bluuebunny/crossref_metadata_2025 huggingface dataset:
Transfer of Cobalt Nanoparticles in a Simplified Food Web: From Algae to Zooplankton to Fish
Authors: Mei Nanxuan , Hedberg Jonas , Ekvall Mikael T. , Kelpsiene Egle , Hansson Lars-Anders , Cedervall Tommy , Blomberg Eva , Odnevall Inger
Published: July 2021

Cobalt (Co) nanoparticles (NPs) may be diffusely dispersed into natural ecosystems from various anthropogenic sources such as traffic settings and eventually end up in aquatic systems. As environmentally dispersed Co NPs may be transferred through an aquatic food web, this study investigated this transfer from algae (Scendesmus sp.) to zooplankton (Daphnia magna) to fish (Crucian carp, Carassius carassius). Effects of interactions between naturally excreted biomolecules from D. magna and Co NPs were investigated from an environmental fate perspective. ATR-FTIR measurements showed the adsorption of both algae constituents and excreted biomolecules onto the Co NPs. Less than 5% of the Co NPs formed heteroagglomerates with algae, partly an effect of both agglomeration and settling of the Co NPs. The presence of excreted biomolecules in the solution did not affect the extent of heteroagglomeration. Despite the low extent of heteroagglomeration between Co NPs and algae, the Co NPs were transferred to the next trophic level (D. magna). The Co uptake in D. magna was 300 times larger than the control samples (without Co NP), which were not influenced by the addition of excreted biomolecules to the solution. Significant uptake of Co was observed in the intestine of the fish feeding on D. magna containing Co NPs. No bioaccumulation of Co was observed in the fish. Moreover, 10–20% of the transferred Co NP mass was dissolved after 24 h in the simulated gut solution of the zooplankton (pH 7), and 50–60% was dissolved in the simulated gut solution of the fish (pH 4). The results elucidate that Co NPs gain different properties upon trophic transfer in the food web. Risk assessments should hence be conducted on transformed and weathered NPs rather than on pristine particles.
Stellar Turbulent Convection: The Multiscale Nature of the Solar Magnetic Signature
Authors: Scardigli Stefano , Berrilli Francesco , Del Moro Dario , Giovannelli Luca
Published: July 2021

The multiscale dynamics associated with turbulent convection present in physical systems governed by very high Rayleigh numbers still remains a vividly disputed topic in the community of astrophysicists, and in general, among physicists dealing with heat transport by convection. The Sun is a very close star for which detailed observations and estimations of physical properties on the surface, connected to the processes of the underlying convection zone, are possible. This makes the Sun a unique natural laboratory in which to investigate turbulent convection in the hard turbulence regime, a regime typical of systems characterized by high values of the Rayleigh number. In particular, it is possible to study the geometry of convection using the photospheric magnetic voids (or simply voids), the quasi-polygonal quiet regions nearly devoid of magnetic elements, which cover the whole solar surface and which form the solar magnetic network. This work presents the most extensive statistics, both in the spatial scales studied (1–80 Mm) and in the temporal duration (SC 23 and SC 24), to investigate the multiscale nature of solar magnetic patterns associated with the turbulent convection of our star. We show that the size distribution of the voids, in the 1–80 Mm range, for the 317,870 voids found in the 692 analyzed magnetograms, is basically described by an exponential function.
Review of the JCAP/JATOP Air Quality Model Study in Japan
Authors: Shibata Yoshiaki , Morikawa Tazuko
Published: July 2021

Around 1997, when JCAP (the Japan Clean Air Program) began, Japan’s atmospheric environment did not meet the environmental standards for NO2 and suspended particle matters (SPM), and strict reduction requirements for automobile exhaust gas were required. To achieve environmental standards, further cooperation between the automobile technology and fuel technology sectors was needed. In Europe and the United States, Auto-Oil programs were being implemented to reduce automobile exhaust gas, and JCAP was established as an Auto-Oil program in Japan. The Air Quality Model Study was one of the research themes and research activities continued for a total of 21 years, including JCAP I/II and JATOP I/II/III (the Japan AuTo Oil Program). JATOP was the successor program of JCAP. This paper describes the outline and main results of the JCAP/JATOP Air Quality Model Study.
Reconciling Reduced Red Meat Consumption in Canada with Regenerative Grazing: Implications for GHG Emissions, Protein Supply and Land Use
Authors: Dyer James A. , Desjardins Raymond L.
Published: July 2021

This paper reconciled the soil ecology benefits of forages and ruminants with reducing GHG emissions from beef. A scenario analysis compared four integrated systems for beef, pork and broilers. Slaughter cattle diets were either business as usual (BAU) or grass fed (GF), and the combined red meat consumption could not exceed the recommendation for human health. The four consumption scenarios included (PS1) equal beef and pork with BAU beef, (PS2) equal beef and pork with GF beef, (PS3) more pork and less beef with GF beef and (PS4) more pork and less beef with BAU beef. Broiler consumption was increased to force all four scenarios to provide the same amount of protein. All four scenarios required similar feed grain areas (2.5 to 3 Mha). At 2.3, 4.4, 2.2 and 1.2 Mha for PS1, PS2, PS3 and PS4, respectively, the areas in harvestable forage showed much greater variation. From high to low GHG emissions, the ranking of scenarios was PS2, PS1, PS3 and PS4. Although allowing for avoidance of soil organic matter loss changed this ranking, the carbon footprint of beef production was still double or more that of pork in all four PS. To reconcile the agro-ecological benefits of beef with reducing GHG emissions, PS3 may be better than PS4. Along with eating more pork and broilers, and less red meat overall, consumers can choose GF beef as an occasional alternative.
Association of Cardiovascular Disease and Long-Term Exposure to Fine Particulate Matter (PM2.5) in the Southeastern United States
Authors: Valdez R. Burciaga , Al-Hamdan Mohammad Z. , Tabatabai Mohammad , Hood Darryl B. , Im Wansoo , Wilus Derek , Nori-Sarma Amruta , Ramesh Aramandla , Donneyong Macarius M. , Langston Michael A. , Mouton Charles P. , Juárez Paul D.
Published: July 2021

There is a well-documented association between ambient fine particulate matter air pollution (PM2.5) and cardiovascular disease (CVD) morbidity and mortality. Exposure to PM2.5 can cause premature death and harmful and chronic health effects such as heart attack, diabetes, and stroke. The Environmental Protection Agency sets annual PM2.5 standards to reduce these negative health effects. Currently above an annual average level of 12.0 µg/m is considered unhealthy. Methods. We examined the association of long-term exposure to PM2.5 and CVD in a cohort of 44,610 individuals who resided in 12 states recruited into the Southern Community Cohort Study (SCCS). The SCCS was designed to recruit Black and White participants who received care from Federally Qualified Health Centers; hence, they represent vulnerable individuals from low-income families across this vast region. This study tests whether SCCS participants who lived in locations exposed to elevated ambient levels of PM2.5 concentrations were more likely to report a history of CVD at enrollment (2002–2009). Remotely sensed satellite data integrated with ground monitoring data provide an assessment of the average annual PM2.5 in urban and rural locations where the SCCS participants resided. We used multilevel logistic regression to estimate the associations between self-reported CVD and exposure to elevated ambient levels of PM2.5. Results. We found a 13.4 percent increase in the odds of reported CVD with exposure to unhealthy levels of PM2.5 exposure at enrollment. The SCCS participants with medical histories of hypertension, hypercholesterolemia, and smoking had, overall, 385 percent higher odds of reported CVD than those without these clinical risk factors. Additionally, Black participants were more likely to live in locations with higher ambient PM2.5 concentrations and report high levels of clinical risk factors, thus, they may be at a greater future risk of CVD. Conclusions: In the SCCS participants, we found a strong relation between exposures to high ambient levels of PM2.5 and self-reported CVD at enrollment.
Relativistic B-Spline R-Matrix Calculations for Electron Collisions with Ytterbium
Authors: Hamilton Kathryn , Bartschat Klaus , Zatsarinny Oleg
Published: July 2021

We have applied the full-relativistic Dirac B-Spline R-matrix method to obtain cross sections for electron scattering from ytterbium atoms. The results are compared with those obtained from a semi-relativistic (Breit-Pauli) model-potential approach and the few available experimental data.
Popularity Prediction of Online Contents via Cascade Graph and Temporal Information
Authors: Shang Yingdan , Zhou Bin , Wang Ye , Li Aiping , Chen Kai , Song Yichen , Lin Changjian
Published: July 2021

Predicting the popularity of online content is an important task for content recommendation, social influence prediction and so on. Recent deep learning models generally utilize graph neural networks to model the complex relationship between information cascade graph and future popularity, and have shown better prediction results compared with traditional methods. However, existing models adopt simple graph pooling strategies, e.g., summation or average, which prone to generate inefficient cascade graph representation and lead to unsatisfactory prediction results. Meanwhile, they often overlook the temporal information in the diffusion process which has been proved to be a salient predictor for popularity prediction. To focus attention on the important users and exclude noises caused by other less relevant users when generating cascade graph representation, we learn the importance coefficient of users and adopt sample mechanism in graph pooling process. In order to capture the temporal features in the diffusion process, we incorporate the inter-infection duration time information into our model by using LSTM neural network. The results show that temporal information rather than cascade graph information is a better predictor for popularity. The experimental results on real datasets show that our model significantly improves the prediction accuracy compared with other state-of-the-art methods.
Fast and Effective Retrieval for Large Multimedia Collections
Authors: Wagenpfeil Stefan , Vu Binh , Mc Kevitt Paul , Hemmje Matthias
Published: July 2021

The indexing and retrieval of multimedia content is generally implemented by employing feature graphs. These graphs typically contain a significant number of nodes and edges to reflect the level of detail in feature detection. A higher level of detail increases the effectiveness of the results, but also leads to more complex graph structures. However, graph traversal-based algorithms for similarity are quite inefficient and computationally expensive, especially for large data structures. To deliver fast and effective retrieval especially for large multimedia collections and multimedia big data, an efficient similarity algorithm for large graphs in particular is desirable. Hence, in this paper, we define a graph projection into a 2D space (Graph Code) and the corresponding algorithms for indexing and retrieval. We show that calculations in this space can be performed more efficiently than graph traversals due to the simpler processing model and the high level of parallelization. As a consequence, we demonstrate experimentally that the effectiveness of retrieval also increases substantially, as the Graph Code facilitates more levels of detail in feature fusion. These levels of detail also support an increased trust prediction, particularly for fused social media content. In our mathematical model, we define a metric triple for the Graph Code, which also enhances the ranked result representations. Thus, Graph Codes provide a significant increase in efficiency and effectiveness, especially for multimedia indexing and retrieval, and can be applied to images, videos, text and social media information.
Biocomposite Inks for 3D Printing
Authors: Chinga-Carrasco Gary
Published: July 2021

Three-dimensional (3D) printing has evolved massively during the last years and is demonstrating its potential in tissue engineering, wound dressings, cell culture models for drug testing, and prosthesis, to name a few [...]
Kinetic Analysis of Lidocaine Elimination by Pig Liver Cells Cultured in 3D Multi-Compartment Hollow Fiber Membrane Network Perfusion Bioreactors
Authors: Catapano Gerardo , Unger Juliane K. , Zanetti Elisabetta M. , Fragomeni Gionata , Gerlach Jörg C.
Published: July 2021

Liver cells cultured in 3D bioreactors is an interesting option for temporary extracorporeal liver support in the treatment of acute liver failure and for animal models for preclinical drug screening. Bioreactor capacity to eliminate drugs is generally used for assessing cell metabolic competence in different bioreactors or to scale-up bioreactor design and performance for clinical or preclinical applications. However, drug adsorption and physical transport often disguise the intrinsic drug biotransformation kinetics and cell metabolic state. In this study, we characterized the intrinsic kinetics of lidocaine elimination and adsorption by porcine liver cells cultured in 3D four-compartment hollow fiber membrane network perfusion bioreactors. Models of lidocaine transport and biotransformation were used to extract intrinsic kinetic information from response to lidocaine bolus of bioreactor versus adhesion cultures. Different from 2D adhesion cultures, cells in the bioreactors are organized in liver-like aggregates. Adsorption on bioreactor constituents significantly affected lidocaine elimination and was effectively accounted for in kinetic analysis. Lidocaine elimination and cellular monoethylglicinexylidide biotransformation featured first-order kinetics with near-to-in vivo cell-specific capacity that was retained for times suitable for clinical assist and drug screening. Different from 2D cultures, cells in the 3D bioreactors challenged with lidocaine were exposed to close-to-physiological lidocaine and monoethylglicinexylidide concentration profiles. Kinetic analysis suggests bioreactor technology feasibility for preclinical drug screening and patient assist and that drug adsorption should be accounted for to assess cell state in different cultures and when laboratory bioreactor design and performance is scaled-up to clinical use or toxicological drug screening.
BICD Cargo Adaptor 1 (BICD1) Downregulation Correlates with a Decreased Level of PD-L1 and Predicts a Favorable Prognosis in Patients with IDH1-Mutant Lower-Grade Gliomas
Authors: Huang Shang-Pen , Li Chien-Hsiu , Chang Wei-Min , Lin Yuan-Feng
Published: July 2021

Although several biomarkers have been identified to predict the prognosis of lower-grade (Grade II/III) gliomas (LGGs), we still need to identify new markers to facilitate those well-known markers to obtain more accurate prognosis prediction in LGGs. Bioinformatics data from The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), and the Cancer Cell Line Encyclopedia (CCLE) datasets were used as the research materials. In total, 34 genes associated with the HIF1A pathway were analyzed using the hierarchical method to search for the most compatible gene. The BICD cargo adaptor 1 (BICD1) gene (BICD1) was shown to be significantly correlated with The hypoxic inducible factor 1A (HIF1A) expression, the World Health Organization (WHO) grade, and IDH1 mutation status. In addition, BICD1 downregulation was significantly correlated with a higher Karnofsky performance score (KPS), IDH1/TP53/ATRX mutations, wild-type EGFR, and younger patient age in the enrolled LGG cohort. Moreover, BICD1 expression was significantly upregulated in wild-type IDH1 LGGs with EGFR mutations. Kaplan–Meier survival analysis revealed that BICD1 downregulation predicts a favorable overall survival (OS) in LGG patients, especially in those with IDH1 mutations. Intriguingly, we found a significant correlation between BICD1 downregulation and a decreased level of CD274, GSK3B, HGF, or STAT3 in LGGs. Our findings suggest that BICD1 downregulation could be a potential biomarker for a favorable prognosis of LGGs.
Novel Anti-Fungal d-Laminaripentaose-Releasing Endo-β-1,3-glucanase with a RICIN-like Domain from Cellulosimicrobium funkei HY-13
Authors: Bai Lu , Kim Jonghoon , Son Kwang-Hee , Shin Dong-Ha , Ku Bon-Hwan , Kim Do Young , Park Ho-Yong
Published: July 2021

Endo-β-1,3-glucanase plays an essential role in the deconstruction of β-1,3-d-glucan polysaccharides through hydrolysis. The gene (1650-bp) encoding a novel, bi-modular glycoside hydrolase family 64 (GH64) endo-β-1,3-glucanase (GluY) with a ricin-type β-trefoil lectin domain (RICIN)-like domain from Cellulosimicrobium funkei HY-13 was identified and biocatalytically characterized. The recombinant enzyme (rGluY: 57.5 kDa) displayed the highest degradation activity for laminarin at pH 4.5 and 40 °C, while the polysaccharide was maximally decomposed by its C-terminal truncated mutant enzyme (rGluYΔRICIN: 42.0 kDa) at pH 5.5 and 45 °C. The specific activity (26.0 U/mg) of rGluY for laminarin was 2.6-fold higher than that (9.8 U/mg) of rGluYΔRICIN for the same polysaccharide. Moreover, deleting the C-terminal RICIN domain in the intact enzyme caused a significant decrease (>60%) of its ability to degrade β-1,3-d-glucans such as pachyman and curdlan. Biocatalytic degradation of β-1,3-d-glucans by inverting rGluY yielded predominantly d-laminaripentaose. rGluY exhibited stronger growth inhibition against Candida albicans in a dose-dependent manner than rGluYΔRICIN. The degree of growth inhibition of C. albicans by rGluY (approximately 1.8 μM) was approximately 80% of the fungal growth. The superior anti-fungal activity of rGluY suggests that it can potentially be exploited as a supplementary agent in the food and pharmaceutical industries.
Altered L-Arginine Metabolic Pathways in Gastric Cancer: Potential Therapeutic Targets and Biomarkers
Authors: Bednarz-Misa Iwona , Fleszar Mariusz G. , Fortuna Paulina , Lewandowski Łukasz , Mierzchała-Pasierb Magdalena , Diakowska Dorota , Krzystek-Korpacka Małgorzata
Published: July 2021

There is a pressing need for molecular targets and biomarkers in gastric cancer (GC). We aimed at identifying aberrations in L-arginine metabolism with therapeutic and diagnostic potential. Systemic metabolites were quantified using mass spectrometry in 293 individuals and enzymes’ gene expression was quantified in 29 paired tumor-normal samples using qPCR and referred to cancer pathology and molecular landscape. Patients with cancer or benign disorders had reduced systemic arginine, citrulline, and ornithine and elevated symmetric dimethylarginine and dimethylamine. Citrulline and ornithine depletion was accentuated in metastasizing cancers. Metabolite diagnostic panel had 91% accuracy in detecting cancer and 70% accuracy in differentiating cancer from benign disorders. Gastric tumors had upregulated NOS2 and downregulated ASL, PRMT2, ORNT1, and DDAH1 expression. NOS2 upregulation was less and ASL downregulation was more pronounced in metastatic cancers. Tumor ASL and PRMT2 expression was inversely related to local advancement. Enzyme up- or downregulation was greater or significant solely in cardia subtype. Metabolic reprogramming in GC includes aberrant L-arginine metabolism, reflecting GC subtype and pathology, and is manifested by altered interplay of its intermediates and enzymes. Exploiting L-arginine metabolic pathways for diagnostic and therapeutic purposes is warranted. Functional studies on ASL, PRMT2, and ORNT1 in GC are needed.
Suppressive Effects of Rosmarinic Acid Rich Fraction from Perilla on Oxidative Stress, Inflammation and Metastasis Ability in A549 Cells Exposed to PM via C-Jun, P-65-Nf-Κb and Akt Signaling Pathways
Authors: Pintha Komsak , Chaiwangyen Wittaya , Yodkeeree Supachai , Suttajit Maitree , Tantipaiboonwong Payungsak
Published: July 2021

Particulate matter from forest fires (PMFF) is an environmental pollutant causing oxidative stress, inflammation, and cancer cell metastasis due to the presence of polycyclic aromatic hydrocarbons (PAHs). Perilla seed meal contains high levels of polyphenols, including rosmarinic acid (RA). The aim of this study is to determine the anti-oxidative stress, anti-inflammation, and anti-metastasis actions of rosmarinic acid rich fraction (RA-RF) from perilla seed meal and its underlying molecular mechanisms in A549 cells exposed to PMFF. PMFF samples were collected via the air sampler at the University of Phayao, Thailand, and their PAH content were analyzed using GC-MS. Fifteen PAH compounds were detected in PMFF. The PMFF significantly induced intracellular reactive oxygen species (ROS) production, the mRNA expression of pro-inflammatory cytokines, MMP-9 activity, invasion, migration, the overexpression of c-Jun and p-65-NF-κB, and Akt phosphorylation. Additionally, the RA-RF significantly reduced ROS production, IL-6, IL-8, TNF-α, and COX-2. RA-RF could also suppress MMP-9 activity, migration, invasion, and the phosphorylation activity of c-Jun, p-65-NF-κB, and Akt. Our findings revealed that RA-RF has antioxidant, anti-inflammatory, and anti-metastasis properties via c-Jun, p-65-NF-κB, and Akt signaling pathways. RA-RF may be further developed as an inhalation agent for the prevention of lung inflammation and cancer metastasis induced by PM exposure.
High-Density Lipoproteins and Cardiovascular Disease: The Good, the Bad and the Future
Authors: Julve Josep , Escolà-Gil Joan Carles
Published: July 2021

Epidemiological studies have shown that low levels of plasma high-density lipoprotein cholesterol (HDL-C) are associated with increased atherosclerotic cardiovascular disease (CVD) [...]
TNBC: Potential Targeting of Multiple Receptors for a Therapeutic Breakthrough, Nanomedicine, and Immunotherapy
Authors: Singh Desh Deepak , Yadav Dharmendra Kumar
Published: July 2021

Triple-negative breast cancer (TNBC) is a heterogeneous, recurring cancer associated with a high rate of metastasis, poor prognosis, and lack of therapeutic targets. Although target-based therapeutic options are approved for other cancers, only limited therapeutic options are available for TNBC. Cell signaling and receptor-specific targets are reportedly effective in patients with TNBC under specific clinical conditions. However, most of these cancers are unresponsive, and there is a requirement for more effective treatment modalities. Further, there is a lack of effective biomarkers that can distinguish TNBC from other BC subtypes. ER, PR, and HER2 help identify TNBC and are widely used to identify patients who are most likely to respond to diverse therapeutic strategies. In this review, we discuss the possible treatment options for TNBC based on its inherent subtype receptors and pathways, such as p53 signaling, AKT signaling, cell cycle regulation, DNA damage, and programmed cell death, which play essential roles at multiple stages of TNBC development. We focus on poly-ADP ribose polymerase 1, androgen receptor, vascular endothelial growth factor receptor, and epidermal growth factor receptor as well as the application of nanomedicine and immunotherapy in TNBC and discuss their potential applications in drug development for TNBC.
Good Statistical Practices for Contemporary Meta-Analysis: Examples Based on a Systematic Review on COVID-19 in Pregnancy
Authors: Zhao Yuxi , Lin Lifeng
Published: July 2021

Systematic reviews and meta-analyses have been increasingly used to pool research findings from multiple studies in medical sciences. The reliability of the synthesized evidence depends highly on the methodological quality of a systematic review and meta-analysis. In recent years, several tools have been developed to guide the reporting and evidence appraisal of systematic reviews and meta-analyses, and much statistical effort has been paid to improve their methodological quality. Nevertheless, many contemporary meta-analyses continue to employ conventional statistical methods, which may be suboptimal compared with several alternative methods available in the evidence synthesis literature. Based on a recent systematic review on COVID-19 in pregnancy, this article provides an overview of select good practices for performing meta-analyses from statistical perspectives. Specifically, we suggest meta-analysts (1) providing sufficient information of included studies, (2) providing information for reproducibility of meta-analyses, (3) using appropriate terminologies, (4) double-checking presented results, (5) considering alternative estimators of between-study variance, (6) considering alternative confidence intervals, (7) reporting prediction intervals, (8) assessing small-study effects whenever possible, and (9) considering one-stage methods. We use worked examples to illustrate these good practices. Relevant statistical code is also provided. The conventional and alternative methods could produce noticeably different point and interval estimates in some meta-analyses and thus affect their conclusions. In such cases, researchers should interpret the results from conventional methods with great caution and consider using alternative methods.
An Overview of Artificial Olfaction Systems with a Focus on Surface Plasmon Resonance for the Analysis of Volatile Organic Compounds
Authors: El Kazzy Marielle , Weerakkody Jonathan S. , Hurot Charlotte , Mathey Raphaël , Buhot Arnaud , Scaramozzino Natale , Hou Yanxia
Published: July 2021

The last three decades have witnessed an increasing demand for novel analytical tools for the analysis of gases including odorants and volatile organic compounds (VOCs) in various domains. Traditional techniques such as gas chromatography coupled with mass spectrometry, although very efficient, present several drawbacks. Such a context has incited the research and industrial communities to work on the development of alternative technologies such as artificial olfaction systems, including gas sensors, olfactory biosensors and electronic noses (eNs). A wide variety of these systems have been designed using chemiresistive, electrochemical, acoustic or optical transducers. Among optical transduction systems, surface plasmon resonance (SPR) has been extensively studied thanks to its attractive features (high sensitivity, label free, real-time measurements). In this paper, we present an overview of the advances in the development of artificial olfaction systems with a focus on their development based on propagating SPR with different coupling configurations, including prism coupler, wave guide, and grating.
The Neural Bases of Egocentric Spatial Representation for Extracorporeal and Corporeal Tasks: An fMRI Study
Authors: Leplaideur Stephanie , Moulinet-Raillon Annelise , Duché Quentin , Chochina Lucie , Jamal Karim , Ferré Jean-Christophe , Bannier Elise , Bonan Isabelle
Published: July 2021

(1) Background: Humans use reference frames to elaborate the spatial representations needed for all space-oriented behaviors such as postural control, walking, or grasping. We investigated the neural bases of two egocentric tasks: the extracorporeal subjective straight-ahead task (SSA) and the corporeal subjective longitudinal body plane task (SLB) in healthy participants using functional magnetic resonance imaging (fMRI). This work was an ancillary part of a study involving stroke patients. (2) Methods: Seventeen healthy participants underwent a 3T fMRI examination. During the SSA, participants had to divide the extracorporeal space into two equal parts. During the SLB, they had to divide their body along the midsagittal plane. (3) Results: Both tasks elicited a parieto-occipital network encompassing the superior and inferior parietal lobules and lateral occipital cortex, with a right hemispheric dominance. Additionally, the SLB > SSA contrast revealed activations of the left angular and premotor cortices. These areas, involved in attention and motor imagery suggest a greater complexity of corporeal processes engaging body representation. (4) Conclusions: This was the first fMRI study to explore the SLB-related activity and its complementarity with the SSA. Our results pave the way for the exploration of spatial cognitive impairment in patients.
Reorganization of the Social Brain in Individuals with Only One Intact Cerebral Hemisphere
Authors: Kliemann Dorit , Adolphs Ralph , Paul Lynn K. , Tyszka J. Michael , Tranel Daniel
Published: July 2021

Social cognition and emotion are ubiquitous human processes that recruit a reliable set of brain networks in healthy individuals. These brain networks typically comprise midline (e.g., medial prefrontal cortex) as well as lateral regions of the brain including homotopic regions in both hemispheres (e.g., left and right temporo-parietal junction). Yet the necessary roles of these networks, and the broader roles of the left and right cerebral hemispheres in socioemotional functioning, remains debated. Here, we investigated these questions in four rare adults whose right (three cases) or left (one case) cerebral hemisphere had been surgically removed (to a large extent) to treat epilepsy. We studied four closely matched healthy comparison participants, and also compared the patient findings to data from a previously published larger healthy comparison sample (n = 33). Participants completed standardized socioemotional and cognitive assessments to investigate social cognition. Functional magnetic resonance imaging (fMRI) data were obtained during passive viewing of a short, animated movie that distinctively recruits two social brain networks: one engaged when thinking about other agents’ internal mental states (e.g., beliefs, desires, emotions; so-called Theory of Mind or ToM network), and the second engaged when thinking about bodily states (e.g., pain, hunger; so-called PAIN network). Behavioral assessments demonstrated remarkably intact general cognitive functioning in all individuals with hemispherectomy. Social-emotional functioning was somewhat variable in the hemispherectomy participants, but strikingly, none of these individuals had consistently impaired social-emotional processing and none of the assessment scores were consistent with a psychiatric disorder. Using inter-region correlation analyses, we also found surprisingly typical ToM and PAIN networks, as well as typical differentiation of the two networks (in the intact hemisphere of patients with either right or left hemispherectomy), based on idiosyncratic reorganization of cortical activation. The findings argue that compensatory brain networks can process social and emotional information following hemispherectomy across different age levels (from 3 months to 20 years old), and suggest that social brain networks typically distributed across midline and lateral brain regions in this domain can be reorganized, to a substantial degree.
Differential NPY-Y1 Receptor Density in the Motor Cortex of ALS Patients and Familial Model of ALS
Authors: Clark Courtney M. , Clark Rosemary M. , Hoyle Joshua A. , Chuckowree Jyoti A. , McLean Catriona A. , Dickson Tracey C.
Published: July 2021

Destabilization of faciliatory and inhibitory circuits is an important feature of corticomotor pathology in amyotrophic lateral sclerosis (ALS). While GABAergic inputs to upper motor neurons are reduced in models of the disease, less understood is the involvement of peptidergic inputs to upper motor neurons in ALS. The neuropeptide Y (NPY) system has been shown to confer neuroprotection against numerous pathogenic mechanisms implicated in ALS. However, little is known about how the NPY system functions in the motor system. Herein, we investigate post-synaptic NPY signaling on upper motor neurons in the rodent and human motor cortex, and on cortical neuron populations in vitro. Using immunohistochemistry, we show the increased density of NPY-Y1 receptors on the soma of SMI32-positive upper motor neurons in post-mortem ALS cases and SOD1G93A excitatory cortical neurons in vitro. Analysis of receptor density on Thy1-YFP-H-positive upper motor neurons in wild-type and SOD1G93A mouse tissue revealed that the distribution of NPY-Y1 receptors was changed on the apical processes at early-symptomatic and late-symptomatic disease stages. Together, our data demonstrate the differential density of NPY-Y1 receptors on upper motor neurons in a familial model of ALS and in ALS cases, indicating a novel pathway that may be targeted to modulate upper motor neuron activity.
Increased Vocalization of Rats in Response to Ultrasonic Playback as a Sign of Hypervigilance Following Fear Conditioning
Authors: Olszyński Krzysztof H. , Polowy Rafał , Wardak Agnieszka D. , Grymanowska Aneta W. , Filipkowski Robert K.
Published: July 2021

We investigated the effects of prior stress on rats’ responses to 50-kHz (appetitive) and 22-kHz (aversive) ultrasonic playback. Rats were treated with 0, 1, 6 or 10 shocks (1 s, 1.0 mA each) and were exposed to playbacks the following day. Previous findings were confirmed: (i) rats moved faster during 50-kHz playback and slowed down after 22-kHz playback; (ii) they all approached the speaker, which was more pronounced during and following 50-kHz playback than 22-kHz playback; (iii) 50-kHz playback caused heart rate (HR) increase; 22-kHz playback caused HR decrease; (iv) the rats vocalized more often during and following 50-kHz playback than 22-kHz playback. The previous shock affected the rats such that singly-shocked rats showed lower HR throughout the experiment and a smaller HR response to 50-kHz playback compared to controls and other shocked groups. Interestingly, all pre-shocked rats showed higher locomotor activity during 50-kHz playback and a more significant decrease in activity following 22-kHz playback; they vocalized more often, their ultrasonic vocalizations (USV) were longer and at a higher frequency than those of the control animals. These last two observations could point to hypervigilance, a symptom of post-traumatic stress disorder (PTSD) in human patients. Increased vocalization may be a valuable measure of hypervigilance used for PTSD modeling.
Wooden Additional Floors in Old Apartment Buildings: Perspectives of Housing and Real Estate Companies from Finland
Authors: Karjalainen Markku , Ilgın Hüseyin , Somelar Dennis
Published: July 2021

This paper examined various stages and advantages of wooden additional floors from the perspective of Finnish housing and real estate companies through interviews with professionals involved in these projects. Main findings highlighted: (1) commercial conditions should be carefully analyzed for return on investment; (2) city plan change and the presence of a potential contractor and an expert were generally considered important issues; (3) considerations regarding city planning, parking spaces, load-carrying capacity, and new building codes were highlighted as critical factors for feasibility study; (4) existing building regulations and building rights regarding the subscription fee and tax issues should be considered during project planning; (5) city plan change and building rights with different tendering conditions were reported as important parameters in implementation planning; (6) an efficient flow of information between the parties involved was vital to the successful progress of the construction phase. Wooden additional floor construction, which requires commitment, investment, and cooperation between interested parties, has great potential regarding construction technology and contracting mechanisms. Additionally, this sustainable approach has many advantages concerning the environment, economy, energy efficiency, and aesthetics. In this sense, it is believed that this study will contribute to the diffusion of wooden additional floor construction in other countries besides Finland.
Anastasis: Return Journey from Cell Death
Authors: Zaitceva Victoria , Kopeina Gelina S. , Zhivotovsky Boris
Published: July 2021

For over 20 years, it has been a dogma that once the integrity of mitochondria is disrupted and proapoptotic proteins that are normally located in the intermembrane space of mitochondria appeared in the cytoplasm, the process of cell death becomes inevitable. However, it has been recently shown that upon removal of the death signal, even at the stage of disturbance in the mitochondria, cells can recover and continue to grow. This phenomenon was named anastasis. Here, we will critically discuss the present knowledge concerning the mechanisms of cell death reversal, or development of anastasis, methods for its detection, and what role signaling from different intracellular compartments plays in anastasis stimulation.
Optimization of New Catalytic Topoisomerase II Inhibitors as an Anti-Cancer Therapy
Authors: Matias-Barrios Victor M. , Radaeva Mariia , Ho Chia-Hao , Lee Joseph , Adomat Hans , Lallous Nada , Cherkasov Artem , Dong Xuesen
Published: July 2021

Clinically used topoisomerase II (TOP2) inhibitors are poison inhibitors that induce DNA damage to cause cancer cell death. However, they can also destroy benign cells and thereby show serious side effects, including cardiotoxicity and drug-induced secondary malignancy. New TOP2 inhibitors with a different mechanism of action (MOA), such as catalytic TOP2 inhibitors, are needed to more effectively control tumor growth. We have applied computer-aided drug design to develop a new group of small molecule inhibitors that are derivatives of our previously identified lead compound T60. Particularly, the compound T638 has shown improved solubility and microsomal stability. It is a catalytic TOP2 inhibitor that potently suppresses TOP2 activity. T638 has a novel MOA by which it binds TOP2 proteins and blocks TOP2–DNA interaction. T638 strongly inhibits cancer cell growth, but exhibits limited genotoxicity to cells. These results indicate that T638 is a promising drug candidate that warrants further development into clinically used anticancer drugs.
PlasmiR: A Manual Collection of Circulating microRNAs of Prognostic and Diagnostic Value
Authors: Tastsoglou Spyros , Miliotis Marios , Kavakiotis Ioannis , Alexiou Athanasios , Gkotsi Eleni C. , Lambropoulou Anastasia , Lygnos Vasileios , Kotsira Vasiliki , Maroulis Vasileios , Zisis Dimitrios , Skoufos Giorgos , Hatzigeorgiou Artemis G.
Published: July 2021

Only recently, microRNAs (miRNAs) were found to exist in traceable and distinctive amounts in the human circulatory system, bringing forth the intriguing possibility of using them as minimally invasive biomarkers. miRNAs are short non-coding RNAs that act as potent post-transcriptional regulators of gene expression. Extensive studies in cancer and other disease landscapes investigate the protective/pathogenic functions of dysregulated miRNAs, as well as their biomarker potential. A specialized resource amassing experimentally verified, circulating miRNA biomarkers does not exist. We queried the existing literature to identify articles assessing diagnostic/prognostic roles of miRNAs in blood, serum, or plasma samples. Articles were scrutinized in order to exclude instances lacking sufficient experimental documentation or employing no biomarker assessment methods. We incorporated information from more than 200 biomedical articles, annotating crucial meta-information including cohort sizes, inclusion-exclusion criteria, disease/healthy confirmation methods and quantification details. miRNAs and diseases were systematically characterized using reference resources. Our circulating miRNA biomarker collection is provided as an online database, plasmiR. It consists of 1021 entries regarding 251 miRNAs and 112 diseases. More than half of plasmiR’s entries refer to cancerous and neoplastic conditions, 183 of them (32%) describing prognostic associations. plasmiR facilitates smart queries, emphasizing visualization and exploratory modes for all researchers.
Transcriptome Profiling and Metagenomic Analysis Help to Elucidate Interactions in an Inflammation-Associated Cancer Mouse Model
Authors: Sakai Kazuko , De Velasco Marco A. , Kura Yurie , Nishio Kazuto
Published: July 2021

Colitis is a risk factor for colorectal cancer (CRC) and can change the dynamics of gut microbiota, leading to dysbiosis and contributing to carcinogenesis. The functional interactions between colitis-associated CRC and microbiota remain unknown. In this study, colitis and CRC were induced in BALB/c mice by the administration of dextran sodium sulfate (DSS) and/or azoxymethane (AOM). Whole transcriptome profiling of normal colon was then performed, and gene set enrichment analysis (GSEA) revealed enriched fatty acid metabolism, oxidative phosphorylation, and PI3K-Akt-mTOR signaling in the tissues from DSS/AOM mice. Additionally, immunohistochemical staining showed increased expression levels of phosphorylated S6 ribosomal protein, a downstream target of the PI3K-Akt-mTOR pathway in the inflamed mucosa of DSS/AOM mice. Fecal microbes were characterized using 16S rDNA gene sequencing. Redundancy analysis demonstrated a significant dissimilarity between the DSS/AOM group and the others. Functional analysis inferred from microbial composition showed enrichments of the sphingolipid signal and lipoarabinomannan biosynthetic pathways. This study provides additional insights into alterations associated with DSS/AOM-induced colitis and associates PI3K-Akt-mTOR, sphingolipid-signaling and lipoarabinomannan biosynthetic pathways in mouse DSS/AOM-induced colitis.
Lobular Breast Cancer: Histomorphology and Different Concepts of a Special Spectrum of Tumors
Authors: Christgen Matthias , Cserni Gábor , Floris Giuseppe , Marchio Caterina , Djerroudi Lounes , Kreipe Hans , Derksen Patrick W. B. , Vincent-Salomon Anne
Published: July 2021

Invasive lobular breast cancer (ILC) is the most common special histological type of breast cancer (BC). This review recapitulates developments in the histomorphologic assessment of ILC from its beginnings with the seminal work of Foote and Stewart, which was published in 1941, until today. We discuss different concepts of ILC and their implications. These concepts include (i) BC arising from mammary lobules, (ii) BC growing in dissociated cells and single files, and (iii) BC defined as a morpho-molecular spectrum of tumors with distinct histological and molecular characteristics related to impaired cell adhesion. This review also provides a comprehensive overview of ILC variants, their histomorphology, and differential diagnosis. Furthermore, this review highlights recent advances which have contributed to a better understanding of the histomorphology of ILC, such as the role of the basal lamina component laminin, the molecular specificities of triple-negative ILC, and E-cadherin to P-cadherin expression switching as the molecular determinant of tubular elements in CDH1-deficient ILC. Last but not least, we provide a detailed account of the tumor microenvironment in ILC, including tumor infiltrating lymphocyte (TIL) levels, which are comparatively low in ILC compared to other BCs, but correlate with clinical outcome. The distinct histomorphology of ILC clearly reflects a special tumor biology. In the clinic, special treatment strategies have been established for triple-negative, HER2-positive, and ER-positive BC. Treatment specialization for patients diagnosed with ILC is just in its beginnings. Accordingly, ILC deserves greater attention as a special tumor entity in BC diagnostics, patient care, and cancer research.
Targeted Oral Delivery of Paclitaxel Using Colostrum-Derived Exosomes
Authors: Kandimalla Raghuram , Aqil Farrukh , Alhakeem Sara S. , Jeyabalan Jeyaprakash , Tyagi Neha , Agrawal Ashish , Yan Jun , Spencer Wendy , Bondada Subbarao , Gupta Ramesh C.
Published: July 2021

Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small-cell lung cancer (NSCLC) is the most common type accounting for 84% of all lung cancers. Paclitaxel (PAC) is a widely used drug in the treatment of a broad spectrum of human cancers, including lung. While efficacious, PAC generally is not well tolerated and its limitations include low aqueous solubility, and significant toxicity. To overcome the dose-related toxicity of solvent-based PAC, we utilized bovine colostrum-derived exosomes as a delivery vehicle for PAC for the treatment of lung cancer. Colostrum provided higher yield of exosomes and could be loaded with higher amount of PAC compared to mature milk. Exosomal formulation of PAC (ExoPAC) showed higher antiproliferative activity and inhibition of colony formation against A549 cells compared with PAC alone, and also showed antiproliferative activity against a drug-resistant variant of A549. To further enhance its efficacy, exosomes were attached with a tumor-targeting ligand, folic acid (FA). FA-ExoPAC given orally showed significant inhibition (>50%) of subcutaneous tumor xenograft while similar doses of PAC showed insignificant inhibition. In the orthotopic lung cancer model, oral dosing of FA-ExoPAC achieved greater efficacy (55% growth inhibition) than traditional i.v. PAC (24–32% growth inhibition) and similar efficacy as i.v. Abraxane (59% growth inhibition). The FA-ExoPAC given i.v. exceeded the therapeutic efficacy of Abraxane (76% growth inhibition). Finally, wild-type animals treated with p.o. ExoPAC did not show gross, systemic or immunotoxicity. Solvent-based PAC caused immunotoxicity which was either reduced or completely mitigated by its exosomal formulations. These studies show that a tumor-targeted oral formulation of PAC (FA-ExoPAC) significantly improved the overall efficacy and safety profile while providing a user-friendly, cost-effective alternative to bolus i.v. PAC and i.v. Abraxane.
Serum sCD25 Protein as a Predictor of Lack of Long-Term Benefits from Immunotherapy in Non-Small Cell Lung Cancer: A Pilot Study
Authors: Siemiątkowska Anna , Bryl Maciej , Kosicka-Noworzyń Katarzyna , Tvrdoň Jakub , Gołda-Gocka Iwona , Barinow-Wojewódzki Aleksander , Główka Franciszek K.
Published: July 2021

Prognosis of advanced non-small cell lung carcinoma (NSCLC) is poor. Even though it can improve with anti-PD-1/PD-L1 agents, most patients do not respond to treatment. We hypothesized that the serum soluble form of the unit α of the interleukin-2 receptor (sCD25) could be used as a biomarker of successful immunotherapy in NSCLC. We recruited patients dosed with atezolizumab (n = 42) or pembrolizumab (n = 20) and collected samples at baseline and during the treatment. Levels of sCD25 were quantified with the ELISA kits. Patients with a high sCD25 at baseline (sCD25.0 ≥ 5.99 ng/mL) or/and at the end of the fourth treatment cycle (sCD25.4 ≥ 7.73 ng/mL) progressed faster and lived shorter without the disease progression and serious toxicity. None of the patients with high sCD25 at both time points continued therapy longer than 9.3 months, while almost 40% of patients with low sCD25 were treated for ≥12.3 months. There was a 6.3-times higher incidence of treatment failure (HR = 6.33, 95% CI: 2.10–19.06, p = 0.001) and a 6.5-times higher incidence of progression (HR = 6.50, 95% CI: 2.04–20.73, p = 0.002) in patients with high compared with low sCD25.0 and sCD25.4. Serum levels of sCD25 may serve as a non-invasive biomarker of long-term benefits from the anti-PD-1/PD-L1s in NSCLC.