bluuebunny/crossref_metadata_2025 huggingface dataset:
A regional model for soil moisture concentration from remote sensing data and its application for agricultural drought hazard mapping
Authors: Eghtedarnezhad Mina , Malekinezhad Hossein , Rafiei-Sardooi Elham , Parteli Eric J. R.
Published: May 2024

Soil moisture constitutes one essential variable in agriculture drought monitoring. However, because spatial and temporal soil moisture datasets from in situ observations are not accessible for all locations, remote sensing constitutes an indispensable approach in the assessment of surface soil moisture on a regional scale. In this study, a method to estimate regional-scale distribution of soil moisture (0–30 cm) from remote sensing observations is presented and applied to produce a drought hazard map, taking as case study area the arid region of Jiroft plain, Iran. For this study area, we dispose of remote sensing data available within the broad time span from 2007 to 2022, including satellite Vegetation Index and Land Surface Temperature, as well as observed soil moisture at a regional scale with a spatial resolution of 1 km2. Based on the spatial distribution of soil moisture appraise from these datasets, we calculate the relative exit of soil moisture associated with eight severe droughts in the Jiroft plain and the associated inventory map of agricultural drought. Machine learning models, including improved regression trees, multivariate discriminant analysis and support vector machine, are then applied to predict agricultural drought hazards. Using these different models, a model for agricultural drought hazard (ADH) is produced from ten independent variables characterizing environmental factors in the area. We find that plant available water capacity constitutes, together with soil moisture, the most important factor in ADH modeling. Furthermore, our results further indicate that, over the machine learning methods considered in our study, the support vector machine leads to the highest model accuracy in agricultural drought mapping (AUC = 0.95). We show how the ADH estimated with our model can be applied for predicting drought occurrence throughout Jiroft plain in future years. The results of our study provide quantitative information for drought risk assessment and management in Jiroft plain, and deliver insights that will help in the future development of agricultural drought hazard mapping in other arid regions of our planet – especially in areas with limited hydro-meteorological data.
Association between smoke exposure and headache among U.S adolescents: a cross-sectional study from the NHANES 1999-2004
Authors: Guo Yu , Wang Changli , Yan Shushu , Wang Jiafeng , Deng Xiaoming
Published: May 2024

Background
Headaches are increasingly common among adolescents, with smoking considered a contributing risk factor. Cotinine, a nicotine metabolite, serves as an objective measure of smoke exposure. However, there is limited clinical data on the relationship between serum cotinine levels and headaches in adolescents.
Methods
A cross-sectional study design was applied, and participants aged 12 to 19 years from the National Health and Nutrition Examination Survey (NHANES) 1999–2004 were included in the analysis. Headache data were obtained through interviews and self-reports. Smoke exposure levels were categorized as unexposed, low secondhand smoke (SHS) exposure, high SHS exposure, and active smoking groups based on serum cotinine levels. The main analyses employed weighted multivariable logistic regression models, accounting for the complex multi-stage sampling design of NHANES. Additionally, a restricted cubic spline model was used to investigate the non-linear relationship between serum cotinine levels and headache. Furthermore, a subgroup analysis was conducted.
Results
The analysis included 5590 adolescents aged 12 to 19 years, among whom 1442 (24.99%) experienced headaches. After adjusting for all covariates, a positive association was found between log2-transformed serum cotinine and headaches (odds ratio, R=1.04 (1.01, 1.07), P = 0.008). Adolescents with high SHS exposure (serum cotinine levels of 0.316 –10 ng/ml) and those in the active smoking group (serum cotinine≥10 ng/ml) had a higher risk of experiencing headaches compared to the unexposed group (serum cotinine < 0.05 ng/ml) [OR = 1.42 (1.07, 1.90), OR = 1.55 (1.06, 2.27), P for trend = 0.006]. A linear dose-response relationship was observed between log2-transformed serum cotinine and the risk of headaches (P non-linearity > 0.05). Subgroup analysis revealed that the positive associations remained regardless of gender and varied depending on age and central obesity.
Conclusion
In conclusion, higher smoke exposure, as measured by elevated cotinine levels, was significantly associated with an increased risk of headaches among adolescents. Future research should focus on identifying effective strategies to eliminate smoke exposure and discourage tobacco use in adolescents prevent in adolescents to prevent headaches.
FLT4 gene polymorphisms influence isolated ventricular septal defects predisposition in a Southwest China population
Authors: Zhang Yunhan , Dong Xiaoli , Zhang Jun , Zhao Miao , Wang Jiang , Chu Jiayou , Yang Zhaoqing , Ma Shaohui , Lin Keqin , Luo Zhiling , Sun Hao
Published: May 2024

Background
Ventricular septal defect (VSD) is the most common congenital heart disease. Although a small number of genes associated with VSD have been found, the genetic factors of VSD remain unclear. In this study, we evaluated the association of 10 candidate single nucleotide polymorphisms (SNPs) with isolated VSD in a population from Southwest China.
Methods
Based on the results of 34 congenital heart disease whole-exome sequencing and 1000 gene databases, 10 candidate SNPs were selected. A total of 618 samples were collected from the population of Southwest China, including 285 VSD samples and 333 normal samples. Ten SNPs in the case group and the control group were identified by SNaPshot genotyping. The χ2 test was used to evaluate the relationship between VSD and each candidate SNP. The SNPs that had significant p values in the initial stage were further analysed using linkage disequilibrium, and haplotypes were assessed in 34 congenital heart disease whole-exome sequencing samples using Haploview software. The bins of SNPs that were in very strong linkage disequilibrium were further used to predict haplotypes by Arlequin software. ViennaRNA v2.5.1 predicted the haplotype mRNA secondary structure. We evaluated the correlation between mRNA secondary structure changes and ventricular septal defects.
Results
The χ2 results showed that the allele frequency of FLT4 rs383985 (P = 0.040) was different between the control group and the case group (P < 0.05). FLT4 rs3736061 (r2 = 1), rs3736062 (r2 = 0.84), rs3736063 (r2 = 0.84) and FLT4 rs383985 were in high linkage disequilibrium (r2 > 0.8). Among them, rs3736061 and rs3736062 SNPs in the FLT4 gene led to synonymous mutations of amino acids, but predicting the secondary structure of mRNA might change the secondary structure of mRNA and reduce the free energy.
Conclusions
These findings suggest a possible molecular pathogenesis associated with isolated VSD, which warrants investigation in future studies.
Field Robot Self-Exploration Based on Deep Reinforcement Learning and Obstacle Avoidance Strategy
Authors: Kang Jipeng , Zhang Zhibin , He Liqiang , Chen Xu
Published: May 2024

This paper addresses the challenges posed by deep reinforcement learning (DRL) algorithms when deployed for reactive robotic navigation in agricultural settings. These challenges include the complexity of network models, extensive parameterization, substantial computational demands, and susceptibility to local optima. The intricacies of farmland environments further complicate the application of conventional indoor navigation methods, which falter in tasks such as crop monitoring and interaction with humans. To overcome these obstacles, we introduce the Field Robot Autonomous Navigation System (FRANS), which employs DRL to facilitate the autonomous exploration of unknown farmlands by robots. FRANS is composed of two primary modules: Global Navigation (GN) and Local Navigation (LN). The GN module sets destination points and implements a robust control mechanism to navigate the robot, effectively mitigating issues associated with local optima. Meanwhile, the LN module leverages a streamlined DRL framework to formulate a motion strategy that directs the robot towards these waypoints. Crucially, FRANS operates without prior environmental knowledge and dynamically adapts its navigation strategy in response to real-time environmental changes. The system continuously updates the map as the robot traverses the terrain. Experimental evaluations show that FRANS surpasses competing methodologies in performance.
Rational Engineering of a Thermostable α-Oxoamine Synthase Biocatalyst Expands the Substrate Scope and Synthetic Applicability
Authors: Campopiano Dominic , Ashley Ben , Zhu Yaoyi , Mathew Sam , Sajjad Mariyah , Baslé Arnaud , Marles-Wright Jon
Published: May 2024

Carbon-carbon bond formation is one of the key pillars of organic synthesis. Green, selective and efficient biocatalytic methods for such are therefore highly desirable. The α-oxoamine synthases (AOSes) are a class of pyridoxal 5’-phosphate (PLP)-dependent, irreversible, carbon-carbon bond-forming enzymes, which have been limited previously by their narrow substrate specificity and requirement of acyl-CoA thioester substrates. We recently characterized a thermophilic enzyme from Thermus thermophilus (ThAOS) with a much broader substrate scope and described its use in a chemo-biocatalytic cascade process to generate pyrroles in good yields and timescales. Herein, we report the structure-guided engineering of ThAOS to arrive at variants able to use a greatly expanded range of amino acid and simplified N-acetylcysteamine (SNAc) acyl-thioester substrates. The crystal structure of the improved ThAOS V79A mutant with a bound PLP:penicillamine external aldimine ligand, provides insight into the properties of the engineered biocatalyst.
Opportunities for decentralised solar power to improve reliability, reduce emissions and avoid stranded assets
Authors: Nelson Jenny , Sandwell Philip , Beath Hamish , Winchester Benedict , Markides Christos N. , Mittal Shivika
Published: May 2024

Despite recent improvements to electricity access in lower-income countries, reliability remains low for many. Local renewable
energy infrastructure supplementing the national grid offers a promising route to improved reliability for rural communities.
However, improvements in the reliability of national grids create risks for investors including the possibility of “stranded”
renewable assets. We use energy-system modelling to explore ways in which solar PV-based mini-grids could be interconnected
with national grids. We explore the impact of reduced demand to quantify the investment risks of losing customers. Our results
indicate that national grid-connected mini-grids can reduce the unit electricity costs for communities whilst also increasing
reliability and reducing the carbon intensity of electricity in line with SDG 7 goals. Reductions in demand have a minimal impact
at lower levels but at moderate levels are likely to undermine economic viability. Finally, we discuss policy interventions to
facilitate and protect investing in national grid-connected mini-grids.
Pros and cons of counselling at online-only pharmacies – a mixed methods case study.
Authors: Pjengaard Daniel , Rasmussen Lærke Louise , Rossing Charlotte Verner , Norgaard Lotte Stig
Published: May 2024

Background:The proliferation of online-only pharmacies globally is notable, yet there remains a dearth of literature regarding the practices of counseling within these platforms.
Aim: This study aims to explore the breadth, content, and various platforms utilized for counseling within an online-only pharmacy in Denmark. It further seeks to delineate the advantages and disadvantages of online counseling as perceived by the pharmacy staff.
Method: Employing a mixed methods approach, the study involved quantitative data extraction utilizing a statistical tool (e-track), two days of observation of pharmacy staff, and six semi-structured interviews with pharmacy staff.
Results: Analysis revealed that the majority of inquiries received by the pharmacy via email pertained to prescription medicines (52%), while chat inquiries primarily focused on "other goods and skin care" (24%). Observations indicated that inquiries across telephone, chat, and email channels predominantly related to "other goods" and "technical questions". The pharmacy demonstrated particular efficacy in counseling on discreet topics, though there was a tendency towards inadequately patient-centered written communication. Furthermore, pharmacy staff occasionally overlooked non-verbal cues in counseling interactions.
Conclusion: The online-only pharmacy utilized three distinct counseling channels—telephone, chat, and email—each presenting unique advantages and challenges. Customer demographics varied, influencing the nature of counseling inquiries. Future research should explore patient experiences and preferences regarding counseling, as well as their specific informational channel preferences.
Assessing Relative Significance of Key Risk Factors for Child Undernutrition: Evidence from Pakistan
Authors: Burki Abid Aman
Published: May 2024

Background
Child undernutrition remains a critical issue worldwide, with Pakistan particularly struggling in South Asia. While recent studies have identified some risk factors, their relative importance is unclear. This study examines the extent of child undernutrition and the relative importance of risk factors in Punjab, Pakistan's largest province.
Methods
The study presents a trend analysis to examine undernutrition patterns in Punjab’s high-risk districts between 2004 and 2018 using data from five rounds of the Multiple Indicator Cluster Survey (MICS). Additionally, it uses binary logit regressions to assess the relative significance of 25 risk factors associated with stunting, underweight, and wasting among 38,495 preschool-age children from MICS 2018. The paper ranks a set of significant environmentally modifiable risk factors based on their strongest effect sizes. The sample of children aged 0 to 59 months was also divided into two subsets: children aged 0 to 5 months and those aged 6 to 35 months.
Results
The study observed significant reductions in stunting, underweight, and wasting, particularly in Central-North Punjab, though stunting rates have risen in 13 of 36 districts, and South Punjab experiences persistent regional disparities in underweight rates. Five key predictors identified for stunting and underweight include household poverty, maternal education, short birth intervals, underage childbirth, and low birth weight; and for wasting low birth weight, maternal education, incomplete vaccination, and recent fever. Lack of dietary diversity for children aged 6–35 months and non-exclusive breastfeeding and non-assisted deliveries for those aged 0–5 months are major challenges. A sensitivity analysis revealed consistent effect sizes, while an analysis of children with severe undernutrition revealed stable major correlates and some differences in their relative rankings.
Conclusions
The study suggests that the intervention strategies implemented in Punjab post-2007 have been partially effective in reducing childhood undernutrition, providing valuable insights. The analysis of risk factors highlights the need for a comprehensive, multifaceted approach that combines socioeconomic strategies with nutritional investment programs to effectively address undernutrition in the province. These policy implications are crucial for shaping future interventions aimed at reducing childhood undernutrition.
Design and Implementation of Collaborative Energy Efficient IoT-Based LoRa WAN
Authors: G Ravi Kumar M , Sarvagya Mrinal , Prasad S N , Kavya B S
Published: May 2024

Wireless sensor network (WSN) architectures involve multiple sensor nodes that cover large areas. It is difficult to deploy such nodes efficiently. However, based on clustering and collaboration, WSNs can organize efficiently and prolong system lifetime. In this paper, we discuss the design and implementation of a collaborative LoRa WAN using ultra-low-energy hardware and smart utilization of battery power. We have chosen the robust LoRa modulation technique and clustering method to design the end nodes. The sensor data from each of the end nodes are transmitted using low-power, long distance, and noise-resilient LoRa radio channels to their corresponding Cluster Heads(CHs), where it is first stored and then processed before transmitting further to the Gateways. The storing and then transmitting technique reduces the bandwidth requirement significantly. Also, the stored sensor data can be analyzed for system optimization. Immediately after transmission, the microcontroller goes to hibernation mode, whereas, the sensor system and the LoRa module are powered off until the next cycle. In this way, the power consumption by the end node is kept at its minimum and the battery life is extended to 35 years. Several challenges related to hardware design and network parameters optimization to achieve energy-efficient IoT-based LoRa WAN are presented and discussed.
Wide spectrum multiple Fano resonances for high sensitivity detection of refractive index and temperature in MIM waveguides coupled with racetrack resonator nanorod-arrays
Authors: Bahri Hocine , Bensalah Hocine , Ingebrandt Sven , Hocini Abdsselam , Pachauri Vivek
Published: May 2024

In this paper, we designed a metal-insulator-metal (MIM) waveguides based plasmonic sensor coupled with a racetrack cavity adorned with zero Dimensional (0D) nanorod-arrays exhibiting high sensitivity detection of refractive index variations measured as spectral shifts in the resonance wavelengths. The finite-difference time-domain method (FDTD) was used to simulate and study the optical platform based on MIM waveguide and nanorod-array racetrack resonator as a detection refractive index (RI) sensor and for temperature and Diabetes sensing, with sensitivity as high as 4250 nm per RIU and 0.42 nm/°C and 3204 nm/RIU, respectively. The nanorod arrays on the racetrack resonator enhance the light-matter interaction. Which increased the sensitivity. We evaluated the impacts of radius and refractive index on the racetrack resonator's sensitivity using the spectra shifts as sensor performance. As a result, the proposed plasmonic structures exhibit strong potential for a variety of sensor applications for offering high-sensitivity detection of low concentrations of small molecules similar to glucose and temperature.
RCS reduction of wide-band, high-gain antenna array based on asymmetric transmission metasurfaces
Authors: WU TING , YAN LEI , ZHANG ZIKANG
Published: May 2024

In this paper, an ultra-wideband stealth antenna with high gain on the basis of asymmetric transmission metasurface (ATMS) is proposed. ATMS can convert an incident y-polarised sphere wave into an x-polarised plane wave at the front side and controls the scattering of the incident y-polarised wave to the back side. Excitation of ATMS via a horn antenna, a low radar cross-section (RCS) and wideband antenna system is designed. Furthermore, through design of the meta-atoms and optimization of the macrosequencing, broadband RCS reduction is achieved. The experimental data indicated the reduction of the RCS of the antenna system by up to 10 dB and more than 20 dB in the frequency range of 10.1 GHz to 18 GHz (relative bandwidth is 56.2%) and 13.9 GHz to 18 GHz (relative bandwidth is 25.7%), respectively. In addition, a 3 dB gain relative bandwidth of 57.4% is achieved between 10 GHz and 18 GHz, with a peak gain of 28.2 dB. It is noteworthy that the high gain and low scattering performance of the antenna are achieved in the same spectral range (10 GHz ~ 18 GHz), and there is no interference between the scattering performance and radiation performance of the antenna, which could be controlled separately.
LncRNAH19 acts as a ceRNA of let-7g to facilitate EndMT in hypoxic pulmonary hypertension via regulating TGF-β signalling pathway
Authors: Yu xin , Huang Jiabing , Liu Xu , Li Juan , Yu Miao , Li Minghui , Xie Yuliang , Li Ye , Qiu Junyu , Xu Zhou , Zhu Tiantian , Zhang Weifang
Published: May 2024

Background
Hypoxic pulmonary hypertension (HPH) is a challenging lung arterial disorder with remarkably high incidence and mortality rates, and the efficiency of current HPH treatment strategies is unsatisfactory. Endothelial-to-mesenchymal transition (EndMT) in the pulmonary artery plays a crucial role in HPH. Previous studies have shown that lncRNA-H19 (H19) is involved in many cardiovascular diseases by regulating cell proliferation and differentiation but the role of H19 in EndMT in HPH has not been defined.
Methods
In this research, the expression of H19 was investigated in PAH human patients and rat models. Then, we established a hypoxia-induced HPH rat model to evaluate H19 function in HPH by Echocardiography and hemodynamic measurements. Moreover, luciferase reporter gene detection, and western blotting were used to explore the mechanism of H19.
Results
Here, we first found that the expression of H19 was significantly increased in the endodermis of pulmonary arteries and that H19 deficiency obviously ameliorated pulmonary vascular remodelling and right heart failure in HPH rats, and these effects were associated with inhibition of EndMT. Moreover, an analysis of luciferase activity indicated that microRNA-let-7g (let-7g) was a direct target of H19. H19 deficiency or let-7g overexpression can markedly downregulate the expression of TGFβR1, a novel target gene of let-7g. Furthermore, inhibition of TGFβR1 induced similar effects to H19 deficiency.
Conclusions
In summary, our findings demonstrate that the H19/let-7g/TGFβR1 axis is crucial in the pathogenesis of HPH by stimulating EndMT. Our study may provide new ideas for further research on HPH therapy in the near future.
WITHDRAWN: The Surface Area of Red Blood Cell Via PDE Method
Authors: Ahmed Jiyar Jafar
Published: May 2024

The full text of this preprint has been withdrawn, as it was submitted in error. Therefore, the authors do not wish this work to be cited as a reference. Questions should be directed to the corresponding author.
IQI-UNet: A Robust Gaussian Noise Removal in Image Quality Improvement]{IQI-UNet: A Robust Gaussian Noise Removal in Image Quality Improvement
Authors: AMMAR Sonda , Kchaou Amina , Hamed Bassem Ben
Published: May 2024

Image quality enhancement is a rapidly advancing field in computer vision, with researchers exploring various techniques. This paper introduces a robust Gaussian noise removal, denoted as IQI-UNet, based on the U-Net deep learning architecture, which excels in image denoising. The key advantage of our model is its ability to operate without a reference image or prior knowledge of the application context. Our study investigates the impact of incorporating additional blocks into the autoencoder, resulting in an optimized architecture. The performance of the proposed IQI-UNet model is evaluated against twelve well-known methods using three datasets, namely Set5, Set14, and CBSD68. The proposed model demonstrates superior performance compared to established methods, achieving a remarkable 43% improvement in PSNR and a 29% improvement in SSIM. Furthermore, we introduce Shannon entropy as a metric to assess both the quantity and the quality of retained data. The evaluation, conducted on benchmark datasets, reaffirms the efficacy of IQI-UNet in enhancing image quality. The outcomes are highlighted by statistical tests, which implies that the obtained results are statistically significant.
Assessing the Effectiveness of Case-Based Learning and Concept Mapping Approaches in Developing Theoretical and Metacognitive Skills in Medical Students
Authors: Çetinkaya Levent
Published: May 2024

This research utilizes a mixed-method approach, integrating quasi-experimental design and quantitative triangulation methods to determine the impact of Case-Based Learning (CBL) and CBL supported by Concept Maps (CMs) on the theoretical knowledge comprehension abilities and metacognitive skills of medical students. In the first phase of the two-stage evaluation process, researchers administered a pre-test/post-test achievement test focusing on students' comprehension levels of theoretical knowledge; the data were analyzed using two-way ANOVA. The analysis results indicated a statistically significant increase in the average achievement scores across all learning environments; however, it was determined that this increase was not attributable to differences specific to the learning environments. In the second phase of the assessment, a new test was administered to not only assess the students' theoretical knowledge but also how they apply this knowledge in new and uncertain situations. The data obtained from this test, which targeted students' metacognitive skills and was administered after the experimental process, were analyzed using One-Way ANOVA to determine the effectiveness of the learning environments. The analysis results revealed that CBL significantly impacts metacognitive skills, and this effect is enhanced when supported by CMs. The findings demonstrate that CBL and CMs-supported educational approaches play a significant role in enhancing medical students' ability to effectively apply theoretical knowledge in the face of new and uncertain situations. These findings highlight the extensive utility of CBL and CM-supported approaches in enhancing critical metacognitive skills, essential for medical education. Furthermore, they suggest practical ways for integrating these methodologies into future curricula and refining educational strategies.
Cellular senescence induced by cholesterol accumulation is mediated by lysosomal ABCA1 in APOE4 and AD
Authors: Wang Shaowei , Li Boyang , Cai Zhiheng , Hugo Cristelle , Li Jie , Sun Yi , Qian Lu , Remaley Alan T. , TCW Julia , Chui Helena C. , Bennett David A. , Arvanitakis Zoe , Kerman Bilal , Yassine Hussein
Published: May 2024

Background
Cellular senescence is a hallmark of aging and has been implicated in Alzheimer’s disease (AD) pathogenesis. Cholesterol accumulation drives cellular senescence; however, the underlying mechanisms are unclear. ATP-binding cassette transporter A1 (ABCA1) plays an important role in cholesterol homeostasis. ABCA1 expression and its trafficking is altered in APOE4 and AD cellular and mouse models. However, whether ABCA1 trafficking is involved in cellular senescence in APOE4 and AD remains unknown.
Methods
We examined the association between cellular senescence and ABCA1 expression in human postmortem brain samples using transcriptomic, histological, and biochemical analyses. An unbiased proteomic screening was performed to identify targets that mediate cellular ABCA1 trafficking. APOE4-TR mice, immortalized, primary and induced pluripotent stem cell (iPSC) models were used to examine the cholesterol-ABCA1-senescence pathways.
Results
Bulk and single nuclei transcriptomic profiling of the human dorsolateral prefrontal cortex from the Religious Order Study/Memory Aging Project (ROSMAP) revealed upregulation of cellular senescence transcriptome signatures in AD, which was strongly correlated with ABCA1 expression. Immunofluorescence and immunoblotting analyses confirmed increased ABCA1 expression in AD brain tissues, which was associated with lipofuscin-stained lipids and mTOR phosphorylation. Using discovery proteomics, caveolin-1, a sensor of cellular cholesterol accumulation, was identified to promote ABCA1 endolysosomal trafficking. Greater caveolin-1 expression was found in both APOE4-TR mouse models and AD human brains. Cholesterol induced mTORC1 activation was regulated by ABCA1 expression or its lysosomal trapping. Reducing cholesterol by cyclodextrin in APOE4-TR mice reduced ABCA1 lysosome trapping and increased ABCA1 recycling to efflux cholesterol to HDL particles, reducing mTORC1 activation and senescence-associated neuroinflammation. In human iPSC-derived astrocytes, the reduction of cholesterol by cyclodextrin attenuated inflammatory responses.
Conclusions
Cholesterol accumulation in APOE4 and AD induced caveolin-1 expression, which traps ABCA1 in lysosomes to activate mTORC1 pathways and induce cellular senescence. This study provided novel insights into how cholesterol accumulation in APOE4 and AD accelerates senescence.
Fast anion reorientations in ammine yttrium borohydride compounds Y(BH4 )3 ·xNH3 (x = 3 and 7): a nuclear magnetic resonance study
Authors: Babanova O. A. , Skoryunov R. V. , Soloninin A. V. , Skripov A. V.
Published: May 2024

The ammine borohydride compounds Y(BH4)3·xNH3 belong to the emerging class of materials, where the application-relevant properties can be tuned by introducing neutral NH3 ligands. To study the dynamical properties of Y(BH4)3·3NH3 and Y(BH4)3·7NH3, we have measured the 1H and 11B nuclear spin-lattice relaxation rates and nuclear magnetic resonance (NMR) spectra in these compounds over a wide temperature range (6–298 K). Our measurements have revealed that both compounds retain the unusually high reorientational mobility of BH4− anions down to low temperatures. In particular, for the fastest BH4 reorientational process, the corresponding H jump rate is of the order of 108 s− 1 near 96 K in Y(BH4)3·3NH3 and near 33 K in Y(BH4)3·7NH3. The fast reorientational motion of BH4− anions is discussed in terms of the coordination environment of BH4 groups in Y(BH4)3·xNH3.
Metabolic stress-induced dysregulation of the Hippo signaling pathway inhibits the occurrence of hepatocarcinoma
Authors: Li Ziyi , Tao Qianqian , Jing Wenshan , Lu Xingyang , Zhang Qi , Hu Gaobin , Huang Long , Zhang Liangliang , Peng Hui , Feng Qiyu , Yu Qinsheng
Published: May 2024

Liver fibrosis is the natural stress response of the liver to injury and a critical intermediate stage in the progression of most liver diseases. Here, we first demonstrated via a retrospective clinical study that the incidence of advanced hepatocellular carcinoma (HCC) was significantly higher in patients infected with hepatitis B virus (HBV) than in those with hepatolenticular degeneration (HLD). Further analyses involving miRNA and proteomics were conducted to investigate the distinct mechanisms underlying liver fibrosis induced by HBV and HLD. Results showed significant changes in metabolic pathways and molecules, especially in AMPK and Hippo signaling pathways, which play crucial roles in cellular glucose and lipid metabolism. Characteristic of HLD is a mutation/deletion in the ATPase Copper Transporting Beta (ATP7B) gene. Subsequent studies indicated that the knockdown or overexpression of ATP7B mutants activates the AMPK and Hippo signaling pathways, resulting in the inhibition of proliferation and transformation of HCC cells. AMPK phosphorylation indicates the presence of metabolic stress. Thus, this finding might partly explain why patients with HLD-related liver fibrosis are more likely to develop liver failure rather than HCC, providing new insights into the intricate mechanisms linking metabolic orchestration and tumor development.
Ethyl 2,2-difluoro-2-(2-oxo-2H-chromen-3-yl) acetate inhibits the malignant biological behaviors of colorectal cancer by restricting the phosphorylation and nuclear translocation of STAT3
Authors: LIN JIE , LIU Weijing , LI Xiaodan , LIN Jiansuo , FANG Xuehong , LIANG Yanwen , ZHANG Wen , REN Jianwei , WAGN Feng , ZOU Liyi , LIU Yi
Published: May 2024

To investigate the effect of a novel coumarin derivative, ethyl 2,2-difluoro-2 - (2-oxo-2H-chromen-3-yl) acetate (C2F), on the malignant biological behaviors of colorectal cancer (CRC) and elucidate its mechanism. In vitro, the effects of C2F on the proliferation, apoptosis, migration, invasion, and cell cycle of CRC cells were analyzed by MTT assay, EdU stainning, colony formation assay, flow cytometry, wound healing and transwell assay. The anti-CRC activity of C2F was evaluated in a nude mice xenograft model in vivo. Western blot was conducted to detect the expression of protein in cells and mice tissue. Then, the potential targets of C2F in CRC were predicted by network pharmacology analysis and molecular docking. The localization of STAT3 was observed through immunofluorescence experiment. C2F inhibits CRC cell proliferation, promotes CRC cell apoptosis, hinders CRC cell migration and invasion, and prevents the cell cycle from entering the G2/M phase. In vivo, C2F inhibited tumor growth in xenograft model. C2F inhibited signal transduction and activator of transcription 3 (STAT3) phosphorylation and blocked interleukin-6 (IL-6)-induced STAT3 nuclear translocation. C2F inhibits the malignant biological behavior of CRC by limiting STAT3 phosphorylation and entry into the nucleus.
Predicting colorectal cancer liver metastases histological growth patterns: inflammation on the primary tumor is associated with desmoplastic growth pattern
Authors: Abrantes Ana Margarida , Oliveira Rui Caetano , Oliveiros Bárbara , Cipriano Maria Augusta , Tralhão José Guilherme
Published: May 2024

Background: More than 50% of patients diagnosed with colorectal cancer (CRC) will develop liver metastases (CRCLM), which is the main cause of death for more than 60% of these patients. The aim of this study was to correlate the clinical and pathological characteristics of the primary CRC and CRCLM, with emphasis in predicting the histological growth pattern of the CRCLM.
Methods: Cohort of seventy-three patients with CRC. Analysis of clinical data and blinded pathological review was performed related with primary tumor and CRCLM features. The analysis was performed in SPSS (version 27) with a significance level of 5%.
Results: A statistically significant association was found between tumor size and metastasis growth pattern (p=0.002), with larger tumors giving rise to metastases with a non-desmoplastic growth pattern. Lymphovascular invasion (LVI) was associated with metachronous CRCLM (p=0.043). In the absence of LVI, the time required for CRCLM to appear was significantly longer (p=0.011). The number of metastases was significantly higher (p=0.049) in tumors without LVI when compared to tumors with LVI. There was a statistically significant association between CRC high-grade inflammation and the desmoplastic metastases growth pattern of the CRCLM (p= 0.017).
Conclusion: The possibility of predicting the CRCLM histological growth pattern resorting to primary CRC characteristics would be useful for proper patient selection for surgery and adapting biological therapies.
CTCF regulates SFPQ to promote cancerous progression of osteosarcoma
Authors: 仲 新宇 , Li Dapeng , zheng Qiping , Mao Lianghao , Jiang Pan , YIN Zhengyu
Published: May 2024

CCCTC-binding factor (CTCF) is a candidate tumor regulatory gene encoding multifunctional transcription factors, but its role and related mechanisms in osteosarcoma are still unclear. Studies have found that SFPQ plays an oncogenic role in OS. This study aimed to clarify the transcriptional regulation of SFPQ by CTCF in osteosarcoma, and the effect of CTCF regulation of SFPQ expression on the proliferation, migration, and invasion of osteosarcoma cells. The potential transcription factor of SFPQ was identified as CTCF by the online transcription factor analysis website and UCSC database. qRT-PCR and WB are two techniques used to detect the expression level of CTCF in osteosarcoma cell lines. The regulatory relationship between CTCF and SFPQ in osteosarcoma cell lines and their common influence on the biological behavior of osteosarcoma cells were investigated by cell function test, double luciferase report test, and rescue test.UCSC and GEPIA2 databases identified CTCF as a potential transcription factor of SFPQ, and there was a moderate correlation between them. qRT-PCR and WB experiments showed that CTCF was highly expressed in osteosarcoma cell lines. After overexpression of CTCF in osteosarcoma cell lines, the proliferation, migration, and invasion of osteosarcoma cells were enhanced. CTCF can bind to the promoter sequence of SFPQ and enhance its expression level. Rescue experiments showed that overexpression of CTCF could reduce the inhibition of SFPQ knockdown on the proliferation, migration, and invasion of osteosarcoma cell lines. CTCF plays a carcinogenic role in osteosarcoma. As a transcriptional activator of SFPQ, CTCF positively regulates and promotes the expression of SFPQ, and increases the osteosarcoma cells' malignant biological behavior.
Predict progression free survival and overall survival using objective response rate for anti - PD1 / PDL1 therapy development
Authors: Yang Lei , Raveendran Geethanjali , Meng Xiang , Lin Ji , Meng Zhaoling
Published: May 2024

Background: In anti - PD1 (programmed death-1) / PDL1 (programmed death ligand 1) therapy development for solid tumors, the objective response rate (ORR) is a commonly used clinical endpoint for early phase study decision making, while progression free survival (PFS) and overall survival (OS) are widely used for late phase study decision making. Developing predictive models for median PFS (mPFS) and median OS (mOS) based on early phase clinical outcome ORR could inform late phase study design optimization and probability of success (POS) evaluation. In the existing literature, there are ORR / mPFS / mOS associations and surrogacy investigations with limited number of included clinical trials. In this paper, without establishing surrogacy, we attempt to predict mPFS and mOS based on early efficacy in ORR and to optimize late phase trial design for anti - PD1 / PDL1 therapy development.
Methods: In order to include an adequate number of eligible clinical trials, we built a comprehensive clinical trial quantitative landscape database (QLD) by combining information from different sources, such as clinicaltrial.gov, publications, company press releases for relevant indications and therapies. We developed a generalizable algorithm to systematically extract structured data and manual curation for scientific accuracy and completeness. More than 150 late phase clinical trials were identified for ORR / mPFS (ORR / mOS) predictive model development, while existing literature included at most 40 trials. A tree-based machine learning regression model was derived to account for ORR / mPFS (ORR / mOS) relationship heterogeneity across tumor type, stage, line of therapy, treatment class and borrow strength simultaneously when homogeneity persists.
Results: The proposed method ensures that the predictive model is robust and has explicit structure for clinical interpretation. Over 1000 times cross validation, the average predictive mean square error of the proposed model is competitive to random forest and extreme gradient boosting methods and outperforms commonly used additive or interaction linear regression models.
Conclusions: An example application of the proposed ORR / mPFS (ORR / mOS) predictive model on late phase trial POS evaluation for anti - PD1 / PDL1 combination therapy was illustrated.
Evaluating the Merits of an Integrated Medical Education Approach and Multidisciplinary Diagnostics in Continuing Medical Education for Complex Hepatic Diseases
Authors: Ren Shan , Zheng Sujun , Chen Xinyue
Published: May 2024

Background: This study explores the value of applying integrated medical education and the multidisciplinary diagnostic treatment mode in continuing clinical education for complex liver diseases.
Methods: A total of 62 resident and continuing education doctors from the the first Department of Liver Disease Center, Beijing You'an Hospital, Capital Medical University, were selected as the subjects of this study. They were randomly divided into an experimental group (integrated medical education and multidisciplinary diagnostic treatment) and a traditional teaching group. The former used a teaching model guided by problems, centered on real cases, and multidisciplinary consultation, while the latter adopted traditional teaching combined with clinical rotation and mini-lectures. In the end, the training effects of three teaching methods, namely, the accurate rate of medical record analysis, job competence, and self-evaluation of teaching effects, were adopted.
Results: The experimental group scored higher than the traditional teaching group in terms of the accuracy rate of liver disease case analysis, patient management and decision-making, professional knowledge and skills, and learning ability. The differences were statistically significant (P<0.05). Compared with the traditional teaching group, after the experimental group completed training based on integrated medical education and multidisciplinary diagnostic treatment mode, the scores on the self-evaluation questionnaire (stimulating interest in learning, enhancing problem analysis ability, helping to understand, remember theoretical knowledge, expanding clinical thinking, activating class atmosphere, and hoping to continue this teaching mode) were better than those in the traditional classroom group, and the differences were statistically significant (P<0.05).
Conclusion: Training based on integrated medical education and multidisciplinary diagnostic treatment mode can improve the accuracy of resident doctors and continuing education doctors in diagnosing complex liver diseases, enhance their learning ability, and clinical decision-making, and increase doctor satisfaction. It has essential application value in the continuing clinical education of complex liver diseases.
α-Synuclein fibrils enhance HIV-1 infection of human T cells, macrophages and microglia
Authors: Kirchhoff Frank , Olari Lia , Liu Sichen , Arnold Franziska , Kühlwein Julia , Miró Marta Gil , Updahaya Ajeet Rijal , Stuerzel Christina , Thal Dietmar , Walther Paul , Danzer Karin , Münch Jan
Published: May 2024

HIV-associated neurocognitive disorders (HAND) and viral reservoirs in the brain remain a significant challenge. Despite their importance, the mechanisms allowing HIV-1 entry and replication in the central nervous system (CNS) are poorly understood. Here, we show that α-synuclein and (to a lesser extent) Aβ40 fibrils associated with neurological diseases, enhance HIV-1 entry and replication in human T cells, macrophages, and microglia. Additionally, an HIV-1 Env-derived amyloidogenic peptide accelerated amyloid formation by α-synuclein and Aβ peptides. Mechanistic studies showed that α-synuclein and Aβ40 fibrils interact with HIV-1 particles and promote virion attachment and fusion with target cells. Despite an overall negative surface charge, these fibrils facilitate interactions between viral and cellular membranes. Enhancing effects of human brain extracts on HIV-1 infection correlated with binding to Thioflavin T commonly used to stain amyloids. Our results suggest a detrimental interplay between HIV-1 and brain amyloids that may contribute to the development of neurodegenerative diseases.
Children with Unilateral Molar-Incisor Hypomineralization May Exhibit Contralateral Muscle Hyperactivity
Authors: Gonçalves Ligia Maria Napolitano , Molena Kelly Fernanda , Carvalho Milena Rodrigues , Regalo Simone Cecilio Hallak , Siéssere Selma , de Paula-Silva Francisco Wanderley Garcia , de Queiroz Alexandra Mussolino , de Carvalho Fabrício Kitazono
Published: May 2024

Objectives
This study aimed to assess unilateral molar-incisor hypomineralization (MIH) on the stomatognathic system in children, investigating if greater impairment exists on the affected side in terms of postural and masticatory activities and occlusal force contacts.
Materials and Methods
Fourteen children with unilateral MIH (mean age: 7.92 years) were included in this cross-sectional split-mouth observational study. Electromyography (EMG) evaluated masseter and temporal muscle activity during various jaw postures and habitual chewing. Occlusal force contacts were measured using T-SCAN®. The analyses compared the side with MIH to the side without the defect. Statistical analysis employed the Shapiro-Wilk test, Wilcoxon signed-rank test, and paired t-test.
Results
Muscle hyperactivity was observed on the unaffected side, indicating greater voluntary contraction compared to the affected side for the temporal muscle at rest (p = 0.01) and masseter muscle in right laterality (p = 0.02). No significant difference was found in occlusal force between the sides analyzed.
Conclusions
Children with MIH exhibit compromised stomatognathic system functionality, with enamel defects potentially disrupting balance and leading to functional limitations.
Clinical Relevance:
Children with unilateral MIH may present muscle hyperactivity on the unaffected side, suggesting enamel defects could lead to stomatognathic system imbalances with clinical implications for dentists.
Artificial Intelligence Attitudes Inventory (AIAI): Development and Validation Using Rasch Methodology
Authors: Krägeloh Christian U. , Melekhov Vladimir , Alyami Mohsen M. , Medvedev Oleg N.
Published: May 2024

With the rapid advancements in artificial intelligence (AI), it is vital to develop psychometrically sound measures of public attitudes toward this technology. The present study aimed to refine a pool of candidate items to create a concise yet robust inventory for assessing attitudes toward AI. Using a dataset of 604 participants from the general population of the United States, a pool of 96 candidate items was subjected to iterative Rasch analysis to reduce the number of items while ensuring psychometric robustness. The resulting scale, named the Artificial Intelligence Attitudes Inventory (AIAI), consists of two 8-item subscales measuring positive and negative attitudes toward AI. Analyses revealed that these subscales are distinct constructs rather than opposites on a single continuum, and they are only weakly related to psychological distress. The AIAI provides a concise yet comprehensive measure of positive and negative attitudes toward AI that can be efficiently administered alongside other measures. The findings underscore the multifaceted nature of public perceptions of AI and highlight the need for further research into the profiles and determinants of these attitudes. As AI continues to shape our world, the AIAI offers a valuable tool for understanding and monitoring public sentiment toward this transformative technology.
Analysis of Government Budget Deficit in Ethiopia: The Vector Auto Regression Model Approach
Authors: Alene Desta Birru
Published: May 2024

Over the previous several decades, Ethiopia's economy has been troubled by an ongoing budget deficit. Taking the problem into consideration, this paper used vector auto-regression model estimation techniques to shed light on the drivers, trends, and threshold levels of budget deficit in Ethiopia from 1979/80 to 2021/2022. The model estimation revealed that current account balance, consumer price index, and domestic borrowing have a positive effect on budget deficits, whereas institutional quality, financial deepening, and real gross domestic product havenegative effect in the long run. In the short run, domestic borrowing positively affects budget deficit whereas borrowing, institutional quality, and real gross domestic product affect negatively. The findings of the threshold study indicate that the projected threshold level of budget deficits is 3%. Any ratio of budget deficits over this threshold, on the other hand, has a positive impact on the current account balance, while any rate below this threshold has a negative impact. In order to lower the government budget deficit, it is advised that sensible economic policies be adopted, such as a simple and effective tax system, import substitution, and export promotion.