROS1 testing scenario produced additional 157.5 life years and 121.3 quality-adjusted life years (QALYs) compared with no-ROS1 testing scenario. Total direct costs were increased up to € 2,244,737 for ROS1 testing scenario. The incremental cost-utility ratio (ICUR) was 18,514 €/QALY. Robustness of the base-case results were confirmed by the sensitivity analysis.Conclusions: Our study shows that ROS1 testing in addition to EGFR and ALK is a cost-effective strategy compared to no-ROS1 testing, and it generates more than 120 QALYs in Spain over a lifetime horizon. Despite the low prevalence of ROS1 rearrangements in NSCLC patients, the clinical and economic consequences of ROS1 testing should encourage centers to test all advanced or metastatic NSCLC (non-squamous and never-smoker squamous) patients.
Soil Microbial Community Composition and Diversity Remained Unchanged in a Semiarid Grassland in Northwestern China After 7 Years of Nitrogen Addition
Authors: Guo Qian , Wen Zhongming , Ghanizadeh Hossein , Zheng Cheng , Fan Yongming , Lu Jinxin , Yang Xue , Yan Xinhui , Chen Sihui , Li Wei
Published: December 2021

Aims

Nitrogen (N) deposition is a global environmental problem that can alter community compositions and functions, and consequently, the ecosystem services. In this study, we assessed the responses of aboveground vegetation, surface soil properties and microbial communities to N addition, and explored the drivers of microbial community in a semiarid steppe ecosystem in northwest of China.
Methods

Thirty-six 6×10-m2 plots composed of six N addition levels and six replicates were distributed in six columns and six rows. Nine vegetation characteristics and seven soil properties were measured and calculated. Soil microbial characteristics were analyzed by 16S rRNA high-throughput sequencing.
Results

N addition positively affected aboveground vegetation traits such as the community weighted-mean of leaf nitrogen content (LNCWM). High N inputs significantly altered the microbial community assembly process from random to deterministic. The microbial community diversity and composition, however, were not sensitive to N addition. A piecewise structural equation model (SEM) further showed that the microbial community composition was affected by both aboveground vegetation and soil properties. The composition of bacterial communities was mainly regulated by the composition of plant communities and soil total N. In contrast, the composition of fungal communities was driven by soil pH and the community weighted-mean of specific leaf area (SLACWM). Microbial diversity and composition remained unchanged because their drivers were not affected by N addition. The results of this research improved our understanding of the response of grassland ecosystems to N deposition, and provided a theoretical basis for grassland utilization and management under N deposition.
Regression-Based Beam Training for UAV mmWave Communications
Authors: Zhang Junjie , Zhong Weizhi , Gu Yong , Zhu Qiuming , Zhang Lulu
Published: December 2021

For the unmanned aerial vehicle (UAV) Millimeter-Wave (mmWave) communication systems, an efficient and accurate beam training method is urgently required to overcome the severe path loss. By taking into account the mmWave propagation environment,a three-dimensional (3D) intelligent beam training strategy by leveraging the polynomial regression model and optimized beam patterns is proposed in this paper. We treat the mmWave beam selection as a polynomial regression problem. The regression function is obtained by a machine learning (ML) method based on the dataset and a special beam pattern is achieved to obtain the dataset consisting of measured powers and estimated angles. Furthermore, a noise suppression method involving the use of denoising autoencoder (DAE) is developed to improve the robustness of the proposed regression model.Numerical simulation results demonstrate that our proposed beam training strategy is capable of getting the same precision as the exhaustive search methods with a shorter time.
Efficacy of First-Third generation EGFR inhibitor combined with chemotherapy as first-line treatment for advanced lung adenocarcinoma in a real-world setting
Authors: Chen Ming-Wei Chen Ming-Wei , . An-Tai He , . Yi Pei
Published: December 2021

BackgroundTo explore the optimal treatment strategy for patients who harbor sensitive EGFR mutations, a head-to-head study was performed to compare chemotherapy and gefitinib-erlotinip, osimertinib treatment in combination or with either agent alone as first-line therapy, in terms of efficacy and safety.MethodsA total of 200 untreated patients with advanced lung adenocarcinoma who harbored sensitive EGFR mutations were randomly assigned to receive gefitinib-erlotinip combined with pemetrexed and carboplatin group, gefitinib-erlotinip osimertinib combined with pemetrexed and carboplatin group, pemetrexed plus carboplatin alone group, or gefitinib-erlotinip alone group, osimertinib alone group.ResultsThe progression-free survival (PFS) of patients in the gefitinib-erlotinip combination group Mean Survival Time PFS 22.00 month,95%CI[16.29,27.70] and osimertinib gefitinib-erlotinip combination group Mean Survival Time PFS 40.00 month,95%CI[28.12,51.87]was longer than that of patients in the chemotherapy alone group PFS10,81 months, 95% CI,[ 8.99–12.64],gefitinib-erlotinip alone group PFS14.00 month.95%CI[11.98-20.01], osimertinib alone group PFS 26.66 month 95%CI[24.77-29.22].The gefitinib-erlotinip osimertinib combinational resulted in longer overall survival (OS) than chemotherapy alone (HR = 0.46, p = 0.016) or gefitinib-erlotinip alone (HR = 0.36, p = 0.01). osimertinib alone (HR = 0.26, p = 0.01).ConclusionsOur finding suggested that treatment with pemetrexed plus carboplatin combined with gefitinib-erlotinip and pemetrexed plus carboplatin combined with gefitinib-erlotinip osimertinib group could provide better survival benefits for patients with lung adenocarcinoma harboring sensitive EGFR mutations.
Identification of Key Genes Involved in the Pathogenesis of Recurrent Pelvic Organ Prolapse Using Bioinformatics Analysis
Authors: Zhu Ling , Ni Xiaoling , Tang Shanshan , Liu Wenhua
Published: December 2021

Background: The causes of the recurrence of pelvic organ prolapse (POP) are sufficiently understood. However, few studies investigate the key genes of recurrence POP. The present study aimed to screen the hub genes of recurrence POP. Microarray data of 4 recurrent POP and 4 primary POP uterosacral ligaments in the GSE28660 gene expression dataset were used as research objects. we used the online Gene Expression Omnibus (GEO) microarray expression profiling dataset to identify differentially expressed genes (DEGs). Also, functional enrichment and protein-protein interaction (PPI) network analyses were performed, and the key modules were identified. Then, we investigated the differential immune cell infiltration between recurrent POP and primary POP tissues using the CIBERSORT algorithm.Results: In total, 84 upregulated and 32 downregulated genes were identified in the differential expression analysis.Conclusion: This human genome DNA microarrays analysis identified a recurrence POP signature of 116 genes, and 2 hub genes, including cell death-inducing DFFA-like effector (CIDEA) and hemoglobin subunit delta (HBD) may participate in the pathogenesis of recurrence POP, giving them a certain diagnostic and therapeutic value.
Engineered Exosomes for the Targeted Delivery of a Novel Therapeutic Cargo to Enhance Sorafenib-Mediated Ferroptosis in Hepatocellular Carcinoma.
Authors: Li Xiaoju , Yu Qianqian , Guo Xinyan , Liu Chenlin , Zhao Runze , Zhang Kuo , Zhang Wangqian , Liu Jinghan , Sun Guanchao , Wang Shuning , Hao Qiang , Li Weina , Li Meng , Zhang Yingqi , Zhang Cun , Gao Yuan
Published: December 2021

Background

Sorafenib is one of the few effective first-line drugs approved for the treatment of advanced hepatocellular carcinoma (HCC). However, the development of drug resistance is common among individuals with HCC. Thus, there is an urgent need to solve this problem.
Results

Recent evidence indicated that the anticancer activity of sorafenib mainly relies on the induction of ferroptosis. In our study, genes that suppress ferroptosis, especially GPX4 and DHODH, were enriched in sorafenib-resistant cells and primary tissues and were associated with poor prognosis of HCC patients who received sorafenib treatment. Therefore, silencing GPX4 and DHODH might be a novel and effective strategy to overcome sorafenib resistance. Here, a novel ferroptosis inducer comprising a multiplex small interfering RNA (multi-siRNA) capable of simultaneously silencing GPX4 and DHODH was created. Then, exosomes with high multi-siRNA loading and HCC-specific targeting were established by fusing the SP94 peptide and the N-terminal RNA recognition motif (RRM) of U1-A with the exosomal membrane protein Lamp2b. The results from the in vitro and in vivo experiments indicate that this tumor-targeting nanodelivery system (ExoSP94−lamp2b−RRM-multi-siRNA) could enhance sorafenib-induced ferroptosis and overcome sorafenib resistance, which might open a new avenue for clinically overcoming sorafenib resistance.
Conclusions

We designed HCC-targeted exosomes (ExoSP94−Lamp2b−RRM) that can deliver a novel ferroptosis inducer. Our data show that ExoSP94−lamp2b−RRM-multi-siRNA could enhance sorafenib-induced ferroptosis by silencing GPX4 and DHODH expression and consequently increase HCC sensitivity to sorafenib. This is the first study to describe the use of engineered exosomes to overcome acquired sorafenib resistance with respect to ferroptosis.
Fixed-Time Adaptive Neural Network Tracking Control for Output-Constrained High-Order Systems Using Command Filtered Strategy
Authors: Chen Lian , Wang Qing
Published: December 2021

This paper proposes a fixed time adaptive neural command filtered controller for a category of high-order systems based on adding a power integrator technique. Different from existing research, the presented controller has the following distinguishing advantages: i) fixed-time control framework is extended to the tracking control problem of high-order systems. ii) the error compensation mechanism eliminates filter errors that arise from dynamic controllers. iii) growth assumptions about unknown functions are relaxed with the help of adaptive neural networks. iv) more general systems: the developed controller can apply to high-order systems subject to uncertain dynamics, unknown gain functions and asymmetric constraints. Stability analysis shows that all states are semi-globally bounded, and the convergence rate of tracking error is independent of initial conditions. The main innovation of our work is that the presented controller considers simultaneously filter errors, fixed-time convergence, growth conditions and asymmetric output constraint for the tracking control issue of high-order systems. Finally, the simulation results validate the advantages and efficacy of the developed control scheme.
Nomogram Models Based on Gene Expression in Prediction of Breast Cancer Bone Metastasis
Authors: Fan Teng-di , Bei Di-kai , Li Song-wei
Published: December 2021

Objective: To design a weighted co-expression network and build gene expression signature-based nomogram (GESBN) models for predicting the likelihood of bone metastasis in breast cancer (BC) patients. Methods: Dataset GSE124647 was used as a training set, and GSE14020 was taken as a validation set. In the training cohort, limma package in R was adopted to obtain differentially expressed genes (DEGs) between BC non-bone metastasis and bone metastasis patients, which were used for functional enrichment analysis. After weighted co-expression network analysis (WGCNA), univariate Cox regression and Kaplan-Meier plotter analyses were performed to screen potential prognosis-related genes. Then, GESBN models were constructed and evaluated. Further, the expression levels of genes in the models were explored in the training set, which was validated in GSE14020. Finally, the prognostic value of hub genes in BC was explored. Results: A total of 1858 DEGs were obtained. WGCNA result showed that the blue module was most significantly related to bone metastasis and prognosis. After survival analyses, GAJ1, SLC24A3, ITGBL1, and SLC44A1 were subjected to construct a GESBN model for overall survival. While GJA1, IGFBP6, MDFI, ITGFBI, ANXA2, and SLC24A3 were subjected to build a GESBN model for progression-free survival. Kaplan-Meier plotter and receiver operating characteristic analyses presented the reliable prediction ability of the models. Besides, GJA1, IGFBP6, ITGBL1, SLC44A1, and TGFBI expressions were significantly different between the two groups in GSE124647 and GSE14020. The hub genes had a significant impact on patient prognosis. Conclusion: Both the four-gene signature and six-gene signature could accurately predict patient prognosis, which may provide novel treatment insights for BC bone metastasis.
Enhanced Biosynthesis of D-arabitol by Metschnikowia Reukaufii Through Optimizing Medium Composition and Fermentation Conditions
Authors: Huang Jiaqi , An Yingfeng , Zabed Hossain M. , Ravikumar Yuvaraj , Zhao Mei , Yun Junhua , Zhang Guoyan , Zhang Yufei , Li Xiaolan , Qi Xianghui
Published: December 2021

D-arabitol is an important functional sugar alcohol, which can be used in the preparation of foods, chemicals, and medicines. Despite biological production of D-arabitol from low-cost substrates has recently been the focus of research, low yield of this technology has limited its large-scale exploitation. Optimization of this bioprocess could be a promising option to improve the yield of D-arabitol. In this study, one-factor-at-a-time (OFAT) strategy and Box-Behnken design (BBD) were used to increase D-arabitol production by Metschnikowia reukaufii CICC 31858 through optimizing the fermentation conditions and medium composition. The OFAT optimization provided the optimal conditions for temperature, agitation speed, and fermentation time of 30℃, 220 rpm, and 144 h, respectively. Likewise, the optimum concentrations of peptone, ammonium sulfate, KH2PO4, MgSO4·7H2O, and fumaric acid in the fermentation medium were (g/L) 7.5, 1, 2 , 0.5 and 7.5, respectively. Under these optimum conditions, 80.43 g/L of D-arabitol was produced from 200 g/L of glucose, with a productivity of 0.56 g/L/h. The BBD optimization with three important components of fermentation medium (KH2PO4, MgSO4·7H2O and fumaric acid) showed that the predicted titer of D-arabitol varied from 47.21 g/L to 89.27 g/L, and the actual titer of D-arabitol ranged from 47.36 to 89.83 g/L. The optimum concentrations (g/L) of KH2PO4, MgSO4·7H2O, and fumaric acid in the fermentation medium were found to be 1.0, 0.5, and 4.7g/L, respectively. Under the optimum conditions, 92.45 g/L of D-arabitol was finally produced with the yield and productivity of 0.46 g/g and 0.64 g/L/h, respectively.
Targeting CDA-Directed Metabolism With 5-Formyl-2'-Deoxycytidine For ALK Inhibitor–Resistant Lung Cancer Therapy
Authors: Heo Haejeong , Kim Jong-Hwan , Lim Hyun Jung , Kim Jeong-Hwan , Kim Miso , Koh Jaemoon , Im Joo-Young , Kim Bo-Kyung , Won Misun , Park Ji-Hwan , Yun Mi Ran , Cho Byoung Chul , Kim Yong Sung , Kim Seon-Young , Kim Mirang
Published: December 2021

Background: Acquired resistance to inhibitors of anaplastic lymphoma kinase (ALK) is a major clinical challenge for ALK fusion–positive non-small-cell lung cancer (NSCLC). In the absence of secondary ALK mutations, epigenetic reprogramming is one of the main mechanisms of drug resistance as it leads to phenotype switching that occurs during the epithelial-to-mesenchymal transition (EMT). While drug-induced epigenetic reprogramming is believed to alter the sensitivity of cancer cells to anticancer treatments, there is still much to learn about overcoming drug resistance. Methods: We used an in vitro model of ceritinib-resistant NSCLC and employed genome-wide DNA methylation analysis in combination with single-cell (sc) RNA-seq to identify cytidine deaminase (CDA), a pyrimidine salvage pathway enzyme, as a candidate drug target. Molecular biology was used to characterize the role of CDA in drug resistance. Integrated analysis of scRNA-seq and scATAC-seq identified gene regulatory networks in resistant cells. Clinical relevance of CDA was evaluated using TCGA datasets, patient-derived cells, and tumor biopsies. Results: CDA was hypomethylated and upregulated in ceritinib-resistant cells. CDA-overexpressing cells were rarely but definitively detected in the na¨ıve cell population by scRNA-seq, and their abundance increased in the acquired-resistance population. Knockdown of CDA had antiproliferative e↵ects on resistant cells and reversed the EMT phenotype. Treatment with epigenome-related nucleosides such as 5-formyl-2’-deoxycytidine selectively ablated CDA-overexpressing resistant cells via accumulation of DNA damage. Conclusions: Targeting CDA metabolism using epigenome-related nucleosides represents a potential new therapeutic strategy for overcoming ALK-inhibitor resistance in NSCLC.
Complete Genome Sequence of Vallota Mosaic Virus Detected In A Narcissus Bulb Imported From The United States to Japan
Authors: Imamura Yuya , Oishi Moritsugu , Fujiwara Yuji , Yanagisawa Hironobu
Published: December 2021

Narcissus (Narcissus albidus) imported from the United States exhibited leaf chlorosis during post-entry quarantine. We employed next-generation sequencing (NGS) on symptomatic leaf samples and detected vallota mosaic virus (ValMV) belonging to the genus Potyvirus, family Potyviridae, as the viral agent. Sanger sequencing of PCR and rapid amplification of cDNA ends based on NGS contigs revealed that ValMV was 9,451 nucleotides (nt) in length, excluding the poly(A) tail. Nucleotide and amino acid (aa) sequences of the coat protein region had over 98% identity to previously reported ValMV isolates. At each of the 10 mature protein regions, however, sequence identity with other potyviruses was 49.5–71.9% nt and 18.3–78.9% aa, values that are below the species demarcation criteria for Potyviridae. Phylogenetic analysis revealed that our ValMV isolate is most closely related to known ValMV and is grouped within other potyviruses. Taken together, our results indicate that the newly isolated ValMV belongs to a distinct species of Potyvirus. This study provides the first report of the complete ValMV genome sequence and the first record of this virus from the narcissus.
Hamming Distance and the onset of quantum criticality
Authors: Yi TianCheng , Scalettar Richard , Mondaini Rubem
Published: December 2021

Simulating models for quantum correlated matter unveils the inherent limitations of deterministic classical computations. In particular, in the case of quantum Monte Carlo methods, this is manifested by the emergence of negative weight configurations in the sampling, that is, the sign problem (SP). There have been several recent calculations which exploit the SP to locate underlying critical behavior. Here, utilizing a metric that quantifies phase-space ergodicity in such sampling, the Hamming distance, we suggest a significant advance on these ideas to extract the location of quantum critical points in various fermionic models, in spite of the presence of a severe SP. Combined with other methods, exact diagonalization in our case, it elucidates both the nature of the different phases as well as their location, as we demonstrate explicitly for the honeycomb and triangular Hubbard models, in both their U(1) and SU(2) forms. Our approach charts a path to circumvent inherent limitations imposed by the SP, allowing the exploration of the phase diagram of a variety of fermionic quantum models hitherto considered to be impractical via quantum Monte Carlo simulations.
A mathematical justification for metronomic chemotherapy in oncology
Authors: Fernández Luis Alberto Fernández , Pola Cecilia , Sáinz-Pardo: Judith
Published: December 2021

We mathematically justify metronomic chemotherapy as the best strategy to apply most cytotoxic drugs in oncology for both curative and palliative approaches, assuming the classical pharmacokinetic model together with the Emax pharmacodynamic and the Norton-Simon hypothesis.From the mathematical point of view, we will consider two mixed-integer nonlinear optimization problems, where the unknowns are the number of the doses and the quantity of each one, adjusting the administration times a posteriori.Mathematics Subject Classification: 93C15, 92C50, 90C30
Multi-Elliptic Rogue Wave Clusters of the Nonlinear Schrodinger Equation on Different Backgrounds
Authors: Nikolic Stanko N , Washahi Sarah Al , Ashour Omar A. , Chin Siu A. , Aleksic Najdan B. , Belic Milivoj R.
Published: December 2021

In this work we analyze the multi-elliptic rogue wave clusters as new solutions of the nonlinear Schr\"odinger equation (NLSE). Such structures are obtained on uniform backgrounds by using the Darboux transformation scheme of order $n$ with the first $m$ evolution shifts that are equal, nonzero, and eigenvalue-dependent, while the imaginary parts of all eigenvalues tend to one. We show that an Akhmediev breather of $n-2m$ order appears at the origin of the $(x,t)$ plane and can be considered as the central rogue wave of the cluster. We show that the high-intensity narrow peak, with characteristic intensity distribution in its vicinity, is enclosed by $m$ ellipses consisting of the first-order Akhmediev breathers. The number of maxima on each ellipse is determined by its index and the solution order. Since rogue waves in nature usually appear on a periodic background, we utilize the modified Darboux transformation scheme to build these solutions on a Jacobi elliptic dnoidal background. We analyze the minor semi-axis of all ellipses in a cluster as a function of an absolute evolution shift. We show that the cluster radial symmetry in the $(x,t)$ plane is violated when the shift values are increased above a threshold. We apply the same analysis on Hirota equation, to examine the influence of a free real parameter and Hirota operator on the cluster appearance. The same analysis can be extended to the infinite hierarchy of extended NLSEs.
Influence of Hydrate Exploitation On Stability of Submarine Slopes
Authors: Zhao Yapeng , Kong Liang , Liu Lele , Liu Jiaqi
Published: December 2021

The decomposition of natural gas hydrate will reduce the cementation effect of hydrate and produce ultra-static pore pressure, which will change the mechanical characteristics of the reservoir. Eventually, a series of geological disasters could be triggered, of which the submarine landslide is a typical example. In order to analyze the stability of hydrate-bearing submarine slopes and to explore the internal relationship between hydrate decomposition and submarine landslides, a “two-step reduction method” was described in this paper. This method was based on a strength reduction approach, which can be used to assess the effects of the initial geostress balance and hydrate decomposition on substrate strength reduction. This method was used to reveal the essence of hydrate decomposition and then a joint operation mode of multi-well was proposed. The internal relationship between hydrate decomposition and submarine landslides were analyzed in detail. And the development process and mechanism of submarine landslide were deeply discussed. The results showed that hydrate decomposition is a dynamic process of stress release and displacement, where the “stress inhomogeneity” distributed along the slope is transformed into “displacement inhomogeneity”. We concluded that hydrate decomposition could trigger a submarine landslide, especially along a sliding surface. The formation of submarine landslide is a gradual development process, and presents the dual characteristics of time and space.