bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Climate Warming on the Potential Northern Planting Boundaries of Three Main Grain Crops in China
Authors: Zhuo Wen , Fang Shibo , Ma Yuping , Zhang Rui , Wang Lei , Li Mengqian , Zhang Jiansu , Gao Xinran
Published: May 2022

The production of wheat, maize and rice accounts for more than 90% of the total grain production of China. Assessing the impact of climate warming on suitable planting regions, especially the potential northern planting boundaries of these crops, is therefore critical to help guide agricultural policymaking and further maintain food security. In this study, we analyzed the effect of climate warming on the potential northern planting boundaries of three specific crops (winter wheat, spring maize, double and triple rice cropping systems) during two time periods (1961–1990 and 1991–2020) using meteorological data from 2437 national weather stations. Results show that the potential planting boundaries of these crops present a northward movement and a westward expansion during the time period of 1991–2020 under the background of temperature increase compared with the time period of 1961–1990. Moreover, the boundaries of winter wheat and spring maize also show a trend of expansion to high-altitude areas (e.g., the Qinghai–Tibet Plateau). The average moving distance of these crops ranged from 20 km to 300 km. In general, the potential planting boundaries of winter wheat, spring maize, double and triple rice cropping systems changed significantly due to climate warming, and the suitable planting area was increased. Our study aims to provide a more recent and accurate result than those of previous studies, which is expected to strengthen our understanding of the effect of climate change on the potential northern planting boundaries of the three main grain crops in China.
Curcumin, Polydatin and Quercetin Synergistic Activity Protects from High-Glucose-Induced Inflammation and Oxidative Stress
Authors: Matacchione Giulia , Valli Debora , Silvestrini Andrea , Giuliani Angelica , Sabbatinelli Jacopo , Giordani Chiara , Coppari Sofia , Rippo Maria Rita , Albertini Maria Cristina , Olivieri Fabiola
Published: May 2022

Chronic hyperglycemia, the diagnostic biomarker of Type 2 Diabetes Mellitus (T2DM), is a condition that fosters oxidative stress and proinflammatory signals, both involved in the promotion of cellular senescence. Senescent cells acquire a proinflammatory secretory phenotype, called SASP, exacerbating and perpetuating the detrimental effects of hyperglycemia. Bioactive compounds can exert antioxidant and anti-inflammatory properties. However, the synergistic anti-inflammatory and antioxidant effects of the most extensively investigated natural compounds have not been confirmed yet in senescent cells and in hyperglycemic conditions. Here, we exposed young and replicative senescent HUVEC (yHUVEC and sHUVEC) to a high-glucose (HG) condition (45 mM) and treated them with Polydatin (POL), Curcumin (CUR) and Quercetin (QRC), alone or in combination (MIX), to mirror the anti-inflammatory component OxiDefTM contained in the novel nutraceutical GlicefenTM (Mivell, Italy). In both yHUVEC and sHUVEC, the MIX significantly decreased the expression levels of inflammatory markers, such as MCP-1, IL-1β and IL-8, and ROS production. Importantly, in sHUVEC, a synergistic effect of the MIX was observed, suggesting its senomorphic activity. Moreover, the MIX was able to reduce the expression level of RAGE, a receptor involved in the activation of proinflammatory signaling. Overall, our data suggest that the consumption of nutraceuticals containing different natural compounds could be an adjuvant supplement to counteract proinflammatory and pro-oxidative signals induced by both hyperglycemic and senescence conditions.
Cardioprotective Antioxidant and Anti-Inflammatory Mechanisms Induced by Intermittent Hypobaric Hypoxia
Authors: González-Candia Alejandro , Candia Alejandro A. , Paz Adolfo , Mobarec Fuad , Urbina-Varela Rodrigo , Campo Andrea del , Herrera Emilio A. , Castillo Rodrigo L.
Published: May 2022

More than 80 million people live and work (in a chronic or intermittent form) above 2500 masl, and 35 million live in the Andean Mountains. Furthermore, in Chile, it is estimated that 100,000 people work in high-altitude shifts, where stays in the lowlands are interspersed with working visits in the highlands. Acute exposure to high altitude has been shown to induce oxidative stress in healthy human lowlanders due to increased free radical formation and decreased antioxidant capacity. However, intermittent hypoxia (IH) induces preconditioning in animal models, generating cardioprotection. Here, we aim to describe the responses of a cardiac function to four cycles of intermittent hypobaric hypoxia (IHH) in a rat model. The twelve adult Wistar rats were randomly divided into two equal groups, a four-cycle of IHH and a normobaric hypoxic control. Intermittent hypoxia was induced in a hypobaric chamber in four continuous cycles (1 cycle = 4 days of hypoxia + 4 days of normoxia), reaching a barometric pressure equivalent to 4600 m of altitude (428 Torr). At the end of the fourth cycle, cardiac structural and functional variables were also determined by echocardiography; furthermore, cardiac oxidative stress biomarkers (4-Hydroxynonenal, HNE; nitrotyrosine, NT), antioxidant enzymes, and NLRP3 inflammasome panel expression are also determined. Our results show a higher ejection and a shortening fraction of the left ventricle function by the end of the fourth cycle. Furthermore, cardiac tissue presented a decreased expression of antioxidant proteins. However, a decrease in IL-1β, TNF-αn, and oxidative stress markers is observed in IHH compared to normobaric hypoxic controls. Non-significant differences were found in protein levels of NLRP3 and caspase-1. IHH exposure determines structural and functional heart changes. These findings suggest that initial states of IHH are beneficial for cardiovascular function and protection.
Numerical Analysis of the Settlement Behavior of Soft Soil Improved with Stone Columns
Authors: Grizi Athina , Al-Ani Wisam , Wanatowski Dariusz
Published: May 2022

The use of column-like elements for improving both the settlement performance and bearing capacity of foundations constructed over soft soils is well understood for large groups of columns supporting an infinitely wide load, such as embankments and slabs. However, little is still understood for lightly loaded, low-rise structures supported by pad foundations constructed on a finite number of stone columns, particularly when a crust layer is present at the top of the soft soil. In this study, a comprehensive 3D finite element analysis is used to investigate the influence of key design parameters, such as column spacing, column length, footing shape, and the presence of a crust layer, on the settlement behavior of stone columns to support shallow foundations. The results show that the modeling of a well-characterized soft soil profile predicts well the long-term settlement using both drained and undrained analyses. It was found that the presence of a stiff crust layer has a significant influence on the deformational mode of the stone columns which is not captured by laboratory modeling.
Preliminary Study on Safety Assessment of 10 Hz Transcranial Alternating Current Stimulation in Rat Brain
Authors: Oh Sung Suk , Lee Yoon Bum , Jeon Jae Sun , An Sang-Hyun , Choi Jong-ryul
Published: May 2022

Assessment of the safety of transcranial electrical stimulation devices that contact the scalp and apply electrical stimulations to brain tissues is essential for the prevention of unexpected brain damage caused by electromagnetic fields. In particular, safety studies on transcranial alternating current stimulation (tACS) are needed for active applications to treat brain diseases and for the development of medical devices, because there is a lack of research on the safety of tACS, in contrast to transcranial direct current stimulation. In this study, the safety of tACS with selected parameters, i.e., a stimulation intensity of 1.0 to 2.0 mA, a frequency of 10 Hz, and a treatment time of 20 min, was examined at a preclinical stage using small animals (rats). The results of magnetic resonance imaging and histopathological imaging indicated that the conditions applied in this study provided safe tACS without damaging brain tissues or neuronal components in the acute phase. In addition, the temperature did not increase above 41 °C, which is a temperature limitation for contact-type medical devices, even after 20 min of tACS application.
Numerical Simulation of Non-Stationary Parameter Creep Large Deformation Mechanism of Deep Soft Rock Tunnel
Authors: Xu Jiancong , Wen Haiyang , Sun Chen , Yang Chengbin , Rui Guorong
Published: May 2022

The accelerated creep plays an important role in the disasters of soft-rock tunnels under high stress. However, most of previous studies only involved attenuation creep and uniform creep. Large deformation disasters of soft rock occurred during the tunneling process in the Qianzhou–Sanyangchuan Tunnel, Gusu Province, China. In the paper, we developed the nonlinear generalized Nishihara rheological model with non-stationary parameter creep (NGNRM) to simulate the accelerated creep behaviors of soft rocks under high stress, and implemented it in ABAQUS, to reveal the mechanism of large deformation of soft rock. We proposed the multi-objective back analysis method of surrounding rock mechanical parameters based on the eXtreme Gradient Boosting and the non-dominated sorting genetic algorithm-II. In addition, the orthogonal test design method was used to determine the main parameters affecting the displacement of the tunnel. Using the proposed method, we can evaluate the large deformation mechanism of deep soft rock tunnels, and scientifically determine when to reinforce to prevent a large deformation disaster of the tunnel.
5D Gauss Map Perspective to Image Encryption with Transfer Learning Validation
Authors: Salunke Sharad , Ahuja Bharti , Hashmi Mohammad Farukh , Marriboyina Venkatadri , Bokde Neeraj Dhanraj
Published: May 2022

Encryption of visual data is a requirement of the modern day. This is obvious and greatly required due to widespread use of digital communication mediums, their wide range of applications, and phishing activities. Chaos approaches have been shown to be extremely effective among many encryption methods. However, low-dimensional chaotic schemes are characterized by restricted system components and fundamental structures. As a result, chaotic signal estimation algorithms may be utilized to anticipate system properties and their initial values to breach the security. High-dimensional chaotic maps on the other hand, have exceptional chaotic behavior and complex structure because of increased number of system parameters. Therefore, to overcome the shortcomings of the lower order chaotic map, this paper proposes a 5D Gauss Map for image encryption for the first time. The work presented here is an expansion of the Gauss Map’s current 1D form. The performance of the stated work is evaluated using some of the most important metrics as well as the different attacks in the field. In addition to traditional and well-established metrics such as PSNR, MSE, SSIM, Information Entropy, NPCR, UACI, and Correlation Coefficient that have been used to validate encryption schemes, classification accuracy is also verified using transfer learning. The simulation was done on the MATLAB platform, and the classification accuracy after the encryption-decryption process is compared.
Age-Related Changes in Landing Mechanics in Elite Male Youth Soccer Players: A Longitudinal Study
Authors: Lehnert Michal , Krejčí Jakub , Janura Miroslav , De Ste Croix Mark
Published: May 2022

The aim of this longitudinal observational study was to examine the age differences in jump landing kinematics in 13–17-year-old male soccer players. Landing technique was evaluated in three consecutive seasons in U14 (n = 15) and the U16 (n = 10) competition age groups using the Landing Error Scoring System (LESS). For the LESS, ANOVA revealed no significant interaction effect (p = 0.81, η2 = 0.009) or main effect for groups (p = 0.15, η2 = 0.086), but a significant year effect was observed (p < 0.001, η2 = 0.265). The LESS score in the U14 group decreased significantly in the second year (5.7 ± 1.9, p = 0.006, d = 0.84) and in the third year (5.9 ± 2.0, p = 0.020, d = 0.70) compared to the first year (7.1 ± 1.7). The LESS score in the U16 group decreased significantly in the second year (5.1 ± 0.9 points, p = 0.034, d = 0.77) and in the third year (4.9 ± 1.4, p = 0.013, d = 0.92) compared to the first year (6.4 ± 1.2). This trend was supported by the results of the separate assessment of the sagittal plane joint displacement. These findings support previous limited findings from cross-sectional studies, which point to improved landing mechanics during maturation. However, the LESS scores in both groups indicate that players who were around and/or post-peak height velocity during the observed periods may be considered “at-risk”, and suggest that preventive training programs should be introduced at earlier stages of players’ development.
Multiparameter Analysis of the Ultrasonic Transducer Transfer Function Using a Genetic Algorithm
Authors: Gudra Tadeusz , Banasiak Dariusz
Published: May 2022

The transfer function is an important parameter describing ultrasonic transducers which are designed to operate in various media. The typically high impedance of piezoelectric transducers is matched to a particular loading medium (gas, liquid, biological medium) by using multicomponent matching layers, which have specific impedances and thicknesses in accordance with the generally known matching criteria: Chebyshev, DeSilets or Souquet. When properly selected, the materials used for the matching layers allow the most optimal parameters to be obtained for both transmitting and the receiving ultrasonic energy. However, studies rarely focus on the possibility of shaping the obtained transfer function, which is also a parameter that is important in some applications of transducers intended for pulse operation, especially in liquid media (e.g., in hydroacoustics) or in biological media (e.g., in ultrasound imaging). The values and shapes of such a function are influenced by factors which are identical to the parameters describing the matching layers. This article presents the possibilities and advantages of using a genetic algorithm to shape the characteristics of the transfer functions that have a particular importance in the search for an optimal (typically the greatest) bandwidth of a transducer intended for operation in a particular medium.
Experimental and Numerical Investigation of the Seismic Performance of Bridge Columns with High-Strength Reinforcement and Concrete
Authors: Sharma Raju , Liu Kuang-Yen , Witarto Witarto
Published: May 2022

Despite the numerous advantages high-strength reinforcement (HSR) and high-strength concrete (HSC) offer over conventional materials, the practical use of these materials for bridge column design in seismic zones has somewhat been limited. This is due to the insufficient research data and guidelines for the seismic design of bridges using HSC and HSR and the lack of a reliable analytical model. Therefore, to address this issue and promote the application of HSR and HSC, this paper investigates high-strength bridge columns’ seismic performance experimentally and numerically. Six large-scale reinforced concrete (RC) bridge columns and one multi-column bent frame were tested under a quasi-static cyclic loading with constant axial compression. The primary design parameters were axial load ratio, longitudinal and transverse reinforcement yield strength, and transverse reinforcement spacing. The failure pattern of high-strength columns was similar to conventional RC columns and satisfied the requirements for seismic design in terms of failure mode, hysteresis behavior, ductility, and energy dissipation capacity. The experimental ductility values of the high-strength columns were satisfactory and capable of meeting the ductility demand of most codes. Furthermore, a numerical model was built using the OpenSees program to predict the seismic performance of the specimens and then verified by comparing them with the test results of 12 columns. The numerical model’s results were in good agreement with the experimental results. The results suggested that numerical modeling techniques commonly used for normal strength concrete (NSC) columns can be used for HSC bridge columns by incorporating a proper material model.
An Intelligent Product Service System for Adaptive Maintenance of Engineered-to-Order Manufacturing Equipment Assisted by Augmented Reality
Authors: Angelopoulos John , Mourtzis Dimitris
Published: May 2022

Under the framework of Industry 4.0, machines and machine tools have evolved to smart and connected things, comprising the Internet of Things (IoT) and leading to the Mass Personalization (MP) paradigm, which enables the production of uniquely made products at scale. MP, fueled by individualization trends and enabled by increasing digitalization, has the potential to go beyond current mass customization. Although this evolution has enabled engineers to gain useful insight for the production, the machine status, the quality of products, etc., machines have become more complex. Thus, Maintenance Repair and Overhaul (MRO) operations should be undertaken by specialized personnel. Additionally, Augmented Reality (AR) can support remote maintenance assistance to handle unexpected malfunctions. Moreover, due to advances regarding Product Service Systems (PSS), manufacturing companies are offering many services to improve user experience. Consequently, in this manuscript the design and development of a method based on the principles of servitization for the provision of an intelligent and adaptable maintenance service assisted by AR are presented. The contribution of the manuscript extends to the provision of an optimization algorithm for adapting the schedules of the stakeholders based on the energy supplier predictions. The developed method was tested and validated on an industrial case study of injection mold maintenance, achieving 11% energy reduction, 50% less time for mold inspection, and a 20% rise in on-time mold deliveries.
Improved Structural Local Thermal Energy Planning Based on Prosumer Profile: Part A
Authors: Papatsounis Adamantios G. , Botsaris Pantelis N. , Katsavounis Stefanos
Published: May 2022

The transition to a carbon-reduced future for one of the most energy-intensive actors, the building sector, requires the development of appropriate tools and methods. One such approach is local energy communities (LECs), especially thermal LECs (TLECs), which provide a promising vector towards that transition. LECs exploit energy users as key actors in the energy production process. However, their formation, creation, and continuation are still an ongoing endeavor. Many research efforts focus on creating and continuing LECs in an economic, legal, and incentivized manner, sparsely addressing the formation process. In this Part A, a collective tool for decision-making for potential TLECs is presented. The current study proposes a unified approach to classify the prosumers of energy (consumers who both produce and consume energy) using conventional methodologies (RenewIslands, Kaya Identity). A case study is presented in a fully operating LEC in Kimmeria, Greece, in which both the traditional methods of classifying users are applied as well as the proposed methodology, in comparison. The results indicate a significant improvement to the conventional solutions, which tend to overestimate the needed equipment, leading to extensive installation and operational costs.
Spectral and Divergence Characteristics of Plateau High-Order Harmonics Generated by Femtosecond Chirped Laser Pulses in a Semi-Infinite Gas Cell
Authors: Petrakis Stylianos , Bakarezos Makis , Tatarakis Michael , Benis Emmanouil P. , Papadogiannis Nektarios A.
Published: May 2022

The generation of high-order harmonics in a semi-infinite cell by femtosecond laser pulses is a common practice for reliable coherent and low divergence XUV source beams for applications. Despite the relative simplicity of the experimental method, several phenomena coexist that affect the generated spectral and divergence characteristics of the high harmonic XUV frequency comb. The ionisation degree of the medium and the consequent plasma formation length imposes a spatiotemporal evolution of the fundamental EM field and XUV absorption. Varying the laser pulse chirp and the focusing conditions, as well as the gas density, we measured intense harmonic spectral and divergence variations attributed mainly to self-phase modulations of the laser EM field in the partially ionised medium. Additionally, low-divergence high harmonics are observed for certain laser chirp values attributed to the strong phase matching of only the short electron quantum path. Thus, a tunable, low divergent, and coherent XUV source can be realised for spatiotemporal imaging applications in the nanoscale.
Adaptive Enhancement for Coal-Rock Cutting Sound Based on Parameter Self-Tuning Bistable Stochastic Resonance Model
Authors: Xu Jie , Xu Jing , Ren Chaofan , Liu Yanxin , Sun Ning
Published: May 2022

The traditional bistable stochastic resonance model has always had the drawback of being difficult when choosing accurate system parameters when a weak signal is enhanced. This paper proposes a parameter self-tuning adaptive optimization method based on the bat optimization algorithm to address this issue. The cubic mapping strategy of chaos optimization is introduced in the initial process of the individual position of the bat algorithm. Chaos is characterized by randomness, sensitivity, fractal dimension, and universality. The initial problem of the algorithm falling into local extremums is overcome. The global search capability of the basic bat optimization algorithm has been improved. The improved bat optimization algorithm’s objective function is the signal-to-noise ratio (SNR) of the target weak signal output by the bistable stochastic resonance model. An adaptive signal enhancement algorithm based on the improved bat optimization algorithm and bistable stochastic resonance (IBA-BSR) model is constructed to increase the proportion of weak signals in the mixed signal. Simulation signals are created to validate the proposed algorithm’s feasibility. The engineering application effect of this algorithm is further demonstrated by enhancing the sound signal of coal and rock cutting by a shearer in a coal face. Engineering test results demonstrate that this algorithm can significantly increase the SNR of coal and rock cutting sound signals by 42.4537 dB, and the effect is remarkable.
Edge Neighbor Toughness of Graphs
Authors: Feng Xin , Wei Zongtian , Yang Yucheng
Published: May 2022

A new graph parameter, edge neighbor toughness is introduced to measure how difficult it is for a graph to be broken into many components through the deletion of the closed neighborhoods of a few edges. Let G=(V,E) be a graph. An edge e is said to be subverted when its neighborhood and the two endvertices are deleted from G. An edge set S⊆E(G) is called an edge cut-strategy if all the edges in S has been subverted from G and the survival subgraph, denoted by G/S, is disconnected, or is a single vertex, or is. The edge neighbor toughness of a graph G is defined to be tEN(G)=minS⊆E(G){|S|c(G/S)}, where S is any edge cut strategy of G, c(G/S) is the number of the components of G/S. In this paper, the properties of this parameter are investigated, and the proof of the computation problem of edge neighbor toughness is NP-complete; finally, a polynomial algorithm for computing the edge neighbor toughness of trees is given.
Telemedicine Improves HCV Elimination among Italian People Who Use Drugs: An Innovative Therapeutic Model to Increase the Adherence to Treatment into Addiction Care Centers Evaluated before and during the COVID-19 Pandemic
Authors: Rosato Valerio , Nevola Riccardo , Conturso Vincenza , Perillo Pasquale , Mastrocinque Davide , Pappalardo Annalisa , Le Pera Teresa , Del Vecchio Ferdinando , Claar Ernesto
Published: May 2022

People who use drugs (PWUDs) are generally considered “hard-to-treat” patients, due to adherence to HCV antiviral therapy or re-infection concerns. Linkage-to-care still remains a significant gap for HCV elimination, worsened by the COVID-19 pandemic. To reduce time-to-treat and improve treatment adherence, we have developed a patient-tailored model-of-care, decentralized within the addiction center and supervised remotely by hepatologists. From January 2017 to December 2020, patients were enrolled in one addiction care center in Southern Italy, where a complete hepatologic assessment, including blood chemistry, ultrasound, and transient elastography examination, was provided. DAAs treatment has been adapted on clinical features, also performing a daily administration during an outpatient visit, and monitored remotely by specialists via telemedicine interactions. Adherence was evaluated on the accomplishment of therapy or on the percentage of attended visits. From a total of 690 PWUDs, 135 had an active HCV infection and were enrolled in the study. All patients started the treatment within 3 weeks after HCV diagnosis. Six drop-outs were recorded, obtaining a sustained virological response at week 12 (SVR12) in 98.5% of PWUDs. There were only two cases of treatment failure, one of which is re-infection. No differences were found between the SVR12 rates before and during the COVID-19 pandemic. We obtained a high SVR12 rate, providing a comprehensive assessment within the addiction care center, tailoring the drug administration with a hepatologic remote stewardship. Our therapeutic model should improve the time-to-treat and treatment adherence in PWUDs.
Early Life History and Recruitment Processes of a Tropical Anguillid Eel Anguilla marmorata to the Pacific Coast, as Revealed by Otolith Sr:Ca Ratios and Microstructure
Authors: Arai Takaomi
Published: May 2022

Recent progress in otolith microchemistry especially in strontium:calcium (Sr:Ca) ratios has revealed significant features of life histories in fishes. A catadromous eel, Anguilla marmorata, has the widest distribution among anguillid eels throughout the Indo-Pacific region. However, its dispersal and recruitment mechanisms in the ocean are still unknown. The temporal and spatial variations of early life history characteristics in a tropical anguillid eel A. marmorata were examined by means of otolith Sr:Ca ratios and microstructure to understand the larval transport and recruitment processes to the coasts in the Pacific region. Durations of the larval stage and age at recruitment to the southern part of Japan ranged from 79 to 157 d and 113 to 192, respectively. No significant differences were found between recruitment months in those parameters. The early life characteristics such as larval duration and age at recruitment were constant throughout the recruitment period in the southern part of Japan. The early life history characteristics in combination with the oceanic current regime possibly determine the larval transportation and dispersion processes and further recruitment dynamics to the Pacific coast of A. marmorata. The present study also provides useful information on its biogeographic distribution in the species as determined by otolith Sr:Ca ratios and microstructure.
Nitric-Oxide-Mediated Signaling in Podocyte Pathophysiology
Authors: Semenikhina Marharyta , Stefanenko Mariia , Spires Denisha R. , Ilatovskaya Daria V. , Palygin Oleg
Published: May 2022

Nitric oxide (NO) is a potent signaling molecule involved in many physiological and pathophysiological processes in the kidney. NO plays a complex role in glomerular ultrafiltration, vasodilation, and inflammation. Changes in NO bioavailability in pathophysiological conditions such as hypertension or diabetes may lead to podocyte damage, proteinuria, and rapid development of chronic kidney disease (CKD). Despite the extensive data highlighting essential functions of NO in health and pathology, related signaling in glomerular cells, particularly podocytes, is understudied. Several reports indicate that NO bioavailability in glomerular cells is decreased during the development of renal pathology, while restoring NO level can be beneficial for glomerular function. At the same time, the compromised activity of nitric oxide synthase (NOS) may provoke the formation of peroxynitrite and has been linked to autoimmune diseases such as systemic lupus erythematosus. It is known that the changes in the distribution of NO sources due to shifts in NOS subunits expression or modifications of NADPH oxidases activity may be linked to or promote the development of pathology. However, there is a lack of information about the detailed mechanisms describing the production and release of NO in the glomerular cells. The interaction of NO and other reactive oxygen species in podocytes and how NO-calcium crosstalk regulates glomerular cells’ function is still largely unknown. Here, we discuss recent reports describing signaling, synthesis, and known pathophysiological mechanisms mediated by the changes in NO homeostasis in the podocyte. The understanding and further investigation of these essential mechanisms in glomerular cells will facilitate the design of novel strategies to prevent or manage health conditions that cause glomerular and kidney damage.
Vasoconstrictor and Pressor Effects of Des-Aspartate-Angiotensin I in Rat
Authors: Wangensteen Rosemary , Gómez-Guzmán Manuel , Banegas Inmaculada , Rodríguez-Gómez Isabel , Jiménez Rosario , Duarte Juan , García-Estañ Joaquín , Vargas Félix
Published: May 2022

This study investigated the vasoactive effects of des-aspartate-angiotensin-I (DAA-I) in male Wistar rats on whole body vascular bed, isolated perfused kidneys, and aortic rings. Dose–response curves to DAA-I were compared with those to angiotensin II (Ang II). The Ang II-type-1 (AT1) receptor blocker, losartan, was used to evaluate the role of AT1 receptors in the responses to DAA-I. Studies were also conducted of the responsiveness in aortic rings after endothelium removal, nitric oxide synthase inhibition, or AT2 receptor blockade. DAA-I induced a dose-related systemic pressor response that was shifted to the right compared with Ang II. Losartan markedly attenuated the responsiveness to DAA-I. DAA-I showed a similar pattern in renal vasculature and aortic rings. In aortic rings, removal of endothelium and nitric oxide inhibition increased the sensitivity and maximal response to DAA-I and Ang II. AT2 receptor blockade did not significantly affect the responsiveness to DAA-I. According to these findings, DAA-I increases the systemic blood pressure and vascular tone in conductance and resistance vessels via AT1 receptor activation. This vasoconstrictor effect of DAA-I participates in the homeostatic control of arterial pressure, which can also contribute to the pathogenesis of hypertension. DAA-I may therefore be a potential therapeutic target in cardiovascular disease.
Pain after Interventional Radiology in Oncology: A Case-Control Study from a 5-Year Cohort
Authors: Ayaden Narimane , Sitbon Philippe , Pages Arnaud , Tselikas Lambros , Bourgain Jean-Louis
Published: May 2022

Background: Interventional radiology plays a major role in oncology both for curative and palliative treatment, but few reports address post-procedural pain. The purpose of this study was to quantify postoperative pain after interventional radiology procedures in oncology and to identify major pain-associated pre and intraoperative factors. Methods: From 2015 to 2019, all patients treated with interventional radiology were included retrospectively in a cohort study. Anesthetic protocols were standardized by the type of radiological procedure. Demographic data, preoperative treatments, analgesic agents, pain score levels, and morphine consumption from the post-anesthesia care unit (PACU) to hospital discharge were collected from databases. In an additional case-control study, patients reporting strong or intolerable pain in PACU were compared to those with no pain. Matching to control cases was based on the type of intervention, sex, and age. Results: From 4411 procedures, severe pain in PACU was more frequent in women (p < 0.04) and the youngest patients (p < 0.0001), after general anesthesia (p < 0.0001). Higher pain levels were associated with certain procedures, such as arterial embolization, limb cementoplasty, osteosynthesis, and abdominal tumor ablation, and when the intervention duration exceeded 160 min (p = 0.038). In the cohort study, high-dose remifentanil (≥0.055 µg/kg/min) was a risk factor for post-procedural high pain levels (p < 0.001). Intraoperative ketoprofen was associated with a decrease in high pain level incidence (p < 0.0001). Severe pain in PACU was a risk factor for severe pain in wards from day 0 until discharge. Conclusion: Severe pain depends on the type and duration of interventional radiology, type of anesthesia, and preoperative use of opiates. Limiting doses of remifentanil and injecting intraoperative analgesics, especially ketoprofen, may reduce the incidence of post-intervention severe pain.
Pancreatic Ductal Adenocarcinoma: Current and Emerging Therapeutic Uses of Focused Ultrasound
Authors: Lafond Maxime , Lambin Thomas , Drainville Robert Andrew , Dupré Aurélien , Pioche Mathieu , Melodelima David , Lafon Cyril
Published: May 2022

Pancreatic ductal adenocarcinoma (PDAC) diagnosis accompanies a somber prognosis for the patient, with dismal survival odds: 5% at 5 years. Despite extensive research, PDAC is expected to become the second leading cause of mortality by cancer by 2030. Ultrasound (US) has been used successfully in treating other types of cancer and evidence is flourishing that it could benefit PDAC patients. High-intensity focused US (HIFU) is currently used for pain management in palliative care. In addition, clinical work is being performed to use US to downstage borderline resectable tumors and increase the proportion of patients eligible for surgical ablation. Focused US (FUS) can also induce mechanical effects, which may elicit an anti-tumor response through disruption of the stroma and can be used for targeted drug delivery. More recently, sonodynamic therapy (akin to photodynamic therapy) and immunomodulation have brought new perspectives in treating PDAC. The aim of this review is to summarize the current state of those techniques and share our opinion on their future and challenges.
Molecular Oncology of Bladder Cancer from Inception to Modern Perspective
Authors: Lokeshwar Soum D. , Lopez Maite , Sarcan Semih , Aguilar Karina , Morera Daley S. , Shaheen Devin M. , Lokeshwar Bal L. , Lokeshwar Vinata B.
Published: May 2022

Within the last forty years, seminal contributions have been made in the areas of bladder cancer (BC) biology, driver genes, molecular profiling, biomarkers, and therapeutic targets for improving personalized patient care. This overview includes seminal discoveries and advances in the molecular oncology of BC. Starting with the concept of divergent molecular pathways for the development of low- and high-grade bladder tumors, field cancerization versus clonality of bladder tumors, cancer driver genes/mutations, genetic polymorphisms, and bacillus Calmette-Guérin (BCG) as an early form of immunotherapy are some of the conceptual contributions towards improving patient care. Although beginning with a promise of predicting prognosis and individualizing treatments, “-omic” approaches and molecular subtypes have revealed the importance of BC stem cells, lineage plasticity, and intra-tumor heterogeneity as the next frontiers for realizing individualized patient care. Along with urine as the optimal non-invasive liquid biopsy, BC is at the forefront of the biomarker field. If the goal is to reduce the number of cystoscopies but not to replace them for monitoring recurrence and asymptomatic microscopic hematuria, a BC marker may reach clinical acceptance. As advances in the molecular oncology of BC continue, the next twenty-five years should significantly advance personalized care for BC patients.
Model Cell Lines and Tissues of Different HGSOC Subtypes Differ in Local Estrogen Biosynthesis
Authors: Pavlič Renata , Gjorgoska Marija , Rižner Tea Lanišnik
Published: May 2022

Ovarian cancer (OC) is highly lethal and heterogeneous. Several hormones are involved in OC etiology including estrogens; however, their role in OC is not completely understood. Here, we performed targeted transcriptomics and estrogen metabolism analyses in high-grade serous OC (HGSOC), OVSAHO, Kuramochi, COV632, and immortalized normal ovarian epithelial HIO-80 cells. We compared these data with public transcriptome and proteome data for the HGSOC tissues. In all model systems, high steroid sulfatase expression and weak/undetected aromatase (CYP19A1) expression indicated the formation of estrogens from the precursor estrone-sulfate (E1-S). In OC cells, the metabolism of E1-S to estradiol was the highest in OVSAHO, followed by Kuramochi and COV362 cells, and decreased with increasing chemoresistance. In addition, higher HSD17B14 and CYP1A2 expressions were observed in highly chemoresistant COV362 cells and platinum-resistant tissues compared to those in HIO-80 cells and platinum-sensitive tissues. The HGSOC cell models differed in HSD17B10, CYP1B1, and NQO1 expression. Proteomic data also showed different levels of HSD17B10, CYP1B1, NQO1, and SULT1E1 between the four HGSOC subtypes. These results suggest that different HGSOC subtypes form different levels of estrogens and their metabolites and that the estrogen-biosynthesis-associated targets should be further studied for the development of personalized treatment.
Inhibition of HDAC and Signal Transduction Pathways Induces Tight Junctions and Promotes Differentiation in p63-Positive Salivary Duct Adenocarcinoma
Authors: Nakano Masaya , Ohwada Kizuku , Shindo Yuma , Konno Takumi , Kohno Takayuki , Kikuchi Shin , Tsujiwaki Mitsuhiro , Ishii Daichi , Nishida Soshi , Kakuki Takuya , Obata Kazufumi , Miyata Ryo , Kurose Makoto , Kondoh Atsushi , Takano Kenichi , Kojima Takashi
Published: May 2022

Background: The p53 family p63 is essential for the proliferation and differentiation of various epithelial basal cells. It is overexpressed in several cancers, including salivary gland neoplasia. Histone deacetylases (HDACs) are thought to play a crucial role in carcinogenesis, and HDAC inhibitors downregulate p63 expression in cancers. Methods: In the present study, to investigate the roles and regulation of p63 in salivary duct adenocarcinoma (SDC), human SDC cell line A253 was transfected with siRNA-p63 or treated with the HDAC inhibitors trichostatin A (TSA) and quisinostat (JNJ-26481585). Results: In a DNA array, the knockdown of p63 markedly induced mRNAs of the tight junction (TJ) proteins cingulin (CGN) and zonula occuludin-3 (ZO-3). The knockdown of p63 resulted in the recruitment of the TJ proteins, the angulin-1/lipolysis-stimulated lipoprotein receptor (LSR), occludin (OCLN), CGN, and ZO-3 at the membranes, preventing cell proliferation, and leading to increased cell metabolism. Treatment with HDAC inhibitors downregulated the expression of p63, induced TJ structures, recruited the TJ proteins, increased the epithelial barrier function, and prevented cell proliferation and migration. Conclusions: p63 is not only a diagnostic marker of salivary gland neoplasia, but it also promotes the malignancy. Inhibition of HDAC and signal transduction pathways is, therefore, useful in therapy for p63-positive SDC cells.
Tracking miR-17-5p Levels following Expression of Seven Reported Target mRNAs
Authors: Du Kevin Y. , Qadir Javeria , Yang Burton B. , Yee Albert J. , Yang Weining
Published: May 2022

As the most prominent member of the miR-17-92 cluster, miR-17-5p is well associated with tumorigenesis and cancer progression. It can exert both oncogenic and tumor-suppressive functions by inducing translational repression and/or mRNA decay. The complexity of the tissue-specific expression of the targeted transcripts seems to contribute to the differential functions of miR-17-5p in different types of cancers. In this study, we selected 12 reported miR-17-5p targeting genes with mRNA levels unaffected by miR-17-5p expression and analyzed their expression in 31 organ tissues in transgenic mice by real-time PCR. Surprisingly, miR-17-5p expressing transgenic mice showed a positive correlation in these tissues between miR-17-5p expression levels and the selected miR-17-5p targeted transcripts; with high expression of the miRNA in organs with high selected miRNA-targeted mRNA levels. In cancer cell lines, overexpression of 7 reported miR-17-5p targeted genes’ 3′-UTRs promoted miR-17-5p expression; meanwhile, transfection of 3′-UTRs with mutations had no significant effect. Moreover, an increase in AGO2 mRNA was associated with 3′-UTR expression as confirmed by real-time PCR. Hence, miR-17-5p regulation by these target genes might be an alternative mechanism to maintain miR-17-5p expression at tissue-specific levels.
Proton Therapy for Squamous Cell Carcinoma of the Head and Neck: Early Clinical Experience and Current Challenges
Authors: Nuyts Sandra , Bollen Heleen , Ng Sweet Ping , Corry June , Eisbruch Avraham , Mendenhall William M , Smee Robert , Strojan Primoz , Ng Wai Tong , Ferlito Alfio
Published: May 2022

Proton therapy (PT) is a promising development in radiation oncology, with the potential to further improve outcomes for patients with squamous cell carcinoma of the head and neck (HNSCC). By utilizing the finite range of protons, healthy tissue can be spared from beam exit doses that would otherwise be irradiated with photon-based treatments. Current evidence on PT for HNSCC is limited to comparative dosimetric analyses and retrospective single-institution series. As a consequence, the recognized indications for the reimbursement of PT remain scarce in most countries. Nevertheless, approximately 100 PT centers are in operation worldwide, and initial experiences for HNSCC are being reported. This review aims to summarize the results of the early clinical experience with PT for HNSCC and the challenges that are currently faced.
Systemic Therapy of Metastatic Pancreatic Adenocarcinoma: Current Status, Challenges, and Opportunities
Authors: Chakrabarti Sakti , Kamgar Mandana , Mahipal Amit
Published: May 2022

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by nonspecific presenting symptoms, lack of a screening test, rapidly progressive clinical course, and presentation with an advanced-stage disease in the majority of patients. PDAC is essentially a systemic disease irrespective of the initial stage, as most patients with non-metastatic PDAC undergoing curative-intent treatment eventually experience metastatic relapse. Currently, cytotoxic chemotherapy remains the cornerstone of treatment in patients with advanced disease. However, the current standard treatment with multiagent chemotherapy has modest efficacy and results in median overall survival (OS) of less than a year and a 5-year OS of about 10%. The pathobiology of PDAC poses many challenges, including a unique tumor microenvironment interfering with drug delivery, intratumoral heterogeneity, and a strongly immunosuppressive microenvironment that supports cancer growth. Recent research is exploring a wide range of novel therapeutic targets, including genomic alterations, tumor microenvironment, and tumor metabolism. The rapid evolution of tumor genome sequencing technologies paves the way for personalized, targeted therapies. The present review summarizes the current chemotherapeutic treatment paradigm of advanced PDAC and discusses the evolving novel targets that are being investigated in a myriad of clinical trials.
Ring Finger Protein 125 Is an Anti-Proliferative Tumor Suppressor in Hepatocellular Carcinoma
Authors: Kodama Takahiro , Kodama Michiko , Jenkins Nancy A. , Copeland Neal G. , Chen Huanhuan Joyce , Wei Zhubo
Published: May 2022

Hepatocellular carcinoma (HCC) is one of the deadliest cancers worldwide and the only cancer with an increasing incidence in the United States. Recent advances in sequencing technology have enabled detailed profiling of liver cancer genomes and revealed extensive inter- and intra-tumor heterogeneity, making it difficult to identify driver genes for HCC. To identify HCC driver genes, we performed transposon mutagenesis screens in a mouse HBV model of HCC and discovered many candidate cancer genes (SB/HBV-CCGs). Here, we show that one of these genes, RNF125 is a potent anti-proliferative tumor suppressor gene in HCC. RNF125 is one of nine CCGs whose expression was >3-fold downregulated in human HCC. Depletion of RNF125 in immortalized mouse liver cells led to tumor formation in transplanted mice and accelerated growth of human liver cancer cell lines, while its overexpression inhibited their growth, demonstrating the tumor-suppressive function of RNF125 in mouse and human liver. Whole-transcriptome analysis revealed that RNF125 transcriptionally suppresses multiple genes involved in cell proliferation and/or liver regeneration, including Egfr, Met, and Il6r. Blocking Egfr or Met pathway expression inhibited the increased cell proliferation observed in RNF125 knockdown cells. In HCC patients, low expression levels of RNF125 were correlated with poor prognosis demonstrating an important role for RNF125 in HCC. Collectively, our results identify RNF125 as a novel anti-proliferative tumor suppressor in HCC.
Immune Response in Vitamin D Deficient Metastatic Colorectal Cancer Patients: A Player That Should Be Considered for Targeted Vitamin D Supplementation
Authors: Morelli Cristina , Rofei Michela , Riondino Silvia , Fraboni Daniela , Torino Francesco , Orlandi Augusto , Tesauro Manfredi , Del Vecchio Blanco Giovanna , Federici Massimo , Arkenau Hendrik-Tobias , Formica Vincenzo , Roselli Mario
Published: May 2022

Background: Vitamin D deficiency is a poor prognostic factor in metastatic colorectal cancer (mCRC); however, targeted supplementation trials have so far yielded limited results. We investigated clinical-laboratory parameters influencing vitamin D deficiency, with a particular focus on immune response, and the effect on survival. These parameters could help optimize targeted supplementation therapy. Methods: Association of plasma 25-hydroxyvitamin D (25(OH])D) with overall survival (OS) was assessed with the Hazard Ratio Smoothed Curve with Restricted Cubic Splines (HRSC-RCS) and maximally selected rank statistics (MSRS) in mCRC patients who underwent first-line chemotherapy. Several hematobiochemical variables were evaluated as predictors of vitamin D deficiency by means of Least Absolute Shrinkage and Selection Operator (LASSO) analysis. In a patient subset, peripheral lymphocyte subpopulations were also analyzed. Results: One hundred thirty-three mCRC patients were included. The median(m) baseline 25(OH)D was 10.8 ng/mL (range 3–53.4). HRSC-RCS revealed a linear association between 25(OH)D and OS. MSRS found 10 ng/mL as the optimal 25(OH)D cut-off. The median OS for 25(OH)D < 10 (n = 60) vs. > 10 ng/mL (n = 73) was 12.3 and 24.5 months, respectively (p = 0.002). The LASSO analysis identified high neutrophil-to-lymphocyte ratio (NLR > 3.5) as the strongest predictor of vitamin D deficiency (Odds Ratio 3.35, p 0.0009). Moreover, patients with low 25(OH)D levels (< 10 ng/mL) and high NLR (>3.5) had the shortest survival and patients with 25(OH)D >10 ng/mL and NLR <3.5 had the longest: mOS 8.1 and 28.1 months, respectively, HR 3.40 (1.76–6.59), p 0.0004. Besides the significant difference in NLR between 25(OH)D < and > 10 ng/mL patients (mNLR 3.6 vs. 2.9, p 0.03), the lymphocyte subpopulation analysis revealed that vitamin D deficiency was associated with high T- CD4+ (p = 0.04) and low B (p = 0.03) lymphocyte frequency. Conclusions: NLR is a powerful predictor of Vitamin D deficiency and can further help in stratifying prognosis. Vitamin D deficiency was associated with significant variations in peripheral immune cells. We hypothesize that integrated targeted interventions to both vitamin D and immune system would improve the prognosis of mCRC patients.