bluuebunny/crossref_metadata_2025 huggingface dataset:
Endothelial NOX5 Expression Modulates Thermogenesis and Lipolysis in Mice Fed with a High-Fat Diet and 3T3-L1 Adipocytes through an Interleukin-6 Dependent Mechanism
Authors: García Jorge G. , de Miguel Carlos , Milagro Fermín I. , Zalba Guillermo , Ansorena Eduardo
Published: December 2021

Obesity is a global health issue associated with the development of metabolic syndrome, which correlates with insulin resistance, altered lipid homeostasis, and other pathologies. One of the mechanisms involved in the development of these pathologies is the increased production of reactive oxygen species (ROS). One of the main producers of ROS is the family of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, among which NOX5 is the most recently discovered member. The aim of the present work is to describe the effect of endothelial NOX5 expression on neighboring adipose tissue in obesity conditions by using two systems. An in vivo model based on NOX5 conditional knock-in mice fed with a high-fat diet and an in vitro model developed with 3T3-L1 adipocytes cultured with conditioned media of endothelial NOX5-expressing bEnd.3 cells, previously treated with glucose and palmitic acid. Endothelial NOX5 expression promoted the expression and activation of specific markers of thermogenesis and lipolysis in the mesenteric and epididymal fat of those mice fed with a high-fat diet. Additionally, the activation of these processes was derived from an increase in IL-6 production as a result of NOX5 activity. Accordingly, 3T3-L1 adipocytes treated with conditioned media of endothelial NOX5-expressing cells, presented higher expression of thermogenic and lipolytic genes. Moreover, endothelial NOX5-expressing bEnd.3 cells previously treated with glucose and palmitic acid also showed interleukin (IL-6) production. Finally, it seems that the increase in IL-6 stimulated the activation of markers of thermogenesis and lipolysis through phosphorylation of STAT3 and AMPK, respectively. In conclusion, in response to obesogenic conditions, endothelial NOX5 activity could promote thermogenesis and lipolysis in the adipose tissue by regulating IL-6 production.
Integrated Metabolomics and Transcriptomic Analysis of Hepatopancreas in Different Living Status Macrobrachium nipponense in Response to Hypoxia
Authors: Xu Lei , Zhang Wenyi , Qiao Hui , Jiang Sufei , Xiong Yiwei , Jin Shubo , Gong Yongsheng , Fu Hongtuo
Published: December 2021

As the basic element of aerobic animal life, oxygen participates in most physiological activities of animals. Hypoxia stress is often the subject of aquatic animal research. Macrobrachium nipponense, an economically important aquatic animal in southern China, has been affected by hypoxia for many years and this has resulted in a large amount of economic loss due to its sensitivity to hypoxia; Metabolism and transcriptome data were combined in the analysis of the hepatopancreas of M. nipponense in different physiological states under hypoxia; A total of 108, 86, and 48 differentially expressed metabolites (DEMs) were found in three different comparisons (survived, moribund, and dead shrimps), respectively. Thirty-two common DEMs were found by comparing the different physiological states of M. nipponense with the control group in response to hypoxia. Twelve hypoxia-related genes were identified by screening and analyzing common DEMs. GTP phosphoenolpyruvate carboxykinase (PEPCK) was the only differentially expressed gene that ranked highly in transcriptome analysis combined with metabolome analysis. PEPCK ranked highly both in transcriptome analysis and in combination with metabolism analysis; therefore, it was considered to have an important role in hypoxic response. This manuscript fills the one-sidedness of the gap in hypoxia transcriptome analysis and reversely deduces several new genes related to hypoxia from metabolites. This study contributes to the clarification of the molecular process associated with M. nipponense under hypoxic stress.
The Effect of MICP on Physical and Mechanical Properties of Silt with Different Fine Particle Content and Pore Ratio
Authors: Zhao Yang , Wang Qian , Yuan Mengnan , Chen Xi , Xiao Zhiyang , Hao Xiaohong , Zhang Jing , Tang Qiang
Published: December 2021

Microbial-induced calcium carbonate precipitation (MICP) is a new soil remediation technology, which can improve the physical and mechanical properties of soil by transporting bacterial solution and cementation solution to loose soil and precipitating calcium carbonate precipitation between soil particles through microbial mineralization. Based on this technique, the effects of different fine particle content and pore ratio on the physical and chemical properties of silt after reinforcement were studied. The content of calcium carbonate, the ability of silt to fixed bacteria, unconfined compressive strength (UCS), permeability coefficient and microstructure of the samples were determined. The results showed the following: In the process of calcium carbonate precipitation induced by microorganisms, more than 50% bacterial suspension remained on the surface of silt particles and their pores. The higher the bacterial fixation rate of silt, the more CaCO3 was generated during the solidification process. The bacterial fixation rate and CaCO3 content both decreased with the increase in the pore ratio and increased with the increase in the fine particle content. XRD and SEM images show that the calcium carbonate is mainly composed of spherical vaterite and acicular cluster aragonite. There is an obvious correlation between unconfined compressive strength and CaCO3 content of silt. When CaCO3 content accumulates to a certain extent, its strength will be significantly improved. The unconfined compressive strength of silt A with pore ratio of 0.75 and fine particle content of 75% is 2.22 MPa when the single injection amount of cementing fluid is 300 mL. The permeability coefficient of cured silt can be reduced by 1 to 4 orders of magnitude compared with that of untreated silt. In particular, the permeability of MICP-treated silt A is almost impermeable.
EdgeX over Kubernetes: Enabling Container Orchestration in EdgeX
Authors: Lee Seunghwan , Phan Linh-An , Park Dae-Heon , Kim Sehan , Kim Taehong
Published: December 2021

With the exponential growth of the Internet of Things (IoT), edge computing is in the limelight for its ability to quickly and efficiently process numerous data generated by IoT devices. EdgeX Foundry is a representative open-source-based IoT gateway platform, providing various IoT protocol services and interoperability between them. However, due to the absence of container orchestration technology, such as automated deployment and dynamic resource management for application services, EdgeX Foundry has fundamental limitations of a potential edge computing platform. In this paper, we propose EdgeX over Kubernetes, which enables remote service deployment and autoscaling to application services by running EdgeX Foundry over Kubernetes, which is a product-grade container orchestration tool. Experimental evaluation results prove that the proposed platform increases manageability through the remote deployment of application services and improves the throughput of the system and service quality with real-time monitoring and autoscaling.
Copper Nanoparticles: Synthesis and Characterization, Physiology, Toxicity and Antimicrobial Applications
Authors: Crisan Michaela Corina , Teodora Mocan , Lucian Mocan
Published: December 2021

Metallic nanoparticles are a new class of materials with applications in medicine, pharmaceutical and agriculture. Using biological, chemical and physical approaches, nanoparticles with amazing properties are obtained. Copper is one of the most-found elements and plays an important part in the normal functioning of organisms. Coper nanoparticles have superior antibacterial properties when comparing them to present day antibiotics. Moreover, apart from their antibacterial role, antifungal, antiviral and anticancer properties have been described. Although the mechanism of actions is not completely understood, copper nanoparticles can become a viable alternative in fighting multi-resistant bacteria strains. We hereby review the already existing data on copper nanoparticle synthesis, effects and mechanisms of action as well as toxicity.
Custom-Made Alloplastic Prosthetic Implant to Treat Temporomandibular Joint Ankylosis in Pediatric Patients: A Case Study
Authors: Lazzarotto Andrea , Tel Alessandro , Nocini Riccardo , Raccampo Luca , Sembronio Salvatore , Costa Fabio , Robiony Massimo
Published: December 2021

Temporomandibular Joint (TMJ) ankylosis represents a fairly common condition which surgeons need to face. According to Rowe, it can be defined as a restricted functional capacity of the jaw with limited movements owing to bony or fibrous adhesions between the condyle and either glenoid fossa, disc or eminence (or both). It can become a disease which impacts patients’ daily life, who suffer from limited mandibular excursion with reduced intercisal opening, anterior open bite, inability to swallow, sleep disorders, and speech problems. In children this may also result in abnormal mandibular and facial growth. In this paper, we deal with the case of a child with an important momolateral ankylosis, previously treated surgically with Costochondral Grafting arthroplasty without success and subsequently treated with a custom-made prosthesis.
Ontology-Based Nutritional Recommender System
Authors: Mckensy-Sambola Dexon , Rodríguez-García Miguel Ángel , García-Sánchez Francisco , Valencia-García Rafael
Published: December 2021

Obesity is considered an epidemic that is continuously growing around the world. Heart diseases, diabetes, and bone and joint diseases are some of the diseases that people who are overweight or obese can develop. One of the vital causes of those disorders is poor nutrition education; there is no raising awareness about eating healthy food and practicing physical activities to burn off the excess energy. Therefore, it is necessary to use new technologies to build methods/tools that help people to overcome these avoidable nutrition disorders. For this reason, we implemented a recommendation engine capable of identifying the different levels of overweight and obesity in users and providing dietary strategies to mitigate them. To do so, we defined the Ontology of Dietary Recommendations (ODR) with axioms to model recipes, ingredients, and a set of diets to assist people who suffer from obesity. We validated the defined model by using a real set of individuals who were anonymized. A panel of advisors evaluated each individual record and suggested the most appropriate diets from those included in the ontology. Then, the proposed system was asked to also provide diet recommendations for each individual, which were compared with those proposed by the advisors (ground truth), reaching a mean accuracy of 87%.
Enhanced Quasi Type-1 PLL-Based Multi-Functional Control of Single-Phase Dynamic Voltage Restorer
Authors: Ahmed Hafiz , Biricik Samet , Komurcugil Hasan , Benbouzid Mohamed
Published: December 2021

This paper considers the reference signal generation problem for the multi-functional operation of single-phase dynamic voltage restorers. For this purpose, a single-phase quasi type-1 phase-locked loop (QT1-PLL) is proposed. The pre-loop filter part of this PLL is composed of a frequency-fixed delayed signal cancellation method and a two-stage all-pass filter. Thanks to the frequency-fixed nature, the pre-loop filter is easy to implement and can provide rejection of any measurement offset. Moreover, this PLL benefits from the excellent harmonic robustness property of the conventional QT1-PLL. Small-signal modeling and gain tuning procedures are detailed in this paper. In order to track the reference voltage signals generated by the proposed PLL, a super-twisting sliding mode controller is also presented, which helps to achieve fast dynamic responses. Laboratory-scale prototype-based experimental studies were conducted to validate the developed reference generator and the controller. Experimental results show that the proposed method is fast in detecting and compensating any grid voltage anomalies to maintain constant load voltage despite voltage sag, swell, and harmonic distortions.
Modeling Hot Deformation of 5005 Aluminum Alloy through Locally Constrained Regression Models with Logarithmic Transformations
Authors: Cho Jeongho , Song Shin-Hyung
Published: December 2021

This study presents the adoption of locally constrained regression models (LCRMs) with logarithmic transformations in order to model the flow stress behavior of the high-temperature deformation of 5005 aluminum alloy. Hot tensile tests for 5005 aluminum alloy were conducted under the temperatures of 290 °C, 360 °C, 430 °C, and 500 °C, and the strain rates of 0.0003/s, 0.003/s, and 0.03/s. The flow stress behavior was analyzed based on variations in temperature and strain rate. The flow stress during the hot deformation was modeled using the traditional Arrhenius type constitutive equation and the neural network approach. Then, for improved prediction accuracy, the flow stress was modeled using LCRMs. The prediction accuracies of the models were compared by calculating the MAE (Maximum Absolute Error) and RMSE (Root-Mean-Squared Errors) values. The MAE and RMSE of the LCRMs were lower than the errors of the Arrhenius equation and the neural network model. The results show that LCRMs can be useful in modeling the flow stress of 5005 aluminum alloy, and that the developed model can accurately predict the flow stress.
Contrastive Analysis on the Ventilation Performance of a Combined Solar Chimney
Authors: Liu Huifang , Li Peijia , Yu Bendong , Zhang Mingyi , Tan Qianli , Wang Yu , Zhang Yi
Published: December 2021

A combined solar chimney is proposed in this paper that integrates an inclined-roof solar chimney with a traditional Trombe wall. The ventilation performance of the combined solar chimney is analyzed numerically and then compared with the Trombe wall and the inclined-roof solar chimney. The feasibility of different operation modes and the ventilation effect under different environment conditions are also discussed. The results show that when the ambient temperature ranges from 298 to 303 K in the summer, a natural ventilation mode is appropriate. Otherwise, an anti-overheating mode is recommended. When the ambient temperature is lower than 273 K in the winter, a space heating mode has a better heating effect. A preheating mode can be employed to improve the indoor air quality when the ambient temperature is higher than 278 K. The simulation results indicates that the ventilation effect of the combined solar chimney is better than that of the Trombe wall and the inclined-roof solar chimney, and the problem of overheating can be avoided. The study provides guidance for the optimal operation of a combined solar chimney.
Comparative Analysis of the Indirect Calorimetry and the Metabolic Power Method to Calculate Energy Expenditure in Team Handball
Authors: Fuchs Patrick , Luteberget Live S. , Fuchs Philip X. , Wagner Herbert
Published: December 2021

Monitoring physical activity, e.g., training load and energy expenditure (EE), is important to optimize the training process in various sports. Especially in team handball, where there is little information about EE in training and competition. The objective of the study was to compare EE in team handball derived from a respiratory gas exchange analysis (spiroergometry) and a local position measurement (LPM) system. Eleven participants completed a validated, team handball game-based performance test and wore a portable spiroergometry system (K5 Cosmed) and an LPM transponder (Catapult ClearSky T6). EE was determined via indirect calorimetry for spiroergometry data and via the metabolic power model for EE for LPM data. EE estimated via the metabolic power model was −66 to −63 ± 12% lower than via indirect calorimetry (p < 0.001, pη2 = 0.97). No correlation was found for the overall test (r = 0.32, p = 0.34), nor for every single heat (r ≤ 0.44, 0.18 ≤ p ≤ 0.99). Therefore, regression analyses predicting spiroergometry data based on LPM data were not feasible. In line with previous studies, the metabolic power model for EE in team handball (including short-distance movements, great accelerations, and non-locomotive actions) is not suitable.
Associations of Urinary Collagen II Neoepitope C2C with Total Knee Replacement Outcomes: Is OA a Systemic Disease in Rapidly Progressive Cases?
Authors: Kuhi Liisa , Tamm Ann E. , Kumm Jaanika , Järv Kristel , Märtson Aare , Tamm Agu O. , Kisand Kalle
Published: December 2021

The objective of this study was to investigate the dynamics of the urinary collagen type II C-terminal cleavage neoepitope (uC2C) before and after total knee replacement (TKR) in rapid knee OA progressors. C2C in the urine was measured by IBEX-uC2C assay in 86 patients (mean age: 59.9 years) with symptomatic knee OA (kOA) undergoing TKR, assessed before surgery and 3 and 12 months after. The patients’ condition was determined by self-assessment questionnaires, by lower limb performance tests, and by radiography. In the preoperative period, the uC2C level was significantly higher in females than in males, and was associated with the radiographic severity of kOA. A weak correlation between the C2C and knee pain was observed in the whole group and in males, but not in females. The individual dynamics of uC2C after TKR were heterogenic. In general, uC2C increased three months after TKR, but fell to the preoperative level after 12 months. A higher preoperative uC2C implied the tendency to diminish as a result of TKR, and vice versa. TKR did not stop the degradation of Coll2 in the tissues in the majority of cases. The pre-TKR uC2C predicts the postoperative uC2C level. The uC2C dynamic seems to be sex-specific, so it could be considered a prospective pre- and post-TKR biomarker for progressive kOA.
Downscaling of Future Precipitation in China’s Beijing-Tianjin-Hebei Region Using a Weather Generator
Authors: Liao Yaoming , Chen Deliang , Han Zhenyu , Huang Dapeng
Published: December 2021

To project local precipitation at the existing meteorological stations in China’s Beijing-Tianjin-Hebei region in the future, local daily precipitation was simulated for three periods (2006–2030, 2031–2050, and 2051–2070) under RCP 4.5 and RCP 8.5 emission scenarios. These projections were statistically downscaled using a weather generator (BCC/RCG-WG) and the output of five global climate models. Based on the downscaled daily precipitation at 174 stations, eight indices describing mean and extreme precipitation climates were calculated. Overall increasing trends in the frequency and intensity of the mean and extreme precipitation were identified for the majority of the stations studied, which is in line with the GCMs’ output. However, the downscaling approach enables more local features to be reflected, adding value to applications at the local scale. Compared with the baseline during 1961–2005, the regional average annual precipitation and its intensity are projected to increase in all three future periods under both RCP 4.5 and RCP 8.5. The projected changes in the number of days with precipitation are relatively small across the Beijing-Tianjin-Hebei region. The regional average annual number of days with precipitation would increase by 0.2~1.0% under both RCP 4.5 and RCP 8.5, except during 2031–2050 under RCP 8.5 when it would decrease by 0.7%. The regional averages of annual days with precipitation ≥25 mm and ≥40 mm, the greatest one-day and five-day precipitation in the Beijing-Tianjin-Hebei region, are projected to increase by 8~30% during all the three periods. The number of days with daily precipitation ≥40 mm was projected to increase most significantly out of the eight indices, indicating the need to consider increased flooding risk in the future. The average annual maximum number of consecutive days without precipitation in the Beijing-Tianjin-Hebei region is projected to decrease, and the drought risk in this area is expected to decrease.
Patterns and Controls of the Latent and Sensible Heat Fluxes in the Brazilian Pampa Biome
Authors: Rubert Gisele Cristina Dotto , de Arruda Souza Vanessa , Zimmer Tamíres , Veeck Gustavo Pujol , Mergen Alecsander , Bremm Tiago , Ruhoff Anderson , de Gonçalves Luis Gustavo Gonçalves , Roberti Débora Regina
Published: December 2021

Energy and water exchange between the surface and the atmosphere are important drivers to Earth’s climate from local to global scale. In this study, the energy dynamic and the biophysical mechanisms that control the energy partitioning over a natural grassland pasture over the Brazilian Pampa biome are investigated using two micrometeorological sites located 300 km apart, in Southern Brazil. The latent heat flux, LE, was the main component of the energy balance in both autumn-winter (AW) and spring-summer (SS) periods. Annually, approximately 60% of the available energy is used for evapotranspiration (ET). However, the Bowen ratio presents seasonal variability greater in AW than SS. Global radiation, Rg, is the atmospheric variable controlling LE and sensible heat flux, H. Hysteresis curves in the daily cycle were observed for ET and surface conductance, Cs, regarding the environmental variables, net radiation, vapor pressure deficit, and air temperature. Among the variables analyzed in the Pampa biome, surface conductance and evapotranspiration respond more strongly to the vapor pressure deficit. The hysteresis cycles formed by ET and conductance show a substantial biophysical control in the ET process. The results obtained here allowed a comprehension of the biophysical mechanisms involved in the energy partition process in natural grassland. Therefore, this study can be used as a base for research on land-use changes in this unique ecosystem of the Pampa biome.
The Association between Circadian Clock Gene Polymorphisms and Metabolic Syndrome: A Systematic Review and Meta-Analysis
Authors: Škrlec Ivana , Talapko Jasminka , Džijan Snježana , Cesar Vera , Lazić Nikolina , Lepeduš Hrvoje
Published: December 2021

Metabolic syndrome (MetS) is a combination of cardiovascular risk factors associated with type 2 diabetes, obesity, and cardiovascular diseases. The circadian clock gene polymorphisms are very likely to participate in metabolic syndrome genesis and development. However, research findings of the association between circadian rhythm gene polymorphisms and MetS and its comorbidities are not consistent. In this study, a review of the association of circadian clock gene polymorphisms with overall MetS risk was performed. In addition, a meta-analysis was performed to clarify the association between circadian clock gene polymorphisms and MetS susceptibility based on available data. The PubMed and Scopus databases were searched for studies reporting the association between circadian rhythm gene polymorphisms (ARNTL, BMAL1, CLOCK, CRY, PER, NPAS2, REV-ERBα, REV-ERBβ, and RORα) and MetS, and its comorbidities diabetes, obesity, and hypertension. Thirteen independent studies were analyzed with 17,381 subjects in total. The results revealed that the BMAL1 rs7950226 polymorphism was associated with an increased risk of MetS in the overall population. In contrast, the CLOCK rs1801260 and rs6850524 polymorphisms were not associated with MetS. This study suggests that some circadian rhythm gene polymorphisms might be associated with MetS in different populations and potentially used as predictive biomarkers for MetS.
Multi-Modal Regulation of Circadian Physiology by Interactive Features of Biological Clocks
Authors: Lee Yool , Wisor Jonathan P.
Published: December 2021

The circadian clock is a fundamental biological timing mechanism that generates nearly 24 h rhythms of physiology and behaviors, including sleep/wake cycles, hormone secretion, and metabolism. Evolutionarily, the endogenous clock is thought to confer living organisms, including humans, with survival benefits by adapting internal rhythms to the day and night cycles of the local environment. Mirroring the evolutionary fitness bestowed by the circadian clock, daily mismatches between the internal body clock and environmental cycles, such as irregular work (e.g., night shift work) and life schedules (e.g., jet lag, mistimed eating), have been recognized to increase the risk of cardiac, metabolic, and neurological diseases. Moreover, increasing numbers of studies with cellular and animal models have detected the presence of functional circadian oscillators at multiple levels, ranging from individual neurons and fibroblasts to brain and peripheral organs. These oscillators are tightly coupled to timely modulate cellular and bodily responses to physiological and metabolic cues. In this review, we will discuss the roles of central and peripheral clocks in physiology and diseases, highlighting the dynamic regulatory interactions between circadian timing systems and multiple metabolic factors.
Comparison of Semi-Quantitative Scoring and Artificial Intelligence Aided Digital Image Analysis of Chromogenic Immunohistochemistry
Authors: Bencze János , Szarka Máté , Kóti Balázs , Seo Woosung , Hortobágyi Tibor G. , Bencs Viktor , Módis László V. , Hortobágyi Tibor
Published: December 2021

Semi-quantitative scoring is a method that is widely used to estimate the quantity of proteins on chromogen-labelled immunohistochemical (IHC) tissue sections. However, it suffers from several disadvantages, including its lack of objectivity and the fact that it is a time-consuming process. Our aim was to test a recently established artificial intelligence (AI)-aided digital image analysis platform, Pathronus, and to compare it to conventional scoring by five observers on chromogenic IHC-stained slides belonging to three experimental groups. Because Pathronus operates on grayscale 0-255 values, we transformed the data to a seven-point scale for use by pathologists and scientists. The accuracy of these methods was evaluated by comparing statistical significance among groups with quantitative fluorescent IHC reference data on subsequent tissue sections. The pairwise inter-rater reliability of the scoring and converted Pathronus data varied from poor to moderate with Cohen’s kappa, and overall agreement was poor within every experimental group using Fleiss’ kappa. Only the original and converted that were obtained from Pathronus original were able to reproduce the statistical significance among the groups that were determined by the reference method. In this study, we present an AI-aided software that can identify cells of interest, differentiate among organelles, protein specific chromogenic labelling, and nuclear counterstaining after an initial training period, providing a feasible and more accurate alternative to semi-quantitative scoring.
Nigella sativa L. Phytochemistry and Pharmacological Activities: A Review (2019–2021)
Authors: Dalli Mohammed , Bekkouch Oussama , Azizi Salah-eddine , Azghar Ali , Gseyra Nadia , Kim Bonglee
Published: December 2021

Medicinal and aromatic plants are mainly characterized by the presence of different bioactive compounds which exhibit various therapeutic activities. In order to investigate the different pharmacological properties of different Nigella sativa extracts, a multitude of research articles published in the period between 2019 and 2021 were obtained from different databases (Scopus, Science Direct, PubMed, and Web of Science), and then explored and analyzed. The analysis of the collected articles allows us to classify the phytochemicals and the pharmacological activities through their underlying molecular mechanisms, as well as to explore the pharmacological activities exhibited by several identified compounds in Nigella sativa which allow a better understanding, and better elucidation, of the bioactive compounds responsible for the pharmacological effects. Also shown are the existence of other bioactive compounds that are still unexplored and could be of great interest. This review could be taken as a guide for future studies in the field.
Automatic Activity Arising in Cardiac Muscle Sleeves of the Pulmonary Vein
Authors: Bredeloux Pierre , Pasqualin Come , Bordy Romain , Maupoil Veronique , Findlay Ian
Published: December 2021

Ectopic activity in the pulmonary vein cardiac muscle sleeves can both induce and maintain human atrial fibrillation. A central issue in any study of the pulmonary veins is their difference from the left atrial cardiac muscle. Here, we attempt to summarize the physiological phenomena underlying the occurrence of ectopic electrical activity in animal pulmonary veins. We emphasize that the activation of multiple signaling pathways influencing not only myocyte electrophysiology but also the means of excitation–contraction coupling may be required for the initiation of triggered or automatic activity. We also gather information regarding not only the large-scale structure of cardiac muscle sleeves but also recent studies suggesting that cellular heterogeneity may contribute to the generation of arrythmogenic phenomena and to the distinction between pulmonary vein and left atrial heart muscle.
SCN2A Pathogenic Variants and Epilepsy: Heterogeneous Clinical, Genetic and Diagnostic Features
Authors: Epifanio Roberta , Giorda Roberto , Merlano Maria Carolina , Zanotta Nicoletta , Romaniello Romina , Marelli Susan , Russo Silvia , Cogliati Francesca , Bassi Maria Teresa , Zucca Claudio
Published: December 2021

Pathogenic variants of the SCN2A gene (MIM 182390) are associated with several epileptic syndromes ranging from benign familial neonatal-infantile seizures (BFNIS) to early infantile epileptic encephalopathy. The aim of this work was to describe clinical features among five patients with concomitant SCN2A gene variants and cryptogenic epileptic syndromes, thus expanding the SCN2A spectrum of phenotypic heterogeneity. De novo variants were identified in four patients, while one inherited variant was identified in a patient with an unaffected carrier biological father with somatic mosaicism. Two of five patients were diagnosed with a neonatal epileptic encephalopathy. The remaining three patients manifested a focal epileptic syndrome associated with autistic spectrum disorders (ASD) or with a variable degree of intellectual disability (ID), one of them displaying a hitherto unreported atypical late onset epilepsy. Overall, the pattern of clinical manifestations among these patients suggest that any observed neurological impairment may not be directly related to the severity of the electroclinical pattern, but instead likely associated with the mutation itself. Moreover, our results highlight the importance of SCN2A mutational screening in cases of ID/ASD with or without epilepsy.
Architectural Characteristics of Different Configurations Based on New Geometric Determinations for the Conoid
Authors: Cabeza-Lainez Joseph
Published: December 2021

The aim of this article is to orient the evolution of new architectural forms offering up-to-date scientific support. Unlike the volume, the expression for the lateral area of a regular conoid has not yet been obtained by means of direct integration or a differential geometry procedure. In this type of ruled surface, the fundamental expressions I and II, for other curved figures have proved not solvable thus far. As this form is frequently used in architectural engineering, the inability to determine its surface area represents a serious hindrance to solving several problems that arise in radiative transfer, lighting and construction, to cite just a few. To address such drawback, we conceived a new approach that, in principle, consists in dividing the surface into infinitesimal elliptic strips of which the area can be obtained in an approximate fashion. The length of the ellipse is expressed with certain accuracy by means of Ramanujan’s second formula. By integrating the so-found perimeter of the differential strips for the whole span of the conoid, an unexpected solution emerges through a newly found number that we call psi (ψ). In this complex process, projected shapes have been derived from an original closed form composed of two conoids and called Antisphera for its significant parallels with the sphere. The authors try to demonstrate that the properties of the new surfaces have relevant implications for technology, especially in building science and sustainability, under domains such as structures, radiation and acoustics. Fragments of the conoid have occasionally appeared in modern and contemporary architecture but this article discusses how its use had been discontinued, mainly due to the uncertainties that its construction posed. The new knowledge provided by the authors, including their own proposals, may help to revitalize and expand such interesting configurations in the search for a revolution of forms.
Research on the Driving Factors for the Development of Inclusive Finance in Rural Commercial Banks: Market Competition or Government Intervention?
Authors: Zhu Chenlu , Dong Xiaolin , Ding Liren , Lin Chen
Published: December 2021

Based on the survey data of 43 rural commercial banks in Jiangsu Province, China, from 2015 to 2018, 14 indicators among 3 dimensions—coverage, business implementation and service quality—were selected to establish the inclusive finance index of rural commercial banks. The impact of market competition and government intervention on the development of the inclusive finance of rural commercial banks and the mechanism were empirically tested. The heterogeneous performance of market competition and government intervention in different market conditions were also thoroughly discussed. The results show that both market competition and government intervention can help reduce the pricing level and broaden the service coverage of rural commercial banks, which can promote the development of inclusive finance. But the role of market competition has a stronger impact than that of government intervention. The heterogeneity test shows that market competition plays a more significant role in the regions with higher levels of market competition and financial development, and in the southern and central Jiangsu Province, where the economy is relatively more developed. However, in the regions with lower levels of market competition and financial development, as well as in the northern Jiangsu Province, with a relatively backward economy, government intervention significantly improves the degree of inclusive finance of rural commercial banks. Finally, we advocate that the roles of market and government should be applied according to local conditions, and the development of the inclusive finance in rural commercial banks needs to be continuously promoted.
Validation of Pre-/Post-TACE-Predict Models among Patients with Hepatocellular Carcinoma Receiving Transarterial Chemoembolization
Authors: Kim David Sooik , Kim Beom Kyung , Lee Jae Seung , Lee Hye Won , Park Jun Yong , Kim Do Young , Ahn Sang Hoon , Kim Seung Up
Published: December 2021

This study attempted to validate the prognostic performance of the proposed Pre- and Post-TACE (transarterial chemoembolization)-Predict models, in comparison with other models for prognostication. One-hundred-and-eighty-seven patients with HCC who underwent TACE were recruited. Regarding overall survival (OS), the predictive performance of the Pre-TACE-Predict model (one-year integrated area under the curve (iAUC) 0.685 (95% confidence interval (CI) 0.593–0.772)) was better than that of the Post-TACE-Predict model (iAUC 0.659 (95% CI 0.580–0.742)). However, there was no significant statistical difference between two models at any time point. For comparison between models using pre-treatment factors, the modified hepatoma arterial embolization prognostic (mHAP)-II model demonstrated significantly better predictive performance at one year (iAUC 0.767 (95% CI 0.683–0.847)) compared with Pre-TACE-Predict. For comparison between models using first TACE response, the SNACOR model was significantly more predictive at one year (iAUC 0.778 (95% CI 0.687–0.866) vs. 0.659 (95% CI 0.580–0.742), respectively) and three years (iAUC 0.707 (95% CI 0.646–0.770) vs. 0.624 (95% CI 0.564–0.688), respectively) than the Post-TACE-Predict model. mHAP-II and SNACOR may be preferred over the Pre- and Post-TACE-Predict models, respectively, considering their similar or better performance and the ease of application.
Activation of the Unfolded Protein Response (UPR) Is Associated with Cholangiocellular Injury, Fibrosis and Carcinogenesis in an Experimental Model of Fibropolycystic Liver Disease
Authors: Chen Chaobo , Wu Hanghang , Ye Hui , Tortajada Agustín , Rodríguez-Perales Sandra , Torres-Ruiz Raúl , Vidal August , Peligros Maria Isabel , Reissing Johanna , Bruns Tony , Mohamed Mohamed Ramadan , Zheng Kang , Lujambio Amaia , Iraburu Maria J. , Colyn Leticia , Latasa Maria Ujue , Arechederra María , Fernández-Barrena Maite G. , Berasain Carmen , Vaquero Javier , Bañares Rafael , Nelson Leonard J. , Trautwein Christian , Davis Roger J. , Martinez-Naves Eduardo , Nevzorova Yulia A. , Villanueva Alberto , Avila Matias A. , Cubero Francisco Javier
Published: December 2021

Fibropolycystic liver disease is characterized by hyperproliferation of the biliary epithelium and the formation of multiple dilated cysts, a process associated with unfolded protein response (UPR). In the present study, we aimed to understand the mechanisms of cyst formation and UPR activation in hepatocytic c-Jun N-terminal kinase 1/2 (Jnk1/2) knockout mice. Floxed JNK1/2 (Jnkf/f) and Jnk∆hepa animals were sacrificed at different time points during progression of liver disease. Histological examination of specimens evidenced the presence of collagen fiber deposition, increased α-smooth muscle actin (αSMA), infiltration of CD45, CD11b and F4/80 cells and proinflammatory cytokines (Tnf, Tgfβ1) and liver injury (e.g., ALT, apoptosis and Ki67-positive cells) in Jnk∆hepa compared with Jnkf/f livers from 32 weeks of age. This was associated with activation of effectors of the UPR, including BiP/GRP78, CHOP and spliced XBP1. Tunicamycin (TM) challenge strongly induced ER stress and fibrosis in Jnk∆hepa animals compared with Jnkf/f littermates. Finally, thioacetamide (TAA) administration to Jnk∆hepa mice induced UPR activation, peribiliary fibrosis, liver injury and markers of biliary proliferation and cholangiocarcinoma (CCA). Orthoallografts of DEN/CCl4-treated Jnk∆hepa liver tissue triggered malignant CCA. Altogether, these results suggest that activation of the UPR in conjunction with fibrogenesis might trigger hepatic cystogenesis and early stages of CCA.
Targeting Estrogens and Various Estrogen-Related Receptors against Non-Small Cell Lung Cancers: A Perspective
Authors: Maitra Radhashree , Malik Parth , Mukherjee Tapan Kumar
Published: December 2021

Non-small cell lung cancers (NSCLCs) account for ~85% of lung cancer cases worldwide. Mammalian lungs are exposed to both endogenous and exogenous estrogens. The expression of estrogen receptors (ERs) in lung cancer cells has evoked the necessity to evaluate the role of estrogens in the disease progression. Estrogens, specifically 17β-estradiol, promote maturation of several tissue types including lungs. Recent epidemiologic data indicate that women have a higher risk of lung adenocarcinoma, a type of NSCLC, when compared to men, independent of smoking status. Besides ERs, pulmonary tissues both in healthy physiology and in NSCLCs also express G-protein-coupled ERs (GPERs), epidermal growth factor receptor (EGFRs), estrogen-related receptors (ERRs) and orphan nuclear receptors. Premenopausal females between the ages of 15 and 50 years synthesize a large contingent of estrogens and are at a greater risk of developing NSCLCs. Estrogen—ER/GPER/EGFR/ERR—mediated activation of various cell signaling molecules regulates NSCLC cell proliferation, survival and apoptosis. This article sheds light on the most recent achievements in the elucidation of sequential biochemical events in estrogen-activated cell signaling pathways involved in NSCLC severity with insight into the mechanism of regulation by ERs/GPERs/EGFRs/ERRs. It further discusses the success of anti-estrogen therapies against NSCLCs.
Clinical Outcome Assessment in Cancer Rehabilitation and the Central Role of Patient-Reported Outcomes
Authors: Lehmann Jens , Rothmund Maria , Riedl David , Rumpold Gerhard , Grote Vincent , Fischer Michael J. , Holzner Bernhard
Published: December 2021

The aim of cancer rehabilitation is to help patients regain functioning and social participation. In order to evaluate and optimize rehabilitation, it is important to measure its outcomes in a structured way. In this article, we review the different types of clinical outcome assessments (COAs), including Clinician-Reported Outcomes (ClinROs), Observer-Reported Outcomes (ObsROs), Performance Outcomes (PerfOs), and Patient-Reported Outcomes (PROs). A special focus is placed on PROs, which are commonly defined as any direct report from the patient about their health condition without any interpretation by a third party. We provide a narrative review of available PRO measures (PROMs) for relevant outcomes, discuss the current state of PRO implementation in cancer rehabilitation, and highlight trends that use PROs to benchmark value-based care. Furthermore, we provide examples of PRO usage, highlight the benefits of electronic PRO (ePRO) collection, and offer advice on how to select, implement, and integrate PROs into the cancer rehabilitation setting to maximize efficiency.
CXCL12 in Pancreatic Cancer: Its Function and Potential as a Therapeutic Drug Target
Authors: Malik Shivani , Westcott Jill M. , Brekken Rolf A. , Burrows Francis J.
Published: December 2021

Pancreatic ductal adenocarcinoma (PDAC) is a disease with limited therapeutic options and dismal long-term survival. The unique tumor environment of PDAC, consisting of desmoplastic stroma, immune suppressive cells, and activated fibroblasts, contributes to its resistance to therapy. Activated fibroblasts (cancer-associated fibroblasts and pancreatic stellate cells) secrete chemokines and growth factors that support PDAC growth, spread, chemoresistance, and immune evasion. In this review, we focus on one such chemokine, CXCL12, secreted by the cancer-associated fibroblasts and discuss its contribution to several of the classical hallmarks of PDAC and other tumors. We review the various therapeutic approaches in development to target CXCL12 signaling in PDAC. Finally, we propose an unconventional use of tipifarnib, a farnesyl transferase inhibitor, to inhibit CXCL12 production in PDAC.
Features of Metabolic Support of Physical Performance in Highly Trained Cross-Country Skiers of Different Qualifications during Physical Activity at Maximum Load
Authors: Parshukova Olga I. , Varlamova Nina G. , Potolitsyna Natalya N. , Lyudinina Aleksandra Y. , Bojko Evgeny R.
Published: December 2021

The purpose of our study was to identify the features of metabolic regulation in highly trained cross-country skiers of different qualifications at different stages of the maximum load test. We examined 124 highly trained cross-country skiers (male, ages 17–24). The group consisted of two subgroups based on their competition performance: 61 nonelite athletes (Group I) and 63 elite athletes (group II), who were current members of the national team of the Komi Republic and Russia. The bicycle ergometer test was performed by using the OxyconPro system (Erich Jaeger, Hoechberg, Germany). All the examined athletes performed the exercise test on a cycle ergometer “until exhaustion”. The results of our research indicate that the studied groups of athletes with high, but different levels of sports qualifications are a convenient model for studying the molecular mechanisms of adaptation to physical loads of maximum intensity. Athletes of higher qualifications reveal additional adaptive mechanisms of metabolic regulation, which is manifested in the independence of serum lactate indicators under conditions of submaximal and maximum power from maximal oxygen uptake, and they have an NO-dependent mechanism for regulating lactate levels during aerobic exercise, including work at the anaerobic threshold.
Up-Regulation of Fibroblast Growth Factor 23 Gene Expression in UMR106 Osteoblast-like Cells with Reduced Viability
Authors: Münz Sina , Feger Martina , Edemir Bayram , Föller Michael
Published: December 2021

Fibroblast growth factor 23 (FGF23) controls vitamin D and phosphate homeostasis in the kidney and has additional paracrine effects elsewhere. As a biomarker, its plasma concentration is associated with progression of inflammatory, renal, and cardiovascular diseases. Major stimuli of FGF23 synthesis include active vitamin D and inflammation. Antineoplastic chemotherapy treats cancer by inducing cellular damage ultimately favoring cell death (apoptosis and necrosis) and causing inflammation. Our study explored whether chemotherapeutics and other apoptosis inducers impact on Fgf23 expression. Experiments were performed in osteoblast-like UMR106 cells, Fgf23 gene expression and protein synthesis were determined by qRT-PCR and ELISA, respectively. Viability was assessed by MTT assay and NFκB activity by Western Blotting. Antineoplastic drugs cisplatin and doxorubicin as well as apoptosis inducers procaspase-activating compound 1 (PAC-1), a caspase 3 activator, and serum depletion up-regulated Fgf23 transcripts while reducing cell proliferation and viability. The effect of cisplatin on Fgf23 transcription was paralleled by Il-6 up-regulation and NFκB activation and attenuated by Il-6 and NFκB signaling inhibitors. To conclude, cell viability-decreasing chemotherapeutics as well as apoptosis stimulants PAC-1 and serum depletion up-regulate Fgf23 gene expression. At least in part, Il-6 and NFκB may contribute to this effect.
The Effects of a Preconception Lifestyle Intervention on Childhood Cardiometabolic Health—Follow-Up of a Randomized Controlled Trial
Authors: Mintjens Stijn , van Poppel Mireille N. M. , Groen Henk , Hoek Annemieke , Mol Ben Willem , Painter Rebecca C. , Gemke Reinoud J. B. J. , Roseboom Tessa J.
Published: December 2021

Maternal obesity is associated with adverse metabolic outcomes in her offspring, from the earliest stages of development leading to obesity and poorer cardiometabolic health in her offspring. We investigated whether an effective preconception lifestyle intervention in obese women affected cardiometabolic health of their offspring. We randomly allocated 577 infertile women with obesity to a 6-month lifestyle intervention, or to prompt infertility management. Of the 305 eligible children, despite intensive efforts, 17 in the intervention and 29 in the control group were available for follow-up at age 3–6 years. We compared the child’s Body Mass Index (BMI) Z score, waist and hip circumference, body-fat percentage, blood pressure Z scores, pulse wave velocity and serum lipids, glucose and insulin concentrations. Between the intervention and control groups, the mean (±SD) offspring BMI Z score (0.69 (±1.17) vs. 0.62 (±1.04)) and systolic and diastolic blood pressure Z scores (0.45 (±0.65) vs. 0.54 (±0.57); 0.91 (±0.66) vs. 0.96 (±0.57)) were similar, although elevated compared to the norm population. We also did not detect any differences between the groups in the other outcomes. In this study, we could not detect effects of a preconception lifestyle intervention in obese infertile women on the cardiometabolic health of their offspring. Low follow-up rates, perhaps due to the children’s age or the subject matter, combined with selection bias abating contrast in periconceptional weight between participating mothers, hampered the detection of potential effects. Future studies that account for these factors are needed to confirm whether a preconception lifestyle intervention may improve the cardiometabolic health of children of obese mothers.