bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fast and reliable voltammetric determination of menaquinone (vitamin K2) produced in-vitro by Bacillus subtilis cultures
Authors: Smajdor Joanna , Porada Radosław , Lipińska Justyna , Więcek Grażyna , Jedlińska Katarzyna , Baś Bogusław , Strus Magdalena 
Published: February 2023

Abstract
Vitamin K2 (VK2) is one of two natural forms of vitamin K, necessary for the proper functioning of organisms. Currently, it is sourced from chemical synthesis, nonetheless, it is worth reaching out to its natural sources.
The aim of the study was to devise a voltammetric procedure for the determination of vitamin K2 (VK2) produced by bacteria in order to find the strain that exhibits the highest efficiency of VK2 production. Bacillus subtilis, isolated from traditional Japanese food (Nattō), was chosen as a model strain. Employment of the Controlled Growth Mercury Drop Electrode (CGMDE) was crucial, as it is the only electrode that allows performing the measurement on the surface specifically renewed directly before, thus minimizing the influence of interferents.
This new method was successfully applied for VK2 determination in supernatant samples. Developed procedure is robust and easily adjustable for the variety of biological matrixes. Strong differences in VK2 production depending on cultivation time were observed, but no direct correlation between the VK2 concentration in the breeding medium and the cultivation time was found.
The devised protocol will be used in further measurements with different bacteria species, that have the ability to produce VK2 and settle in the human intestine.
Analysis of sex disparities in under-five mortality rates in Ghana: Insights from vector autoregressive modeling
Authors: Essel  , Appiah Simon Kojo , Mensah Isaac Adjei 
Published: February 2023

Abstract
International monitoring organizations call for child mortality indicators to be disaggregated by gender. However, there remains a paucity of studies, especially, from the sub-Saharan region aimed at producing accurate forecasts of child mortality indicators with their sex variations. This study aims at investigating disparities in indicators of childhood mortality rates by sex in Ghana by employing vector autoregressive (VAR) model to analyze jointly annual recorded data on total, male and female under-five mortality rates (TU5MR, MU5MR, FU5MR, respectively). The results show gradual declining under-five mortality trends among sexes in both the historical and forecasted rates. The trivariate traditional and instantaneous Granger causality analyses found that any of the mortality indicators Granger causes the other two combinations, except TU5MR to MU5MR and FU5MR. The forecast error variance decomposition analyses revealed that FU5MR was the most exogenous variable while long-term impulse response function analyses indicated that unit shocks in FU5MR significantly increased TU5MR. The VAR(2) model forecast constructed revealed that contrary to recent predictions based on wider interval data derived from demographic health surveys, Ghana may meet the SDG 3.2.2 if ongoing efforts are sustained and that focusing policies and interventions on reducing FU5MR would largely contribute to reducing TU5MR in Ghana.
First-in-Human Automated Endovascular Aortic Repair With the Novel Endovascular Surgical Robot
Authors: Lu Qingsheng 
Published: February 2023

Abstract

Background Endovascular interventional robots have influenced the practice of vascular surgery. However, most of them remain at a low level of automation and cannot complete the whole process of endovascular surgeries automatically. Materials and Methods Two patients with thoracic and abdominal aortic aneurysm respectively confirmed by computed tomography angiography were enrolled in this study. Both patients were performed automated endovascular aortic repair with the novel endovascular surgical robot. We use the image processing software to generate preoperative planning pathways and lists of surgical steps and the endovascular surgical robot is programmed to execute the list automatically. The operation time, blood loss, total contrast volume, fluoroscopy time, and radiation exposure were measured during the operations. Technical success was defined as completion of surgeries without extra manual measures. The patients were followed up to six months after procedures. Results A 100% technical success rate was achieved in two operations. No adverse clinical effects associated with the endovascular robotic system were reported. Both patients had no documented in-hospital and six-month major adverse cardiac events. After surgeries, all patients were discharged within 72 hours. The surgeon radiation exposure was 96.5% lower than that at the procedure table and the other indices were in line with those reported in published literature. Conclusions The novel endovascular surgical robot can perform automated TEVAR and EVAR surgeries with acceptable accuracy and safety to provide standardized therapies, reduce empirical interference of surgeons and reduce workload of surgeons.
Institutional arrangements for water reuse: assessing challenges for the transition to water circularity
Authors: Riazi Fayaz , Fidélis Teresa , Matos Manuel Victor , Sousa Maria Carolina , Teles Filipe , Roebeling Peter 
Published: February 2023

Abstract
Water scarcity and security drive attention to water reuse in policy and business. However, water reuse may generate new water loops and challenge water governance with new and different types of water, risks, involved actors, and responsibilities. These challenges demand robust institutional arrangements related to water governance. This article assesses the institutional arrangements associated with four case studies in Spain, Italy, Croatia, and Israel. The findings reveal that the more diverse the water uses and users, the more challenges and risks, particularly those associated with institutional arrangements such as quality standards, sanctions, and conflict prevention, are likely to emerge. The weaknesses of governance models and regulations to deal with changes, uncertainties, and public resistance call for special attention to the design of the institutional arrangements before the adoption. Independent of the type of technology adopted, governance may be improved by ensuring internal and external water monitoring; integrating water management with spatial concerns; improving training, expert engagement, and civil society awareness; and reducing water reuse costs. In addition, alternative models that guarantee the efficiency of governance in attaining objectives and assuring the participation of new water users in the management of water reuse loops may also improve governance.
Current Trends in the Development of EGFR Inhibitors as Promising Anticancer
Agents: Sar and Synthetic Studies from (2010-2020)
Authors: Mondal Sitanshu , S. Vishakha , Kajal Kumari Das , Wahan Simranpreet K. , Kurmi Balak Das , Patel Preeti 
Published: February 2023

Abstract:
The EGFR (Epidermal Growth Factor Receptor) regulates cell proliferation, survival,
and differentiation. The EGFR is a cell surface receptor that belongs to the ErbB tyrosine
kinase family. One of the most important targets for cancer therapy is EGFR inhibition. Because
EGFR over-activation is seen in a wide range of malignancies, targeting EGFR and its
downstream signaling cascades is a sensible and beneficial strategy in cancer therapy. This
review highlighted the most potent EGFR inhibitors with SAR studies and their synthetic
chemical pathways discovered between 2010-2020, employed for treating Liver, Breast, Lung,
Pancreatic, and Colorectal cancers. We also include the clinical trials and the registered patents
in our review.
A New Risk Model based on the Machine Learning Approach for
Prediction of Mortality in the Respiratory Intensive Care Unit
Authors: Yan Peng , Huang Siwan , Li Ye , Chen Tiange , Li Xiang , Zhang Yuan , Wu Huan , Xu Jianqiao , Xie Guotong , Xie Lixin , Mo Guoxin 
Published: February 2023

Background:
Intensive care unit (ICU) resources are inadequate for the large population
in China, so it is essential for physicians to evaluate the condition of patients at admission. In
this study, our objective was to construct a machine-learning risk prediction model for mortality in
respiratory intensive care units (RICUs).

Methods:
This study involved 817 patients who made 1,063 visits and who were admitted to the
RICU from 2012 to 2017. Potential predictors such as demographic information, laboratory results,
vital signs and clinical characteristics were considered. We constructed eXtreme Gradient
Boosting (XGBoost) models and compared performances with random forest models, logistic
regression models and clinical scores such as Acute Physiology and Chronic Health Evaluation II
(APACHE II) and the sequential organ failure assessment (SOFA) system. The model was externally
validated using data from Medical Information Mart for Intensive Care (MIMIC-III) database.
A web-based calculator was developed for practical use.

Results:
Among the 1,063 visits, the RICU mortality rate was 13.5%. The XGBoost model
achieved the best performance with the area under the receiver operating characteristics curve
(AUROC) of 0.860 (95% confidence interval (CI): 0.808 - 0.909) in the test set, which was significantly
greater than APACHE II (0.749, 95% CI: 0.674 - 0.820; P = 0.015) and SOFA (0.751,
95% CI: 0.669 - 0.818; P = 0.018). The Hosmer-Lemeshow test indicated a good calibration of our
predictive model in the test set with a P-value of 0.176. In the external validation dataset, the
AUROC of XGBoost model was 0.779 (95% CI: 0.714 - 0.813). The final model contained variables
that were previously known to be associated with mortality, but it also included some features
absent from the clinical scores. The mean N-terminal pro-B-type natriuretic peptide (NTproBNP)
of survivors was significantly lower than that of the non-survival group (2066.43 pg/mL
vs. 8232.81 pg/mL; P < 0.001).

Conclusions:
Our results showed that the XGBoost model could be a suitable model for predicting
RICU mortality with easy-to-collect variables at admission and help intensivists improve clinical
decision-making for RICU patients. We found that higher NT-proBNP can be a good indicator of
poor prognosis.
Pilot Study of the Ex Vivo Blood Leukocytes’ Proteomic Response to Prednisone Stimulation in Corticosteroid-responsive Asthma
Authors: Nikolic Aleksandra , Mark Kevin J. , Dragicevic Sandra , Babic Tamara , Milosevic Katarina , Nestorovic Branimir , Beskoski Vladimir 
Published: February 2023

Background:Leukocytes are key cellular effectors of inflammation in asthma and understanding their function in this disease is of crucial importance. Blood leukocytes reflect the actions of their counterparts in the lungs and they can be obtained through minimal invasive procedures as part of the peripheral blood.Objective:The aim of the study was to identify proteins in blood leukocyte proteomes that respond to ex vivo treatment by prednisone in order to pinpoint candidates for predictive biomarkers in corticosteroid- responsive asthma.Methods:The study included five children diagnosed with asthma and five healthy children. After the ex vivo treatment of blood samples with prednisone, lysis of erythrocytes was performed and proteins were extracted from the remaining leukocytes by ultrasonic disintegration. Protein extracts were analyzed by reversed phase nano-liquidchromatography–tandem mass spectrometry (LC–MS/MS).Results:The stimulation of asthmatics' leukocytes with prednisone has led to an increase in the levels of FYB (fold change 3.4) and LYZ (fold change 2.2) with a statistical significance of p<0.005. The two proteins with expressions significantly altered upon the prednisone treatment should be further explored as tools to evaluate the patient's response before therapy administration, especially when lung function measurements are not possible, as is the case with young pediatric patients.Conclusion:The approach that entails ex vivo response of blood leukocytes to therapeutics can facilitate asthma management and help overcome the need for therapeutic adjustments in a clinical setting.
Molecular Dynamic Simulation and 3d-pharmacophore Modeling of Alpha
Mangostin and Its Derivatives against Estrogen Alpha Receptor
Authors: Setyawati Luthfi Utami , Binti Parlan Fateen Izzah Haziqah , Khairul Ikram Nur Kusaira , Yusuf Muhammad , Muchtaridi Muchtaridi 
Published: February 2023

Background:
Human estrogen receptor alpha (ERα), which is known to play a role in mediating
cell proliferation, metastasis, and resistance to apoptosis, is one of the targets of breast cancer therapies.
Alpha mangostin (AM) is an active xanthone compound from Garcinia mangostana L. which has
activity as an ERα inhibitor.

Objectives:
This research aims to predict the pharmacokinetic and toxicity, and to study the molecular
interactions of AM derivatives with the ERα using computer-aided simulation approaches through molecular
docking, molecular dynamic, and pharmacophore screening to develop novel anti-breast cancer
agents.

Methods:
Marvinsketch and Chimera programs were used to design and optimize the structure of AM and
its derivatives. For screening the pharmacokinetic and toxicity profiles, the PreADMET web was used.
The AutoDockTools 1.5.6 and LigandScout 4.4.3 Advanced software were used to conduct the molecular
docking simulation and pharmacophore screening, respectively, while the molecular dynamic simulation
was performed using AMBER 16. The results were visualized by Biovia Discovery Studio.

Results:
Molecular docking using Autodock showed that FAT10 derivate has lower binding free energy
(ΔG) (-12.04 kcal/mol) than AM (-8.45 kcal/mol) when docking to ERα and both performed the same
hydrogen bond with Thr347. These support the results of the MMPBSA calculation on dynamic simulation
which shows FAT10 (-58.4767 kcal/mol) has lower ΔG than AM (-42.7041 kcal/mol) and 4-OHT (-
49.0821 kcal/mol). The pharmacophore screening results also showed that FAT10 fitted the pharmacophore
with a fit score of 47.08.

Conclusion:
From the results, it can be suggested that FAT10 has promising activity as ERα antagonist.
Further in vitro and in vivo experiments should be carried out to support these in silico studies.
Coumarin-pyrazoline Hybrids as Selective Inhibitors of the Tumor-associated
Carbonic Anhydrase IX and XII
Authors: Redij Aditi , Carradori Simone , Petreni Andrea , Supuran Claudiu T. , Toraskar Mrunmayee P. 
Published: February 2023

Aim:
Human carbonic anhydrase (CA, EC 4.2.1.1) isoforms IX and XII are validated antitumor/
antimetastatic drug and tumor imaging targets with sulfonamide inhibitors and monoclonal antibodies in clinical
development. Coumarins act as isoform-selective inhibitors of these isoforms over the cytosolic and mitochondrial
ones.

Methods:
We report the synthesis and in vitro CA inhibitory evaluation of a large panel of coumarins incorporating
pyrazole-1-carboxamide moieties. Compounds were fully characterized before the assessment of their inhibitory activity.
A stopped-flow CO2 hydrase assay was performed for the biological test.

Results:
These coumarins did not inhibit the widespread, off-target isoforms CA I and II (KI >50 μM), but they were
sub-micromolar CA IX/XII inhibitors with an interesting selectivity index higher than the reference compound. Selectivity
between α- and β-class of CAs was also promising.

Conclusion:
These compounds may be used as leads for the rational design and development of non-sulfonamide CA
IX/XII effective inhibitors.
Nicotine Abuse and Neurodegeneration: Novel Pharmacogenetic Targets
to Aid Quitting and Reduce the Risk of Dementia
Authors: Almahasneh Fatimah , Gerges Romany H. , Abu-El-Rub Ejlal , Khasawneh Ramada R. 
Published: February 2023

Abstract:
Nicotine dependence has deleterious neurological impacts. Previous studies found an association
between cigarette smoking and accelerating age-related thinning of the brain's cortex and subsequent
cognitive decline. Smoking is considered the third most common risk factor for dementia,
which prompted the inclusion of smoking cessation in dementia prevention strategies. Traditional
pharmacologic options for smoking cessation include nicotine transdermal patches, bupropion and
varenicline. However, based on smokers’ genetic makeup, pharmacogenetics can be used to develop
novel therapies to replace these traditional approaches. Genetic variability of cytochrome P450 2A6
has a major impact on smokers’ behavior and their response to quitting therapies. Gene polymorphism
in nicotinic acetylcholine receptor subunits also has a great influence on the ability to quit smoking. In
addition, polymorphism of certain nicotinic acetylcholine receptors was found to affect the risk of dementia
and the impact of tobacco smoking on the development of Alzheimer's disease. Nicotine dependence
involves the activation of pleasure response through the stimulation of dopamine release.
Central dopamine receptors, catechol-o-methyltransferase and the dopamine transporter protein, regulate
synaptic dopamine levels. The genes of these molecules are potential targets for novel smoking
cessation drugs. Pharmacogenetic studies of smoking cessation also investigated other molecules, such
as ANKK1 and dopamine-beta-hydroxylase (DBH). In this perspective article, we aim to highlight the
promising role of pharmacogenetics in the development of effective drugs for smoking cessation,
which can increase the success rate of smoking quitting plans and ultimately reduce the incidence of
neurodegeneration and dementia.
Roles of the Stereochemical Code and the Entropic Index q in the
Protein Folding Process: How to Map Out Folding Intermediate
Conformations
Authors: Dal Molin João Paulo , Ribeiro Silva Victor Henrique , de Rosa Letícia Antonelli , dos Santos Soares Ricardo Oliveira , Silva Pablo Andrei , Caliri Antonio 
Published: February 2023

Background:
Here, the inverse protein folding problem is approached from
the viewpoint of the entropic index q. We present a brief overview of the problem. Further,
we provide general information about the three-dimensional structure of proteins
and the universal characteristics of the folding process.

Methods:
We explain how the stereochemical model was conceived. Our main objective
is to change how Monte Carlo (MC) simulations are performed. We replace the Boltzmann
weight with the Tsallis weight in order to achieve better sampling. This change
leads to the q Monte Carlo method (MCq). There are two main ways to employ the index
q: one is to set it as a fixed parameter (MCq*), and the other is to set it as an autonomous
variable associated with the instantaneous molecular radius of gyration, a feature that is
allowed by the Beck-Cohen superstatistics. In addition, we propose a meaningful physical
interpretation for the index q. Furthermore, we explain how to assemble amino acid
sequences for the inverse problem.

Results:
We present several results and discuss the implications associated with the MC
and MCq methods. The latter method is an efficient approach to tracking down folding
intermediate conformations, which can enable us to better find and define folding pathways
for successive configurations of a polymeric chain kept in solution at the same
macroscale temperature, T.

Conclusion:
We have explained how and why protein kinetics becomes significantly
more advantageous when we employ q ≠ 1. However, this is only possible if we set the
correct upper value of qmax.
Phytochemical, GC-MS, FTIR and Amino acid profile of methanol extract of Tetrapleura tetraptera fruit
Authors: Nsofor Winifred Njideka , Nwaoguikpe Reginald Nwazue , Ujowundu Favour Ntite , Keke Collins Obinna , Uba Muhammad Tasi’u , Edom Chibuike Valentine 
Published: February 2023

The methanolic fruit extract of Tetrapleura tetraptera was analyzed for the presence of phytocompounds, their bioactivity, the functional groups involved in this activity, and its amino acid profile using standard procedures. Phytochemicals such as tannins, phenols, flavonoids, and alkaloids were identified as being highly present. Gas chromatographic-mass spectrometric (GC-MS) analysis identified 16 bioactive compounds, with 2-thiopheneethanol (58.77%) being the most abundant. Curcumin, with the most diverse pharmacological role, and other bioactive compounds such as cedren-13-ol, 8 (1.56%), N-benzyl stearamide (4.46%), a prominent fatty acid amide hydrolase (FAAH) inhibitor; pthalic acid, butyl undecyl ester (1.49%); and phenol, 2, 6-bis (1,1 dimethyl ethyl) (1.46%), were also present. Fourier transform infrared (FTIR) analysis confirmed the presence of alkanes, esters, benzene rings, aliphatic, sulfonic acid, and methylene chains. Also, the amino acid analysis of the T. tetraptera revealed that the fruit contains 18 amino acids. Leucine (4.20%), phenylalanine (3.37%), and valine (3.25%) were the most abundant essential amino acids identified, with glutamic (7.20%) and aspartic acid (5.61%) having the highest concentrations as non-essential amino acids. This therefore indicates that T. tetraptera fruit could be used as a pharmacological or therapeutic agent as well as a dietary condiment, particularly at this time when there is a demand for novel protein sources.
Keywords: Tetrapleura tetraptera, phytochemicals, GC-MS, FTIR, amino acid, curcumin
Antihyperglycemic Effects of Methanol Extract and Fractions of Oxytenanthera abyssinica Leaf (A. Rich.) Munro (Poaceae) in Alloxan-Induced Diabetic Albino Wistar Rats
Authors: ATCHRIMI KOMI SAGNAN , TOUGOMA ATEHEZI , OMALE SIMEON , BATAWILA KOMLAN , EGESIE GIDEON UMEZURUIKE , ODEH SAMUEL ODU 
Published: February 2023

The present study was carried out to investigate the antihyperglycemic effect of Oxytenanthera abyssinica leaf extract and fractions. Diabetes was induced in rats by administering a single dose of 150 mg/kg of alloxan monohydrate. Single doses of 100 and 200 mg/kg of methanol extract (Met-E), n-hexane fraction (nHex-F), ethyl-acetate fraction (EA-F) and methanol fraction (Met-F) were orally administered to diabetic rats. Met-E and Met-F were selected and administered at 400 mg/kg. The plasma glucose level was checked at 0, 1, 2, 4, 8, 12, and 24 h after treatment in acute effect study. Then once daily administration dose effect of 400 mg/kg of Met-E and Met-F was evaluated in chronic study for 28 days. The dose of 200 mg/kg of Met-E and Met-F significantly (p<0.05) decreased the plasma glucose level at 12th hour after treatment while their marked decrease effect at 400 mg/kg was observed at 4th hour after treatment. The repeated administration of Met-E showed a significant (p<0.05) decrease effect in plasma glucose level at the end of 1st, 3rd and 4th weeks while Met-F showed a significant (p<0.05) decrease effect at the end of 2nd, 3rd and 4th weeks. Treatment with Met-E and Met-F reduced pancreatic tissue deterioration compared to diabetic control. The present results showed that methanol extract and fraction of Oxytenanthera abyssinica exerted antihyperglycemic effect both in acute and chronic administration, which might be due to an amelioration of alloxan-induced pancreatic islet’s tissue damages.
Keywords: Alloxan, Oxytenanthera abyssinica, Antihyperglycemic effect, Pancreas, Methanol extract, Methanol fraction.