bluuebunny/crossref_metadata_2025 huggingface dataset:
A Randomized, Placebo‐Controlled Study of Methotrexate to Increase Response Rates in Patients with Uncontrolled Gout Receiving Pegloticase: Primary Efficacy and Safety Findings
Authors: Botson John K. , Saag Kenneth , Peterson Jeff , Parikh Naval , Ong Stephen , La Dan , LoCicero Karon , Obermeyer Katie , Xin Yan , Chamberlain Jason , LaMoreaux Brian , Verma Supra , Sainati Stephen , Grewal Suneet , Majjhoo Amar , Tesser John R. P. , Weinblatt Michael E.
Published: September 2022

Objective

To assess efficacy, safety, pharmacokinetics, and immunogenicity of pegloticase plus methotrexate (MTX) versus pegloticase plus placebo cotreatment for uncontrolled gout in a randomized, placebo‐controlled, double‐blind trial.

Methods

This study included adults with uncontrolled gout, defined as serum urate ≥7 mg/dl, oral urate‐lowering therapy failure or intolerance, and presence of ongoing gout symptoms including ≥1 tophus, ≥2 flares in the past 12 months, or gouty arthritis. Key exclusion criteria included MTX contraindication, current immunosuppressant use, G6PDH deficiency, and estimated glomerular filtration rate <40 ml/minute/1.73 m2. Patients were randomized 2:1 to 52 weeks of pegloticase (8 mg biweekly) with either oral MTX (15 mg/week) or placebo. The primary end point was the proportion of treatment responders during month 6 (defined as serum urate <6 mg/dl for ≥80% of visits during weeks 20–24). Efficacy was evaluated in all randomized patients (intent‐to‐treat population), and safety was evaluated in all patients receiving ≥1 blinded MTX or placebo dose.

Results

A total of 152 patients were randomized, 100 to receive pegloticase plus MTX, 52 to receive pegloticase plus placebo. Significantly higher treatment response occurred during month 6 in the MTX group versus the placebo group (71.0% [71 of 100 patients] versus 38.5% [20 of 52 patients], respectively; between‐group difference 32.3% [95% confidence interval 16.3%, 48.3%]) (P < 0.0001 for between‐group difference). During the first 6 months of pegloticase plus MTX or pegloticase plus placebo treatment, 78 (81.3%) of 96 MTX patients versus 47 (95.9%) of 49 placebo patients experienced ≥1 adverse event (AE), most commonly gout flare (64 [66.7%] of 96 MTX patients and 34 [69.4%] of 49 placebo patients). Reports of AEs and serious AEs were comparable between groups, but the infusion reaction rate was considerably lower with MTX cotherapy (4.2% [4 of 96 MTX patients, including 1 patient who had anaphylaxis]) than with placebo cotherapy (30.6% [15 of 49 placebo patients, 0 who had anaphylaxis]) (P < 0.001). Antidrug antibody positivity was also lower in the MTX group.

Conclusion

MTX cotherapy markedly increased pegloticase response rate over placebo (71.0% versus 38.5%) during month 6 with no new safety signals. These findings verify higher treatment response rate, lower infusion reaction incidence, and lower immunogenicity when pegloticase is coadministered with MTX.
Morphology‐ and composition‐controlled silver‐containing rhodium nanoparticles for the oxygen reduction reaction
Authors: Hwang Gyu Seop , Shin Woojun , Yim Gyeonghye , Choi Jae Hyuk , Kim Young‐Kwan , Jang Hongje , Kim Yang‐Rae
Published: September 2022

Rh nanoparticles (RhNPs) have attracted significant attention due to their superior electrocatalytic activity in several energy conversion reactions. However, studies relating their morphology and performance are rare. In this study, three types of RhNPs, i.e., nanoshells, nanoframes, and porous nanoplates, were synthesized via inverse‐directional galvanic replacement. The relationship between the performance of the RhNPs at catalyzing the oxygen reduction reaction (ORR) and their morphology was investigated using cyclic voltammetry, linear sweep voltammetry, the Tafel slope, and electrochemical impedance spectroscopy. X‐ray photoelectron spectroscopy and X‐ray diffraction data revealed that the RhNPs contained different Rh/Ag ratios. All the RhNPs exhibited long‐term stability under acidic conditions. In particular, nanoshell‐structured RhNPs exhibited superior ORR activity as determined from the slope of the Tafel plot, the number of electrons, and the onset potential compared to a commercial Rh electrocatalyst and other RhNPs. Evidently, controlling the morphology and composition of RhNPs greatly facilitates efficient electrocatalysis.
Serum metabolomics using ultra‐high performance liquid chromatography–Q‐Exactive tandem mass spectrometry reveals the mechanism of action of exercise training on chronic obstructive pulmonary disease rats
Authors: Du Yan , Wu Jing , Tian Yange , Zhang Lanxi , Zhao Peng , Li Jiansheng
Published: September 2022

Exercise training is the cornerstone component of pulmonary rehabilitation, which results in symptom‐reducing, psychosocial, and health economic benefits for chronic obstructive pulmonary disease (COPD) patients. However, the potential mechanisms of its action are poorly understood. This study conducted serum metabolomics using ultra‐high performance liquid chromatography–Q‐Exactive tandem mass spectrometry to determine the metabolic changes in COPD rats, and the effects of exercise training on improvement in COPD were further investigated. Twelve differential metabolites—which are primarily related to tryptophan metabolism, sphingolipid metabolism, glycerophospholipid metabolism, riboflavin metabolism, pantothenate and CoA biosynthesis, and lysine degradation—were identified in relation to COPD. After the intervention of exercise training, the levels of most metabolites were restored, and the changes in five metabolites were statistically significant, which suggested that exercise training provided effective protection against COPD and might play its role by rebalancing disordered metabolism pathways. This work enhanced our comprehension of the protective mechanism of exercise training on COPD.
Design, Synthesis, Antiviral Evaluation, and Molecular Dynamics Simulation Studies of New Spirocyclic Thiopyrimidinones as Anti HCoV‐229E
Authors: Ragab Sherif S. , Sweed Ayman M.K. , Elrashedy Ahmed A. , Allayeh Abdou K.
Published: September 2022

The current pandemic threat presented by viral pathogens like SARS‐CoV‐2 (COVID‐19) suggests that virus emergence and dissemination are not geographically confined. As a result, the quest for antiviral agents has become critical to control this pandemic. In the current study, we provide a novel family of spirocyclic thiopyrimidinone derivatives whose cytotoxicity and antiviral efficacy were investigated against human coronavirus 229E (HCoV‐229E) as a model for the Coronaviridae family. We utilized MTT and cytopathic effect (CPE) inhibitory tests on green monkey kidney (vero‐E6) cell lines. The new molecules showed varied degrees of antiviral activity against the vero‐E6 cell lines with minimal cytotoxicity. With a high level of a selective index (SI=14.8), compound 9 showed outstanding inhibitory ability and could effectively suppress the human coronavirus 229E. Molecular dynamics simulation (MD) studies were performed to measure the interaction and stability of the protein‐ligand complex in motion. The MD results for the most active compound 9 explored remarkable interactions with the binding pockets of the main protease (Mpro) of SARS‐CoV‐2 enzyme confirming the results gained from in vitro experiments. ADMET properties were also predicted for all the tested compounds. All these results demonstrated that the novel spirocyclic thiopyrimidinone derivatives would have the potential to be safe, low‐cost chemical compounds that might be used as a novel therapeutic option for Coronaviridae viruses like COVID‐19.
Montmorillonite K10 Clay Catalyzed Synthesis of Novel β‐Aminocarbonyl Compounds and Their Biological Evaluation
Authors: Rambabu Gottimukkala , Kiran Yarragudi Bathal Reddy , Tarakeswar Yadamari , Khalivulla Shaik Ibrahim , Barbosa Luiz Claudio Almeida , Vijayakumar Vijayaparthasarathi
Published: September 2022

An efficient and reusable green catalyst for the synthesis of β‐aminocarbonyl compounds has been developed. In this new and greener approach, β‐aminocarbonyl compounds (1a–1r) were obtained by Montmorillonite K10 clay catalyzed reaction of aryl amines, aliphatic/aromatic aldehydes and β‐ketoesters. Molecular docking investigations were performed for all compounds (1a–1r) with the proteins PDB ID: 1JIJ and 1KZN for S. aureus and E. coli, respectively. For all compounds good to strong interactions with the active sites were observed. The biological activities of β‐aminocarbonyl compounds were further assessed for their antibacterial and antioxidant activities. The results confirmed that β‐aminocarbonyl compounds could be further developed into new drugs with potent antibacterial and antioxidant activities.
Two New C21Steroidal Glycosides from Selaginella Braunii Baker
Authors: Li Gui‐Hua , Zhang Yan , Wu Jian‐Ping , Wang Yu‐Yan , Deng Gui‐Ming , Zeng Hong‐Liang , He Xiao‐Ai , Long Hong‐Ping , Zhu Gang‐Zhi , Chen Zu‐Hui , Cheng Fei , Xu Kang‐Ping
Published: September 2022

Two new C21 steroidal glycosides, brapreguanes A and B (1–2) were isolated from 75 % aqueous ethanol extract of Selaginella braunii Baker. Their structures were established by spectroscopic analyses (1D/2D NMR spectra and HR‐ESI‐MS). The absolute configurations of sugar were elucidated by enzymatic hydrolysis and GCMS analysis. In addition, all compounds were evaluated for the anti‐proliferative activities against various human cancer cells in vitro. Compounds exhibited no inhibition to various human cancer cells.
A comprehensive bioinformatic analysis revealed novel MicroRNA biomarkers of Parkinson's disease
Authors: Rahimpour Alireza , Heidarzadehpilehrood Roozbeh , Abdollahi Sepideh , Ranjbari Haidar , Shams Zinat , Ghasemi Seyed Abbas , Najmaei Shima , Pirhoushiaran Maryam
Published: September 2022

Parkinson's disease (PD) is categorized as a neurodegenerative disorder. Different studies have focused on the role of microRNAs (miRNAs) on PD progression. Due to its complexity in initiation and progression, a considerable requirement has arisen to identify novel miRNA biomarkers in a noninvasive manner. In silico analysis has been used to select differentially expressed miRNAs (DE‐miRNAs) and key pathways in this disease. In this manner, several data sets of different neurodegenerative diseases have been analyzed to purify the findings of the present study. Totally, 15 DE miRNAs showed significant changes compared to healthy controls and other neurodegenerative diseases. Then, the targets of the miRNAs were predicted through miRTarBase and TargetScan databases. Besides, enrichment analysis was implemented for predicted target genes. Most of the target genes were enriched in the TRAIL signaling pathway, Regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolism, protein serine/threonine kinase activity, and Cytoplasm. Moreover, a protein−protein interaction network was constructed to find the most key DE miRNAs and targets in this disease. The results of the present study may help researchers shed light on the discovery of novel biomarkers for PD.
False lumen patency status and outcomes after endovascular repair of uncomplicated chronic type B dissection
Authors: Kong Minjian , Ni Ming , Zhu Xian , Qian Jianfang , Duan Qunjun , Song Jiangwei , Feng Zhanzeng , Dong Aiqiang
Published: September 2022

Background

Thoracic endovascular aortic repair (TEVAR) remains a controversial treatment for uncomplicated chronic type B aortic dissection (cTBAD). This study was performed to investigate the postoperative outcomes of TEVAR, such as survival and reintervention, and the risk factors for prognoses.

Methods

In total, 41 patients with uncomplicated cTBAD who underwent TEVAR from 2014 to 2021 were reviewed. The patients were divided into two groups: those with false lumen complete thrombosis (FLCT) and false lumen partial thrombosis (FLPT) based on computed tomography angiography (CTA) images. Kaplan–Meier analysis was performed to estimate survival and freedom from reintervention. Binary logistic analysis was performed to estimate risk factors for partial thrombosis.

Results

During a mean follow‐up of 31 (1–78) months, five deaths and six reinterventions had occurred at 5 years. By 1 week, thoracic FLCT had occurred in 23 (56.1%) patients and thoracic FLPT had occurred in 18 (43.9%). The rate of freedom from reintervention was significantly lower in the FLCT than in the FLPT group (p = 0.04). The 5‐year survival rate of the two groups was not statistically significant (p = 0.14). Risk factors for thoracic FLPT were the distance between the re‐entry site and the graft (p = 0.02) and the proximal oversizing ratio (p = 0.04).

Conclusions

TEVAR is an effective and safe treatment for uncomplicated cTBAD and has a low mortality rate. Thoracic FLCT is associated with less reintervention, but overall survival is not impacted by this difference. Patients treated with TEVAR without certain risk factors can have a good prognosis.
Antisynthetase Syndrome after chikungunya infection: A case report
Authors: Tuão Raiza Cansian , Macabú Mariana de Oliveira , Athayde Paula dos Santos , Moulaz Isac Ribeiro , Dalmaso Barbara Ferraço , Cristo Valéria Valim , Machado Ketty Lysie Libardi Lira
Published: September 2022

Chikungunya is an arboviral disease caused by a virus with wide geographical distribution in endemic areas. This case report documents a patient with antisynthetase syndrome post‐chikungunya infection. Autoimmune diseases result from breakdown of immune tolerance. Among all triggers, viruses represent the greatest environmental potential to precipitate inflammatory myopathy.
COVID‐19 vaccination and alopecia areata: a case report and literature review
Authors: Ganjei Zakiye , Yazdan Panah Mohammad , Rahmati Rahem , Zari Meidani Fatemeh , Mosavi Azam
Published: September 2022

Coronavirus disease 2019 (COVID‐19) is a major concern worldwide and various vaccines have been developed and approved for it, however some immune‐related issues of COVID‐19 vaccines should be considered and individualized for patients. In this study we report two cases of rapidly progressive hair loss following COVID‐19 vaccination.
Phase Control of Lithium Silicates for Process‐Friendly Prelithiated SiO Anode Materials**
Authors: Bhat Asif , Sireesha Pedaballi , Chen Yue‐Sheng , Su Yu‐Sheng
Published: September 2022

A low‐level metallic lithium thermal prelithiation strategy has been developed for boosting the performance of SiO anode materials with aqueous slurry processability. This facile prelithiation method can alter the phase and crystalline size of lithium silicates by controlling the parameters such as lithium contents and processing temperatures. The prelithiated graphene‐SiO composite anode material thus obtained under the optimized condition offers a high reversible capacity of 1062 mAh g−1 and the initial Coulombic efficiency of 80.8 %. Additionally, both the cycle life and cycling Coulombic efficiency are extremely stable, preserving over 90.3 % of the capacity after 200 cycles and more than 99.7 % of the efficiency on average during cycling. The significantly enhanced battery performance of the prelithiated SiO anode materials is owing to the size control of crystal silicon and Li2SiO3 phases. The existence of Li2Si2O5 and suppression of Li4SiO4 formation also guarantee homogeneous prelithiation results. This facile low‐level prelithiation approach is remarkably effective to improve the initial Coulombic efficiency for commercial SiO anode materials and simultaneously maintain superior reversible capacity, cycle life, cycling efficiency, and aqueous slurry processability.
Ermittlung der mechanischen Eigenschaften eines Silikondichtstoffs
Authors: Sitte Sigurd
Published: September 2022

Die Kenntnis der mechanischen Dichtstoffeigenschaften ist erforderlich, um Verhalten und Leistungsfähigkeit wetterseitiger Dichtfugen zu beurteilen. Fassadeningenieure und Projektplaner sind oftmals daran interessiert, Dichtstoffe über die in technischen Datenblättern genannten Grenzen hinaus einzusetzen oder suchen nach verlässlichen Messergebnissen als Basis für detaillierte Berechnungen, z. B. mit Finite‐Element‐Methoden bei seismischer Belastung oder sehr großen Fassadenelementen. Zur korrekten Auslegung von Dichtfugen ist die Kenntnis der maximal zu erwartenden Fugenbewegungen sowie anderer Einflussfaktoren erforderlich (z. B. Bewitterung, Strahlung, Verschmutzung, Fassadenreinigungsmittel). Ein in Europa verbreiteter Silikondichtstoff für Fassaden ist DOWSIL™ 791. Da für diesen Dichtstoff bisher nur wenige Daten bekannt waren, wurde eine Untersuchung zur Ermittlung der mechanischen Eigenschaften gestartet. Durchgeführt wurden verschiedene Standardtests sowie Prüfungen spezieller Proben mit realen Fugengeometrien. Mit den Erkenntnissen können Dichtfugen ausgelegt und der Versagenspunkt bestimmt werden.

Evaluation of mechanical properties for a weatherproofing silicone. The knowledge of mechanical sealant properties is mandatory to understand and predict behaviour and performance of weatherproofing joints. Facade engineering consultants and project planners regularly rise questions to understand, if weatherproofing sealants could be used in applications requiring higher movement capabilities than declared in technical datasheets or if measured data are available for advanced calculation methods such as finite element analysis. This can be required in case of seismic events, for very large pane sizes or high movements. To specify correctly sealant dimensions it is mandatory to know the maximum movements. Applied movements must be safely below the maximum capability of the sealant, considering many load cycles and long‐term ageing (e. g. weathering, sun radiation, facade cleaning products, dirt and air pollution). One of the most commonly used silicone weatherproofing sealant for facades in Europe is DOWSIL™ 791. Because only few data are available for this product, an evaluation has been performed and should help to understand better the mechanical properties and behaviour of this product. Both sample testing following to standardized test methods and specifically designed sample shapes illustrating the joint in its function were used. Using the results of this evaluation, weatherproofing joints can be dimensioned more safely and the failure point can be predicted.
Der Weg zur erfolgreichen baupraktischen Umsetzung von tragenden Silikonklebfugen in Deutschland
Authors: Baitinger Mascha , Wachter Nicolas , Teich Martien
Published: September 2022

Die Anwendung der Klebtechnik im Glasfassadenbau erfordert bereits in frühen Projektphasen die sorgfältige Wahrnehmung von Planungsaufgaben und Abstimmung zwischen den Projektbeteiligten. Um Fehler zu vermeiden, bedarf es besonderer theoretischer und praktischer wie auch baurechtlicher Kenntnisse. Neben dem konstruktiven Entwurf sowie umfassender Berechnungs‐ und Bemessungsaufgaben nimmt die klebtechnische Ausführung und Qualitätssicherung eine entscheidende Rolle ein. Aktuelle Kenntnisse zur erfolgreichen Umsetzung tragender Silikonklebfugen finden sich im Merkblatt FKG 01/2021. Der folgende Artikel fasst die wichtigsten Punkte des Merkblatts zusammen, die es bei strukturellen Klebfugen konkret zu beachten gilt.

Successful practical implementation of load‐bearing silicone adhesive joints in Germany. The application of adhesive bonding technology in glass facade construction requires the careful performance of planning tasks and coordination between the project participants already in the early project phases. In order to avoid mistakes, special theoretical and practical knowledge as well as knowledge of regulatory rules is required. In addition to the structural design, calculation methods and static dimensioning, adhesive bonding and quality assurance play a decisive role. Current knowledge on the successful implementation of load‐bearing silicone adhesive joints can be found in the Technical Note FKG 01/2021. The following article summarises the most important points of the Technical Note that must be specifically observed for structural adhesive joints.
Regiodivergent Asymmetric Pyridinium Additions: Mechanistic Insight and Synthetic Applications
Authors: Grigolo Thiago A. , Smith Joel M.
Published: September 2022

A practical protocol for the first regiodivergent asymmetric addition of aryl and alkenyl organometallic reagents to substituted N‐alkyl pyridinium heterocycles is described. The couplings proceed with high regiochemical and stereochemical selectivities, and provide access to chiral 1,2,3‐ and 1,3,4‐trisubstituted dihydropyridine products, controlled by judicious choice of nitrogen activating agent. To this end, a correlation was found between the parameterized size of the activating group and the C2/C4 regioselectivity in the couplings. The utility of the described chemistry was demonstrated in two concise asymmetric syntheses of (+)‐N‐methylaspidospermidine and (−)‐paroxetine.
Overview on Grant Writing for Graduate Student Research
Authors: Smith Diane , Chowdhury Abu Sayeed , Oxford Julia Thom
Published: September 2022

Grant writing is an important skill to develop during graduate school. This article provides an overview of grant writing for graduate students. Specific topics covered include understanding your funding needs, identifying appropriate grant opportunities, analyzing the guidelines for the proposal, planning and time management, understanding the priorities of the funding agency or organization, proposal organization and writing strategies, additional forms and letters of support that may be required, the editing and revising process, and submission of your grant proposal. Courses and workshops are an efficient and effective way to be guided through the grant proposal writing process with a greater potential for positive outcomes. © 2022 Wiley Periodicals LLC.
Thickness and yttria percentage influences the fracture resistance of laminate veneer zirconia restorations
Authors: Malallah Ali Dhahee , Hasan Nadia H.
Published: September 2022

Objectives

Mechanical properties are cardinal for the long‐term clinical success of laminate veneer restorations but the selection of new restorative materials should ideally be based on clinical evidence, therefore, in vitro testing of dental materials is a good alternative to evaluate their properties and understand their behavior so this study aimed to compare and evaluate the effect of two different thicknesses and yttria percentage on the fracture resistance of laminate veneer zirconia restorations.

Materials and Methods

Forty laminate veneer restoration prepared from partial sintering zirconia of 3Y (yttria), 5Y (yttria), combined 3Y&5Y (yttria), and lithium disilicate. Specimens were assigned into four main groups according to their percentage of yttria content (n = 10) and subgrouped into two thicknesses (0.5 mm thickness and 0.3 mm thickness) (n = 5) as follows: Group I, II, III, and IV (Group I for lithium disilicate (control), Group II for 3Y zirconia, Group III for 5Y zirconia, and Group IV for combined 3Y&5Y zirconia), each of them subdivided according to their thickness into two subgroups (n = 5 for each one) and resistance to fracture for each restoration was evaluated using a universal testing machine. Data were analyzed using a one‐way analysis of variance and Duncan's tests at a 5% level of significance.

Results

The thickness of laminate veneer restoration significantly affects the fracture resistance value of all type of laminate veneers restorations (fracture resistance mean value was highest for 0.5 mm thickness and lower for 0.3 mm thickness restorations) and yttria percentage significantly affect fracture resistance value of zirconia laminate veneer restorations (fracture resistance mean value was highest for 0.5 mm thickness of 3Y zirconia [865 N] and combined 3Y&5Y zirconia [846 N]).

Conclusions

Reducing the thickness of laminate zirconia veneer restorations to 0.3 mm reduces its fracture resistance and increasing yttria percentage had an adverse effect on fracture resistance of zirconia laminate veneer restorations.
A generalized analysis of high‐order N‐path filters
Authors: Moradino Vahid , Najafiaghdam Esmaeil
Published: September 2022

In N‐path filter analysis, assumptions are used to simplify their analysis to avoid the complexity of the calculations. These assumptions limit the number of examinable circuits. This paper analyzes a general system including an arbitrary number of N‐path filters to generalize the analysis. In the proposed method, due to the calculation of harmonic transfer functions for each independent capacitor in each time interval, it is possible to examine N‐path filters in the presence of common capacitors between multiple branches, leakage resistors, and branches with asymmetric switching. The absence of discontinuous jumps during the switching moments and switching operation in a non‐overlapping fashion with a specified periodicity are the only assumptions of the proposed method. As a result, more LPTV (linear periodically time‐varying) systems can be analyzed using the calculations provided. After presenting the method, we show the proposed method's ability by analyzing a recently published impedance‐transforming N‐path filter and examining its details.
Magnesium Promoted Active and Isoselective ROP of rac‐Lactide and ϵ‐Caprolactone Under Mild Conditions
Authors: Sagar Shweta , Bano Kulsum , Sarkar Alok , Pal Kuntal , Panda Tarun K.
Published: September 2022

A novel amidophosphine sulfur‐supported magnesium complex, [Ph2P(S)NCH2CH2N−(CH2CH2)O]Mg(C4H9)(THF)] (2) enabling efficient ring‐opening polymerization of rac‐lactide (LA) and ϵ‐caprolactone (CL) is disclosed. Achieved incredible selectivity for ROP of rac‐lactide for the first time using a magnesium catalyst affording isoselective PLA with a Pi value of 0.77. The polymerization of rac‐LA as well as ϵ‐CL proceeded under mild reaction conditions in absence of any external initiator, to yield corresponding polyesters with a great control over the molecular weight. The kinetic studies reveal that both sulfur and magnesium centers simultaneously work together to drive high yield and selectivity.
Near‐Infrared Squaraine Dyes as Bright Fluorescent Probes: A Structure–Activity Photophysical Investigation in Liposomes
Authors: Renno Giacomo , Cardano Francesca , Ilieva Viktoria , Viscardi Guido , Fin Andrea
Published: September 2022

The efficient investigation of biological membranes is a constant demand in chemical biology. Several families of Near Infra‐Red (NIR) dyes have been already studied for the selective staining of a plethora of biological structures, macro and supramolecular assemblies. In this context, a small library of symmetrical and unsymmetrical NIR squaraine dyes have been synthetized and investigated as fluorescent probes to stain the lipid bilayer membrane in large unilamellar vesicles (LUVs) as cell membrane model. The hydrophobic‐hydrophilic character of the NIR dyes has been modulated by introducing carboxylic moieties on the aromatic core, as well as by varying the length of the alkyl chains used in the quaternarization of the indolenine nitrogen. The photophysical properties and the kinetic of the insertion into different LUVs models have been analysed with respect to the probe structures. The discussed results represent versatile key data to support the design of new NIR sensors for bioimaging.
Interplay between cellular changes in the knee joint, circulating lipids and pain behaviours in a slowly progressing murine model of osteoarthritis
Authors: Gowler Peter R. W. , Turnbull James , Shahtaheri Mohsen , Walsh David A. , Barrett David A. , Chapman Victoria
Published: September 2022

Background

Synovial inflammation has known contributions to chronic osteoarthritis (OA) pain, but the potential role in transitions from early to late stages of OA pain is unclear.

Methods

The slowly progressing surgical destabilization of the medial meniscus (DMM) murine OA model and sham control, was used in male C57BL/6J mice to investigate the interplay between knee inflammation, plasma pro‐ and anti‐inflammatory oxylipins and pain responses during OA progression. Changes in joint histology, macrophage infiltration, chemokine receptor CX3CR1 expression, weight bearing asymmetry, and paw withdrawal thresholds were quantified 4, 8 and 16 weeks after surgery. Plasma levels of multiple bioactive lipid mediators were quantified using liquid chromatography with tandem mass‐spectrometry (LC–MS/MS).

Results

Structural joint damage was evident at 8 weeks post‐DMM surgery onwards. At 16 weeks post‐DMM surgery, synovial scores, numbers of CD68 and CD206 positive macrophages and pain responses were significantly increased. Plasma levels of oxylipins were negatively correlated with joint damage and synovitis scores at 4 and 8 weeks post‐DMM surgery. Higher circulating levels of the pro‐resolving oxylipin pre‐cursor 17‐HDHA were associated with lower weight bearing asymmetry at week 16.

Conclusions

The transition to chronic OA pathology and pain is likely influenced by both joint inflammation and plasma oxylipin mediators of inflammation and levels of pro‐resolution molecules.

Significance

Using a slow progressing surgical model of osteoarthritis we show how the changing balance between local and systemic inflammation may be of importance in the progression of pain behaviours during the transition to chronic osteoarthritis pain.
Production prediction and main controlling factors in a highly heterogeneous sandstone reservoir: Analysis on the basis of machine learning
Authors: Wang Zhao , Tang Hongming , Cai Hui , Hou Yawei , Shi Hongfu , Li Jingling , Yang Tao , Feng Yutian
Published: September 2022

Owing to a lengthy oil‐bearing interval, strong anisotropism, and significant difference in the fluid properties of the sandstone oil reservoir in P Oilfield, it is quite challenging to accurately the productivity of the oil well at the initial stage. In this study, a deep neural network model is established, based on a gradient boosting algorithm, XGBoost, to forecast the initial productivity of oil wells, followed by an evaluation of the main controlling factors of productivity. One hundred oil wells in the study area were divided into training and verification groups. With a specific productivity index of an oil well with a stable period of approximately 6 months at the initial production stage as the target data, and geological, engineering, and oil reservoir parameters as input data, hyper‐parameters for adjustment and optimization were selected, and a deep‐learning‐based unconsolidated sandstone productivity forecast model was established to forecast the initial productivity of oil wells in the target area. The mean square root error of the forecast result was <0.15, which is highly consistent with actual productivity. Finally, by adopting the XGBoost algorithm, the weight ranking of the controlling factors of productivity was clarified as follows: microscopic pore structure parameter > crude oil viscosity > median grain size > lithology index > well completion method > flow zone indicator. Machine learning has the advantages of effective forecasting of oil well productivity and the main controlling factors using multiple dimensions and big data.
Solar‐light‐driven ZnO/biochar treatment of pesticides contaminated wastewater: A practical and computational study
Authors: Samy Mahmoud , Gar Alalm Mohamed , Ezeldean Eman , El‐Dissouky A. , Badr Nadia B. E. , Al‐Muhtaseb Ala'a , Alhajeri Nawaf S. , Osman Ahmed I. , Tawfik Ahmed
Published: September 2022

Biochar (BC) was prepared by carbonizing sludge from agricultural lignocellulosic waste fermentation and then used to adsorb lambda‐cyhalothrin (LM), malathion (MA), and oxamyl (OX) as potential pesticides in agrochemical industrial wastewater. Additionally, the photodegradation performance of ZnO and ZnO/Fe was evaluated using various catalyst doses in a constructed parabolic solar collector reactor. The optimal ZnO catalyst dose and reaction time was 1.0 g/L and 135 min. OX, MA, and LM removal increased from 38%, 30%, and 24% in pristine ZnO to 55%, 70%, and 46.9% in the case of the addition of BC with ZnO (ZnO/BC), respectively. The doping of ZnO with iron did not improve the photodegradation efficiency due to the reduction of crystallinity and catalyst affinity towards the pollutants after introducing those ions. The mechanism of degradation was proposed, and the by‐products generated were identified. The total cost was estimated for pure ZnO, the addition of BC with ZnO (ZnO/BC), and the addition of BC with iron‐doped ZnO (ZnO/Fe/BC). The highest binding energy of −44.74 was recorded for BC–OX complex, followed by BC–LM at −42.97. The adsorption of LM, MA, and OX by ZnO/BC is primarily due to the hydrophobic interaction, hydrogen bonding, and π–π interaction. After three cycles of recycling ZnO/BC, the degradation efficiency remained 55–52.5% for OX, 70–65% for MA, and 46.9–42.8% for LM, indicating excellent reusability and stability of the composite catalyst. The low cost of the solar‐light‐driven ZnO/BC process may improve the technique's feasibility for large‐scale implementation.
Phenolic compounds of sugar beet (Beta vulgaris L.): Separation method, chemical characterization, and biological properties
Authors: Arjeh Edris , Khodaei Seyedeh Mahsa , Barzegar Mohsen , Pirsa Sajad , Karimi Sani Iraj , Rahati Shiva , Mohammadi Farzad
Published: September 2022

Sugar beet (Beta vulgaris L.) is a good source of bioactive compounds. However, information on the biological properties of sugar beet root is limited and its beneficial effects have not been completely understood. In this work, 10 phenolic compounds have been separated and identified in various parts of sugar beet for the first time, including the most abundant epicatechin (31.16 ± 1.89 mg/100 g), gallic acid (30.57 ± 2.69 mg/100 g), and quercetin‐3‐O‐rutinoside (30.14 ± 3.63 mg/100 g). The biological activity tests indicated that sugar beet peel potently scavenged the nitric oxide and DPPH (2,2‐diphenyl‐1‐picrylhydrazyl) free radicals with IC50 values of 88.17 ± 05.14 and 28.77 ± 0.62 μg/ml, respectively. In addition, sugar beet peel exhibited the highest reducing power, IC50 values of 11.98 ± 1.20 μg/ml, and the highest ion‐chelating activity, IC50 values of 48.52% and 55.21% for cupric and ferrous ions at 250 μg/ml, respectively. Compared to synthetic antioxidants, sugar beet showed promising biological activities, which could be considered further in future studies.
Primary health care in China: A decade of development after the 2009 health care reform
Authors: Wu You , Zhang Zeyu , Zhao Ning , Yan Yue , Zhao Lina , Song Qi , Ma Rong , Li Changfeng , Li Jinyi , Liu Suibin , Bi Xinran , Zhang Zongjiu
Published: September 2022

Over 40 years ago, primary health care (PHC) was defined in the Alma‐Ata Declaration as a critical component of the health care system to address the basic health demand of the people. In China, the Government attaches great importance to health care at the primary level. After the launch of the historical Reform of the Medical and Health Care System in 2009, the PHC system in China has witnessed major progress and breakthroughs, especially in its steadily increased capacity, continuously improved accessibility, and betterment in equality. In this review, we summarized published literatures and official policies, synthesized data from the electronic registration information system of the National Health Commission, national statistical reports, and yearbooks in health care. The review is intended to describe the systematic development of PHC in China in the last decade. The main results include: the solid national policy foundation, increasing number of PHC institutions and workforce, better training of PHC professionals, major achievements in primary health indicators, government financial support to PHC institutions, improved PHC budgeting and insurance coverage, and the advancement of supporting technologies. Challenges and prospects are also discussed.
Multistep screening and selection of COVID‐19 convalescent plasma donors at the early stage of the SARS‐CoV‐2 pandemic: A retrospective analysis
Authors: Brosig Andreas M. , Ossner Thomas , Pamler Irene , Friedinger Susanne , Bica Adelina‐Florina , Mohrez Morad , Tlili Ikram , Mueller Viktoria , Becke Christine , Haehnel Viola , Baeuerlein Veronika , Stemmer Barbara , Burkhardt Ralph , Offner Robert
Published: September 2022

Background and Aims

The COVID‐19 pandemic reached Bavaria in February 2020. Almost simultaneously, Chinese physicians published reports on the first successful treatments with plasma from COVID‐19 convalescent donors. With these silver linings on the horizon, we decided to establish the manufacturing of anti‐severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) antibody‐containing plasma from COVID‐19 convalescent donors at our site. Here we describe our donor selection process, built from the ground up, which enabled us to cope with the immense resonance after our social media call for donors.

Methods

As a first step, we created a specific questionnaire for telephone interviews applied by trained students to filter the wave of callers interested in plasma donation. Afterward, the medical staff evaluated the hotline questionnaires and chose eligible donors to be invited for on‐site donor evaluation. Data documentation was performed with MS Excel, and statistical analyses were calculated with GraphPad Prism 8. A quantitative in‐house ELISA was used to detect anti‐SARS‐CoV‐2 antibodies and determine specific titers.

Results

Out of 1465 calls from potential plasma donors, we could register 420 persons with a completed questionnaire. Evaluation of questionnaires identified 222 of 420 persons as eligible for donation, and 55 were directly asked for on‐site donor qualification. Subsequently, as anti‐SARS‐CoV‐2 antibody titers ≥1:800 were required, we invited 89 of 222 potential donors for an antibody screening. This procedure resulted in another 28 potential donors for an on‐site evaluation. Finally, 12 donors qualified with a titer of 1:400 and 24 with ≥1:800.

Conclusion

Identifying suitable COVID‐19 convalescent plasma donors was expected to be highly time‐consuming. Implementing a screening procedure with our hotline questionnaire helped us streamline the donor selection process and reduce the workload for the staff. We propose combining the described selection process with the later introduced on‐site antibody screening as an effective strategy.
Thermal Transients in Three‐Core Power Cable Systems: First Principle Modelling and Verification
Authors: Brynem Frode , Kokkula Satyanarayana
Published: September 2022

This paper presents research related to developing a thermal model for three‐core power cable systems used in offshore wind farms. Three‐core power cable systems are a significantly more complicated thermo‐electrical system than single‐core power cables, primarily due to the geometric asymmetry and the number of heat sources. There are tools available that can model thermal transients in three‐core cable systems, but these tools demand a nontrivial level of prerequisite knowledge and training on the part of the user. Therefore, this research aimed at developing and testing a first principle model specifically tuned for thermal transients in three‐core cables. The model has been tested by comparing its predictions with empirical temperature data collected from heat cycle testing on three‐core cables at Nexans' facilities. To increase the quality of the predictions, part of the research was also to measure the thermal properties of swellable tape and filling compound (used in three‐core cables). The first principle model's predictions correspond well with the empirical data, the research results are promising. The model must be tested more thoroughly with different use cases before it can complement or replace current working methods.
Complexity identification in major infrastructure project information systems using graph theory
Authors: Murphy Joseph , Dickerson Charles , Thorpe Tony , Goodier Chris , Zahiroddiny Sonia , Pestana Andrew
Published: September 2022

Information management for major infrastructure projects is a critical task requiring ever increasing time and resources. Whilst the digitisation of construction industry information has progressed over multiple dimensions, there are still gaps in machine readable information for adequate suitability assessment of projects against their requirements. With digital twins at the heart of the digitisation agenda, it is vital that the industry expand the information available to validate and verify asset and network outcomes throughout their lifecycle. Within the construction industry, systems engineering is being deployed for asset and information requirements and model‐based systems engineering can support digital techniques in managing construction information requirements. However, as an intensive task it must be selectively deployed to obtain value within a complex operating system. An opportunity exists to use data and relationships held in electronic document management systems that currently store project requirements. To achieve this, graph/network theory can be used to visualise and analyse the connectivity of document datapoints. This study deploys a python modelling environment to create digraphs that are used to visualise and identify key data from a document management system, identifying the highest degree and betweenness for documents from a sample size of 20 queries producing 327 vertices. It demonstrates a useful means of interrogating the data rapidly that is quick to scale and expand. There are opportunities to deploy this across multiple digital systems to further map complexity and interactions between them. Identification is the critical first step for data driven point of application ‘surgical’ model‐based systems engineering.
Serious Games with SysML: Gamifying Threat Modelling in a Small Business Setting
Authors: Georgsen R.E. , Køien G. Myrdahl
Published: September 2022

This paper describes using casual games to capture and disseminate expert security knowledge with a digital model at a small company. Most companies in the global supply chain are Very Small Entities (VSE), meaning they employ five (5) to twenty‐five (25) people. These companies represent a risk because they have little to no security proficiency and limited resources and incentive to prioritize system security. Moreover, this is a hidden risk because the companies higher up in the supply chain rely on contractual mechanisms to enforce compliance with security requirements. Small companies rely on informal methods in their daily work and are resistant to change. Threat modelling in the context of Agile Model‐Based Systems Engineering (AMBSE) can provide VSEs with a structure that allows them to retain their informal operational agility. When modelling using games, the security expert plays the dual role of modeler and educator, and the engineering team is gaining security proficiency, improving the quality of both their current and future work. Players reported improved understanding of other stakeholders' perspectives. Agility, proficiency, and stakeholder alignment are among the critical foundation concepts identified by the INCOSE led Future of Systems Engineering Initiative (FuSE) to improve system security.
Situational awareness and human factors when designing complex systems
Authors: Helle Dag Eirik , Frølich Marcus , Langen Tommy , Muller Gerrit
Published: September 2022

The background for this paper is to prepare for the execution of a research project in systems engineering about situational awareness and human factors. The authors use a major defense company as the case for this research. The company is developing a new weapon system that allows one operator to operate multiple remote weapon systems. The systems will produce a large amount of data that the operators must use in their decision‐making process. To make the right decisions, the operators need good situational awareness.

The authors have examined publications about situational awareness and human factors and elaborated on the research design for the upcoming research project. Findings in the literature suggest that situational awareness consists of three levels. In all three levels, several factors affect an operator's ability to build and maintain situational awareness. The hypothesis for the upcoming research project is that the company lacks in‐depth knowledge about situational awareness.
Revisiting the synthesis of bis(2‐hydroxy‐3,5‐di‐t‐butylphenyl)methanone
Authors: Lin Xin‐Jie , Huang Shih‐Peng , Huang Min‐Jie , Wang Chien‐Lung , Peng Chi‐How , Liu Hsueh‐Ju , Wu Yen‐Ku
Published: September 2022

Described is our effort toward establishing a practical and sustainable synthesis of bis(2‐hydroxy‐3,5‐di‐t‐butylphenyl)methanone. In it, we found the phenol‐aldehyde condensation could be efficiently catalyzed by sulfonic acid‐functionalized microporous carbon spheres (MCS‐SO3H). Additionally, we developed practical and sustainable procedures for the synthesis of the title ligand by applying readily available reagents in lieu of toxic chromium trioxide and fuming boron tribromide.
Validation of high concentrated thrombin time assay for unfractionated heparin monitoring
Authors: Apipongrat Dollapak , Police Pornnapa , Lamool Rattapan , Butthep Punnee , Chantkran Wittawat
Published: September 2022

Background

The high concentrated thrombin time (hcTT), a thrombin time modified by increasing the thrombin concentration, is a possible alternative assay to activated partial thromboplastin time (aPTT) in unfractionated heparin (UFH) monitoring. This study aimed to determine the optimal thrombin concentration used in the hcTT assay for UFH monitoring.

Methods

A total of 30 blood samples obtained from healthy volunteers were included in this study. Thrombin concentrations of 10.0, 15.0, 20.0, and 25.0 IU/ml were used in the hcTT assay. The consistency between the hcTT and anti‐FXa assays was evaluated. To validate the hcTT assay, linearity, repeatability, reproducibility, and diagnostic performance of the assay were assessed.

Results

The hcTT assay using thrombin concentration of 15.0 IU/ml showed a strong correlation to the anti‐FXa assay with R2 of 0.72 and the Spearman's correlation coefficient (rs) of 0.97 (95% CI, 0.96–0.98). Within‐run and day‐to‐day run variabilities of the assay were satisfactory (all coefficients of variation <10%). We found an excellent correlation between the results which were measured using different reagents with intra‐ or inter‐laboratory instruments. Notably, as compared to the aPTT assay, the hcTT assay showed a significantly better performance in identifying the samples which contain UFH at the supratherapeutic level, with an AUC of 0.97 vs. 0.91, p = 0.049.

Conclusion

The hcTT assay can be used as an alternative assay for UFH therapy monitoring. A further study using clinical samples is recommended to confirm the appropriateness of the hcTT assay for clinical application.