bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel photocatalyst system to deep desulfurization of petroleum model and gas condensate by Box–Behnken design
Authors: Raeisi Ilnaz , Derakhshi Pirouz , Azar Parviz Aberoomand , Tehrani Mohammad Saber
Published: September 2022

In this research, cobalt (Co)/molybdenum (Mo) and nickel (Ni) doped with titanium dioxide (TiO2) were loaded onto multi-walled carbon nanotubes (MWCNTs). Then, the magnetization catalyst, iron oxide (Fe3O4), was loaded on them, which was used for the deep desulfurization of dibenzothiophene (DBT). These catalysts were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, energy-dispersive X-ray spectroscopy, differential reflectance spectroscopy, and Brunauer–Emmett–Teller, Barrett–Joyner–Halenda, and vibrating sample magnetometer techniques. The photocatalytic activity of these catalysts was experienced under visible light using DBT. The response surface methodology based on the Box–Behnken design was used to evaluate parameters, including catalyst dosage (g), time (min), and concentration of DBT (mg L−1). The highest degradation efficiency under optimal conditions for CoMoNi/TiO2/MWCNTs/Fe3O4catalysts with a catalyst dosage of 0.3 g, a time of 180 min, and a concentration of 50 mg L−1was 99.99%. Optimum conditions were studied for desulfurization of the gas condensate. The highest desulfurization efficiency (90.33%) was obtained by the CoMoNi/TiO2/MWCNTs/Fe3O4catalyst.
Relationships among water, food, energy, and ecosystems in the Mid-Latitude Region in the context of sustainable development goals
Authors: Wang Sonam Wangyel , Kim Whijin , Song Cholho , Park Eunbeen , Jo Hyun-Woo , Kim Jiwon , Lee Woo-Kyun
Published: September 2022

The progress of the global effort to achieve Sustainable Development Goals (SDGs) is increasingly impeded by the degradation of critical and fundamental resources such as water, food, energy, and ecosystem services. The Mid-Latitude Region (MLR) of the world is at the forefront of confronting these challenges due to rapid population growth, increasing poverty, and drought and climate change that are exacerbating the transition of semi-arid landscapes to deserts. While scientific studies are accumulating around the water–food–energy–ecosystem nexus, efforts to simulate how the linkages among the elements relate to SDGs are lacking in the MLR. We attempt to review and analyze existing literature about how water–food–energy–ecosystems operate, interact, and relate to SDGs. We identified 37 relationships and ascertained the nature of their interactions, of which 12 are significant and have direct bearings on the SDGs. The findings show that most studies and approaches that address the nexus challenges in the MLR exist in silos. In addition, there is a lack of a scientific approach to quantify how the nexus operates and relates to SDGs. For instance, past studies show that deforestation for agriculture could increase food security. However, there is a weak focus on trade-offs (e.g., loss of ecosystem services due to deforestation). Deforestation is also shown to have a negative relationship with the quantity and quality of water (SDG6) as well as the functionality of an ecosystem (SDG15). Furthermore, the review has indicated a negative relationship between irrigated agriculture and water and a positive relationship with food. This directly implies that water and food issues must be addressed in tandem and not separately if we are to achieve SDGs 2 and 6. The review supports the idea that water, food, energy, and ecosystem services cannot be managed separately, and that future approaches must focus on integrating and optimizing the connections among them to ensure sustainable development.
FIRST COME, FIRST SERVED: INVESTIGATING STRATEGIES TO OVERCOME CONSUMER LEAPFROGGING BEHAVIOUR
Authors: KILLMER JAN F. , HEIDENREICH SVEN
Published: September 2022

The phenomenon of ‘consumer leapfrogging’ represents a conscious shift of consumers’ purchase decision for an innovation to a future product generation, and results in lower-than-expected demand. As consumers skip product generations, new product diffusion for the initial innovation and corresponding company turnover is capped. While previous studies highlight the importance of consumer leapfrogging behaviour, effective marketing strategies to attenuate detrimental consequences are lacking. To close this research gap, this paper empirically tests the effectiveness of various marketing strategies (trade-in program, bonus program, money-back guarantee, and product bundles) as potential countermeasures to consumer leapfrogging via a scenario-based online experiment with a 5 (four marketing strategies and control group) × 2 (low/high radical product) between-subjects design. Our results reveal that trade-in and bonus programs as well as money-back guarantees are effective countermeasures to consumer leapfrogging behaviour. Furthermore, our findings also show that the effectiveness of the instruments decreases with the degree of product radicality.
Describing UI Screenshots in Natural Language
Authors: Leiva Luis A. , Hota Asutosh , Oulasvirta Antti
Published: September 2022

Being able to describe any user interface (UI) screenshot in natural language can promote understanding of the main purpose of the UI, yet currently it cannot be accomplished with state-of-the-art captioning systems. We introduce XUI, a novel method inspired by the global precedence effect to create informative descriptions of UIs, starting with an overview and then providing fine-grained descriptions about the most salient elements. XUI builds upon computational models for topic classification, visual saliency prediction, and natural language generation (NLG). XUI provides descriptions with up to three different granularity levels that, together, describe what is in the interface and what the user can do with it. We found that XUI descriptions are highly readable, are perceived to accurately describe the UI, and score similarly to human-generated UI descriptions. XUI is available as open-source software.
Fundamental Neutron Physics at Spallation Sources
Authors: Fomin Nadia , Fry Jason , Pattie Robert W. , Greene Geoffrey L.
Published: September 2022

Low-energy neutrons have been a useful probe in fundamental physics studies for more than 70 years. With advances in accelerator technology, many new sources are spallation based. These new, high-flux facilities are becoming the sites for many next-generation fundamental neutron physics experiments. In this review, we present an overview of the sources and the current and upcoming fundamental neutron physics programs.
Hypoxia offsets the decline in brachial artery flow-mediated dilation after acute inactivity
Authors: Hanson Brady E. , Iwamoto Erika , Mouser Bryan L. , Miller Kayla A. , Casey Darren P.
Published: September 2022

Intermittent (IH), as opposed to continuous hypoxia (CH), is thought to have beneficial effects on cardiovascular function and health. In the present study, we examined the acute effects of IH and CH (∼80% pulse oxygen saturation via 10% oxygen tank) on peripheral vascular function. Brachial artery flow-mediated dilation (FMD) was used to assess vascular function in 12 young adults (23 ± 5 yr; 8 M/4 F) before and after 50 min of IH (5 cycles; 4-min normoxia/6-min hypoxia per cycle), CH (20-min normoxia followed by 30-min hypoxia), or time control (50-min normoxia) interventions. Brachial artery diameter and velocity were measured using Doppler ultrasound to assess blood flow and shear rate. The total change in shear rate was greater during IH (634 ± 1,073·s−1, P < 0.05) and CH (321 ± 833·s−1, P = 0.05) than during time control (−412 ± 789·s−1). %FMD was reduced following time control (7.4 ± 1.2 to 5.9 ± 1.1%, P < 0.05) but was maintained following both hypoxia trials (IH: 7.2 ± 1.5 to 7.5 ± 1.5%, P = 0.52; CH: 6.9 ± 1.6 to 6.8 ± 1.4%, P = 0.73). Normalized %FMD for shear rate area under the curve (%FMDSRAUC) was reduced following the time control trial (4.2 ± 1.4 to 3.7 ± 0.9%, P < 0.05) with no change observed with CH (4.0 ± 1.5 to 3.9 ± 1.4%, P = 0.71). However, %FMDSRAUC increased with IH (3.8 ± 1.1 to 4.5 ± 1.5%, P < 0.05). Our data suggest that acute exposure to hypoxia (both intermittently and continuously) offsets the decline in vascular function after brief inactivity. The potential beneficial effect of hypoxia on peripheral vascular function observed in the current study may be associated with enhanced brachial artery shear in response to the hypoxic challenge.
Mathematical Model Formulation and Analysis for COVID-19 Transmission with Virus Transfer Media and Quarantine on Arrival
Authors: Ega Tesfaye Tadesse , Ngeleja Rigobert Charles
Published: September 2022

An outbreak of severe acute respiratory syndrome (COVID-19) killed 287,355 with 4, 257,578 cases worldwide as of May 12, 2020. In this paper, we propose an

S
E
Q

I

s

I

a

R
M

deterministic mathematical model which contains compartments for both human-to-human transmission and transmission through contaminated surfaces. Without intervention, the role of symptomatic and asymptomatic cases in humans is found to be very high in the transmission of the virus. Sensitive parameters which are associated with increased transmission of the COVID-

19

virus were identified. According to the sensitivity results, the most sensitive parameters were disease-induced death rates of symptomatic and asymptomatic infectious people (

σ

), the rate of removal of virus from surfaces and environment (

ν

), and the rate of infection by asymptomatic infectious people (

λ

2

) and symptomatic infectious people (

λ

1

). The numerical results of our model confirm the sensitivity results that there are more new incidences of asymptomatic cases than symptomatic cases, which escalates the transmission of the virus in the community. Combined interventions like increasing both the rate of removal of viruses from surfaces and environment and decreasing the rate of infection in asymptomatic cases can play a significant role in reducing the average number of secondary infection (

R

0

) to less than unity, causing COVID-

19

to die out.
Effects of Carbon Emission on the Environment of High-Speed Vehicles on Highways for Intelligent Transportation Systems
Authors: Liu Yuanyuan , Liu Jingwei , Dou Huili
Published: September 2022

The emergence of intelligent applications of the Internet of things (IoT) is facilitating human beings up to a great extent. However, numerous applications of the IoT have an adverse impact on our society and environment as well that needs to be dealt with properly to provide smart services to the end-users. For instance, the carbon emissions of vehicles from intelligent transportation systems (ITS) driving on highways are high due to low-carbon traffic management. Therefore, this paper studies the impact of high-speed vehicles on the road causing carbon emissions. For this purpose, Ford, Volkswagen, and Toyota models were used as test subjects to count relevant parameters during May and October 2020. Carbon emissions and vehicle speed on highways were calculated. The relationship between vehicle speed and fuel consumption on the expressway was also analyzed. The results confirm that the fuel consumption of Ford, Volkswagen, and Toyota is the lowest when the vehicle speed is 70 km/h, 80 km/h, and 90 km/h, respectively. The relationship between vehicle speed and carbon emissions in sunny and rainy weather is also analyzed based on the proposed model. It was concluded that the carbon emissions of Ford, Volkswagen, and Toyota are 6.24 mg/1000 km, 6.52 mg/1000 km, and 9.29 mg/1000 km, respectively, under sunny weather conditions. In contrast, the emissions continue to increase when the car accelerates. The driving speed range corresponding to the minimum carbon emissions per hundred kilometres of the three vehicles is 60–120 km/h. However, the carbon emissions of the three vehicles change in rainy weather. The minimum carbon emission of Ford is 6.07 mg/1000 km when the driving speed is within the range of 80–100 km/h. In comparison, Volkswagen and Toyota have the lowest carbon emissions of 6.23 mg/1000 km and 9.15 mg/1000 km, respectively, when the vehicle speed is in the range of 80–120 km/h. The results obtained in this paper establish a unique relationship between vehicle speed, type of vehicle, weather, and highway conditions for any application of the ITS.
Evaluation of 3,5-Diphenyl-2-Pyrazolines for Antimitotic Activity by Inhibition of Tubulin Polymerization
Authors: Shin Soon Young , Jung Euitaek , Lee Young Han , Lim Yoongho , Ahn Seunghyun , Koh Dongsoo
Published: September 2022

Chalcones have a skeleton of diphenyls connected via an α,β-unsaturated carbonyl group. Many chalcone derivatives have been shown to interact with tubulin. Based on previous reports, chalcones derived by substitution of a carbonyl group with 2-pyrazoline can be expected to inhibit tubulin polymerization. Therefore, 3,5-diphenyl-2-pyrazolines were prepared to investigate their ability to inhibit tubulin polymerization. The clonogenic long-term survival assay showed that derivative 4, 5-(3,5-dimethoxyphenyl)-3-(2-methoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide, was the most effective at inhibiting the clonogenicity of HCT116 human colon cancer cells. Derivative 4 induced G2/M cell cycle arrest. In addition, derivative 4 caused dispersed microtubules, a disorganized spherical arrangement of chromosomes, and inhibition of mitotic spindle formation. The binding mode between tubulin and derivative 4 was elucidated by in silico molecular docking. Derivative 4 was superimposed with colchicine and entered the colchicine-binding site well. These results suggest that derivative 4 inhibits tubulin polymerization by binding to the colchicine binding site of tubulin, thus preventing mitotic spindle formation during mitosis in HCT116 colon cancer cells. We propose that derivative 4 could be used as a promising antimitotic chemotherapeutic agent.
Statistical Estimation of Blast Fragmentation by Applying 3D Laser Scanning to Muck Pile
Authors: Liu Qiang , Shi Fuqiang , Wang Xuguang , Zhao Mingsheng
Published: September 2022

Run-of-mine fragmentation is an important aspect of mine productivity optimization, as it affects all mine-to-mill processes. The current blasting fragmentation calculation methods do not consider the 3D geometric information. Therefore, their calculation results are imprecise. 3D laser scanning is a technique for extracting the 3D geometric information of an object by constructing a 3D point cloud model, with which extra information on the geometrical characteristics of an object could be captured than with the technique of 2D image processing. In this paper, 3D laser scanning technology was utilized for the calculation of the rock blocks on the surface of a muck pile, and the information about the surface blocks was utilized as the samples for the statistical estimation of blasting fragmentation of muck pile (BFMP). Monte Carlo simulation was utilized as the statistical estimation method for the BFMP. In the lab experiment, results from 2D image processing technique and from 3D laser scanning technique combined with statistical estimate were compared with the physical measurements utilizing a water tank, which show that results with 3D laser scanning are more similar to the physical measurement. Finally, the applicability of 3D laser scanning technology combined with statistical methods to the calculation of blast fragmentation was estimated through field tests in Biesikuduke and Santanghu mine, two open-pit coal mines in Xinjiang Province of western China. Results show that the accuracy of the statistical estimation results of BFMP has a particle size deviation of 1–3 cm.
Networking Method for the Structure of a Large Modular Deployable Space Antenna
Authors: Tian Dake , Fan Xiaodong , Zhang Junwei , Jin Lu , Liu Rongqiang , Zhang Yu
Published: September 2022

A high-precision networking method for a modular deployable antenna with ultramultiple modules is proposed to solve the problem of achieving an accurate formation of the structure of a large-aperture modular deployable space antenna. In accordance with the general requirements for the deployment surface of deployable antennas, the structure composition and deployment principle of a deployable antenna are analyzed, and the topological law of a hexagonal prism modular structure is expounded. On the basis of basic theories of differential geometry, analytical geometry, and robotics, the mathematical model of an envelope circle and that of its center are established. Then, a networking model of structure that includes 61 modules in the fully deployed state is established. Finally, the established model is verified via a numerical simulation method, and the influence law of structural parameters on networking characteristics is analyzed and studied. Simulation results show that the networking method can realize an accurate connection of multiple modules. The networking method for the structure of a modular deployable antenna proposed in this study can provide a reference for research on basic theory of a deployable antenna’s mechanism and related engineering applications.
An Integrated Test-Based Nonlinear Aeroelastic Analysis Method to Freeplay-Induced Limit-Cycle Oscillations
Authors: Sun Yukai , Wu Zhigang , Yang Chao , Wang Xiangyu , Wang Chuansheng
Published: September 2022

The nonlinear limit-cycle oscillations induced by aileron rotational freeplay are investigated by numerical simulation and flutter wind tunnel tests. An integrated nonlinear aeroelastic analysis method and procedure based on the nonlinear system identification technology is proposed. Based on the characteristics of the structure, a low-speed nonlinear flutter wing-aileron model that considers both the linear flutter test and the nonlinear limit-cycle oscillation test with aileron rotational freeplay is designed. The wind tunnel tests are conducted with the model, and the stable limit-cycle oscillation is observed by accelerometers under the linear flutter boundary with a 0° angle of attack. Higher-order harmonic vibration is also observed with a low proportion compared to the fundamental oscillation, and the limit-cycle oscillation grows gradually with the increase of airspeed until flutter occurs. The comparison of numerical and experimental investigation shows high consistency.
Optimization, Characterization, and Anticancer Potential of Silver Nanoparticles Biosynthesized Using Olea europaea
Authors: Felimban Afnan I. , Alharbi Njud S. , Alsubhi Nehad S.
Published: September 2022

Green synthesis has attracted significant attention as an eco-friendly, low-cost, energy-efficient, and non-toxic method for preparing silver nanoparticles (AgNPs) for cancer therapy. This study optimized the green synthesis of AgNPs using Olea europaea extracts and evaluated their anticancer potential. The biosynthesized AgNPs were characterized using various methods, showing stable AgNPs with a desirable morphology and high yield, improving the properties of AgNPs for various medicinal applications. The biosynthesized AgNPs were predominantly spherical, with small sizes ranging from 13 to 21 nm and highly stable at −23 and −24 mV. The findings of this study suggest that green-synthesized AgNPs using Olea europaea and sunlight possess significant anticancer activity against cancer cells in vitro. Further investigation of green synthesis would help to form high-quality AgNPs that have promising potential in treating disease and fighting undesirable pathogens.
Analysis on the Bus Arrival Time Prediction Model for Human-Centric Services Using Data Mining Techniques
Authors: Shanthi N. , V E Sathishkumar , Upendra Babu K. , Karthikeyan P. , Rajendran Sukumar , Allayear Shaikh Muhammad
Published: September 2022

The human-computer interaction has become inevitable in digital world. HCI helps humans to incorporate technology to resolve even their day-to-day problems. The main objective of the paper is to utilize HCI in Intelligent Transportation Systems. In India, the most common and convenient mode of transportation is the buses. Every state government provides the bus transportation facility to all routes at an affordable cost. The main difficulty faced by the passengers (humans) is lack of information about bus numbers available for the particular route and Estimated Time of Arrival (ETA) of the buses. There may be different reasons for the bus delay. These include heavy traffic, breakdowns, and bad weather conditions. The passengers waiting in the bus stops are neither aware of the delay nor the bus arrival time. These issues can be resolved by providing an HCI-based web/mobile application for the passengers to track their bus locations in real time. They can also check the Estimated Time of Arrival (ETA) of a particular bus, calculated using machine learning techniques by considering the impacts of environmental dynamics, and other factors like traffic density and weather conditions and track their bus locations in real time. This can be achieved by developing a real-time bus management system for the benefit of passengers, bus drivers, and bus managers. This system can effectively address the problems related to bus timing transparency and arrival time forecasting. The buses are equipped with real-time vehicle tracking module containing Raspberry Pi, GPS, and GSM. The traffic density in the current location of the bus and weather data are some of the factors used for the ETA prediction using the Support Vector Regression algorithm. The model showed RMSE of 27 seconds when tested. The model is performing well when compared with other models.
Traditional Chinese Medicine Based Acupoint Application for Asthma Treatment in Children: A Meta-Analysis and Systematic Review
Authors: Wang Yijie , Guo Tingting , Yang Fushuang , Li Yongjun , Liu Lujia , Lin Kexin , Li Zhijun , Wang Youpeng
Published: September 2022

Objective. By conducting a systematic review of the efficacy of acupoint application on children with asthma. Methods. We searched Chinese databases (CNKI, VIP, and Wanfang) and English databases (PubMed, Embase, and Cochrane Library) for studies from the establishment of the database to October 2021. The included literature studies were randomized control studies investigating the treatment of asthma in children by acupoint application. The primary outcomes included the cure rate, the resolution time of cough, and the resolution time of wheezing. The secondary outcomes included pulmonary function and interleukins. Stata 15 and RevMan 5.4 were used to analyze the extracted data. Results. A total of 24 related studies were included containing 2716 cases. The meta-analysis showed that TCM group was superior to control group in terms of cure rate, pulmonary function (FEV1), and resolution time of wheezing in children with asthma [RR = 1.26,95% (1.21,1.31),

P
<
0.05

; SMD = 0.81, 95%CI (0.05,1.56),

P
<
0.05

; WMD = −1.40, 95%CI (−1.75, −1.05),

P
<
0.05

]. Conclusions. The present study shows that acupoint application is an effective treatment for children with asthma in China, especially in alleviating wheezing and improving quality of life.
Investigation on Modulus of Elasticity of Badminton String by Response Surface Methodology
Authors: Ji Feng
Published: September 2022

Modulus of elasticity (MOE) is one of the important indexes to evaluate the performance of badminton string. In this work, a series of tensile testing were performed to explore the changes in MOE at different temperature, humidity, and tensile rate. Based on the experimental results, an MOE model for badminton string was developed by using response surface methodology. Meanwhile, the significant contribution of each variable and two-factor interactions on MOE were investigated by analysis of variance. The special aim of this work was to determine the optimal processing parameters for maximum MOE for the higher performance of badminton string, and those processing parameters are temperature of 10.7°C, humidity of 0.19%, and tensile rate of 59.98 mm/min, which were propped to be adopted for the actual use of badminton string.
Estimation of the Serial Interval and the Effective Reproductive Number of COVID-19 Outbreak Using Contact Data in Burkina Faso, a Sub-Saharan African Country
Authors: Somda Serge M. A. , Ouedraogo Boukary , Pare Constant B. , Kouanda Seni
Published: September 2022

The COVID-19 outbreak has spread all around the world in less than four months. However, the pattern of the epidemic was different according to the countries. We propose this paper to describe the transmission network and to estimate the serial interval and the reproductive number of the novel coronavirus disease (COVID-19) in Burkina Faso, a Sub-Saharan African country. Data from the COVID-19 response team was analyzed. Information on the 804 first detected cases were pulled together. From contact tracing information, 126 infector-infectee pairs were built. The principal infection clusters with their index cases were observed, principally the two major identified indexes in Burkina. However, the generations of infections were usually short (less than four). The serial interval was estimated to follow a gamma distribution with a shape parameter 1.04 (95% credibility interval: 0.69–1.57) and a scale parameter of 5.69 (95% credibility interval: 3.76–9.11). The basic reproductive number was estimated at 2.36 (95% confidence interval: 1.46–3.26). However, the effective reproductive number decreases very quickly, reaching a minimum value of 0.20 (95% confidence interval: 0.06–0.34). Estimated parameters are made available to monitor the outbreak in Sub-Saharan African countries. These show serial intervals like in the other continents but less infectiousness.
Retinal Thickness Associates with Cognition Dysfunction in Young Adult with Type 1 Diabetes in Taiwan
Authors: Hsu Jung-Lung , Gu Pei-Shin , Kang Eugene Yu-Chuan , Lai Chi-Chun , Lo Fu-Sung
Published: September 2022

Background. Several factors could affect the cognitive dysfunction in patients with type 1 diabetes (T1D). Objectives. To report the characteristic of cognitive dysfunction in T1D and find its association with the retinal thickness. Subjects. We recruited one hundred and seven patients with T1D in our study. Methods. Detailed clinical and demographic factors and Cambridge Automated Neuropsychological Test Battery (CANTAB) were performed in all participants. The age at

onset
>

5 years old and ≤5 years old groups was defined as old- and young-onset groups. The levels of the average values of 5-year glycated hemoglobin (HbA1c_5) before study were collected. Ophthalmic study and central retinal thickness (CRT) were performed. Results. The median age of T1D was 24.9 years old and 57 participants were women. The median age at onset was 7.4 years old, and mean disease duration was 17.2 years. After adjusting off multiple covariates by the regression analyses, the young-onset group had significantly a longer latency in sustained attention than old-onset group (

P
=
0.02

). The HbA1c_5 showed a significantly negative association with the sustained attention (

P
=
0.03

). The average values of CRT showed significantly negative correlations with the reaction time in sustained attention and visual searching (

P
=
0.04

and

P
<
0.01

, respectively). Conclusions. Our results suggest that age at onset and glycemic control had significant impacts on different cognitive domains in T1D. The CRT had a significant correlation with sustained attention, which could be a surrogate markers of brain structural changes in T1D.
Transient Systemic Autophagy Inhibition Is Selectively and Irreversibly Deleterious to Lung Cancer
Authors: Khayati Khoosheh , Bhatt Vrushank , Lan Taijin , Alogaili Fawzi , Wang Wenping , Lopez Enrique , Hu Zhixian Sherrie , Gokhale Samantha , Cassidy Liam , Narita Masashi , Xie Ping , White Eileen , Guo Jessie Yanxiang
Published: September 2022

Autophagy is a conserved catabolic process that maintains cellular homeostasis. Autophagy supports lung tumorigenesis and is a potential therapeutic target in lung cancer. A better understanding of the importance of tumor cell-autonomous versus systemic autophagy in lung cancer could facilitate clinical translation of autophagy inhibition. Here, we exploited inducible expression of Atg5 shRNA to temporally control Atg5 levels and to generate reversible tumor-specific and systemic autophagy loss mouse models of KrasG12D/+;p53−/− (KP) non–small cell lung cancer (NSCLC). Transient suppression of systemic but not tumor Atg5 expression significantly reduced established KP lung tumor growth without damaging normal tissues. In vivo13C isotope tracing and metabolic flux analyses demonstrated that systemic Atg5 knockdown specifically led to reduced glucose and lactate uptake. As a result, carbon flux from glucose and lactate to major metabolic pathways, including the tricarboxylic acid cycle, glycolysis, and serine biosynthesis, was significantly reduced in KP NSCLC following systemic autophagy loss. Furthermore, systemic Atg5 knockdown increased tumor T-cell infiltration, leading to T-cell-mediated tumor killing. Importantly, intermittent transient systemic Atg5 knockdown, which resembles what would occur during autophagy inhibition for cancer therapy, significantly prolonged lifespan of KP lung tumor-bearing mice, resulting in recovery of normal tissues but not tumors. Thus, systemic autophagy supports the growth of established lung tumors by promoting immune evasion and sustaining cancer cell metabolism for energy production and biosynthesis, and the inability of tumors to recover from loss of autophagy provides further proof of concept that inhibition of autophagy is a valid approach to cancer therapy.

Significance:

Transient loss of systemic autophagy causes irreversible damage to tumors by suppressing cancer cell metabolism and promoting antitumor immunity, supporting autophagy inhibition as a rational strategy for treating lung cancer.

See related commentary by Gan, p. 4322
Dynamic Changes in the NK-, Neutrophil-, and B-cell Immunophenotypes Relevant in High Metastatic Risk Post Neoadjuvant Chemotherapy–Resistant Early Breast Cancers
Authors: Gazinska Patrycja , Milton Charlotte , Iacovacci Jacopo , Ward Joseph , Buus Richard , Alaguthurai Thanussuyah , Graham Rosalind , Akarca Ayse , Lips Esther , Naidoo Kalnisha , Wesseling Jelle , Marafioti Teresa , Cheang Maggie , Gillett Cheryl , Wu Yin , Khan Aadil , Melcher Alan , Salgado Roberto , Dowsett Mitch , Tutt Andrew , Roxanis Ioannis , Haider Syed , Irshad Sheeba
Published: September 2022

Purpose:

To identify potential immune targets in post-neoadjuvant chemotherapy (NAC)–resistant triple-negative breast cancer (TNBC) and ER+HER2– breast cancer disease.

Experimental Design:

Following pathology review, 153 patients were identified as having residual cancer burden (RCB) II/III disease (TNBC n = 80; ER+HER2–n = 73). Baseline pre-NAC samples were available for evaluation for 32 of 80 TNBC and 36 of 73 ER+HER2– cases. Bright-field hematoxylin and eosin assessment allowed for tumor-infiltrating lymphocyte (TIL) evaluation in all cases. Multiplexed immunofluorescence was used to identify the abundance and distribution of immune cell subsets. Levels of checkpoints including PD-1/PD-L1 expression were also quantified. Findings were then validated using expression profiling of cancer and immune-related genes. Cytometry by time-of-flight characterized the dynamic changes in circulating immune cells with NAC.

Results:

RCB II/III TNBC and ER+HER2– breast cancer were immunologically “cold” at baseline and end of NAC. Although the distribution of immune cell subsets across subtypes was similar, the mRNA expression profiles were both subtype- and chemotherapy-specific. TNBC RCB II/III disease was enriched with genes related to neutrophil degranulation, and displayed strong interplay across immune and cancer pathways. We observed similarities in the dynamic changes in B-cell biology following NAC irrespective of subtype. However, NAC induced changes in the local and circulating tumor immune microenvironment (TIME) that varied by subtype and response. Specifically, in TNBC residual disease, we observed downregulation of stimulatory (CD40/OX40L) and inhibitory (PD-L1/PD-1) receptor expression and an increase in NK cell populations (especially non-cytolytic, exhausted CD56dimCD16–) within both the local TIME and peripheral white cell populations.

Conclusions:

This study identifies several potential immunologic pathways in residual disease, which may be targeted to benefit high-risk patients.
Treatment Strategies and Mechanisms Associated with the Prevention of NASH-Associated HCC by a Toll-like Receptor 4 Inhibitor
Authors: Kwan Suet-Ying , Slayden Alyssa N. , Coronado Aubrey R. , Marquez Rosamaria C. , Chen Huiqin , Wei Peng , Savage Michelle I. , Vornik Lana A. , Fox Jennifer T. , Sei Shizuko , Liang Dong , Stevenson Heather L. , Wilkerson Gregory K. , Gagea Mihai , Brown Powel H. , Beretta Laura
Published: September 2022

We evaluated the cancer preventive efficacy of TAK-242, an inhibitor of Toll-like receptor 4 (TLR4), in a mouse model of hepatocellular carcinoma (HCC) occurring in the context of nonalcoholic steatohepatitis (NASH). We also assessed the cellular events associated with the preventive treatment efficacy. We tested oral administration of TAK-242, at clinically relevant but toxicity-reducing doses and scheduling, in mice with hepatocyte-specific deletion of Pten (HepPten−). The optimal dose and oral gavage formulation of TAK-242 were determined to be 30 mg/kg in 5% DMSO in 30% 2-hydroxypropyl-β-cyclodextrin. Daily oral administration of 30 mg/kg TAK-242 over 18 weeks was well tolerated and resulted in reduced development of tumors (lesions > 7.5 mm3) in HepPten− mice. This effect was accompanied by reduced macrovesicular steatosis and serum levels of alanine aminotransferase. In addition, 30 mg/kg TAK-242 daily treatment of small preexisting adenomas (lesions < 7.5 mm3) over 18 weeks, significantly reduced their progression to HCC. RNA sequencing identified 220 hepatic genes significantly altered upon TAK-242 treatment, that significantly correlated with tumor burden. Finally, cell deconvolution analysis revealed that TAK-242 treatment resulted in reduced hepatic populations of endothelial cells and myeloid-derived immune cells (Kupffer cells, Siglec-H high dendritic cells, and neutrophilic granule protein high neutrophils), while the proportion of mt-Nd4 high hepatocytes significantly increased, suggesting a decrease in hepatic inflammation and concomitant increase in mitochondrial function and oxidative phosphorylation upon TLR4 inhibition. In conclusion, this study identified treatment strategies and novel molecular and cellular mechanisms associated with the prevention of HCC in the context of NASH that merit further investigations.

Prevention Relevance:

Means to prevent development of HCC or progression of small adenomas to HCC in patients with NASH are urgently needed to reduce the growing mortality due to HCC. We characterized the chemopreventive effect of oral administration of the TLR4 inhibitor TAK-242 in a model of NASH-associated HCC.
Butyricimonas virosa Peritonitis in Peritoneal Dialysis Patient: A Case Report and Review
Authors: Lau Siew Yan , Bee Boon Cheak , Wong Hin-Seng , Abdul Hameed Ahneez
Published: September 2022

Butyricimonas virosa is a Gram-negative bacillus, which was first discovered in rat faeces in 2009. To date, only seven human infections have been reported in literature. To our knowledge, this is the first reported case of peritoneal dialysis (PD)-related peritonitis due to B. virosa. A 65-year-old Chinese man presented to the hospital with complaints of dizziness and vomiting. On admission, the drained peritoneal dialysate was cloudy. He was empirically treated as a case of PD-related peritonitis with intraperitoneal (IP) cefazolin, ceftazidime, and gentamicin. B. virosa was isolated from peritoneal fluid sample and the antibiotics were changed to IP imipenem and amikacin. Three weeks after completion of the antibiotics, the patient presented again with cloudy peritoneal dialysate and blood stained diarrhoea. IP imipenem and amikacin were recommenced. Multiple peritoneal dialysate samples were sent to the microbiology laboratory, but this time no microorganism was isolated. Colonoscopy examination revealed the presence of extensive rectosigmoidal ulcerations. IP imipenem was replaced with IP piperacillin-tazobactam when the patient developed imipenem-associated neurotoxicity at Day 9 of treatment. The patient recovered fully after completing 3 weeks of IP piperacillin-tazobactam and 2 weeks of IP amikacin. This is the first reported case of PD-related peritonitis due to B. virosa. Susceptibility data for B. virosa are scarce, but a 3-week course of IP piperacillin-tazobactam, imipenem, or meropenem could be potentially useful in treating PD-related peritonitis caused by this organism.
More Drug Monitoring and Less CT Scans of the Brain: Gabapentin Overdose in Two Peritoneal Dialysis Patients
Authors: Lehmann Kijanosh , Diab Sara , Meyer Torsten M. , Kielstein Jan T. , Eden Gabriele
Published: September 2022

In parallel with the decline of renal excretory function, drug dosing of many drugs becomes more challenging. Finding the right dose is even more difficult if kidney replacement therapy is instituted. This is further aggravated by the fact that even for substances with a narrow therapeutic range, drug monitoring is only rarely offered, let alone advocated. This holds also true for gabapentin, an anticonvulsant drug that is increasingly prescribed for indications such as cancer-related pain, restless legs syndrome, migraine, or uremic pruritus. The drug is excreted unchanged in urine, so plasma clearance of gabapentin is directly proportional to creatinine clearance. Hence, renal impairment reduces gabapentin excretion and increases plasma gabapentin concentrations in a linear fashion. Therefore, the elimination half-life of gabapentin is between 5 and 9 h, in patients with normal renal function but increases to 132 h in patients on dialysis. Epidemiological data from the USRDS underline this problem. About 19% of the 140,899 adult USA patients enrolled in Medicare coverage received gabapentin in 2011. Its use was associated with an increased risk of altered mental status, fall, and fracture. We report 2 patients in which overdose of gabapentin occurred. In 1 patient, severe neurological symptoms prompted an extensive diagnostic work up, while the underlying cause of the clinical presentation was a supra-therapeutic drug level of gabapentin. Consequently, symptoms subsided with the discontinuation of the drug. Indication and drug dose of gabapentin in dialysis patients should be tightly controlled, and drug monitoring used to avoid unintended overdose.
Liver Metastasis Occurring within Four Months of Early Breast Cancer Diagnosis: A Case Report and Literature Review
Authors: Xu Zhi , Yuan Jing Jing , Jiang Jie , Ma Lei
Published: September 2022

Liver metastasis commonly occurs; however, the luminal-type liver metastasis rarely develops at the early stage of breast cancer, posing key challenges in screening patients, giving early targeted treatment, and providing an opportunity to prolong survival. A 44-year-old female was diagnosed with breast cancer (pT2N0M0, IIa) and luminal B type postoperatively. The latest guidelines indicated four cycles of albumin-paclitaxel and cyclophosphamide chemotherapy. After 4 months of treatment, the patient was found to have hypoechoic nodules in the liver due to other diseases and was thereby diagnosed with breast cancer with liver metastasis. The latest guidelines did not recommend routine imaging and hematological examination of asymptomatic early breast cancer during follow-up. We suggest that follow-up should be strengthened for high-risk patients to maximize their benefits from early diagnosis and treatment.
Hemadsorption: A New Therapeutic Option for Selected Cases of Bromazepam Intoxication
Authors: Mekeirele Michaël , Verheyen Silke , Van Lancker Ruth , Wuyts Stephanie , Balthazar Tim
Published: September 2022

Benzodiazepine ingestion is frequent in patients admitted to ICU for intoxications. Generally, a supportive approach by securing the airway, breathing, and circulation is sufficient. Flumazenil is a well-known antidote for benzodiazepines but does not influence its elimination. Following preclinical data, we applied for the first time in humans a hemadsorption filter in a patient with a bromazepam intoxication. This technique proved to be effective in eliminating bromazepam in a patient with CHILD-C cirrhosis. We conclude that hemadsorption is a viable option to reduce length of ICU stay or intubation in slow metabolizers without contraindications.
Fibromatosis-Like Metaplastic Carcinoma: A Triple-Negative Breast Cancer with Clinically Indolent Behavior
Authors: Pham Khoa Hong , Nguyen Chu Van , Do Tu Anh , Pham Han Thi , Do Kien Hung , Le Duc Thanh
Published: September 2022

Fibromatosis-like metaplastic carcinoma is a special variant of spindle cell carcinoma, a type of metaplastic carcinomas. It has a favorable prognosis, unlike other metaplastic carcinomas, with a particular clinical behavior characterized by frequent local recurrence, the meager potential for axillary lymph nodes, and distant metastases. We presented the case of a 51-year-old female with a large mass on the left breast, which was successfully removed by surgical resection. The pathological diagnosis was fibromatosis-like metaplastic carcinoma with the help of morphology and immunohistochemistry adjustment.
Brolucizumab Intravitreal Injection in Macular Neovascularization Type 1: VA, SD-OCT, and OCTA Parameter Changes during a 16-Week Follow-Up
Authors: Toto Lisa , Ruggeri Maria Ludovica , D’Aloisio Rossella , De Nicola Chiara , Trivigno Chiara , Cerino Luca , Di Marzio Guido , Di Nicola Marta , Porreca Annamaria , Mastropasqua Rodolfo
Published: September 2022

Introduction: The aim of this study was to assess early anatomical and functional changes after brolucizumab intravitreal injection (BIVI) in patients with age-related macular degeneration (AMD) and macular neovascularization type 1 (MNV1). Methods: A total of 24 eyes of 24 patients suffering from naïve AMD with MNV1 candidates to BIVI as per label with q12/q8 dosing regimen after the loading dose were enrolled in this prospective study. Main outcome measures during a 16-week follow-up period included changes in best corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal subretinal fluid (SSRF) thickness (SSRFT), subfoveal sub-retinal pigment epithelium (RPE) fluid thickness (SSRPEFT), subfoveal choroidal thickness (SFCT), and pigment epithelial detachment (PED) maximum height (PED-MH). In addition, MNV1 flow area; percentages of eyes with intraretinal fluid (IRF), subretinal fluid, and sub-RPE fluid at different time points; and percentages of eyes candidates to a q8 or q12 injection interval after disease activity assessment at week 16 were evaluated. Results: BCVA improved significantly from baseline (T0) to week 12 (T3) (p = 0.028). CMT showed a significant reduction from 456 ± 123 µm at T0 to 265 ± 85 µm at T3 (p < 0.001). SSRFT and SSRPEFT reduced significantly as well (p < 0.001 and p = 0.049, respectively). PED-MH and SFCT reduced significantly at the different time points (p = 0.020; p = 0.006, respectively). IRF presence changed significantly from 41.7% of eyes at T0 to 20.8% at T3 (p = 0.045). SSRF reduced significantly during follow-up, being present in 62.5% of eyes at T0 and 4.2% of eyes at T3 (p < 0.001). Subfoveal sub-RPE fluid decreased significantly during time, being present in 20.8% of eyes at T0 and 0% at T3 (p = 0.013). Most of the eyes (18 eyes, 75%) at week 16 after disease activity assessment were shifted in the q12 interval, and only a minority of eyes shifted in a q8 interval (6 eyes, 25%). Conclusion: Brolucizumab is efficient in AMD patients with MNV1 by reducing all retinal fluids during the loading phase and shows reduction of macular thickness, choroidal thickness, and PED height. Most eyes at disease activity assessment (75%) fall into 12-week interval and the minority (25%) into the 8-week interval.
Translation, Cultural Adaption, and Validation of the Persian Version of the Pediatric Eating Assessment Tool
Authors: Alavi Seyede Fatemeh , Ghoreishi Zahra Sadat , Zanjari Nasibeh , Pados Britt Frisk , Choopani Roya
Published: September 2022

Introduction: The Pediatric Eating Assessment Tool (PediEAT) is a parent-report tool to assess feeding problems in children aged 6 months to 7 years. This study aimed to translate and adapt the PediEAT to Persian and determine its psychometric properties. Methods: The PediEAT was translated and culturally adapted the following guidelines for health-related instruments. Face and content validity was assessed using an expert panel. This study also aimed to evaluate psychometric properties using a sample of 160 children without feeding problems and 43 children with diagnosed feeding problems. Known-groups validation was used to compare PediEAT scores between children with and without feeding problems. In criterion validity, pediatricians’ opinions were used as a criterion. To calculate internal consistency, Cronbach’s alpha was used. After 2 weeks, temporal stability was assessed with 40 parents who repeated the PediEAT. Results: Face and content validity showed that all tool items had CVI and kappa coefficients higher than 0.8. Known-group validity showed that the total and subscale scores significantly differed between children with and without feeding problems (p < 0.001). Criterion validity showed that criterion measurements correlated with questionnaire measurements. All four subscales and the total scale showed acceptable internal consistency reliability (Cronbach’s alpha > 0.74). Test-retest reliability was acceptable (ICC = 0.987, p < 0.001). Conclusions: The PediEAT-Persian version is a valid and reliable tool for assessing symptoms of problematic feeding in Persian children aged 6 months to 7 years.
Escrita e persona nos "Cadernos de Lanzarote"
Authors: Silva Marcelo Brito da , Pereira Vinícius Carvalho
Published: September 2022

O presente artigo aborda a construção textual de uma imagem de si nos diários de José Saramago, intitulados Cadernos de Lanzarote, destacando a frontalidade e o compromisso como traços proeminentes na escrita de si do autor. Toma como ponto de partida a discussão de Luiz Costa Lima, na qual a persona é apresentada como construção e não como essência, assumindo, por um lado, a identidade entre autor, narrador e personagem e, por outro, que qualquer relato pessoal se constrói num regime de defasagens e aproximações. Por meio da análise de algumas entradas nos diários, ressaltamos como Saramago se vale de discursos memorialísticos não apenas para narrar eventos de sua vida, senão também para expor seus pontos de vista sobre si mesmo, sobre o mundo que o cerca e sobre o projeto literário de que sua vida não se aparta.
"Evangelho segundo Jesus Cristo": um exercício de fricção textual
Authors: Cerdeira Teresa Cristina
Published: September 2022

Resumo: Leitura do romance Evangelho segundo Jesus Cristo a partir dos processos de apropriação e metamorfose de textos anteriores. O conceito de paródia recuperado para além de uma figura de linguagem que visa à desconstrução pela ironia, privilegiando-se a sua origem etimológica de canto ao lado de. O romance resgata não apenas os fatos e seus significados (tantas vezes invertidos ou deslocados), mas ainda a tessitura formal dos textos bíblicos da tradição: o ritmo da frase, as reiterações dos verbos discentes, o uso do discurso direto, os ecos de sintagmas bíblicos. Esse roubo consciente do modelo e o salto promovido pelo novo olhar resultam numa revolução que opera menos no sentido de uma profanação do sagrado em nome do sacrílego e mais no sentido de uma consagração do que antes era considerado profano.