bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Potential Anti‐COVID‐19 Drug Leads from Medicinal Plants through Virtual High‐Throughput Screening
Authors: Firouzi Rohoullah , Ashouri Mitra 
Published: February 2023

AbstractNatural compounds are widely used as attractive and valuable starting points for drug lead discovery. The present study aims to identify phytochemical compounds found in medicinal plants as potential COVID‐19 inhibitors, using ensemble docking simulations. To this end, a phytochemical library from the PHCD database – a database of natural chemical compositions of Persian medicinal herbs (https://persianherb.com) – have been virtually screened against four key protein targets in the SARS‐CoV‐2 life cycle – the Mpro and PLpro proteases and the Spike and human ACE2 proteins. Several potential antiviral lead candidates have been identified based on the “Computational Multitarget Screening” approach, in which favourite candidates interact simultaneously with all four targets. Four of the bioactive phytochemicals identified – Chelidimerine, Gallagyldilacton, Hinokiflavone, and Physalin Z – show the highest binding affinities to all the targets and are suggested to be the best choices for drug design research. Also, several important medicinal plants, including Chelidonium majus L., Punica granatum, Rhus coriaria, Capparis spinose, Cichorium intybus, and Cynara scolymus, with the most phytochemicals interacting with all the host and viral proteins, have been identified that can be considered as the most important herbal resources for drug development with the medicinal plant formulations against COVID‐19.
Synthesis of Enantiomers of Chiral Ester Derivatives Containing an Amide Group and Their Chiral Recognition by 1H NMR Spectroscopy
Authors: Li Yan‐Lin , Zhao Hong‐Mei , Ren Yu‐Qing , Qiu Meng , Zhang Hai‐Tong , Gao Guang‐Peng , Zheng Li , Stavropoulos Pericles , Ai Lin 
Published: February 2023

AbstractEnantiomers of chiral ester derivatives containing an amide group, and possessing one or two stereogenic centers were prepared from L‐ and D‐α‐amino acids, and glycine with (S)‐ and (R)‐mandelic acid for probing their chiral recognition as a new class of chiral guests by 1H NMR spectroscopy, since chiral ester derivatives have been rarely used as chiral substrates for chiral recognition by 1H NMR technology. The results indicated that these chiral ester derivatives have been successfully differentiated in the presence of tetraaza macrocyclic chiral solvating agents (TAMCSAs) 1 a–1 c. In order to better understand their chiral discriminating behavior, Job plots, association constants (Ka), and theoretical calculations of (S,S)‐G1 and (R,R)‐G1, as a representative example, were performed, respectively. In order to evaluate their practical application, the 1H NMR spectra of G1 and G9 with various optical purities were measured (up to 98 % ee). In this work, a practical strategy has been effectively established for chiral recognition of chiral ester derivatives containing an amide group and possessing one or two chiral centers in the presence of tetraaza macrocyclic chiral solvating agents 1 a–1 c by means of 1H NMR spectroscopy.
Fluorenone Appended Colorimetric Sensor for Cascade Detection of Fluoride and Calcium Gluconate with Applications in Solid State and Logic Gate Systems
Authors: Sharma Neha , Kaur Navneet 
Published: February 2023

AbstractA novel fluorenone derived Schiff base chemosensor (1) has been synthesized as a colorimetric sensor for fluoride (F−) ions in CH3CN and characterized by various analytical techniques. The chemosensor 1 perceived high selectivity for F− ion detection in the presence of other anions along with naked eye color change from yellow to orange‐red with quantitative detection limit of 900 nM. The UV‐vis changes, density functional theoretical (DFT) calculations and 1H NMR titration studies pointed to F− ion induced deprotonation of −OH of sensor 1 that has been proposed to be responsible for the observed absorption as well as color changes. The sensor 1 has also been efficiently applied for the solid state concentration dependent naked eye detection of F− ions in the form of filter paper strips and smartphone applications. The in‐situ generated 1‐F− complex was further utilized for cascade recognition of calcium gluconate (CG). The reversible and reproducible changes produced by the addition of F− ions and CG enabled 1 to be used as “INHIBIT” molecular logic system and “SET/RESET” memorized device at the molecular level.
A pH‐responsive Zr‐based metal organic framework PCN‐777 as a potential oral drug carrier
Authors: He Qing , Lu Wenwen , Jiang Xiaoying , Han Yuanbo , Yu Hongliu , Zhao Hong , Guan Xinghua , Lin Wenxin 
Published: February 2023

AbstractA Zr‐based metal‐organic framework PCN‐777 with good biocompatibility was synthesized by solvothermal method using 2,4,6‐Tris(4‐Carboxyphenyl)‐1,3,5‐Triazine and ZrOCl2 ⋅ 8H2O as raw materials. Its structure was identified and the results showed that it had good crystallinity. Then the anti‐inflammatory drug ibuprofen sodium was loaded into PCN‐777 to establish an IBUNa@PCN‐777 compound and the maximum loading capacity was tested. When the mass ratio of IBUNa to PCN‐777 was 4 : 1, the loading of IBUNa in IBUNa@PCN‐777 reached the maximum value 72.53 wt %. Biocompatibility investigation indicated PCN‐777 and IBUNa@PCN‐777 had good biocompatibility. Moreover, the drug release behavior of IBUNa@PCN‐777 testified the drug release at pH 7.4(>80 %) was greater than that at pH 2.0(<20 %). indicated that IBUNa@PCN‐777 had good pH response in simulated digestive environments. The above results demonstrated that PCN‐777 had potential application prospects as an oral drug carrier.
Reconstruction of spectra and an algorithm based on the theorems of Darboux and Puiseux
Authors: Grozdanov Sašo , Lemut Timotej 
Published: February 2023

Abstract
Assuming only a known dispersion relation of a single mode in the spectrum of a meromorphic two-point function (in the complex frequency plane at fixed wavevector) in some quantum field theory, we investigate when and how the reconstruction of the complete spectrum of physical excitations is possible. In particular, we develop a constructive algorithm based on the theorems of Darboux and Puiseux that allows for such a reconstruction of all modes connected by level-crossings. For concreteness, we focus on theories in which the known mode is a gapless excitation described by the hydrodynamic gradient expansion, known at least to some (preferably high) order. We first apply the algorithm to a simple algebraic example and then to the transverse momentum excitations in the holographic theory that describes a stack of M2 branes and includes momentum diffusion as its gapless excitation.
Embracing complexity: making sense of diet, nutrition, obesity and type 2 diabetes
Authors: Forouhi Nita G. 
Published: February 2023

AbstractNutrition therapy has been emphasised for decades for people with type 2 diabetes, and the vital importance of diet and nutrition is now also recognised for type 2 diabetes prevention. However, the complexity of diet and mixed messages on what is unhealthy, healthy or optimal have led to confusion among people with diabetes and their physicians as well as the general public. What should people eat for the prevention, management and remission of type 2 diabetes? Recently, progress has been made in research evidence that has advanced our understanding in several areas of past uncertainty. This article examines some of these issues, focusing on the role of diet in weight management and in the prevention and management of type 2 diabetes. It considers nutritional strategies including low-energy, low-fat and low-carbohydrate diets, discusses inter-relationships between nutrients, foods and dietary patterns, and examines aspects of quantity and quality together with new developments, challenges and future directions.
Graphical abstract
De novo tryptophanase-based indole production by metabolically engineered Corynebacterium glutamicum
Authors: Mindt Melanie , Ferrer Lenny , Bosch Dirk , Cankar Katarina , Wendisch Volker F. 
Published: February 2023

Abstract

Indole has an increasing interest in the flavor and fragrance industry. It is used in dairy products, tea drinks, and fine fragrances due to its distinct floral odor typical of jasmine blossoms. The current production of indole based on isolation from coal tar is non-sustainable and its isolation from plants is often unprofitable due to low yields. To offer an alternative to the conventional production, biosynthesis of indole has been studied recently. A glucose-based indole production was achieved by employing the Corynebacterium glutamicum tryptophan synthase α-subunit (TrpA) or indole-3-glycerol phosphate lyase (IGL) from wheat Triticum aestivum in a genetically-engineered C. glutamicum strain. In addition, a highly efficient bioconversion process using C. glutamicum heterologously expressing tryptophanase gene (tnaA) from Providencia rettgeri as a biocatalyst was developed. In this work, de novo indole production from glucose was enabled by expressing the P. rettgeri tnaA in a tryptophan-producing C. glutamicum strain. By metabolic engineering of a C. glutamicum shikimate accumulating base strain, tryptophan production of 2.14 ± 0.02 g L-1 was achieved. Introduction of the tryptophanase form P. rettgeri enabled indole production, but to low titers, which could be improved by sequestering indole into the water-immiscible solvent tributyrin during fermentation and a titer of 1.38 ± 0.04 g L-1 was achieved. The process was accelerated by decoupling growth from production increasing the volumetric productivity about 4-fold to 0.08 g L-1 h-1.

Key points
• Efficient de novo indole production via tryptophanases from glucose
• Increased indole titers by product sequestration and improved precursor supply
• Decoupling growth from production accelerated indole production
Utilization of delactosed whey permeate for the synthesis of ethyl acetate with Kluyveromyces marxianus
Authors: Hoffmann Andreas , Franz Alexander , Walther Thomas , Löser Christian 
Published: February 2023

Abstract
Ethyl acetate is an important organic solvent and currently produced from fossil carbon resources. Microbial synthesis of this ester from sugar-rich waste could be an interesting alternative. Therefore, synthesis of ethyl acetate by Kluyveromyces marxinanus DSM 5422 from delactosed whey permeate (DWP) was studied in an aerated stirred bioreactor at 40 °C. DWP is mainly composed of residual lactose and minerals. The minerals inhibited yeast growth, as witnessed by an increased lag period, a reduced growth rate, and an extended process duration. All experiments were therefore carried out with diluted DWP. In a series of batch experiments, the pH of iron-deficient DWP medium varied between 4.8 and 5.9. The pH of the cultivation medium significantly influenced cell growth and product syntheses, with the highest ethyl acetate yield of 0.347 g g–1 and lowest by-product formation achieved at pH 5.1. It is likely that this effect is due to pH-dependent iron chelation, which affects the iron bioavailability and the intracellular iron content, thus affecting growth and metabolite synthesis. The viability of yeast cells was always high despite the harsh conditions in DWP medium, which enabled extended usage of the biomass in repeated-batch and fed-batch cultivations. These two culture techniques increased the volume of DWP processed per time by 32 and 84% for the repeated-batch and the fed-batch cultivation, respectively, without a drop of the ester yield.

Key points
• Delactosed whey permeate was converted to ethyl acetate with a high rate and yield.
• The formation of ethyl acetate in DWP medium at iron limitation is pH-dependent.
• Highly active yeasts from batch processes enabled extension as fed and repeated batch.

Graphical Abstract
First clinical experience using a novel automated mapping algorithm for mapping of ventricular arrhythmias
Authors: Imnadze Guram , Sommer Philipp , Fink Thomas , Hamriti Mustapha El , Khalaph Moneeb , Braun Martin , Sciacca Vanessa , Isgandarova Khuraman , Guckel Denise , Sohns Christian 
Published: February 2023

AbstractA new automated vector-based mapping algorithm (AMA) for 3-dimensional (3D) mapping has been introduced. The aim of this study was to present our experience using AMA to recognize additional catheter ablation targets in patients with ventricular arrhythmias (VA). A total of 16 patients (ICM; ischemic cardiomyopathy, n = 6; NICM; non-ischemic cardiomyopathy n = 10) suffering from VA underwent catheter ablation. Following bipolar voltage mapping, AMA was utilized to reveal zones of decelerated conduction velocity vectors (CVV) and this information was superimposed onto the 3D reconstructions and compared with the presence of scar. Mapping time was 28.1 ± 10 min for the endocardial reconstruction of the left ventricle (LV) and 17 ± 5.4 min for the epicardium (n = 6 patients). The mean area of LV low voltage was 13.9 ± 15% (endocardial) and 11.9 ± 5.7% (epicardial). Decelerating CVV zones were revealed in all patients (mean conduction velocity threshold of 39.3 ± 13%). Sustained VA have been terminated through ablation and substrate modification was performed in all patients. Correlation between the presence of CVV deceleration zones and areas of abnormal low voltage from bipolar mapping was revealed in only 37.5% of patients, but there was good correlation between scar from unipolar voltage mapping and the presence of CCV deceleration zones (94%; p = 0.008). The novel AMA may improve the understanding of individual VA substrates due to the visualization of decelerated CVV zones and their correlation with abnormal low voltage predominantly from unipolar mapping.
Are physical performance and frailty assessments useful in targeting and improving access to adjuvant therapy in patients undergoing resection for pancreatic cancer?
Authors: Powell-Brett S. , Hodson J. , Pande R. , Mann S. , Freer Alice , Wyrko Zoe , Hughes Clare , Isaac J. , Sutcliffe R. P. , Roberts K. 
Published: February 2023

Abstract
Background
Many patients fail to receive adjuvant chemotherapy following pancreatic cancer surgery. This study implemented a multimodal, multidisciplinary approach to improving recovery after pancreatoduodenectomy (the ‘Fast Recovery’ programme) and measured its impact on adjuvant chemotherapy uptake and nutritional decline. The predictive accuracies of a bundle of frailty and physical performance assessments, with respect to the recipient of adjuvant chemotherapy, were also evaluated.

Results
The N = 44 patients treated after the introduction of the ‘Fast Recovery’ programme were not found to have a significantly higher adjuvant chemotherapy uptake than the N = 409 treated before the pathway change (80.5 vs. 74.3%, p = 0.452), but did have a significantly lower average weight loss at six weeks post-operatively (mean: 4.3 vs. 6.9 kg, p = 0.013). Of the pre-operative frailty and physical performance assessments tested, the 6-min walk test was found to be the strongest predictor of the receipt of adjuvant chemotherapy (area under the ROC curve: 0.91, p = 0.001); all patients achieving distances ≥ 360 m went on to receive adjuvant chemotherapy, compared to 33% of those walking < 360 m.

Conclusions
The multimodal ‘Fast Recovery’ programme was not found to significantly improve access to adjuvant chemotherapy, but did appear to have benefits in reducing nutritional decline. Pre-operative assessments were found to be useful in identifying patients at risk of non-receipt of adjuvant therapies, with markers of physical performance appearing to be the best predictors. As such, these markers could be useful in targeting pre- and post-habilitation measures, such as physiotherapy and improved dietetic support.
The imbalance between Bregs, Tfh, and Tregs in patients with anti-N-methyl-D-aspartate receptor encephalitis
Authors: Li Yatong , Zhang Jing , Liu Lei , Cui Shilei , Sun Houliang , Jiang Hanqiu , Guo Yanjun , Zhang Jingxiao , Xie Zhuxiao , Wang Jiawei 
Published: February 2023

Abstract
Objective
To detect the alteration of regulatory B cells (Bregs), follicular helper T cells (Tfh), and regulatory T cells (Tregs) frequencies in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. Analyze their association with clinical severity and activity, and explore the effects of different immunotherapies on those immune cell subsets.

Methods
We enrolled 21 patients with anti-NMDAR encephalitis, 22 patients with neuromyelitis optica spectrum disorder (NMOSD), 14 patients with idiopathic intracranial hypertension (IIH), and 20 healthy controls (HC) in our study. The frequencies of various immune cell subsets were determined using flow cytometry.

Results
Compared to patients with IIH and HC, the frequencies of CD24hiCD38hi transitional B cells as well as Tregs were significantly lower while the frequency of Tfh was significantly higher in patients with anti-NMDAR encephalitis. The frequency of CD24hiCD38hi transitional B cells was significantly lower in the acute stage than in the recovery stage, and was negatively correlated with the modified Rankin scale (mRS) and the clinical assessment scale for autoimmune encephalitis (CASE). The frequency of CD24hiCD38hi transitional B cells at the last follow-up after rituximab (RTX) treatment was significantly higher than those treated with oral immunosuppressants or untreated. There was no clear difference between anti-NMDAR encephalitis and NMOSD in the above immune cell subsets.

Conclusion
We suggested that the frequencies of CD24hiCD38hi transitional B cells and Tregs were decreased while the frequency of Tfh was increased in patients with anti-NMDAR encephalitis. CD24hiCD38hi transitional B cells frequency may be a potential indicator to estimate the disease activity and severity.
The Consequences of Financial Leverage: Certified B Corporations’ Advantages Compared to Common Commercial Firms
Authors: Paeleman Ine , Guenster Nadja , Vanacker Tom , Siqueira Ana Cristina O. 
Published: February 2023

AbstractFirms usually need to attract debt to form and grow, but increasing financial leverage also entails increased risks and costs for stakeholders, such as customers and employees. Accordingly, past research suggests that for common commercial firms (CCFs), which prioritize profits, higher leverage leads to lower sales growth and higher employment costs. However, Certified B Corporations (CBCs) distinguish themselves by having a credible prosocial mission and, therefore, might be better insulated against the adverse effects of higher leverage. Using a European multi-country matched sample of 136 CBCs and 136 CCFs, we find that the negative relationship between leverage and sales growth and the positive relationship between leverage and employment costs are weaker for CBCs than CCFs. Taken together, due to their certified prosocial mission, CBCs enjoy an advantage in debt financing compared to CCFs.
Oxygen saturation in intraosseous sternal blood measured by CO-oximetry and evaluated non-invasively during hypovolaemia and hypoxia – a porcine experimental study
Authors: Näslund Erik , Lindberg Lars-Göran , Strandberg Gunnar , Apelthun Catharina , Franzén Stephanie , Frithiof Robert 
Published: February 2023

AbstractPurpose: This study intended to determine, and non-invasively evaluate, sternal intraosseous oxygen saturation (SsO2) and study its variation during provoked hypoxia or hypovolaemia. Furthermore, the relation between SsO2 and arterial (SaO2) or mixed venous oxygen saturation (SvO2) was investigated. Methods: Sixteen anaesthetised male pigs underwent exsanguination to a mean arterial pressure of 50 mmHg. After resuscitation and stabilisation, hypoxia was induced with hypoxic gas mixtures (air/N2). Repeated blood samples from sternal intraosseous cannulation were compared to arterial and pulmonary artery blood samples. Reflection spectrophotometry measurements by a non-invasive sternal probe were performed continuously. Results: At baseline SaO2 was 97.0% (IQR 0.2), SsO2 73.2% (IQR 19.6) and SvO2 52.3% (IQR 12.4). During hypovolaemia, SsO2 and SvO2 decreased to 58.9% (IQR 16.9) and 38.1% (IQR 12.5), respectively, p < 0.05 for both, whereas SaO2 remained unaltered (p = 0.44). During hypoxia all saturations decreased; SaO2 71.5% (IQR 5.2), SsO2 39.0% (IQR 6.9) and SvO2 22.6% (IQR 11.4) (p < 0.01), respectively. For hypovolaemia, the sternal probe red/infrared absorption ratio (SQV) increased significantly from baseline (indicating a reduction in oxygen saturation) + 5.1% (IQR 7.4), p < 0.001 and for hypoxia + 19.9% (IQR 14.8), p = 0.001, respectively. Conclusion: Sternal blood has an oxygen saturation suggesting a mixture of venous and arterial blood. Changes in SsO2 relate well with changes in SvO2 during hypovolaemia or hypoxia. Further studies on the feasibility of using non-invasive measurement of changes in SsO2 to estimate changes in SvO2 are warranted.
On Transient Analysis of $$\Delta _N$$-Markov Chains
Authors: Reed Stephanie , Ziadé Elia 
Published: February 2023

AbstractConsider a cyber-physical system which has the purpose of maintaining the security of some physical asset. A particularly relevant scenario is one in which the system must perform its functions while at the same time enduring malicious attacks for an extended amount of time without energy renewal. We will study a theoretical model analogous to this cyber-physical system with an arbitrary number of nodes. The nodes in this system are able to communicate with one another and have the task of maintaining the security of the system. Initially all nodes comprising this system are in working order, however, due to attacks they can eventually become corrupted and then work against the security of the system. Of particular interest is the calculation of a number of metrics related to reliability of the system including the reliability function and the mean-time to failure. A particular case of this model has been examined by many researchers in the past, mostly using numerical methods. The contribution of this paper is the presentation of explicit expressions for the transient-state transition probabilities, reliability function, and the mean-time to failure along with rigorous proofs for the validity of these expressions. A result such as this is stronger than previous results via numerical methods and is an extension of previous analytical results where additional constraints on the model were imposed.
Genomic-based microsatellite development for Ternstroemia (Pentaphylacaceae) and transferability to other Ericales
Authors: Alvarado-Sizzo Hernán , Alcántara-Ayala Othón , Espinosa David , Rivas Gerardo , Oyama Ken , Luna-Vega Isolda 
Published: February 2023

Abstract
Background
The genus Ternstroemia is associated with the vulnerable tropical montane cloud forest in Mexico and with other relevant vegetation types worldwide. It contains threatened and pharmacologically important species and has taxonomic issues regarding its species limits. This study describes 38 microsatellite markers generated using a genomic-based approach.

Methods and results
We tested 23 of these markers in a natural population of Ternstroemia lineata. These markers are highly polymorphic (all loci polymorphic with 3–14 alleles per locus and expected heterozygosity between 0.202 and 0.908), most of them (19 out of 23) are in Hardy-Weinberg Equilibrium and free of null alleles (18 out of 23). Also we found no evidence of linkage among them. Finally, we tested the transferability to six other American species of Ternstroemia, two other Pentaphylacaceae species, and four species from different families within the order Ericales.

Conclusions
These molecular resources are promising tools to investigate genetic diversity loss and as barcodes for ethnopharmacological applications and species delimitation in the family Pentaphylacaceae and some Ericales, among other applications.