bluuebunny/crossref_metadata_2025 huggingface dataset:
Oblique Flow of Shear Thinning Fluid through an Absorptive Radiative Medium with Hall Effect
Authors: Rana S. , Mahmud K. , Mehmood R. , Bhatti M. M.
Published: April 2023

The assumption of Hall current and ion slip is extremely crucial in several industrial and manufacturing processes, such as MHD (magneto hydrodynamics) accelerators, preservation coils, transmission lines, electric converters, and heating elements. Keeping this in view, the main aim of this article is to present a computational analysis of MHD ion Hall current with nonlinear thermal radiation on the sloping flow of shear thinning fluid through a porous medium on a stretching sheet that allows fluid suction and injection. The major mathematical modelling of governed problems is converted into a system of nonlinear ODEs (ordinary differential equations) by means of appropriate similarity relations. The influence of all relative physical parameters on velocity and temperature is studied through graphs and discussed in a detailed physical manner. Some beneficial mathematical quantities from the practical engineering and industrial point of view, such as skin friction factor and heat transfer rate at the porous surface, are calculated numerically and presented through graphs. It has been observed that flow may become unstable when M is small and the existence of a magnetic field and a porous ground contributes to a highly rough flow over the stretching surface. Suction is actually a resistive force which results in higher skin friction that is beneficial in controlling flow separation. Temperature of the fluid rises with stronger magnetic field and higher thermal radiation effects. The local heat flux decreases as the magnetic field strength and permeability parameter increase.
An Intelligent Energy Management Information System with Machine Learning Algorithms in Oil and Gas Industry
Authors: Li Jun , Guo Yidong , Fu Zhanbao , Zhang Xiangyang , Shen Fei
Published: April 2023

Oil and gas will continue to play an increasingly important role in global economy development and prosperity for the upcoming years. However, a fact which sometimes is ignored is that the oil and gas industry is an intensive energy-consumption industry and a major contributor to greenhouse gas emissions as well. Recently, with the arrival of the “double carbon” era, the energy-intensive production of oil and gas has caused people to pay more attention. Currently, big data technologies as well as the Internet of things (IoT) are developing at a rapid pace, and the metering infrastructure technology also shows huge advancement; oil and gas companies have built many information systems and developed many functions to acquire the energy consumption and oil production data for the aim of reducing the oil production cost via the emerging information technologies, and it turned out that these investments do improve the energy efficiency and lower oil production cost. Unfortunately, due to the different development standards, some systems store the same data with different values; so, therefore, there is a “data barrier” among these systems and somehow discount the share and analysis of these data resources. To this end, in our work, based on these rich data resources from the other information systems, we discussed an intelligent energy management information system with four machine learning algorithms to enhance the analysis of data resources over energy consumption and oil production. First, we presented the innovation of energy consumption data fusion with the method “Data Lake”; then, four different machine learning algorithms: Support Vector Machine (SVM), Linear Regression (LR), Extreme Learning Machine (ELM), and Artificial Neural Networks (ANN) are installed in the proposed system for predicting the oil and gas production and total energy consumption. In order to aggregate these data into dashboard views that help managers make decisions about operations, we also demonstrated the process of energy consumption data visualization with emerging open-source software tool ECharts. Finally, a real life application of the proposed system was summarized in case of total energy consumption prediction and the system output shows good prediction accuracy which proves the feasibility and benefits of the intelligent energy management information system.
Mesoscopic Freeze-Thaw Damage Evolution Characteristics of Fractured Sandstone at Different Saturations
Authors: Song Yongjun , Zhou Yue , Yang Huimin , Li Chenjing , Cao Jinghui , Sun Yinwei , Han Dongyang
Published: April 2023

To study the effect of saturation on the freeze-thaw damage of fractured rocks in cold regions, five prefabricated oval double-hole red sandstones with different saturations were prepared. Three-dimensional images of rock fractures were obtained by CT technology. The freeze-thaw damage mechanism and critical saturation of the red sandstone were explored through the fracture propagation evolution and quantitative characterization of the pore structure. The experimental results show that the pore size distribution can reflect the complex pore structure. Pores can be divided according to their sizes: small pores, mesopores, and macropores; mesopores account for the largest proportion and more than 70% of the total, and the proportion of mesopores in high-saturation sandstone (90% or 100%) increases under the action of freeze-thaw cycle. This is also accompanied by a small increase in the proportion of macropores. An 80% critical saturation of the sandstone was obtained. In addition, prefabricated cracks make the ice separation mechanism more likely to occur. The low-saturation sandstone mainly damaged the fracture area during freeze-thaw cycles, while the prefabricated cracks provided a good seepage channel for high-saturation sandstone. The corresponding rock bridge area eventually demonstrated a connectivity trend. This study more realistically reflects the freeze-thaw damage of actual rock masses in cold regions and provides a theoretical basis for the prediction of rock mass engineering disasters in cold regions.
A New High-Performance Photovoltaic Emulator Suitable for Simulating and Validating Maximum Power Point Tracking Controllers
Authors: Harrison Ambe , Alombah Njimboh Henry
Published: April 2023

Photovoltaic (PV) research is rapidly growing, and the need for controlled environments to validate new MPPT controllers is becoming increasingly important. Currently, researchers face several challenges in testing MPPT algorithms due to the unpredictable nature of solar PV power generation. In this paper, we propose a new photovoltaic emulator (PVE) that could replace solar panels and ensure a highly controllable environment suitable for testing photovoltaic (PV) systems. In this PVE, the complex nonlinear equations of the PV cell/module are fast computed and resolved by a new linearization technique which involves the systematic breakdown of the current-voltage (

I

-

V

) curve of the PV into twelve linear segments. Based on input environmental conditions, an artificial neural network (ANN) was constructed to assist the linearization process by predicting the current-voltage boundary coordinates of these segments. Using simple linear equations, with the segment boundary coordinates, a reference voltage was generated for the PVE. A nonlinear backstepping controller was designed to exploit the reference voltage and stabilize the power conversion stage (PCS). The PVE was optimized using particle swarm optimization (PSO). Several tests have shown that the proposed nonlinear controller provides better dynamic and robust performance than the PI controller, the most reputable and recurrent control method in the area of PVE. The PVE was coupled with a recently proposed integral backstepping MPPT controller and analyzed under several dynamic conditions, including the MPPT test specified by EN 50530. It was found that the accuracy of the proposed PVE measured by its relative error is less than 0.5%, with an MPPT efficiency of greater than 99.5%. The attractive results achieved by this PVE make it especially suitable for simulating and validating MPPT controllers.
Comparative Analysis of Proximate Compositions, Physical Properties, and Sensory Attributes of Kersting’s Groundnut (Macrotyloma geocarpum (Harms) Maréchal & Baudet) Accessions
Authors: Fassinou Finagnon Toyi Kevin , Agoyi Eric Etchikinto , Affonfere Marius , Sacla Aide Edmond , Assogbadjo Achille Ephrem , Chadare Flora Josiane
Published: April 2023

Kersting’s groundnut (Macrotyloma geocarpum, Harms) is a legume crop with nutritional potential in West Africa where it is widely consumed due to its palatability. The present study investigated the physical characteristics, nutritional composition, and organoleptic properties of five Kersting’s groundnut accessions selected based on their yield performance, stability, and seed color. Physical characteristics (seed size, length, and thickness) were determined using a Vernier Caliper while a laboratory weighing scale was used to determine 100-seed weight. Protein and fat contents were analyzed using micro-Kjeldahl and Soxhlet systems, respectively. Dietary fiber content was determined using the AOAC method while carbohydrate content was determined using the method of difference. Amino acids were hydrolyzed and determined using the liquid chromatography method. Ten trained panelists participated in testing the cookability of the samples while 30 untrained panelists were involved in the acceptability test. Results showed that accessions ranged between 8.1 ± 0.1 and 9.3 ± 0.2 mm for seed length, 5.7 ± 0.4 and 6.0 ± 0.2 mm for the width, and 4.0 ± 0.0 and 4.9 ± 0.4 mm for thickness. The 100-seed weight ranged from 11.7 ± 0.8 to 16.7 ± 1.6 g. Protein, fat, and carbohydrate contents ranged from 20.5 ± 0.2 to 22.0 ± 0.2, 1.2 ± 0.0 to 2.3 ± 0.0, and 56.5 ± 0.0 to 59.4 ± 0.1 (g/100 g dw), respectively. The lowest and highest cooking times were 78 and 124 minutes, respectively. All accessions recorded good sensory acceptability (>50%) except the accession BUR 16 which was liked only by 23.3%. Overall, accession OUA had the highest protein, medium cooking time, and highest overall acceptability score (>70%), hence recommended for wide production. Future studies need to be performed on the antinutritional content of this accession and to find out the effect of cooking on the nutritional value of derived meals and starch modification.
Numerical Study of the Effect of Angle and Location of the First and Second Steps on the Performance of Planing Hull and Their Optimization Using the Taguchi Statistical Method
Authors: Ghadimi Parviz , Sajedi Sayyed Mahdi , Sheikholeslami Mohammad , Ghadimi Aliakbar
Published: April 2023

Providing steps at the bottom of a high‐speed craft could decrease the resistance and enhance the longitudinal stability by dividing a single pressure hump into several ones and extending the hydrodynamic pressure towards aft of the vessel. In the present paper, the effects of the fore and aft steps’ locations and angles on double‐stepped hulls are investigated systematically via a numerical approach. The parent model investigated in this study is a model of a high‐speed recreational craft called Cougar, with a 1 : 5 scale. The three‐dimensional analysis of the model is conducted via the finite volume method, and the free surface is tracked using the volume of the fluid technique. The computational domain is discretized by the overset technique, and the calculations are validated via experimental data. Overall, 27 numerical tests designed by the Taguchi experiment design method are simulated, and the resistance, trim, and rise‐up values are calculated at 8 to 10 m/s speeds. The findings support the notion that the resistance increases by increasing the distance between the fore step and vessel stern. In addition, increasing the distance between the aft step and vessel stern and the increase of the angle of the fore step leads to reducing the vessel resistance. However, the results showed that finding a sensible relationship between the angle of the aft step and resistance requires more investigation. The findings revealed that the interactional effects between the angles of the aft and fore steps are the most considerable among all studied interactional effects. Among the all studied configurations, the lowest resistance was experienced by the model with an aft step at 25% of the vessel’s length to the stern, having an angle of 150°, and a fore step at 40% of the vessel’s length to the stern, having an angle of 180°.
Dynamic Performance Improvement of a Single-Phase VSI with Digital Implementation of an On-Line Optimal Trajectory Control Algorithm
Authors: Zaman Shah , Zhang Yan , Liu Jinjun , Yang Danni , Li Zhenchao
Published: April 2023

A single-phase voltage source inverter (VSI) still suffers from a long settling time and significant voltage overshoot/undershoot under the abrupt step-change of load current. This article analyzes the comprehensive large-signal dynamic process and limitation of the linear controller during step change in load current. The combination of linear and nonlinear control is presented which is a realistic, simple, and low-cost technique for enhancing the dynamic response of the single-phase VSI. A nonlinear controller based on the simplified capacitor charge balance algorithm is employed to drive the inductor current and capacitor voltage to attain the target value by precisely following the projected optimal trajectory during the transient process in a brief period. A linear PI controller is utilized during the steady-state operations such as input voltage variations, temperature drifts, and component ageing. The complete mathematical derivation as well as a design method is presented to guide the practical hardware implementation for the given main circuit parameters and identified load step change. Even though accurate time instants can be obtained using off-line numerical calculations, reasonable simplifications are provided for real-time practical engineering applications in DSP. Finally, simulation and experimental verifications prove that the single-phase VSI achieves a substantial settling time decrease and reduced voltage oscillations.
GPR176 Is a Biomarker for Predicting Prognosis and Immune Infiltration in Stomach Adenocarcinoma
Authors: Ni Lin , Chen Shuming , Liu Jianyong , Li He , Zhao Hu , Zheng Chunhua , Zhang Yawei , Huang Hancong , Huang Junjie , Wang Bing , Lin Chengzhi
Published: April 2023

Immunotherapy based on immune checkpoint inhibitors (ICIs) is considered to be a promising treatment for stomach adenocarcinoma (STAD), but only a minority of patients benefit from it. It is believed that the poor therapeutic efficacy is attributed to the complex tumor immune microenvironment (TIM) of STAD. Therefore, elucidating the specific regulatory mechanism of TIM in STAD is critical. Previous study suggests that GRP176 may be involved in regulating the pace of circadian behavior, and its role in tumors has not been reported. In this study, we first found that GPR176 was highly expressed in STAD and negatively correlated with patient prognosis. Next, we investigated the relationship between GPR176 and clinical characteristics, and the results showed that the stage is closely related to the level of GPR176. In addition, our further analysis found that GRP176 expression level was significantly correlated with chemotherapeutic drug sensitivity and ICI response. KEGG and GO analyses showed that GPR176 might be involved in stromal remodeling of STAD. Furthermore, we analyzed the association between GPR176 expression and immune implication, and the results revealed that GPR176 was negatively related to the infiltration of various immune cells. Interestingly, GPR176 induced the conversion of TIM while reducing the tumor immune burden (TMB). The expression of GRP176 is closely related to the level of various immunomodulators. Moreover, we performed univariate and multivariate regression analyses on the immunomodulators and finally obtained 4 genes (CRCR4, TNSF18, PDCD1, and TGFB1). Then, we constructed a GRP176-related immunomodulator prognostic model (GRIM) based on the above 4 genes, which was validated to have good predictive power. Finally, we developed a nomogram based on the risk score of GRIM and verified its accuracy. These results suggested that GPR176 is closely related to the prognosis and TIM of STAD. GPR176 may be a new potential target for immunotherapy in STAD.
[Retracted] Uncertainty Analysis of Key Influencing Factors on Stability of Tailings Dam Body
Authors: Qian Shanguang , Hou Kepeng
Published: April 2023

With the continuous expansion of the mining scale of mineral resources, many tailings are produced. In order to avoid the impact of harmful substances in the tailings on the residents around the tailings pond, it is necessary to explain the stability improvement. The dam safety monitoring system is mainly composed of observation sensors, telemetry data acquisition module, industrial control network, and automatic monitoring system. Through the work of the computer, the dam observation data can be automatically collected, processed, analyzed, and calculated. This paper adopts the automated system that makes preliminary judgments and graded alarms on whether the dam’s behavior is normal or not to provide early safety warning reports for monitoring objects. In this paper, combined with a specific example of a tailings reservoir dam body, the comprehensive uncertainty method is used to analyze factors such as the height of the tailings dam, the height of the wetting line, the cohesion of the tailings soil layer, and the internal friction angle, and the stability of the dam body is calculated. The results show that the sensitivity order of the dam stability safety factor K to each factor is as follows: internal friction angle of the tailing silt layer > the height of the wetting line > dam body height > the cohesion of the tailing silt layer. The most dangerous slip surface will jump at the 19‐level subdam of the tailings pond. The remediation measures are of great significance for maintaining the ecology around the tailings pond and ensuring the personal safety of residents.
The Impact of Digital Transformation on Corporate Tax Avoidance: Evidence from China
Authors: Xie Kun , Huang Wei
Published: April 2023

Digital transformation plays an important role in reshaping the core competitiveness of enterprises and achieving high-quality development. Based on panel data of Chinese A-share listed companies in Shanghai and Shenzhen from 2009 to 2019, this study examines the impact of digital transformation on corporate internals from the perspective of corporate tax avoidance. It finds that digital transformation significantly inhibits corporate tax avoidance by improving the quality of corporate internal controls; its inhibitory effect on corporate tax avoidance shows significant heterogeneity when firms are in different tax collection intensities and receive different amounts of government subsidies; and the inhibition of corporate tax avoidance significantly improves the efficiency of corporate investment. The research in this study expands the theoretical understanding of digital transformation and corporate tax avoidance and provides relevant insights for the government to promote the deep integration of the digital economy with the real economy.
Macroalgae Improve the Growth and Physiological Health of White Shrimp (Litopenaeus vannamei)
Authors: Zhang Zhuofan , Shi Xiaohui , Wu Zijie , Wu Wenbo , Zhao Qun , Li Erchao
Published: April 2023

This study compared and evaluated the effects of nine native macroalgae species on the tropic coast of China on the growth and physiological health performance of white shrimp (Litopenaeus vannamei). Nine hundred juvenile shrimps weighing

1.6
±
0.02

 g were fed with nine different types of macroalgae for 28 days. The experimental groups were as follows: Con (the diet without macroalgae), CRA (Caulerpa racemosa), CLA (Caulerpa lentillifera), CSS (Caulerpa sertularioides), CLM (Chaetomorpha linum), ULA (Ulva lactuca), GBE (Gracilaria bailiniae), ASA (Acanthophora spicifera), SVC (Sargassum ilicifolium var. conduplicatum), and BGE (Betaphycus gelatinae). Results showed that the growth performance of shrimps fed on the macroalgae meals was significantly higher than that of the control group (

P
<
0.05

). The immune defense capacity (total hemocyte count, phagocytosis respiratory bursts, prophenoloxidase system, hemagglutination activity, and antibacterial and bacteriolytic activities) and antioxidant capacity (total antioxidant capacity, superoxide dismutase, catalase, glutathione peroxidase, and malondialdehyde) of L. vannamei fed on macroalgae meals were significantly higher than those of the control group (

P
<
0.05

). Specifically, the shrimps in the ASA group had the significantly higher physiological health level than shrimps in the other macroalgae groups (

P
<
0.05

), and the expression of immune and antioxidation-related genes was also significantly higher in the ASA group (

P
<
0.05

). Principal component analysis (PCA) demonstrated that optimal growth and physiological health efficacy were observed in the ASA group. In summary, this study suggested dietary manipulation using macroalgae to improve the growth performance, immune performance, and antioxidant capacity of L. vannamei, with the optimal macroalgae for the diet being Acanthophora spicifera.
Differential Evolution without the Scale Factor and the Crossover Probability
Authors: Zhang Xiaowei
Published: April 2023

Differential evolution has made great achievements in various fields such as computational sciences, engineering optimization, and operations management in the past decades. It is well known that the control parameter setting plays a very important role in terms of the performance improvement of differential evolution. In this paper, a differential evolution without the scale factor and the crossover probability is presented, which eliminates almost all control parameters except for the population size. The proposed algorithm looks upon each individual as a charged particle to decide on the shift of the individual in the direction of the difference based on the attraction-repulsion mechanism in Coulomb’s Law. Moreover, Taguchi’s parameter design method with the two-level orthogonal array is merged into the crossover operation in order to obtain better individuals in the next generation by means of better combination of factor levels. What is more, a new ratio of the signal-to-noise is proposed for the purpose of fair comparison of the numerical experiment for the tested functions which have an optimal value with 0. Numerical experiments show that the proposed algorithm outperforms the other 5 compared algorithms for the 10 benchmark functions.
Research on Forecasting of the Compressor Geometric Variable System Based on the MAE Model
Authors: Xia Cunjiang , Zhan Yuyou , Tan Yan , Wu Wenqing
Published: April 2023

The compressor geometric variable system is vital for aeroengines, as it affects their performance and design. To monitor the compressor geometric variable system states and detect anomalies in real time, a

t

-step forecasting method based on the MAE (masked autoencoders) model was proposed in this article. Unlike previous studies that used simulated or lab-generated data, we use actual flight data recorded by the aircraft data acquisition system to make our results more realistic. Through our experimental efforts, the feasibility of forecasting the compressor geometric variable system based on the MAE model is verified. That is not only the first application of transformer models with a masked pretraining mechanism in time series forecasts but also taking the lead in exploring the possibility of this key system forecast. We also test the generalizability of our method across different types of aeroengines. Finally, to make our theories more reasonable and convincing, experiments on different aeroengine states, including the transition state and the steady state, are carried out.
[Retracted] Construction and Case Analysis of Sensor News Whole Chain Production Model Based on Artificial Intelligence Technology
Authors: Bolaji Damilola Adetola
Published: April 2023

In the current era of data explosion, people’s media have access to a large amount of information through the Internet. How to generate effective and realistic news and let interested people accept it is a hot topic in the current news media industry. The continuous development of sensor technology and the application of artificial intelligence technology enable the directional push of intelligent sensor news to be realized. Intelligent sensor media uses sensor technology to monitor and collect information and then combines artificial intelligence and big data to process the information. After obtaining effective media information, it will be pushed in a targeted way and tracked for analysis. By analyzing the current situation and difficulties of sensor news, this paper seeks for an effective combination of artificial intelligence technology and sensor news and establishes a whole process directional push model for sensor news production and thermal tracking analysis. This model is pioneering and practical in the media field. In order to further verify the effectiveness of the model, the important application field of sensor news is selected as the simulation research object, and the specific selection and layout of sensors, the data analysis obtained by sensors, the push of environmental news, and the thermal tracking analysis are simulated. The results show that through data analysis, news editing, and targeted push of water pollution environmental news, the news has gained a certain degree of attention among the main design media. The popularity index is estimated based on the number of likes and comments forwarded by the current mainstream Internet media platforms (Toutiao, Tiktok, and Weibo). The environmental pollution news thermal index of the sensor reached the highest thermal index score of 12 on the 26th day after the activity. On the Weibo client, the message reached the highest heat index of 14 points on the 28th. The simulation analysis of actual cases further illustrates the advantages of this design framework.
Analysis on the Difference of Micropore Structure Characteristics and Physical Properties of Mixed Rock Reservoir
Authors: Chen Jinghua , Dong Fengjuan , Yuan Dongjiao , Zhou Jiayi , Ding Xiaojun , Bai Jinlian , Zhao Haizhu , Lu Xuefei
Published: April 2023

The accumulation of multiple source components leads to the superposition of multiple pore throat systems and similar pore throat distribution may correspond to different seepage capacity in the mixed rock reservoir. Taking the mixed rock reservoir of III+IV oil formation in Nanyishan Oilfield, Chaidamu Basin, as an example, the development characteristics of pore throat system and its controlling factors in the mixed rock were summarized by means of thin slice, scanning electron microscopy, X-ray diffraction and high pressure mercury injection, and the reservoir physical property differences and their genetic controlling mechanism were analyzed. The results show that the reservoir space of the mixed reservoir mainly consists of intergranular pore fracture, micropore fracture, and micropore-dissolution pore. The diverse and complex pore types make the reservoir space combination type, capillary pressure curve shape and reservoir physical properties are not completely corresponding. The higher the content of brittle minerals, the higher the reservoir permeability. However, the development of iron dolomite mainly destroys the reservoir. The permeability of reservoir is mainly controlled by the development degree of macropores and the pore size which is the main contribution to permeability, and the proportion of macropores increases with the increase of permeability.
On the Non‐Fourier’s Heat and Non‐Fick’s Mass Flux for the Quadratic Convection Flow of a Couple Stress Nanofluid with Wu’s Slip
Authors: Ibrahim Wubshet , Gamachu Dachasa , Tesfaye Abebe
Published: April 2023

The overall goal of this paper is to look at how non‐Fick’s and non‐Fourier’s concepts affect the quadratic convection flow of a couple stress nanofluid across an extending surface under Wu’s slip, convective heating, and convective mass transfer conditions. The governing equations in the investigation are also initially stated as higher‐order partial differential equations and thereafter rehabilitated into ordinary differential equations via similarity conversions. Finally, the numerical approach of the bvp5c solver in MATLAB R2019a is engaged to solve the resultant equations. It has been researched and shown using graphs and tables how physical characteristics affect the velocity, temperature, and concentration fields. The results show that the velocity profile along the x‐direction grows with intensifying values of the couple stress, quadratic convection, buoyancy, and third‐order slip constraints, whereas it declines with intensifying values of the fourth‐order slip and magnetic field constraints. Also, the results show that as the velocity ratio constraint is increased, the velocity field along the y‐axis increases. Furthermore, an augment in the values of the quadratic convection constraint and Schmidt number, respectively, causes a diminution in temperature and concentration distributions. The results of the current study can be used to increase lubricant production and reduce machinery deterioration. Furthermore, this theoretical and numerical deliberation has the potential to be beneficial in the field of bio‐fluid dynamics and biomedicine.
Collagen-Anchored Interleukin-2 and Interleukin-12 Safely Reprogram the Tumor Microenvironment in Canine Soft-Tissue Sarcomas
Authors: Stinson Jordan A. , Sheen Allison , Momin Noor , Hampel Jordan , Bernstein Rebecca , Kamerer Rebecca , Fadl-Alla Bahaa , Samuelson Jonathan , Fink Elizabeth , Fan Timothy M. , Wittrup K. Dane
Published: April 2023

Purpose:

Cytokine therapies such as IL2 and IL12 suffer from impractically small therapeutic windows driven by their on-target, off-tumor activity, limiting their clinical potential despite potent antitumor effects. We previously engineered cytokines that bind and anchor to tumor collagen following intratumoral injection, and sought to test their safety and biomarker activity in spontaneous canine soft-tissue sarcomas (STS).

Experimental Design:

Collagen-binding cytokines were canine-ized to minimize immunogenicity and were used in a rapid dose-escalation study in healthy beagles to identify a maximum tolerated dose. Ten client-owned pet dogs with STS were then enrolled into trial, receiving cytokines at different intervals prior to surgical tumor excision. Tumor tissue was analyzed through IHC and NanoString RNA profiling for dynamic changes within treated tumors. Archived, untreated STS samples were analyzed in parallel as controls.

Results:

Intratumorally administered collagen-binding IL2 and IL12 were well tolerated by STS-bearing dogs, with only Grade 1/2 adverse events observed (mild fever, thrombocytopenia, neutropenia). IHC revealed enhanced T-cell infiltrates, corroborated by an enhancement in gene expression associated with cytotoxic immune function. We found concordant increases in expression of counter-regulatory genes that we hypothesize would contribute to a transient antitumor effect, and confirmed in mouse models that combination therapy to inhibit this counter-regulation can improve responses to cytokine therapy.

Conclusions:

These results support the safety and activity of intratumorally delivered, collagen-anchoring cytokines for inflammatory polarization of the canine STS tumor microenvironment. We are further evaluating the efficacy of this approach in additional canine cancers, including oral malignant melanoma.
Data from Reallocating Cervical Cancer Preventive Service Spending from Low to High-Value Clinical Scenarios
Authors: Rockwell Michelle S. , Armbruster Shannon D. , Capucao Jillian C. , Russell Kyle B. , Rockwell John A. , Perkins Karen E. , Huffstetler Alison N. , Mafi John N. , Fendrick A Mark.
Published: April 2023

Abstract
Timely follow-up care after an abnormal cervical cancer screening test result is critical to the prevention and early diagnosis of cervical cancer. The current inadequate and inequitable delivery of these potentially life-saving services is attributed to several factors, including patient out-of-pocket costs. Waiving of consumer cost-sharing for follow-up testing (e.g., colposcopy and related cervical services) is likely to improve access and uptake, especially among underserved populations. One approach to defray the incremental costs of providing more generous coverage for follow-up testing is reducing expenditures on ‘low value’ cervical cancer screening services. To explore the potential fiscal implications of a policy that redirects cervical cancer screening resources from potentially low to high-value clinical scenarios, we analyzed 2019 claims from the Virginia All-Payer Claims Database to quantify: 1) total spending on low-value cervical cancer screening and 2) out-of-pocket costs associated with colposcopy and related cervical services among commercially-insured Virginians. In a cohort of 1,806,921 female patients (aged 48.1 + 24.8 years), 295,193 claims for cervical cancer screening were reported, 100,567 (34.0%) of which were determined to be low-value ($4,394,361 total; $4,172,777 for payers and $221,584 out-of-pocket [$2/patient]). Claims for 52,369 colposcopy and related cervical services were reported ($40,994,016 total; $33,457,518 for payers and $7,536,498 out-of-pocket [$144/patient]). These findings suggest that reallocating savings incurred from unnecessary spending to fund more generous coverage of necessary follow-up care is a feasible approach to enhancing cervical cancer prevention equity and outcomes.
Antibiotics in the Treatment of Uncomplicated Cystitis: A Google Trends Analysis
Authors: Değer Müslim Doğan , Madendere Serdar , Öztekin Çetin Volkan
Published: April 2023

Introduction: Using Google Trends (GT) data, the trend variations for the most common antibiotics used to treat uncomplicated cystitis were analyzed by time and region since 2004. Methods: GT was used to create a “line-graph” that shows how interest in a topic in certain locations has grown or decreased over time. The relative search volume, which is displayed on a scale of 0–100, was used to index the search values for specific phrases. Nitrofurantoin (NFN), fosfomycin (FOS), trimethoprim (TMP), pivmecillinam (PIV), and cefadroxil are among the antibiotics recommended by the European Association of Urology (EAU) and the American Urological Association for the treatment of uncomplicated cystitis. Using the “global” inquiry category, the data was searched “worldwide” from 1 February 2004 to 31 December 2021. Results: In the regression analysis, all antibiotics exhibited positive trends (p < 0.05). With a steady rise in popularity, NFN is the most popular antibiotic today. Search trend for cefadroxil stayed nearly stable until 2012, the rate of rise in the last 10 years increased, and cefadroxil is the second most popular antibiotic. In the previous 5 years, there was a decline in interest in TMP. In recent years, there was an increase in the trends for FOS and PIV. Conclusion: Clinicians and patients all around the world increasingly use the web to search for antibiotic therapies for uncomplicated cystitis. Antibiotics used to treat uncomplicated cystitis have various trends in different continents throughout the world. The web trends seem to be compatible with daily use.
Effect of Plasma Unit Weight and Donor Sex on Post-Donation Citrate Level: An Experimental Study on Plasmapheresis Donors
Authors: Marraccini Chiara , Schiroli Davide , Mancuso Pamela , Molinari Giuseppe , Razzoli Agnese , Gavioli Gaia , Fasano Tommaso , Baricchi Roberto , Giorgi Rossi Paolo , Merolle Lucia
Published: April 2023

Introduction: Plasmapheresis donation is considered safe and well tolerated, although long-term effects need to be clarified. The volumes of anticoagulant (ACD-A) used are variable and depend primarily on hematocrit (HCT), total blood processed, amount of plasma collected, and donor characteristics. To elucidate the effect of the plasma unit weight setting on plasmapheresis efficiency and ACD-A distribution, we enrolled male donors undergoing a controlled apheresis process donating 700 g and 720 g in two different sessions. In parallel, we investigated a possible effect of sex, recruiting women donating 700 g of plasma. Methods: The study was conducted on men donating 720 g and (12 months later) 700 g of plasma, and on women donating 700 g of plasma. The main outcomes were pre-/post-donation delta (Δ) citrate concentration in donor plasma and ACD-A reinfused to the donor. Information concerning the annual check-up and the procedure was also collected. Intergroup comparisons (men donating 720 g vs. men donating 700 g and men vs. women both donating 700 g) and intragroup associations with donor and procedural characteristics were reported. Results: With the procedure set at 720 g, the machine processed around 44 mL more whole blood to collect 20 g more plasma, and 720 g donors received around 12 mL more anticoagulant than 700 g donors. Accordingly, Δ citrate concentration was 1.5 times higher (12 μm), with a greater variability observed for 720 g donations. Citrate concentration in the plasma unit was lower in the 720 g group, although not significantly. Comparing outcomes between women and men donating 700 g, we observed higher (and highly variable) Δ citrate and reinfused ACD-A in women, accompanied by lower anticoagulant levels in the unit. Increased Δ citrate is inversely associated with HCT and age in men and with HCT and triglycerides in women. Reinfused ACD-A correlates with HCT in women but not in men. Conclusion: Unit weight setting and sex influence an ACD-A shift from the estimated values toward an increased reinfusion to donor. In parallel, we observed an impact of age and sex on post-donation citrate metabolism. Altogether, these elements should be taken into account for the development of tailored approaches aimed at maintaining similar safety profiles for all donors using different plasmapheresis settings.
Identification of a Novel NRG1 Fusion with Targeted Therapeutic Implications in Locally Advanced Pediatric Cholangiocarcinoma: A Case Report
Authors: Mitchell Sarah G. , Basu Gargi D. , Eaton Bree , Goodman Laurie J. , Goldsmith Kelly C.
Published: April 2023

Locally advanced cholangiocarcinoma has a poor prognosis, with long-term survival only for patients where complete surgical resection is achieved. Median overall survival with chemotherapy alone is less than 1 year. Novel strategies combining conventional chemotherapy and radiotherapy followed by targeted agents can lead to durable treatment responses and are applicable to cholangiocarcinoma management. Pediatric cholangiocarcinoma is exceedingly rare, with an estimate of 15–22 cases reported in the last 40 years. As such, no standard therapeutic regimen exists. We present a case of a 16-year-old previously healthy patient with unresectable cholangiocarcinoma whose tumor genetic sequencing revealed a novel, actionable neuregulin-1 (NRG1) gene translocation. The patient underwent standard systemic chemotherapy with gemcitabine and cisplatin followed by hypofractionated proton radiation therapy for local control. The patient then started an oral pan-ERBB (erythroblastic B receptor tyrosine kinases including ErbB1/EGFR, ErbB2/HER2, ErbB3/HER3, ErbB4/HER4) family inhibitor as a maintenance medication, remaining with stable disease and excellent quality of life for over 2 years. This case highlights a novel NRG1 fusion in a rare clinical entity that provided an opportunity to utilize a multimodal therapeutic strategy in the pediatric setting.
Mild Tricuspid Regurgitation: A Marker of Disease Burden Independently Associated with Increased Mortality
Authors: Gotsman Israel , Zwas Donna R , Elbaz Greener Gabby , Planer David , Amir Offer , Leibowitz David
Published: April 2023

Introduction: Tricuspid regurgitation (TR) is a common finding which appears to be associated with a worse prognosis. There are conflicting data regarding the prognostic impact of mild TR. We examined the clinical characteristics and echocardiographic properties of subjects with TR and its impact on clinical outcome with particular emphasis on subjects with mild TR. Methods: Consecutive echocardiography examinations during 5 years were evaluated for TR severity and outcome including mortality and cardiovascular hospitalizations. Results: The study included 21,429 subjects; 45% of the subjects had mild TR, 15% had moderate TR, and 6.5% had severe TR. Primary organic TR was evident in 7% of the subjects, a percentage that increased with increasing TR severity. TR severity was incrementally associated with older subjects with an increasing number of comorbidities and echocardiographic abnormalities. 29% of the subjects died at a median follow-up duration of 8.7 years. Increasing severity of TR was independently and incrementally associated with mortality. Subjects with mild TR had a 25% increased mortality rate compared to subjects with minimal TR (HR 1.25, 95% CI: 1.12–1.39, p < 0.001) after adjustment for significant clinical parameters. TR severity was also an independent incrementally graded predictor of cardiovascular hospitalization and mortality (mild TR: HR 1.23, 95% CI: 1.12–1.34, p < 0.001). Conclusions: TR is associated with older and sicker patients with numerous comorbidities. TR severity is a predictor of a worse clinical outcome. Mild TR was independently associated with decreased survival. TR should be considered a marker of a disease burden with a poor prognosis.
Variation in the Dopamine-4-Receptor Gene in Patients with Type 1 Diabetes
Authors: Słomiński Bartosz , Skrzypkowska Maria , Myśliwiec Małgorzata , Trzonkowski Piotr
Published: April 2023

Introduction: Because dopaminergic signaling pathways are one of the regulators of autoimmunity, we hypothesize that the −521C>T DRD4 gene polymorphism may associate with the risk of diabetes mellitus type 1 (DM1) and its comorbidities. Methods: In this case-control study, we have examined 300 patients with DM1 in comparison to 300 healthy age-matched controls. Utilizing the amplification refractory mutation system-polymerase chain reaction method, we have analyzed the −521C>T polymorphism of dopamine D4 receptor-encoding gene. Obtained results have been evaluated according to diabetes comorbidities, inflammatory markers, CD14++CD16−, and CD14+CD16+ monocyte subsets as well as lipid profile. Results: The key results of our study are as follows: (1) CC genotype and C allele are associated with a reduced risk of DM1 development (OR = 0.593, p = 0.005 and OR = 0.725, p = 0.003, respectively), whereas TT genotype and T allele are associated with a higher risk of DM1 (OR = 1.408, p = 0.04 and OR = 1.380, p = 0.003, respectively); (2) CC genotype is associated with an increased risk of dyslipidemia and retinopathy in diabetic patients (OR = 2.376, p = 0.001 and OR = 2.111, p = 0.01, respectively); (3) CC genotype and C allele carriers had the highest frequency of pro-inflammatory CD16+ monocytes (p = 2*10−4 and 0.04, respectively); (4) the DRD4 −521C>T polymorphism modifies the inflammatory status as well as lipid profile in DM1 patients. Conclusion: Our data imply that the dopaminergic signaling pathways may play an important role in the etiology of DM1 as well as its comorbidities and will provide a new insight into the DM1 risk management. The −521C>T DRD4 gene polymorphism could be considered a genetic marker to predict susceptibility to DM1 as well as retinopathy and dyslipidemia progress in patients with already established disease.
Bioinspired Approaches to Engineer Antithrombogenic Medical Devices for Vascular Intervention
Authors: Hong Jun Ki , Waterhouse Anna
Published: April 2023

Medical devices form a critical component of health care systems for treating and maintaining patient health. However, devices exposed to blood are prone to blood clotting (thrombosis) and bleeding complications leading to device occlusion, device failure, embolism and stroke, and increased morbidity and mortality. Over the years, developments in innovative material design strategies have been made to help reduce the occurrence of thrombotic events on medical devices, but complications persist. Here, we review material and surface coating technologies that have taken bioinspiration from the endothelium to reduce medical device thrombosis, either by mimicking aspects of the glycocalyx to prevent adhesion of proteins and cells to the material surface or mimicking the bioactive function of the endothelium through immobilized or released bioactive molecules to actively inhibit thrombosis. We highlight newer strategies that take inspiration from multiple aspects of the endothelium or are stimuli responsive, only releasing antithrombotic biomolecules when thrombosis is triggered. Emerging areas of innovation target inflammation to decrease thrombosis without increasing bleeding, and interesting results are coming from underexplored aspects of material properties, such as material interfacial mobility and stiffness, which show that increased mobility and decreased stiffness are less thrombogenic. These exciting new strategies require further research and development before clinical translation, including consideration of longevity, cost, and sterilization, but show capacity for the development of more sophisticated antithrombotic medical device materials.
Magnetic Resonance Imaging of Mouse Cerebral Cavernomas Reveal Differential Lesion Progression and Variable Permeability to Gadolinium
Authors: Fisher Delaney G. , Sharifi Khadijeh A. , Ulutas E. Zeynep , Kumar Jeyan S. , Kalani M. Yashar S. , Miller G. Wilson , Price Richard J. , Tvrdik Petr
Published: April 2023

Background:

Cerebral cavernous malformations, also known as cavernous angiomas, are blood vessel abnormalities comprised of clusters of grossly enlarged and hemorrhage-prone capillaries. The prevalence in the general population, including asymptomatic cases, is estimated to be 0.5%. Some patients develop severe symptoms, including seizures and focal neurological deficits, whereas others remain asymptomatic. The causes of this remarkable presentation heterogeneity within a primarily monogenic disease remain poorly understood.

Methods:

We established a chronic mouse model of cerebral cavernous malformations, induced by postnatal ablation of
Krit1
with
Pdgfb-CreERT2
, and examined lesion progression in these mice with T2-weighted 7T magnetic resonance imaging (MRI). We also established a modified protocol for dynamic contrast-enhanced MRI and produced quantitative maps of gadolinium tracer gadobenate dimeglumine. After terminal imaging, brain slices were stained with antibodies against microglia, astrocytes, and endothelial cells.

Results:

These mice develop cerebral cavernous malformations lesions gradually over 4 to 5 months of age throughout the brain. Precise volumetric analysis of individual lesions revealed nonmonotonous behavior, with some lesions temporarily growing smaller. However, the cumulative lesional volume invariably increased over time and after about 2 months followed a power trend. Using dynamic contrast-enhanced MRI, we produced quantitative maps of gadolinium in the lesions, indicating a high degree of heterogeneity in lesional permeability. MRI properties of the lesions were correlated with cellular markers for endothelial cells, astrocytes, and microglia. Multivariate comparisons of MRI properties of the lesions with cellular markers for endothelial and glial cells revealed that increased cell density surrounding lesions correlates with stability, whereas denser vasculature within and surrounding the lesions may correlate with high permeability.

Conclusions:

Our results lay a foundation for better understanding individual lesion properties and provide a comprehensive preclinical platform for testing new drug and gene therapies for controlling cerebral cavernous malformations.