bluuebunny/crossref_metadata_2025 huggingface dataset:
High-Order Semi-Lagrangian Schemes for the Transport Equation on Icosahedron Spherical Grids
Authors: Lu Fuqiang , Zhang Fengyuan , Wang Tian , Tian Guozhong , Wu Feng
Published: November 2022

The transport process is an important part of the research of fluid dynamics, especially when it comes to tracer advection in the atmosphere or ocean dynamics. In this paper, a series of high-order semi-Lagrangian methods for the transport process on the sphere are considered. The methods are formulated entirely in three-dimensional Cartesian coordinates, thus avoiding any apparent artificial singularities associated with surface-based coordinate systems. The underlying idea of the semi-Lagrangian method is to find the value of the field/tracer at the departure point through interpolating the values of its surrounding grid points to the departure point. The implementation of the semi-Lagrangian method is divided into the following two main procedures: finding the departure point by integrating the characteristic equation backward and then interpolate on the departure point. In the first procedure, three methods are utilized to solve the characteristic equation for the locations of departure points, including the commonly used midpoint-rule method and two explicit high-order Runge–Kutta (RK) methods. In the second one, for interpolation, four new methods are presented, including (1) linear interpolation; (2) polynomial fitting based on the least square method; (3) global radial basis function stencils (RBFs), and (4) local RBFs. For the latter two interpolation methods, we find that it is crucial to select an optimal value for the shape parameter of the basis function. A Gauss hill advection case is used to compare and contrast the methods in terms of their accuracy, and conservation properties. In addition, the proposed method is applied to standard test cases, which include solid body rotation, shear deformation of twin slotted cylinders, and the evolution of a moving vortex. It demonstrates that the proposed method could simulate all test cases with reasonable accuracy and efficiency.
Experimentation of Mitigation Strategies to Contrast the Urban Heat Island Effect: A Case Study of an Industrial District in Italy to Implement Environmental Codes
Authors: Ciacci Cecilia , Banti Neri , Di Naso Vincenzo , Montechiaro Riccardo , Bazzocchi Frida
Published: November 2022

The European goals to reduce CO2 emissions by up to 40% by 2030 and reach carbon neutrality by 2050 cannot ignore the building sector, that accounts for 27% of global greenhouse gas emissions. In the context of the sustainable development goals, it is a key point to consider the reduction of the heat island effect in the urban environment. Considering this background and the proven absence of the clear promotion of urban mitigation measures, the research aims at investigating the influence on several micro-climate parameters of different retrofitting strategies at the building level (green façades) and the cooling strategies at the urban scale (e.g., cool pavements, trees). As a case study, the application of these measures in an industrial district located in Italy is evaluated. ENVI-met software was adopted to perform the outdoor environmental simulations, in order to assess the effectiveness of the mitigation strategies proposed, considering both the whole district and a portion, focusing on urban canyons. Cool pavements proved to be the most promising strategy to both reduce the air temperature and increase the relative humidity. Slighter effects on environmental conditions can be achieved by planting trees and installing green walls that, by contrast, significantly affect the mean radiant temperature and buildings’ surface temperatures, respectively.
Harmonic Analysis of the Relationship between GNSS Precipitable Water Vapor and Heavy Rainfall over the Northwest Equatorial Coast, Andes, and Amazon Regions
Authors: Serrano-Vincenti Sheila , Condom Thomas , Campozano Lenin , Escobar León A. , Walpersdorf Andrea , Carchipulla-Morales David , Villacís Marcos
Published: November 2022

This study finds the relationship between increases in precipitable water vapor (PWV), and intense rainfall events in four different climatological regions of South America’s equatorial northwest: the coast, Andes valley, high mountains, and Amazon. First, the PWV was derived from tropospheric zenith delay measured by Global Navigation Satellite System (GNSS) instrumentation located near meteorological stations within the regions of interest using hourly data from the year 2014. A harmonic analysis approach through continuous wavelet cross-spectrum and coherence, as well as discrete wavelets, was used to determine a measure of the lags found between PWV and specific heavy rain events and then compared with satellite IR images and meteorological anomalies. The link between PWV peaks and rainfall was the most evident on the coast, and less discernible in the other stations possibly due to local dynamic factors. The results showed a lag of 11 h between the preceding PWV increase and an intense rainfall event. This was apparent in all of the stations, except in Amazon where it was 6 h, with the highest precision at the coast and with the largest dispersion in the high mountains. The interpretation of this lag for each region is also discussed.
Spatial-Temporal Variation in Health Impact Attributable to PM2.5 and Ozone Pollution in the Beijing Metropolitan Region of China
Authors: Huo Mingqun , Yamashita Ken , Chen Fang , Sato Keiichi
Published: November 2022

This study aimed to estimate and compare the spatial-temporal variation in health impact attributable to PM2.5, including the major particulate constituents and anthropogenic emission sectors of PM2.5, and ozone in the Beijing–Tianjin–Hebei (BTH) region using monitoring data from 2013 to 2020. The liquid phase reaction may play an important role in PM2.5 formation in winter. We estimated that 110,613 [(95% CI): 91,913, 128,615] and 9921 (95% CI: 3325, 13,191) cases of all-cause mortality in 2020 were attributable to exposure to PM2.5 and ozone in the BTH region, respectively. The control of PM2.5 pollution is currently a priority over that of ozone. An appropriate co-control policy for PM2.5 and ozone pollution is necessary for the surrounding areas of Beijing City to protect public health. From 2013 to 2020, the mortality owing to exposure to PM2.5 dropped significantly. The reduction in carbonaceous components in PM2.5 can have the most effective health benefits. The top two contributing emission sectors to the mortality from PM2.5 in Beijing were regional transportation and vehicles which could explain approximately 6.5% and 5.1% of the total mortality, respectively. The mortality owing to PM2.5 was higher in Beijing than in Tokyo and Bangkok in East Asia.
A Probe into a (2 + 1)-Dimensional Combined Cosmological Model in f(R, T) Gravity
Authors: Islam Safiqul , Aamir Muhammad , Radinschi Irina , Bandyopadhyay Dwiptendra
Published: November 2022

This research is an extension of our earlier published (2+1) dimensional cosmological models in f(R,T) gravity with Λ(R,T) (IOP Conf. Ser. J. Phys. Conf. Ser. 2019, 1258, 012026). A different class of cosmological space model is studied under modified theories of f(R,T) gravity, where the cosmological constant Λ is expressed as a function of the Ricci scalar R and the trace of the stress-energy momentum tensor T. We call such a model as “Λ(R,T) gravity”. Such a specific form of Λ(R,T) has been defined in the dust as well as in the perfect fluid case. We intend to search for a combined model that satisfies the equation of state for dark energy matter or quintessence matter or perfect matter fluid. Some geometric and intrinsic physical properties of the model are also described. The energy conditions, pressure and density are discussed both when Λ=Λ(r) is a function of the radial parameter r, as well as when Λ is zero. We study the effective mass function and also the gravitational redshift function, both of which are found to be positive as per the latest observations. The cosmological model is studied in f(R,T) modified theory of gravity, where the gravitational Lagrangian is expressed both in terms of the Ricci scalar R and the trace of the stress-energy tensor T. The equation of state parameter is discussed in terms of ω corresponding to the three cases mentioned above. The behaviour of the cosmological constant is separately examined in the presence of quintessence matter, dark energy matter and perfect fluid matter.
Long-Term Survival and Curative-Intent Treatment in Hepatitis B or C Virus-Associated Hepatocellular Carcinoma Patients Diagnosed during Screening
Authors: Izzo Francesco , Mason Meredith C. , Silberfein Eric J. , Massarweh Nader N. , Hsu Cary , Tran Cao Hop S. , Palaia Raffaele , Piccirillo Mauro , Belli Andrea , Patrone Renato , Fusco Roberta , Granata Vincenza , Curley Steven A.
Published: November 2022

Background: We initiated a prospective screening trial in patients with hepatitis to diagnose HCC in the early stage and to evaluate the impact on long-term survival. Methods: From 1993–2006, 10,372 patients with chronic hepatitis B (14%), hepatitis C (81%), or both (5%) were enrolled in an HCC screening program. All patients underwent liver biopsy at enrollment. Transabdominal ultrasonography and serum alpha-fetoprotein were evaluated every 6 months. Abnormal screening results led to axial imaging and tumor biopsy. Results: Cirrhosis was confirmed on biopsy in 2074 patients (20%). HCC was diagnosed in 1016 patients (9.8%), all of whom had cirrhosis (49.0% HCC incidence in patients with cirrhosis). HCC was diagnosed at the initial screening in 165 patients (16.2%) and on follow-up in 851 patients (83.8%). The HCC diagnosis median time during follow-up screening was 6 years (range 4–10). Curative-intent treatment (resection, ablation, or transplant) was performed in 713 patients (70.2%). Overall survival at 5 and 10 years in those 713 patients was 30% and 4%, respectively, compared to no 5-year survivors in the 303 patients with advanced-stage disease (p < 0.001). Cause of death at 5 years in the 713 patients treated with curative intent was HCC in 371 patients (52%), progressive cirrhosis in 116 patients (16%), and other causes in 14 patients (2%). At 10 years, 456 patients (64%) had died from HCC, 171 (24%) from progressive cirrhosis, and 57 (8%) from other causes. Conclusions: Our screening program diagnosed early-stage HCC, permitting curative-intent treatment in 70%, but the 10-year survival rate is 4% due to HCC recurrence and progressive cirrhosis.
Bio-Multifunctional Sponges Containing Alginate/Chitosan/Sargassum Polysaccharides Promote the Healing of Full-Thickness Wounds
Authors: Quan Weiyan , Li Puwang , Wei Jinsong , Jiang Yuwei , Liang Yingye , Zhang Weilin , Chen Qizhou , Wu Kefeng , Luo Hui , Ouyang Qianqian
Published: November 2022

Creation of bio-multifunctional wound dressings with potent hemostatic, antibacterial, anti-inflammatory, and angiogenesis features for bolstering the healing of full-thickness wounds is sought after for clinical applications. We created bio-multifunctional composite sponges by coupling alginate and chitosan with Sargassum pallidum polysaccharides through electrostatic interactions, calcium ion (Ca2+) crosslinking, and lyophilization. Alginate/chitosan (AC) sponges with different concentrations of Sargassum pallidum polysaccharides were obtained and termed AC, ACS—1%, ACS—2.5%, and ACS—5%. ACS—1% and ACS—2.5% sponges exhibited uniform porosity, high water vapor transmission rate, high water absorption, as well as good hemostatic and antibacterial abilities. ACS—2.5% sponges facilitated wound closure and promoted angiogenesis and re-epithelialization in the dermis. These data suggest that ACS sponges containing a certain amount of Sargassum pallidum polysaccharides could be employed for treatment of full-thickness skin wounds.
Ultrasensitive Fluorescence Lateral Flow Assay for Simultaneous Detection of Pseudomonas aeruginosa and Salmonella typhimurium via Wheat Germ Agglutinin-Functionalized Magnetic Quantum Dot Nanoprobe
Authors: Tu Zhijie , Yang Xingsheng , Dong Hao , Yu Qing , Zheng Shuai , Cheng Xiaodan , Wang Chongwen , Rong Zhen , Wang Shengqi
Published: November 2022

Point-of-care testing methods for the rapid and sensitive screening of pathogenic bacteria are urgently needed because of the high number of outbreaks of microbial infections and foodborne diseases. In this study, we developed a highly sensitive and multiplex lateral flow assay (LFA) for the simultaneous detection of Pseudomonas aeruginosa and Salmonella typhimurium in complex samples by using wheat germ agglutinin (WGA)-modified magnetic quantum dots (Mag@QDs) as a universal detection nanoprobe. The Mag@QDs-WGA tag with a 200 nm Fe3O4 core and multiple QD-formed shell was introduced into the LFA biosensor for the universal capture of the two target bacteria and provided the dual amplification effect of fluorescence enhancement and magnetic enrichment for ultra-sensitivity detection. Meanwhile, two antibacterial antibodies were separately sprayed onto the two test lines of the LFA strip to ensure the specific identification of P. aeruginosa and S. typhimurium through one test. The proposed LFA exhibited excellent analytical performance, including high capture rate (>80%) to the target pathogens, low detection limit (<30 cells/mL), short testing time (<35 min), and good reproducibility (relative standard deviation < 10.4%). Given these merits, the Mag@QDs-WGA-based LFA has a great potential for the on-site and real-time diagnosis of bacterial samples.
Sensory Processing Disorders in Children and Adolescents: Taking Stock of Assessment and Novel Therapeutic Tools
Authors: Passarello Noemi , Tarantino Vincenza , Chirico Andrea , Menghini Deny , Costanzo Floriana , Sorrentino Pierpaolo , Fucà Elisa , Gigliotta Onofrio , Alivernini Fabio , Oliveri Massimiliano , Lucidi Fabio , Vicari Stefano , Mandolesi Laura , Turriziani Patrizia
Published: November 2022

Sensory processing disorders (SPDs) can be described as difficulty detecting, modulating, interpreting, and/or responding to sensory experiences. Because SPDs occur in many individuals with autism spectrum disorder and in other populations with neurodevelopmental disorders, it is important to distinguish between typical and atypical functioning in sensory processes and to identify early phenotypic markers for developing SPDs. This review considers different methods for diagnosing SPDs to outline a multidisciplinary approach useful for developing valid diagnostic measures. In particular, the advantages and limitations of the most commonly used tools in assessment of SPDs, such as caregiver reports, clinical observation, and psychophysical and neuroimaging studies, will be reviewed. Innovative treatment methods such as neuromodulation techniques and virtual reality will also be suggested.
Electrophysiological Evidence for A Number–Action Mapping in Infancy
Authors: Decarli Gisella , Rämä Pia , Granjon Lionel , Veggiotti Ludovica , de Hevia Maria Dolores
Published: November 2022

In the last decades, a growing body of literature has focused on the link between number and action. Many studies conducted on adult participants have provided evidence for a bidirectional influence between numerosity processing and grasping or reaching actions. However, it is not yet clear whether this link is functional in early infancy. Here, we used the event-related potential (ERP) technique to record electrical activity of the brain in response to number–hand pairings. We implemented a cueing paradigm where 3- to 4-month-old infants observed images showing either congruency (e.g., a large numerosity primed by a large hand opening) or incongruency (e.g., a large numerosity primed by a small hand opening). Infants’ brain activity was modulated by the congruency of the pairings: amplitudes recorded over frontal and parietal-occipital scalp positions differed for congruent versus incongruent pairings. These findings suggest that the association between number and hand action processing is already functional early in life.
Personality Factors as Predictors in Burnout Level Changes for Surgical Area Nurses
Authors: Velando-Soriano Almudena , Cañadas Gustavo R. , Monsalve-Reyes Carolina S. , Romero-Béjar José L. , Esquivel Francisco Javier , De la Fuente-Solana Emilia I. , Cañadas-De la Fuente Guillermo Arturo
Published: November 2022

Surgical area nurses provide comprehensive care to patients throughout the surgical process. Increases in life expectancy lead to the appearance and development of diseases, translating into an increase in the number of necessary interventions. Increases in the workload can be another risk factor for the development of burnout in professionals in this area. Knowledge of psychological and personality-related variables provides relevant information of level changes in the dimensions of burnout syndrome. Three logistic regression models, based on a cross-sectional study with 214 nurses working in the surgical area in the Andalusian Health Service, Spain, were built for each dimension. These models included different variables related to depression and personality, with some being significant at the population level and consequently true risk or protection factors. Friendliness, responsibility and extraversion are protection factors for the personal accomplishment dimension, whilst neuroticism is a risk factor for this dimension. Friendliness is also a protection factor for depersonalization, whilst depression is a risk factor. Finally, neuroticism, responsibility and depression are risk factors for the emotional exhaustion dimension of burnout. These findings provide relevant information that makes anticipation of this syndrome in this group easier.
Does the Internet Bring People Closer Together or Further Apart? The Impact of Internet Usage on Interpersonal Communications
Authors: Li Chao , Ning Guangjie , Xia Yuxin , Guo Kaiyi , Liu Qianqian
Published: November 2022

The complementarity interference (CI) model suggests that the Internet may either inhibit or facilitate interpersonal communications. This paper empirically examines the impact of Internet usage on interpersonal interactions, using a micro dataset from China to answer whether the Internet brings people closer together or further apart. The empirical results demonstrate, first, that Internet usage significantly increases both the time and frequency of people’s communications with their family and friends, rather than causing them to feel more disconnected and isolated. Holding other factors constant, for each one-standard-deviation increase in Internet usage, weekly communications with family members increases by an average of 102.150 min, while there is an average increase of 54.838 min in interactions with friends. These findings as to its positive effects are robust when using other regression models and interpersonal contact measures, as well as the instrumental variable method. Second, Internet usage also contributes to decreased loneliness; it exerts this effect primarily by improving people’s interactions with their family members. However, communications with friends do not significantly mediate such impacts. Third, the positive role of Internet usage on communications is more prominent for people with more frequent online socialization and self-presentation, better online skills, younger age, higher educational level, and who are living in urban areas. In addition, the beneficial effects of Internet usage are larger for communications with family members in the case of migrants. Therefore, in the context of the rapid development of information technology, the network infrastructure should be improved to make better use of the Internet to facilitate interpersonal communications and promote people’s wellness.
Reducing Life Cycle Embodied Energy of Residential Buildings: Importance of Building and Material Service Life
Authors: Rauf Abdul
Published: November 2022

Energy use in the building sector is considered among major contributors of greenhouse gas emissions and related environmental impacts. While striving to reduce the energy consumption from this sector, it is important to avoid burden shifting from one building life cycle stage to another; thus, this requires a good understanding of the energy consumption across the building life cycle. The literature shows greater emphasis on operational energy reduction but less on embodied energy, although both have a clear impact on the building’s footprint and associated environmental impact. In previous studies the importance these energy aspects have been presented; however, the critical role of embodied energy linked to the replacement of materials over a building’s life is not well documented. Therefore, there is a knowledge gap in the available the literature about the ways to reduce the embodied energy requirements of buildings over their useful life. Service life of buildings and their constituent materials may play an important role in this regard. However, their potential role in this respect have not been explored in the previous research. This study critically addresses the above-mentioned gaps in the literature by investigating the combined effect of building and material service life on life cycle embodied energy requirements of residential buildings. Life cycle embodied energy of a case study house for an assessment period of 150 years was calculated based on minimum, average and maximum material service life values for the building service life of 50, 100 and 150 years. A comprehensive input–output hybrid analysis based on the bill of quantities was used for the embodied energy assessment of the initial and recurrent embodied energy calculation for each scenario. The combined effect of building and material service life variations was shown to result in a reduction in the life cycle embodied energy demand in the order of up to 61%. This provides quantifiable and verifiable data that shows the importance of building and material service life considerations in designing, constructing, and managing the buildings in efforts to reduce energy consumption by buildings. A secondary contribution of this paper is a detailed sensitivity analysis which was carried out by varying the material service life values of each building material and the embodied energies for each new scenario was recalculated for two assessment periods. The findings show that, for each material service life variation, the LCEE increases as BSL increases for a 50-year assessment period, but the LCEE decreases for a 150-year assessment period.
Seismic Vulnerability Analysis of Masonry Structures Built with Disassembled Brick Wall Sections
Authors: Su Zhiming , Zheng Wenzhong , Wang Ying , Hou Xiaomeng
Published: November 2022

Disassembling brick wall pieces into brick wall sections and constructing masonry buildings with disassembled brick wall sections (DBWSs) can reduce construction waste production at source and help achieve carbon peak and carbon neutrality. A finite element model (FEM) for typical MSBD is established based on the calibrated finite element analysis method to evaluate the seismic performance of masonry structures built with disassembled brick wall sections (MSBD). Subsequently, the peak ground acceleration is selected as the ground motion intensity index, and the maximum inter-story displacement angle is chosen as the structural damage index. The 20 ground motion records are selected and scaled by peak acceleration in 0.2 g steps to form 120 structure-ground vibration samples for incremental dynamic analysis (IDA) and seismic vulnerability analysis. The IDA results indicated that with the gradual increase in peak ground acceleration, the maximum inter-story displacement angle increases and the model transits from the elastic stage to the elastoplastic stage. Because the characteristics of ground motion records are different, the order of structural plasticity development will be different and the number of ground motion records needs to be considered in the seismic performance assessment. The calculation model will not collapse under the 7 and 8 degree design-based earthquake and the probability of moderate and severe damage of the structure under the rare earthquake is minimal, according to the seismic vulnerability curves. The seismic vulnerability analysis results indicate that MSBD has good seismic performance under earthquakes and meets the requirements of “perfect subjected to frequent earthquake, reparable subjected to design based earthquake, no collapse subjected to rare earthquake.” The seismic vulnerability analysis based on probability statistics can provide a reference for seismic design and evaluation of earthquake damage.
Diagnosis of Depth of Submucosal Invasion in Colorectal Cancer with AI Using Deep Learning
Authors: Minami Soichiro , Saso Kazuhiro , Miyoshi Norikatsu , Fujino Shiki , Kato Shinya , Sekido Yuki , Hata Tsuyoshi , Ogino Takayuki , Takahashi Hidekazu , Uemura Mamoru , Yamamoto Hirofumi , Doki Yuichiro , Eguchi Hidetoshi
Published: November 2022

The submucosal invasion depth predicts prognosis in early colorectal cancer. Although colorectal cancer with shallow submucosal invasion can be treated via endoscopic resection, colorectal cancer with deep submucosal invasion requires surgical colectomy. However, accurately diagnosing the depth of submucosal invasion via endoscopy is difficult. We developed a tool to diagnose the depth of submucosal invasion in early colorectal cancer using artificial intelligence. We reviewed data from 196 patients who had undergone a preoperative colonoscopy at the Osaka University Hospital and Osaka International Cancer Institute between 2011 and 2018 and were diagnosed pathologically as having shallow submucosal invasion or deep submucosal invasion colorectal cancer. A convolutional neural network for predicting invasion depth was constructed using 706 images from 91 patients between 2011 and 2015 as the training dataset. The diagnostic accuracy of the constructed convolutional neural network was evaluated using 394 images from 49 patients between 2016 and 2017 as the validation dataset. We also prospectively tested the tool from 56 patients in 2018 with suspected early-stage colorectal cancer. The sensitivity, specificity, accuracy, and area under the curve of the convolutional neural network for diagnosing deep submucosal invasion colorectal cancer were 87.2% (258/296), 35.7% (35/98), 74.4% (293/394), and 0.758, respectively. The positive predictive value was 84.4% (356/422) and the sensitivity was 75.7% (356/470) in the test set. The diagnostic accuracy of the constructed convolutional neural network seemed to be as high as that of a skilled endoscopist. Thus, endoscopic image recognition by deep learning may be able to predict the submucosal invasion depth in early-stage colorectal cancer in clinical practice.
The Histone Methyltransferase SETD8 Regulates the Expression of Tumor Suppressor Genes via H4K20 Methylation and the p53 Signaling Pathway in Endometrial Cancer Cells
Authors: Kukita Asako , Sone Kenbun , Kaneko Syuzo , Kawakami Eiryo , Oki Shinya , Kojima Machiko , Wada Miku , Toyohara Yusuke , Takahashi Yu , Inoue Futaba , Tanimoto Saki , Taguchi Ayumi , Fukuda Tomohiko , Miyamoto Yuichiro , Tanikawa Michihiro , Mori-Uchino Mayuyo , Tsuruga Tetsushi , Iriyama Takayuki , Matsumoto Yoko , Nagasaka Kazunori , Wada-Hiraike Osamu , Oda Katsutoshi , Hamamoto Ryuji , Osuga Yutaka
Published: November 2022

The histone methyltransferase SET domain-containing protein 8 (SETD8), which methylates histone H4 lysine 20 (H4K20) and non-histone proteins such as p53, plays key roles in human carcinogenesis. Our aim was to determine the involvement of SETD8 in endometrial cancer and its therapeutic potential and identify the downstream genes regulated by SETD8 via H4K20 methylation and the p53 signaling pathway. We examined the expression profile of SETD8 and evaluated whether SETD8 plays a critical role in the proliferation of endometrial cancer cells using small interfering RNAs (siRNAs). We identified the prognostically important genes regulated by SETD8 via H4K20 methylation and p53 signaling using chromatin immunoprecipitation sequencing, RNA sequencing, and machine learning. We confirmed that SETD8 expression was elevated in endometrial cancer tissues. Our in vitro results suggest that the suppression of SETD8 using siRNA or a selective inhibitor attenuated cell proliferation and promoted the apoptosis of endometrial cancer cells. In these cells, SETD8 regulates genes via H4K20 methylation and the p53 signaling pathway. We also identified the prognostically important genes related to apoptosis, such as those encoding KIAA1324 and TP73, in endometrial cancer. SETD8 is an important gene for carcinogenesis and progression of endometrial cancer via H4K20 methylation.
Nuclear Membrane Protein SUN5 Is Highly Expressed and Promotes Proliferation and Migration in Colorectal Cancer by Regulating the ERK Pathway
Authors: Song Xiaoyue , Li Ruhong , Liu Gang , Huang Lihua , Li Peng , Feng Wanjiang , Gao Qiujie , Xing Xiaowei
Published: November 2022

SUN5 was first identified as a nuclear envelope protein involved in spermatocyte division. We found that SUN5 was highly expressed in some cancers, but its function and mechanism in cancer development remain unclear. In the present study, we demonstrated that SUN5 was highly expressed in colorectal cancer (CRC) tissues and cells, as indicated by bioinformatics analysis, and SUN5 promoted cell proliferation and migration in vitro. Moreover, the overexpression of SUN5 upregulated phosphorylated ERK1/2 (pERK1/2), whereas the knockdown of SUN5 yielded the opposite results. PD0325901 decreased the level of pERK1/2 to inhibit cell proliferation and migration, which was partially reversed by SUN5 overexpression, indicating that drug resistance existed in patients with high SUN5 expression. The xenograft transplantation experiment showed that SUN5 accelerated tumor formation in vivo. Furthermore, we found that SUN5 regulated the ERK pathway via Nesprin2 mediation and promoted the nuclear translocation of pERK1/2 by interacting with Nup93. Thus, these findings indicated that highly expressed SUN5 promoted CRC proliferation and migration by regulating the ERK pathway, which may contribute to the clinical diagnosis and new treatment strategies for CRC.
A Clinical Outcome of the Anti-PD-1 Therapy of Melanoma in Polish Patients Is Mediated by Population-Specific Gut Microbiome Composition
Authors: Pietrzak Bernadeta , Tomela Katarzyna , Olejnik-Schmidt Agnieszka , Galus Łukasz , Mackiewicz Jacek , Kaczmarek Mariusz , Mackiewicz Andrzej , Schmidt Marcin
Published: November 2022

The gut microbiota is considered a key player modulating the efficacy of immune checkpoint inhibitor therapy. The study investigated the association between the response to anti-PD-1 therapy and the baseline gut microbiome in a Polish cohort of melanoma patients, alongside selected agents modifying the microbiome. Sixty-four melanoma patients enrolled for the anti-PD-1 therapy, and ten healthy subjects were recruited. The response to the treatment was assessed according to the response evaluation criteria in solid tumors, and patients were classified as responders or non-responders. The association between selected extrinsic factors and response was investigated using questionnaire-based analysis and the metataxonomics of the microbiota. In the responders, the Bacteroidota to Firmicutes ratio was higher, and the richness was decreased. The abundance of Prevotella copri and Bacteroides uniformis was related to the response, whereas the non-responders’ gut microbiota was enriched with Faecalibacterium prausnitzii and Desulfovibrio intestinalis and some unclassified Firmicutes. Dietary patterns, including plant, dairy, and fat consumption as well as gastrointestinal tract functioning were significantly associated with the therapeutic effects of the therapy. The specific gut microbiota along with diet were found to be associated with the response to the therapy in the population of melanoma patients.
The Proliferative Role of Immune Checkpoints in Tumors: Double Regulation
Authors: Tang Xi-Yang , Luo Zhong-Lin , Xiong Yan-Lu , Yang Jie , Shi An-Ping , Zheng Kai-Fu , Liu Yu-Jian , Shu Chen , Ma Nan , Lu Qiang , Zhao Jin-Bo
Published: November 2022

Cancer remains a serious social health problem, and immunotherapy has become the major treatments in tumor treatment. Additionally, improving the efficiency and safety of treatment is necessary. Further, more therapy targets are warranted for future tumor treatments. In this review, in addition to examining the currently recognized role of immune regulation, we focus on the proliferative role of 15 immune checkpoints in various tumors, including PD1, PD-L1, FGL1, CD155, CD47, SIRPα, CD276, IDO1, SIGLEC-15, TIM3, Galectin-9, CD70, CD27, 4-1BBL, and HVEM. We managed to conclude that various immune checkpoints such as PD1/PD-L1, FGL1, CD155, CD47/SIRPα, CD276, and SIGLEC-15 all regulate the cell cycle, and specifically through Cyclin D1 regulation. Furthermore, a variety of signal pathways engage in proliferation regulation, such as P13K, AKT, mTOR, and NK-κB, which are also the most common pathways involved in the regulation of immune checkpoint proliferation. Currently, only PD1/PD-L1, CD47/SIRPα, TIM3/Galectin-9, and CD70/CD27 checkpoints have been shown to interact with each other to regulate tumor proliferation in pairs. However, for other immune checkpoints, the role of their receptors or ligands in tumor proliferation regulation is still unknown, and we consider the enormous potential in this area. An increasing number of studies have validated the various role of immune checkpoints in tumors, and based on this literature review, we found that most of the immune checkpoints play a dual regulatory role in immunity and proliferation. Therefore, the related pathways in proliferation regulation can served the role of therapy targets in tumor therapy. Further, great potential is displayed by IDO1, SIGLEC-15, 4-1BBL, and HVEM in tumor proliferation regulation, which may become novel therapy targets in tumor treatment.
Dysbiosis of the Fecal and Biliary Microbiota in Biliary Tract Cancer
Authors: Ito Zensho , Koido Shigeo , Kato Kumiko , Odamaki Toshitaka , Horiuchi Sankichi , Akasu Takafumi , Saruta Masayuki , Hata Taigo , Kumagai Yu , Fujioka Shuichi , Misawa Takeyuki , Xiao Jin-zhong , Sato Nobuhiro , Ohkusa Toshifumi
Published: November 2022

Characteristic bile duct and gut microbiota have been identified in patients with chronic biliary tract disease. This study aimed to characterize the fecal and bile microbiota in biliary tract cancer (BTC) patients and their relationship. Patients with BTC (n = 30) and benign biliary disease (BBD) without cholangitis (n = 11) were included. Ten healthy, age-matched subjects were also recruited for fecal microbiota comparison. The fecal and bile duct microbiotas were analyzed by sequencing the 16S rRNA gene V3-V4 region. Live bacteria were obtained in the bile from three BTC patients by culture, and metagenomics-based identification was performed. Linear discriminant analysis effect size showed a higher Enterobacteriaceae abundance and a lower Clostridia abundance, including that of Faecalibacterium and Coprococcus, in the BTC patients than in the other subjects. Ten of 17 operational taxonomic units (OTUs) assigned to Enterobacteriaceae in the bile were matched with the OTUs found in the BTC subject fecal samples. Furthermore, a bile-isolated strain possessed the carcinogenic bacterial colipolyketide synthase-encoding gene. Enterobacteriaceae was enriched in the BTC feces, and more than half of Enterobacteriaceae in the bile matched that in the feces at the OTU level. Our data suggests that fecal microbiota dysbiosis may contribute to BTC onset.
Clinical Features, Phenotypic Markers and Outcomes of Diffuse Large B-Cell Lymphoma between HIV-Infected and HIV-Uninfected Chinese Patients
Authors: Zhou Minghan , Cheng Jinlin , Zhao Handan , Yang Min , Yu Wenjuan , Qin Jiaying , Lang Guanjing , Tao Ran , Cao Qing , Huang Ying , Zhu Biao , Xu Lijun
Published: November 2022

Background: The effect of HIV infection on the clinicopathological characteristics of diffuse large B-cell lymphoma (DLBCL) remains debatable. Methods: Fifty-three HIV-infected and ninety-three HIV-uninfected DLBCL patients were enrolled in the retrospective study by propensity score matching for sex, age, body mass index and international prognostic index (IPI) at a ratio of 1:2. The clinicopathological characteristics were compared between the two groups. Results: HIV-infected DLBCL patients had lower white blood cell counts [×109/L; 4.4 (3.4–5.6) vs. 6.1 (4.2–8.2), p < 0.001], platelet counts (×109/L; 184.7 ± 89.3 vs. 230.0 ± 113.9, p = 0.014) and serum albumin (g/L; 37.3 ± 6.9 vs. 41.3 ± 6.2, p < 0.001) but higher incidences of central nervous system (CNS) involvement (9.4% vs. 1.1%, p = 0.014), bone marrow involvement (24.5% vs. 11.5%, p = 0.044) and Epstein–Barr viremia (61.1% vs. 26.7%, p = 0.002) than HIV-uninfected patients. In terms of histopathology, HIV-infected patients had higher positivity of Epstein–Barr virus-encoded small RNA (EBER) (41.7% vs. 6.7%, p = 0.002), but lower CD20 (90.2% vs. 98.7%, p= 0.029) and CD79a (23.1% vs. 53.7%, p < 0.001) expression. The overall response rate (ORR) at the end of chemotherapy (70.2% vs. 87.8%, p= 0.012) and 1-year overall survival (OS) (61.7% vs. 84.2%, log-rank p = 0.006) in HIV-infected patients were significantly lower than those in HIV-uninfected patients. Multivariate analysis suggested IPI ≤2.0 [adjusted odds ratio (AOR) (95% confidence interval): 5.0 (1.2–21.2), p = 0.030] was associated with ORR, hypoalbuminemia [AOR: 3.3 (1.3–9.1), p = 0.018] and CNS involvement [AOR: 3.3 (1.0–10.5), p = 0.044] were associated with reduced 1-year OS in HIV-infected patients. Conclusion: HIV-infected DLBCL patients have unique blood profiles and phenotypic markers. Low ORR and 1-year OS were observed in HIV-infected DLBCL patients in our study, even in the HAART era.
A Comprehensive Overview of Recent Advances in Epigenetics in Pediatric Acute Lymphoblastic Leukemia
Authors: Drożak Paulina , Bryliński Łukasz , Zawitkowska Joanna
Published: November 2022

Recent years have brought a novel insight into our understanding of childhood acute lymphoblastic leukemia (ALL), along with several breakthrough treatment methods. However, multiple aspects of mechanisms behind this disease remain to be elucidated. Evidence suggests that leukemogenesis in ALL is widely influenced by epigenetic modifications. These changes include: DNA hypermethylation, histone modification and miRNA alteration. DNA hypermethylation in promoter regions, which leads to silencing of tumor suppressor genes, is a common epigenetic alteration in ALL. Histone modifications are mainly caused by an increased expression of histone deacetylases. A dysregulation of miRNA results in changes in the expression of their target genes. To date, several hundred genes were identified as suppressed by epigenetic mechanisms in ALL. What is promising is that epigenetic alterations in ALL may be used as potential biomarkers for classification of subtypes, predicting relapse and disease progression and assessing minimal residual disease. Furthermore, since epigenetic lesions are potentially reversible, an activation of epigenetically silenced genes with the use of hypomethylating agents or histone deacetylase inhibitors may be utilized as a therapeutic strategy for ALL. The following review summarizes our current knowledge about epigenetic modifications in ALL and describes potential uses of epigenetics in the clinical management of this disease.
Multi-Target Potential of Berberine as an Antineoplastic and Antimetastatic Agent: A Special Focus on Lung Cancer Treatment
Authors: Achi Ijeoma Theresa , Sarbadhikary Paromita , George Blassan P. , Abrahamse Heidi
Published: November 2022

Despite therapeutic advancements, lung cancer remains the principal cause of cancer mortality in a global scenario. The increased incidence of tumor reoccurrence and progression and the highly metastatic nature of lung cancer are of great concern and hence require the investigation of novel therapies and/or medications. Naturally occurring compounds from plants serve as important resources for novel drugs for cancer therapy. Amongst these phytochemicals, Berberine, an alkaloid, has been extensively explored as a potential natural anticancer therapeutic agent. Several studies have shown the effectiveness of Berberine in inhibiting cancer growth and progression mediated via several different mechanisms, which include cell cycle arrest, inducing cell death by apoptosis and autophagy, inhibiting cell proliferation and invasion, as well as regulating the expression of microRNA, telomerase activity, and the tumor microenvironment, which usually varies for different cancer types. In this review, we aim to provide a better understanding of molecular insights of Berberine and its various derivative-induced antiproliferative and antimetastatic effects against lung cancer. In conclusion, the Berberine imparts its anticancer efficacy against lung cancers via modulation of several signaling pathways involved in cancer cell viability and proliferation, as well as migration, invasion, and metastasis.
Altering Brain Amyloidosis by Intra-Lingual and Extra-Nasal Exposure of Aβ Aggregates
Authors: Gamez Nazaret , Bravo-Alegria Javiera , Huang Yumeng , Perez-Urrutia Nelson , Dongarwar Deepa , Soto Claudio , Morales Rodrigo
Published: November 2022

Extensive experimental and human-derived evidence suggest that misfolded Aβ particles spread similarly to infectious prions. Moreover, peripheral administration of Aβ seeds accelerates brain amyloidosis in both susceptible experimental animals and humans. The mechanisms and elements governing the transport of misfolded Aβ from the periphery to the brain are not fully understood, although circulation and retrograde axonal transport have been proposed. Here, we demonstrate that injection of Aβ seeds in the tongue, a highly innervated organ, substantially accelerates the appearance of plaques in Tg2576 mice. In addition, the extra-nasal exposure of Aβ aggregates increased amyloid pathology in the olfactory bulb. Our results show that exposing highly innervated tissues to Aβ seeds accelerates AD-like pathological features, and suggest that Aβ seeds can be transported from peripheral compartments to the brain by retrograde axonal transport. Research in this direction may be relevant on different fronts, including disease mechanisms, diagnosis, and risk-evaluation of potential iatrogenic transmission of Aβ misfolding.
Osteogenic Potential of Sheep Mesenchymal Stem Cells Preconditioned with BMP-2 and FGF-2 and Seeded on an nHAP-Coated PCL/HAP/β-TCP Scaffold
Authors: Stamnitz Sandra , Krawczenko Agnieszka , Szałaj Urszula , Górecka Żaneta , Antończyk Agnieszka , Kiełbowicz Zdzisław , Święszkowski Wojciech , Łojkowski Witold , Klimczak Aleksandra
Published: November 2022

Mesenchymal stem cells (MSCs) attract interest in regenerative medicine for their potential application in bone regeneration. However, direct transplantation of cells into damaged tissue is not efficient enough to regenerate large bone defects. This problem could be solved with a biocompatible scaffold. Consequently, bone tissue engineering constructs based on biomaterial scaffolds, MSCs, and osteogenic cytokines are promising tools for bone regeneration. The aim of this study was to evaluate the effect of FGF-2 and BMP-2 on the osteogenic potential of ovine bone marrow-derived MSCs seeded onto an nHAP-coated PCL/HAP/β-TCP scaffold in vitro and its in vivo biocompatibility in a sheep model. In vitro analysis revealed that cells preconditioned with FGF-2 and BMP-2 showed a better capacity to adhere and proliferate on the scaffold than untreated cells. BM-MSCs cultured in an osteogenic medium supplemented with FGF-2 and BMP-2 had the highest osteogenic differentiation potential, as assessed based on Alizarin Red S staining and ALP activity. qRT-PCR analysis showed increased expression of osteogenic marker genes in FGF-2- and BMP-2-treated BM-MSCs. Our pilot in vivo research showed that the implantation of an nHAP-coated PCL/HAP/β-TCP scaffold with BM-MSCs preconditioned with FGF-2 and BMP-2 did not have an adverse effect in the sheep mandibular region and induced bone regeneration. The biocompatibility of the implanted scaffold-BM-MSC construct with sheep tissues was confirmed by the expression of early (collagen type I) and late (osteocalcin) osteogenic proteins and a lack of an elevated level of proinflammatory cytokines. These findings suggest that FGF-2 and BMP-2 enhance the osteogenic differentiation potential of MSCs grown on a scaffold, and that such a tissue engineering construct may be used to regenerate large bone defects.
High Fat-High Fructose Diet Elicits Hypogonadotropism Culminating in Autophagy-Mediated Defective Differentiation of Ovarian Follicles
Authors: Rejani Chalikkaran Thilakan , Navin Ajit Kumar , Mumthaz Thekkey Madathil Valappil , Bhuvarahamurthy Venugopal
Published: November 2022

Pituitary gonadotropins directly govern ovarian functions, which are in turn regulated by the ovarian steroid hormones. The precise interplay of gonadotropins and steroid hormones is critical for follicle growth and differentiation. Furthermore, autophagy regulates ovarian follicle differentiation. However, how the high-fat-high fructose (HFD-HF) diet regulates gonadotropins and facilitates autophagy-mediated follicular differentiation in the ovary is obscure. We fed prepubertal rats (PND 25) an HFD-HF diet until PND 90. The results showed diminished adenohypophyseal GnRHR, PR, and aromatase expression, whereas AR, ERα, PRLR, and inhibin were augmented, resulting in gonadotropins decline. Interestingly, autophagy biomarkers, Beclin-1, ATG5, ATG12, LC3-II, and LAMP1 were reduced but SQSTM1/p62 was augmented in the ovaries of HFD-HF-fed rats, causing autolysosome to aggregation. The diet altered T, E2, P4, PRL, and their receptors status in the ovary, disturbed estrous cyclicity, and delayed vaginal opening. Ovarian histomorphology exhibited numerous cystic and atretic follicles, along with disturbed follicular maturation and ovulation. Moreover, the reduction of FSHR; steroidogenic proteins; receptor proteins AR, ERβ, PR; and signaling proteins Wnt2 and β-catenin was also noticed in the ovary, whereas PRLR, inhibin, and pGSK3β were augmented. In conclusion, exposure to a prepubertal HFD-HF diet leads to hypogonadotropism and the autophagy-mediated defective differentiation of ovarian follicles, abating fertility in adult rats.