bluuebunny/crossref_metadata_2025 huggingface dataset:
Geranylgeranylacetone Ameliorates Skin Inflammation by Regulating and Inducing Thioredoxin via the Thioredoxin Redox System
Authors: Jin Tiancheng , You Yitong , Fan Wenjie , Wang Junyang , Chen Yuhao , Li Shujing , Hong Siyuan , Wang Yaxuan , Cao Ruijie , Yodoi Junji , Tian Hai
Published: August 2023

Geranylgeranylacetone (GGA) exerts cytoprotective activity against various toxic stressors via the thioredoxin (TRX) redox system; however, its effect on skin inflammation and molecular mechanism on inducing the TRX of GGA is still unknown. We investigated the effects of GGA in a murine irritant contact dermatitis (ICD) model induced by croton oil. Both a topical application and oral administration of GGA induced TRX production and Nrf2 activation. GGA ameliorated ear swelling, neutrophil infiltration, and inhibited the expression of TNF-α, IL-1β, GM-CSF, and 8-OHdG. GGA’s cytoprotective effect was stronger orally than topically in mice. In vitro studies also showed that GGA suppressed the expression of NLRP3, TNF-α, IL-1β, and GM-CSF and scavenged ROS in PAM212 cells after phorbol myristate acetate stimulation. Moreover, GGA induced endogenous TRX production and Nrf2 nuclear translocation in PAM212 cells (dependent on the presence of ROS) and activated the PI3K-Akt signaling pathway. GGA significantly downregulated thioredoxin-interacting protein (TXNIP) levels in PAM212 cells treated with or without Nrf2 siRNA. After knocking down Nrf2 in PAM212 cells, the effect of GGA on TRX induction was significantly inhibited. This suggests that GGA suppress ICD by inducing endogenous TRX, which may be regulated by PI3K/Akt/Nrf2 mediation of the TRX redox system.
Enhancing Production Prediction in Shale Gas Reservoirs Using a Hybrid Gated Recurrent Unit and Multilayer Perceptron (GRU-MLP) Model
Authors: Ma Xianlin , Hou Mengyao , Zhan Jie , Zhong Rong
Published: August 2023

Shale gas has revolutionized the global energy supply, underscoring the importance of robust production forecasting for the effective management of well operations and gas field development. Nonetheless, the intricate and nonlinear relationship between gas production dynamics and physical constraints like shale formation properties and engineering parameters poses significant challenges. This investigation introduces a hybrid neural network model, GRU-MLP, to proficiently predict shale gas production. The GRU-MLP architecture can capture sequential dependencies within production data as well as the intricate nonlinear correlations between production and the governing constraints. The proposed model was evaluated employing production data extracted from two adjacent horizontal wells situated within the Marcellus Shale. The comparative analysis highlights the superior performance of the GRU-MLP model over the LSTM and GRU models in both short-term and long-term forecasting. Specifically, the GRU model’s mean absolute percentage error of 4.7% and root mean squared error of 120.03 are notably 66% and 80% larger than the GRU-MLP model’s performance in short-term forecasting. The accuracy and reliability of the GRU-MLP model make it a promising tool for shale gas production forecasting. By providing dependable production forecasts, the GRU-MLP model serves to enhance decision-making and optimize well operations.
Enhancing Antibacterial Performance: Structure, Phase Composition, and Microroughness of Selective Plated Copper Coatings on Medical-Grade Stainless Steel 1.4021 and Nickel Alloy Ni200
Authors: Veselinov Deyan , Skulev Hristo , Yankova Radostina , Ivanov Stoyan , Moriarty Thomas Fintan , Gueorguiev Boyko
Published: August 2023

This study presents a preliminary characterization of selective plated antibacterial copper coatings on medical-grade stainless steel 1.4021 and nickel alloy Ni200 substrates using two different copper electrolyte solutions with acidic and alkaline pH. The characterizations included analysis of the microstructure, phase composition, surface roughness, and antibacterial activity against Gram-positive Staphylococcus aureus ATCC 29213 and Gram-negative Escherichia coli ATCC 25922 bacteria. The results revealed uniform and continuous layers of single-phase solid-solution copper coatings without any cracks or defects. The coatings, produced using acidic or alkaline solutions, exhibited approximately 20% or 40% lower surface roughness compared to the substrate roughness. This suggests that the plating process led to a smoother surface finish. Importantly, all of the selective plated copper coatings exhibited antibacterial properties. Inhibition zones were identified, indicating the ability of the coatings to inhibit the growth of both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli bacteria. The use of the alkaline copper solution resulted in slightly larger inhibition zones compared to the acidic solution, indicating enhanced antibacterial activity. These findings suggest that the selective plated copper coatings on medical-grade stainless steel 1.4021 and nickel alloy Ni200 substrates have the potential to be effective antibacterial surfaces.
Optimization of Car Use Time for Different Maintenance and Repair Scenarios Based on Life Cycle Assessment
Authors: Danilecki Krzysztof , Smurawski Piotr , Urbanowicz Kamil
Published: August 2023

New propulsion technologies and the development of electromobility increase the environmental efficiency of the transport sector. However, the current structure of car fleets with a large number of old cars with worse environmental parameters undermines the benefits of technological progress in the automotive industry. Older cars may require a more extensive service, involving a thorough overhaul, repair or even replacement of many parts. The result of using additional resources is a deterioration of environmental performance. This study considers various maintenance and repair scenarios and focuses on the use phase using the example of the popular Ford Focus passenger car model. The life cycle optimization model was used for environmental assessment, which determines the optimal duration of the car use phase, accounting for detailed service information and the type and environmental efficiency class of the different fuel versions. This model can be an effective tool for car fleet management and car replacement policy. Detailed life cycle inventories of 40 Ford Focus II diesel and petrol cars that represent all maintenance and repairs are the inputs to the life cycle optimization model. The inventory data were provided by the Ford Service Center in Szczecin (Poland), which regularly serviced the cars with a mileage of up to 200,000 km. Inventory at other stages of the cars’ life cycles was modeled using Ecoinvent data. The results show that by considering these vehicle servicing aspects on the basis of more detailed data, impact assessments are better represented compared to other studies. Depending on the replacement policy, the contribution of vehicle maintenance and repair can account for almost half of the cumulative life cycle burdens.
Comparative Study on Vibration Characteristics of Biaxial Carbon/Glass Hybrid Wind Turbine Blades
Authors: Jiang Xin , Jiang Yiming , Zhao Ke , Gao Mingze , Sun Jiayi , Fu Lingfeng , Wen Shidong , Gao Xiaoping
Published: August 2023

Endeavor to investigate the effect of carbon/glass hybrid ratio on blade flutter vibration characteristics. Based on the theory of strength of materials, the influence of carbon/glass hybrid ratio on the tensile strength of the sample under concentrated load was analyzed experimentally. The 10 KW wind turbine blade model was taken as the research object, and different carbon/glass hybrid ratios (2:6, 4:4, and 6:2) were selected as the blade reinforcement materials. The blade vibration characteristics were analyzed from three aspects: deformation displacement, blade mode, and stress distribution. The results showed that the blade hybrid ratio was between 6:2 and 4:4, and the maximum improvement in tensile performance was achieved. The hybrid ratios of 4:4 and 6:2 significantly improved the deformation resistance of the blades and required a shorter time to reach equilibrium. The blade stress was mainly concentrated at 1/3 of the blade, which was one of the main reasons for the phenomenon of blade waving.
An Experimental Study on the Combustion Characteristics of a Methane Diffusion Flame within a Confined Space under Sub-Atmospheric Pressure
Authors: Zhang Jingkun , Du Yongbo , Zong Siyu , Zhao Nan , Da Yaodong , Deng Lei , Che Defu
Published: August 2023

Gas-fired boilers, gas stoves, and wall-mounted gas boilers are the main consumers of gas fuel, but they generally encounter problems when operating at high altitudes, such as reduced thermal efficiency and increased pollutant emissions. Previous studies on gas combustion characteristics under sub-atmospheric pressure were mostly carried out in a large space, which is quite different from chamber combustion equipment. Therefore, it is insufficient to guide the design and operation optimization of plateau gas equipment. In this paper, experimentations were carried out to explore the characteristics of a methane diffusion flame under sub-atmospheric pressures. The mass flow rates of methane and air remain consistent under different pressure conditions. The centerline temperature (Tc) distribution, flame appearance, smoke point, CO emission, and NOx emission under different pressures (ranging from 61.66 to 97.75 kPa) were examined under both fuel rich and lean conditions. The results show that Tc at the rear and front of furnace variation with pressure is opposite under fuel-lean and -rich combustion. The Tc at the front of furnace decreases with decreasing pressure, whereas Tc at the rear of furnace increases with decreasing pressure. With decreasing pressure, flame length decreases under lean combustion, but increases under rich combustion. The smoke point fuel flow rate, flame length, and residence time increases with decreasing pressure, following the law of negative exponent. The CO emission decreases with decreasing pressure, which indicates that the reduced pressure makes methane combustion more complete. For NO emission, the reduced pressure results in an opposite tendency under fuel-lean and -rich combustion. With decreasing pressure, the NO emission decreases under fuel-lean combustion but increases under fuel-rich combustion.
Biocatalytic Insights for The Synthesis of New Potential Prodrugs: Design of two Ibuprofen Derivatives
Authors: Zappaterra Federico , Presini Francesco , Venturi Valentina , Lerin Lindomar Alberto , Giovannini Pier Paolo , Costa Stefania
Published: August 2023

Due to its effectiveness, ibuprofen is one of the most popular anti-inflammatory drugs worldwide. However, the poor water solubility of this active ingredient severely limits its spectrum of pharmaceutical formulations (and often results in severe adverse effects due to high administered doses). To overcome these limitations, in this work, we enzymatically synthesized more hydrophilic derivatives of ibuprofen through its covalent attachment to two biobased polyalcohols: erythritol and glycerol. Herein, we report the optimized reaction conditions to produce an IBU–erythritol ester (82% ± 4% of conversion) by using Candida antarctica lipase B (CalB). Furthermore, we also report the enantioselective solventless esterification of (S)-ibuprofen with glycerol (83% ± 5% of conversion), exploiting immobilized Rhizomucor miehei lipase as a biocatalyst. The full NMR characterizations of the prodrug esters were performed via 1H, 13C-NMR, DEPT, COSY, HSQC, and HMBC-NMR. The approach reported in this work can be extended to a large variety of poorly water-soluble active pharmaceutical ingredients (APIs).
Acute Effects of Mini Trampoline Training Session on Leg Stiffness and Reactive Power
Authors: Di Rocco Francesca , Papale Olga , Festino Emanuel , De Maio Marianna , Cortis Cristina , Fusco Andrea
Published: August 2023

The purpose of this study was to evaluate the acute effects of a mini trampoline training session (SuperJump®) on leg stiffness and reactive power (RP) while examining its relation to participants’ sex. A total of 20 participants (11 females, age: 24.4 ± 1.0 yrs; 9 males, age: 27.3 ± 2.9 yrs) performed continuous jump repetitions (RJs), measured on a force plate, before (PRE) and after (POST) a 30 min Superjump® session. Linear repeated measures mixed models were used to examine the effects of the Superjump® session on the leg stiffness mean (KMEAN), mean of the best RJs (KBEST), and RP in relation to sex. Before and after the mini trampoline training session, females showed lower KMEAN and KBEST values compared with males. Despite the significant (p < 0.002) decreases in RP after the Superjump® session in both males (PRE: 23.1 ± 6.5 W/kg; POST: 21.2 ± 6.1 W/kg) and females (PRE: 23.6 ± 5.5 W/kg; POST: 21.9 ± 5.3 W/kg), leg stiffness remained unchanged, suggesting a potential protective effect of mini trampoline training on leg stiffness during acute adaptations. These findings suggest that Superjump® training might exert a protective effect on leg stiffness, which prevents acute decreases that are commonly observed in other training modalities. The sex-related differences emerging from the present study emphasize the need for personalized approaches when integrating this innovative training tool into athletes’ regimens.
Impact of Soil Properties’ Spatial Correlation Lengths and Inclination on Permanent Slope Displacements Due to Earthquake Excitation
Authors: Alamanis Nikolaos , Dakoulas Panagiotis
Published: August 2023

Natural disasters, when and where they occur, often cause serious social and economic consequences, which require an urgent solution to the problem. In particular, Greece, which is characterized by a complex geological structure and intense tectonic stress, has suffered and continues to suffer the consequences of such catastrophic phenomena. Among the various destructive phenomena recorded on the Earth’s surface, two of the most important problems are landslides and land subsidence. The above phenomena may cause, in addition to the serious case of loss of human life, a threat to the social and economic fabric affecting sustainability in general, i.e., the quality of life of an area (destruction of property, filling of reservoirs, blockage of streams and rivers, etc.). In fact, landslides are a phenomenon with enormous social and economic consequences, since apart from the financial burden due to the collapse of a technical project or the interruption of transportation, they are accompanied by the loss of human life. This research examines the stochastic characteristics of a slopes’ stability to investigate the variation range of permanent earthquake movements. More specifically, the influence of inclination as well as the lengths of the spatial correlation of ground are investigated. The method in the present study follows the development of arbitrary fields of soil properties, which follow the Gaussian distribution characterized by autocorrelation lengths lx and ly in the horizontal and vertical directions, respectively, mean value μ, standard deviation σ, and cross-correlation coefficients ρij. The estimation of permanent displacements is performed by the combination of the Local Average Subdivision algorithm and the FLAC software (Fast Lagrangian Analysis of Continua) used in the parametric investigation of this work. The results of this research showed that the spatial correlation of the properties has an important impact on the permanent displacements of slopes caused by strong earthquake excitations.
Initial Student Attention-Allocation and Flight-Performance Improvements Based on Eye-Movement Data
Authors: Yang Junli , Qu Ziang , Song Zhili , Qian Yu , Chen Xing , Li Xiuyi
Published: August 2023

At the onset of their flight careers, novice pilots often lack clarity regarding the standard attention-allocation pattern. Therefore, to enhance the efficiency of initial flight training, it is crucial for students to develop a comprehensive understanding of flight control and attention-allocation behavior during the learning process. In this study, flight-performance data and eye-movement data from experienced instructors in no-power stall scenarios were collected to create an attention-allocation training course. An experimental group underwent the attention-allocation training course, while a control group followed the traditional teaching curriculum. The disparities between the flight performance and eye-movement indices of the two groups after they completed their respective courses were compared to evaluate the effectiveness of the training. The finding indicate significant differences between the speed losses, altitude losses, and mean course deviations of the instructors and the control group; these indicators had p-values of 0.01, 0.004, and 0.001, respectively. Moreover, significant differences were observed between the altitude losses and mean course deviations of the instructors and the experimental group; these indicators had p-values of 0.006 and 0.001, respectively. The experimental group, which underwent attention-allocation training, exhibited eye-movement indices that closely resembled those of the instructor group, and its instrument scanning was more strategic, thereby resulting in improved flight performance from that of the control group. Additionally, correlations were observed between flight-performance indices and eye-movement indices of the students. Overall, this study demonstrates the effectiveness of an attention-allocation training course designed specifically for a no-power stall scenario. It effectively enhanced the training outcomes of novice pilots, promoted an appropriate allocation of attention to instrument displays, introduced a novel approach to flight training, and ultimately contributed to aviation safety.
Seasonality Is the Main Determinant of Microbial Diversity Associated to Snow/Ice around Concordia Station on the Antarctic Polar Plateau
Authors: Stoppiello Gerardo A. , Coleine Claudia , Moeller Ralf , Ripa Caterina , Billi Daniela , Selbmann Laura
Published: August 2023

The French–Italian Concordia Research Station, situated on the Antarctic Polar Plateau at an elevation of 3233 m above sea level, offers a unique opportunity to study the presence and variation of microbes introduced by abiotic or biotic vectors and, consequently, appraise the amplitude of human impact in such a pristine environment. This research built upon a previous work, which explored microbial diversity in the surface snow surrounding the Concordia Research Station. While that study successfully characterized the bacterial assemblage, detecting fungal diversity was hampered by the low DNA content. To address this knowledge gap, in the present study, we optimized the sampling by increasing ice/snow collected to leverage the final DNA yield. The V4 variable region of the 16S rDNA and Internal Transcribed Spacer (ITS1) rDNA was used to evaluate bacterial and fungal diversity. From the sequencing, we obtained 3,352,661 and 4,433,595 reads clustered in 930 and 3182 amplicon sequence variants (ASVs) for fungi and bacteria, respectively. Amplicon sequencing revealed a predominance of Basidiomycota (49%) and Ascomycota (42%) in the fungal component; Bacteroidota (65.8%) is the main representative among the bacterial phyla. Basidiomycetes are almost exclusively represented by yeast-like fungi. Our findings provide the first comprehensive overview of both fungal and bacterial diversity in the Antarctic Polar Plateau’s surface snow/ice near Concordia Station and to identify seasonality as the main driver of microbial diversity; we also detected the most sensitive microorganisms to these factors, which could serve as indicators of human impact in this pristine environment and aid in planetary protection for future exploration missions.
Cisplatin Dependent Secretion of Immunomodulatory High Mobility Group Box 1 (HMGB1) Protein from Lung Cancer Cells
Authors: Gillespie Kevin P. , Pirnie Ross , Mesaros Clementina , Blair Ian A.
Published: August 2023

High mobility group box 1 (HMGB1) is secreted from activated immune cells, necrotic cells, and certain cancers. Previous studies have reported that different patterns of post-translational modification, particularly acetylation and oxidation, mediate HMGB1 release and confer distinct extracellular HMGB1 signaling activity. Here we report that cisplatin but not carboplatin induces secretion of HMGB1 from human A549 non-small cell lung cancer (NSCLC) cells. Cisplatin-mediated HMGB1 secretion was dose-dependent and was regulated by nuclear exportin 1 (XPO1) also known as chromosomal maintenance 1 (CRM1) rather than adenosine diphosphate (ADP)-ribosylation, acetylation, or oxidation. HMGB1, as well as lysine acetylation and cysteine disulfide oxidation of secreted HMGB1, were monitored by sensitive and specific assays using immunoprecipitation, stable isotope dilution, differential alkylation, and nano liquid chromatography parallel reaction monitoring/high-resolution mass spectrometry (nano-LC-PRM/HRMS). A major fraction of the HMGB1 secreted by low-dose cisplatin treatment of A549 NSCLC cells was found to be in the fully reduced form. In contrast, mainly oxidized forms of HMGB1 were secreted by dimethyl sulfoxide (DMSO)-mediated apoptosis. These findings suggest that inhibition of XPO1 could potentiate the anti-tumor activity of cisplatin by increasing the nuclear accumulation of HMGB1 protein, an inhibitor of cisplatin DNA-adduct repair. Furthermore, low-dose cisplatin therapy could modulate the immune response in NSCLC through the established chemokine activity of extracellular reduced HMGB1. This could potentially enhance the efficacy of subsequent immunotherapy treatment.
Olfactory Dysfunction Is Associated with Cerebral Amyloid Deposition and Cognitive Function in the Trajectory of Alzheimer’s Disease
Authors: Wang Sheng-Min , Kang Dong Woo , Um Yoo Hyun , Kim Sunghwan , Lee Chang Uk , Lim Hyun Kook
Published: August 2023

Olfactory dysfunction is consistently observed in individuals with Alzheimer’s disease (AD), but its association with beta-amyloid (Aβ) deposition remains unclear. This study aimed to investigate the relationship among olfactory function, cerebral Aβ deposition, and neuropsychological profiles in individuals with no cognitive impairment (NCI), mild cognitive impairment (MCI), and AD dementia. A total of 164 participants were included, and olfactory function was assessed using the brief smell identification test (B-SIT). Cerebral Aβ deposition was measured using [18F]-flutemetamol PET imaging (A-PET). The results show a significant group difference in olfactory function, with the highest impairment observed in the Aβ-positive MCI and AD dementia groups, and the impairment was the lowest in Aβ-negative NCI. Olfactory dysfunction was positively associated with cognitive impairments across multiple domains. Furthermore, individuals with Aβ deposition had lower olfactory function compared to those without Aβ, even within the same neuropsychological stage. The association between olfactory dysfunction and Aβ deposition was observed globally and in specific cortical regions. These findings suggest that olfactory dysfunction is associated with both cognitive function and cerebral Aβ pathology in the trajectory of AD. Olfactory deficits may serve as an additional marker for disease progression and contribute to understanding the underlying mechanisms of AD.
Creation of an iPSC-Based Skeletal Muscle Model of McArdle Disease Harbouring the Mutation c.2392T>C (p.Trp798Arg) in the PYGM Gene
Authors: Cerrada Victoria , García-Consuegra Inés , Arenas Joaquín , Gallardo M. Esther
Published: August 2023

McArdle disease is a rare autosomal recessive condition caused by mutations in the PYGM gene. This gene encodes the skeletal muscle isoform of glycogen phosphorylase or myophosphorylase. Patients with McArdle disease have an inability to obtain energy from their muscle glycogen stores, which manifests as a marked exercise intolerance. Nowadays, there is no cure for this disorder and recommendations are intended to prevent and mitigate symptoms. There is great heterogeneity among the pathogenic variants found in the PYGM gene, and there is no obvious correlation between genotypes and phenotypes. Here, we present the generation of the first human iPSC-based skeletal muscle model harbouring the second most frequent mutation in PYGM in the Spanish population: NM_005609.4: c.2392T>C (p.Trp798Arg). To this end, iPSCs derived from a McArdle patient and a healthy control were both successfully differentiated into skeletal muscle cells using a small molecule-based protocol. The created McArdle skeletal muscle model was validated by confirming distinctive biochemical aspects of the disease such as the absence of myophosphorylase, the most typical biochemical feature of these patients. This model will be very valuable for use in future high-throughput pharmacological screenings.
Wearable Biosensor with Molecularly Imprinted Conductive Polymer Structure to Detect Lentivirus in Aerosol
Authors: Batra Jaskirat Singh , Chi Ting-Yen , Huang Mo-Fan , Zhu Dandan , Chen Zheyuan , Lee Dung-Fang , Kameoka Jun
Published: August 2023

The coronavirus disease (COVID-19) pandemic has increased pressure to develop low-cost, compact, user-friendly, and ubiquitous virus sensors for monitoring infection outbreaks in communities and preventing economic damage resulting from city lockdowns. As proof of concept, we developed a wearable paper-based virus sensor based on a molecular imprinting technique, using a conductive polyaniline (PANI) polymer to detect the lentivirus as a test sample. This sensor detected the lentivirus with a 4181 TU/mL detection limit in liquid and 0.33% to 2.90% detection efficiency in aerosols at distances ranging from 30 cm to 60 cm. For fabrication, a mixture of a PANI monomer solution and virus were polymerized together to form a conductive PANI sensing element on a polyethylene terephthalate (PET) paper substrate. The sensing element exhibited formation of virus recognition sites after the removal of the virus via ultrasound sonication. A dry measurement technique was established that showed aerosol virus detection by the molecularly imprinted sensors within 1.5 h of virus spraying. This was based on the mechanism via which dispensing virus droplets on the PANI sensing element induced hybridization of the virus and molecularly imprinted virus recognition templates in PANI, influencing the conductivity of the PANI film upon drying. Interestingly, the paper-based virus sensor was easily integrated with a wearable face mask for the detection of viruses in aerosols. Since the paper sensor with molecular imprinting of virus recognition sites showed excellent stability in dry conditions for long periods of time, unlike biological reagents, this wearable biosensor will offer an alternative approach to monitoring virus infections in communities.
Effects of Robot Animacy and Emotional Expressions on Perspective-Taking Abilities: A Comparative Study across Age Groups
Authors: Hu Xucong , Tong Song
Published: August 2023

The global population is inevitably aging due to increased life expectancy and declining birth rates, leading to an amplified demand for innovative social and healthcare services. One promising avenue is the introduction of companion robots. These robots are designed to provide physical assistance as well as emotional support and companionship, necessitating effective human–robot interaction (HRI). This study explores the role of cognitive empathy within HRI, focusing on the influence of robot facial animacy and emotional expressions on perspective-taking abilities—a key aspect of cognitive empathy—across different age groups. To this end, a director task involving 60 participants (30 young and 30 older adults) with varying degrees of robot facial animacy (0%, 50%, 100%) and emotional expressions (happy, neutral) was conducted. The results revealed that older adults displayed enhanced perspective-taking with higher animacy faces. Interestingly, while happiness on high-animacy faces improved perspective-taking, the same expression on low-animacy faces reduced it. These findings highlight the importance of considering facial animacy and emotional expressions in designing companion robots for older adults to optimize user engagement and acceptance. The study’s implications are pertinent to the design and development of socially effective service robots, particularly for the aging population.
Unlocking Drug Resistance in Multiple Myeloma: Adipocytes as Modulators of Treatment Response
Authors: Ochiai Maria , Fierstein Sara , XsSali Farouq , DeVito Nicholas , Purkey Laura R. , May Rebecca , Correa-Medina Abraham , Kelley Mary , Page Thomas D. , DeCicco-Skinner Kathleen
Published: August 2023

Multiple myeloma (MM) is an incurable hematological malignancy characterized by the clonal proliferation of malignant plasma cells. Despite the development of a diverse array of targeted drug therapies over the last decade, patients often relapse and develop refractory disease due to multidrug resistance. Obesity is a growing public health threat and a risk factor for multiple myeloma, although the mechanisms by which obesity contributes to MM growth and progression have not been fully elucidated. In the present study, we evaluated whether crosstalk between adipocytes and MM cells promoted drug resistance and whether this was amplified by obesity. Human adipose-derived stem cells (ASCs) from nineteen normal (BMI = 20–25 kg/m2), overweight (25–30 kg/m2), or obese (30–35 kg/m2) patients undergoing elective liposuction were utilized. Cells were differentiated into adipocytes, co-cultured with RPMI 8226 or U266B1 multiple myeloma cell lines, and treated with standard MM therapies, including bortezomib or a triple combination of bortezomib, dexamethasone, and lenalidomide. We found that adipocytes from overweight and obese individuals increased cell adhesion-mediated drug resistance (CAM-DR) survival signals in MM cells, and P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) drug transporter expression. Further, co-culture enhanced in vitro angiogenesis, MMP-2 activity, and protected MM cells from drug-induced decreases in viability. In summary, we provide an underlying mechanism by which obesity can impair the drug response to MM and allow for recurrence and/or disease progression.
Aquaglyceroporins in Human Breast Cancer
Authors: Kirkegaard Teresa , Riishede Andreas , Tramm Trine , Nejsum Lene N.
Published: August 2023

Aquaporins are water channels that facilitate passive water transport across cellular membranes following an osmotic gradient and are essential in the regulation of body water homeostasis. Several aquaporins are overexpressed in breast cancer, and AQP1, AQP3 and AQP5 have been linked to spread to lymph nodes and poor prognosis. The subgroup aquaglyceroporins also facilitate the transport of glycerol and are thus involved in cellular metabolism. Transcriptomic analysis revealed that the three aquaglyceroporins, AQP3, AQP7 and AQP9, but not AQP10, are overexpressed in human breast cancer. It is, however, unknown if they are all expressed in the same cells or have a heterogeneous expression pattern. To investigate this, we employed immunohistochemical analysis of serial sections from human invasive ductal and lobular breast cancers. We found that AQP3, AQP7 and AQP9 are homogeneously expressed in almost all cells in both premalignant in situ lesions and invasive lesions. Thus, potential intervention strategies targeting cellular metabolism via the aquaglyceroporins should consider all three expressed aquaglyceroporins, namely AQP3, AQP7 and AQP9.
Interconversion and Removal of Inorganic Nitrogen Compounds via UV Irradiation
Authors: Senn Alejandro M. , Quici Natalia
Published: August 2023

Dissolved inorganic nitrogen (DIN) species are key components of the nitrogen cycle and are the main nitrogen pollutants in groundwater. This study investigated the interconversion and removal of the principal DIN compounds (NO3−, NO2− and NH4+) via UV light irradiation using a medium-pressure mercury lamp. The experiments were carried out systematically at relatively low nitrogen concentrations (1.5 mM) at varying pHs in the presence and absence of oxygen to compare the reaction rates and suggest the reaction mechanisms. NO3− was fully converted into NO2− at a pH > 3 in both oxic and anoxic conditions, and the reaction was faster when the pH was increased following a first-order kinetic at pH 11 (k = 0.12 min−1, R2 = 0.9995). NO2− was partially converted into NO3− only at pH 3 and in the presence of oxygen and was stable at an alkaline pH. This interconversion of NO3− and NO2− did not yield nitrogen loss in the solution. The addition of formic acid as an electron donor led to the reduction of NO3− to NH4+. Conversely, NH4+ was converted into NO2−, NO3− and to an unidentified subproduct in the presence of O2  at pH 10. Finally, it was demonstrated that NO2− and NH4+ react via UV irradiation with stoichiometry 1:1 at pH 10 with the total loss of nitrogen in the solution. With these results, a strategy to remove DIN compounds via UV irradiation was proposed with the eventual use of solar light.
A Case of Acrodermatitis Dysmetabolica in a Child Affected by Citrullinemia Type I: When Early Diagnosis and Timely Treatment Are Not Enough
Authors: Bruni Laura , Cassio Alessandra , Di Natale Valeria , Baronio Federico , Ortolano Rita , Pession Andrea , Piraccini Bianca Maria , Neri Iria
Published: August 2023

An infant with a prenatal diagnosis of citrullinemia, who started standard treatment at birth (L-arginine; sodium benzoate and a personalized diet characterized by a low protein intake and supplementation of essential nutrients and amino acids), presented at 4 months of age with extended, progressive, and severe skin lesions consistent with acrodermatitis dysmetabolica. Guidelines for the diagnosis and management of urea cycle disorders underline that a low-protein diet places patients at risk of essential fatty acids, trace elements, and vitamin deficiency. At hospital admission, our patient had normal levels of zinc and alkaline phosphatases. The plasmatic amino acid profile revealed a severe and generalized deficiency. In particular, the serum levels of arginine, valine, and isoleucine were very low and the dermatitis did not improve until the blood levels of these amino acids increased. In our patient, skin lesions happened despite an early diagnosis of citrullinemia and timely treatment due to compliance issues as a consequence of linguistic barriers.
Just Play Cognitive Modern Board and Card Games, It’s Going to Be Good for Your Executive Functions: A Randomized Controlled Trial with Children at Risk of Social Exclusion
Authors: Moya-Higueras Jorge , Solé-Puiggené Marina , Vita-Barrull Nuria , Estrada-Plana Verónica , Guzmán Núria , Arias Sara , Garcia Xesca , Ayesa-Arriola Rosa , March-Llanes Jaume
Published: August 2023

Modern board and card games are usually used for leisure. Few studies have focused on the type of game played in vulnerable populations. Therefore, the main aim of this study was to test the effectiveness of playing modern board and card games to enhance updating, inhibition, and flexibility in children at risk of social exclusion using games that activated specific basic executive functions. We developed a quadruple-blind randomized clinical trial during the COVID-19 pandemic. Sixty-eight participants (7–12 years old) were divided into two experimental groups: 35 children played games that directly activated basic executive functions, and 33 played games that directly triggered other cognitive domains. The primary statistical analysis consisted of mixed models. We found significant time effects in cognitive flexibility and inhibition and, to a lesser extent, in working memory in both gaming groups. We analyzed the cognitive profile of the games and found that all the games activated basic executive functions significantly, irrespective of the experimental group. Therefore, it is possible that playing any type of modern board and card game (excluding games with a high incidence of luck) could be beneficial for children at risk of social exclusion.
Multisensory Texture Perception in Individuals with Williams Syndrome
Authors: Cheam Caroline , Barisnikov Koviljka , Gentaz Edouard , Lejeune Fleur
Published: August 2023

The sensory profile of people with Williams syndrome (WS) is characterised by atypical visual and auditory perceptions that affect their daily lives and learning. However, no research has been carried out on the haptic perception, in particular in multisensory (visual and haptic) situations. The aim of this study was to evaluate the communication of texture information from one modality to the other in people with WS. Children and adults with WS were included, as well as typically developing (TD) participants matched on chronological age (TD-CA), and TD children matched on mental age (TD-MA). All participants (N = 69) completed three matching tasks in which they had to compare two fabrics (same or different): visual, haptic and visuo-haptic. When the textures were different, the haptic and visual performances of people with WS were similar to those of TD-MA participants. Moreover, their visuo-haptic performances were lower than those of the two TD groups. These results suggest a delay in the acquisition of multisensory transfer abilities in individuals with WS. A positive link between MA and visual and visuo-haptic abilities only in people with WS suggests that they could benefit from an early intervention to develop their abilities to process and transfer multisensory information.
The Intestinal Microbiome and the Metabolic Syndrome—How Its Manipulation May Affect Metabolic-Associated Fatty Liver Disease (MAFLD)
Authors: Malnick Stephen D. H. , Ohayon Michael Sheral
Published: August 2023

Metabolic-associated fatty liver disease (MAFLD) is now the predominant liver disease worldwide consequent to the epidemic of obesity. The intestinal microbiome (IM), consisting of the bacteria, fungi, archaea, and viruses residing in the gastrointestinal tract, plays an important role in human metabolism and preserving the epithelial barrier function. Disturbances in the IM have been shown to influence the development and progression of MAFLD and play a role in the development of metabolic syndrome (MS). The main treatment for MAFLD involves lifestyle changes, which also influence the IM. Manipulation of the IM by fecal microbial transplantation (FMT) has been approved for the treatment of recurrent Closteroides difficile infection. This may be administered by endoscopic administration from the lower or upper GI tract. Other methods of administration include nasogastric tube, enema, and oral capsules of stool from healthy donors. In this narrative review, we elaborate on the role of the IM in developing MS and MAFLD and on the current experience with IM modulation by FMT on MAFLD.
Genetic Variants in the Mitochondrial Thymidylate Biosynthesis Pathway Increase Colorectal Cancer Risk
Authors: Arrait Entesar M. , Al-Ghafari Ayat B. , Al Doghaither Huda A.
Published: August 2023

We assess the contributions of genetic variants for the enzymes involved in capecitabine metabolism to colorectal cancer (CRC) development risk. In this case-control study, DNA samples were collected from 66 patients (King Abdulaziz University Hospital) and 65 controls (King Fahad General Hospital) between April and November 2022 to be used in PCR-RFLP. The chi-square (χ2) test at a significance level of p ˂ 0.05 was used to estimate genotype and allele frequencies. The Lys27Gln variant of cytidine deaminase (CDA) showed a risk ratio (RR) of 1.47 for heterozygous (AC) carriers, with genotype distributions for patients (χ2 = 1.97) and controls (χ2 = 14.7). Homozygous (AA) Ala70Thr carriers demonstrated a three-fold higher risk, with genotype distributions for patients (χ2 = 3.85) and controls (χ2 = 4.23). Genotype distributions of the 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T variant for patients were (χ2 = 22.43) and for controls were (χ2 = 0.07); for the MTHFR A1298C variant, they were (χ2 = 54.44) for patients and (χ2 = 4.58) for controls. Heterozygous (AC) carriers of the A1298C variant demonstrated highly significant protection against CRC development (RR = 0.2, p = 0.001), while a two-fold higher risk for CRC was estimated for homozygous genotype (CC) carriers. In conclusion, the heterozygous genotype of CDA Lys27Gln, the homozygous genotype of CDA Ala70Thr, and the homozygous genotype of MTHFR A1298C were associated with CRC development risk. The heterozygous genotype of MTHFR A1298C variant provided highly significant protection against CRC development. Further examinations using a larger population size are needed to reliably confirm our findings.
Addressing Inequity in Spatial Access to Lung Cancer Screening
Authors: Simkin Jonathan , Khoo Edwin , Darvishian Maryam , Sam Janette , Bhatti Parveen , Lam Stephen , Woods Ryan R.
Published: August 2023

Background: The successful implementation of an equitable lung cancer screening program requires consideration of factors that influence accessibility to screening services. Methods: Using lung cancer cases in British Columbia (BC), Canada, as a proxy for a screen-eligible population, spatial access to 36 screening sites was examined using geospatial mapping and vehicle travel time from residential postal code at diagnosis to the nearest site. The impact of urbanization and Statistics Canada’s Canadian Index of Multiple Deprivation were examined. Results: Median travel time to the nearest screening site was 11.7 min (interquartile range 6.2–23.2 min). Urbanization was significantly associated with shorter drive time (p < 0.001). Ninety-nine percent of patients with ≥60 min drive times lived in rural areas. Drive times were associated with sex, ethnocultural composition, situational vulnerability, economic dependency, and residential instability. For example, the percentage of cases with drive times ≥60 min among the least deprived situational vulnerability group was 4.7% versus 44.4% in the most deprived group. Conclusions: Populations at risk in rural and remote regions may face more challenges accessing screening services due to increased travel times. Drive times increased with increasing sociodemographic and economic deprivations highlighting groups that may require support to ensure equitable access to lung cancer screening.
Genome-Wide Analysis of SPL Gene Families Illuminate the Evolution Patterns in Three Rubber-Producing Plants
Authors: Su Renping , Yuan Boxuan , Yang Yang , Ao Guoen , Wang Juanying
Published: August 2023

Transcription factors SQUAMOSA Promoter-binding Protein-like (SPL) play a crucial role in regulating plant response to stress, root development, and flower production. However, analysis of SPL gene families in the three rubber-producing plants Taraxacum kok-saghyz, Hevea brasiliensis, and Eucommia ulmoides, renowned for their natural rubber production, has not yet been conducted. In this study, we utilized reference genomes to perform genome-wide analysis, and obtained new insights on the evolution of SPL gene families in these three rubber-producing plants. Our results revealed the following: (1) T. kok-saghyz, H. brasiliensis, and E. ulmoides harbored 25, 16, and 13 SPL genes, respectively, containing conserved structural domains of SBP. (2) A phylogenetic analysis categorized 90 SPL proteins from 25 TkSPLs, 16 HbSPLs, 13 EuSPLs, 17 AtSPLs, and 19 OsSPLs into eight groups. (3) Analysis of cis-acting elements demonstrated that the promoters of EuSPLs contained a significant number of light response elements, hormone regulatory elements, and stress response elements. (4) Transcriptome data analysis revealed that the EuSPL8 gene had strong expression in bark, as well as TkSPL4 and TkSPL8 exhibit high expression levels specifically in roots and latex. This study provides valuable insights into the biological functions of the SPL gene family in the three rubber plants and might serve as a reference for identifying efficient genes.
Parkinson’s Disease Detection Using Filter Feature Selection and a Genetic Algorithm with Ensemble Learning
Authors: Ali Abdullah Marish , Salim Farsana , Saeed Faisal
Published: August 2023

Parkinson’s disease (PD) is a neurodegenerative disorder marked by motor and non-motor symptoms that have a severe impact on the quality of life of the affected individuals. This study explores the effect of filter feature selection, followed by ensemble learning methods and genetic selection, on the detection of PD patients from attributes extracted from voice clips from both PD patients and healthy patients. Two distinct datasets were employed in this study. Filter feature selection was carried out by eliminating quasi-constant features. Several classification models were then tested on the filtered data. Decision tree, random forest, and XGBoost classifiers produced remarkable results, especially on Dataset 1, where 100% accuracy was achieved by decision tree and random forest. Ensemble learning methods (voting, stacking, and bagging) were then applied to the best-performing models to see whether the results could be enhanced further. Additionally, genetic selection was applied to the filtered data and evaluated using several classification models for their accuracy and precision. It was found that in most cases, the predictions for PD patients showed more precision than those for healthy individuals. The overall performance was also better on Dataset 1 than on Dataset 2, which had a greater number of features.
Assessing the Efficacy of Inferior Vena Cava Collapsibility Index for Predicting Hypotension after Central Neuraxial Block: A Systematic Review and Meta-Analysis
Authors: Chang Ying-Jen , Liu Chien-Cheng , Huang Yen-Ta , Wu Jheng-Yan , Hung Kuo-Chuan , Liu Ping-Hsin , Lin Chien-Hung , Lin Yao-Tsung , Chen I-Wen , Lan Kuo-Mao
Published: August 2023

The use of ultrasonography to predict spinal-induced hypotension (SIH) has gained significant attention. This diagnostic meta-analysis aimed to investigate the reliability of the inferior vena cava collapsibility index (IVCCI) in predicting SIH in patients undergoing various surgeries. Databases, including Embase, Cochrane Library, Medline, and Google Scholar, were screened until 28 July 2023, yielding 12 studies with 1076 patients (age range: 25.6–79 years) undergoing cesarean section (CS) (n = 4) or non-CS surgeries (n = 8). Patients with SIH had a significantly higher IVCCI than those without SIH (mean difference: 11.12%, 95% confidence interval (CI): 7.83–14.41). The pooled incidence rate of SIH was 40.5%. IVCCI demonstrated satisfactory overall diagnostic reliability (sensitivity, 77%; specificity, 82%). The pooled area under the curve (AUC) was 0.85, indicating its high capability to differentiate patients at risk of PSH. The Fagan nomogram plot demonstrated a positive likelihood ratio (PLR) of 4 and a negative likelihood ratio (NLR) of 0.28. The results underscore the robustness and discriminative ability of IVCCI as a predictive tool for SIH. Nevertheless, future investigations should focus on assessing its applicability to high-risk patients and exploring the potential enhancement in patient safety through its incorporation into clinical practice.