bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunophenotyping characteristics of COVID‐19 patients: Peripheral blood CD8+ HLA‐DR+ T cells as a biomarker for mortality outcome
Authors: Mirsharif Ensie Sadat , Chenary Maryam Rajabnia , Bozorgmehr Mahmood , Mohammadi Saeed , Hashemi Seyed Mahmoud , Ardestani Susan Kabudanian , Beigmohammadi Mohammad‐Taghi , Abdollahi Alireza , Sadeghipour Alireza , Kariminia Amina , Tuserkani Fatemeh , Ghazanfari Tooba
Published: October 2022

Introduction

The goal of this study was to identify biomarker(s) to assign risk of mortality in COVID‐19 patients to improve intensive care unit (ICU) and coronary care unit  management. A total of 100 confirmed COVID‐19 patients admitted at Imam Khomeini Hospital in Tehran, were compared to 70 control subjects. Peripheral blood leukocyte was studied using staining reagents included CD3, CD4, CD8, HLA‐DR, CD19, CD16, and CD56. The immunophenotyping analysis was evaluated using the FACSCalibur instrument. To investigate the cell density of lung infiltrating T cells, postmortem slides of needle necropsies taken from the lung tissue of 3 critical patients were evaluated by immunohistochemistry staining. The number of lymphocyte subpopulations was significantly lower in COVID‐19 patients than in the control group. Regarding the disease severity, the absolute count of T, NK, and HLA‐DR+ T cells were significantly reduced in severe patients compared to the moderate ones. The critical patients had a significantly lower count of CD8‐HLA‐DR+ T cells than the moderate cases. Regarding the disease mortality, based on univariate analysis, the count of HLA‐DR+ T, CD8− HLA‐DR+ T, and CD8+ HLA‐DR+ T cells was associated with mortality in COVID‐19 patients. Receiver operating characteristic curve analysis showed the count of CD8+ HLA‐DR+ T cells is the best candidate as a biomarker for mortality outcome. Furthermore, pulmonary infiltration of T cells in the lung tissue showed only slight infiltrations of CD3+ T cells, with an equal percentage of CD4+ and CD8+ T cell subpopulation in the lung tissue. These findings suggest that close monitoring of the value of CD8+ HLA‐DR+ T cells in COVID‐19 patients may be helpful to identify high‐risk patients. However, further studies with larger sample size are needed.
Biosynthesis of poly(3‐hydroxybutyrate‐co‐3‐hydroxvalerate) from volatile fatty acids by Cupriavidus necator
Authors: Cai Fanfan , Lin Ming , Jin Wenxiong , Chen Chang , Liu Guangqing
Published: October 2022

A promising strategy to alleviate the plastic pollution from traditional petroleum‐based plastics is the application of biodegradable plastics, in which polyhydroxyalkanoates (PHAs) have received increasing interest owing to their considerable biodegradability. In the PHAs family, poly(3‐hydroxybutyrate‐co‐3‐hydroxvalerate) (PHBV) has better mechanical properties, which possesses broader application prospects. With this purpose, the present study adopted Cupriavidus necator to synthesize PHBV utilizing volatile fatty acids (VFAs) as sole carbon sources. Results showed that the concentration and composition of VFAs significantly influenced the production of PHAs. Especially, even carbon VFAs (acetate and butyrate) synthesized only poly(3‐hydroxybutyrate) (PHB), while the addition of odd carbon VFAs (propionate and valerate) resulted in PHBV production. The 3‐hydroxyvalerate (3HV) contents in PHBV were directly determined by the specific VFAs compositions, in which valerate was the preferred substrate for 3HV accumulation. After optimization by response surface methodology, the highest PHBV accumulation achieved 79.47% in dry cells, and the conversion efficiency of VFAs to PHBV reached 40%, with the PHBV production of 1.20 ± 0.05 g/L. This study revealed the metabolic rule of VFAs converting into PHAs by C. necator and figured out the optimal VFAs condition for PHBV accumulation, which provides a valuable reference for developing downstream strategies of PHBV production in industrial applications in future.
High‐energy open‐fracture model with initial experience of fluorescence‐guided bone perfusion assessment
Authors: Demidov Valentin V. , Clark Megan A. , Streeter Samuel S. , Sottosanti Joseph S. , Gitajn Ida Leah , Elliott Jonathan Thomas
Published: October 2022

High‐energy orthopedic injuries cause severe damage to soft tissues and are prone to infection and healing complications, making them a challenge to manage. Further research is facilitated by a clinically relevant animal model with commensurate fracture severity and soft‐tissue damage, allowing evaluation of novel treatment options and techniques. Here we report a reproducible, robust, and clinically relevant animal model of high‐energy trauma with extensive soft‐tissue damage, based on compressed air‐driven membrane rupture as the blast wave source. As proof‐of‐principle showing the reproducibility of the injury, we evaluate changes in tissue and bone perfusion for a range of different tibia fracture severities, using dynamic contrast‐enhanced fluorescence imaging and microcomputed tomography. We demonstrate that fluorescence tracer temporal profiles for skin, femoral vein, fractured bone, and paw reflect the increasing impact of more powerful blasts causing a range of Gustilo grade I–III injuries. The maximum fluorescence intensity of distal tibial bone following 0.1 mg/kg intravenous indocyanine green injection decreased by 35% (p < 0.01), 75% (p < 0.001), and 87% (p < 0.001), following grade I, II, and III injuries, respectively, compared to uninjured bone. Other kinetic parameters of bone and soft tissue perfusion extracted from series of fluorescence images for each animal also showed an association with severity of trauma. In addition, the time‐intensity profile of fluorescence showed marked differences in wash‐in and wash‐out patterns for different injury severities and anatomical locations. This reliable and realistic high‐energy trauma model opens new research avenues to better understand infection and treatment strategies. Level of evidence: Level III; Case–control.
The order of surgery and chemotherapy matters: Multimodality therapy and stage‐specific differences in survival in gastric cancer
Authors: Ramos‐Santillan Vicente , Friedmann Patricia , Eskander Mariam , Chuy Jennifer , Parides Michael , In Haejin
Published: October 2022

Background and Objectives

Multimodality treatment improves survival for gastric cancer (GC). However, the effect of treatment sequence by stage remains unclear. We aim to compare outcomes between patients receiving neoadjuvant(neoadj) and adjuvant chemotherapy (adj).

Methods

Nonmetastatic GC patients with clinical stage ≥ T2N0 who underwent both resection and neoadj or adj were identified using the National Cancer Database (2005−2014). Multivariable Cox regression analyses were performed on propensity score‐matched (PSM) cohorts stratified by stage to compare overall survival (OS).

Results

We identified 11 984 patients; 55% stage I (SI), 76% stage II (SII) and 57% stage III (SIII) received neoadj. Unadjusted analysis showed worse survival among SI neoadj patients (hazard ratio [HR] 1.195, confidence interval [CI] 1.04−1.38) and improved survival for SII (HR 0.93 CI 0.87−0.998) and SIII (HR 0.75, CI 0.68−0.84). After PSM, SI patients with neoadj had worse OS with increased risk of death compared to Adj (HR 1.186, CI 1.004−1.402). SII patients had no difference in OS (HR 0.98, CI 0.91−1.07) and SIII patients had improved OS (HR 0.78, CI 0.69−0.90).

Conclusions

In patients who received surgery and chemotherapy, the benefit of neoadj was limited to SIII with worse survival for SI. A clinical trial to examine the optimal sequence of chemotherapy is warranted.
High‐Throughput Multichannel Parallelized Diffraction Convolutional Neural Network Accelerator
Authors: Hu Zibo , Li Shurui , Schwartz Russell L. T. , Solyanik‐Gorgone Maria , Miscuglio Mario , Gupta Puneet , Sorger Volker J.
Published: October 2022

Convolutional neural networks are paramount in image and signal processing, and are responsible for the majority of image recognition power consumption today, concentrated mainly in convolution computations. With convolution operations being computationally intensive, next‐generation hardware accelerators need to offer parallelization and high efficiency. Diffractive optics offers the promise of low‐latency, highly parallel convolution operations. However, thus far parallelism is only partially harvested, thereby significantly underdelivering in comparison to its throughput potential. Here, a parallelized operation high‐throughput Fourier optic convolutional accelerator is demonstrated. For the first time, simultaneous processing of multiple kernels in Fourier domain enabled by optical diffraction orders is achieved alongside input parallelism. The proposed approach can offer ≈100× speedup over the previous generation optical diffraction‐based processor and 10× speedup over other state‐of‐the‐art optical Fourier classifiers.
Blood flow analyses by intraoperative transit‐time flow measurements of free flaps for head and neck reconstructions: A prospective single‐center study
Authors: Ritschl Lucas M. , Niu Minli , Wolff Constantin T. , Schwarz Matthias , Roth Maximilian , Wolff Klaus‐Dietrich , Fichter Andreas M.
Published: October 2022

Background

The behavior of blood flow changes within free flaps following microvascular anastomosis is not well described in the literature. The aim of this study was to determine the immediate blood flow behavior of different free flaps as reference values for various clinical applications.

Methods

Intraoperative transit‐time flow measurements were performed on patients receiving free flap transfer in the head and neck area comprising radial forearm flaps (RFF), peroneal artery perforator flaps (PAP), anterolateral thigh flaps (ALT), vastus lateralis flaps (VLF), parascapular flaps (PSF), latissimus dorsi flaps (LDF), fibula free flaps (FFF), deep circumflex iliac artery flaps (DCIA), and scapular flaps (SF). In accordance with a structured protocol, measurements took place at the pedicle directly before flap harvesting and at the recipient vessels 1 h after flap transfer. Heart rate, transplant weight, and other patient characteristics were recorded and analyzed.

Results

A total of 129 were enrolled, comprising 66 RFF, 8 ALT, 6 PAP, 11 VLF, 3 PSF, 2 LDF, 24 FFF, 7 DCIA, and 2 SF. In most of the transplant groups, arterial perfusion increased after anastomosis at the recipient site. The arterial pulsatility index developed indirectly proportionally to arterial blood flow, whereas venous blood drainage did not show any statistically significant changes. Muscle flaps had the highest arterial perfusion before flap transfer. Composite transplants with hard and soft tissue presented the greatest increase in arterial perfusion. The lowest arterial blood flow after anastomosis was measured in PAP and RFF. In contrast, RFF and PAP presented the highest arterial perfusion per 100 g transplant weight.

Conclusions

Arterial perfusion changed, whereas venous blood flow did not show any statistically significant variations in any transplant group. Perfusion of free flaps does not only depend on the recipient vessel and the recipient bed, but also on flap‐specific anatomy and physiology.
The use of vertical postero‐medial thigh flap as lymphatic flow‐through flap for upper thigh defect reconstruction and lymphatic sequelae prevention in sarcoma surgery: A case report
Authors: Calabrese Sara , Meroni Matteo , Scaglioni Mario F.
Published: October 2022

Among the various histologic subpopulations of soft tissue sarcomas, undifferentiated pleomorphic sarcoma (UPS) is one of the most common subtypes in the adult population. Radical surgery remains the primary treatment for UPS, associated with postsurgical radiotherapy or chemotherapy. We herein report the case of a 65‐year‐old man presenting a recurrent UPS in his right upper thigh region. The patient received radical resection of the tumor and the remaining defect measured ~22 cm × 18 cm. A soft tissue functional reconstruction with lymphatic‐flow‐through pedicled postero‐medial thigh flap (PMT) was planned. A 24 cm × 16 cm flap was harvested in vertical fashion (vPMT), carefully preserving a superficial vein for the following lymphovenous anastomosis (LVA) at recipient site. The flap was then rotated and transferred to the defect area through a tunnel under the adductor longus muscle, and LVA was then performed between flap's additional venous pedicle and a nearby leaking lymphatic vessel. The postoperative course was uneventful and at 12 months follow‐up no complications were encountered. No signs of lymphedema were reported. When dealing with the groin and upper thigh area, which is notably rich in lymphatic tissue, the possibility of prophylactically re‐route lymphatic fluid into the venous system by means of microsurgical anastomosis, lays in the thrilling possibility to prevent secondary lymphedema, instead of curing it. With the described technique, we achieved optimal functional and esthetic outcomes setting at zero both donor and recipient sites morbidity.
Solving an inverse nodal problem with Herglotz–Nevanlinna functions in boundary conditions using the second‐kind Chebyshev wavelets method
Authors: Akbarpoor Kiasary Shahrbanoo , Yilmaz Emrah
Published: October 2022

This study considers Sturm–Liouville (S–L) equation with a special function which includes spectral parameter at boundary conditions and expresses asymptotic forms of inverse problem solution, nodal points, and lengths. Furthermore, it proves some uniqueness theorems. Doing this, approximate solution of inverse S–L problem is obtained by second‐kind Chebyshev polynomials whereby the second‐kind Chebyshev wavelets (SCW) method is used to solve these types of problems. Finally, effectiveness of the method is demonstrated in a few examples.
A novel modified Kock–Snowflake fractal MIMO antenna for 4G/5G UWB communication gadgets
Authors: Sohi Arashpreet K. , Kaur Amanpreet
Published: October 2022

A dual‐port, tapered‐fed fractal antenna with a partial ground is proposed for effective implementation in portable ultra‐wideband–multiple‐input multiple‐output devices. The array is modeled on a 41 × 71 × 1.57 mm3 dielectric FR4 substrate. Each circular radiator defected with a modified Koch–Snowflake fractal (4th iteration) provides 46.7% size miniaturization. The array yields 14.7 GHz bandwidth (3.3–18 GHz, 138%) by defecting the partial ground and offsetting the tapered feedlines. By embedding an H‐shaped decoupler and plus‐shaped slots in the ground, significant isolation (S21/S12 ≤ −16 dB) is accomplished. Various diversity metrics are investigated and are found to follow their permissible standards. To justify the simulated results, the fabricated array is tested where a favorable match between the results makes it a suitable candidate for high data‐rate wireless applications.
Application of a coupled hydro‐mechanical interface model in simulating uplifting problems
Authors: Peng Maozhu , Tian Yinghui , Gaudin Christophe , Zhang Lihai , Sheng Daichao
Published: October 2022

This paper presents the detailed formulation of a coupled hydro‐mechanical structure‐soil interface and demonstrates its application in simulating uplifting problems. This interface features real‐time prediction of the pore pressure generation and structure‐soil separation, and thus rate dependency and ‘breakaway’ can be modeled without user intervention. Constitutive relations of this interface were derived by considering the coupling between soil skeleton and fluid along the interface. A complete finite element formulation and numerical implementation of the interface is provided based on an eight‐node element. The performance of this interface is demonstrated by simulating lifting a surface footing at varying rates (spanning across undrained, partially drained and drained conditions), compared with existing theoretical solutions, numerical results and experimental data. The good agreement achieved indicates that this interface is capable of modelling uplift at varying rates, which is an extremely challenging topic in offshore engineering. Sensitivity studies were conducted to investigate the parameters affecting uplifting behaviour. A unified backbone curve was established correspondingly, which is shown to be different from existing studies in compression, due to the difference in the mechanism between the two cases.
A modified walk‐on‐sphere method for high dimensional fractional Poisson equation
Authors: Jiao Caiyu , Li Changpin , Wang Hexiang , Zhang Zhongqiang
Published: October 2022

We develop walk‐on‐sphere method for fractional Poisson equations with Dirichilet boundary conditions in high dimensions. The walk‐on‐sphere method is based on probabilistic representation of the fractional Poisson equation. We propose efficient quadrature rules to evaluate integral representation in the ball and apply rejection sampling method to drawing from the computed probabilities in general domains. Moreover, we provide an estimate of the number of walks in the mean value for the method when the domain is a ball. We show that the number of walks is increasing in the fractional order and the distance of the starting point to the origin. We also give the relationship between the Green function of fractional Laplace equation and that of the classical Laplace equation. Numerical results for problems in 2–10 dimensions verify our theory and the efficiency of the modified walk‐on‐sphere method.
Preparation of MOF‐Zn@ZnO composite and its properties in SBR
Authors: Lei Zhiqiang , Wu Yankang , Tang Liping , Chen Jian
Published: October 2022

The synthesis and application of metal–organic skeleton materials (MOFs) have attracted much attention in recent years due to their special structures and properties. In order to expand the application field of MOFs materials, this paper designed experiments to explore the application prospect of MOFs materials in the field of rubber. In this study, zinc acetate dihydrate was used as the central metal ion source, terephthalic acid as organic ligand and deionized water as solvent. MOF‐Zn was prepared by hydrothermal method and ZnO nanoparticles were grown on the surface of MOF‐Zn in situ to obtain MOF‐Zn@ZnO. At the same time, the composite material is filled into the SBR by mechanical blending method. The experimental results show that ZnO nanoparticles adsorb on the MOF‐Zn surface and have strong interfacial interaction with MOF‐Zn. Moreover, MOF‐Zn@ZnO was uniformly dispersed in the rubber matrix, which improved the cross‐linking effect of the composite material and promoted the vulcanization of rubber. Compared with ZnOC/SBR composites, the modulus and tensile strength of MOF‐Zn@ZnO/SBR composites at 100%, 200%, and 300% elongation are increased by 33.6%, 38.2%, 30.8%, and 16.8%, respectively. The excellent performance of MOF‐Zn@ZnO/SBR composite is due to the inhibition of agglomeration of ZnO nanoparticles by MOF‐Zn, which can be used as an effective vulcanization activator in rubber. This study provides a simple synthesis route for the preparation of ZnO nanofillers for high performance SBR composites.
The influence of hole quality on mechanical behavior and strain distribution of open‐hole CFRP laminates subject to different machining processes
Authors: Li Maojun , Jiang Xiaoyang , Su Ting
Published: October 2022

Machining process is generally required for cutting composite material of structural components prior to final assembly in aerospace industry. This study aimed to investigate surface quality and mechanical behavior of open‐hole composite laminates following different machining processes including abrasive waterjet cutting, high power fiber laser machining, conventional drilling and ultraviolet laser machining. Hole quality was quantified for further understanding the correlation between surface damage and mechanical behavior. Experimental results demonstrated that the hole geometrical accuracy and mechanical property were highly dependent on the machining methods. Digital image correlation technique was implemented to capture the strain distribution and strain evolution around open holes during tensile loading. Machining methods exhibited significant impact on , and strain levels around hole edges, while limited influence on strain distribution patterns. and concentrated in the regions consisting of fibers perpendicular to and along the loading direction respectively, and shear strain featured with X shape around hole edge.
Data Fusion‐based Discovery (DAFdiscovery) pipeline to aid compound annotation and bioactive compound discovery across diverse spectral data
Authors: Borges Ricardo Moreira , das Neves Costa Fernanda , Chagas Fernanda O. , Teixeira Andrew Magno , Yoon Jaewon , Weiss Márcio Barczyszyn , Crnkovic Camila Manoel , Pilon Alan Cesar , Garrido Bruno C. , Betancur Luz Adriana , Forero Abel M. , Castellanos Leonardo , Ramos Freddy A. , Pupo Mônica T. , Kuhn Stefan
Published: October 2022

Introduction

Data Fusion‐based Discovery (DAFdiscovery) is a pipeline designed to help users combine mass spectrometry (MS), nuclear magnetic resonance (NMR), and bioactivity data in a notebook‐based application to accelerate annotation and discovery of bioactive compounds. It applies Statistical Total Correlation Spectroscopy (STOCSY) and Statistical HeteroSpectroscopy (SHY) calculation in their data using an easy‐to‐follow Jupyter Notebook.

Method

Different case studies are presented for benchmarking, and the resultant outputs are shown to aid natural products identification and discovery. The goal is to encourage users to acquire MS and NMR data from their samples (in replicated samples and fractions when available) and to explore their variance to highlight MS features, NMR peaks, and bioactivity that might be correlated to accelerated bioactive compound discovery or for annotation–identification studies.

Results

Different applications were demonstrated using data from different research groups, and it was shown that DAFdiscovery reproduced their findings using a more straightforward method.

Conclusion

DAFdiscovery has proven to be a simple‐to‐use method for different situations where data from different sources are required to be analyzed together.
Spin‐spray‐assisted layer‐by‐layer assembly of thick polymer films with self‐healing, UV‐protection, and anti‐fog properties
Authors: Kashem Md Nayeem Hasan , Liu Xu , Ding Zhenya , Li Wei
Published: October 2022

Layer‐by‐layer (LbL) deposition of oppositely charged polyelectrolytes has been widely used to make responsive and multifunctional smart films. Herein, a high‐performance and multifunctional LbL film was fabricated by using a spin‐spray‐assisted (SSA‐LbL) assembly method with poly(diallyldimethylammonium chloride) (PDDA) and poly(acrylic acid) (PAA). The SSA‐LbL method was found to be more efficient and time‐saver in making a homogeneous thick film in tens of micrometers, compared to the conventional immersive assembly method which makes thin films in the nanometer range. When scratches occur, the film shows a quick and durable self‐healing capability due to the dynamic movement of the flexible polyelectrolyte complex chains at the edges of the scratches. An effective UV‐block performance was incorporated into the film by using the graphene oxide (GO) and titanium dioxide (TiO2) nanoparticles as UV‐blocking additives. Due to the hydrophilic feature of PDDA/PAA molecules, the film also showed the anti‐fog property in different environmental conditions. The effect of the concentration of GO and TiO2 nanoparticles on self‐healing and UV‐protection properties were investigated. Also, the optimum range of concentration of GO and TiO2 nanoparticles in polyelectrolyte solutions was determined to fabricate the film with the combined features of self‐healable, UV‐blocking, and anti‐fog.
Nitrocellulose‐Based Green‐Light Illuminants: A Study of Barium Nitrate Particle Size on Spectral Performance
Authors: Kotter Lance N. , Groven Lori J.
Published: October 2022

While a typical military flare includes a metal fuel (aluminum, magnesium, boron, etc.) to increase combustion temperature and therefore spectral performance, the replacement of these fuels to reduce smoke (non‐light emitting species) is still desired. Nitrocellulose (NC) is known to be a “smokeless” propellant and, in this work, used solely as the fuel component in the pyrotechnic flare composition. Two levels of nitration, 12.2% N and 13.4% N content, are studied and while the influence of nitration content is shown, this work focuses on the role of barium nitrate (Ba(NO3)2) particle size. For formulations with 13.4% N content, reducing the Ba(NO3)2 particle size fraction from 250–300 μm to ≤25 μm results in the dominant wavelength being reduced from 569 nm to 558 nm. Combustion products collected from formulations using the 250–300 μm Ba(NO3)2, were characterized and indicated barium carbonate (BaCO3) as the major condensed phase product. This indicates that the formation of barium oxide (BaO) from the slow decomposition of Ba(NO3)2, coupled with the release of CO2 from NC, likely results in the following reaction: BaO+CO2→BaCO3. While unexpected, this implies that controlling early chemistry during combustion may allow significant improvements in spectral performance by inhibiting non‐light emitting specie formation.
Identification of natural small molecule modulators of MurB from Salmonella enterica serovar Typhi Ty2 strain using computational and biophysical approaches
Authors: Haque Md. Anzarul , Singh Mandeep , Tripathi Manish Kumar , Ethayathulla Abdul Samath , Kaur Punit
Published: October 2022

The increase of antibiotic‐resistant bacterial pathogens has created challenges in treatment and warranted the design of antibiotics against comparatively less exploited targets. The peptidoglycan (PG) biosynthesis delineates unique pathways for the design and development of a novel class of drugs. Mur ligases are an essential component of bacterial cell wall synthesis that play a pivotal role in PG biosynthesis to maintain internal osmotic pressure and cell shape. Inhibition of these enzymes can interrupt bacterial replication and hence, form attractive targets for drug discovery. In the present work, we focused on the PG biosynthesis pathway enzyme, UDP‐N‐acetylpyruvylglucosamine reductase, from Salmonella enterica serovar Typhi (stMurB). Biophysical characterization of purified StMurB was performed to gauge the molecular interactions and estimate thermodynamic stability for determination of attributes for possible therapeutic intervention. The thermal melting profile of MurB was monitored by circular dichroism and validated through differential scanning calorimetry experiment. Frequently used chemical denaturants, GdmCl and urea, were employed to study the chemical‐induced denaturation of stMurB. In the search for natural compound‐based inhibitors, against this important drug target, an in silico virtual screening based investigation was conducted with modeled stMurB structure. The three top hits (quercetin, berberine, and scopoletin) returned were validated for complex stability through molecular dynamics simulation. Further, fluorescence binding studies were undertaken for the selected natural compounds with stMurB alone and with NADPH bound form. The compounds scopoletin and berberine, displayed lesser binding to stMurB whereas quercetin exhibited stronger binding affinity than NADPH. This study suggests that quercetin can be evolved as an inhibitor of stMurB enzyme.
Application of physiologically‐based pharmacokinetic model approach to predict pharmacokinetics and drug–drug interaction of rivaroxaban: A case study of rivaroxaban and carbamazepine
Authors: Ngo Lien Thi , Yang Sung‐yoon , Shin Sooyoung , Cao Duc Tuan , Van Nguyen Hung , Jung Sangkeun , Lee Jae‐Young , Lee Jong‐Hwa , Yun Hwi‐yeol , Chae Jung‐woo
Published: October 2022

Rivaroxaban (RIV; Xarelto; Janssen Pharmaceuticals, Beerse, Belgium) is one of the direct oral anticoagulants. The drug is a strong substrate of cytochrome P450 (CYP) enzymes and efflux transporters. This study aimed to develop a physiologically‐based pharmacokinetic (PBPK) model for RIV. It contained three hepatic metabolizing enzyme reactions (CYP3A4, CYP2J2, and CYP‐independent) and two active transporter‐mediated transfers (P‐gp and BCRP transporters). To illustrate the performance of the developed RIV PBPK model on the prediction of drug–drug interactions (DDIs), carbamazepine (CBZ) was selected as a case study due to the high DDI potential. Our study results showed that CBZ significantly reduces the exposure of RIV. The area under the concentration‐time curve from zero to infinity (AUCinf) of RIV was reduced by 35.2% (from 2221.3 to 1438.7 ng*h/ml) and by 25.5% (from 2467.3 to 1838.4 ng*h/ml) after the first dose and at the steady‐state, respectively, whereas the maximum plasma concentration (Cmax) of RIV was reduced by 37.7% (from 266.3 to 166.1 ng/ml) and 36.4% (from 282.3 to 179.5 ng/ml), respectively. The developed PBPK model of RIV could be paired with PBPK models of other interested perpetrators to predict DDI profiles. Further studies investigating the extent of DDI between CBZ and RIV should be conducted in humans to gain a full understanding of their safety and effects.
A meta‐analytic framework to adjust for bias in external control studies
Authors: Incerti Devin , Bretscher Michael T. , Lin Ray , Harbron Chris
Published: October 2022

While randomized controlled trials (RCTs) are the gold standard for estimating treatment effects in medical research, there is increasing use of and interest in using real‐world data for drug development. One such use case is the construction of external control arms for evaluation of efficacy in single‐arm trials, particularly in cases where randomization is either infeasible or unethical. However, it is well known that treated patients in non‐randomized studies may not be comparable to control patients—on either measured or unmeasured variables—and that the underlying population differences between the two groups may result in biased treatment effect estimates as well as increased variability in estimation. To address these challenges for analyses of time‐to‐event outcomes, we developed a meta‐analytic framework that uses historical reference studies to adjust a log hazard ratio estimate in a new external control study for its additional bias and variability. The set of historical studies is formed by constructing external control arms for historical RCTs, and a meta‐analysis compares the trial controls to the external control arms. Importantly, a prospective external control study can be performed independently of the meta‐analysis using standard causal inference techniques for observational data. We illustrate our approach with a simulation study and an empirical example based on reference studies for advanced non‐small cell lung cancer. In our empirical analysis, external control patients had lower survival than trial controls (hazard ratio: 0.907), but our methodology is able to correct for this bias. An implementation of our approach is available in the R packageecmeta.
Metamodel‐based optimization of shift planning in high‐bay warehouse operations
Authors: Kirchhoff Dominik , Kirberg Marc , Kuhnt Sonja , Clausen Uwe
Published: October 2022

Gaussian process (GP) models of time‐consuming computer simulations are nowadays widely used within metamodel‐based optimization. In recent years, GP models with mixed inputs have been proposed to handle both numerical and categorical inputs. Using a case study of a high‐bay warehouse, we demonstrate the use of GP models with low‐rank correlation (LRC) kernels in the context of efficient global optimization (EGO). As is common in many logistics applications, the high‐bay warehouse is modeled with a discrete‐event simulation model. Input variables include, for example, the choice between different task assignment strategies. A shift scheduling problem is considered in which personnel and energy costs as well as the delay of tasks are to be minimized at the same time. Evaluations of an initial experimental design provide a first approximation of the Pareto front, which we manage to extend substantially within only 15 iterations of identifying new points using the expected hypervolume improvement (EHI) and the metric selection (SMS) criteria. We penalize the criteria in the last five iterations using the known total costs of proposed points to guide the search towards a more desired area. The resulting Pareto front approximation provides a selection of shift plans that have different characteristics. This enables decision makers in practice to choose a shift plan with desirable features.
Thin layer chromatography/desorption flame‐induced atmospheric pressure chemical ionization/mass spectrometry for the analysis of volatile and semi‐volatile mixtures
Authors: Shiea Jentaie , Lin Hsing‐Jung , Bhat Suhail Muzaffar , Lee Chi‐Yang , Huang Min‐Zong , Ponnusamy Vinoth Kumar , Cheng Sy‐Chyi
Published: October 2022

Flame‐induced atmospheric pressure chemical ionization (FAPCI) has been used to directly characterize chemical compounds on a glass rod and drug tablet surfaces. In this study, FAPCI was further applied to interface thin layer chromatography (TLC) and mass spectrometry (MS) for mixture analysis.

Methods

A micro‐sized oxyacetylene flame was generated using a small concentric tube system. Hot gas flow and primary reactive species from the micro‐flame were directed toward a developed TLC gel plate to thermally desorb and ionize analytes on the gel surface. The resulting analyte ions subsequently entered the MS inlet for detection.

Results

A 1–1.5‐mm‐wide light‐brown line was observed on the TLC plate after the desorption FAPCI/MS (DFAPCI/MS) analysis, revealing that the gel surface withstood a high temperature from the impact of the micro‐flame. Volatile and semi‐volatile chemical compounds, including amine and amide standards, drugs, and aromatherapy oils, were successfully desorbed, ionized, and detected using this TLC/DFAPCI/MS. The limit of detection of TLC‐DFAPCI/MS was determined to be 5 ng/spot for dibenzylamine and ethenzamide.

Conclusions

TLC/DFAPCI/MS is one of the simplest TLC‐MS interfaces showing the advantages such as low costs and an easy set up. The technique is useful for characterizing thermally stable volatile and semi‐volatile compounds in a mixture.
An Overview of Natural and Synthetic Phthalides Involved in Cancer Studies: Past, Present, and Future
Authors: Sadıkoğulları Bleda Can , Şenel Pelin , Çini Nejla , Faysal Abdullah Al , Odabaşoğlu Mustafa , Özdemir Ayşe Daut , Gölcü Ayşegül
Published: October 2022

Phthalides, mainly isolated from two genera: Ligusticum and Angelica of the Apiceae (syn Umbelliferae) family, are thought to be a potent natural compound with many therapeutic effects, such as antiplatelet, antitussive, antinociceptive, anti‐inflammatory, antibacterial, antiviral, and immunosuppressive activities. They also have antifungal, antioxidant, and anticancer activities. Phthalides are responsible for the characteristic odor of celery. Since ancient times, phthalides containing plants have been used in Asia, Europe, and North America as traditional medicines and food flavoring agents. In this review, we have provided the data regarding the mechanisms of action related with phthalides on different cancer cells, their chemopreventive properties, and their possible therapeutic potential against various types of human cancer. Our attempt is to make a case for the use of phthalide and their derivatives as one of the plant‐based compounds in targeting metabolic treatment of cancer diseases.
Assembly of Artificial Light‐Harvesting Systems Based on Supramolecular Self‐Assembly Metallogels
Authors: Ma Xinxian , Wang Yipei , Lai Yingshan , Ren Tianqi , Tang Jiahong , Gao Yang , Geng Yutao , Zhang Jiali , Yue Jinlong
Published: October 2022

We have designed and constructed two artificial light‐harvesting systems (ALHSs), which are based on the supramolecular self‐assembly of acylhydrazone functionalized quinoline (L), Al3+ and fluorescent dyes. The L‐Al3+ supramolecular assembly distinctly improved aggregation‐induced emission enhancement and served as a donor for ALHSs. Acridine yellow and acridine orange were found to be good acceptors to realize the energy transfer process with good efficiency.
Interwire and Intrawire Magnetostatic Interactions in Fe‐Au Barcode Nanowires with Alternating Ferromagnetically Strong and Weak Segments
Authors: Samardak Aleksei Yu. , Jeon Yoo Sang , Samardak Vadim Yu. , Kozlov Alexey G. , Rogachev Kirill A. , Ognev Alexey V. , Jeong Eunjin , Kim Gyu Won , Ko Min Jun , Samardak Alexander S. , Kim Young Keun
Published: October 2022

Metallic barcode nanowires (BNWs) composed of repeating heterogeneous segments fabricated by template‐assisted electrodeposition can offer extended functionality in magnetic, electrical, mechanical, and biomedical applications. The authors consider such nanostructures as a 3D system of magnetically interacting elements with magnetic behavior strongly affected by complex magnetostatic interactions. This study discusses the influence of geometrical parameters of segments on the character of their interactions and the overall magnetic behavior of the array of BNWs having alternating magnetization, because the Fe and Au segments are made of Fe‐Au alloys with high and low magnetizations. By controlling the applied current densities and the elapsed time in the electrodeposition, the dimension of the Fe‐Au BNWs can be regulated. This study reveals that the influence of the length of magnetically weak Au segments on the interaction field between nanowires is different for samples with magnetically strong 100 and 200 nm long Fe segments using the first‐order reversal curve (FORC) diagram method. With the help of micromagnetic simulations, three types of magnetostatic interactions in the BNW arrays are discovered and analy. This study demonstrates that the dominating type of interaction depends on the geometric parameters of the Fe and Au segments and the interwire and intrawire distances.
Low‐Energy Hydrogen Ions Enable Efficient Room‐Temperature and Rapid Plasma Hydrogenation of TiO2 Nanorods for Enhanced Photoelectrochemical Activity
Authors: Wang Xiaodan , Mayrhofer Leonhard , Keunecke Martin , Estrade Sonia , Lopez‐Conesa Lluis , Moseler Michael , Waag Andreas , Schaefer Lothar , Shi Weidong , Meng Xiangjian , Chu Junhao , Fan Zhiyong , Shen Hao
Published: October 2022

Hydrogenation is a promising technique to prepare black TiO2 (H‐TiO2) for solar water splitting, however, there remain limitations such as severe preparation conditions and underexplored hydrogenation mechanisms to inefficient hydrogenation and poor photoelectrochemical (PEC) performance to be overcome for practical applications. Here, a room‐temperature and rapid plasma hydrogenation (RRPH) strategy that realizes low‐energy hydrogen ions of below 250 eV to fabricate H‐TiO2 nanorods with controllable disordered shell, outperforming incumbent hydrogenations, is reported. The mechanisms of efficient RRPH and enhanced PEC activity are experimentally and theoretically unraveled. It is discovered that low‐energy hydrogen ions with fast subsurface transport kinetics and shallow penetration depth features, enable them to directly penetrate TiO2 via unique multiple penetration pathways to form controllable disordered shell and suppress bulk defects, ultimately leading to improved PEC performance. Furthermore, the hydrogenation‐property experiments reveal that the enhanced PEC activity is mainly ascribed to increasing band bending and bulk defect suppression, compared to reported H‐TiO2, a superior photocurrent density of 2.55 mA cm−2 at 1.23 VRHE is achieved. These findings demonstrate a sustainable strategy which offers great promise of TiO2 and other oxides to achieve further‐improved material properties for broad practical applications.
Unraveling the Synergy of Anion Modulation on Co Electrocatalysts by Pulsed Laser for Water Splitting: Intermediate Capturing by In Situ/Operando Raman Studies
Authors: Begildayeva Talshyn , Theerthagiri Jayaraman , Lee Seung Jun , Yu Yiseul , Choi Myong Yong
Published: October 2022

Herein, the authors produce Co‐based (Co3(PO4)2, Co3O4, and Co9S8) electrocatalysts via pulsed laser ablation in liquid (PLAL) to explore the synergy of anion modulation on phase‐selective active sites in the electrocatalytic hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). Co3(PO4)2 displays an ultralow overpotential of 230 mV at 10 mA cm−2 with 48.5 mV dec−1 Tafel slope that outperforms the state‐of‐the‐art Ir/C in OER due to its high intrinsic activity. Meanwhile, Co9S8 exhibits the highest HER performance known to the authors among the synthesized Co‐based catalysts, showing the lowest overpotential of 361 mV at 10 mA cm−2 with 95.8 mV dec−1 Tafel slope in the alkaline medium and producing H2 gas with ≈500 mmol g−1 h−1 yield rate under −0.45 V versus RHE. The identified surface reactive intermediates over in situ electrochemical–Raman spectroscopy reveal that cobalt(hydr)oxides with higher oxidation states of Co‐cation forming under oxidizing potentials on the electrode–electrolyte surface of Co3(PO4)2 facilitate the OER, while Co(OH)2 facilitate the HER. Notably, the fabricated two‐electrode electrolyzers using Co3(PO4)2, Co3O4, and Co9S8 electrocatalysts deliver the cell potentials ≈2.01, 2.11, and 1.89 V, respectively, at 10 mA cm−2. This work not only shows PLAL‐synthesized electrocatalysts as promising candidates for water splitting, but also provides an underlying principle for advanced energy‐conversion catalysts and beyond.
A provably secure, shortest, and efficient identity based signcryption technique in the standard model
Authors: Aithekar Ashutosh , Gupta Pratik , Dharminder Dharminder
Published: October 2022

Singcryption is a very important concept to bind confidentiality and authenticity. This is a logical step to reduce both computation and communication costs. The proposed an identity based signcryption that removes the overhead of certificates. The proposed design is provably secure in the standard model (a widely accepted model). Furthermore, the IBSC design uses modified bilinear Diffie‐Hellman inversion and modified strong bilinear Diffie‐Hellman assumption as building blocks of the security. The proposed design is secure, efficient, and shortest to the best of our knowledge. In this design, a user does pairing free computation, and he sends only a triplet on the public channel, that makes it efficient in terms of computation and communication costs.
Leveraging spatiotemporal genomic breeding value estimates of dry matter yield and herbage quality in ryegrass via random regression models
Authors: Bornhofen Elesandro , Fè Dario , Lenk Ingo , Greve Morten , Didion Thomas , Jensen Christian Sig , Asp Torben , Janss Luc
Published: October 2022

Joint modeling of correlated multienvironment and multiharvest data of perennial crop species may offer advantages in prediction schemes and a better understanding of the underlying dynamics in space and time. The goal of the present study was to investigate the relevance of incorporating the longitudinal dimension of within‐season multiple measurements of forage perennial ryegrass (Lolium perenne L.) traits in a reaction‐norm model setup that additionally accounts for genotype × environment (G × E) interactions. Genetic parameters and accuracy of genomic estimated breeding value (gEBV) predictions were investigated by fitting three genomic random regression models (gRRMs) using Legendre polynomial functions to the data. Genomic DNA sequencing of family pools of diploid perennial ryegrass was performed using DNA nanoball‐based technology and yielded 56,645 single‐nucleotide polymorphisms, which were used to calculate the allele frequency‐based genomic relationship matrix. Biomass yield's estimated additive genetic variance and heritability values were higher in later harvests. The additive genetic correlations were moderate to low in early measurements and peaked at intermediates with fairly stable values across the environmental gradient except for the initial harvest data collection. This led to the conclusion that complex (G × E) arises from spatial and temporal dimensions in the early season with lower reranking trends thereafter. In general, modeling the temporal dimension with a second‐order orthogonal polynomial improved the accuracy of gEBV prediction for nutritive quality traits, but no gain in prediction accuracy was detected for dry matter yield (DMY). This study leverages the flexibility and usefulness of gRRM models for perennial ryegrass breeding and can be readily extended to other multiharvest crops.
Multi‐trait genomic prediction improves selection accuracy for enhancing seed mineral concentrations in pea
Authors: Atanda Sikiru Adeniyi , Steffes Jenna , lan Yang , Al Bari Md Abdullah , Kim Jeong‐Hwa , Morales Mario , Johnson Josephine P. , Saludares Rica , Worral Hannah , Piche Lisa , Ross Andrew , Grusak Mike , Coyne Clarice , McGee Rebecca , Rao Jiajia , Bandillo Nonoy
Published: October 2022

Multi‐trait genomic selection (MT‐GS) has the potential to improve predictive ability by maximizing the use of information across related genotypes and genetically correlated traits. In this study, we extended the use of sparse phenotyping method into the MT‐GS framework by split testing of entries to maximize borrowing of information across genotypes and predict missing phenotypes for targeted traits without additional phenotyping expenditure. Using 300 advanced breeding lines from North Dakota State University (NDSU) pulse breeding program and ∼200 USDA accessions that were evaluated for 10 nutritional traits, our results show that the proposed sparse phenotyping aided MT‐GS can further improve predictive ability by >12% across traits compared with univariate (UNI) genomic selection. The proposed strategy departed from the previous reports that weak genetic correlation is a limitation to the advantage of MT‐GS over UNI genomic selection, which was evident in the partially balanced phenotyping‐enabled MT‐GS. Our results point to heritability and genetic correlation between traits as possible metrics to optimize and further improve the estimation of model parameters, and ultimately, prediction performance. Overall, our study offers a new approach to optimize the prediction performance using the MT‐GS and further highlight strategy to maximize the efficiency of GS in a plant breeding program. The sparse‐testing‐aided MT‐GS proposed in this study can be further extended to multi‐environment, multi‐trait GS to improve prediction performance and further reduce the cost of phenotyping and time‐consuming data collection process.
Chapter 4: The Matrix-Variate Gaussian Distribution
Authors: Mathai Arak , Provost Serge , Haubold Hans
Published: October 2022

This chapter relies on various results presented in Chap. 1. We introduce a class of integrals called the real matrix-variate Gaussian integrals and complex matrix-variate Gaussian integrals wherefrom a statistical density referred to as the matrix-variate Gaussian density and, as a special case, the multivariate Gaussian or normal density will be obtained, both in the real and complex domains. Moment generating functions, marginal and conditional distributions, as well as parameter estimates, are derived. Singular distributions are also considered.
Chapter 9: Principal Component Analysis
Authors: Mathai Arak , Provost Serge , Haubold Hans
Published: October 2022

The requisite theory for the study of Principal Component Analysis has already been introduced in Chap. 1, namely, the problem of optimizing a real quadratic form that is subject to a constraint. We formulate the problem with respect to a practical situation consisting of selecting the most ``relevant'' variables in a study. Principal component analysis is actually a dimension reduction technique that projects the data onto a set of orthogonal axes. Sample principal components are defined and certain associated distributional aspects are discussed.