bluuebunny/crossref_metadata_2025 huggingface dataset:
A Multi-scale Combined Prediction on Tourist Flow: Does Internet Big Data Matter？
Authors: Liu Jinpei , Zhao Xiaoman , Chen Yi , Dai Yujie
Published: September 2023

This article proposes a multi-scale combination prediction method for tourism traffic driven by internet big data. Firstly, process data on tourist traffic, Baidu index, and online reviews. Use Principal Component Analysis (PCA) to reduce the dimensionality of Baidu Index, and then use Snownlp to calculate the emotional value of each online comment. Secondly, a mixed multi-scale decomposition method is used to decompose tourism traffic and processed data, and sample entropy is used to reconstruct the decomposition results into high-frequency, low-frequency, and trend components. Thirdly, LSTM, BPNN, and SVR are used to predict high-frequency, low-frequency, and trend components, respectively, to obtain the predicted values under the three decomposition paths. The optimal weighted combination is used to obtain the final prediction result. Finally, the empirical analysis of tourism flow in Jiuzhaigou Valley,the result shows that the Internet big data can significantly improve the prediction effect of tourism flow.
Osteocalcin and Chinese visceral adiposity index are associated with the risk of atherosclerotic cardiovascular disease and arterial stiffness in patients with type 2 diabetes mellitus：a case control study
Authors: Gong Caixia , Chen Chongyang , Zhao Yangting , Wang Yawen , Li Kai , Lv Xiaoyu , Liu Jingfang
Published: September 2023

Background
Current risk assessments for atherosclerotic cardiovascular disease (ASCVD) in patients with type 2 diabetes mellitus (T2DM) are limit. Recent evidence strongly supports a close correlation between serum osteocalcin, the Chinese visceral adiposity index (CVAI), and T2DM, and cardiovascular events. However, their association with ASCVD risk in patients with T2DM remains unknown, and their impact on arterial stiffness also remains unclear.
Methods
An analysis of 646 T2DM patients aged 18 and older was conducted in this cross-sectional study. The ASCVD risk was assessed using the China-PAR equation, with patients categorized into low- or medium-high-risk groups. Osteocalcin was detected through electrochemical luminescence, whereas arterial stiffness was defined using ankle-brachial index and brachial-ankle pulse wave velocity. Logistic regression analysis was conducted to examine the correlation between serum osteocalcin levels, CVAI, ASCVD risk, and arterial stiffness.
Results
Osteocalcin levels were significantly lower in men patients with T2DM in the medium-high-risk ASCVD group compared to the low-risk ASCVD group, whereas CVAI levels was significantly higher in women patients with T2DM in the medium-high-risk ASCVD group than the low-risk ASCVD group. Logistic regression analysis identified osteocalcin and CVAI as independent risk factors for both medium-high-risk ASCVD (osteocalcin: men, OR,0.958, 95%CI 0.923, 0.99, women, OR, 0.788, 95%CI 0.645, 0.96, respectively)(CVAI: men, OR,1.010, 95%CI 1.00, 1.02, women, OR,1.084, 95%CI 1.00, 1.17, respectively) and arterial stiffness (osteocalcin: men, OR, 0.958, 95%CI 0.92, 1.00, women, OR, 0.925, 95%CI 0.86, 0.99, respectively)(CVAI: men, OR,1.011, 95%CI 1.003, 1.02, women, OR,1.0217, 95%CI 1.00, 1.03, respectively) in both men and women patients with T2DM. Combining osteocalcin levels and CVAI improved the prediction accuracy of arterial stiffness in men patients with T2DM (difference of AUC (Model 4 vs. Model 1):1.4%). All P-values were < 0.05.
Conclusion
Osteocalcin levels and CVAI are independent risk factors for ASCVD risk and arterial stiffness in T2DM. Combining osteocalcin and CVAI can enhance the early detection of atherosclerosis through men patients with T2DM.
Identification of Potential Acetylcholinesterase (AChE) inhibitors from Vitis vinifera: A Case study of Alzheimer’s Disease (AD)
Authors: Sofela Salimat O. , Ibrahim Abdulwasiu , Bodun Damilola S. , Nwankwo Daniel O. , Mafimisebi Mojirade , Abdulrasheed Buhari , Balogun Toheeb , Opeyemi Isaac
Published: September 2023

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease that affects people aged 60 years and above. Yet, the discovery of potent therapeutic agents against this disease has no utmost progress and a number of drug candidates could not make it out of the clinical trials at varied stages. At the same time, the currently available anti-cholinesterase for the treatment of AD can only improve the clinical symptoms while the recently approved immunotherapy agent “remains questionable. Thus, the need for novel therapeutic agents with the potential to treat the aetiology of the disease. Herein, this study sought to examine the potential of a number of bioactive compounds derived fromVitis viniferaas a promising agent against AChE. Using a computational approach via molecular docking 23 bioactive agents were screened against AChE and the compounds with a binding score below that of the standard ligand were further subjected to drug-likeness and pharmacokinetic screening. Eight of the studied agents optimally saturated the active pocket of the AChE, forming principal interactions with a number of amino acids at its active pocket and among these compounds only rutin failed the drug-likeness test by violating four parameters while all showed moderate pharmacokinetics features. A number ofVitis vinifera-derived bioactive compounds show excellent inhibitory potential against AChE and moderate pharmacokinetic features when compared to the reference ligand (tacrine). These compounds are therefore proposed as novel AChE inhibitors for the treatment of AD and wet-lab analysis is necessary to affirm their potency.
Acarbose reduces Pseudomonas aeruginosa respiratory tract infection in type 2 diabetic mice
Authors: Liu Lin , Fan Haiyang , Li Liang , Fan Yunping
Published: September 2023

Background
Type 2 diabetes mellitus (T2DM) is widely prevalent worldwide, and respiratory tract infections have become the primary cause of death in T2DM patients who develop concurrent infections. Among these, Pseudomonas aeruginosa infection has been found to exhibit a high mortality rate and poor prognosis and is frequently observed in bacterial infections that are concurrent with COVID-19. Studies have suggested that acarbose can be used to treat T2DM and reduce inflammation. Our objective was to explore the effect of acarbose on P. aeruginosa respiratory tract infection in T2DM individuals and elucidate its underlying mechanism.
Methods
High-fat diet (HFD) induction and P. aeruginosa inhalation were used to establish a respiratory tract infection model in T2DM mice. The effect and mechanism of acarbose administered by gavage on P. aeruginosa respiratory tract infection were investigated in T2DM and nondiabetic mice using survival curves, pathological examination, and transcriptomics.
Results
We found that P. aeruginosa respiratory tract infection was more severe in T2DM mice than in nondiabetic individuals, which could be attributed to the activation of the NF-κB and TREM-1 signaling pathways. When acarbose alleviated P. aeruginosa respiratory tract infection in T2DM mice, both HIF-1α and NF-κB signaling pathways were inhibited. Furthermore, inhibition of the calcium ion signaling pathway and NF-κB signaling pathway contributed to the attenuation of P. aeruginosa respiratory tract infection by acarbose in nondiabetic mice.
Conclusions
This study confirmed the attenuating effect of acarbose on P. aeruginosa respiratory tract infections in T2DM and nondiabetic mice and investigated its mechanism, providing novel support for its clinical application in related diseases.
Feasibility Study of PERCIST In The Efficacy Evaluation of [ 18 F] -PSMA-1007 PET/CT In Patients With Prostate Cancer Receiving Systematic Treatment
Authors: Li Yunxuan , Wang Zhuonan , Li Yan , Zheng Anqi , Gao Jungang , Dong Weixuan , Duan Xiaoyi
Published: September 2023

Purpose
Positron Emission Tomography (PET) Response Criteria in Solid Tumors (PERCIST) is a tumor efficacy evaluation standard developed for 2-deoxy-2-[18F]fluoro-D-glucose ([18F]-FDG) PET/CT, We applied this standard to [18F]-coagulate specific membrane antigen-1007 (PSMA) PET/CT in patients with prostate cancer, the standardized uptake value corrected for lean body mass (SUL)was used as metabolic parameter. We compared the consistency between the efficacy evaluation of SUL and prostate specific antigen (PSA), and analyzed the effect of prostate cancer-related clinical factors on consistency. Finally, we attempted to apply the new PSMA efficacy evaluation criteria in 2021 Consensus Statements to this study.
Procedures
: We enrolled 41 men with prostate cancer, who underwent [18F] -PSMA-1007 PET/CT before and after therapy with radiation, androgen deprivation, or chemotherapy, quantitative analysis of positive lesions (at most 5 lesions in a single examination), obtain metabolic parameters,including Summed SULmax,Summed SULmean, Summed SULpeak, whole-body PSMA tumor volume (PSMA-TV), whole-body total lesion PSMA (TL-PSMA). The efficacy of the enrolled patients was evaluated according to PERCIST criteria, Kappa consistency test was carried out between the evaluation results of different parameters and the changes of serum PSA. Logistics regression was used to analyze the impact of clinical factors related to prostate cancer on the efficacy evaluation of PSMA. The new disease progression criteria in 2021 Consensus Statements are used to evaluate efficacy.
Result
41 patients received systematic treatment, 6 patients achieved complete response(CR) to biochemical indicators PSA, 20 patients partial response(PR), 6 patients stable disease(SD), 9 patients progressive disease(PD), Summed SULmax (22/41, Kappa 0.306), Summed SULmean (23/41, Kappa 0.342), Summed SULpeak (23/41, Kappa 0.381), PSMA-TV (22/41, Kappa 0.331), TL-PSMA(26/41, Kappa 0.431). Logistic regression analysis showed that clinical factors associated with prostate cancer(including PSA level, Gleason score, metastatic status, and sensitivity to hormone therapy) did not affect the consistency of PSMA PET/CT metabolic parameters with PSA assessment(P > 0.05). The progress criteria in 2021 consensus statements changed the outcome of the metabolic parameters assessment in 2 patients.
Conclusions
SUL metabolic parameters were consistent with PSA in the efficacy assessment of [18F]-PSMA PET/CT, and were not affected by clinical factors related to prostate cancer, the PERCIST standard can be used in PSMA imaging. Progress criteria in 2021 Consensus Statements could improve consistency between PSMA metabolic parameters and PSA assessment in some patients.
Li adsorption and diffusion on the surfaces of molybdenum dichalcogenides MoX 2 (X=S, Se, Te) monolayers for lithium-ion batteries application: A DFT study
Authors: BOUNBAA Malak , KHUILI Mohamed , FAZOUAN Nejma , ATMANI El Houssine , Allaoui Isam , Houmad Mohamed
Published: September 2023

In this work, we study some of the most high performance electrode materials for lithium-ion batteries. These comprise molybdenum dichalcogenide MoX2 (molybdenum disulfide MoS2, molybdenum diselenide MoSe2, molybdenum ditelluride MoTe2). Using first principal calculations, structural and electronic proprieties of 2D material MoX2 are determinate. The stability estimation by cohesive energy, formation energy, adsorption, theoretical capacity and path diffusion of Lithium are calculated. Our study findings suggest that the adsorption of Li on various sites on the surface of the MoX2 monolayer maintains its semiconductor behavior, and MoX2 demonstrates negative adsorption energies for Li-ion. All of this indicates that the MoX2 is well suited as an anode material for lithium-ion batteries. Our research can offer new ideas for experimental and theoretical design and new anode materials for lithium-ion batteries (LIB).
Homogenous Ensemble Boosting Approach to Improve the Consistency in the Accuracy of Text Data Classification
Authors: Azam Muhammad , Sabah Fahad , Raheem Abdul , Ahmad Nadeem , Irfan Danish , Sarwar Raheem
Published: September 2023

The rapid growth of the internet in recent years has produced an enormous amount of data. The significant chunk of this data is unstructured. This unstructured data requires critical analysis and modelling to become useful for decision making. Due to the wild spread of internet across the globe, several applications are being developed every day. These applications have direct interaction with end-users, and users can provide their opinions, sentiments, reviews etc. about the products, services, events, etc. These sentiments, reviews and opinions are very useful for individuals, organizations, businesses, and governments for future decision making. Surveys from last few years confer those online opinions have more prominent financial effect compared to traditional media advertisement. The significant task of sentiment analysis is used to locate the useful information from the client sentiment. While this substance is intended to be valuable, most of this client produced content requires using the data mining methods and sentiment analysis. However, a few difficulties are confronting sentiment analysis. Sentiment analysis includes the applications of natural language processing and text analysis methods to recognize and separate the useful information from text data. Machine learning techniques are widely used for sentiment classification. In this paper, we provide a deep understanding of different machine learning systems for sentiment classification. An extensive study of homogenous ensemble-based machine learning techniques in the domain of sentiment classification has been carried out to enhance the efficiency and consistency by implementing various learning algorithms to gain better accuracy that can be attained from any of the individual learning algorithms. Our methodology in this paper is to explore the whole process from data preprocessing to classification accuracy. Various preprocessing steps are applied to selected text data to prepare data for classification. Many classification models (NB, NNET, KNN, RPART, SVM, LDA, CTREE) are explored from a different family of classifiers for classification purpose. Lastly, homogeneous ensemble techniques (Boosting (GBM) and Bagging (RF)) are used and compared with individual classifiers. And results obtained shows that Boosting ensemble model is more consistent and accurate than all other discussed models.
Association between neutrophil-lymphocyte-ratio and oxygen delivery in patients after the Norwood operation
Authors: Loomba Rohit , Farias Juan , Villarreal Enrique , flores Saul
Published: September 2023

Background Both neutrophil-lymphocyte-ratio and renal oxygen extraction have been demonstrated to be associated with adverse events after cardiac surgery. The association between neutrophil-lymphocyte-ratio and renal oxygen extraction has not previously been studies. The aim of this study was to characterize the association between neutrophil-lymphocyte ratio and renal oxygen extraction. Methods High fidelity hemodynamic monitoring data was retrieved for patients who underwent the Norwood operation. Bayesian regression analyses were conducted to identify what hemodynamic variables, including renal oxygen extraction, were associated with neutrophil-lymphocyte ratio. Results A total of 27,270 datapoints were collected over 1,338 patient-hours for nine unique patients. Renal oxygen extraction ratio had an area under the curve of 0.72 to identify renal oxygen extraction of over 35%. An increase in renal oxygen extraction by 1 was associated with a 0.15 increase in the neutrophil-lymphocyte-ratio. Conclusion In patients after the Norwood procedure, there is a correlation between the neutrophil-lymphocyte-ratio and renal oxygen extraction. A neutrophil-lymphocyte-ratio of greater than 2.95 has fair-performance in identifying renal extraction of greater than 35%.
Adaptive event-triggered fault-tolerant control for leader-followering consensus of multi-agent systems
Authors: Cui Guofei , Wu Libing , Wu Meng
Published: September 2023

This paper focuses on the distributed fault-tolerant leader-followering synchronization problem for linear multi-agent systems (MASs) with the event triggering strategy. Firstly, in order to compensate effectively for the actuator faults and bounded inputs from the leader, a distributed event-triggered algorithm with adaptive techniques is proposed. Secondly, the trigger function with adaptive parameters is designed to enhance the self-regulation of the trigger mechanism, which is relevant to the state of the agents and time, but not to the number of agents. Then, it is demonstrated that the developed consensus protocol can achieve not only the synchronization of agents without continuous communication , but also the exclusion of Zeno behavior. Finally, example of numerical simulation illustrates the effectiveness of the presented control protocol.
Universal and facile sol-gel approach for fabrication of multitudinous yolk- shell architectures
Authors: Li Hongqing , Xu Wenqi , Xu Jiaqi , Zhu Mengxuan , Wang Rui , Jiang Heng , Jin Changzi
Published: September 2023

The nanoreactors with yolk-shell configuration have been one of the most attractive objects because of their unique performance in specific reactions. However, complicated synthesis procedures have restricted the truth understanding and wide application of the yolk-shell architectures. This article presents a universal and facile sol-gel process for fabrication of mesoporous silica hollow structure and derived yolk-shell composites with extended Stöber resorcinol-formaldehyde resin as sacrificed template. The crucial influence factors for the morphology of products are investigated. A series of yolk-shell composites with multitudinous components have been successfully designed and are further catalytic tested by different reactions. This work has provided a universal avenue for the fabrication of yolk-shell nanoreactors to suit specific reaction needs.
Comprehensive analysis to investigate the association between IL-8 gene polymorphisms and the risk of cancer from 135 case-control studies
Authors: Xu Bin , Yan Yidan
Published: September 2023

Background
The association between polymorphisms in the interleukin-8 (IL-8) gene and the development of cancer risk have been investigated in many studies. Nonetheless, the past findings have needed to be more consistent and conclusive. Thus, the current study aims to comprehensively evaluate the association between IL-8 gene polymorphisms and cancer risk.
Methods
The literature survey was conducted across multiple databases. The search comprised all relevant publications conducted on June 23, 2023.
Results
In accordance with the predefined search criteria for assessing cancer susceptibility, an inclusive meta-analysis was conducted, containing 135 case-control studies. This investigation yielded a collection of six distinct polymorphisms (-251, -353, + 678, +1633, + 2767, +781), which were identified and documented. The association strength was evaluated via odds ratios with 95% confidence intervals. This research has made a significant discovery regarding the − 251 polymorphism and its potential association with increased cancer risk. The resulting analyses encompassed various populations, including Asians and individuals of mixed ancestry, as well as different sources of control, precisely hospital-based sources. Furthermore, the study examined multiple types of cancer, such as gastric, glioma, bladder, and colorectal. These examinations suggest that the − 251 polymorphism may have been implicated in elevating the susceptibility to these malignancies. The − 353 polymorphism was identified as a potential risk factor that indicated its involvement in cancer development, while the + 781 polymorphism was also linked with elevated cancer risk.
Conclusions
Overall, the investigation has revealed that IL-8 gene polymorphisms significantly influence vulnerability to cancer development.
Reduction in D-dimer Levels After Treatment with Auxora in Patients with Severe Covid-19 Pneumonia Reflects Endothelial Stabilization
Authors: Hou Peter C. , Miller Joseph , Bruen Charles , Youssef Fady , Schnaus Michael J. , Brouillette Kathyrn , Mendoza-Ayala Raul , Zhang Jeffrey , Stauderman Kenneth , Hebbar Sudarshan
Published: September 2023

Background
Auxora, a calcium release-activated channel (CRAC) inhibitor, was demonstrated to improve recovery and decrease mortality in patients with severe COVID-19 pneumonia initially in an open-label trial and then in CARDEA, a phase 2, randomized, double-blind, placebo-controlled trial. In the open-label trial, treatment with Auxora was noted to be associated with a decrease in D-Dimer levels. To confirm these findings, blood samples were collected in CARDEA and tested for D-dimer levels. In a subset of patients, additional biomarkers were assessed to elucidate a potential mechanism of action of Auxora in decreasing D-dimer levels.
Methods
In patients enrolled in CARDEA, blood samples were collected prior to randomization and again at 72 hours after the start of the first infusion of Auxora for testing of D-dimer levels. In patients who consented for additional biomarker testing, blood samples were collected prior to randomization and again at 96 hours for testing of Angiopoietin-1, Angiopoietin-2, renin, and sCD25 levels.
Results
The baseline mean D-dimer level in the Auxora group was 2.61 mg/L and in the placebo group 2.05 mg/L. Patients treated with Auxora had a significant decrease in D-dimer levels within the first 72 hours compared to those treated with placebo. The difference was − 0.92 (95% CI: -1.82, -0.02; P < 0.0460). The decrease in D-dimer levels correlated with an increase in imputed PaO2/FiO2 (P/F) at 72 hours (r: -0.193; P < 0.05) which in turn correlated with improved clinical outcomes at 168 hours (r: 0.218, P < 0.01). Additional biomarker testing demonstrated that treatment with Auxora reduced levels of Angiopoietin-2 and sCD25 and increased Angiopoietin-1 levels at 96 hours.
Conclusion
In patients with severe COVID-19 pneumonia, Auxora reduced D-dimer levels which correlated with improved oxygenation and clinical outcomes. In addition, Auxora appears to have decreased endothelial activation through a reduction in systemic inflammation and likely had a direct effect on endothelium stabilization.
This trial is registered at ClinicalTrials.gov number, NCT04345614.
DELIVER: Extending the benefits of SGLT-2 inhibitors
Authors: Samaan Kerollos , Wagdy Kerolos
Published: September 2023

The DELIVER trial investigated the efficacy and safety of dapagliflozin in patients with heart failure and preserved or mildly reduced ejection fraction. The trial demonstrated that dapagliflozin significantly reduced the risk of worsening heart failure or cardiovascular death compared to placebo. The benefit was mainly driven by a decrease in heart failure hospitalizations, with no significant impact on mortality. Patients with different ejection fractions and diabetes status showed similar treatment effects. Dapagliflozin also improved functional capacity and quality of life. These findings support the use of SGLT-2 inhibitors in HFpEF and HFmrEF, potentially influencing clinical practice and future guidelines.
Navigating the challenges of bicuspid aortic valve-aortopathy
Authors: Kanagala Sai Gautham , Sawhney Aanchal , Parikh Kinna , Gupta Vasu , Mahmood Talha , Anamika FNU , Jain Rohit , Garg Nikita
Published: September 2023

Bicuspid aortic valve (BAV) is a congenital heart defect that affects 0.5-2% of the general population with familial predominance. The modifications in hemodynamics and structure change at cellular level contribute to the dilation of aorta, resulting in bicuspid aortopathy, which can result in catastrophic aortic events. The American Heart Association recommends screening first-degree relatives of patients with bicuspid aortic valve and aortic root disease. BAV may or may not be associated with a syndrome, with the non-syndromic variety having a higher chance of predisposition to congenital and vascular abnormalities. Many genes have been implicated in the etiology of non-syndromic aortic aneurysm such as ACTA2, MYH11, FLNA, and SMAD3. Common diagnostic modalities include transthoracic echocardiography (TTE), transesophageal echocardiography (TEE), multi system computer tomography (MSCT), and cardiac MRI. Medical management reduces the rate of disease progression and surgical management is indicated based on the diameter of the ascending aorta, which differs in American and European guidelines. Our article aims to explore the current understanding of the pathophysiology, clinical aspects, and surgical management of bicuspid aortic valve disease. Additionally, we have included a discussion on the management of this condition in special populations, such as athletes and pregnant women, who require distinct treatment recommendations.
Myocarditis and COVID-19 related issues
Authors: Ciabatti Michele , Zocchi Chiara , Olivotto Iacopo , Bolognese Leonardo , Pieroni Maurizio
Published: September 2023

The recent COVID-19 (Coronavirus Disease 2019) pandemic by SARS-CoV2 infection has caused millions of deaths and hospitalizations across the globe. In the early pandemic phases, the infection had been initially considered a primary pulmonary disease. However, increasing evidence has demonstrated a wide range of possible cardiac involvement. Most of systemic and cardiac damage is likely sustained by a complex interplay between inflammatory, immune-related and thrombotic mechanisms. Biventricular failure and myocardial damage with elevation of cardiac biomarkers have been reported in COVID-19 patients, although histological demonstration of acute myocarditis has been rarely documented. Indeed while cardiac magnetic resonance findings include different patterns of myocardial involvement in terms of late gadolinium enhancement, histological data from necropsy and endomyocardial biopsy showed peculiar inflammatory patterns, mostly composed by macrophages. On the other hand COVID-19 vaccines based on mRN technology have been also associated with increased risk of myocarditis. COVID-19 and mRNA vaccine-related myocarditis present different clinical and imaging presentations and recent data suggest the presence of distinctive immunological mechanisms involved.
Ciência e tecnologia militar: “política por outros meios”?
Authors: William de Sousa Moreira
Published: September 2023

A ciência e a tecnologia impulsionaram o potencial econômico e militar das potências que souberam investir nesse binômio e compreender suas inter-relações com a política. O poder gerado e acumulado se refletiu amplamente na ordem internacional vigente. Um exemplo emblemático da interação entre ciência, tecnologia, poder e política foi o surgimento da arma atômica, em 1945, produto de um extraordinário esforço combinado de pesquisa cientifica e mobilização política. É notável que essa empreitada tenha se iniciado nas décadas anteriores em ambiente de cooperação acadêmico-científica, algo que mudou quando os cientistas perceberam o potencial da energia que estavam descobrindo. Merece atenção, nesse caso, como foram estimuladas conexões entre ciência básica, tecnologia e política de estado e, ainda, como essa última se sobrepôs a todas as outras. O presente trabalho tem por objetivo explorar e expor essas inter-relações entre ciência, tecnologia e política, suas influências recíprocas, buscando na experiência histórica e na literatura especializada os fundamentos que permitem desvelar a dimensão instrumental da ciência e tecnologia militar como “política por outros meios”.
Assessing seasonal variation and trends in rainfall patterns of Madhya Pradesh, Central India
Authors: Kumar Amit , Kumar Siddharth , Rautela Kuldeep Singh , Shekhar Sulochana , Ray Tapas , Thangavel Mohanasundari
Published: September 2023

Climate change is a worldwide problem caused by various anthropogenic activities, leading to changes in hydroclimatic variables like temperature, rainfall, riverine flow, and extreme hydrometeorological events. In India, significant changes are noted in its natural resources and agriculture sectors. In this study, we analysed the long-term spatio-temporal change in rainfall patterns of Madhya Pradesh, Central India, using Indian Meteorological Department high-resolution gridded data from 439 grid points. The coefficient of variance analysis showed low variability in annual and monsoon rainfall but significant variability in pre-monsoon, post-monsoon, and winter seasons, indicating considerable seasonal variation. Pre-monsoon rainfall exhibited an increasing trend (0.018 mm annually), while annual, monsoon, post-monsoon, and winter rainfall showed decreasing trends. Change point analysis identified shifts in rainfall patterns in 1998 (monsoon, annual), 1955 (pre-monsoon), 1987 (post-monsoon), and 1986 (winter). Spatio-temporal distribution maps depicted irregular rainfall, with some areas experiencing drastic declines in precipitation after 1998. The maximum average annual rainfall reduced from 1,769 to 1,401 mm after 1998 affecting water availability. The study's findings highlight a significant shift in Madhya Pradesh's seasonal rainfall distribution after 1998, urging researchers and policymakers to address water-intensive cropping practices and foster climate resilience for a sustainable future in the region.
The technological development of drinking water treatment plants in the Czech Republic
Authors: Orderud Geir Inge , Porcal Petr , Eikebrokk Bjørnar , Sláma Jiří , Vogt Rolf David , Hejzlar Josef , Haaland Ståle
Published: September 2023

Several actors have an impact on the quality of drinking water, but ultimately drinking water treatment plants (DWTPs) play a decisive role in ensuring that water quality complies with public regulations. Several developing technologies are combined in water treatment processes. In this paper, we are analysing the technological development of DWTPs in the South Bohemian region of the Czech Republic. The empirical basis is five DWTPs of varying size, and data are gathered through semi-structured interviews with relevant staff inside and outside of the five DWTPs. This study identifies the interplay of factors driving technological development: public regulations, the economic capacity of local DWTP owners together with subsidies from the European Union and national authorities, political priorities by local authorities, and the knowledge network. The paper addressess learning–knowledge–change processes of DWTPs, thereby contributing to our understanding of developing competence in producing drinking water. Generally, large DWTPs are front-runners in introducing new technologies while the smaller ones are lagging. Still, private companies operating small plants on behalf of municipal owners ensure that those DWTPs are part of a wider knowledge network, aiding to introduce a necessary and cost-effective upgrade to treatment steps
A atuação do jornalismo na construção da legitimidade da participação de duas organizações da sociedade civil nas políticas nacionais de educação
Authors: Carrilo Moreno Rosangela , Charles Marques Bundai Stephanie
Published: September 2023

As organizações da sociedade civil ganharam uma posição legítima para avaliar, analisar e propor políticas nacionais de educação. Interessado em compreender a construção da legitimidade dessas organizações no campo da política, este trabalho aborda um domínio pouco estudado na área de educação, o jornalismo, para indagar a sua participação nesse processo. Para isso, utilizamos como fontes documentais o acervo de três jornais de grande circulação e os relatórios de atividades de duas organizações de grande visibilidade (Todos pela Educação e Campanha Nacional pelo Direito à Educação). Se a análise dos materiais por um lado permitiu verificar o verdadeiro trabalho de construção da imagem de cada organização e de seus representantes como especialistas em políticas de educação nacional, por outro, esses grupos têm buscado nas mídias o apoio para construir sua legitimidade na política, o que não significa que tenham alcançado a mesma visibilidade.
The Influence of Atorvastatin, Amlodipine and Ethoxidol on Ubiquinol and Ubiquinone
Endogenous Plasma Concentrations in Patients with Chronic Heart Failure
Authors: Zozina V.I. , Kondratenko S.N. , Shikh E.V. , Krasnykh L.M. , Melnikov E.S. , Kukes V.G.
Published: September 2023

Background:

Coenzyme Q10 is a key component of the mitochondrial respiratory chain and a fat-soluble
endogenous antioxidant performing many vital functions in the human body. Many researchers studied the plasma
concentrations of ubiquinol, ubiquinone, total CoQ10 and the redox state (ubiquinol/ubiquinone ratio) of CoQ10 in
healthy volunteers. However, these parameters in the plasma of patients with chronic heart failure (CHF) remain
almost uninvestigated.

Objective:

The aim of this case-control study was to investigate the effect of atorvastatin, amlodipine and ethoxidol
on endogenous plasma concentrations of ubiquinol, ubiquinone, total CoQ10 and its redox state in patients with CHF.

Methods:

The study included 62 patients with CHF divided into four groups depending on the prescribed therapy.
For the quantitative determination of ubiquinol, ubiquinone, and total CoQ10 in the plasma of patients, HPLCMS/
MS was used.

Results:

It was established that the endogenous plasma concentration of total CoQ10 in patients with CHF is significantly
lower than in healthy volunteers, and the ratio of reduced and oxidized forms of CoQ10 is shifted towards
ubiquinone. It was a statistically significant effect of drugs with different physicochemical structures and pharmacological
action on the plasma concentrations of ubiquinol, ubiquinone and total CoQ10: atorvastatin administration led
to a decrease in the concentration of ubiquinol (-33.3Δ%), and total CoQ10 (-15Δ%), administration of amlodipine
contributed to an increase in the levels of ubiquinol (+27.7Δ%) and total CoQ10 (+18.2Δ%), and the administration
of ethoxidol caused an increase in the concentration of ubiquinol (+25Δ%), ubiquinone (+17.7Δ%) and total CoQ10
(+20.2Δ%).

Conclusion:

Amlodipine is able to neutralize the negative effect of atorvastin on the redox balance of CoQ10 in
patients with CHF. An additional prescription of the antioxidant ethoxidol to standard therapy for patients with CHF
was substantiated. Determination of the redox state of CoQ10 in plasma can be used to diagnose and assess the degree
of oxidative stress in patients with cardiovascular diseases, as well as to assess the efficacy and safety of ongoing
pharmacotherapy.
Recent Advances in Xanthine Oxidase Inhibitors
Authors: Sun Zhi-Gang , Wu Kai-Xiang , Ullah Inam , Zhu Hai-Liang
Published: September 2023

Uric acid is a product of purine nucleotide metabolism, and high concentrations of uric acid
can lead to hyperuricemia, gout and other related diseases. Xanthine oxidase, the only enzyme that
catalyzes xanthine and hypoxanthine into uric acid, has become a target for drug development against
hyperuricemia and gout. Inhibition of xanthine oxidase can reduce the production of uric acid, so xanthine
oxidase inhibitors are used to treat hyperuricemia and related diseases, including gout. In recent
years, researchers have obtained new xanthine oxidase inhibitors through drug design, synthesis, or
separation of natural products. This paper summarizes the research on xanthine oxidase inhibitors
since 2015, mainly including natural products, pyrimidine derivatives, triazole derivatives, isonicotinamide
derivatives, chalcone derivatives, furan derivatives, coumarin derivatives, pyrazole derivatives,
and imidazole derivatives, hoping to provide valuable information for the research and development
of novel xanthine oxidase inhibitors.
Impact of Structural GLA Protein Changes on Peripheral GLA Activity and Substrate Accumulation in Fabry Disease Patients
Authors: Da Silva Jorge Diogo , Ribeiro Isaura , Caseiro Carla , Pinto Eugénia , Rocha Sónia , Ribeiro Helena , Ferreira Célia , Silva Elisabete , Laranjeira Francisco , Tkachenko Nataliya , Lacerda Lúcia , Quelhas Dulce
Published: September 2023

Introduction:

Fabry disease is an X-linked lysosomal storage disorder caused by pathogenic variants in the GLA gene, leading to decreased/absent α-galactosidase activity. In clinical practice, enzyme activity and substrate/byproduct accumulation play a role in diagnosis and disease-monitoring biomarkers. However, interpreting biomarker levels is not straightforward and can change according to the underlying GLA protein abnormality.

Objective:

Our goals were to understand how disrupting specific protein regions changes biomarker behaviour and to establish specific patterns for individual variants.

Methodology:

We analysed data from the Biochemical Genetics Laboratory regarding GLA variants, GLA enzyme activity (in dried blood spots, plasma or white blood cells), plasma LysoGb3 accumulation, and urinary Gb3 excretion. We assessed correlations, trends, and potential predictor models of biomarker behaviour.

Results:

We assessed 169 hemizygous male and 255 heterozygous female patients. For both groups, substrate accumulation correlates inversely with GLA activity. Variants affecting residues buried within the protein core or the active site were associated with more severe biomarker changes, while those affecting residues that establish disulfide bonds or are glycosylated were similar to other variants. For each non-truncating variant, we also established specific profiles of biomarker behaviour. Finally, we also designed predictor models of biomarker behaviour based on structural variant information. This study provides the groundwork for the impact of GLA protein variation on GLA activity and substrate accumulation.

Conclusion:

This knowledge is of extreme relevance for diagnostic labs and clinicians, as some genetic variants are challenging to interpret regarding pathogenicity. Assessing whether biomarker changes are in the expected range for a specific variant may help diagnostic evaluation. This study also contributes to recognising non-disease-causing variants, considering their overall biochemical impact, and providing a comparative reference for biomarker discovery studies. In the future, the correlation of these findings with disease severity may be of great relevance for diagnosis and monitoring progression.
Glutaric Acidemia Type 1: Diagnosis, Clinical features, and Outcome in a Portuguese Cohort
Authors: Pinto Patrícia Lipari , Câmara Beatriz , Florindo Cristina , Loureiro Rita Santos , Jardim Inês , Sousa Carmen , Vilarinho Laura , Janeiro Patrícia , Tavares de Almeida Isabel , Gaspar Ana
Published: September 2023

Introduction:

Glutaric acidemia type 1 (GA1) is a rare autosomal recessive disorder characterized by a deficiency of glutaryl-CoA dehydrogenase, resulting in the accumulation of glutaric acid (GA), 3-hydroxyglutaric acid, and glutarylcarnitine, especially in the brain. GA1-affected children are clinically characterized by macrocephaly. Neurological abnormalities usually appear between 6 and 18 months of age, often triggered by a catabolic event. On the other hand, several biochemically affected individuals may remain asymptomatic or experience an insidious onset of mild neurological abnormalities.

Methods:

Retrospective study of GA1 patients followed at a Portuguese Hereditary Metabolic Disease Center, to characterize the phenotypic and genotypic variations associated with GA1. Therefore, we analyzed the clinical, neuroradiological, biochemical, and genetic information from 14 patients.

Results:

14 patients (four months-27 years old) were identified in the last 26 years, 9 were male, 1 was from a consanguineous family. 11 were diagnosed by newborn screening (NBS), and 3 identified following clinical symptoms (later diagnosed, LD). There were 3 phenotypic presentations: 6 asymptomatic, 3 with a motor disability after encephalopathic crisis (EC), and 5 with insidious onset. Acute EC occurred in 1/3 of the LD patients and in 2/11 NBS-identified patients. About urinary GA concentrations: 5 were low excretors (LE), 9 were high excretors (HE). All LE showed symptoms, and 2 had EC. Concerning HE, 3 showed symptoms and 1 had EC. GCDH analysis showed: 6 compound heterozygotes and 8 homozygotes. most frequent variant was c.1204C>T (p.R402W). All of them received appropriate therapy from the time of diagnosis, with a mean age of 23.3 months in LD patients and 13.3 days in NBS-identified patients.

Conclusion:

The outcomes were different between the two groups: all the LD patients presented motor dysfunction however in the NBS-identified patients only 5 developed this symptom. Patients identified by NBS had better outcomes showing that NBS enables an early diagnosis, and treatment, and consequently improves the clinical outcomes for these patients. No correlation was observed with clinical phenotype between LE and HE, as both groups can suffer the most severe neurological manifestations. These conclusions are in agreement with previous cohorts described in the literature.
Pilot Study on Newborn Screening for Spinal Muscular Atrophy
Authors: Fonseca Helena , Ribeiro Diogo , Guimarães Fabio , Pinto Conceição , Marcão Ana , Sousa Carmen , Carvalho Ivone , Lopes Lurdes , Rodrigues Diogo , Rocha Hugo , Vilarinho Laura
Published: September 2023

Introduction:

Newborn screening (NBS) in Portugal is a significant public health measure to provide early detection for specific disorders so that early treatment is possible. Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder that causes degeneration of anterior horn cells in the human spinal cord and subsequent loss of motor neurons. Its incidence is estimated in 1.6000-11.800 live births. A pilot study on 100.000 newborns is being carried out at the neonatal screening laboratory with the aim of determining the specificity, sensitivity, and feasibility of the SMA screening at the NBS laboratory in Portugal.

Methods:

The study presented here was based on data obtained from neonatal screening, involving the analysis of 25.000 newborns. SMA screening is performed by a qualitative detection of exon 7 of the SMN1 gene. The assay was performed using a commercially available real-time PCR, the Eonis SMN1, TREC, and KREC kit.

Results/Case report:

The dried blood spots of a total of 25.000 newborns were tested; among these newborns, two were diagnosed as having SMA with survival motor neuron 1 (SMN1) deletion. These two SMA-positive samples were sent to a specialized clinical centre and a peripheral blood sample was sent to the reference laboratory for confirmation of the exon 7 deletion and determination of the SMN2 copy number.

Conclusion:

Early diagnosis and intervention are important for SMA treatment to be effective; the treatment should be started at the pre-symptomatic stage of SMA. Thus, newborn screening for SMA is strongly recommended. Currently, targeted therapies for SMA are available, and attempts are being made worldwide to include SMA screening in newborns.
Green Synthesis of Silver Nanoparticles using Morinda citrifolia Linn Leaf
Extract and its Antioxidant, Antibacterial and Anticancer Potential
Authors: Datkhile Kailas D. , Chakraborty Shuvronil , Durgawale Pratik P. , Patil Satish R.
Published: September 2023

Introduction:

Nanomedicine has emerged as a revolutionary regimen for moderating communicable
as well as non-communicable diseases.

Purpose:

This study demonstrated the phytosynthesis of silver nanoparticles using M. citrifolia leaf
extract (MC-AgNPs) and their in vitro antioxidant, antibacterial and anticancer potential.

Materials and Methods:

The Biosynthesis of MC-AgNPs was studied by spectroscopy and characterized
by SEM, TEM, XRD and FTIR analysis. The antibacterial activity was checked by minimum
inhibition concentration assay. The HeLa and MCF-7 cancer cell lines were used to explore the cytotoxicity
and genotoxicity activity of biogenic MC-AgNPs.

Results:

The free radical scavenging potential of MC-AgNPs was studied by in vitro DPPH and ABTS assays, which confirmed significant radical scavenging activity in a dose-dependent manner with IC50 of 17.70 ± 0.36 µg/mL for DPPH and 13.37 ± 3.15 µg/mL for ABTS radicals. The bactericidal effects of MC-AgNPs confirmed by MIC showed 0.1 mg/mL concentration of MC-AgNPs with greater sensitivity for E.coli (93.33 ± 0.89), followed by K. pneumoniae (90.99 ± 0.57), S. aureus (87.26 ± 2.80) and P. aeruginosa strains (44.68 ± 0.73). The cytotoxicity results depicted strong dose and time-dependent toxicity of biogenic MC-AgNPs against cancer cell lines fifty percent inhibitory concentration MC-AgNPs against HeLa cells were 13.56 ± 1.22 µg/mL after 24h and 5.57 ± 0.12 µg/mL after 48 h exposure, likewise 16.86 ± 0.88 µg/mL and 11.60 ± 0.97 µg/mL respectively for MCF-7 cells.

Conclusions:

The present study revealed the green synthesis of silver nanoparticles using M. citrifolia
and their significant antioxidant, antibacterial and anticancer activities.
Homology Modelling: A Computational Tool in Drug Design and Discovery
Authors: Agarwal Shivangi , Verma Ekta , Kashaw Sushil K.
Published: September 2023

A drug takes many years to develop and reach the market using the
conventional drug discovery procedure. Computer-aided drug design (CADD) is an
emerging technology that accelerates the process of drug discovery and minimizes the
total expenditure associated with labour and resources. In the current scenario, the
computational aided drug design (CADD) techniques play a significant role in the
design and development of lead molecules for the treatment of various lethal
pathological conditions. The prediction of the tertiary structure of a protein is a big
concern in drug design and discovery. A typical drug discovery procedure starts with
the tertiary structure of a protein. At present, a total of 184,407 protein structures are
available in the protein data bank, which are determinedusing experimental methods.
However, the procedures are difficult and time-consuming. A more advanced technique
has been developed for the prediction of the 3D structure of a protein using a
computational method. This technique has played a vital role in drug discovery. It has
not only facilitated but also hastened the process of drug discovery. The method is
named homology modeling since it involves the building of a protein model based on
its homology to similar evolutionary proteins. The method is based on the fact that
evolutionary related proteins have similar structures. In homology modelling, the 3D
structure of a protein is derived from its primary sequence based on its similarity to the
existing protein templates. There are many computational tools for homology
modelling such as Modeller, Swiss model, Composer, 3D-JIGSAW, etc. The proposed
book chapter will cover the introduction to homology modelling, step-by-step guide to
building a protein model, various challenges and how to refine and validate the model,
different algorithms related to sequence alignment, similarity search, and the
applications of homology modelling in drug design and discovery. The chapter would
be very fruitful to the readers to get insights into protein modelling, which will
facilitate their research activities. It will be of great application in various
disciplines,such as bioinformatics, physics, structural biology, and molecular biology.
The content of the chapter will cover various research papers, review papers, and
corresponding reference books.