bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics and Potential Inhalation Exposure Risks of Environmentally Persistent Free Radicals in Atmospheric Particulate Matter and Solid Fuel Combustion Particles in High Lung Cancer Incidence Area, China
Authors: Xiao Kai , Lin Yichun , Wang Qingyue , Lu Senlin , Wang Weiqian , Chowdhury Tanzin , Enyoh Christian Ebere , Rabin Mominul Haque
Published: November 2021

Environmentally persistent free radicals (EPFRs) were previously considered an unrecognized composition of air pollutants and might help explain the long-standing medical mystery of why non-smokers develop tobacco-related diseases such as lung cancer. However, there is no investigated on EPFRs in Xuanwei rural areas, especially in high prevalence of lung cancer areas. In this study, we selected six types of coal and three types of biomass in Xuanwei, then conducted simulated combustion, and six group of atmospheric particulate matters (APMs) to explore the content and particle size distribution pattern of EPFRs and a new health risk assessment method to evaluate the risk of EPFRs in PM for adults and children. Our results show that the contribution of EPFRs for biomass combustion, coal combustion and APMs were mainly distributed in the size range of <1.1 μm, which accounted for 76.15 ± 4.14%, 74.85 ± 10.76%, and 75.23 ± 8.18% of PM3.3. The mean g factors and ΔHp-p indicated that the EPFRs were mainly oxygen-centered radicals in PM in Xuanwei. The results suggest that the health risk of EPFRs is significantly increased when the particle size distribution of EPFRs is taken into account, and coal combustion particulate matter (174.70 ± 37.86 cigarettes for an adult, 66.39 ± 14.39 cigarettes per person per year for a child) is more hazardous to humans than biomass combustion particulate matter (69.41 ± 4.83 cigarettes for an adult, 26.37 ± 1.84 cigarettes per person per year for), followed by APMs (102.88 ± 39.99 cigarettes for an adult, 39.10 ±15.20 cigarettes per person per year for) in PM3.3. Our results provides a new perspective and evidence for revealing the reason for the high incidence of lung cancer in Xuanwei, China.
Tropospheric Refractivity Profile Estimation by GNSS Measurement at China Big-Triangle Points
Authors: Dong Xiang , Sun Fang , Zhu Qinglin , Lin Leke , Zhao Zhenwei , Zhou Chen
Published: November 2021

Atmospheric radio refractivity has an obvious influence on the signal transmission path and communication group delay effect. The uncertainty of water vapor distribution is the main reason for the large error of tropospheric refractive index modeling. According to the distribution and characteristics of water vapor pressure, temperature, and pressure, which are the basic components of the refractive index, a method for retrieving atmospheric refractivity profile based on GNSS (Global Navigation Satellite System) and meteorological sensor measurement is introduced and investigated in this study. The variation of the correlation between zenith wet delay and water vapor pressure is investigated and analyzed in detail. The partial pressure profiles of water vapor are retrieved with relevance vector machine method based on tropospheric zenith wet delay calculated by single ground-based GPS (Global Positioning System) receiver. The atmospheric temperature and pressure is calculated with the least square method, which is used to fit the coefficients of the polynomial model based on a large number of historical meteorological radiosonde data of local stations. By combining the water vapor pressure profile retrieving from single ground-based GPS and temperature and pressure profile from reference model, the refractivity profile can be obtained, which is compared to radiosonde measurements. The comparison results show that results of the proposed method are consistent with the results of radiosonde. By using over ten years’ (through 2008 to 2017) historical radiosonde meteorological data of different months at China Big-Triangle Points, i.e., Qingdao, Sanya, Kashi, and Jiamusi radiosonde stations, tropospheric radio refractivity profiles are retrieved and modeled. The comparison results present that the accuracies of refractivity profile of the proposed method at Qingdao, Sanya, Kashi, and Jiamusi are about 5.48, 5.63, 3.58, and 3.78 N-unit, respectively, and the annual average relative RMSE of refractivity at these stations are about 1.66, 1.53, 1.49, and 1.23%, respectively.
The Impact of Intense Winter Saharan Dust Events on PM and Optical Properties at Urban Sites in the Southeast of the Iberian Peninsula
Authors: López-Caravaca Alba , Castañer Ramón , Clemente Alvaro , Yubero Eduardo , Galindo Nuria , Crespo Javier , Nicolás Jose Francisco
Published: November 2021

The influence of three Saharan dust events (SDE) on particulate matter (PM) concentrations and aerosol optical properties (AOP) during February 2021 was studied. The physical characteristics of the African aerosol were different for each episode. Therefore, the impacts of the three events on PM and AOP were analyzed separately. The monitoring sites were placed in Elche, in the southeast of the Iberian Peninsula. The sites can be classified as urban background locations. The procedure used to obtain the contribution of SDE to PM10 mass concentrations was the 40th percentile method. Nearly half of the days during the study period were under the influence of Saharan air masses. The average contribution of mineral dust (MD) to the PM10 mean concentration was ~50%, which was the highest contribution during the month of February in the last 14 years. The results show that those events characterized by a high input of fine particles (PM1 and PM2.5) caused larger increases in the absorption (σap) and scattering (σsp) coefficients than SDE in which coarse particles predominated. Nevertheless, as expected, SAE (Scattering Angström Exponent) values were lowest during these episodes. AAE (Absorption Angström Exponent) values during SDE were slightly higher than those observed in the absence of African dust, suggesting some contribution from MD to the absorption process.
Numerical Modeling of Ozone Loss in the Exceptional Arctic Stratosphere Winter–Spring of 2020
Authors: Smyshlyaev Sergey P. , Vargin Pavel N. , Motsakov Maksim A.
Published: November 2021

Dynamical processes and changes in the ozone layer in the Arctic stratosphere during the winter of 2019–2020 were analyzed using numerical experiments with a chemistry-transport model (CTM) and reanalysis data. The results of numerical calculations using CTM with Dynamic parameters specified from the Modern Era Retrospective analysis for Research and Applications, version 2 (MERRA-2) reanalysis data, carried out according to several scenarios of accounting for the chemical destruction of ozone, demonstrated that both Dynamic and chemical processes contribute significantly to ozone changes over the selected World Ozone and Ultraviolet Radiation Data Centre network stations, both in the Eastern and in the Western hemispheres. Based on numerical experiments with the CTM, the specific Dynamic conditions of winter–spring 2019–2020 described a decrease in ozone up to 100 Dobson Units (DU) in the Eastern Hemisphere and over 150 DU in the Western Hemisphere. In this case, the photochemical destruction of ozone in both the Western and Eastern Hemispheres at a maximum was about 50 DU with peaks in April in the Eastern Hemisphere and in March and April in the Western Hemisphere. Heterogeneous activation of halogen gases on the surface of polar stratospheric clouds, on the one hand, led to a sharp increase in the destruction of ozone in chlorine and bromine catalytic cycles, and, on the other hand, decreased its destruction in nitrogen catalytic cycles. Analysis of wave activity using 3D Plumb fluxes showed that the enhancement of upward wave activity propagation in the middle of March over the Gulf of Alaska was observed during the development stage of the minor sudden stratospheric warming (SSW) event that led to displacement of the stratospheric polar vortex to the north of Canada and decrease of polar stratospheric clouds’ volume.
Estimating the Impact of Global Warming on Aircraft Takeoff Performance in China
Authors: Yuan Wei , Dai Panxi , Xu Mengxiang , Song Wei , Zhang Peng
Published: November 2021

Aviation operations are significantly affected by weather conditions, such as high-temperature days. Under global warming, rising temperatures decrease the air density and thus, reduce the maximum takeoff weight of an aircraft. In this study, we investigate the impact of global warming on the aircraft takeoff performance in 53 airports in China by combining observational data and CMIP6 climate projections. There is a distinct geographic inhomogeneity of critical temperature, above which the takeoff weight decreases significantly with the increasing air temperature, mostly due to differences in airport elevations. By the end of the century, under the SSP5-8.5 scenario (with average warming of 5.2 °C in China), the daily maximum temperature for nearly all summer days in West China and for about half of the summer days in East China exceeds critical temperature, indicating that frequent weight restriction will be necessary. We further examine the reduction in carrying capacity due to climate change. By the end of the century, under the SSP5-8.5 scenario, the summer total carrying capacity will be reduced by about 2.8% averaged over all 53 airports. The impacts on airports in West China are nearly four times greater than those in East China, due to the higher vulnerability and stronger warming in West China.
Effect of Air Heat Pump Cooling System as a Greener Energy Source on the Air Quality, Housing Environment and Growth Performance in Pig House
Authors: Rathnayake Dhanushka , Mun Hong-Seok , Dilawar Muhammad Ammar , Chung Il-Byung , Park Kwang-Woo , Lee Sang-Ro , Yang Chul-Ju
Published: November 2021

The present study examined the cooling effects of an air heat pump (AHP) system. An AHP system was installed in a pig house to compare the effects with a traditional cooling system on the growth performance, noxious gas emission, housing environment and consumption of electricity. During the 19-week experimental trial, the internal temperature in the AHP cooling system-connected pig house was significantly decreased (p < 0.05) than the conventional house. Similarly, the temperature–humidity index (THI) was significantly reduced (p < 0.05) in the growing and late finishing period. The carbon dioxide (CO2) and electricity consumption were also reduced significantly in the AHP cooling system relative to the control. The concentration of ammonia (NH3) during the weaning and finishing phase and the concentration of hydrogen sulfide (H2S) during all periods were lower in the AHP-installed pig house (p < 0.05). From 0–19 weeks, there was no significant difference was observed (p > 0.05) in terms of the growth performance of pigs in both houses. These results show that the AHP cooling system can be implemented as an environmentally friendly renewable energy source in swine farms for sustainable pig production and better air quality without adversely affecting productivity parameters.
New Integral Inequalities via Generalized Preinvex Functions
Authors: Tariq Muhammad , Shaikh Asif Ali , Sahoo Soubhagya Kumar , Ahmad Hijaz , Sitthiwirattham Thanin , Reunsumrit Jiraporn
Published: November 2021

The theory of convexity plays an important role in various branches of science and engineering. The objective of this paper is to introduce a new notion of preinvex functions by unifying the n-polynomial preinvex function with the s-type m–preinvex function and to present inequalities of the Hermite–Hadamard type in the setting of the generalized s-type m–preinvex function. First, we give the definition and then investigate some of its algebraic properties and examples. We also present some refinements of the Hermite–Hadamard-type inequality using Hölder’s integral inequality, the improved power-mean integral inequality, and the Hölder-İşcan integral inequality. Finally, some results for special means are deduced. The results established in this paper can be considered as the generalization of many published results of inequalities and convexity theory.
Perovskite Solid-State Electrolytes for Lithium Metal Batteries
Authors: Yan Shuo , Yim Chae-Ho , Pankov Vladimir , Bauer Mackenzie , Baranova Elena , Weck Arnaud , Merati Ali , Abu-Lebdeh Yaser
Published: November 2021

Solid-state lithium metal batteries (LMBs) have become increasingly important in recent years due to their potential to offer higher energy density and enhanced safety compared to conventional liquid electrolyte-based lithium-ion batteries (LIBs). However, they require highly functional solid-state electrolytes (SSEs) and, therefore, many inorganic materials such as oxides of perovskite La2/3−xLi3xTiO3 (LLTO) and garnets La3Li7Zr2O12 (LLZO), sulfides Li10GeP2S12 (LGPS), and phosphates Li1+xAlxTi2−x(PO4)3x (LATP) are under investigation. Among these oxide materials, LLTO exhibits superior safety, wider electrochemical window (8 V vs. Li/Li+), and higher bulk conductivity values reaching in excess of 10−3 S cm−1 at ambient temperature, which is close to organic liquid-state electrolytes presently used in LIBs. However, recent studies focus primarily on composite or hybrid electrolytes that mix LLTO with organic polymeric materials. There are scarce studies of pure (100%) LLTO electrolytes in solid-state LMBs and there is a need to shed more light on this type of electrolyte and its potential for LMBs. Therefore, in our review, we first elaborated on the structure/property relationship between compositions of perovskites and their ionic conductivities. We then summarized current issues and some successful attempts for the fabrication of pure LLTO electrolytes. Their electrochemical and battery performances were also presented. We focused on tape casting as an effective method to prepare pure LLTO thin films that are compatible and can be easily integrated into existing roll-to-roll battery manufacturing processes. This review intends to shed some light on the design and manufacturing of LLTO for all-ceramic electrolytes towards safer and higher power density solid-state LMBs.
Response of Annual Herbaceous Plant Leaching and Decomposition to Periodic Submergence in Mega-Reservoirs: Changes in Litter Nutrients and Soil Properties for Restoration
Authors: Hu Xin , Xie Tingting , Arif Muhammad , Ding Dongdong , Li Jiajia , Yuan Zhongxun , Li Changxiao
Published: November 2021

Litter decomposition is an important soil nutrient source that promotes vegetation in deteriorated riparian zones worldwide. The periodic submergence and sediment burial effects on two prominent annual herbaceous plants (Echinochloa crusgali and Bidens tripartite) are little known in mega-reservoir settings. Our study focuses on the mass and carbon loss and nutrient release from E. crusgali and B. tripartitle litter and changes in soil properties, which are important for riparian zone rehabilitation in the Three Gorges Dam Reservoir, China. This study adopted the litter bag method to explore the nutrient change characteristics and changes in soil properties at different sediment burial depths under flooding scenarios. Three burial depths (0 cm, 5 cm, and 10 cm) were used for these two plants, and the experiment lasted for 180 days. The results revealed that the litter decay rate was high at first in the incubation experiment, and the nutrient loss rate followed the pattern of K > P > N > C. The relationship between % C remaining and % mass remaining was nearly 1:1, and the total amount of P exhibited a leaching–enrichment–release state in the decomposition process. Nutrients were changed significantly in the soil and overlying water at the first decomposition stage. Still, the total soil nutrient change was insignificant at the end, except for the 10 cm burial of B. tripartitle. Moreover, oxidation–reduction potential was the main factor in the litter decomposition process at different burial depths. This study indicated that sediment deposition reduced litter mass loss, slowed down the release of N and P, and retained more C, but promoted the release of K. Conclusively, in litter decomposition under waterlogging, the total soil nutrient content changed little. However, litter does more to the soil than that. Therefore, it is necessary to study the residual soil litter’s continuous output after the water level declines for restoration purposes.
Emerging Status of Multidrug-Resistant Bacteria and Fungi in the Arabian Peninsula
Authors: Borgio J. Francis , Rasdan Alia Saeed , Sonbol Bayan , Alhamid Galyah , Almandil Noor B. , AbdulAzeez Sayed
Published: November 2021

We aimed to identify the prevalence and emerging status of multidrug-resistant bacteria and fungi and their associated mortality in nine countries in the Arabian Peninsula. Original research articles and case studies regarding multidrug-resistant bacteria and fungi in the Arabian Peninsula, published during the last 10 years, were retrieved from PubMed and Scopus. A total of 382 studies were included as per the inclusion and exclusion criteria, as well as the PRISMA guidelines, from a thorough screening of 1705 articles, in order to analyse the emerging status and mortality. The emerging nature of >120 multidrug-resistant (MDR) bacteria and fungi in the Arabian Peninsula is a serious concern that requires continuous monitoring and immediate preventive measures. More than 50% (n = 453) of multidrug-resistant, microbe-associated mortality (n = 871) in the Arabian Peninsula was due to MDR Acinetobacter baumannii, Mycobacterium tuberculosis and Staphylococcus aureus infection. Overall, a 16.51% mortality was reported among MDR-infected patients in the Arabian Peninsula from the 382 articles of this registered systematic review. MDR A. baumannii (5600 isolates) prevailed in all the nine countries of the Arabian Peninsula and was one of the fastest emerging MDR bacteria with the highest mortality (n = 210). A total of 13,087 Mycobacterium tuberculosis isolates were reported in the region. Candida auris (580 strains) is the most prevalent among the MDR fungal pathogen in the Arabian Peninsula, having caused 54 mortalities. Active surveillance, constant monitoring, the development of a candidate vaccine, an early diagnosis of MDR infection, the elimination of multidrug resistance modulators and uninterrupted preventive measures with enhanced data sharing are mandatory to control MDR infection and associated diseases of the Arabian Peninsula. Accurate and rapid detection methods are needed to differentiate MDR strain from other strains of the species. This review summarises the logical relation, prevalence, emerging status and associated mortality of MDR microbes in the Arabian Peninsula.
Humoral and Cellular Defense Mechanisms in Rebel Workers of Apis mellifera
Authors: Strachecka Aneta , Migdał Paweł , Kuszewska Karolina , Skowronek Patrycja , Grabowski Marcin , Paleolog Jerzy , Woyciechowski Michał
Published: November 2021

The physiological state of an insect depends on efficiently functioning immune mechanisms such as cellular and humoral defenses. However, compounds participating in these mechanisms also regulate reproductive caste formation and are responsible for reproductive division of labor as well as for labor division in sterile workers. Divergent reaction of the same genotype yielding reproductive queens and worker castes led to shaping of the physiological and behavioral plasticity of sterile or reproductive workers. Rebels that can lay eggs while maintaining tasks inside and outside the colony exhibit both queen and worker traits. So, we expected that the phagocytic index, JH3 titer, and Vg concentration would be higher in rebels than in normal workers and would increase with their age. We also assumed that the numbers of oenocytes and their sizes would be greater in rebels than in normal workers. The rebels and the normal workers were collected at the age of 1, 7, 14, and 21 days, respectively. Hemolymph and fat bodies were collected for biochemical and morphological analyses. The high levels of JH, Vg, and the phagocytic index, as well as increased numbers and sizes of oenocytes in the fat body cells demonstrate the physiological and phenotypic adaptation of rebels to the eusocial life of honeybees.
Internalized Nanoceria Modify the Radiation-Sensitivity Profile of MDA MB231 Breast Carcinoma Cells
Authors: Bibb Emory , Alajlan Noura , Alsuwailem Saad , Mitchell Benjamin , Brady Amy , Maqbool Muhammad , George Remo
Published: November 2021

Owing to its unique redox properties, cerium oxide (nanoceria) nanoparticles have been shown to confer either radiosensitization or radioprotection to human cells. We investigated nanoceria’s ability to modify cellular health and reactive oxygen species (ROS) at various absorbed doses (Gray) of ionizing radiation in MDA-MB231 breast carcinoma cells. We used transmission electron microscopy to visualize the uptake and compartmental localization of nanoceria within cells at various treatment concentrations. The effects on apoptosis and other cellular health parameters were assessed using confocal fluorescence imaging and flow cytometry without and with various absorbed doses of ionizing radiation, along with intracellular ROS levels. Our results showed that nanoceria were taken up into cells mainly by macropinocytosis and segregated into concentration-dependent large aggregates in macropinosomes. Confocal imaging and flow cytometry data showed an overall decrease in apoptotic cell populations in proportion to increasing nanoparticle concentrations. This increase in cellular health was observed with a corresponding reduction in ROS at all tested absorbed doses. Moreover, this effect appeared pronounced at lower doses compared to unirradiated or untreated populations. In conclusion, internalized nanoceria confers radioprotection with a corresponding decrease in ROS in MDA-MB231 cells, and this property confers significant perils and opportunities when utilized in the context of radiotherapy.
The Role of TGF-β in Bone Metastases
Authors: Trivedi Trupti , Pagnotti Gabriel M. , Guise Theresa A. , Mohammad Khalid S.
Published: November 2021

Complications associated with advanced cancer are a major clinical challenge and, if associated with bone metastases, worsen the prognosis and compromise the survival of the patients. Breast and prostate cancer cells exhibit a high propensity to metastasize to bone. The bone microenvironment is unique, providing fertile soil for cancer cell propagation, while mineralized bone matrices store potent growth factors and cytokines. Biologically active transforming growth factor β (TGF-β), one of the most abundant growth factors, is released following tumor-induced osteoclastic bone resorption. TGF-β promotes tumor cell secretion of factors that accelerate bone loss and fuel tumor cells to colonize. Thus, TGF-β is critical for driving the feed-forward vicious cycle of tumor growth in bone. Further, TGF-β promotes epithelial-mesenchymal transition (EMT), increasing cell invasiveness, angiogenesis, and metastatic progression. Emerging evidence shows TGF-β suppresses immune responses, enabling opportunistic cancer cells to escape immune checkpoints and promote bone metastases. Blocking TGF-β signaling pathways could disrupt the vicious cycle, revert EMT, and enhance immune response. However, TGF-β’s dual role as both tumor suppressor and enhancer presents a significant challenge in developing therapeutics that target TGF-β signaling. This review presents TGF-β’s role in cancer progression and bone metastases, while highlighting current perspectives on the therapeutic potential of targeting TGF-β pathways.
Similarities in DSG1 and KRT3 Downregulation through Retinoic Acid Treatment and PAX6 Knockdown Related Expression Profiles: Does PAX6 Affect RA Signaling in Limbal Epithelial Cells?
Authors: Latta Lorenz , Knebel Igor , Bleil Constanze , Stachon Tanja , Katiyar Priya , Zussy Claire , Fries Fabian Norbert , Käsmann-Kellner Barbara , Seitz Berthold , Szentmáry Nóra
Published: November 2021

Congenital PAX6-aniridia is a rare panocular disease resulting from limbal stem cell deficiency. In PAX6-aniridia, the downregulation of the retinol-metabolizing enzymes ADH7 (All-trans-retinol dehydrogenase 7) and ALDH1A1/A3 (Retinal dehydrogenase 1, Aldehyde dehydrogenase family 1 member A3) have been described in limbal epithelial cells (LECs) and conjunctival epithelial cells. The aim of this study was to identify the role of retinol derivates in the differentiation of human LEC and its potential impact on aniridia-associated keratopathy development. Human LEC were isolated from healthy donor corneas and were cultured with retinol, retinoic acid, or pan-retinoic acid receptor antagonist (AGN 193109) acting on RARα, β, γ (NR1B1, NR1B2 NR1B3) or were cultured with pan-retinoid X receptor antagonist (UVI 3003) acting on RXR α, β, γ (retinoid X receptor, NR2B1, NR2B2, BR2B3). Using qPCR, differentiation marker and retinoid-/fatty acid metabolism-related mRNA expression was analysed. DSG1 (Desmoglein 1), KRT3 (Keratin 3), and SPINK7 (Serine Peptidase Inhibitor Kazal Type 7) mRNA expression was downregulated when retinoid derivates were used. AGN 193109 treatment led to the upregulation of ADH7, KRT3, and DSG1 mRNA expression and to the downregulation of KRT12 (Keratin 12) and KRT19 (Keratin 19) mRNA expression. Retinol and all-trans retinoic acid affect some transcripts of corneal LEC in a similar way to what has been observed in the LEC of PAX6-aniridia patients with the altered expression of differentiation markers. An elevated concentration of retinol derivatives in LEC or an altered response to retinoids may contribute to this pattern. These initial findings help to explain ocular surface epithelia differentiation disorders in PAX6-aniridia and should be investigated in patient cells or in cell models in the future in more detail.
Analysis of Transition of Patients with Parkinson’s Disease into Institutional Care: A Retrospective Pilot Study
Authors: Jensen Ida , Lescher Emily , Stiel Stephanie , Wegner Florian , Höglinger Günter , Klietz Martin
Published: November 2021

Parkinson’s disease (PD) is a neurodegenerative disease which gives a person a high risk of becoming care-dependent. During disease progression, the amount of care concerning activities of daily living can increase, possibly resulting in transition of the people with Parkinson’s disease (PwP) to a care facility. However, there is a lack of knowledge concerning the factors leading to institutionalization of PwP and the consequences for them and their informal caregivers. The aim of this cross-sectional retrospective study was to investigate reasons leading to the transition into an institutional care facility, the process of decision-making and its effects on PwP symptoms and caregiver burden. Participating PwP had to be institutionalized for at most one year after transition at study inclusion. Participants completed a range of semiquantitative questionnaires as well as the caregiving tasks questionnaire. Fourteen patient–caregiver pairs were included. PwP suffered from late-stage PD symptoms with high dependence on help, experiencing several hospitalizations before transition. Analyses revealed a significant decrease in caregiver burden and depressive symptoms of the caregivers after PwP institutionalization. Factors influencing the transition were, e.g., fear of PwP health issues and concerns about caregivers’ health. This study presents new insights into the process of institutionalization and its influence on caregiver burden, including aspects for discussions of physicians with PwP and their caregivers for counselling the decision to move to institutional care.
Visual Short-Term Memory for Coherent and Sequential Motion: A rTMS Investigation
Authors: Pavan Andrea , Ghin Filippo , Campana Gianluca
Published: November 2021

We investigated the role of the human medio-temporal complex (hMT+) in the memory encoding and storage of a sequence of four coherently moving random dot kinematograms (RDKs), by applying repetitive transcranial magnetic stimulation (rTMS) during an early or late phase of the retention interval. Moreover, in a second experiment, we also tested whether disrupting the functional integrity of hMT+ during the early phase impaired the precision of the encoded motion directions. Overall, results showed that both recognition accuracy and precision were worse in middle serial positions, suggesting the occurrence of primacy and recency effects. We found that rTMS delivered during the early (but not the late) phase of the retention interval was able to impair not only recognition of RDKs, but also the precision of the retained motion direction. However, such impairment occurred only for RDKs presented in middle positions along the presented sequence, where performance was already closer to chance level. Altogether these findings suggest an involvement of hMT+ in the memory encoding of visual motion direction. Given that both position sequence and rTMS modulated not only recognition but also the precision of the stored information, these findings are in support of a model of visual short-term memory with a variable resolution of each stored item, consistent with the assigned amount of memory resources, and that such item-specific memory resolution is supported by the functional integrity of area hMT+.
A Novel Thromboplastin-Based Rat Model of Ischemic Stroke
Authors: Ostrova Irina V. , Kalabushev Sergei N. , Ryzhkov Ivan A. , Tsokolaeva Zoya I.
Published: November 2021

The thromboembolic ischemia model is one of the most applicable for studying ischemic stroke in humans. The aim of this study was to develop a novel thromboembolic stroke model, allowing, by affordable tools, to reproduce cerebral infarction in rats. In the experimental group, the left common carotid artery, external carotid artery, and pterygopalatine branch of maxillary artery were ligated. A blood clot that was previously formed (during a 20 min period, in a catheter and syringe, by mixing with a thromboplastin solution and CaCl2) was injected into the left internal carotid artery. After 10 min, the catheter was removed, and the incision was sutured. The neurological status of the animals was evaluated using a 20-point scale. Histological examination of brain tissue was performed 6, 24, 72 h, and 6 days post-stroke. All groups showed motor and behavioral disturbances 24 h after surgery, which persisted throughout the study period. A histological examination revealed necrotic foci of varying severity in the cortex and subcortical regions of the ipsilateral hemisphere, for all experimental groups. A decrease in the density of hippocampal pyramidal neurons was revealed. Compared with existing models, the proposed ischemic stroke model significantly reduces surgical time, does not require an expensive operating microscope, and consistently reproduces brain infarction in the area of the middle cerebral artery supply.
Latest Advances in Human Brain Dynamics
Authors: Dimitriadis Stavros I.
Published: November 2021

It is paramount for every neuroscientist to understand the nature of emerging technologies and approaches in investigating functional brain dynamics [...]
Physiological Factors Linking Insecure Attachment to Psychopathology: A Systematic Review
Authors: Tironi Marta , Charpentier Mora Simone , Cavanna Donatella , Borelli Jessica L. , Bizzi Fabiola
Published: November 2021

Although many studies have documented associations between insecure attachment and psychopathology, attachment may not confer risk for psychopathology independently, but rather through its interaction with emotional, social, and biological factors. Understanding the variables through which attachment may lead to psychopathology is therefore important. Within this domain of research, the role of physiological factors is poorly investigated. What are the relevant domains and why, when, or for whom do they influence mental disorders relating to attachment? The current systematic review aims to answer these questions. Results reveal that physiological indices of emotional regulation play a role in explaining and/or determining the relationship between attachment and psychopathology. Specifically: (1) combined with insecure attachment, higher skin conductance level (SCL), lower cardiac slowing, and respiratory sinus arrhythmia modulation (RSA) contribute to different psychopathological indicators and behavioral/psychological dysfunctions, although the latter predicts a contradictory pattern of findings; (2) insecure-avoidant attachment is more consistently linked with stress and emotional dysregulation when combined with RSA, while anxious attachment confers risk of depressive symptoms when combined with SCL. We concluded our discussion of the results of seven studies by outlining a plan to move the field forward. We discuss the quality of the assessment, methodological limitations, and future directions, highlighting the need to extend the research to clinical samples.
Experimental Behavior of Existing RC Columns Strengthened with HPFRC Jacket under Concentric and Eccentric Compressive Load
Authors: Cassese Paolino , Menna Costantino , Occhiuzzi Antonio , Asprone Domenico
Published: November 2021

Reinforced concrete (RC) structures built before the 1970 represent a large portion of the existing European buildings stock. Their obsolescence in terms of design criteria, materials, and functionality is becoming a critical issue for guaranteeing adequate compliance with current structural codes. Recently, a new jacketing system based on the use of high-performance fiber-reinforced concrete (HPFRC) has been introduced for strengthening existing RC building members. Despite the promising aspects of the HPFRC jacketing technique, currently, a comprehensive and systematic technical framework for its implementation is still missing. In this paper, the experimental performance of RC columns strengthened with the HPFRC jacket subjected to pure axial load and combined axial load-bending moment uncoupled from shear is investigated. The test outcomes confirmed a significant improvement of the structural performance for the strengthened columns, especially for higher values of eccentricity. Finally, a standard-based practice-oriented analytical tool for designing retrofit interventions using the HPFRC jacket is proposed. The comparison between the calculated and experimental results revealed a satisfactory prediction capability.
VISTA Is a Diagnostic Biomarker and Immunotherapy Target of Aggressive Feline Mammary Carcinoma Subtypes
Authors: Gameiro Andreia , Nascimento Catarina , Correia Jorge , Ferreira Fernando
Published: November 2021

Feline mammary carcinoma (FMC) is a common neoplasia, showing aggressive clinicopathological features, without viable therapeutic options. The study of tumor microenvironment has gained importance, due to the ability to control tumor progression by regulating the immune response. Considering the lack of knowledge, feline serum VISTA levels from cats with mammary carcinoma were compared with healthy controls, and with serum levels of PD-1/PD-L1, CTLA-4, LAG-3, IL-6, and TNF-α. In parallel, VISTA tumor expression was evaluated in FMC samples. The obtained data revealed that serum VISTA levels were significantly higher in cats presenting HER2-positive (p = 0.0025) or triple-negative subtypes (p = 0.0019), with higher serum levels in luminal A (p = 0.0025) correlated to the presence of metastasis (p = 0.0471). Furthermore, in HER2-positive or triple-negative tumors, correlations were obtained between serum VISTA levels and the serum levels of the above-mentioned molecules. In tumors, VISTA expression revealed a stronger intensity in cancer cells, when compared to TILs (p < 0.0001). Stratifying the samples by subtypes, a higher number of VISTA-positive TILs was observed in the HER2-positive subtype, compared with triple-negative tumors (p = 0.0138). In conclusion, results support the development of therapeutic strategies for HER2-positive and triple-negative FMC subtypes, reinforcing the use of cats as a human oncology model.
Topological Analysis of γH2AX and MRE11 Clusters Detected by Localization Microscopy during X-ray-Induced DNA Double-Strand Break Repair
Authors: Hahn Hannes , Neitzel Charlotte , Kopečná Olga , Heermann Dieter W. , Falk Martin , Hausmann Michael
Published: November 2021

DNA double-strand breaks (DSBs), known as the most severe damage in chromatin, were induced in breast cancer cells and normal skin fibroblasts by 2 Gy ionizing photon radiation. In response to DSB induction, phosphorylation of the histone variant H2AX to γH2AX was observed in the form of foci visualized by specific antibodies. By means of super-resolution single-molecule localization microscopy (SMLM), it has been recently shown in a first article about these data that these foci can be separated into clusters of about the same size (diameter ~400 nm). The number of clusters increased with the dose applied and decreased with the repair time. It has also been shown that during the repair period, antibody-labeled MRE11 clusters of about half of the γH2AX cluster diameter were formed inside several γH2AX clusters. MRE11 is part of the MRE11–RAD50–NBS1 (MRN) complex, which is known as a DNA strand resection and broken-end bridging component in homologous recombination repair (HRR) and alternative non-homologous end joining (a-NHEJ). This article is a follow-up of the former ones applying novel procedures of mathematics (topology) and similarity measurements on the data set: to obtain a measure for cluster shape and shape similarities, topological quantifications employing persistent homology were calculated and compared. In addition, based on our findings that γH2AX clusters associated with heterochromatin show a high degree of similarity independently of dose and repair time, these earlier published topological analyses and similarity calculations comparing repair foci within individual cells were extended by topological data averaging (2nd-generation heatmaps) over all cells analyzed at a given repair time point; thereby, the two dimensions (0 and 1) expressed by components and holes were studied separately. Finally, these mean value heatmaps were averaged, in addition. For γH2AX clusters, in both normal fibroblast and MCF-7 cancer cell lines, an increased similarity was found at early time points (up to 60 min) after irradiation for both components and holes of clusters. In contrast, for MRE11, the peak in similarity was found at later time points (2 h up to 48 h) after irradiation. In general, the normal fibroblasts showed quicker phosphorylation of H2AX and recruitment of MRE11 to γH2AX clusters compared to breast cancer cells and a shorter time interval of increased similarity for γH2AX clusters. γH2AX foci and randomly distributed MRE11 molecules naturally occurring in non-irradiated control cells did not show any significant topological similarity.
MicroRNA-21 Plays Multiple Oncometabolic Roles in Colitis-Associated Carcinoma and Colorectal Cancer via the PI3K/AKT, STAT3, and PDCD4/TNF-α Signaling Pathways in Zebrafish
Authors: Lai Chi-Yu , Yeh Kun-Yun , Liu Bi-Feng , Chang Tzu-Ming , Chang Chuan-Hsun , Liao Yung-Feng , Liu Yi-Wen , Her Guor Mour
Published: November 2021

Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Patients with inflammatory bowel disease (IBD) have a high risk of developing CRC. Inflammatory cytokines are regulated by complex gene networks and regulatory RNAs, especially microRNAs. MicroRNA-21 (miR-21) is amongst the most frequently upregulated microRNAs in inflammatory responses and cancer development. miR-21 has become a target for genetic and pharmacological regulation in various diseases. However, the association between inflammation and tumorigenesis in the gut is largely unknown. Hence, in this study, we generated a zebrafish model (ImiR-21) with inducible overexpression of miR-21 in the intestine. The results demonstrate that miR-21 can induce CRC or colitis-associated cancer (CAC) in ImiR-21 through the PI3K/AKT, PDCD4/TNF-α, and IL-6/STAT3 signaling network. miR-21 activated the PI3K/AKT and NF-κB signaling pathways, leading to initial inflammation; thereafter, miR-21 and TNF-α repressed PDCD4 and its tumor suppression activity. Eventually, active STAT3 stimulated a strong inflammatory response and activated the invasion/metastasis process of tumor cells. Hence, our findings indicate that miR-21 is critical for the development of CRC/CAC via the PI3K/AKT, STAT3, and PDCD4/TNF-α signaling networks.
Faecal Diagnostic Biomarkers for Colorectal Cancer
Authors: Cruz Andrea , Carvalho Carla M. , Cunha Alexandra , Crespo Anais , Iglesias Águeda , García-Nimo Laura , Freitas Paulo P. , Cubiella Joaquín
Published: November 2021

Background: Colorectal cancer (CRC) is a major cause of cancer-related death worldwide. Cancer progression, including invasion and metastasis, is a major cause of death among CRC patients. Current methods for CRC screening commonly consist of a combination of faecal immunochemical test (FIT) for stool occult blood detection and invasive procedures such as colonoscopy. Considering the slow progression of CRC, and that symptoms usually emerge at advanced stages, its early diagnostic can limit cancer’s spread and provide a successful treatment. Biomarkers have a high potential for the diagnosis of CRC in either blood or stool samples. Methods: In this study, we analysed the diagnostic value of six different biomarkers in stool samples of patients with CRC, advanced adenomas, other lesions and healthy individuals. We have also assessed the overall performance of the combination of these biomarkers for CRC detection. Results: The results indicate that haemoglobin (Hb) and M2-pyruvate kinase (M2-PK) levels were increased in CRC patients in comparison to the controls. Conversely, the concentrations of matrix metalloproteinase (MMP)-2, MMP-9, and tumour necrosis factor-alpha (TNF-α) were not significantly different between the tested groups. Conclusion: The combination of FIT-Hb with the M2-PK levels increased the specificity or sensitivity for CRC detection and thus present potential as faecal diagnostic biomarkers for CRC.
Dual Hyaluronic Acid and Folic Acid Targeting pH-Sensitive Multifunctional 2DG@DCA@MgO-Nano-Core–Shell-Radiosensitizer for Breast Cancer Therapy
Authors: Askar Mostafa A. , Thabet Noura M. , El-Sayyad Gharieb S. , El-Batal Ahmed I. , Abd Elkodous Mohamed , El Shawi Omama E. , Helal Hamed , Abdel-Rafei Mohamed K.
Published: November 2021

Globally, breast cancer (BC) poses a serious public health risk. The disease exhibits a complex heterogeneous etiology and is associated with a glycolytic and oxidative phosphorylation (OXPHOS) metabolic reprogramming phenotype, which fuels proliferation and progression. Due to the late manifestation of symptoms, rigorous treatment regimens are required following diagnosis. Existing treatments are limited by a lack of specificity, systemic toxicity, temporary remission, and radio-resistance in BC. In this study, we have developed CD44 and folate receptor-targeting multi-functional dual drug-loaded nanoparticles. This composed of hyaluronic acid (HA) and folic acid (FA) conjugated to a 2-deoxy glucose (2DG) shell linked to a layer of dichloroacetate (DCA) and a magnesium oxide (MgO) core (2DG@DCA@MgO; DDM) to enhance the localized chemo-radiotherapy for effective BC treatment. The physicochemical properties of nanoparticles including stability, selectivity, responsive release to pH, cellular uptake, and anticancer efficacy were thoroughly examined. Mechanistically, we identified multiple component signaling pathways as important regulators of BC metabolism and mediators for the inhibitory effects elicited by DDM. Nanoparticles exhibited sustained DDM release properties in a bio-relevant media, which was responsive to the acidic pH enabling eligibility to the control of drug release from nanoparticles. DDM-loaded and HA–FA-functionalized nanoparticles exhibited increased selectivity and uptake by BC cells. Cell-based assays revealed that the functionalized DDM significantly suppressed cancer cell growth and improved radiotherapy (RT) through inducing cell cycle arrest, enhancing apoptosis, and modulating glycolytic and OXPHOS pathways. By highlighting DDM mechanisms as an antitumor and radio-sensitizing reagent, our data suggest that glycolytic and OXPHOS pathway modulation occurs via the PI3K/AKT/mTOR/NF-κB/VEGFlow and P53high signaling pathway. In conclusion, the multi-functionalized DDM opposed tumor-associated metabolic reprogramming via multiple signaling pathways in BC cells as a promising targeted metabolic approach.
Letermovir Prophylaxis and Cytomegalovirus Reactivation in Adult Hematopoietic Cell Transplant Recipients with and without Acute Graft Versus Host Disease
Authors: Wolfe Delaney , Zhao Qiuhong , Siegel Emma , Puto Marcin , Murphy Danielle , Roddy Julianna , Efebera Yvonne , Tossey Justin
Published: November 2021

Cytomegalovirus (CMV) is the most clinically significant infection after allogeneic hematopoietic-cell transplantation (allo-HCT) and is associated with increased mortality. The risk for CMV reactivation increases with graft versus host disease (GVHD). GVHD contributes to significant morbidity and mortality and is treated with immunosuppressive therapies that can further increase CMV infection risk. Prophylaxis with letermovir, an oral antiviral approved to prevent CMV, has been shown to decrease the incidence of CMV infection post-allo-HCT in patients at high risk of CMV reactivation, but there is a lack of data confirming this benefit in patients with GVHD. In this single-center, retrospective study, we assessed the incidence of clinically significant CMV infection (CS-CMVi) in allo-HCT patients who received letermovir prophylaxis (n = 119) and who developed aGVHD compared to a control group (n = 143) who did not receive letermovir. Among aGVHD patients, letermovir prophylaxis decreased CS-CMVi in patients with aGVHD (HR 0.08 [95% CI 0.03–0.27], p < 0.001), reduced non-relapsed mortality (p = 0.04) and improved overall survival (p = 0.04). This data suggests that letermovir prophylaxis improves outcomes by preventing CS-CMVi in patients with aGVHD.
Screening for the Key Proteins Associated with Rete Testis Invasion in Clinical Stage I Seminoma via Label-Free Quantitative Mass Spectrometry
Authors: Borszéková Pulzová Lucia Borszéková , Roška Jan , Kalman Michal , Kliment Ján , Slávik Pavol , Smolková Božena , Goffa Eduard , Jurkovičová Dana , Kulcsár Ľudovít , Lešková Katarína , Bujdák Peter , Mego Michal , Bhide Mangesh R. , Plank Lukáš , Chovanec Miroslav
Published: November 2021

Rete testis invasion (RTI) is an unfavourable prognostic factor for the risk of relapse in clinical stage I (CS I) seminoma patients. Notably, no evidence of difference in the proteome of RTI-positive vs. -negative CS I seminomas has been reported yet. Here, a quantitative proteomic approach was used to investigate RTI-associated proteins. 64 proteins were differentially expressed in RTI-positive compared to -negative CS I seminomas. Of them, 14-3-3γ, ezrin, filamin A, Parkinsonism-associated deglycase 7 (PARK7), vimentin and vinculin, were validated in CS I seminoma patient cohort. As shown by multivariate analysis controlling for clinical confounders, PARK7 and filamin A expression lowered the risk of RTI, while 14-3-3γ expression increased it. Therefore, we suggest that in real clinical biopsy specimens, the expression level of these proteins may reflect prognosis in CS I seminoma patients.
Metastasis and Tumor Cell Migration of Solid Tumors
Authors: Hoeppner Jens , Bronsert Peter
Published: November 2021

The developmental process of local and distant metastases represents the major and defining trait of malignant tumors, whereby tumor cells sustain the capability to migrate from the initial tumor site, seed, and grow at a location other than that of the initial tumor [...]