bluuebunny/crossref_metadata_2025 huggingface dataset:
Air Pollutants and CO2 Emissions in Industrial Parks and Evaluation of Their Green Upgrade on Regional Air Quality Improvement: A Case Study of Seven Cities in Henan Province
Authors: Hei Wanting , Li Xiao , Gao Gengyu , Wang Shanshan , Zhang Ruiqin , Wang Ke
Published: February 2022

Although central to the promotion of regional economic development, industrial parks discharge large quantities of air pollutants and CO2, counter to the goals of air quality improvement and CO2 reductions in China. In this study, 13 industrial parks in seven cities in Henan Province were chosen to evaluate their emission of air pollutants and CO2 in 2017, their reduction potential under different green measures, and their air quality improvements under a Green Upgrade scenario. The results show that: (1) The total emissions of SO2, NOx, CO, PM10, PM2.5, VOCs and CO2 in the 13 industrial parks were 43, 39, 351, 19, 7, 18, 2 kt and 36 Mt, and would decrease by 72, 56, 19, 30, 26, 77 and 30%, respectively, under the Green Upgrade scenario. (2) The industrial process was the major source of CO, PM2.5, VOCs and NH3, whereas power plants were the largest source of SO2 and NOx, and they would be reduced by 93, 59, 94, 91, 23 and 28%, respectively, under the Green Upgrade scenario. (3) The terminal energy use sector (including industrial boilers and industrial process sources) was the main source of CO2, accounting for 75% of total CO2 emissions, and would be reduced by 76% under the Green Upgrade scenario. (4) WRF-CMAQ simulation results show that, under the Green Upgrade scenario, the concentration of PM2.5 in a transmission channel city would be improved by 1–36 μg/m3, with an annual average value of 9 μg/m3. Our results demonstrate the significant effect of the synergistic reduction in air pollutants and CO2 emissions using Green Technologies in industrial parks and the subsequent improvement in regional air quality.
A Modified Ant Lion Optimization Method and Its Application for Instance Reduction Problem in Balanced and Imbalanced Data
Authors: El Bakrawy Lamiaa M. , Cifci Mehmet Akif , Kausar Samina , Hussain Sadiq , Islam Md. Akhtarul , Alatas Bilal , Desuky Abeer S.
Published: February 2022

Instance reduction is a pre-processing step devised to improve the task of classification. Instance reduction algorithms search for a reduced set of instances to mitigate the low computational efficiency and high storage requirements. Hence, finding the optimal subset of instances is of utmost importance. Metaheuristic techniques are used to search for the optimal subset of instances as a potential application. Antlion optimization (ALO) is a recent metaheuristic algorithm that simulates antlion’s foraging performance in finding and attacking ants. However, the ALO algorithm suffers from local optima stagnation and slow convergence speed for some optimization problems. In this study, a new modified antlion optimization (MALO) algorithm is recommended to improve the primary ALO performance by adding a new parameter that depends on the step length of each ant while revising the antlion position. Furthermore, the suggested MALO algorithm is adapted to the challenge of instance reduction to obtain better results in terms of many metrics. The results based on twenty-three benchmark functions at 500 iterations and thirteen benchmark functions at 1000 iterations demonstrate that the proposed MALO algorithm escapes the local optima and provides a better convergence rate as compared to the basic ALO algorithm and some well-known and recent optimization algorithms. In addition, the results based on 15 balanced and imbalanced datasets and 18 oversampled imbalanced datasets show that the instance reduction proposed method can statistically outperform the basic ALO algorithm and has strong competitiveness against other comparative algorithms in terms of four performance measures: Accuracy, Balanced Accuracy (BACC), Geometric mean (G-mean), and Area Under the Curve (AUC) in addition to the run time. MALO algorithm results show increment in Accuracy, BACC, G-mean, and AUC rates up to 7%, 3%, 15%, and 9%, respectively, for some datasets over the basic ALO algorithm while keeping less computational time.
A Class of Quasilinear Equations with Riemann–Liouville Derivatives and Bounded Operators
Authors: Fedorov Vladimir E. , Turov Mikhail M. , Kien Bui Trong
Published: February 2022

The existence and uniqueness of a local solution is proved for the incomplete Cauchy type problem to multi-term quasilinear fractional differential equations in Banach spaces with Riemann–Liouville derivatives and bounded operators at them. Nonlinearity in the equation is assumed to be Lipschitz continuous and dependent on lower order fractional derivatives, which orders have the same fractional part as the order of the highest fractional derivative. The obtained abstract result is applied to study a class of initial-boundary value problems to time-fractional order equations with polynomials of an elliptic self-adjoint differential operator with respect to spatial variables as linear operators at the time-fractional derivatives. The nonlinear operator in the considered partial differential equations is assumed to be smooth with respect to phase variables.
The Local Antimagic Total Chromatic Number of Some Wheel-Related Graphs
Authors: Yang Xue , Bian Hong , Yu Haizheng , Liu Dandan
Published: February 2022

Let G=(V,E) be a connected graph with |V|=n and |E|=m. A bijection f:V(G)∪E(G)→{1,2,⋯,n+m} is called local antimagic total labeling if, for any two adjacent vertices u and v, ωt(u)≠ωt(v), where ωt(u)=f(u)+∑e∈E(u)f(e), and E(u) is the set of edges incident to u. Thus, any local antimagic total labeling induces a proper coloring of G, where the vertex x in G is assigned the color ωt(x). The local antimagic total chromatic number, denoted by χlat(G), is the minimum number of colors taken over all colorings induced by local antimagic total labelings of G. In this paper, we present the local antimagic total chromatic numbers of some wheel-related graphs, such as the fan graph Fn, the bowknot graph Bn,n, the Dutch windmill graph D4n, the analogous Dutch graph AD4n and the flower graph Fn.
Cayley Graphs Defined by Systems of Equations
Authors: Yang Fuyuan , Sun Qiang , Zhou Hongbo , Zhang Chao
Published: February 2022

Let R be a finite ring. In this paper, we mainly explore the conditions to ensure the graph BΓn defined by a system of equations {fi|i=2,…,n} to be a Cayley graph or a Hamiltonian graph. More precisely, we prove that BΓn is a Cayley graph with G=⟨ϕ,A⟩ a group of dihedral type if and only if the system Fn={fi|i=2,…,n} is Cayley graphic of dihedral type in R. As an application, the well-known Lova´sz Conjecture, which states that any finite connected Cayley graph has a Hamilton cycle, holds for the connected BΓn defined by Cayley graphic system Fn of dihedral type in the field GF(pk).
Existence Results for Coupled Implicit \({\psi}\)-Riemann–Liouville Fractional Differential Equations with Nonlocal Conditions
Authors: Jiang Dinghong , Bai Chuanzhi
Published: February 2022

In this paper, we study the existence and uniqueness of solutions for a coupled implicit system involving ψ-Riemann–Liouville fractional derivative with nonlocal conditions. We first transformed the coupled implicit problem into an integral system and then analyzed the uniqueness and existence of this integral system by means of Banach fixed-point theorem and Krasnoselskiis fixed-point theorem. Some known results in the literature are extended. Finally, an example is given to illustrate our theoretical result.
Engineering Novel Lentiviral Vectors for Labelling Tumour Cells and Oncogenic Proteins
Authors: Akgül Seçkin , Offenhäuser Carolin , Kordowski Anja , Day Bryan W.
Published: February 2022

Lentiviral vectors are unique and highly efficient genetic tools to incorporate genetic materials into the genome of a variety of cells whilst conserving biosafety. Their rapid acceptance made it necessary to improve existing protocols, including molecular engineering and cloning, production of purified lentiviral particles, and efficient infection of target cells. In addition to traditional protocols, which can be time-consuming, several biotechnology companies are providing scientists with commercially available lentiviral constructs and particles. However, these constructs are limited by their original form, tend to be costly, and lack the flexibility to re-engineer based on the ever-changing needs of scientific projects. Therefore, the current study organizes the existing methods and integrates them with novel ideas to establish a protocol that is simple and efficient to implement. In this study we, (i) generated an innovative site-directed nucleotide attachment/replacement and DNA insertion method using unique PCR primers, (ii) improved traditional methods by integrating plasmid clarification steps, (iii) utilized endogenous mRNA as a resource to construct new lentiviruses, and (iv) identified an existing purification method and incorporated it into an organized workflow to produce high-yield lentiviral particle collection. Finally, (v) we verified and demonstrated the functional validity of our methods using an infection strategy.
Cell Culture Process Scale-Up Challenges for Commercial-Scale Manufacturing of Allogeneic Pluripotent Stem Cell Products
Authors: Lee Brian , Jung Sunghoon , Hashimura Yas , Lee Maximilian , Borys Breanna S. , Dang Tiffany , Kallos Michael S. , Rodrigues Carlos A. V. , Silva Teresa P. , Cabral Joaquim M. S.
Published: February 2022

Allogeneic cell therapy products, such as therapeutic cells derived from pluripotent stem cells (PSCs), have amazing potential to treat a wide variety of diseases and vast numbers of patients globally. However, there are various challenges related to manufacturing PSCs in single-use bioreactors, particularly at larger volumetric scales. This manuscript addresses these challenges and presents potential solutions to alleviate the anticipated bottlenecks for commercial-scale manufacturing of high-quality therapeutic cells derived from PSCs.
Leelamine Modulates STAT5 Pathway Causing Both Autophagy and Apoptosis in Chronic Myelogenous Leukemia Cells
Authors: Jung Young Yun , Um Jae-Young , Chinnathambi Arunachalam , Govindasamy Chandramohan , Sethi Gautam , Ahn Kwang Seok
Published: February 2022

Leelamine (LEE) has recently attracted significant attention for its growth inhibitory effects against melanoma, breast cancer, and prostate cancer cells; however, its impact on hematological malignancies remains unclear. Here, we first investigate the cytotoxic effects of LEE on several human chronic myeloid leukemia (CML) cells. We noted that LEE stimulated both apoptosis and autophagy in CML cells. In addition, the constitutive activation of signal transducer and activator of transcription 5 (STAT5) was suppressed substantially upon LEE treatment. Moreover, STAT5 knockdown with small interfering RNA (siRNA) increased LEE-induced apoptosis as well as autophagy and affected the levels of various oncogenic proteins. Thus, the targeted mitigation of STAT5 activation by LEE can contribute to its diverse anticancer effects by enhancing two distinct cell death pathways.
RETRACTED: Advantage of Species Diversification to Facilitate Sustainable Development of Aquaculture Sector
Authors: Kim Dae-Young , Shinde Surendra , Kadam Avinash , Saratale Rijuta , Saratale Ganesh , Kumar Manu , Syed Asad , Bahkali Ali , Ghodake Gajanan
Published: February 2022

Intensified agrochemical-based monoculture systems worldwide are under adoption to meet the challenge of human population growth and the ever-growing global demand for food. However, this path has been opposed and criticized because it involves overexploitation of land, monoculture of few species, excessive input of agrochemicals, and adverse impacts on human health and the environment. The wide diversity among polyculture systems practiced across the globe has created confusion over the priority of a single strategy towards sustainable aquaculture development and safer products. Herein, we highlight the significance of polyculture and integrated aquaculture practices in conveying the successful transition of the aquaculture industry towards sustainable development. So far, the established thought is that the precise selection of aquatic species and a focus on compatible and complementary species combinations are supposed to facilitate rapid progress in food production with more profitability and sustainability. Therefore, the advantages of species diversification are discussed from an ecological perspective to enforce aquaculture expansion. This account asserts that a diverse range of aquaculture practices can promote synergies among farmed species, enhance system resilience, enable conservation, decrease ecological footprints, and provide social benefits such as diversified income and local food security.
Manipulation of Meiotic Recombination to Hasten Crop Improvement
Authors: Fayos Ian , Frouin Julien , Meynard Donaldo , Vernet Aurore , Herbert Léo , Guiderdoni Emmanuel
Published: February 2022

Reciprocal (cross-overs = COs) and non-reciprocal (gene conversion) DNA exchanges between the parental chromosomes (the homologs) during meiotic recombination are, together with mutation, the drivers for the evolution and adaptation of species. In plant breeding, recombination combines alleles from genetically diverse accessions to generate new haplotypes on which selection can act. In recent years, a spectacular progress has been accomplished in the understanding of the mechanisms underlying meiotic recombination in both model and crop plants as well as in the modulation of meiotic recombination using different strategies. The latter includes the stimulation and redistribution of COs by either modifying environmental conditions (e.g., T°), harnessing particular genomic situations (e.g., triploidy in Brassicaceae), or inactivating/over-expressing meiotic genes, notably some involved in the DNA double-strand break (DSB) repair pathways. These tools could be particularly useful for shuffling diversity in pre-breeding generations. Furthermore, thanks to the site-specific properties of genome editing technologies the targeting of meiotic recombination at specific chromosomal regions nowadays appears an attainable goal. Directing COs at desired chromosomal positions would allow breaking linkage situations existing between favorable and unfavorable alleles, the so-called linkage drag, and accelerate genetic gain. This review surveys the recent achievements in the manipulation of meiotic recombination in plants that could be integrated into breeding schemes to meet the challenges of deploying crops that are more resilient to climate instability, resistant to pathogens and pests, and sparing in their input requirements.
Novel Therapeutic Target for Prevention of Neurodegenerative Diseases: Modulation of Neuroinflammation with Sig-1R Ligands
Authors: Bogár Ferenc , Fülöp Lívia , Penke Botond
Published: February 2022

Neurodegenerative diseases (NDDs) are characterized by progressive deterioration of the structure and function of cells and their networks in the nervous system. There are currently no drugs or other treatments that can stop the progression of NDDs. NDDs have many similarities and common pathways, e.g., formation of misfolded amyloid proteins, intra- and extracellular amyloid deposits, and chronic inflammation. Initially, the inflammation process has a cytoprotective function; however, an elevated and prolonged immune response has damaging effects and causes cell death. Neuroinflammation has been a target of drug development for treating and curing NDDs. Treatment of different NDDs with non-steroid anti-inflammatory drugs (NSAIDs) has failed or has given inconsistent results. The use of NSAIDs in diagnosed Alzheimer’s disease is currently not recommended. Sigma-1 receptor (Sig-1R) is a novel target for NDD drug development. Sig-1R plays a key role in cellular stress signaling, and it regulates endoplasmic reticulum stress and unfolded protein response. Activation of Sig-1R provides neuroprotection in cell cultures and animal studies. Clinical trials demonstrated that several Sig-1R agonists (pridopidine, ANAVEX3-71, fluvoxamine, dextrometorphan) and their combinations have a neuroprotective effect and slow down the progression of distinct NDDs.
Artificial Intelligence for Risk Prediction of End-Stage Renal Disease in Sepsis Survivors with Chronic Kidney Disease
Authors: Lee Kuo-Hua , Chu Yuan-Chia , Tsai Ming-Tsun , Tseng Wei-Cheng , Lin Yao-Ping , Ou Shuo-Ming , Tarng Der-Cherng
Published: February 2022

Sepsis may lead to kidney function decline in patients with chronic kidney disease (CKD), and the deleterious effect may persist in patients who survive sepsis. We used a machine learning approach to predict the risk of end-stage renal disease (ESRD) in sepsis survivors. A total of 11,661 sepsis survivors were identified from a single-center database of 112,628 CKD patients between 2010 and 2018. During a median follow-up of 3.5 years, a total of 1366 (11.7%) sepsis survivors developed ESRD after hospital discharge. We adopted the random forest, extra trees, extreme gradient boosting, light gradient boosting machine (LGBM), and gradient boosting decision tree (GBDT) algorithms to predict the risk of ESRD development among these patients. GBDT yielded the highest area under the receiver operating characteristic curve of 0.879, followed by LGBM (0.868), and extra trees (0.865). The GBDT model revealed the strong effect of estimated glomerular filtration rates <25 mL/min/1.73 m2 at discharge in predicting ESRD development. In addition, hemoglobin and proteinuria were also essential predictors. Based on a large-scale dataset, we established a machine learning model computing the risk for ESRD occurrence among sepsis survivors with CKD. External validation is required to evaluate the generalizability of this model.
Ovarian Clear Cell Carcinoma and Mature Cystic Teratoma Transformed to PNET and Carcinosarcoma: A Case Report with an Immunohistochemical Investigation
Authors: Matsuo Mikiko , Saigo Chiemi , Takeuchi Tamotsu , Onogi Akane , Watanabe Naoki , Aikyo Shinsuke , Toyoki Hiroshi , Yanai Hiroyuki , Tanaka Takuji
Published: February 2022

Ovarian tumors include neoplasms derived from somatic cells and germ cells, including teratoma. Sometimes, tumors of the somatic cell type may develop from teratoma, causing diagnostic perturbation. We experienced a case of a tumor composed of several types of tissue in the ovary with a teratoma. When findings of teratoma and somatic tumor coexist in an ovary, it is difficult to differentiate whether a somatic tumor was mixed with a teratoma or a teratoma unitarily caused transformation to a somatic cell tumor. A 72-year-old Japanese woman (gravida, 3; para, 1) presented to our hospital with severe constipation and frequent urination, and a large intrapelvic tumor was detected by computed tomography (CT). Soon after admission, ultrasonography (US) and magnetic resonance imaging (MRI) revealed a large multilocular cystic tumor on her left ovary. Based on the clinical diagnosis of ovarian cancer, she underwent a left ovariectomy, appendectomy, and partial omentectomy. We observed an ovarian tumor consisting of teratoma, primitive neuroectodermal tumor (PNET), adenocarcinoma, various types of sarcomas, and clear cell carcinoma on the H and E-stained sections. The component of clear cell carcinoma showed a nuclear positive reaction against PAX8 and napsin A, as well as a loss of ARID1A, suggesting typical endometriosis-derived clear cell carcinoma. On the other hand, the expression of ARID1A was maintained in teratoma, PNET, non-specific adenocarcinoma, and various types of sarcomas, suggesting that these tumors had an origin different from that of clear cell carcinoma. These findings indicated that the ovarian tumor of this patient contained a clear cell carcinoma derived from a somatic cell and a teratoma that transformed to a wide variety of somatic cell types of tumors, which coexisted on one ovary. The appropriate use of immunohistochemistry was diagnostically effective in this case.
The Role of Genetic Factors in the Development of Acute Respiratory Viral Infection COVID-19: Predicting Severe Course and Outcomes
Authors: Minashkin Mikhail M. , Grigortsevich Nataliya Y. , Kamaeva Anna S. , Barzanova Valeriya V. , Traspov Alexey A. , Godkov Mikhail A. , Ageev Farkhad A. , Petrikov Sergey S. , Pozdnyakova Nataliya V.
Published: February 2022

The aim of this study was to identify single nucleotide variants in genes associated with susceptibility to or severe outcomes of COVID-19. A total of 319 genomic DNA samples from patients with varying degrees of disease severity and 78 control DNA samples from people who had regular or prolonged contact with patients with COVID-19 but did not have clinical manifestations and/or antibodies to SARS-CoV-2. Seven SNPs were identified that were statistically associated with disease risk or severe course, rs1799864 in the CCR2 gene (OR = 2.21), rs1990760 in the IFIH1 gene (OR = 2.41), rs1800629 in the TNF gene (OR = 1.98), rs75603675 in the TMPRSS2 gene (OR = 1.86), rs7842 in the C3AR1 gene (OR = 2.08), rs179008 in the gene TLR7 (OR = 1.85), rs324011 in the C3AR1 gene (OR = 2.08), rs179008 in the TLR7 gene (OR = 1.85), and rs324011 in the STAT6 gene (OR = 1.84), as well as two variants associated with protection from COVID-19, rs744166 in the STAT3 gene (OR = 0.36) and rs1898830 in the TLR2 gene (OR = 0.47). The genotype in the region of these markers can be the criterion of the therapeutic approach for patients with COVID-19.
A Simplified and Robust Activation Procedure of Glass Surfaces for Printing Proteins and Subcellular Micropatterning Experiments
Authors: Karimian Tina , Hager Roland , Karner Andreas , Weghuber Julian , Lanzerstorfer Peter
Published: February 2022

Depositing biomolecule micropatterns on solid substrates via microcontact printing (µCP) usually requires complex chemical substrate modifications to initially create reactive surface groups. Here, we present a simplified activation procedure for untreated solid substrates based on a commercial polymer metal ion coating (AnteoBindTM Biosensor reagent) that allows for direct µCP and the strong attachment of proteins via avidity binding. In proof-of-concept experiments, we identified the optimum working concentrations of the surface coating, characterized the specificity of protein binding and demonstrated the suitability of this approach by subcellular micropatterning experiments in living cells. Altogether, this method represents a significant enhancement and simplification of existing µCP procedures and further increases the accessibility of protein micropatterning for cell biological research questions.
An Electrochemical Impedance Spectroscopy-Based Aptasensor for the Determination of SARS-CoV-2-RBD Using a Carbon Nanofiber–Gold Nanocomposite Modified Screen-Printed Electrode
Authors: Amouzadeh Tabrizi Mahmoud , Acedo Pablo
Published: February 2022

Worldwide, human health is affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Hence, the fabrication of the biosensors to diagnose SARS-CoV-2 is critical. In this paper, we report an electrochemical impedance spectroscopy (EIS)-based aptasensor for the determination of the SARS-CoV-2 receptor-binding domain (SARS-CoV-2-RBD). For this purpose, the carbon nanofibers (CNFs) were first decorated with gold nanoparticles (AuNPs). Then, the surface of the carbon-based screen-printed electrode (CSPE) was modified with the CNF–AuNP nanocomposite (CSPE/CNF–AuNP). After that, the thiol-terminal aptamer probe was immobilized on the surface of the CSPE/CNF–AuNP. The surface coverage of the aptamer was calculated to be 52.8 pmol·cm−2. The CSPE/CNF–AuNP/Aptamer was then used for the measurement of SARS-CoV-2-RBD by using the EIS method. The obtained results indicate that the signal had a linear–logarithmic relationship in the range of 0.01–64 nM with a limit of detection of 7.0 pM. The proposed aptasensor had a good selectivity to SARS-CoV-2-RBD in the presence of human serum albumin; human immunoglobulins G, A, and M, hemagglutinin, and neuraminidase. The analytical performance of the aptasensor was studied in human saliva samples. The present study indicates a practical application of the CSPE/CNF-AuNP/Aptamer for the determination of SARS-CoV-2-RBD in human saliva samples with high sensitivity and accuracy.
Caloric Restriction Mimetic 2-Deoxyglucose Reduces Inflammatory Signaling in Human Astrocytes: Implications for Therapeutic Strategies Targeting Neurodegenerative Diseases
Authors: Vallee Kaylie-Anna Juliette , Fields Jerel Adam
Published: February 2022

Therapeutic interventions are greatly needed for age-related neurodegenerative diseases. Astrocytes regulate many aspects of neuronal function including bioenergetics and synaptic transmission. Reactive astrocytes are implicated in neurodegenerative diseases due to their pro-inflammatory phenotype close association with damaged neurons. Thus, strategies to reduce astrocyte reactivity may support brain health. Caloric restriction and a ketogenic diet limit energy production via glycolysis and promote oxidative phosphorylation, which has gained traction as a strategy to improve brain health. However, it is unknown how caloric restriction affects astrocyte reactivity in the context of neuroinflammation. We investigated how a caloric restriction mimetic and glycolysis inhibitor, 2-deoxyglucose (2-DG), affects interleukin 1β-induced inflammatory gene expression in human astrocytes. Human astrocyte cultures were exposed to 2-DG or vehicle for 24 h and then to recombinant IL-1β for 6 or 24 h to analyze mRNA and protein expression, respectively. Gene expression levels of proinflammatory genes (complement component 3, IL-1β, IL6, and TNFα) were analyzed by real-time PCR, immunoblot, and immunohistochemistry. As expected, IL-1β induced elevated levels of proinflammatory genes. 2-DG reversed this effect at the mRNA and protein levels without inducing cytotoxicity. Collectively, these data suggest that inhibiting glycolysis in human astrocytes reduces IL-1β-induced reactivity. This finding may lead to novel therapeutic strategies to limit inflammation and enhance bioenergetics toward the goal of preventing and treating neurodegenerative diseases.
Endovascular Electroencephalogram Records Simultaneous Subdural Electrode-Detectable, Scalp Electrode-Undetectable Interictal Epileptiform Discharges
Authors: Fujimoto Ayataka , Matsumaru Yuji , Masuda Yosuke , Marushima Aiki , Hosoo Hisayuki , Araki Kota , Ishikawa Eiichi
Published: February 2022

Introduction: We hypothesized that an endovascular electroencephalogram (eEEG) can detect subdural electrode (SDE)-detectable, scalp EEG-undetectable epileptiform discharges. The purpose of this study is, therefore, to measure SDE-detectable, scalp EEG-undetectable epileptiform discharges by an eEEG on a pig. Methods: A pig under general anesthesia was utilized to measure an artificially generated epileptic field by an eEEG that was able to be detected by an SDE, but not a scalp EEG as a primary outcome. We also compared the phase lag of each epileptiform discharge that was detected by the eEEG and SDE as a secondary outcome. Results: The eEEG electrode detected 113 (97%) epileptiform discharges (97% sensitivity). Epileptiform discharges that were localized within the three contacts (contacts two, three and four), but not spread to other parts, were detected by the eEEG with a 92% sensitivity. The latency between peaks of the eEEG and right SDE earliest epileptiform discharge ranged from 0 to 48 ms (mean, 13.3 ms; median, 11 ms; standard deviation, 9.0 ms). Conclusion: In a pig, an eEEG could detect epileptiform discharges that an SDE could detect, but that a scalp EEG could not.
Correction: Liu et al. Responsible Genes for Neuronal Migration in the Chromosome 17p13.3: Beyond Pafah1b1(Lis1), Crk and Ywhae(14-3-3ε). Brain Sci. 2022, 12, 56
Authors: Liu Xiaonan , Bennison Sarah A. , Robinson Lozen , Toyo-oka Kazuhito
Published: February 2022

The authors wish to correct the following error in this paper [...]
Does It Count? Pre-School Children’s Spontaneous Focusing on Numerosity and Their Development of Arithmetical Skills at School
Authors: Poltz Nadine , Quandte Sabine , Kohn Juliane , Kucian Karin , Wyschkon Anne , Aster Michael von , Esser Günter
Published: February 2022

Background: Children’s spontaneous focusing on numerosity (SFON) is related to numerical skills. This study aimed to examine (1) the developmental trajectory of SFON and (2) the interrelations between SFON and early numerical skills at pre-school as well as their influence on arithmetical skills at school. Method: Overall, 1868 German pre-school children were repeatedly assessed until second grade. Nonverbal intelligence, visual attention, visuospatial working memory, SFON and numerical skills were assessed at age five (M = 63 months, Time 1) and age six (M = 72 months, Time 2), and arithmetic was assessed at second grade (M = 95 months, Time 3). Results: SFON increased significantly during pre-school. Path analyses revealed interrelations between SFON and several numerical skills, except number knowledge. Magnitude estimation and basic calculation skills (Time 1 and Time 2), and to a small degree number knowledge (Time 2), contributed directly to arithmetic in second grade. The connection between SFON and arithmetic was fully mediated by magnitude estimation and calculation skills at pre-school. Conclusion: Our results indicate that SFON first and foremost influences deeper understanding of numerical concepts at pre-school and—in contrast to previous findings –affects only indirectly children’s arithmetical development at school.
Physical Exercise Ameliorates Anxiety, Depression and Sleep Quality in College Students: Experimental Evidence from Exercise Intensity and Frequency
Authors: Ji Chaoxin , Yang Jun , Lin Lin , Chen Song
Published: February 2022

Background: The main purpose of this study was to investigate the effects of exercise intensity and exercise frequency on anxiety, depression and sleep quality in college students. Methods: All participants came from a university in northeastern China. All participants were tested for Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and were diagnosed with anxiety disorders. The research subjects were divided into six groups, namely the low-intensity and low-frequency group (group 1), low-intensity and moderate-frequency group (group 2), low-intensity and high-frequency group (group 3), high-intensity and low-frequency group (group 4), and high-intensity and moderate-frequency group (group 5) and high-intensity and high-frequency group (group 6). The duration of each physical exercise for each group was 1 h. Participants’ exercise intensity was monitored using Polar H10 HR sensors and the Borg RPE scale. The experiment was carried out for a total of 6 weeks. The researchers conducted pre- and post-test scores on the subjects’ anxiety, depression and sleep quality through questionnaires. Results: Exercise intensity improved anxiety and decreased symptoms of depression better than exercise frequency; sleep quality was more closely related to exercise intensity. Conclusion: Exercise intensity and exercise frequency have different effects on anxiety, depression and sleep quality improvement, indicating that exercise intensity and exercise frequency have different effects on anxiety, depression and sleep quality of college students.
Efficacy of High-Ozonide Oil in Prevention of Cancer Relapses Mechanisms and Clinical Evidence
Authors: Izzotti Alberto , Fracchia Enzo , Rosano Camillo , Comite Antonio , Belgioia Liliana , Sciacca Salvatore , Khalid Zumama , Congiu Matteo , Colarossi Cristina , Blanco Giusi , Santoro Antonio , Chiara Massimo , Pulliero Alessandra
Published: February 2022

Background: Cancer tissue is characterized by low oxygen availability triggering neo angiogenesis and metastatisation. Accordingly, oxidation is a possible strategy for counteracting cancer progression and relapses. Previous studies used ozone gas, administered by invasive methods, both in experimental animals and clinical studies, transiently decreasing cancer growth. This study evaluated the effect of ozonized oils (administered either topically or orally) on cancer, exploring triggered molecular mechanisms. Methods: In vitro, in lung and glioblastoma cancer cells, ozonized oils having a high ozonide content suppressed cancer cell viability by triggering mitochondrial damage, intracellular calcium release, and apoptosis. In vivo, a total of 115 cancer patients (age 58 ± 14 years; 44 males, 71 females) were treated with ozonized oil as complementary therapy in addition to standard chemo/radio therapeutic regimens for up to 4 years. Results: Cancer diagnoses were brain glioblastoma, pancreas adenocarcinoma, skin epithelioma, lung cancer (small and non-small cell lung cancer), colon adenocarcinoma, breast cancer, prostate adenocarcinoma. Survival rate was significantly improved in cancer patients receiving HOO as integrative therapy as compared with those receiving standard treatment only. Conclusions: These results indicate that ozonized oils at high ozonide may represent an innovation in complementary cancer therapy worthy of further clinical studies.
Deep Learning-Based Pan-Cancer Classification Model Reveals Tissue-of-Origin Specific Gene Expression Signatures
Authors: Divate Mayur , Tyagi Aayush , Richard Derek J. , Prasad Prathosh A. , Gowda Harsha , Nagaraj Shivashankar H.
Published: February 2022

Cancer tissue-of-origin specific biomarkers are needed for effective diagnosis, monitoring, and treatment of cancers. In this study, we analyzed transcriptomics data from 37 cancer types provided by The Cancer Genome Atlas (TCGA) to identify cancer tissue-of-origin specific gene expression signatures. We developed a deep neural network model to classify cancers based on gene expression data. The model achieved a predictive accuracy of >97% across cancer types indicating the presence of distinct cancer tissue-of-origin specific gene expression signatures. We interpreted the model using Shapley additive explanations to identify specific gene signatures that significantly contributed to cancer-type classification. We evaluated the model and the validity of gene signatures using an independent test data set from the International Cancer Genome Consortium. In conclusion, we present a robust neural network model for accurate classification of cancers based on gene expression data and also provide a list of gene signatures that are valuable for developing biomarker panels for determining cancer tissue-of-origin. These gene signatures serve as valuable biomarkers for determining tissue-of-origin for cancers of unknown primary.
Border Line Definition Using Hyperspectral Imaging in Colorectal Resections
Authors: Jansen-Winkeln Boris , Dvorak Michelle , Köhler Hannes , Maktabi Marianne , Mehdorn Matthias , Chalopin Claire , Diana Michele , Gockel Ines , Barberio Manuel
Published: February 2022

Background: A perfusion deficit is a well-defined and intraoperatively influenceable cause of anastomotic leak (AL). Current intraoperative perfusion assessment methods do not provide objective and quantitative results. In this study, the ability of hyperspectral imaging (HSI) to quantify tissue oxygenation intraoperatively was assessed. Methods: 115 patients undergoing colorectal resections were included in the final analysis. Before anastomotic formation, the bowel was extracted and the resection line was outlined and imaged using a compact HSI camera, in order to provide instantaneously quantitative perfusion assessment. Results: In 105 patients, a clear demarcation line was visible with HSI one minute after marginal artery transection, reaching a plateau after 3 min. In 58 (55.2%) patients, the clinically determined transection line matched with HSI. In 23 (21.9%) patients, the clinically established resection margin was entirely within the less perfused area. In 24 patients (22.8%), the HSI transection line had an irregular course and crossed the clinically established resection line. In four cases, HSI disclosed a clinically undetected lesion of the marginal artery. Conclusions: Intraoperative HSI is safe, well reproducible, and does not disrupt the surgical workflow. It also quantifies bowel surface perfusion. HSI might become an intraoperative guidance tool, potentially preventing postoperative complications.
Diverse Roles and Targets of miRNA in the Pathogenesis of Testicular Germ Cell Tumour
Authors: Das Mrinal K. , Haugen Øyvind P. , Haugen Trine B.
Published: February 2022

Testicular germ cell tumour (TGCT) is the most common cancer type among young adults in many parts of the world. Although the pathogenesis of TGCT is not well understood, the involvement of heritable components is evident, and the risk is polygenic. Genome-wide association studies have so far found 78 susceptibility loci for TGCT, and many of the loci are in non-coding regions indicating the involvement of non-coding RNAs in TGCT pathogenesis. MicroRNAs (miRNAs), a class of non-coding RNAs, have emerged as important gene regulators at the post-transcriptional level. They are crucial in controlling many cellular processes, such as proliferation, differentiation, and apoptosis, and an aberrant miRNA expression may contribute to the pathogenesis of several cancers, including TGCT. In support of this notion, several studies reported differential expression of miRNAs in TGCTs. We previously demonstrated that miRNAs were the most common group of small non-coding RNAs in TGCTs, and several functional studies of miRNAs in TGCTs suggest that they may act as either oncogene or tumour suppressors. Moreover, individual miRNA targets and downstream pathways in the context of TGCT development have been explored. In this review, we will focus on the diverse roles and targets of miRNAs in TGCT pathogenesis.
Neratinib and Capecitabine for the Treatment of Leptomeningeal Metastases from HER2-Positive Breast Cancer: A Series in the Setting of a Compassionate Program
Authors: Pellerino Alessia , Soffietti Riccardo , Bruno Francesco , Manna Roberta , Muscolino Erminia , Botta Pierangela , Palmiero Rosa , Rudà Roberta
Published: February 2022

Background: Leptomeningeal metastasis is a neurological complication from HER2-positive breast cancer with a poor prognosis and limited treatment options. This study has evaluated the activity of neratinib in association with capecitabine in 10 patients with LM from HER2-positive BC after the failure of multiple lines of treatment, including trastuzumab-based therapy, within a compassionate program, and a comparison was made with a historical control group of 10 patients. Methods: Patients aged ≥ 18 years with histological diagnosis of primary HER2-positive BC, either amplified or mutated, and newly-diagnosed LM were enrolled. Coexistence of BM that has or has not received radiotherapy, as well as prior chemotherapy, hormone therapy, or monoclonal HER2-targeting antibodies or antibody–drug conjugates, were allowed, with the exclusion of lapatinib. Results: Six-months OS was 60% with a median OS of 10 months (95% CI: 2.00–17.0). Three-month intracranial PFS was 60% with a median intracranial PFS of 4.0 months (95% CI: 2.00–6.0). The neurological benefit was observed in 70% of patients with a median duration of neurological response of 6.5 months. The best radiological response was stable disease in 60% of patients. Conclusions: This small series shows that the combination of neratinib and capecitabine is a safe treatment in LM from heavily pretreated HER2-positive BC with clinical efficacy in some patients and is worth investigating in a larger study.
Actively Targeted Nanomedicines in Breast Cancer: From Pre-Clinal Investigation to Clinic
Authors: Fraguas-Sánchez Ana Isabel , Lozza Irene , Torres-Suárez Ana Isabel
Published: February 2022

Breast cancer is one of the most frequently diagnosed tumors and the second leading cause of cancer death in women worldwide. The use of nanosystems specifically targeted to tumor cells (active targeting) can be an excellent therapeutic tool to improve and optimize current chemotherapy for this type of neoplasm, since they make it possible to reduce the toxicity and, in some cases, increase the efficacy of antineoplastic drugs. Currently, there are 14 nanomedicines that have reached the clinic for the treatment of breast cancer, 4 of which are already approved (Kadcyla®, Enhertu®, Trodelvy®, and Abraxane®). Most of these nanomedicines are antibody–drug conjugates. In the case of HER-2-positive breast cancer, these conjugates (Kadcyla®, Enhertu®, Trastuzumab-duocarmycin, RC48, and HT19-MMAF) target HER-2 receptors, and incorporate maytansinoid, deruxtecan, duocarmicyn, or auristatins as antineoplastics. In TNBC these conjugates (Trodelvy®, Glembatumumab-Vedotin, Ladiratuzumab-vedotin, Cofetuzumab-pelidotin, and PF-06647263) are directed against various targets, in particular Trop-2 glycoprotein, NMB glycoprotein, Zinc transporter LIV-1, and Ephrin receptor-4, to achieve this selective accumulation, and include campthotecins, calicheamins, or auristatins as drugs. Apart from the antibody–drug conjugates, there are other active targeted nanosystems that have reached the clinic for the treatment of these tumors such as Abraxane® and Nab-rapamicyn (albumin nanoparticles entrapping placlitaxel and rapamycin respectively) and various liposomes (MM-302, C225-ILS-Dox, and MM-310) loaded with doxorubicin or docetaxel and coated with ligands targeted to Ephrin A2, EPGF, or HER-2 receptors. In this work, all these active targeted nanomedicines are discussed, analyzing their advantages and disadvantages over conventional chemotherapy as well as the challenges involved in their lab to clinical translation. In addition, examples of formulations developed and evaluated at the preclinical level are also discussed.
CHEK2p.I157T Mutation Is Associated with Increased Risk of Adult-Type Ovarian Granulosa Cell Tumors
Authors: Švajdler Peter , Vasovčák Peter , Švajdler Marián , Šedivcová Monika , Urbán Veronika , Michal Michal , Mezencev Roman
Published: February 2022

Pathogenic germline mutations c.1100delC and p.I157T in the CHEK2 gene have been associated with increased risk of breast, colon, kidney, prostate, and thyroid cancers; however, no associations have yet been identified between these two most common European founder mutations of the CHEK2 gene and ovarian cancers of any type. Our review of 78 female heterozygous carriers of these mutations (age > 18 years) found strikingly higher proportion of adult-type granulosa cell tumors of the ovary (AGCTs) among ovarian cancers that developed in these women (~36%) compared to women from the general population (1.3%). Based on this finding, we performed a cross-sectional study that included 93 cases previously diagnosed with granulosa cell tumors, refined and validated their AGCT diagnosis through an IHC study, determined their status for the two CHEK2 mutations, and compared the prevalence of these mutations in the AGCT cases and reference populations. The prevalence ratios for the p.I157T mutation in the AGCT group relative to the global (PR = 26.52; CI95: 12.55–56.03) and European non-Finnish populations (PR = 24.55; CI95: 11.60–51.97) support an association between the CHEK2p.I157T mutation and AGCTs. These rare gynecologic tumors have not been previously associated with known risk factors and genetic predispositions. Furthermore, our results support the importance of the determination of the FOXL2p.C134W somatic mutation for accurate diagnosis of AGCTs and suggest a combination of IHC markers that can serve as a surrogate diagnostic marker to infer the mutational status of this FOXL2 allele.
The Role of Neuroaxis Irradiation in the Treatment of Intraspinal Ewing Sarcoma: A Review and Meta-Analysis
Authors: Troschel Fabian M. , Kröger Kai , Siats Jan J. , Rahbar Kambiz , Eich Hans Theodor , Scobioala Sergiu
Published: February 2022

The role of cranio-spinal irradiation (CSI) for primary extraosseous intraspinal Ewing sarcoma (EwS) remains unclear. Here, we evaluate clinical and survival outcomes in patients with primary intraspinal EwS treated with CSI as part of multimodal primary therapy regimens. We abstracted patient information, including details on treatment application, efficacy, and tolerance from the literature and our hospital database for a cohort of 24 primary intraspinal EwS patients treated with CSI. Median age was 25.5 years, median CSI dose was 36 Gy and mean boost dose was 12.8 Gy. Sixteen patients (66.7%) achieved complete radiological remission, another 5 patients demonstrated partial response and 1 patient showed no response to treatment. Compared to a cohort of patients treated with focal radiotherapy, CSI patients were more likely to have multifocal disease at time of diagnosis (p = 0.001) and intradural tumor location (p < 0.001). Despite over-representation of these unfavorable characteristics, there was no survival difference between groups (p = 0.58). While CSI shows promising results in the treatment of primary intraspinal EwS, treatment should be considered individually based on tumor and patient characteristics in the absence of prospective trials.
Pre- and Post-Resection Urine Metabolic Profiles of Bladder Cancer Patients: Results of Preliminary Studies on Time Series Metabolomics Analysis
Authors: Jacyna Julia , Kordalewska Marta , Artymowicz Małgorzata , Markuszewski Marcin , Matuszewski Marcin , Markuszewski Michał J.
Published: February 2022

The incidence of bladder cancer (BCa) has remained high for many years. Nevertheless, its pathomechanism has not yet been fully understood and is still being studied. Therefore, multiplatform untargeted urinary metabolomics analysis has been performed in order to study differences in the metabolic profiles of urine samples collected at three time points: before transurethral resection of bladder tumor (TURBT), the day after the procedure and two weeks after TURBT. Collected samples were analyzed with the use of high-performance liquid chromatography hyphenated with time-of-flight mass spectrometry detection (HPLC-TOF/MS) and gas chromatography coupled with triple quadrupole mass spectrometry detection (GC-QqQ/MS, in a scan mode). Levels of metabolites selected in our previous study were assessed in order to confirm their potential to differentiate the healthy and diseased samples, regardless of the risk factors and individual characteristics. Hippuric acid, pentanedioic acid and uridine confirmed their potential for sample differentiation. Based on the results of statistical analysis for the paired samples (comparison of metabolic profiles of samples collected before TURBT and two weeks after), a set of metabolites belonging to nucleotide metabolism and methylation processes was also selected. Longitudinal studies proved to be useful for the evaluation of metabolic changes in bladder cancer.