bluuebunny/crossref_metadata_2025 huggingface dataset:
Trichuris trichiura (Linnaeus, 1771) From Human and Non-human Primates: Morphology, Biometry, Host Specificity, Molecular Characterization, and Phylogeny
Authors: Rivero Julia , Cutillas Cristina , Callejón Rocío
Published: February 2021

Human trichuriasis is a Neglected Tropical Disease, which affects hundreds of millions of persons worldwide. Several studies have reported that non-human primates (NHP) represent important reservoirs for several known zoonotic infectious diseases. In this context,Trichurisinfections have been found in a range of NHP species living in natural habitats, including colobus monkeys, macaques, baboons, and chimpanzees. To date, the systematics of the genusTrichurisparasitizing humans and NHP is unclear. During many years,Trichuris trichiurawas considered as the whipworm present in humans and primates. Subsequently, molecular studies suggested thatTrichurisspp. in humans and NHP represent several species that differ in host specificity. This work examines the current knowledge ofT. trichiuraand its relationship to whipworm parasites in other primate host species. A phylogenetic hypothesis, based on three mitochondrial genes (cytochrome c oxidasesubunit 1,cytochromeb, and large subunit rRNA-encoding gene) and two fragments of ribosomal DNA (Internal Transcribed Spacer 1 and 2), allowed us to define a complex of populations ofT. trichiurahosting in a large variety of NHP species, in addition to humans. These populations were divided into four phylogenetic groups with a different degree of host specificity. From these data, we carry out a new morphological and biometrical description of the populations ofTrichurisbased on data cited by other authors as well as those provided in this study. The presence ofT. trichiurais analyzed in several NHP species in captivity from different garden zoos as possible reservoir of trichuriasis for humans. This study contributes to clarify questions that lead to identification of new taxa and will determine parasite transmission routes between these primates, allowing the implementation of appropriate control and prevention measures.
Response to Ammonia Emission Flux to Different pH Conditions under Biochar and Liquid Fertilizer Application
Authors: Kim Min-Suk , Min Hyun-Gi , Koo Namin , Kim Jeong-Gyu
Published: February 2021

For the ammonia generated in Korea, the contribution rate of livestock manure is high, and a large amount of ammonia (NH3) is emitted into the atmosphere during the soil application process. Volatilization of NH3 is affected by soil characteristics as well as manure characteristics, but the current inventory does not sufficiently reflect this. This study was conducted to confirm the change of the NH3 emitted from liquid fertilizer (LF) due to soil pH and to evaluate the impacts of biochar (BC) on the suppression of NH3 volatilization. Estimating the NH3 emission flux using the chamber for 24 soils after LF treatment, it showed a tendency to increase exponentially as the pH in soil increased from 4 to 7. In addition, the parallel treatment of BC and LF increased the soil pH, thereby increasing the NH3 emission flux. The rise of soil pH due to LF treatment is a temporary phenomenon that appears in the early stage, but since NH3 volatilization is also highest at the beginning of LF application, the effect of soil characteristics on emission factor and its inventory should be considered when calculating the amount of NH3 emissions. Therefore, follow-up studies such as subdividing and enhancing the NH3 emission factor by soil characteristics and developing a reduction coefficient to certify the amount of emission reduction are needed.
Resumption of Cyclic Ovarian Activity by Herbal Preparation AyuFertin in Bulgarian Murrah Buffaloes at Early Postpartum
Authors: Ilieva Yordanka , Vasilev Nasko , Fasulkov Ivan , Penchev Pencho , Abadjieva Desislava , Mladenova Vanya , Ilyazova Ayla , Mihaylova Dasha , Yotov Stanimir , Kistanova Elena
Published: February 2021

This study evaluates the phytochemical composition and ability of herbal preparation AyuFertin, supplemented shortly after calving, to resume the cyclic ovarian activity in postpartum Bulgarian Murrah buffaloes. In total, 13 healthy Bulgarian Murrah buffaloes at the age of 4–10 years, calved in March–April 2019 were involved in the experiment. Seven experimental buffaloes were treated individually per os with AyuFertin according to producer instruction. All animals were subjected to regular ultrasound examination of ovaries. GC-MS analysis of fatty acids composition and HPLC-DAD analysis of carotenoid and tocopherol content in AyuFertin were conducted. The determination of estrus occurrence and natural mating were done by a fertile bull. The development of the large follicles (12.5–14.3 mm) in 85.7% of treated animals was observed on day 24 postpartum compared to 0% in controls. Clinical signs of estrus were recorded in 71.4% of the animals, followed by an 80% pregnancy rate versus 16% in controls within 70 days after calving. In conclusion, the supplementation of the bioactive herbal product AyuFertin from day 21 postpartum can stimulate the follicular growth in the buffalo’s ovary, which leads to the development of follicles with ovulatory capacity, followed by successful ovulation. The above-mentioned treatment resulted in a better pregnancy rate in the treated multiparous compared to the control buffaloes bred by natural service.
Equine Cervical Pain and Dysfunction: Pathology, Diagnosis and Treatment
Authors: Story Melinda R. , Haussler Kevin K. , Nout-Lomas Yvette S. , Aboellail Tawfik A. , Kawcak Christopher E. , Barrett Myra F. , Frisbie David D. , McIlwraith C. Wayne
Published: February 2021

Interest in the cervical spine as a cause of pain or dysfunction is increasingly becoming the focus of many equine practitioners. Many affected horses are presented for poor performance, while others will present with dramatic, sometimes dangerous behavior. Understanding and distinguishing the different types of neck pain is a starting point to comprehending how the clinical presentations can vary so greatly. There are many steps needed to systematically evaluate the various tissues of the cervical spine to determine which components are contributing to cervical pain and dysfunction. Osseous structures, soft tissues and the central and the peripheral nervous system may all play a role in these various clinical presentations. After completing the clinical evaluation, several imaging modalities may be implemented to help determine the underlying pathologic processes. There are multiple treatment options available and each must be carefully chosen for an individual horse. Provided is a synopsis of the current knowledge as to different disease processes that can result in cervical pain and dysfunction, diagnostic approaches and treatment strategies. Improving the knowledge in these areas will ideally help to return horses to a state of well-being that can be maintained over time and through the rigors of their job or athletic endeavors.
Bushmeat Species Identification: Recombinase Polymerase Amplification (RPA) Combined with Lateral Flow (LF) Strip for Identification of Formosan Reeves’ Muntjac (Muntiacus reevesi micrurus)
Authors: Hsu Yun-Hsiu , Yang Wei-Cheng , Chan Kun-Wei
Published: February 2021

The identification of animal species of meat in meat products is of great concern for various reasons, such as public health, religious beliefs, food allergies, legal perspectives, and bushmeat control. In this study, we developed a new technique to identify Formosan Reeves’ muntjac in meat using recombinase polymerase amplification (RPA) in combination with a lateral flow (LF) strip. The DNA extracted from a piece of Formosan Reeves’ muntjac meat was amplified by a pair of specific primers based on its mitochondrial cytochrome b gene for 10 min at a constant temperature ranging from 30 to 45 °C using RPA. Using the specific probe added to the RPA reaction system, the amplified products were visualized on the LF strip within 5 min. The total operating time from quick DNA extraction to visualizing the result was approximately 30 min. The RPA-LF system we designed was efficient when using boiled, pan-fried, roasted, stir-fried, or stewed samples. The advantages of simple operation, speediness, and cost-effectiveness make our RPA-LF method a promising molecular detection tool for meat species identification of either raw or variously cooked Formosan Reeves’ muntjac meat. It is also possible to apply this method to identify the meat of other wildlife sources.
Behavioral Responses of Wild Rodents to Owl Calls in an Austral Temperate Forest
Authors: Hernández Mᵃ Carmen , Jara-Stapfer Denise M. , Muñoz Ana , Bonacic Cristian , Barja Isabel , Rubio André V.
Published: February 2021

Ecologically based rodent management strategies are arising as a sustainable approach to rodent control, allowing us to preserve biodiversity while safeguarding human economic activities. Despite predator signals being known to generally repel rodents, few field-based studies have compared the behavioral effects of several predators on different prey species, especially in Neotropical ecosystems. Here, we used camera traps to study the behavior of rodent species native to the Chilean temperate forest (Abrothrix spp., long-tailed pygmy rice rat Oligoryzomys longicaudatus) and an introduced rodent (black rat Rattus rattus). Using playbacks of raptor calls, we experimentally exposed rodents to three predation risk treatments: austral pygmy owl calls (Glaucidium nana), rufous-legged owl calls (Strix rufipes) and a control treatment (absence of owl calls). We evaluated the effects of the treatments on the time allocated to three behaviors: feeding time, locomotor activity and vigilance. Moonlight and vegetation cover were also considered in the analyses, as they can modify perceived predation risk. Results showed that predator calls and environmental factors modified prey behavior depending not only on the predator species, but also on the rodent species. Consequently, owl playbacks could be regarded as a promising rodent control tool, knowing that future studies would be critical to deeply understand differences between species in order to select the most effective predator cues.
Carbonyl Stress in Red Blood Cells and Hemoglobin
Authors: Kosmachevskaya Olga V. , Novikova Natalia N. , Topunov Alexey F.
Published: February 2021

The paper overviews the peculiarities of carbonyl stress in nucleus-free mammal red blood cells (RBCs). Some functional features of RBCs make them exceptionally susceptible to reactive carbonyl compounds (RCC) from both blood plasma and the intracellular environment. In the first case, these compounds arise from the increased concentrations of glucose or ketone bodies in blood plasma, and in the second—from a misbalance in the glycolysis regulation. RBCs are normally exposed to RCC—methylglyoxal (MG), triglycerides—in blood plasma of diabetes patients. MG modifies lipoproteins and membrane proteins of RBCs and endothelial cells both on its own and with reactive oxygen species (ROS). Together, these phenomena may lead to arterial hypertension, atherosclerosis, hemolytic anemia, vascular occlusion, local ischemia, and hypercoagulation phenotype formation. ROS, reactive nitrogen species (RNS), and RCC might also damage hemoglobin (Hb), the most common protein in the RBC cytoplasm. It was Hb with which non-enzymatic glycation was first shown in living systems under physiological conditions. Glycated HbA1c is used as a very reliable and useful diagnostic marker. Studying the impacts of MG, ROS, and RNS on the physiological state of RBCs and Hb is of undisputed importance for basic and applied science.
Exogenous NAD+ Postpones the D-Gal-Induced Senescence of Bone Marrow-Derived Mesenchymal Stem Cells via Sirt1 Signaling
Authors: Wang Jie , Liu Lin , Ding Zhongjie , Luo Qing , Ju Yang , Song Guanbin
Published: February 2021

Cell senescence is accompanied by decreased nicotinamide adenine dinucleotide (NAD+) levels; however, whether exogenous NAD+ affects bone marrow-derived mesenchymal stem cells (BMSCs) senescence and the involved mechanisms is still unclear. Here, we find that exogenous NAD+ replenishment significantly postpones BMSC senescence induced by D-galactose (D-gal). It is also shown that exogenous NAD+ leads to increased intracellular NAD+ levels and reduced intracellular reactive oxygen species in senescent BMSCs here. Further investigation showed that exogenous NAD+ weakened BMSC senescence by increasing Sirtuin 1 (Sirt1) expression. Moreover, exogenous NAD+ reduced senescence-associated-β-galactosidase activity, and downregulated poly (ADP-ribose) polymerase 1 expression. In addition, the reduced expression of Sirt1 by small interfering RNA abolished the beneficial effects of exogenous NAD+ in terms of postponing BMSCs senescence induced by D-gal. Taken together, our results indicate that exogenous NAD+ could postpone D-gal-induced BMSC senescence through Sirt1 signaling, providing a potential method for obtaining high quality BMSCs to support their research and clinical application.
Pharmacotherapy against Oxidative Stress in Chronic Kidney Disease: Promising Small Molecule Natural Products Targeting Nrf2-HO-1 Signaling
Authors: Uddin Md Jamal , Kim Ee Hyun , Hannan Md. Abdul , Ha Hunjoo
Published: February 2021

The global burden of chronic kidney disease (CKD) intertwined with cardiovascular disease has become a major health problem. Oxidative stress (OS) plays an important role in the pathophysiology of CKD. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant responsive element (ARE) antioxidant system plays a critical role in kidney protection by regulating antioxidants during OS. Heme oxygenase-1 (HO-1), one of the targets of Nrf2-ARE, plays an important role in regulating OS and is protective in a variety of human and animal models of kidney disease. Thus, activation of Nrf2-HO-1 signaling may offer a potential approach to the design of novel therapeutic agents for kidney diseases. In this review, we have discussed the association between OS and the pathogenesis of CKD. We propose Nrf2-HO-1 signaling-mediated cell survival systems be explored as pharmacological targets for the treatment of CKD and have reviewed the literature on the beneficial effects of small molecule natural products that may provide protection against CKD.
Effect of Germanium Incorporation on the Electrochemical Performance of Electrospun Fe2O3 Nanofibers-Based Anodes in Sodium-Ion Batteries
Authors: Petrovičovà Beatrix , Ferrara Chiara , Brugnetti Gabriele , Ritter Clemens , Fracchia Martina , Ghigna Paolo , Pollastri Simone , Triolo Claudia , Spadaro Lorenzo , Ruffo Riccardo , Santangelo Saveria
Published: February 2021

Fe2O3 and Fe2O3:Ge nanofibers (NFs) were prepared via electrospinning and thoroughly characterized via several techniques in order to investigate the effects produced by germanium incorporation in the nanostructure and crystalline phase of the oxide. The results indicate that reference Fe2O3 NFs consist of interconnected hematite grains, whereas in Fe2O3:Ge NFs, constituted by finer and elongated nanostructures developing mainly along their axis, an amorphous component coexists with the dominant α-Fe2O3 and γ-Fe2O3 phases. Ge4+ ions, mostly dispersed as dopant impurities, are accommodated in the tetrahedral sites of the maghemite lattice and probably in the defective hematite surface sites. When tested as anode active material for sodium ion batteries, Fe2O3:Ge NFs show good specific capacity (320 mAh g−1 at 50 mA g−1) and excellent rate capability (still delivering 140 mAh g−1 at 2 A g−1). This behavior derives from the synergistic combination of the nanostructured morphology, the electronic transport properties of the complex material, and the pseudo-capacitive nature of the charge storage mechanism.
Comparison of Selected Characteristics of SARS-CoV-2, SARS-CoV, and HCoV-NL63
Authors: Bačenková Darina , Trebuňová Marianna , Špakovská Tatiana , Schnitzer Marek , Bednarčíková Lucia , Živčák Jozef
Published: February 2021

The global pandemic known as coronavirus disease 2019 (COVID-19) was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This review article presents the taxonomy of SARS-CoV-2 coronaviruses, which have been classified as the seventh known human pathogenic coronavirus. The etiology of COVID-19 is also briefly discussed. Selected characteristics of SARS-CoV-2, SARS-CoV, and HCoV-NL63 are compared in the article. The angiotensin converting enzyme-2 (ACE-2) has been identified as the receptor for the SARS-CoV-2 viral entry. ACE2 is well-known as a counter-regulator of the renin-angiotensin system (RAAS) and plays a key role in the cardiovascular system. In the therapy of patients with COVID-19, there has been a concern about the use of RAAS inhibitors. As a result, it is hypothesized that ACE inhibitors do not directly affect ACE2 activity in clinical use. Coronaviruses are zoonotic RNA viruses. Identification of the primary causative agent of the SARS-CoV-2 is essential. Sequencing showed that the genome of the Bat CoVRaTG13 virus found in bats matches the genome of up to (96.2%) of SARS-CoV-2 virus. Sufficient knowledge of the molecular and biological mechanisms along with reliable information related to SARS-CoV-2 gives hope for a quick solution to epidemiological questions and therapeutic processes.
Partial Threading of Pedicle Screws in a Standard Construct Increases Fatigue Life: A Biomechanical Analysis
Authors: Tsuang Fon-Yih , Chen Chia-Hsien , Wu Lien-Chen , Kuo Yi-Jie , Hsieh Yueh-Ying , Chiang Chang-Jung
Published: February 2021

This study proposed a pedicle screw design where the proximal 1/3 of the screw is unthreaded to improve fixation in posterior spinal surgery. This design was also expected to reduce the incidence of mechanical failure often observed when an unsupported screw length is exposed outside the vertebra in deformed or degenerated segments. The aim of this study was to evaluate the fatigue life of the novel pedicle screw design using finite element analysis and mechanical testing in a synthetic spinal construct in accordance with American Society for Testing and Materials (ASTM) F1717. The following setups were evaluated: (i) pedicle screw fully inserted into the test block (EXP-FT-01 and EXP-PU-01; full thread (FT), proximal unthread (PU)) and (ii) pedicle screw inserted but leaving an exposed shaft length of 7.6 mm (EXP-FT-02 and EXP-PU-02). Corresponding finite element models FEM-FT-01, FEM-FT-02, FEM-PU-01, and FEM-PU-02 were also constructed and subjected to the same loading conditions as the experimental groups. The results showed that under a 220 N axial load, the EXP-PU-01 group survived the full 5 million cycles, the EXP-PU-02 group failed at 4.4 million cycles on average, and both EXP-FT-01 and EXP-FT-02 groups failed after less than 1.0 million cycles on average, while the fatigue strength of the EXP-FT-02 group was the lowest at 170 N. The EXP-FT-01 and EXP-FT-02 constructs failed through fracture of the pedicle screw, but a rod fractured in the EXP-PU-02 group. In comparison to the FEM-FT-01 model, the maximum von Mises stress on the pedicle screw in the FEM-PU-01 and FEM-PU-02 models decreased by −43% and −27%, respectively. In conclusion, this study showed that having the proximal 1/3 of the pedicle screw unthreaded can reduce the risk of screw fatigue failure when used in deformed or degenerated segments.
Experimental Analysis of Plantar Fascia Mechanical Properties in Subjects with Foot Pathologies
Authors: Todros Silvia , Biz Carlo , Ruggieri Pietro , Pavan Piero G.
Published: February 2021

Plantar Fascia (PF) is a fibrous tissue that plays a key role in supporting the foot arch; it can be affected by several pathologies that can alter foot biomechanics. The present study aims at investigating the mechanical behavior of PF and evaluating possible correlations between mechanical properties and specific pathologies, namely diabetes and plantar fibromatosis (Ledderhose syndrome). PF samples were obtained from 14 human subjects, including patients with Ledderhose syndrome, patients affected by diabetes and healthy subjects. Mechanical properties of PF tissues were evaluated on three samples from each subject, by cyclic uniaxial tensile tests up to 10% of maximum strain and stress relaxation tests for 300 s, in hydrated conditions at room temperature. In tensile tests, PF exhibits non-linear stress–strain behavior, with a higher elastic modulus (up to 25–30 MPa) in patients affected by Ledderhose syndrome and diabetes with respect to healthy subjects (elastic modulus 10 ÷ 14 MPa). Stress-relaxation tests show that PF of patients affected by Ledderhose syndrome and diabetes develop more intense viscous phenomena. The results presented in this work represent the first experimental data on the tensile mechanical propertied of PF in subjects with foot diseases and can provide an insight on foot biomechanics in pathological conditions.
A Biologically Inspired Sound Localisation System Using a Silicon Cochlea Pair
Authors: Xu Ying , Afshar Saeed , Wang Runchun , Cohen Gregory , Singh Thakur Chetan , Hamilton Tara Julia , van Schaik André
Published: February 2021

We present a biologically inspired sound localisation system for reverberant environments using the Cascade of Asymmetric Resonators with Fast-Acting Compression (CAR-FAC) cochlear model. The system exploits a CAR-FAC pair to pre-process binaural signals that travel through the inherent delay line of the cascade structures, as each filter acts as a delay unit. Following the filtering, each cochlear channel is cross-correlated with all the channels of the other cochlea using a quantised instantaneous correlation function to form a 2-D instantaneous correlation matrix (correlogram). The correlogram contains both interaural time difference and spectral information. The generated correlograms are analysed using a regression neural network for localisation. We investigate the effect of the CAR-FAC nonlinearity on the system performance by comparing it with a CAR only version. To verify that the CAR/CAR-FAC and the quantised instantaneous correlation provide a suitable basis with which to perform sound localisation tasks, a linear regression, an extreme learning machine, and a convolutional neural network are trained to learn the azimuthal angle of the sound source from the correlogram. The system is evaluated using speech data recorded in a reverberant environment. We compare the performance of the linear CAR and nonlinear CAR-FAC models with current sound localisation systems as well as with human performance.
EMG Based Gesture Recognition Using the Unbiased Difference Power
Authors: Kang Kimoon , Shin Hyun-Chool
Published: February 2021

In this paper, we propose an unbiased difference power that is robust against noise as a feature for electromyography (EMG)-based gesture recognition. The proposed unbiased difference power is obtained by subtracting the noise-biased part from the difference power. We derive the difference power equation and discover that the difference power is biased by twice the noise power. For noise power estimation, we utilized the characteristics of the EMG signal and estimated the noise power from the resting period. For performance evaluation, we used EMG signals provided by the open source Ninapro project database. We used the recognition accuracy as an evaluation index. We compare the recognition accuracy of the case using the proposed unbiased feature with those of two conventional cases. Experimental results show that the proposed unbiased difference power improves the accuracy compared with conventional ones. As the noise level increases, cases where the proposed unbiased difference power is used show a clear improvement in accuracy compared with the two conventional cases. For the signal-to-noise ratio (SNR) of 0 dB, the proposed unbiased difference power improves the average accuracy by more than 12%.
Research on Measuring Thermal Conductivity of Quartz and Sapphire Glass Using Rear-Side Photothermal Deflection Method
Authors: Kim Gwantaek , Kim Donghyuk , Kang Sukkyung , Yoo Jaisuk , Kim Hyunjung
Published: February 2021

As the display industry continues to advance, various new materials are being developed for utilizing microtechnology and nanotechnology in display panels. Among these, transparent materials have been widely applied to the internal wiring of displays and flexible substrates, owing to their high optical transmittance, isotropy, and anisotropy. Thus, measurement of the thermophysical properties of various transparent materials is important. This study measured thermal conductivity by selecting quartz, a transparent isotropic material, and sapphire glass, a transparent anisotropic material, as measurement target materials using a rear-side photothermal deflection method. Measurements were made via a three-dimensional unsteady heat conduction equation, to which complex transformation was applied and numerically analyzed using COMSOL Multiphysics. Phase delays for a pump beam and a probe beam for a relative position were derived through a deflection analysis. From the derived phase delays between the numerical analysis and experimental result with optical alignment, the absolute and relative errors of quartz were appropriately confirmed to be 0.069 W/m-K and 5%, respectively, while those of the sapphire glass were likewise confirmed to be 0.55 W/m-K and 1.5%, respectively.
Quantifying the Northward Spread of Ticks (Ixodida) as Climate Warms in Northern Russia
Authors: Vladimirov Leonid N. , Machakhtyrov Grigory N. , Machakhtyrova Varvara A. , Louw Albertus S. , Sahu Netrananda , Yunus Ali P. , Avtar Ram
Published: February 2021

Climate change is affecting human health worldwide. In particular, changes to local and global climate parameters influence vector and water-borne diseases like malaria, dengue fever, and tick-borne encephalitis. The Republic of Sakha in northern Russia is no exception. Long-term trends of increasing annual temperatures and thawing permafrost have corresponded with the northward range expansion of tick-species in the Republic. Indigenous communities living in these remote areas may be severely affected by human and livestock diseases introduced by disease vectors like ticks. To better understand the risk of vector-borne diseases in Sakha, we aimed to describe the increase and spatial spread of tick-bite cases in the Republic. Between 2000 and 2018, the frequency of tick bite cases increased 40-fold. At the start of the period, only isolated cases were reported in southern districts, but by 2018, tick bites had been reported in 21 districts in the Republic. This trend coincides with a noticeable increase in the average annual temperature in the region since the 2000s by an average of 1 °C. Maps illustrate the northward spread of tick-bite cases. A negative binomial regression model was used to correlate the increase in cases with a number of climate parameters. Tick bite case frequency per district was significantly explained by average annual temperature, average temperature in the coldest month of the year, the observation year, as well as Selyaninov’s hydrothermal coefficient. These findings contribute to the growing literature that describe the relationship between tick abundance and spread in Northern Latitudes and changes in temperatures and moisture. Future studies might use these and similar results to map and identify areas at risk of infestation by ticks, as climates continue to change in Sakha.
Positional Nystagmus after Acute Vertiginous Attack in Meniere’s Disease
Authors: Noh Haemin , Lee Dong-Han , Shin Jung Eun , Kim Chang-Hee
Published: February 2021

There have been no reports regarding nystagmus observed immediately after the end of an acute vertiginous attack in patients with Meniere’s disease. The aim of this study was to demonstrate positional direction-changing nystagmus in patients with Meniere’s disease, and to discuss the mechanism that underlies this nystagmus. Video-nystagmography was recorded in two patients with definite Meniere’s disease, who showed positional direction-changing nystagmus during the period immediately after a vertigo attack. In one patient, video-nystagmographic recording was conducted 5 h after an episode of vertigo attack, and it showed very weak, persistent positional geotropic direction-changing nystagmus. In the other patient, video-nystagmographic recording was conducted 23 h after an episode of vertigo attack, and it showed very weak, persistent positional apogeotropic direction-changing nystagmus. Our patients exhibited very weak, persistent positional direction-changing nystagmus, which was geotropic in one and apogeotropic in the other. This type of positional nystagmus has been reported in other inner ear disorders and it cannot be clearly explained by typical benign paroxysmal positional vertigo. The change in chemical composition and/or electrolyte concentration of the inner ear fluid, although still unclear, may underlie the production of this characteristic nystagmus in these patients.
A Three-Phase Fundamental Diagram from Three-Dimensional Traffic Data
Authors: Delle Monache Maria , Chi Karen , Chen Yong , Goatin Paola , Han Ke , Qiu Jing-mei , Piccoli Benedetto
Published: February 2021

This paper uses empirical traffic data collected from three locations in Europe and the US to reveal a three-phase fundamental diagram with two phases located in the uncongested regime. Model-based clustering, hypothesis testing and regression analyses are applied to the speed–flow–occupancy relationship represented in the three-dimensional space to rigorously validate the three phases and identify their gaps. The finding is consistent across the aforementioned different geographical locations. Accordingly, we propose a three-phase macroscopic traffic flow model and a characterization of solutions to the Riemann problems. This work identifies critical structures in the fundamental diagram that are typically ignored in first- and higher-order models and could significantly impact travel time estimation on highways.
Tissue-Specific Landscape of Metabolic Dysregulation during Ageing
Authors: Zhang Fangrong , Kerbl-Knapp Jakob , Akhmetshina Alena , Korbelius Melanie , Kuentzel Katharina Barbara , Vujić Nemanja , Hörl Gerd , Paar Margret , Kratky Dagmar , Steyrer Ernst , Madl Tobias
Published: February 2021

The dysregulation of cellular metabolism is a hallmark of ageing. To understand the metabolic changes that occur as a consequence of the ageing process and to find biomarkers for age-related diseases, we conducted metabolomic analyses of the brain, heart, kidney, liver, lung and spleen in young (9–10 weeks) and old (96–104 weeks) wild-type mice [mixed genetic background of 129/J and C57BL/6] using NMR spectroscopy. We found differences in the metabolic fingerprints of all tissues and distinguished several metabolites to be altered in most tissues, suggesting that they may be universal biomarkers of ageing. In addition, we found distinct tissue-clustered sets of metabolites throughout the organism. The associated metabolic changes may reveal novel therapeutic targets for the treatment of ageing and age-related diseases. Moreover, the identified metabolite biomarkers could provide a sensitive molecular read-out to determine the age of biologic tissues and organs and to validate the effectiveness and potential off-target effects of senolytic drug candidates on both a systemic and tissue-specific level.
Xylan Decomposition in Plant Cell Walls as an Inducer of Surfactin Synthesis by Bacillus subtilis
Authors: Szmigiel Ida , Kwiatkowska Dorota , Łukaszewicz Marcin , Krasowska Anna
Published: February 2021

Hemicellulose is the second most abundant plant heterogenous biopolymer. Among products obtained from a wide range of agro-residues, biosurfactants, e.g., surfactin (SU), are gaining increasing interest. Our previous studies have shown that a Bacillus subtilis strain can successfully produce a significant amount of SU using a rapeseed cake. This work aimed to investigate plant hemicellulose components as substrates promoting SU’s efficient production by B. subtilis 87Y. Analyses of SU production, enzymatic activity and cell wall composition of hulled oat caryopses suggest that the main ingredients of plant hemicellulose, in particular xylan and its derivatives, may be responsible for an increased biosurfactant yield.
Oligosaccharides Derived from Tramesan: Their Structure and Activity on Mycotoxin Inhibition in Aspergillus flavus and Aspergillus carbonarius
Authors: Loncar Jelena , Bellich Barbara , Parroni Alessia , Reverberi Massimo , Rizzo Roberto , Zjalić Slaven , Cescutti Paola
Published: February 2021

Food and feed safety are of paramount relevance in everyday life. The awareness that different chemicals, e.g., those largely used in agriculture, could present both environmental problems and health hazards, has led to a large limitation of their use. Chemicals were also the main tool in a control of fungal pathogens and their secondary metabolites, mycotoxins. There is a drive to develop more environmentally friendly, “green”, approaches to control mycotoxin contamination of foodstuffs. Different mushroom metabolites showed the potential to act as control agents against mycotoxin production. The use of a polysaccharide, Tramesan, extracted from the basidiomycete Trametes versicolor, for controlling biosynthesis of aflatoxin B1 and ochratoxin A, has been previously discussed. In this study, oligosaccharides obtained from Tramesan were evaluated. The purified exopolysaccharide of T. versicolor was partially hydrolyzed and separated by chromatography into fractions from disaccharides to heptasaccharides. Each fraction was individually tested for mycotoxin inhibition in A. flavus and A. carbonarius. Fragments smaller than seven units showed no significant effect on mycotoxin inhibition; heptasaccharides showed inhibitory activity of up to 90% in both fungi. These results indicated that these oligosaccharides could be used as natural alternatives to crop protection chemicals for controlling these two mycotoxins.
A Miniaturized Platform for Multiplexed Drug Response Imaging in Live Tumors
Authors: Bhagavatula Sharath , Thompson Devon , Ahn Sebastian W. , Upadhyaya Kunj , Lammers Alex , Deans Kyle , Dominas Christine , Ferland Benjamin , Valvo Veronica , Liu Guigen , Jonas Oliver
Published: February 2021

By observing the activity of anti-cancer agents directly in tumors, there is potential to greatly expand our understanding of drug response and develop more personalized cancer treatments. Implantable microdevices (IMD) have been recently developed to deliver microdoses of chemotherapeutic agents locally into confined regions of live tumors; the tissue can be subsequently removed and analyzed to evaluate drug response. This method has the potential to rapidly screen multiple drugs, but requires surgical tissue removal and only evaluates drug response at a single timepoint when the tissue is excised. Here, we describe a “lab-in-a-tumor” implantable microdevice (LIT-IMD) platform to image cell-death drug response within a live tumor, without requiring surgical resection or tissue processing. The LIT-IMD is inserted into a live tumor and delivers multiple drug microdoses into spatially discrete locations. In parallel, it locally delivers microdose levels of a fluorescent cell-death assay, which diffuses into drug-exposed tissues and accumulates at sites of cell death. An integrated miniaturized fluorescence imaging probe images each region to evaluate drug-induced cell death. We demonstrate ability to evaluate multi-drug response over 8 h using murine tumor models and show correlation with gold-standard conventional fluorescence microscopy and histopathology. This is the first demonstration of a fully integrated platform for evaluating multiple chemotherapy responses in situ. This approach could enable a more complete understanding of drug activity in live tumors, and could expand the utility of drug-response measurements to a wide range of settings where surgery is not feasible.
Syndecan-1 Overexpressing Mesothelioma Cells Inhibit Proliferation, Wound Healing, and Tube Formation of Endothelial Cells
Authors: Javadi Joman , Heidari-Hamedani Ghazal , Schmalzl Angelika , Szatmári Tünde , Metintas Muzaffer , Aspenström Pontus , Hjerpe Anders , Dobra Katalin
Published: February 2021

Malignant mesothelioma (MM) is an aggressive tumor of the serosal cavities. Angiogenesis is important for mesothelioma progression, but so far, anti-angiogenic agents have not improved patient survival. Our hypothesis is that better understanding of the regulation of angiogenesis in this tumor would largely improve the success of such a therapy. Syndecan-1 (SDC-1) is a transmembrane heparan sulfate proteoglycan that acts as a co-receptor in various cellular processes including angiogenesis. In MM, the expression of SDC-1 is generally low but when present, SDC-1 associates to epithelioid differentiation, inhibition of tumor cell migration and favorable prognosis, meanwhile SDC-1 decrease deteriorates the prognosis. In the present study, we studied the effect of SDC-1 overexpression and silencing on MM cells ability to secrete angiogenic factors and monitored the downstream effect of SDC-1 modulation on endothelial cells proliferation, wound healing, and tube formation. This was done by adding conditioned medium from SDC-1 transfected and SDC-1 silenced mesothelioma cells to endothelial cells. Moreover, we investigated the interplay and molecular functional changes in angiogenesis in a co-culture system and characterized the soluble angiogenesis-related factors secreted to the conditioned media. We demonstrated that SDC-1 over-expression inhibited the proliferation, wound healing, and tube formation of endothelial cells. This effect was mediated by a multitude of angiogenic factors comprising angiopoietin-1 (Fold change ± SD: 0.65 ± 0.07), FGF-4 (1.45 ± 0.04), HGF (1.33 ± 0.07), NRG1-β1 (1.35 ± 0.08), TSP-1 (0.8 ± 0.02), TIMP-1 (0.89 ± 0.01) and TGF-β1 (1.35 ± 0.01). SDC-1 silencing increased IL8 (1.33 ± 0.06), promoted wound closure, but did not influence the tube formation of endothelial cells. Pleural effusions from mesothelioma patients showed that Vascular Endothelial Growth Factor (VEGF) levels correlate to soluble SDC-1 levels and have prognostic value. In conclusion, SDC-1 over-expression affects the angiogenic factor secretion of mesothelioma cells and thereby inhibits endothelial cells proliferation, tube formation, and wound healing. VEGF could be used in prognostic evaluation of mesothelioma patients together with SDC-1.
Transcriptomic Analyses of MYCN-Regulated Genes in Anaplastic Wilms’ Tumour Cell Lines Reveals Oncogenic Pathways and Potential Therapeutic Vulnerabilities
Authors: Szemes Marianna , Melegh Zsombor , Bellamy Jacob , Park Ji Hyun , Chen Biyao , Greenhough Alexander , Catchpoole Daniel , Malik Karim
Published: February 2021

The MYCN proto-oncogene is deregulated in many cancers, most notably in neuroblastoma, where MYCN gene amplification identifies a clinical subset with very poor prognosis. Gene expression and DNA analyses have also demonstrated overexpression of MYCN mRNA, as well as focal amplifications, copy number gains and presumptive change of function mutations of MYCN in Wilms’ tumours with poorer outcomes, including tumours with diffuse anaplasia. Surprisingly, however, the expression and functions of the MYCN protein in Wilms’ tumours still remain obscure. In this study, we assessed MYCN protein expression in primary Wilms’ tumours using immunohistochemistry of tissue microarrays. We found MYCN protein to be expressed in tumour blastemal cells, and absent in stromal and epithelial components. For functional studies, we used two anaplastic Wilms’ tumour cell-lines, WiT49 and 17.94, to study the biological and transcriptomic effects of MYCN depletion. We found that MYCN knockdown consistently led to growth suppression but not cell death. RNA sequencing identified 561 MYCN-regulated genes shared by WiT49 and 17.94 cell-lines. As expected, numerous cellular processes were downstream of MYCN. MYCN positively regulated the miRNA regulator and known Wilms’ tumour oncogene LIN28B, the genes encoding methylosome proteins PRMT1, PRMT5 and WDR77, and the mitochondrial translocase genes TOMM20 and TIMM50. MYCN repressed genes including the developmental signalling receptor ROBO1 and the stromal marker COL1A1. Importantly, we found that MYCN also repressed the presumptive Wilms’ tumour suppressor gene REST, with MYCN knockdown resulting in increased REST protein and concomitant repression of RE1-Silencing Transcription factor (REST) target genes. Together, our study identifies regulatory axes that interact with MYCN, providing novel pathways for potential targeted therapeutics for poor-prognosis Wilms’ tumour.
The Role of Liquid Biopsy in Hepatocellular Carcinoma Prognostication
Authors: Labgaa Ismail , Villanueva Augusto , Dormond Olivier , Demartines Nicolas , Melloul Emmanuel
Published: February 2021

Showing a steadily increasing cancer-related mortality, the epidemiological evolution of hepatocellular carcinoma (HCC) is concerning. Numerous strategies have attempted to prognosticate HCC but their performance is modest; this is partially due to the heterogeneous biology of this cancer. Current clinical guidelines endorse classifications and scores that use clinical variables, such as the Barcelona Clinic Liver Cancer (BCLC) classification. These algorithms are unlikely to fully recapitulate the genomic complexity of HCC. Integrating molecular readouts on a patient-basis, following a precision-medicine perspective, might be an option to refine prognostic systems. The limited access to HCC tissue samples is an important limitation to these approaches but it could be partially circumvented by using liquid biopsy. This concept consists of the molecular analysis of products derived from a solid tumor and released into biological fluids, mostly into the bloodstream. It offers an easy and minimally-invasive access to DNA, RNA, extracellular vesicles and cells that can be analyzed with next-generation sequencing (NGS) technologies. This review aims to investigate the potential contributions of liquid biopsy in HCC prognostication. The results identified prognostic values for each of the components of liquid biopsy, suggesting that this technology may help refine HCC prognostication.
Boosted EfficientNet: Detection of Lymph Node Metastases in Breast Cancer Using Convolutional Neural Networks
Authors: Wang Jun , Liu Qianying , Xie Haotian , Yang Zhaogang , Zhou Hefeng
Published: February 2021

(1) Purpose: To improve the capability of EfficientNet, including developing a cropping method called Random Center Cropping (RCC) to retain the original image resolution and significant features on the images’ center area, reducing the downsampling scale of EfficientNet to facilitate the small resolution images of RPCam datasets, and integrating attention and Feature Fusion (FF) mechanisms with EfficientNet to obtain features containing rich semantic information. (2) Methods: We adopt the Convolutional Neural Network (CNN) to detect and classify lymph node metastasis in breast cancer. (3) Results: Experiments illustrate that our methods significantly boost performance of basic CNN architectures, where the best-performed method achieves an accuracy of 97.96% ± 0.03% and an Area Under the Curve (AUC) of 99.68% ± 0.01% on RPCam datasets, respectively. (4) Conclusions: (1) To our limited knowledge, we are the only study to explore the power of EfficientNet on Metastatic Breast Cancer (MBC) classification, and elaborate experiments are conducted to compare the performance of EfficientNet with other state-of-the-art CNN models. It might provide inspiration for researchers who are interested in image-based diagnosis using Deep Learning (DL). (2) We design a novel data augmentation method named RCC to promote the data enrichment of small resolution datasets. (3) All of our four technological improvements boost the performance of the original EfficientNet.
Recent Advancements in the Mechanisms Underlying Resistance to PD-1/PD-L1 Blockade Immunotherapy
Authors: Yuan Yu , Adam Abdalla , Zhao Chen , Chen Honglei
Published: February 2021

Release of immunoreactive negative regulatory factors such as immune checkpoint limits antitumor responses. PD-L1 as a significant immunosuppressive factor has been involved in resistance to therapies such as chemotherapy and target therapy in various cancers. Via interacting with PD-1, PD-L1 can regulate other factors or lead to immune evasion of cancer cells. Besides, immune checkpoint blockade targeting PD-1/PD-L1 has promising therapeutic efficacy in the different tumors, but a significant percentage of patients cannot benefit from this therapy due to primary and acquired resistance during treatment. In this review, we described the utility of PD-L1 expression levels for predicting poor prognosis in some tumors and present evidence for a role of PD-L1 in resistance to therapies through PD-1/PD-L1 pathway and other correlating signaling pathways. Afterwards, we elaborate the key mechanisms underlying resistance to PD-1/PD-L1 blockade in cancer immunotherapy. Furthermore, promising combination of therapeutic strategies for patients resistant to PD-1/PD-L1 blockade therapy or other therapies associated with PD-L1 expression was also summarized.
Soluble PD-L1 Is an Independent Prognostic Factor in Clear Cell Renal Cell Carcinoma
Authors: Larrinaga Gorka , Solano-Iturri Jon Danel , Errarte Peio , Unda Miguel , Loizaga-Iriarte Ana , Pérez-Fernández Amparo , Echevarría Enrique , Asumendi Aintzane , Manini Claudia , Angulo Javier C. , López José I.
Published: February 2021

(1). Background: Immunohistochemical (IHC) evaluation of programmed death-1 (PD-1) and its ligand (PD-L1) is being used to evaluate advanced malignancies with potential response to immune checkpoint inhibitors. We evaluated both plasma and tissue expression of PD-1 and PD-L1 in the same cohort of patients, including non-metastatic and metastatic clear cell renal cell carcinoma (CCRCC). Concomitant plasma and tissue expression of PD-1 and PD-L1 was evaluated with emphasis on diagnostic and prognostic implications. (2) Methods: we analyzed PD-1 and PD-L1 IHC expression in tumor tissues and soluble forms (sPD-1 and sPD-L1) in plasma from 89 patients with CCRCC, of which 23 were metastatic and 16 received systemic therapy. The primary endpoint was evaluation of overall survival using Kaplan-Meier analysis and the Cox regression model. Plasma samples from healthy volunteers were also evaluated. (3) Results: Interestingly, sPD-1 and sPD-L1 levels were lower in cancer patients than in controls. sPD-1 and sPD-L1 levels and their counterpart tissue expression both at the tumor center and infiltrating front were not associated. Higher expression of both PD-1 and PD-L1 were associated with tumor grade, necrosis and tumor size. PD-1 was associated to tumor stage (pT) and PD-L1 to metastases. sPD-1 and sPD-L1 were not associated with clinico-pathological parameters, although both were higher in patients with synchronous metastases compared to metachronous ones and sPD-L1 was also higher for metastatic patients compared to non-metastatic patients. sPD-1 was also associated with the International Metastatic Renal Cell Cancer Database Consortium (IMDC) prognostic groups in metastatic CCRCC and also to the Morphology, Attenuation, Size and Structure (MASS) response criteria in metastatic patients treated with systemic therapy, mainly tyrosine-kinase inhibitors. Regarding prognosis, PD-L1 immunostaining at the tumor center with and without the tumor front was associated with worse survival, and so was sPD-L1 at a cut-off >793 ng/mL. Combination of positivity at both the tissue and plasma level increased the level of significance to predict prognosis. (4) Conclusions: Our findings corroborate the role of PD-L1 IHC to evaluate prognosis in CCRCC and present novel data on the usefulness of plasma sPD-L1 as a promising biomarker of survival in this neoplasia.