bluuebunny/crossref_metadata_2025 huggingface dataset:
Constellation Evolution Mother Codebook Design in SCMA
Authors: Liu Fang , Feng Yongxin
Published: July 2022

Sparse code multiple access (SCMA) is an emerging technology developed to meet the requirements of 5G and 6G communications and improve the spectral efficiency of systems. The key behind SCMA technology is the design of its codebook method, particularly the design of the mother codebook method, which forms the basis of excellent user codebook design. Considering the limitations of existing mother codebook methods, a constellation evolution mother codebook design method is proposed here. Odd and even constellations are derived using the proposed method, and a multi-dimensional rotation angle is established. Then, the excellent mother constellations (mother codebook) are reconstructed. The proposed mother codebook design method demonstrates excellent performance in terms of the bit error rate and is found to be superior to existing codebook methods. It can provide a universal mother codebook for user codebooks, thus yielding excellent codebooks for efficient SCMA applications and establishing a technical basis for efficient 5G and 6G applications.
Mixed Image Noise Removal by PCNN Combined with Regularization P-M Equation
Authors: Liu Qing , ZHAO Limin , ZHAO Xiaolong , MA Xiaoshu , LING Weijun , ZHAO Yuxiang , LI Xiangbing , LIANG Daping , YANG Xiaoping
Published: July 2022

In order to effectively remove the mixed noise, a novel algorithm for image reducing noise combined Pulse Coupled Neural Networks (PCNN) and regularization of Perona-Malik equation (P-M equation) is put forward. Firstly, the positions of impulse noise pollution are located by using PCNN, and the first stage adaptive noise filtering is applied according to the result of noise detection. Secondly, the multi-direction information median filtering is applied according to the local neighborhood noisy information. And then the Gaussian noise in the image is denoised by utilizing the regularization P-M diffusion equation. The theoretical analysis and experimental results show that the proposed algorithm needs no detection threshold, which has higher accuracy in the noise detection, is effectively able to remove the mixed noise, and can preserve the image details and the edges as well. The proposed algorithm has better subjective vision effect and objective quality than the wiener filter, median filter and other related algorithms. This algorithm put up better filter performance, high signal-to-noise ratio, denoising ability and strong adaptability.
Characteristics Analysis of Urban Space Expansion in Luoyang, China
Authors: Zhang Kaiguang , Meng Hongling , Ba Mingting , Sun Yanmin
Published: July 2022

The characteristics of urban space expansion reflect the changes of urban space layout and space structure, as well as the urban developing direction and urban orientation in the future. Based on the remote sensing image data of 1990, 2000, 2010, and 2020, this paper analyzes the urban space expansion characteristics of Luoyang, by using the urban land compaction index, expansion intensity index, and centroid distribution in 4 time sections and 3 periods.
A Low-Cost Physiological Monitoring Interface for Intensive Care Unit
Authors: Lin Ke-Feng , Lin Shih-Sung , Chen Ping-Nan
Published: July 2022

Background:
During the COVID-19 pandemic, which emerged in 2020, many patients were treated in isolation wards because of the high infectivity and long incubation period of COVID-19. Therefore, monitoring systems have become critical to patient care and to safeguard medical professional safety.
Objective:
The user interface is very important to the surveillance system; therefore, we use web technology to develop a system that can create an interface based on user needs. When the surveillance scene needs to be changed, the surveillance location can be changed at any time, effectively reducing costs and time required, so that patients can achieve timely and appropriate goals of treatment.
Methods:
ZigBee was employed to develop a monitoring system for intensive care units (ICUs). Unlike conventional GUIs, the proposed GUI enables monitoring of various aspects of a patient, and the monitoring interface can be modified according to user needs. A simulated ICU environment monitoring system is designed to test the effectiveness of the system. The simulated environment and monitoring nodes were set up at positions consistent with the actual clinical environments to measure the time required to switch between monitoring scenes or targets on the GUI.
Results:
A low-cost system that can construct ZigBee-simulated graphical monitoring interfaces on demand was proposed in this study. The system can effectively overcome the limitations of conventional design methods for monitoring interfaces.
Conclusion:
This system can be used to simultaneously monitor the basic physiological data of numerous patients, enabling nursing professionals to instantly determine patient status and provide appropriate treatments. The proposed monitoring system can be applied to remote medical care after official adoption.
The Effect of Plant Biodiversity Changes on the Chemical Composition of Steppe Soils during Climate Aridization
Authors: Kudrevatykh Irina Yurevna , Kalinin Pavel , Mitenko Genady
Published: July 2022

AimsIn time to the climate changes occurring in the recent decades, studies on the assessment of the influence of climatic factors on the changing natural ecosystems are becoming particularly relevant. This study assesses the relationship between vegetation response to climate aridization and the effect of these changes on soil properties, which is crucial for understanding the sustainability of steppe among the trend toward further global warming. Methods The study demonstrates the influence of climatic factors on the changes in plant biodiversity and biomass, the dynamics of the total stock and the rate of return of chemical elements to the upper soil horizons with the plant organic matter. The chemical composition of soils of different types of steppe was studied, and the effect of changes in vegetation cover on the variability of these soil parameters was estimated. Results The study revealed that during aridization in the steppe zone, there is a change in plant association, what lead to the biomass and bio-productivity of steppe decrease, and chemical elements associated with salts accumulate in soils (Ca, Mg, Na, S, Sr). The accumulation of Ca, K, Na, S, Cl by arid species leads to further degradation of the soil cover (salinization, forming of cambic horizon) and a decrease in its sustainability.Conclusions The data obtained will contribute to a better understanding of the role of plants in the sustainability of the soil cover of modern steppes, which is necessary to predict the response of landscapes to future climate changes.
Retinal functional ultrasound imaging (rfUS): a novel tool for assessing neurovascular alterations
Authors: Morisset Clementine , Dizeux Alexandre , Larrat Benoit , Selingue Erwan , Boutin Herve , Picaud Serge , Sahel Jose-Alain , Ialy-Radio Nathalie , Pezet Sophie , Tanter Mickael , Deffieux Thomas
Published: July 2022

Dementia is a heterogeneous neurodegenerative condition that affects more than 50 million people worldwide and encompasses diseases such as Alzheimer’s disease, vascular dementia or Parkinson disease. It is associated with both structural and functional alterations of the brain vasculature, which are now believed to be early precursors of the diseases. Here, we investigate how functional ultrasound (fUS) imaging applied to the retina may allow to assess neurovascular alterations through neurovascular coupling in rat models. We first imaged the retinal microvascular architecture with ultrafast ultrasound localization microscopy and retrieved highly detailed maps of the microvasculature including quantitative blood velocities in main vessels. We then performed functional ultrasound trans-orbital imaging to measure light-induced retinal hemodynamic response function in vivo in the TgF344-AD rat model of Alzheimer disease compared to wild-type age-matched control rats. We showed that retinal fUS allows the robust measurement of the neurovascular response in the rat retinal vasculature and to discriminate different neurovascular responses between healthy and transgenic animals, with an average relative increase of blood volume of 21% in the WT versus 37% for the TG group (p = 0.019). rfUS could thus become a promising functional screening tool in clinics in search of pre-symptomatic biomarkers of dementia.
Cisplatin-induced ototoxicity in 401 consecutive Geneva cancer patients
Authors: VORUZ François , VUILLEUMIER Aurélie , MIGLIORINI Denis , NACHER-SOLER German , ROUSSET Francis , De Maesschalck Thibault , Senn Pascal
Published: July 2022

Objective
Robust epidemiological and audiological data are needed to prepare for future clinical trials aiming at preventing cisplatin-induced ototoxicity in this suffering cancer population. We precisely assessed the incidence, severity and potential risk factors of symptomatic cisplatin-induced ototoxicity in a large cohort of adults.
Methods
Retrospective cohort study at a tertiary care university hospital. Study group included 401 consecutive patients over 18 years old treated with cisplatin-based chemotherapy, without concomitant inner ear radiotherapy nor other ototoxic medication. Every participant underwent baseline pre-treatment audiometry and were asked for otological symptoms (tinnitus, hearing loss). If symptomatic, comparative audiometry was performed. Ototoxicity was defined by a threshold shift ≥ 15 dB HL in at least one of the tested frequencies.
Results
A total of n = 401 cancer patients (59% males) with a mean age of 56 years (range 18–80 years). N = 81 patients (20%) developed symptomatic ototoxicity, affecting predominantly the high frequencies from 4 to 8 kHz. Among the patients with cisplatin-induced hearing loss, n = 49 (60%) experienced simultaneous tinnitus, occurring in over half of them after the first cycle of chemotherapy. None of the analyzed potential risk factors age, gender, smoking, hypertension, diabetes, vasculopathy, dyslipidemia, chemotherapeutic regimen and cumulative cisplatin dose was statistically correlated with the occurrence or severity of cisplatin-induced hearing loss.
Conclusion
One out of five adult cancer patients treated with cisplatin chemotherapy developed a symptomatic and predominant high-frequency hearing loss, with simultaneous occurrence of tinnitus in over half of them. Standardized audiological monitoring before and during cisplatin chemotherapy allows to quantitatively assess early and objective signs of ototoxicity and offers to optimize anticancer therapy while minimizing morbidity in a multidisciplinary setting.
The Effects of Vitamin D on Myocardial Function Demonstrated by Speckle Tracking Echocardiography in Children With Βeta Thalassemia
Authors: Yozgat Ayca Koca , Azak Emine , Kaçar Dilek , Işık Melek , Bilir Özlem Arman , Güzelküçük Zeliha , Çetin İbrahim İlker , Özbek Namık Yaşar , Yaralı Neşe
Published: July 2022

Objective: β-thalassemia major is an inherited hemoglobin disorder resulting in chronic hemolytic anemia. Cardiac involvement is the main cause of death in patients. Speckle-tracking echocardiography is feasible method for the evaluation of cardiac function via an assessment of the longitudinal deformation of the myocardium through the cardiac cycle. The aim of our study is to evaluate the association of vitamin D deficiency and deformation of the left ventricular myocardium measured by speckle-tracking echocardiography in children with thalassemia major.Methods: In this prospective study, 33 thalassemic patients with vitamin D deficiency were enrolled. Cardiac magnetic resonance T2* value, conventional echocardiography and speckle tracking, left ventricle longitudinal and circumferential strain values were measured. Vitamin D level <20 ng/ml deficient, 20-30 ng/ml insufficient, >30 ng/ml considered sufficient. Myocardial functions of patients with vitamin D deficiency or insufficiency were evaluated by speckle-tracking echocardiography before and after vitamin D replacement.Results: The mean age of our patients was 15.4 ± 3.09 years, male / female ratio was 18/15. Vitamin D level was deficient in 30 (90%) and insufficient in 3 (10%) of our patients. Speckle-tracking analysis showed a significantly decreased absolute value of left ventricle global longitudinal strain before vitamin D replacement. A significant improvement in the global longitudinal strain of left ventricular after vitamin D replacement was detected (p<0.05). A statistically significant increase was observed in parameters showing left ventricular systolic and diastolic functions after vitamin D replacement.Conclusion: Vitamin D deficiency are frequently observed and vitamin D deficiency causes decreased contractility and leads to an increase in cardiac iron in thalassemic patients. In our study, we observed that our patients cardiac functions had improved after vitamin D replacement therapy. Further prospective studies are needed to evaluate the relationship between vitamin D levels and cardiac function in patients with these patients.
GOLM1 promotes epithelial-mesenchymal transition by activating TGFβ1/Smad2 signaling in prostate cancer
Authors: Qin Xuke , Liu Lin , Li Yanze , Chen Hui , Weng Xiaodong
Published: July 2022

Background
Prostate cancer (PCa) is the one of the most commonly diagnosed cancer in men in worldwide. Epithelial-mesenchymal transition (EMT) is considered to play a crucial role in the development of the metastatic castration resistant prostate cancer (CRPC), which caused the majority of the death cases in prostate cancer. Golgi membrane protein 1 (GOLM1) is highly expressed in PCa and has been identified as a driver factor for EMT in various cancers. However, its biological functions and underlying mechanisms remain ambiguous in PCa.
Method
GOLM1 expression level of PCa was detected by Western blot and immunohistochemistry (IHC) analyses. To investigate GOLM1 functions in cancer cells, we overexpressed and knocked down GOLM1 in different prostate cancaer cell lines. Transwell assay and wound healing assay were used to determine the role of GOLM1 in cell Epithelial-mesenchymal transition, such as migration and invasion abilities. TGF-β1/Smad2 signaling pathway downstream of GOLM1 was detected by Western blot and Transwell assay.
Result
GOLM1 expression is up-regulated in PCa and correlated with worse prognosis. GOLM1 promotes the abilities of migration and invasion in PCa cell lines (DU145 and LNCaP). Furthermore, TGF-β1/Smad2 signaling is positively regulated by GOLM1 to facilitate EMT in PCa, whereas this role can be restored by TGF-β1 after GOLM1 knockdown or be abrogated by p-Smad inhibitor SB431542.
Conclusion
GOLM1 acts as a critical oncogene by promoting PCa cell EMT process. And GOLM1 is able to play oncogenic functions through activating TGF-β1/Smad2 signaling pathway. Therefore, GOLM1 has the potential to be a biomarker for PCa diagnosis and to predict prognosis of PCa patients. It is of great significance to seek effective and specific inhibitor of GOLM1 for PCa treatment as well.
A multi-level approach to study the metabolic effects of chronic exposure to Aldrin in prostate cancer cells
Authors: Bedia Carmen , Dalmau Nuria , Nielsen Lars K. , Tauler Romà , de Mas Igor Marín
Published: July 2022

Despite numerous studies support a dose-effect relation between Endocrine disruptors (EDs) and tumor progression and malignancy, the effects of chronic exposure to non-lethal concentrations of EDs in cancer remains unknown. Previous studies demonstrated induction of the malignant phenotype in DU145 prostate cancer (PCa) cells after chronic exposure to Aldrin (an ED). However, the mechanisms underlying this process remain limited. Here, two complementary computational approaches to investigate the molecular processes involved in the observed malignancy acquisition in Pca are applied. Firstly, the metabolic reprogramming associated to the chronic exposure to Aldrin in DU145 cells was studied by integrating transcriptomics and metabolomics via constraint-based metabolic modeling. Secondly, Gene Set Enrichment Analysis was applied to determine: i) altered regulatory pathways and ii) correlation of changes in the transcriptomic profile between the DU145 Aldrin-exposed cells and tumor progression in different tumor types.The experimentally validated predictions unveiled a dis-regulation in metabolic and regulatory pathways, modifying the triacylglyceride/cholesterol ratio in Aldrin-exposed cells, which is associated with the malignant phenotype reported in Aldrin-exposed cells.This approach can be applied to study the molecular mechanisms triggered by the chronic exposure to sub-lethal concentration of other pollutants ina variety of diseases with potential clinical and environmental applications.
Structural interventions that affect racial inequities and their impact on population health outcomes: a systematic review
Authors: Clark Emily , Cranston Emily , Polin Tionné , Ndumbe-Eyoh Sume , MacDonald Danielle , Betker Claire , Dobbins Maureen
Published: July 2022

Structural racism is the historical and ongoing reinforcement of racism within society due to discriminatory systems and inequitable distribution of key resources. Racism, embedded within institutional structures, processes and values, perpetuates historical injustices and restricts access to structural factors that directly impact health, such as housing, education and employment. Due to the complex and pervasive nature of structural racism, interventions that act at the structural level, rather than the individual level, are necessary to improve racial health equity. This systematic review was conducted to evaluate the effects of structural-level interventions on determinants of health and health outcomes for racialized populations. A total of 28 articles are included in this review, analyzing interventions such as supplemental income programs, minimum wage policies, nutrition safeguard programs, immigration-related policies, and reproductive and family-based policies. Most studies were quasi-experimental or natural experiments. Findings of studies were largely mixed, although there were clear benefits to policies that improve socioeconomic status and opportunities, and demonstrable harms from policies that restrict access to abortion or immigration. Overall, research on the effects of structural-level interventions to address health inequities is lacking, and the evidence base would benefit from well-designed studies on upstream policy interventions that effect the structural determinants of health and health inequities and improve daily living conditions.
Design and analysis of a high-performance terahertz photoconductive modulator enhanced by photonic crystal cavity
Authors: Alihosseini Faramarz , Heshmatpanah Zahra , Zandi Hesam
Published: July 2022

We propose and design a high-speed and high-performance optically controlled terahertz (THz) intensity modulator based on the free carrier modulation of a GaAs semiconductor. The device comprises a photonic crystal cavity-waveguide coupling structure for operation in the THz region. This modulator benefits from the strong interaction between the THz wave and the photoconductive substance to obtain a deep modulation with GHz speed, even with a low external optical power. The finite element method was used to calculate the most important properties of the modulator, such as the modulation depth, insertion loss, and modulation rate. The proposed modulator also demonstrated external optical power-dependent characteristics. The results indicate that the THz intensity can be modulated at a switching frequency of 1 GHz with high modulation depths of 83% and 90.3% under the continuous wave laser pumping of 50 W/cm2 and 80 W/cm2 respectively. In addition, this modulator exhibits efficient performance under the same pumping power with a switching frequency of up to 3 GHz. The device exhibited higher modulation depths with higher laser power intensities. The outstanding properties of the proposed structure are promising for the development of modulators and switches in THz communication systems.
Quantifying mixing in arbitrary fluid domains: A Pade approximation approach
Authors: Anderson Thomas , Bonnet Marc , Veerapaneni Shravan
Published: July 2022

We consider the model problem of mixing of passive tracers by an incompressible viscous fluid. Addressing questions of optimal control in realistic geometric settings or alternatively the design of fluid-confining geometries that successfully effect mixing requires a meaningful norm in which to quantify mixing that is also suitable for easy and efficient computation (as is needed e.g.\ for use in gradient-based optimization methods). We use the physically-inspired reasonable surrogate of a negative index Sobolev norm over the complex fluid mixing domain $\Omega$, a task which could be seen as computationally expensive since it requires the computation of an eigenbasis for $L^2(\Omega)$ by definition. Instead, we compute a representant of the scalar concentration field in an appropriate Sobolev space in order to obtain an equivalent definition of the Sobolev surrogate norm. The representant, in turn, can be computed to high-order accuracy by a Pad\'e approximation to certain fractional pseudo-differential operators, which naturally leads to a sequence of elliptic problems with an inhomogeneity related to snapshots of the time-varying concentration field. Fast and accurate potential theoretic methods are used to efficiently solve these problems, with rapid per-snapshot mix-norm computation made possible by recent advances in numerical methods for volume potentials. We couple the methodology to existing solvers for Stokes and advection equations to obtain a unified framework for simulating and quantifying mixing in arbitrary fluid domains. We provide numerical results demonstrating the convergence of the new approach as the approximation order is increased.
Multi-agent simulation model updating and forecasting for the evaluation of COVID-19 transmission
Authors: Castro Brenno Moura , Reis Marcelo de Miranda , Salles Ronaldo Moreira
Published: July 2022

Agent-based models have been an emerging approach in epidemiological modelling, specifically in investigating the COVID-19 virus. However, there are challenges to its validation due to the absence of real data on specific socio-economic and cognitive aspects. Therefore, this work aims to present a strategy for updating, verifying and validating these models based on applying the particle swarm optimization algorithm to better model a real case. For such application, this work also presents a new framework based on multi-agents that allows estimating the evolution of the pandemic, predicting hospital resources, and estimating adaptive population immunization and population density in specific areas. Evaluation metrics such as the data's Shape Factor (SF), Mean Square Error (RMSE), and statistical and sensitivity analyses of the responses obtained were applied for comparison with the real data. The Brazilian municipality of Passa Vinte, located in the State of Minas Gerais (MG), was used as a case study. The model was updated in cumulative cases until the 365th day of the pandemic. The results obtained in the statistical and sensitivity analysis showed similar patterns around the actual data up to the 500th day of the pandemic. Their mean values ​​of SF and RMSE were 0.96 and 7.22, respectively, showing good predictability and consistency, serving as an adequate tool for decision-making in health policies.
Overlapping pathogenic de novo CNVs in neurodevelopmental disorders and congenital anomalies impacting constraint genes regulating early development
Authors: Shabestari Seyed Ali Safizadeh , Nassir Nasna , Sopariwala Samana , Karimov Islam , Tambi Richa , Zehra Binte , Kosaji Noor , Akter Hosneara , Berdiev Bakhrom K. , Uddin Mohammed
Published: July 2022

Neurodevelopmental disorders (NDDs) and congenital anomalies (CAs) are a collection of rare disorders with complex etiology. In this study, we investigated the less understood genomic overlap of copy number variants (CNVs) in two large cohorts of NDD and CA patients to identify de novo CNVs and candidate genes associated to both NDD and CA phenotypes. We analyzed clinical microarray CNV data from 10,620 NDD and 3,176 CA cases annotated using Horizon platform of GenomeArc Analytics and then applied rigorous downstream analysis to evaluate overlapping genes from NDD and CA CNVs. Out of 154 patients (NDD and CA cases), we extracted genes from overlapping 217 pathogenic de novo CNVs (47.3% (80/169) of NDD and 64.6% (31/48) CA cases) and performed constraint gene analysis. 79 constraint genes (10.1% non-OMIM entries) were found to have significantly enriched genomic overlap within rare de novo pathogenic deletions (P-value = 0.01, OR = 1.58) and 45 constraint genes (13.3% non-OMIM entries) within rare de novo pathogenic duplications (P-value = 0.01, OR = 1.97). Analysis of spatiotemporal transcriptome demonstrated both pathogenic deletion and duplication genes to be highly expressed during the prenatal stage in human developmental brain (P-value = 4.95 X 10− 6). From the list of overlapping genes, EHMT1, an interesting known NDD gene encompassed de novo pathogenic CNVs from both NDD and CA patients, whereas FAM189A1, and FSTL5 are new candidate genes from non-OMIM entries. In summary, we have identified constraint overlapping genes from CNVs in NDD and CA patients that have the potential to play a vital role in common disease etiology.
Escape and precipitation of planetary ions at Mercury under different solar wind conditions
Authors: Aizawa Sae , André Nicolas , Persson Moa , Modolo Ronan , Raines Jim M. , Leblanc Francois , Chaufray Jean-Yves , Nenon Quentin , Murakami Go
Published: July 2022

The escape and precipitation of planetary ions at Mercury under different solar wind conditions have been examined using a global hybrid simulation. The combination of Mercury’s weak intrinsic magnetic field and solar wind conditions at Mercury’s location results in the formation of a relatively small magnetosphere compared to that of Earth. Its magnetosphere is strongly compressed and may disappear when solar wind conditions are extreme. Under these circumstances, the solar wind can directly interact with the thickest part of the exosphere and surface and the escape of planetary ions is expected to be enhanced. By focusing on the dynamic pressure and interplanetary magnetic field dependence, three different solar wind conditions are used in this study. Under the extreme solar wind conditions, planetary protons shows the highest escape rates while planetary sodium ions show the smallest, indicating that the distribution of the sodium ions around the planet is controlled by the size of the magnetosphere. As the Larmor radius of planetary sodium ions is larger than that of planetary protons, they cannot escape and instead precipitate onto the surface during extreme solar wind conditions, when the dayside magnetosphere is well compressed. The precipitation maps of the solar wind protons, planetary protons, and planetary sodium ions) show that the flux from planetary plasmas is sometimes higher than the flux of solar wind plasmas, suggesting that the precipitation of planetary plasmas are probably a non-negligible source of the space weathering of Mercury’s surface, in particular during extreme solar wind conditions.
Effect of Entamoeba histolytica infection on gut microbial diversity and composition in diarrhoeal patients from New Delhi
Authors: Iyer Lakshmi Rani , Chandel Nisha , Verma Anil Kumar , Thakur Vivek , Paul Jaishree , Mandal Ashish Kumar , Bhattacharya Alok
Published: July 2022

During amoebiasis, colonization of the gut by Entamoeba histolytica can lead to alterations of the host microbiota. In this study we have compared the gut microbiota of patients of amoebiasis with healthy controls using 16S rRNA gene variable regions, (V1-V3) and (V3-V5) of the bacterial genome. From this 16S rRNA gene amplicon data one paired end and two single end data sets were selected and compared by the number of OTUs obtained, sequence count and diversity analysis. Our results showed that the V1-V3- paired end data set gave the maximum number of OTUs in comparison to the two single end data sets studied. The amoebiasis patient samples showed a significant drop in richness in the alpha diversity measurements and lower intra group similarity compared to the healthy controls. Bacteria of genus Prevotella, Sutterella and Collinsella were more abundant in healthy controls whereas Escherichia, Klebsiella and Ruminococcus were more abundant in the E. histolytica positive patients. All the healthy controls harboured bacteria belonging to Faecalibacterium, Prevotella, Ruminococcus, Subdoligranulum and Escherichia genera while all the E. histolytica positive patients samples contained genus Enterobacter.
Altered basal forebrain function during whole-brain network activity at pre- and early-plaque stages of Alzheimer’s disease in TgF344-AD rats
Authors: Berg Monica van den , Adhikari Mohit , Verschuuren Marlies , Pintelon Isabel , Vasilkovska Tamara , Audekerke Johan Van , Missault Stephan , Heymans Loran , Ponsaerts Peter , De Vos Winnok H. , Linden Annemie Van der , Keliris Georgios A. , Verhoye Marleen
Published: July 2022

Background: Imbalanced synaptic transmission appears to be an early driver in Alzheimer’s Disease (AD) leading to brain network alterations. Early detection of altered synaptic transmission and insight into mechanisms causing early synaptic alterations would be valuable treatment strategies. This study aimed to investigate how whole-brain networks are influenced at pre- and early-plague stages of AD and if these manifestations are associated with concomitant cellular and synaptic deficits. Methods: To this end, we used an established AD rat model (TgF344-AD) and employed resting state functional MRI and quasi-periodic pattern (QPP) analysis, a method to detect recurrent spatiotemporal motifs of brain activity, in parallel with state-of-the-art immunohistochemistry in selected brain regions. Results: At the pre‑plaque stage, QPPs in TgF344-AD rats showed decreased activity of the basal forebrain (BFB) and the default-mode like network. Histological analyses revealed increased astrocyte abundance restricted to the BFB, in the absence of amyloid plaques, tauopathy and alterations in number of cholinergic, gaba-ergic and glutamatergic synapses. During the early-plaque stage, when mild amyloid-beta (Aβ) accumulation was observed in the cortex and hippocampus, QPPs in the TgF344-AD rats normalized suggesting the activation of compensatory mechanisms during this early disease progression period. Interestingly, astrogliosis observed in the BFB at the early-plaque stage was absent at the early-plaque stage. In wild-type rats, at both time-points, peak activity in the BFB preceded peak activity in other brain regions – indicating its modulatory role during QPPs. However, this pattern was eliminated in TgF344-AD suggesting that alterations in BFB-directed neuromodulation have a pronounced impact in network function in AD. Conclusions: This study demonstrates the value of rsfMRI and advanced network analysis methods to detect early alterations in BFB function in AD, which could aid early diagnosis and intervention in AD. Restoring the global synaptic transmission by modulating astrogliosis in the BFB might be a promising therapeutic strategy to restore brain network function and delay the onset of symptoms in AD.
Development and Validation of the Nomograms for Prognostic analysis in Patients With extremity Synovial Sarcoma
Authors: Li Bo , He Zhiwen , Lin Mingchao , Yu Fan , Zhou Song
Published: July 2022

Background
Extremity Synovial Sarcoma (SS) is a rare and highly malignant disease with a poor prognosis. This study aimed to determine the main factors affecting the prognosis and survival of patients with extremity SS and predict the overall survival (OS) and cancer-specific survival (CSS) by establishing a predictive model.
Methods
The Surveillance, Epidemiology, and End Results (SEER) database was used to screen patients who were diagnosed with extremity SS from 2004 to 2015. Univariate and multivariate Cox regression analyses were used to identify the clinical risk factors, and a prognostic nomogram was established to predict the 5- and 10-years OS and CSS.
Results
A total of 811 patients with extremity SS were divided into training cohort (n = 406) and validation cohort (n = 405) cohorts. Based on the results of data analysis, we found that age, sex, primary site, chemotherapy, surgery, Radiation and SEER stage were independent risk factors for OS and CSS in patients with extremity SS and used them to construct the prognostic nomogram. In the training cohort, the C-indexes of the nomogram were 0.752 (95% CI: 0.717–0.787) and 0.772 (95% CI: 0.735–0.809) for predicting OS and CSS, respectively. In the validation cohort, the corresponding C-indexes were 0.754(95% CI: 0.719–0.789) and 0.779 (95% CI: 0.742–0.816), respectively. The results of the calibration curves of OS and CSS in the training and validation cohorts proved that the 5-year and 10-year survival time were consistent with the survival time predicted by the nomogram.
Conclusions
age, sex, primary site, chemotherapy, surgery, Radiation and SEER stage were independent prognostic risk factors in patients with extremity SS. Compared with the SEER stage model, our nomogram model that we established had more advantages.
Plant growth-promoting properties of the phosphate-solubilizing red yeast Rhodosporidium paludigenum, with fine-tuning capabilities
Authors: Chen Yi-Ru , Kuo Chih-Yen , Fu Shih-Fen , Chou Jui-Yu
Published: July 2022

Phosphorus (P) is one of the essential elements that are necessary for plant development and growth. However, the availability of soluble forms of P for plants in the soils is limited, because a large proportion of it is bound to soil constituents. Thus, the concentration of P available to plants at any time is very low and, moreover, its availability depends on the soil pH. As a solution, phosphate-solubilizing microorganisms (PSMs) are employed that render inorganic P available to plants in soluble form. Thus far, research into PSMs has been insufficient, and only few such organisms have been considered for exploitation as microbial fertilizer strains. The characteristics of plant growth promotion with the plant-PSMs coculture system remain to be elucidated. In the current study, we report on the isolate Rhodosporidium paludigenum JYC100 that exhibits good performance for solubilizing calcium phosphate. We found that it can be regulated by the amount of soluble phosphate. Furthermore, R. paludigenum JYC100 promotes plant growth under specific conditions (P deficiency, but with insoluble phosphate) in different media and soil pots. In contrast, the yeast Aureobasidium pullulans JYC JYC104 exhibited weak phosphate-solubilizing capacities and no plant growth-promoting ability. Compared to control plants, the biomass, shoot height, and cellular inorganic P content of plants increased in plants cocultivated with R. paludigenum JYC100. In addition, histochemical GUS and qRT-PCR assays of phosphate starvation-induced (PSI) genes showed that the expression of these PSI genes is decreased in the plants cocultured with R. paludigenum JYC100. These findings reflect the unique ability of R. paludigenum JYC100 to convert insoluble P compounds to plant-available P, thereby leading to growth promotion. Our study results highlight the use of yeasts as potential substitutes for inorganic phosphate fertilizers to meet the P demands of plants, which may eventually improve yields in sustainable agricultures.
Exosomal circZFR promotes colorectal cancer progression via stabilizing BCLAF1 and regulating the miR-3127-5p/RTKN2 axis
Authors: Chen Jiaxin , Xu Jianbin , Wang Huijuan , Chen Engeng , Meng Qing , Wang Jiawei , Zhou Wei , Shan Ge , Ju Zhenyu , Song Zhangfa
Published: July 2022

Background
Circular RNAs (circRNAs) have gained attention as novel biomarkers for cancer diagnosis and prognosis. Aberrant expression of circRNAs is widely involved in cancer development, whereas the function and mechanism of novel circRNAs in colorectal cancer (CRC) remain unclear.
Methods
CircZFR was identified both in CRC tissues from the GEO database and in serum exosomes by competing endogenous RNA (ceRNA) microarray. The expression of circZFR was evaluated in CRC tissues and serum by qRT-PCR and in tissue microarray (TMA) by FISH. The functional roles were confirmed using a series of in vitro assays and tumor xenografts and pulmonary/hepatic metastasis mouse models. The mechanisms of circZFR were assessed through circRNA pulldown, RNA immunoprecipitation (RIP), dual-luciferase reporter assays and rescue experiments. Lastly, TCP1-CD-QDs nanocarrier was used to carry circZFR siRNA (si-circZFR) to exam the therapeutic potential of circZFR in patient-derived xenograft (PDX) models.
Results
CircZFR was upregulated in cancer tissues and serum exosomes of CRC patients and its level was positively associated to advanced TNM stages and poor prognosis. Serum circZFR was indicative of CRC incidence, advanced-stages and metastasis. Functional experiments demonstrated that circZFR promoted CRC proliferation and metastasis but inhibited apoptosis in vitro and in vivo, exosomes with upregulation of circZFR facilitated growth and migration of cocultured CRC cells. Mechanistically, the generation of circZFR could be improved by epithelial splicing regulatory protein 1 (ESRP1) in CRC cells. CircZFR bound to BCL2-associated transcription factor 1 (BCLAF1) and inhibited its ubiquitinated degradation. Moreover, circZFR sponged miR-3127-5p to increase the expression of rhotekin 2 (RTKN2). Our TCP1-CD-QDs nanocarrier was able to carry si-circZFR and delivered them to the vasculature of CRC tissues and cells, resulting in suppressive tumor growth without obvious adverse effects in PDX models.
Conclusions
Our findings indicate that ESRP1-mediated circZFR exerts oncogenic effects on CRC development and spread through suppressing BCLAF1 degradation and regulating the miR-3127-5P/RTKN2 axis. CircZFR is a promising serum biopsy marker for CRC diagnosis and an attractive target for further therapy.
Abulia major and hypoactive delirium in COVID-19 reversed with methylprednisolone pulse therapy
Authors: Zanella Luiz Gonzaga Francisco de Assis Barros D’Elia , Zanella Luiz Gonzaga Francisco de Assis Barros D’Elia
Published: July 2022

Background: Sars-CoV-2 is a member of the genus Betacoronavirus like the two other coronaviruses viz. SARS-CoV (severe acute respiratory syndrome coronavirus) and MERS-CoV (Middle East respiratory syndrome coronavirus). SARS-CoV-2 infection has been associated with neuropsychiatric manifestations in acute and chronic COVID-19 (long COVID-19 syndrome), bringing social consequences and worsening people's quality of life. Case description: This article exemplifies two cases of neurological manifestations resulting from infection by SARS-CoV-2 that were reversed with methylprednisolone in a pulse therapy regimen. The first case presents a young patient with symptoms similar to those existing in patients with Alzheimer's disease, whose final and presumable diagnosis was Abulia major. The second case exemplifies an elderly person admitted to the hospital due to hypoactive delirium triggered by a urinary tract infection hypothesis. The final diagnosis was hypoactive delirium secondary to COVID-19, with urinary manifestations from SARS-CoV-2 kidney injury. Discussion/Conclusion: The purpose of this article is to warn about phenomena related to COVID-19, whose treatment can be performed with high doses of corticosteroids and with drugs that act positively on dopaminergic and serotonergic pathways. Patient exams and more information are available in the Appendix of this article.
Comparative Analysis of Complete Genome Sequences and Phenotypic Correlation of Klebsiella spp.
Authors: Sundaresan Abhirami Krishnamoorthy , Mohan Ganesh Babu Malli , Murugavel Aravind , Ramakrishnan Jayapradha
Published: July 2022

In recent times K. pneumoniae, a common nosocomial pathogen, tends to evolve more virulent and multidrug-resistant. Urinary tract infections by antibiotic resistant and virulent K. pneumoniae are a growing concern due to the challenging treatment strategies. Hence understanding the genome and validating the genomic profile along with pan-genome analysis will facilitate surveillance of high risk-clones of K. pneumoniae to underpin management strategies toward early detection. Thus, the present study aimed to correlate genotypic and phenotypic antimicrobial resistance and pathogenicity associated with sequence types and virulence factors in Klebsiella spp. The complete genome profile of 3 K. pneumoniae and a K. variicola were analysed in the study which was assigned to ST200, ST45, ST147 and ST of K. variicola are not known. The accessory genome comprised 66% of genes consisting of shell and cloud genes in K. pneumoniae. The phenotypic antimicrobial resistance identified kp3 to have maximum resistance and the susceptibility of environment isolate K. variicola was less resistant to the tested antibiotics. The in vitro and genomic antimicrobial resistance profiling showed concordance with all the tested antibiotics against the 4 study strains. Hypermucoviscosity was not observed for any of the test isolates; this phenotypic character matches perfectly with the absence of rmpA, rmpA2 and magA. Though the genes encoding for major virulence factors; hypermucoviscosity, yersiniabactin and allantoin metabolism were absent, significant pathogenicity and mortality were observed for kp3 isolate in the Zebrafish infection model. In contrast, the isolates predicted with the aerobactin gene were observed with least mortality rate. In the present study virulome and in vivo study illustrate the discrepancies in the virulence. To the best of our knowledge, this is the first report on the presence of ste, stf, stc and sti major fimbrial operons of Salmonella enteric serotype Typhimurium in K. pneumoniae genome, that might contribute to the virulence of kp3. Our study highlights the further necessity of genomic and phenotypic virulence markers for timely diagnosis and immediate treatment for the management of high risk K. pneumoniae clones.
The Role of Vascular-Platelet Hemostasis Disturbances in the Genesis of Respiratory Failure in Patients with COVID-19
Authors: Neymark M. I. , Epp D. P. , Nikolaeva M. G. , Momot A. P. , Proskurin S. N. , Karkavina A. N. , Kontseba V. V. , Mekshun C. V.
Published: July 2022

The objective: to study the relationship between markers of imbalance in the platelet-vascular hemostasis system and lung damage and disease outcome in patients with COVID-19.

Subjects and Methods: the study included 225 patients with the confirmed diagnosis of moderate, severe and extremely severe COVID-19. In all patients, lung damage was confirmed using computed and X-ray diagnostic methods. We studied the concentration of von Willebrand factor (vWF), activity of metalloproteinase ADAMTS-13, concentration of homocysteine, endothelin-1, thrombomodulin and the number of platelets and changes in these parameters on the 1st, 3–5th and 7–10th days from the admission to the intensive care unit (ICU). In deceased patients (n = 106), lung specimens were collected to assess the nature of morphological changes.

Results. It was determined that by the 7–10th days with a lethal outcome of the disease, there was a statistically significant increase in the concentration of vWF by 22.2% (p = 0.0225), the vWF/ADAMTS-13 ratio by 2 times (p = 0.0408) and decrease in the platelet count by 52% (p = 0.0008) versus the initial stage of the study. In all the deceased, the morphological picture of lung tissue damage was characterized by destruction of alveolocytes, proliferation of connective tissue, cellular infiltration, plethora of capillaries, parietal erythrocyte thrombi in the lumen of capillaries, arterioles and venules, and obstructive erythrocyte thrombi in the lumen of vessels of lung microcirculation.

Conclusion. The study showed that a possible cause of thrombosis in the lumen of vessels of lung microcirculation in the case of a lethal outcome of COVID-19 might be a primary imbalance in the vascular-platelet hemostasis characterized by a significant increase in the concentration of the vWF factor, the vWF/ADAMTS-13 ratio and a decrease in the number (consumption) of platelets by the 7–10th day of the disease versus the initial stage of the study.
Hemodynamic Reactions during Removal of Brain Tumors with the Combined Use of Fentanyl and Alpha2-Adrenoagonist
Authors: Rumyantseva M. V. , Tsentsiper L. M. , Kondratiev A. N.
Published: July 2022

Anesthesia including drugs that act on the opioid (fentanyl) and adrenergic (clonidine or dexmedetomidine) neuroregulatory systems, creates optimal conditions for performing brain surgery.

The objective: to study the effect of combination of opioid analgesic fentanyl and alpha2-adrenoagonists on stability (reactivity) and appropriate functional activity of the circulatory system.

Subjects and Methods. The study included 118 patients operated on for a brain tumor. Patients were divided into groups depending on the alpha2-adrenoagonist used, its dosage and position on the operating table.

Results. In all groups, the required level of neurovegetative stabilization with stable hemodynamics was achieved at all stages of the operation. Conclusion. Studies have shown that a lower dose of dexmedetomidine versus clonidine was required to achieve a central sympatho-modulatory effect.
Specific Parameters of Intraoperative Changes in the Hemostasis System during Liver Resection in Children
Authors: Novikov D. I. , Zaitsev A. Yu. , Dubrovin K. V. , Bespalov E. K. , Filin A. V.
Published: July 2022

The objective: to determine severity of changes in the hemostasis system in children occurring at main stages of liver resection as well as the need for their intraoperative correction.

Subjects and Methods. A single-center prospective pilot study of coagulogram and rotational thromboelastometry values was conducted in 25 children aged 0–11 years old with hepatoblastoma after a course of chemotherapy according to the PRETEX IV regimen who underwent hemihepatectomy.

Results. There were no statistically significant differences in parameters of the ROTEM tests both when comparing groups and when comparing hemihepatectomy stages within the same age group of patients. At the beginning of the separation of the liver parenchyma INTEM: CT 200.00 (186.00; 238.00), CFT 88.00 (83.00; 139.00), MCF 54.00 (51.00; 61.00), ML 0.00 (0.00; 5.00) in Group I, CT 191.00 (179.00; 199.00), CFT 84.00 (79.00; 103.00), MCF 60.00 (58.00; 64.00), 4,00 (3.00; 9.00) in Group II, respectively, p > 0.05. After separation of the liver parenchyma INTEM: CT 201.00 (161.00; 237.50), CFT 93.00 (95.00; 112.00), MCF 54.00 (52.50; 59.50), ML 6.00 (2.00; 10.00) in Group I, CT 229.00 (201.00; 285.00), CFT 93.00 (78.00; 177.00), MCF 59.00 (49.00; 60.00), ML 5.00 (5.00; 10.00) in Group II, respectively, p > 0.05.

Conclusion. After chemotherapy courses, children aged 0–11 years suffering from hepatoblastoma, maintain normal functional activity of the hemostasis system at all stages of surgical treatment. In children under 11 years of age, routine hemostasis correction with blood products and prothrombin complex factor concentrate is not required during the main stages of hemihepatectomy.