bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Ovalbumin/β-Cyclodextrin in Improving Structural and Gelling Properties of Culter alburnus Myofibrillar Proteins during Frozen Storage
Authors: Lv Meiwen , Wang Xiukang , Walayat Noman , Zhang Zhongli , Saleem Muhammad Hamzah , Nawaz Asad , Aadil Rana Muhammad , Ahmed Shakeel , Simirgiotis Mario J. , Lorenzo José M. , Jan Basit Latief
Published: December 2021

This study aimed to analyze the cryoprotective effect of a ovalbumin (OVA) and β-cyclodextrin (βCD) mixture (3:1, OVA/βCD) on the structure, rheology and gelling properties of myofibrillar proteins (MPs) during 90 days of frozen storage. A mixture of OVA/βCD at different concentrations (0, 2, 4, and 6%) was added to MPs and stored at −18 °C for 90 days. The addition of OVA/βCD significantly decreased the sulfhydryl contents while it increased the surface hydrophobicity, which was closely connected with tertiary structural changes. Circular dichroism analysis showed that the addition of OVA/βCD enhanced the stability of the secondary structure by inhibiting the decline in the α-helix. Rheological properties analysis indicated that 6% OVA/βCD treatment showed better storage modulus (G’) and loss modulus (G”). In addition, treatment of OVA/βCD showed better gel forming properties than the control group (0%), helping to form a homogeneous and denser gel network. The results proved that 6% OVA/βCD could be act as a promising cryoprotectant, which can improve the structure and gel behavior of Culter alburnus MPs during frozen storage. Moreover, OVA/βCD could be a potential alternative to conventional cryoprotectants at the industrial level to increase the economic and commercial values of seafood products.
Phosphorus and Nitrogen Limitation as a Part of the Strategy to Stimulate Microbial Lipid Biosynthesis
Authors: Wierzchowska Katarzyna , Zieniuk Bartłomiej , Nowak Dorota , Fabiszewska Agata
Published: December 2021

Microbial lipids called a sustainable alternative to traditional vegetable oils invariably capture the attention of researchers. In this study, the effect of limiting inorganic phosphorus (KH2PO4) and nitrogen ((NH4)2SO4) sources in lipid-rich culture medium on the efficiency of cellular lipid biosynthesis by Y. lipolytica yeast has been investigated. In batch cultures, the carbon source was rapeseed waste post-frying oil (50 g/dm3). A significant relationship between the concentration of KH2PO4 and the amount of lipids accumulated has been revealed. In the shake-flask cultures, storage lipid yield was correlated with lower doses of phosphorus source in the medium. In bioreactor culture in mineral medium with (g/dm3) 3.0 KH2PO4 and 3.0 (NH4)2SO4, the cellular lipid yield was 47.5% (w/w). Simultaneous limitation of both phosphorus and nitrogen sources promoted lipid accumulation in cells, but at the same time created unfavorable conditions for biomass growth (0.78 gd.m./dm3). Increased phosphorus availability with limited cellular access to nitrogen resulted in higher biomass yields (7.45 gd.m./dm3) than phosphorus limitation in a nitrogen-rich medium (4.56 gd.m./dm3), with comparable lipid yields (30% and 32%). Regardless of the medium composition, the yeast preferentially accumulated oleic and linoleic acids as well as linolenic acid up to 8.89%. Further, it is crucial to determine the correlation between N/P molar ratios, biomass growth and efficient lipid accumulation. In particular, considering the contribution of phosphorus as a component of coenzymes in many metabolic pathways, including lipid biosynthesis and respiration processes, its importance as a factor in the cultivation of the oleaginous microorganisms was highlighted.
Field Data Forecasting Using LSTM and Bi-LSTM Approaches
Authors: Suebsombut Paweena , Sekhari Aicha , Sureephong Pradorn , Belhi Abdelhak , Bouras Abdelaziz
Published: December 2021

Water, an essential resource for crop production, is becoming increasingly scarce, while cropland continues to expand due to the world’s population growth. Proper irrigation scheduling has been shown to help farmers improve crop yield and quality, resulting in more sustainable water consumption. Soil Moisture (SM), which indicates the amount of water in the soil, is one of the most important crop irrigation parameters. In terms of water usage optimization and crop yield, estimating future soil moisture (forecasting) is an essentially valuable task for crop irrigation. As a result, farmers can base crop irrigation decisions on this parameter. Sensors can be used to estimate this value in real time, which may assist farmers in deciding whether or not to irrigate. The soil moisture value provided by the sensors, on the other hand, is instantaneous and cannot be used to directly compute irrigation parameters such as the best timing or the required water quantity to irrigate. The soil moisture value can, in fact, vary greatly depending on factors such as humidity, weather, and time. Using machine learning methods, these parameters can be used to predict soil moisture levels in the near future. This paper proposes a new Long-Short Term Memory (LSTM)-based model to forecast soil moisture values in the future based on parameters collected from various sensors as a potential solution. To train and validate this model, a real-world dataset containing a set of parameters related to weather forecasting, soil moisture, and other related parameters was collected using smart sensors installed in a greenhouse in Chiang Mai province, Thailand. Preliminary results show that our LSTM-based model performs well in predicting soil moisture with a 0.72% RMSE error and a 0.52% cross-validation error (LSTM), and our Bi-LSTM model with a 0.76% RMSE error and a 0.57% cross-validation error. In the future, we aim to test and validate this model on other similar datasets.
Nonenzymatic Deamidation Mechanism on a Glutamine Residue with a C-Terminal Adjacent Glycine Residue: A Computational Mechanistic Study
Authors: Asai Haruka , Kato Koichi , Nakayoshi Tomoki , Ishikawa Yoshinobu , Kurimoto Eiji , Oda Akifumi , Fukuishi Nobuyuki
Published: December 2021

The deamidation of glutamine (Gln) residues, which occurs non-enzymatically under physiological conditions, triggers protein denaturation and aggregation. Gln residues are deamidated via the cyclic glutarimide intermediates to l-α-, d-α-, l-β-, and d-β-glutamate residues. The production of these biologically uncommon amino acid residues is implicated in the pathogenesis of autoimmune diseases. The reaction rate of Gln deamidation is influenced by the C-terminal adjacent (N +1) residue and is highest in the Gln-glycine (Gly) sequence. Here, we investigated the effect of the (N + 1) Gly on the mechanism of Gln deamidation and the activation barrier using quantum chemical calculations. Energy-minima and transition-state geometries were optimized by the B3LYP density functional theory, and MP2 calculations were used to obtain the single-point energy. The calculated activation barrier (85.4 kJ mol−1) was sufficiently low for the reactions occurring under physiological conditions. Furthermore, the hydrogen bond formation between the catalytic ion and the main chain of Gly on the C-terminal side was suggested to accelerate Gln deamidation by stabilizing the transition state.
Time Series Analysis of Evaporation Duct Height over South China Sea: A Stochastic Modeling Approach
Authors: Hong Fei , Zhang Qi
Published: December 2021

The evaporation duct could significantly affect the work status of maritime microwave communication systems in the South China Sea. Therefore, the exact forecasting of the evaporation duct is vital for the normal operation of the systems. This study presents a stochastic modeling approach to predict the future trends of the evaporation duct over the South China Sea. The autoregressive integrated moving average (ARIMA) model has been used for modeling the monthly evaporation duct height estimated from the Climate Forecast System Reanalysis dataset released by the National Centers for Environment Prediction. The long-term evaporation duct height data were collected for a period of 10 years from 2008 to 2017. The analysis of correlation function reveals the existence of seasonality in the time series. Therefore, a seasonal ARIMA model with the form as ARIMA (0,0,1) × (0,1,2)12 is proposed by fitting the monthly data optimally. The fitted model is further used to forecast the evaporation duct variation for the year 2018 at 95% level of confidence, and high-accuracy results are obtained. Our study demonstrates the feasibility of the proposed stochastic modeling technique to predict the future variations of the evaporation duct over South China Sea.
Seasonal Disparity in the Effect of Meteorological Conditions on Air Quality in China Based on Artificial Intelligence
Authors: Zhang Yongli
Published: December 2021

Air contamination is identified with individuals’ wellbeing and furthermore affects the sustainable development of economy and society. This paper gathered the time series data of seven meteorological conditions variables of Beijing city from 1 November 2013 to 31 October 2017 and utilized the generalized regression neural network optimized by the particle swarm optimization algorithm (PSO-GRNN) to explore seasonal disparity in the impacts of mean atmospheric humidity, maximum wind velocity, insolation duration, mean wind velocity and rain precipitation on air quality index (AQI). The results showed that in general, the most significant impacting factor on air quality in Beijing is insolation duration, mean atmospheric humidity, and maximum wind velocity. In spring and autumn, the meteorological diffusion conditions represented by insolation duration and mean atmospheric humidity had a significant effect on air quality. In summer, temperature and wind are the most significant variables influencing air quality in Beijing; the most important reason for air contamination in Beijing in winter is the increase in air humidity and the deterioration of air diffusion condition. This study investigates the seasonal effects of meteorological conditions on air contamination and suggests a new research method for air quality research. In future studies, the impacts of different variables other than meteorological conditions on air quality should be assessed.
Decomposition, Mapping, and Sum Theorems of ω-Paracompact Topological Spaces
Authors: Al Ghour Samer
Published: December 2021

As a weaker form of ω-paracompactness, the notion of σ-ω-paracompactness is introduced. Furthermore, as a weaker form of σ-ω-paracompactness, the notion of feebly ω-paracompactness is introduced. It is proven hereinthat locally countable topological spaces are feebly ω-paracompact. Furthermore, it is proven hereinthat countably ω-paracompact σ-ω-paracompact topological spaces are ω-paracompact. Furthermore, it is proven hereinthat σ-ω-paracompactness is inverse invariant under perfect mappings with countable fibers, and as a result, is proven hereinthat ω-paracompactness is inverse invariant under perfect mappings with countable fibers. Furthermore, if A is a locally finite closed covering of a topological space X,τ with each A∈A being ω-paracompact and normal, then X,τ is ω-paracompact and normal, and as a corollary, a sum theorem for ω-paracompact normal topological spaces follows. Moreover, three open questions are raised.
Complex Numbers Related to Semi-Antinorms, Ellipses or Matrix Homogeneous Functionals
Authors: Richter Wolf-Dieter
Published: December 2021

We generalize the property of complex numbers to be closely related to Euclidean circles by constructing new classes of complex numbers which in an analogous sense are closely related to semi-antinorm circles, ellipses, or functionals which are homogeneous with respect to certain diagonal matrix multiplication. We also extend Euler’s formula and discuss solutions of quadratic equations for the p-norm-antinorm realization of the abstract complex algebraic structure. In addition, we prove an advanced invariance property of certain probability densities.
Generalized Quantum Integro-Differential Fractional Operator with Application of 2D-Shallow Water Equation in a Complex Domain
Authors: Ibrahim Rabha W. , Baleanu Dumitru
Published: December 2021

In this paper, we aim to generalize a fractional integro-differential operator in the open unit disk utilizing Jackson calculus (quantum calculus or q-calculus). Next, by consuming the generalized operator to define a formula of normalized analytic functions, we present a set of integral inequalities using the concepts of subordination and superordination. In addition, as an application, we determine the maximum and minimum solutions of the extended fractional 2D-shallow water equation in a complex domain.
Tryptophan Production Maximization in a Fed-Batch Bioreactor with Modified E. coli Cells, by Optimizing Its Operating Policy Based on an Extended Structured Cell Kinetic Model
Authors: Maria Gheorghe , Renea Laura
Published: December 2021

Hybrid kinetic models, linking structured cell metabolic processes to the dynamics of macroscopic variables of the bioreactor, are more and more used in engineering evaluations to derive more precise predictions of the process dynamics under variable operating conditions. Depending on the cell model complexity, such a math tool can be used to evaluate the metabolic fluxes in relation to the bioreactor operating conditions, thus suggesting ways to genetically modify the microorganism for certain purposes. Even if development of such an extended dynamic model requires more experimental and computational efforts, its use is advantageous. The approached probative example refers to a model simulating the dynamics of nanoscale variables from several pathways of the central carbon metabolism (CCM) of Escherichia coli cells, linked to the macroscopic state variables of a fed-batch bioreactor (FBR) used for the tryptophan (TRP) production. The used E. coli strain was modified to replace the PTS system for glucose (GLC) uptake with a more efficient one. The study presents multiple elements of novelty: (i) the experimentally validated modular model itself, and (ii) its efficiency in computationally deriving an optimal operation policy of the FBR.
Alzheimer’s Disease: Current Perspectives and Advances in Physiological Modeling
Authors: Josephine Boder E. , Banerjee Ipsita A.
Published: December 2021

Though Alzheimer’s disease (AD) is the most common cause of dementia, complete disease-modifying treatments are yet to be fully attained. Until recently, transgenic mice constituted most in vitro model systems of AD used for preclinical drug screening; however, these models have so far failed to adequately replicate the disease’s pathophysiology. However, the generation of humanized APOE4 mouse models has led to key discoveries. Recent advances in stem cell differentiation techniques and the development of induced pluripotent stem cells (iPSCs) have facilitated the development of novel in vitro devices. These “microphysiological” systems—in vitro human cell culture systems designed to replicate in vivo physiology—employ varying levels of biomimicry and engineering control. Spheroid-based organoids, 3D cell culture systems, and microfluidic devices or a combination of these have the potential to replicate AD pathophysiology and pathogenesis in vitro and thus serve as both tools for testing therapeutics and models for experimental manipulation.
Immunomodulatory Potential of Diuretics
Authors: Bryniarski Paweł , Nazimek Katarzyna , Marcinkiewicz Janusz
Published: December 2021

In this review, diuretics and their immunomodulatory functions are described. The effects on the immune response of this group of drugs are reported in patients suffering from hypertension and under experimental conditions involving animal models and cell line studies. The pathogenesis of hypertension is strongly connected to chronic inflammation. The vast majority of diuretics modulate the immune response, changing it in favor of the anti-inflammatory response, but depending on the drug, these effects may differ. This topic is significantly important in medical practice regarding the treatment of patients who have coexisting diseases with chronic inflammatory pathogenesis, including hypertension or chronic heart failure. In patients with metabolic syndrome, allergies, or autoimmune disorders, the anti-inflammatory effect is favorable, because of the overstimulation of their immune system. Otherwise, in the geriatric population, it is important to find the proper anti- and pro-inflammatory balance to avoid an enhancement of immune response suppression, which can result in reducing the risk of serious infections that can occur due to the age-diminished function of the immune system. This article is intended to facilitate the selection of an antihypertensive drug that depends on the patient’s immune situation.
The Effects of Angiotensin II or Angiotensin 1-7 on Rat Pial Microcirculation during Hypoperfusion and Reperfusion Injury: Role of Redox Stress
Authors: Lapi Dominga , Cammalleri Maurizio , Dal Monte Massimo , Di Maro Martina , Santillo Mariarosaria , Belfiore Anna , Nasti Gilda , Damiano Simona , Trio Rossella , Chiurazzi Martina , De Conno Barbara , Serao Nicola , Mondola Paolo , Colantuoni Antonio , Guida Bruna
Published: December 2021

Renin–angiotensin systems produce angiotensin II (Ang II) and angiotensin 1-7 (Ang 1-7), which are able to induce opposite effects on circulation. This study in vivo assessed the effects induced by Ang II or Ang 1-7 on rat pial microcirculation during hypoperfusion–reperfusion, clarifying the mechanisms causing the imbalance between Ang II and Ang 1-7. The fluorescence microscopy was used to quantify the microvascular parameters. Hypoperfusion and reperfusion caused vasoconstriction, disruption of blood–brain barrier, reduction of capillary perfusion and an increase in reactive oxygen species production. Rats treated with Ang II showed exacerbated microvascular damage with stronger vasoconstriction compared to hypoperfused rats, a further increase in leakage, higher decrease in capillary perfusion and marker oxidative stress. Candesartan cilexetil (specific Ang II type 1 receptor (AT1R) antagonist) administration prior to Ang II prevented the effects induced by Ang II, blunting the hypoperfusion–reperfusion injury. Ang 1-7 or ACE2 activator administration, preserved the pial microcirculation from hypoperfusion–reperfusion damage. These effects of Ang 1-7 were blunted by a Mas (Mas oncogene-encoded protein) receptor antagonist, while Ang II type 2 receptor antagonists did not affect Ang 1-7-induced changes. In conclusion, Ang II and Ang 1-7 triggered different mechanisms through AT1R or MAS receptors able to affect cerebral microvascular injury.
The Association of Serum Circulating Neuropeptide Q and Chemerin Levels with Cardiometabolic Risk Factors among Patients with Metabolic Syndrome
Authors: Pelczyńska Marta , Mikulska Aniceta Ada , Czyżewska Krystyna , Bogdański Paweł , Grzelak Teresa
Published: December 2021

The potential involvement of neuropeptide Q (NPQ) and chemerin (CHEM) in metabolic disorders is yet to be fully elucidated. The aim of this study was to evaluate serum concentrations of NPQ and CHEM and to establish their relationship with cardiometabolic risk factors among individuals with metabolic syndrome. A total of 66 patients with metabolic syndrome (MetS) and 83 healthy volunteers (non-MetS) underwent biochemical, blood pressure, and anthropometric measurements. The concentration of NPQ in the MetS group was significantly lower (0.47 (0.34 ; 0.54) vs. 0.52 (0.43 ; 0.60) ng/mL, p = 0.015) than in non-MetS, while there were no differences in CHEM level. In the entire study population, we observed several negative correlations between NPQ concentration and waist-hip ratio (WHR), visceral adipose tissue, diastolic blood pressure (DBP), triglycerides (TG) along with a positive correlation with high-density lipoprotein (HDL), total muscle mass, and CHEM. Moreover, a negative correlation was observed in the MetS group between NPQ and glycemia. CHEM showed no significant correlations with cardiometabolic risk factors in the study population. In a multiple regression model, the total muscle mass proved to be an independent factor determining NPQ concentration in the population (p < 0.00000001, R2adj = 28.6%). NPQ seems to protect against metabolic disorders correlated with obesity. Thus, it is worth considering NPQ level as a candidate protective biomarker of metabolic syndrome complications.
Activation of the α1β2γ2L GABAA Receptor by Physiological Agonists
Authors: Pierce Spencer R. , Germann Allison L. , Akk Gustav
Published: December 2021

The Cl− permeable GABAA receptor is a major contributor to cellular inhibition in the brain. The receptor is normally activated by synaptically-released or ambient GABA but is sensitive to a number of physiological compounds such as β-alanine, taurine, and neurosteroids that, to various degrees, activate the receptor and modulate responses either to the transmitter or to each other. Here, we describe α1β2γ2L GABAA receptor activation and modulation by combinations of orthosteric and allosteric activators. The overall goal was to gain insight into how changes in the levels of endogenous agonists modulate receptor activity and influence cellular inhibition. Experimental observations and simulations are described in the framework of a cyclic concerted transition model. We also provide general analytical solutions for the analysis of electrophysiological data collected in the presence of combinations of active compounds.
The Effect of Three-Month Vitamin D Supplementation on the Levels of Homocysteine Metabolism Markers and Inflammatory Cytokines in Sera of Psoriatic Patients
Authors: Prtina Alma , Rašeta Simović Nela , Milivojac Tatjana , Vujnić Milorad , Grabež Milkica , Djuric Dragan , Stojiljković Miloš P. , Soldat Stanković Valentina , Čolić Miodrag J. , Škrbić Ranko
Published: December 2021

Psoriasis is an autoimmune and inflammatory skin disease. Psoriatic patients express higher levels of plasma homocysteine (Hcy) concentration and pro-inflammatory mediators than healthy people; this is frequently associated with vitamin D deficiency. The aim of this clinical study was to investigate the effects of high doses of vitamin D supplementation on the parameters of Hcy metabolism and cytokines in sera of psoriatic patients. This prospective study was conducted on 40 psoriatic patients who had the vitamin D deficiency. All patients received vitamin D 5000 IU/day for three months. Clinical and biochemical measurements were taken at baseline and at follow up (3 months). The results showed that the severity of clinical features, measured by the psoriasis area severity index (PASI) score, were considerably improved in patients after vitamin D supplementation. After vitamin D supplementation, most of the patients (n = 25 or 62.5%) had mild clinical form (p < 0.001). After twelve weeks of intervention period, there were significant increases in vitamin D and B12 serum levels in comparison to the levels that had been measured at the beginning of the study (56.77 ± 14.66 nmol/L and 301.08 ± 95.02 pg/mL vs. 103.85 ± 32.20 nmol/L and 362.81 ± 118.56 pg/mL, respectively; p < 0.001). Moreover, serum levels of Hcy and folate were significantly lower at the end of the study in comparison with the initial levels (12.45 ± 1.92 µmol/L and 8.01 ± 3.88 mg/mL vs. 10.38 ± 1.66 µmol/L and 6.27 ± 2.60 mg/mL, respectively). High doses of vitamin D supplementation led to a significant decrease in pro-inflammatory cytokines (IFN-ɤ, TNF-α, IL-1β, IL-6, IL-8, and IL-17) and high-sensitivity C-reactive protein (hsCRP), whereas the production of anti-inflammatory cytokines (IL-10, IL-5) was up-regulated. In conclusion, supplementation with high doses of vitamin D could be one of the possible preventive and therapeutic measures to reduce systemic inflammation in psoriatic patients.
Development of Active Packaging Based on Agar-Agar Incorporated with Bacteriocin of Lactobacillus sakei
Authors: Contessa Camila Ramão , de Souza Nathieli Bastos , Gonçalo Guilherme Battú , de Moura Catarina Motta , da Rosa Gabriela Silveira , Moraes Caroline Costa
Published: December 2021

In the search for new biodegradable materials and greater microbiological safety and stability of perishable food products, this study aimed to develop a bioplastic antibacterial film incorporating bacteriocin for application in commercial curd cheese and monitoring of microbiological stability. Films with good handling characteristics as well as physical, barrier, and mechanical properties were obtained. Regarding the antibacterial activity, the microbial reduction was demonstrated in a food matrix, obtaining a reduction of 3 logarithmic cycles for the group of coagulase positive staphylococci and from 1100 to <3.00 MPN/g in the analysis of thermotolerant coliforms. Therefore, the film presented food barrier characteristics with the external environment and adequate migration of the antibacterial compound to the product, contributing to the reduction of contamination of a food with high initial microbial load.
ACTB Mutations Analysis and Genotype–Phenotype Correlation in Becker’s Nevus
Authors: Dai Shangzhi , Wang Huijun , Lin Zhimiao
Published: December 2021

Becker’s nevus (BN) is a cutaneous hamartoma which is characterized by circumscribed hyperpigmentation with hypertrichosis. Recent studies have revealed that BN patients harbored postzygotic ACTB mutations, which were restricted to arrector pili muscle lineage. We screened for ACTB mutations in 20 Chinese patients with BN and found that recurrent mutations (c.C439A or c.C439T) in ACTB were detected in the majority of BN patients. However, more than 20% of the patients were negative for ACTB mutations, suggesting a possible genetic heterogeneity in Becker’s nevus. Interestingly, these mutations were also detected in dermal tissues outside the arrector pili muscle. We further performed genotype–phenotype correlation analysis, which revealed that lesions above the waistline, including the trunk above the anterior superior spine level, upper limbs and face, or covering more than 1% BSA were more likely to be positive for ACTB mutations. Altogether, our results provide further evidence of postzygotic ACTB mutations in BN patients and suggest a possible genotype–phenotype correlation of BN.
Functional Characterization of Spinocerebellar Ataxia Associated Dynorphin A Mutant Peptides
Authors: Lieb Andreas , Thaler Germana , Fogli Barbara , Trovato Olga , Posch Mitja Amon , Kaserer Teresa , Zangrandi Luca
Published: December 2021

Mutations in the prodynorphin gene (PDYN) are associated with the development of spinocerebellar ataxia type 23 (SCA23). Pathogenic missense mutations are localized predominantly in the PDYN region coding for the dynorphin A (DynA) neuropeptide and lead to persistently elevated mutant peptide levels with neurotoxic properties. The main DynA target in the central nervous system is the kappa opioid receptor (KOR), a member of the G-protein coupled receptor family, which can elicit signaling cascades mediated by G-protein dissociation as well as β-arrestin recruitment. To date, a thorough analysis of the functional profile for the pathogenic SCA23 DynA mutants at KOR is still missing. To elucidate the role of DynA mutants, we used a combination of assays to investigate the differential activation of G-protein subunits and β-arrestin. In addition, we applied molecular modelling techniques to provide a rationale for the underlying mechanism. Our results demonstrate that DynA mutations, associated with a severe ataxic phenotype, decrease potency of KOR activation, both for G-protein dissociation as well as β-arrestin recruitment. Molecular modelling suggests that this loss of function is due to disruption of critical interactions between DynA and the receptor. In conclusion, this study advances our understanding of KOR signal transduction upon DynA wild type or mutant peptide binding.
Comparison of Clinical Outcomes between Salvage and Elective Thoracic Endovascular Aortic Repair in Patients with Advanced Esophageal Cancer with Aortic Invasion: A Retrospective Cohort Study
Authors: Lin Sian-Han , Lee Jang-Ming , Wu I-Hui
Published: December 2021

Aortoesophageal fistula (AEF) caused by esophageal cancer (EC) is a rare but life-threatening complication. However, the optimal management strategy remains undetermined. Previous cases have demonstrated that thoracic endovascular aortic repair (TEVAR) is effective for prophylactic management. In our study, we evaluated the management of AEF with elective TEVAR over salvage TEVAR. In our single-center retrospective cohort study, forty-seven patients with cT4M0 EC were included in this study, and we divided them into salvage (Group S) and elective (Group E) groups based on whether TEVAR was performed before the hemorrhagic AEF occurred. Our study outcomes included survival and complication rate after TEVAR. Group E showed better overall 90-day survival and aortic-event-free survival in 90-day and 180-day over Group S. More patients in Group E could receive subsequent chemoradiotherapy or esophagectomy. Significantly fewer AEF-related complications, including recurrent hemorrhagic events after TEVAR, hypoperfusion-related organ injury, and bloodstream infection, were noted in Group E. In patients with advanced EC-invading aorta, elective TEVAR offered an early overall and aortic-event-free survival benefit compared to salvage TEVAR. By reducing the AEF-related complications, elective TEVAR could provide more patients receiving subsequent curative-intent treatment.
The Visceral Adiposity Index in Non-Alcoholic Fatty Liver Disease and Liver Fibrosis—Systematic Review and Meta-Analysis
Authors: Ismaiel Abdulrahman , Jaaouani Ayman , Leucuta Daniel-Corneliu , Popa Stefan-Lucian , Dumitrascu Dan L.
Published: December 2021

(1) Background: In order to avoid a liver biopsy in non-alcoholic fatty liver disease (NAFLD), several noninvasive biomarkers have been studied lately. Therefore, we aimed to evaluate the visceral adiposity index (VAI) in NAFLD and liver fibrosis, in addition to its accuracy in predicting NAFLD and NASH. (2) Methods: We searched PubMed, Embase, Scopus, and Cochrane Library, identifying observational studies assessing the VAI in NAFLD and liver fibrosis. QUADAS-2 was used to evaluate the quality of included studies. The principal summary outcomes were mean difference (MD) and area under the curve (AUC). (3) Results: A total of 24 studies were included in our review. VAI levels were significantly increased in NAFLD (biopsy-proven and ultrasound-diagnosed), simple steatosis vs. controls, and severe steatosis vs. simple steatosis. However, no significant MD was found according to sex, liver fibrosis severity, simple vs. moderate and moderate vs. severe steatosis, pediatric NAFLD, and NASH patients. The VAI predicted NAFLD (AUC 0.767) and NASH (AUC 0.732). (4) Conclusions: The VAI has a predictive value in diagnosing NAFLD and NASH, with significantly increased values in adult NAFLD patients, simple steatosis compared to controls, and severe steatosis compared to simple steatosis.
Bird Displacement by Wind Turbines: Assessing Current Knowledge and Recommendations for Future Studies
Authors: Marques Ana Teresa , Batalha Helena , Bernardino Joana
Published: December 2021

Wind energy developments can be responsible for negative impacts on birds, including displacement. In this study we performed a systematic review of the literature available on bird displacement due to wind turbines, both onshore and offshore, to: (i) assess overall trends in scientific research; (ii) review the existing knowledge; and (iii) outline recommendations for future studies on this topic in order to overcome the major gaps and limitations found. Our results are based on 286 trials extracted from 71 peer-reviewed studies. The literature on this topic has increased in the past decade but is concentrated in Europe and United States, despite the fact that the wind industry has worldwide coverage. Open habitats—as agricultural fields and grasslands—were the most represented and Accipitriformes, Galliformes, Charadriiformes, Anseriformes and Passeriformes were the most frequently studied taxa. Displacement was recorded in 40.6% of the trials, and Gaviiformes, Anseriformes, Suliformes, Accipitriformes and Falconiformes were the most affected groups. Pelecaniformes, Passeriformes and Charadriiformes were the groups for which no significant effects were more often observed. We provide a list of recommendations, focused on study design, reporting and result dissemination, that should contribute to more robust conclusions of future studies on this topic.
Investigating the Relationships of P3b with Negative Symptoms and Neurocognition in Subjects with Chronic Schizophrenia
Authors: Giordano Giulia , Perrottelli Andrea , Mucci Armida , Di Lorenzo Giorgio , Altamura Mario , Bellomo Antonello , Brugnoli Roberto , Corrivetti Giulio , Girardi Paolo , Monteleone Palmiero , Niolu Cinzia , Galderisi Silvana , Maj Mario ,   The Italian Network for Research on Psychoses
Published: December 2021

Neurocognitive deficits and negative symptoms (NS) have a pivotal role in subjects with schizophrenia (SCZ) due to their impact on patients’ functioning in everyday life and their influence on goal-directed behavior and decision-making. P3b is considered an optimal electrophysiological candidate biomarker of neurocognitive impairment for its association with the allocation of attentional resources to task-relevant stimuli, an important factor for efficient decision-making, as well as for motivation-related processes. Furthermore, associations between P3b deficits and NS have been reported. The current research aims to fill the lack of studies investigating, in the same subjects, the associations of P3b with multiple cognitive domains and the expressive and motivation-related domains of NS, evaluated with state-of-the-art instruments. One hundred and fourteen SCZ and 63 healthy controls (HCs) were included in the study. P3b amplitude was significantly reduced and P3b latency prolonged in SCZ as compared to HCs. In SCZ, a positive correlation was found between P3b latency and age and between P3b amplitude and the Attention-vigilance domain, while no significant correlations were found between P3b and the two NS domains. Our results indicate that the effortful allocation of attention to task-relevant stimuli, an important component of decision-making, is compromised in SCZ, independently of motivation deficits or other NS.
Changes in Brain Volume Resulting from Cognitive Intervention by Means of the Feuerstein Instrumental Enrichment Program in Older Adults with Mild Cognitive Impairment (MCI): A Pilot Study
Authors: Dwolatzky Tzvi , Feuerstein Refael S. , Manor David , Cohen Shlomit , Devisheim Haim , Inspector Michael , Eran Ayelet , Tzuriel David
Published: December 2021

There is increasing interest in identifying biological and imaging markers for the early detection of neurocognitive decline. In addition, non-pharmacological strategies, including physical exercise and cognitive interventions, may be beneficial for those developing cognitive impairment. The Feuerstein Instrumental Enrichment (FIE) Program is a cognitive intervention based on structural cognitive modifiability and the mediated learning experience (MLE) and aims to promote problem-solving strategies and metacognitive abilities. The FIE program uses a variety of instruments to enhance the cognitive capacity of the individual as a result of mediation. A specific version of the FIE program was developed for the cognitive enhancement of older adults, focusing on strengthening orientation skills, categorization skills, deductive reasoning, and memory. We performed a prospective interventional pilot observational study on older subjects with MCI who participated in 30 mediated FIE sessions (two sessions weekly for 15 weeks). Of the 23 subjects who completed the study, there was a significant improvement in memory on the NeuroTrax cognitive assessment battery. Complete sets of anatomical MRI data for voxel-based morphometry, taken at the beginning and the end of the study, were obtained from 16 participants (mean age 83.5 years). Voxel-based morphometry showed an interesting and unexpected increase in grey matter (GM) in the anterolateral occipital border and the middle cingulate cortex. These initial findings of our pilot study support the design of randomized trials to evaluate the effect of cognitive training using the FIE program on brain volumes and cognitive function.
Facilitation of Motor Evoked Potentials in Response to a Modified 30 Hz Intermittent Theta-Burst Stimulation Protocol in Healthy Adults
Authors: Hosel Katarina , Tremblay François
Published: December 2021

Theta-burst stimulation (TBS) is a form of repetitive transcranial magnetic stimulation (rTMS) developed to induce neuroplasticity. TBS usually consists of 50 Hz bursts at 5 Hz intervals. It can facilitate motor evoked potentials (MEPs) when applied intermittently, although this effect can vary between individuals. Here, we sought to determine whether a modified version of intermittent TBS (iTBS) consisting of 30 Hz bursts repeated at 6 Hz intervals would lead to lasting MEP facilitation. We also investigated whether recruitment of early and late indirect waves (I-waves) would predict individual responses to 30 Hz iTBS. Participants (n = 19) underwent single-pulse TMS to assess MEP amplitude at baseline and variations in MEP latency in response to anterior-posterior, posterior-anterior, and latero-medial stimulation. Then, 30 Hz iTBS was administered, and MEP amplitude was reassessed at 5-, 20- and 45-min. Post iTBS, most participants (13/19) exhibited MEP facilitation, with significant effects detected at 20- and 45-min. Contrary to previous evidence, recruitment of early I-waves predicted facilitation to 30 Hz iTBS. These observations suggest that 30 Hz/6 Hz iTBS is effective in inducing lasting facilitation in corticospinal excitability and may offer an alternative to the standard 50 Hz/5 Hz protocol.
Methylation Markers in Cutaneous Melanoma: Unravelling the Potential Utility of Their Tracking by Liquid Biopsy
Authors: Aleotti Valentina , Catoni Cristina , Poggiana Cristina , Rosato Antonio , Facchinetti Antonella , Scaini Maria Chiara
Published: December 2021

Malignant melanoma is the most serious, life-threatening form of all dermatologic diseases, with a poor prognosis in the presence of metastases and advanced disease. Despite recent advances in targeted therapy and immunotherapy, there is still a critical need for a better understanding of the fundamental mechanisms behind melanoma progression and resistance onset. Recent advances in genome-wide methylation methods have revealed that aberrant changes in the pattern of DNA methylation play an important role in many aspects of cancer progression, including cell proliferation and migration, evasion of cell death, invasion, and metastasization. The purpose of the current review was to gather evidence regarding the usefulness of DNA methylation tracking in liquid biopsy as a potential biomarker in melanoma. We investigated the key genes and signal transduction pathways that have been found to be altered epigenetically in melanoma. We then highlighted the circulating tumor components present in blood, including circulating melanoma cells (CMC), circulating tumor DNA (ctDNA), and tumor-derived extracellular vesicles (EVs), as a valuable source for identifying relevant aberrations in DNA methylation. Finally, we focused on DNA methylation signatures as a marker for tracking response to therapy and resistance, thus facilitating personalized medicine and decision-making in the treatment of melanoma patients.
Shooting at Moving and Hidden Targets—Tumour Cell Plasticity and the Notch Signalling Pathway in Head and Neck Squamous Cell Carcinomas
Authors: Kałafut Joanna , Czerwonka Arkadiusz , Anameriç Alinda , Przybyszewska-Podstawka Alicja , Misiorek Julia O. , Rivero-Müller Adolfo , Nees Matthias
Published: December 2021

Head and Neck Squamous Cell Carcinoma (HNSCC) is often aggressive, with poor response to current therapies in approximately 40–50% of the patients. Current therapies are restricted to operation and irradiation, often combined with a small number of standard-of-care chemotherapeutic drugs, preferentially for advanced tumour patients. Only very recently, newer targeted therapies have entered the clinics, including Cetuximab, which targets the EGF receptor (EGFR), and several immune checkpoint inhibitors targeting the immune receptor PD-1 and its ligand PD-L1. HNSCC tumour tissues are characterized by a high degree of intra-tumour heterogeneity (ITH), and non-genetic alterations that may affect both non-transformed cells, such as cancer-associated fibroblasts (CAFs), and transformed carcinoma cells. This very high degree of heterogeneity likely contributes to acquired drug resistance, tumour dormancy, relapse, and distant or lymph node metastasis. ITH, in turn, is likely promoted by pronounced tumour cell plasticity, which manifests in highly dynamic and reversible phenomena such as of partial or hybrid forms of epithelial-to-mesenchymal transition (EMT), and enhanced tumour stemness. Stemness and tumour cell plasticity are strongly promoted by Notch signalling, which remains poorly understood especially in HNSCC. Here, we aim to elucidate how Notch signal may act both as a tumour suppressor and proto-oncogenic, probably during different stages of tumour cell initiation and progression. Notch signalling also interacts with numerous other signalling pathways, that may also have a decisive impact on tumour cell plasticity, acquired radio/chemoresistance, and metastatic progression of HNSCC. We outline the current stage of research related to Notch signalling, and how this pathway may be intricately interconnected with other, druggable targets and signalling mechanisms in HNSCC.
Nucleolar Stress Functions Upstream to Stimulate Expression of Autophagy Regulators
Authors: Dannheisig David P. , Schimansky Anna , Donow Cornelia , Pfister Astrid S.
Published: December 2021

Ribosome biogenesis is essential for protein synthesis, cell growth and survival. The process takes places in nucleoli and is orchestrated by various proteins, among them RNA polymerases I–III as well as ribosome biogenesis factors. Perturbation of ribosome biogenesis activates the nucleolar stress response, which classically triggers cell cycle arrest and apoptosis. Nucleolar stress is utilized in modern anti-cancer therapies, however, also contributes to the development of various pathologies, including cancer. Growing evidence suggests that nucleolar stress stimulates compensatory cascades, for instance bulk autophagy. However, underlying mechanisms are poorly understood. Here we demonstrate that induction of nucleolar stress activates expression of key autophagic regulators such as ATG7 and ATG16L1, essential for generation of autophagosomes. We show that knockdown of the ribosomopathy factor SBDS, or of key ribosome biogenesis factors (PPAN, NPM, PES1) is associated with enhanced levels of ATG7 in cancer cells. The same holds true when interfering with RNA polymerase I function by either pharmacological inhibition (CX-5461) or depletion of the transcription factor UBF-1. Moreover, we demonstrate that RNA pol I inhibition by CX-5461 stimulates autophagic flux. Together, our data establish that nucleolar stress affects transcriptional regulation of autophagy. Given the contribution of both axes in propagation or cure of cancer, our data uncover a connection that might be targeted in future.
Plant Derived Bioactive Compounds, Their Anti-Cancer Effects and In Silico Approaches as an Alternative Target Treatment Strategy for Breast Cancer: An Updated Overview
Authors: Shrihastini Vijayakumar , Muthuramalingam Pandiyan , Adarshan Sivakumar , Sujitha Mariappan , Chen Jen-Tsung , Shin Hyunsuk , Ramesh Manikandan
Published: December 2021

Cancer is one of the most common malignant diseases that occur worldwide, among which breast cancer is the second leading cause of death in women. The subtypes are associated with differences in the outcome and were selected for treatments according to the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor. Triple-negative breast cancer, one of the subtypes of breast cancer, is difficult to treat and can even lead to death. If breast cancer is not treated during the initial stages, it may spread to nearby organs, a process called metastasis, through the blood or lymph system. For in vitro studies, MCF-7, MDA-MB-231, MDA-MB-468, and T47B are the most commonly used breast cancer cell lines. Clinically, chemotherapy and radiotherapy are usually expensive and can also cause side effects. To overcome these issues, medicinal plants could be the best alternative for chemotherapeutic drugs with fewer side effects and cost-effectiveness. Furthermore, the genes involved in breast cancer can be regulated and synergized with signaling molecules to suppress the proliferation of breast cancer cells. In addition, nanoparticles encapsulating (nano-encapsulation) medicinal plant extracts showed a significant reduction in the apoptotic and cytotoxic activities of breast cancer cells. This present review mainly speculates an overview of the native medicinal plant derived anti-cancerous compounds with its efficiency, types and pathways involved in breast cancer along with its genes, the mechanism of breast cancer brain metastasis, chemoresistivity and its mechanism, bioinformatics approaches which could be an effective alternative for drug discovery.
T Cell Aging in Patients with Colorectal Cancer—What Do We Know So Far?
Authors: Thoma Oana-Maria , Neurath Markus F. , Waldner Maximilian J.
Published: December 2021

Colorectal cancer (CRC) continues to be one of the most frequently diagnosed types of cancers in the world. CRC is considered to affect mostly elderly patients, and the number of diagnosed cases increases with age. Even though general screening improves outcomes, the overall survival and recurrence-free CRC rates in aged individuals are highly dependent on their history of comorbidities. Furthermore, aging is also known to alter the immune system, and especially the adaptive immune T cells. Many studies have emphasized the importance of T cell responses to CRC. Therefore, understanding how age-related changes affect the outcome in CRC patients is crucial. This review focuses on what is so far known about age-related T cell dysfunction in elderly patients with colorectal cancer and how aged T cells can mediate its development. Last, this study describes the advances in basic animal models that have potential to be used to elucidate the role of aged T cells in CRC.
The Antiviral Drug Efavirenz in Breast Cancer Stem Cell Therapy
Authors: Chiou Pey-Tsyr , Ohms Stephen , Board Philip G. , Dahlstrom Jane E. , Rangasamy Danny , Casarotto Marco G.
Published: December 2021

Although many breast cancer therapies show initial success in the treatment of the primary tumour, they often fail to eliminate a sub-population of cells known as cancer stem cells (CSCs). These cells are recognised for their self-renewal properties and for their capacity for differentiation often leading to chemo/radio-resistance. The antiviral drug Efavirenz has been shown to be effective in eliminating triple-negative breast cancer cells, and here we examine its effect on breast CSCs. The effects of Efavirenz on CSCs for several breast cancer cell lines were investigated by examining cellular changes upon drug treatment, including CSC numbers, morphology, RNA/microRNA expression and levels of epithelial/mesenchymal CSC subtypes. Efavirenz treatment resulted in a decrease in the size and number of tumorspheres and a reduction in epithelial-type CSC levels, but an increase in mesenchymal-type CSCs. Efavirenz caused upregulation of several CSC-related genes as well as miR-21, a CSC marker and miR-182, a CSC suppressor gene. We conclude that Efavirenz alters the phenotype and expression of key genes in breast CSCs, which has important potential therapeutic implications.