bluuebunny/crossref_metadata_2025 huggingface dataset:
Composite Error-Based Intelligent Adaptive Sliding Mode Control for Uncertain Bilaterally Symmetrical Hybrid Robot with Variational Desired Trajectories
Authors: Qin Qiuyue , Gao Guoqin
Published: March 2021

Some challenging issues exist in trajectory tracking control of an uncertain bilaterally symmetrical hybrid robot (UBSHR) with variational desired trajectories, mainly the uncertainty problem of UBSHR, the synchronization problem of UBSHR’s active joints and bilateral symmetrical hybrid mechanisms, and the flexible control problem of active adaption to different technological requirements without artificially adjusting the control parameters or switching the hardware system. To solve these problems, an adaptive fuzzy neural network in conjunction with subtractive clustering algorithm (SC-AFNN) for UBSHR is proposed. More specifically, a novel composite error is incorporated into the second-order sliding mode control method to generate ideal training data samples and to improve the uncertain system robustness and synchronization performance simultaneously. Furthermore, the SC-AFNN is introduced to realize self-learning and self-adjusting of control rules and control parameters and to enhance the flexible control performance of UBSHR with variational desired trajectories. Strict theoretical proof of the defined errors’ relationship and the stability of the poposed control method is given. Ultimately, simulations and experiments for the prototype system of an UBSHR are conducted to verify the effectiveness of the proposed control method.
Three-Dimensional Assessment of Upper Limb Proprioception via a Wearable Exoskeleton
Authors: Galofaro Elisa , D’Antonio Erika , Patané Fabrizio , Casadio Maura , Masia Lorenzo
Published: March 2021

Proprioception—the sense of body segment’s position and movement—plays a crucial role in human motor control, integrating the sensory information necessary for the correct execution of daily life activities. Despite scientific evidence recognizes that several neurological diseases hamper proprioceptive encoding with consequent inability to correctly perform movements, proprioceptive assessment in clinical settings is still limited to standard scales. Literature on physiology of upper limb’s proprioception is mainly focused on experimental approaches involving planar setups, while the present work provides a novel paradigm for assessing proprioception during single—and multi-joint matching tasks in a three-dimensional workspace. To such extent, a six-degrees of freedom exoskeleton, ALEx-RS (Arm Light Exoskeleton Rehab Station), was used to evaluate 18 healthy subjects’ abilities in matching proprioceptive targets during combined single and multi-joint arm’s movements: shoulder abduction/adduction, shoulder flexion/extension, and elbow flexion/extension. Results provided evidence that proprioceptive abilities depend on the number of joints simultaneously involved in the task and on their anatomical location, since muscle spindles work along their preferred direction, modulating the streaming of sensory information accordingly. These findings suggest solutions for clinical sensorimotor evaluation after neurological disease, where assessing proprioceptive deficits can improve the recovery path and complement the rehabilitation outcomes.
The Potential of a Surface-Modified Titanium Implant with Tetrapeptide for Osseointegration Enhancement
Authors: Syam Syamsiah , Wu Chia-Jen , Lan Wen-Chien , Ou Keng-Liang , Huang Bai-Hung , Lin Yu-Yeong , Saito Takashi , Tsai Hsin-Yu , Chuo Yen-Chun , Yen Ming-Liang , Liu Chung-Ming , Hou Ping-Jen
Published: March 2021

In this study, the innovative dip-coating technique treated titanium (IDCT-Ti) implant with tetrapeptide Gly-Arg-Gly-Asp (GRGD) coating was investigated for its potential to enhance osseointegration. The L929 fibroblast cells were cultured in different concentrations of the GRGD (1%, 2%, and 5%). The cell viability was assessed through 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and live/dead staining. The surface topography and nano-indentation were analyzed by atomic force microscopy. The hemocompatibility was evaluated via field-emission scanning electron microscopy, while contact angle analysis was detected by a goniometer. Radiograph evaluation was determined by panoramic imaging. It was found that the cell growth increased and had a survival rate of more than 70% in 1% GRGD. The mortality of L929 increased with the higher concentration of GRGD. The IDCT-Ti coated with 1% GRGD showed a nano-surface with a Young’s modulus that was similar to human cortical bone, and it displayed greater red blood cell accumulations with abundant fibrin formation. As regards the wettability, the IDCT-Ti coated with 1% GRGD was lower than the SLA (sandblasted, large-grit, and acid-etched) treated implant. The X-ray image exhibited no bone loss around the implant at six months after placement. As a result, this study suggests that the IDCT-Ti implant, coated with 1% GRGD, has a tremendous likeliness to enhance osseointegration.
Storm-Time Features of the Ionospheric ELF/VLF Waves and Energetic Electron Fluxes Revealed by the China Seismo-Electromagnetic Satellite
Authors: Zhima Zeren , Hu Yunpeng , Shen Xuhui , Chu Wei , Piersanti Mirko , Parmentier Alexandra , Zhang Zhenxia , Wang Qiao , Huang Jianping , Zhao Shufan , Yang Yanyan , Yang Dehe , Sun Xiaoying , Tan Qiao , Zhou Na , Guo Feng
Published: March 2021

This study reports the temporal and spatial distributions of the extremely/very low frequency (ELF/VLF) wave activities and the energetic electron fluxes in the ionosphere during an intense storm (geomagnetic activity index Dst of approximately −174 nT) that occurred on 26 August 2018, based on the observations by a set of detectors onboard the China Seismo-Electromagnetic Satellite (CSES). A good correlation of the ionospheric ELF/VLF wave activities with energetic electron precipitations during the various storm evolution phases was revealed. The strongest ELF/VLF emissions at a broad frequency band extending up to 20 kHz occurred from the near-end main phase to the early recovery phase of the storm, while the wave activities mainly appeared at the frequency range below 6 kHz during other phases. Variations in the precipitating fluxes were also spotted in correspondence with changing geomagnetic activity, with the max values primarily appearing outside of the plasmapause during active conditions. The energetic electrons at energies below 1.5 MeV got strong enhancements during the whole storm time on both the day and night side. Examinations of the half-orbit data showed that under the quiet condition, the CSES was able to depict the outer/inner radiation belt as well as the slot region well, whereas under disturbed conditions, such regions became less sharply defined. The regions poleward from geomagnetic latitudes over 50° were found to host the most robust electron precipitation regardless of the quiet or active conditions, and in the equatorward regions below 30°, flux enhancements were mainly observed during storm time and only occasionally in quiet time. The nightside ionosphere also showed remarkable temporal variability along with the storm evolution process but with relatively weaker wave activities and similar level of fluxes enhancement compared to the ones in the dayside ionosphere. The ELF/VLF whistler-mode waves recorded by the CSES mainly included structure-less VLF waves, structured VLF quasi-periodic emissions, and structure-less ELF hiss waves. A wave vector analysis showed that during storm time, these ELF/VLF whistler-mode waves obliquely propagated, mostly likely from the radiation belt toward the Earth direction. We suggest that energetic electrons in the high latitude ionosphere are most likely transported from the outer radiation belt as a consequence of their interactions with ELF/VLF waves.
A Widely Tunable Three-Section DBR Lasers for Multi-Species Gas Detection
Authors: Yu Hongyan , Pan Jiaoqing , Zhou Xuliang , Wang Hui , Xie Liang , Wang Wei
Published: March 2021

We demonstrate a widely tunable distributed Bragg reflector (DBR) laser operating at 1.8-µm, in which the DBR section was butt-jointed InGaAsP (λ = 1.45 μm) material. Through current and temperature tuning, a widely tuning range of over 11 nm with a side mode suppression ratio (SMSR) higher than 30 dB is obtained. Utilizing this DBR laser, the water and methane detection experiment has been successfully implemented, which illustrates the potential capacity of such DBR laser as the light source used for multispecies gas sensing. The work also illustrates that the butt-joint active-passive integration technology developed for the InGaAsP quantum-wells (QWs) can be successfully applied in the InGaAs QWs.
A Comparative Analysis of Active Learning for Biomedical Text Mining
Authors: Naseem Usman , Khushi Matloob , Khan Shah Khalid , Shaukat Kamran , Moni Mohammad Ali
Published: March 2021

An enormous amount of clinical free-text information, such as pathology reports, progress reports, clinical notes and discharge summaries have been collected at hospitals and medical care clinics. These data provide an opportunity of developing many useful machine learning applications if the data could be transferred into a learn-able structure with appropriate labels for supervised learning. The annotation of this data has to be performed by qualified clinical experts, hence, limiting the use of this data due to the high cost of annotation. An underutilised technique of machine learning that can label new data called active learning (AL) is a promising candidate to address the high cost of the label the data. AL has been successfully applied to labelling speech recognition and text classification, however, there is a lack of literature investigating its use for clinical purposes. We performed a comparative investigation of various AL techniques using ML and deep learning (DL)-based strategies on three unique biomedical datasets. We investigated random sampling (RS), least confidence (LC), informative diversity and density (IDD), margin and maximum representativeness-diversity (MRD) AL query strategies. Our experiments show that AL has the potential to significantly reducing the cost of manual labelling. Furthermore, pre-labelling performed using AL expediates the labelling process by reducing the time required for labelling.
Loading Rates of Dust and Bioburden in Dwellings in an Inland City of Southern Europe
Authors: Viegas Carla , Dias Marta , Almeida Beatriz , Vicente Estela , Candeias Carla , Aranha Caetano Liliana , Carolino Elisabete , Alves Célia
Published: March 2021

Sampling campaigns indoors have shown that occupants exposed to contaminated air generally exhibit diverse health outcomes. This study intends to assess the deposition rates of total settleable dust and bioburden in the indoor air of dwellings onto quartz fiber filters and electrostatic dust collectors (EDCs), respectively. EDC extracts were inoculated onto malt extract agar (MEA) and dichloran glycerol (DG18) agar-based media used for fungal contamination characterization, while tryptic soy agar (TSA) was applied for total bacteria assessment, and violet red bile agar (VRBA) for Gram-negative bacteria. Azole-resistance screening and molecular detection by qPCR was also performed. Dust loading rates ranged from 0.111 to 3.52, averaging 0.675 μg cm−2 day−1. Bacterial counts ranged from undetectable to 16.3 colony-forming units (CFU) m−2 day−1 and to 2.95 CFU m−2 day−1 in TSA and VRBA, respectively. Fungal contamination ranged from 1.97 to 35.4 CFU m−2 day−1 in MEA, and from undetectable to 48.8 CFU m−2 day−1 in DG18. Penicillium sp. presented the highest prevalence in MEA media (36.2%) and Cladosporium sp. in DG18 (39.2%). It was possible to observe: (a) settleable dust loadings and fungal contamination higher in dwellings with pets; (b) fungal species considered indicators of harmful fungal contamination; (c) Aspergillus section Candidi identified in supplemented media with voriconazole and posaconazole; (d) specific housing typologies and (e) specific housing characteristics influencing the microbial contamination.
Characteristics and Synoptic Patterns of Regional Extreme Rainfall over the Central and Eastern Tibetan Plateau in Boreal Summer
Authors: Sun Jun , Yao Xiuping , Deng Guowei , Liu Yi
Published: March 2021

In this research, the observation datasets from 106 gauge stations over the central and eastern areas of the Tibetan Plateau (TP) and the ERA (ECMWF Re-Analysis)-Interim reanalysis datasets in the summers of 1981–2016 are used to study the characteristics and synoptic patterns of extreme precipitation events over the TP. By using a modern statistical method, the abnormal circulation characteristics at high, middle, and low latitudes in the Northern Hemisphere during extreme precipitation events over the central-eastern Tibetan Plateau are discussed, and the physical mechanisms related to the extreme precipitation events are investigated. The results show that the largest amount of extreme precipitation is found in the southern and eastern areas of the TP, where the frequency of daily extreme rainfall events (exceeding 25 mm) and the frequency of all extreme precipitation events both show obvious quasi-biweekly oscillation. When the daily extreme precipitation event threshold over the TP is met and more than 5 stations show daily extreme precipitation at the same time, with at least three of them being adjacent to each other, this is determined as a regional extreme precipitation event. As such, 33 regional daily extreme precipitation events occur during the summer periods of 1981–2016. According to the influence system, the 33 regional extreme precipitation events can be divided into three types, namely the plateau trough type, the plateau shear line type, and the plateau vortex type. For the plateau trough type, the South Asian high is anomalously strong at 100 hPa. For the other two types, the South Asian high is slightly weaker than usual. For the plateau shear line type, the development of the dynamic disturbance is the strongest, reaching 200 hPa. In the plateau trough type and plateau vortex type, the water vapor is transported by the westerly belt and the southwesterly flow from the Bay of Bengal.
Convective Characteristics and Formation Conditions in an Extreme Rainstorm on the Eastern Edge of the Tibetan Plateau
Authors: Chen Yongren , Li Yueqing
Published: March 2021

From 7 July to 11 July 2013, an extreme rainstorm occurred in the Sichuan Basin (SCB) of China, which is located at the eastern edge of the Tibetan Plateau, causing severe floods and huge economic losses. The rainstorm event was associated with mesoscale convection systems (MCSs). In this paper, we analyze the evolution characteristics and formation conditions of the MCSs, and the results show that: (1) the continuous activity of MCSs was a direct cause of the formation of extreme rainstorms. Under an “east high and west low” circulation mode, the MCSs formed a “cloud cluster wave train” phenomenon from the plateau to the basin; that is, the MCSs over the basin developed strongly in the process of the MCSs over the plateau area weakening. (2) The activities of MCSs over the rainstorm area was related to ascending branches of the two vertical circulations and topographic gravity wave. Under the influence of meridional vertical circulation, MCSs could move in the south–north direction in the western SCB, while under the influence of zonal circulation, it was difficult for MCSs to develop in the descending airflow east of 106°E. (3) In the mountainous area of the western part of the SCB, the gravity wave stress was obvious and its direction was opposite to the direction of the lower southeast warm–moist airflow. This configuration was able to form a drag effect in the low-level airflow, which was conducive to the convergence of the wind field and strengthening of the vertical ascending movement. These findings help in further understanding the effects of vertical circulation and terrain on MCSs and extreme rainstorms.
Solar Climate Features Taking into Account the Morphometric Conditions of the Area and the Possibility of Using Them in Heliotherapy on the Example of the Cieplice and Kołobrzeg Health Resorts (Poland)
Authors: Szatten Dawid , Więcław Mirosław
Published: March 2021

Global solar radiation is an important atmospheric stimulus affecting the human body and has been used in heliotherapy for years. In addition to environmental factors, the effectiveness of global solar radiation is increasingly influenced by human activity. This research was based on the use of heliographic and actinometric data (1996–2015) and the model distribution of global solar radiation to determine the possibility of heliotherapy with the example of two health resorts: Cieplice and Kołobrzeg (Poland). The solar features of health resorts (sunshine duration and global solar radiation) were characterized, and they were correlated with the spatial distribution of global solar radiation data obtained with the use of remote sensing techniques (System for Automated Geoscientific Analyzes-SAGA), including COoRdination and INformation on the Environment (CORINE) land cover (CLC) data. Using the maximum entropy model (MaxEnt), a qualitative and quantitative relationship between morphometric parameters and solar climate features was demonstrated for individual land cover types. Studies have shown that the period of late spring and summer, due to the climate’s solar features, is advisable for the use of heliotherapy. The human activity that determines the land cover is the main element influencing the spatial differentiation of the possibilities of using this form of health treatment. It also affects topographic indicators shown as significant in the MaxEnt predictive model. In general, areas with high openness were shown as predisposed for health treatment using global solar radiation, which is not consistent with areas commonly used for heliotherapy. The conducted research has shown the need for an interdisciplinary approach to the issue of heliotherapy, which will contribute to the optimization of the use of this form of health treatment from the perspective of climate change and human pressure.
GIS-Based Approach to Spatio-Temporal Interpolation of Atmospheric CO2 Concentrations in Limited Monitoring Dataset
Authors: Bezyk Yaroslav , Sówka Izabela , Górka Maciej , Blachowski Jan
Published: March 2021

Understanding the magnitude and distribution of the mixes of the near-ground carbon dioxide (CO2) components spatially (related to the surface characteristics) and temporally (over seasonal timescales) is critical to evaluating present and future climate impacts. Thus, the application of in situ measurement approaches, combined with the spatial interpolation methods, will help to explore variations in source contribution to the total CO2 mixing ratios in the urban atmosphere. This study presents the spatial characteristic and temporal trend of atmospheric CO2 levels observed within the city of Wroclaw, Poland for the July 2017–August 2018 period. The seasonal variability of atmospheric CO2 around the city was directly measured at the selected sites using flask sampling with a Picarro G2201-I Cavity Ring-Down Spectroscopy (CRDS) technique. The current work aimed at determining the accuracy of the interpolation techniques and adjusting the interpolation parameters for estimating the magnitude of CO2 time series/seasonal variability in terms of limited observations during the vegetation and non-vegetation periods. The objective was to evaluate how different interpolation methods will affect the assessment of air pollutant levels in the urban environment and identify the optimal sampling strategy. The study discusses the schemes for optimization of the interpolation results that may be adopted in areas where no observations are available, which is based on the kriging error predictions for an appropriate spatial density of measurement locations. Finally, the interpolation results were extended regarding the average prediction bias by exploring additional experimental configurations and introducing the limitation of the future sampling strategy on the seasonal representation of the CO2 levels in the urban area.
Hydrogel Models with Stiffness Gradients for Interrogating Pancreatic Cancer Cell Fate
Authors: Chang Chun-Yi , Lin Chien-Chi
Published: March 2021

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer and has seen only modest improvements in patient survival rate over the past few decades. PDAC is highly aggressive and resistant to chemotherapy, owing to the presence of a dense and hypovascularized fibrotic tissue, which is composed of stromal cells and extracellular matrices. Increase deposition and crosslinking of matrices by stromal cells lead to a heterogeneous microenvironment that aids in PDAC development. In the past decade, various hydrogel-based, in vitro tumor models have been developed to mimic and recapitulate aspects of the tumor microenvironment in PDAC. Advances in hydrogel chemistry and engineering should provide a venue for discovering new insights regarding how matrix properties govern PDAC cell growth, migration, invasion, and drug resistance. These engineered hydrogels are ideal for understanding how variation in matrix properties contributes to the progressiveness of cancer cells, including durotaxis, the directional migration of cells in response to a stiffness gradient. This review surveys the various hydrogel-based, in vitro tumor models and the methods to generate gradient stiffness for studying migration and other cancer cell fate processes in PDAC.
Protection against Glucolipotoxicity by High Density Lipoprotein in Human PANC-1 Hybrid 1.1B4 Pancreatic Beta Cells: The Role of microRNA
Authors: Tarlton Jamie M.R. , Lightbody Richard J. , Patterson Steven , Graham Annette
Published: March 2021

High-density lipoproteins provide protection against the damaging effects of glucolipotoxicity in beta cells, a factor which sustains insulin secretion and staves off onset of type 2 diabetes mellitus. This study examines epigenetic changes in small non-coding microRNA sequences induced by high density lipoproteins in a human hybrid beta cell model, and tests the impact of delivery of a single sequence in protecting against glucolipotoxicity. Human PANC-1.1B4 cells were used to establish Bmax and Kd for [3H]cholesterol efflux to high density lipoprotein, and minimum concentrations required to protect cell viability and reduce apoptosis to 30mM glucose and 0.25 mM palmitic acid. Microchip array identified the microRNA signature associated with high density lipoprotein treatment, and one sequence, hsa-miR-21-5p, modulated via delivery of a mimic and inhibitor. The results confirm that low concentrations of high-density lipoprotein can protect against glucolipotoxicity, and report the global microRNA profile associated with this lipoprotein; delivery of miR-21-5p mimic altered gene targets, similar to high density lipoprotein, but could not provide sufficient protection against glucolipotoxicity. We conclude that the complex profile of microRNA changes due to HDL treatment may be difficult to replicate using a single microRNA, findings which may inform current drug strategies focused on this approach.
Microbiome Markers of Pancreatic Cancer Based on Bacteria-Derived Extracellular Vesicles Acquired from Blood Samples: A Retrospective Propensity Score Matching Analysis
Authors: Kim Jae Ri , Han Kyulhee , Han Youngmin , Kang Nayeon , Shin Tae-Seop , Park Hyeon Ju , Kim Hongbeom , Kwon Wooil , Lee Seungyeoun , Kim Yoon-Keun , Park Taesung , Jang Jin-Young
Published: March 2021

Novel biomarkers for early diagnosis of pancreatic cancer (PC) are necessary to improve prognosis. We aimed to discover candidate biomarkers by identifying compositional differences of microbiome between patients with PC (n = 38) and healthy controls (n = 52), using microbial extracellular vesicles (EVs) acquired from blood samples. Composition analysis was performed using 16S rRNA gene analysis and bacteria-derived EVs. Statistically significant differences in microbial compositions were used to construct PC prediction models after propensity score matching analysis to reduce other possible biases. Between-group differences in microbial compositions were identified at the phylum and genus levels. At the phylum level, three species (Verrucomicrobia, Deferribacteres, and Bacteroidetes) were more abundant and one species (Actinobacteria) was less abundant in PC patients. At the genus level, four species (Stenotrophomonas, Sphingomonas, Propionibacterium, and Corynebacterium) were less abundant and six species (Ruminococcaceae UCG-014, Lachnospiraceae NK4A136 group, Akkermansia, Turicibacter, Ruminiclostridium, and Lachnospiraceae UCG-001) were more abundant in PC patients. Using the best combination of these microbiome markers, we constructed a PC prediction model that yielded a high area under the receiver operating characteristic curve (0.966 and 1.000, at the phylum and genus level, respectively). These microbiome markers, which altered microbial compositions, are therefore candidate biomarkers for early diagnosis of PC.
Gene Co-Expression Analysis of Human RNASEH2A Reveals Functional Networks Associated with DNA Replication, DNA Damage Response, and Cell Cycle Regulation
Authors: Marsili Stefania , Tichon Ailone , Kundnani Deepali , Storici Francesca
Published: March 2021

Ribonuclease (RNase) H2 is a key enzyme for the removal of RNA found in DNA-RNA hybrids, playing a fundamental role in biological processes such as DNA replication, telomere maintenance, and DNA damage repair. RNase H2 is a trimer composed of three subunits, RNASEH2A being the catalytic subunit. RNASEH2A expression levels have been shown to be upregulated in transformed and cancer cells. In this study, we used a bioinformatics approach to identify RNASEH2A co-expressed genes in different human tissues to underscore biological processes associated with RNASEH2A expression. Our analysis shows functional networks for RNASEH2A involvement such as DNA replication and DNA damage response and a novel putative functional network of cell cycle regulation. Further bioinformatics investigation showed increased gene expression in different types of actively cycling cells and tissues, particularly in several cancers, supporting a biological role for RNASEH2A but not for the other two subunits of RNase H2 in cell proliferation. Mass spectrometry analysis of RNASEH2A-bound proteins identified players functioning in cell cycle regulation. Additional bioinformatic analysis showed that RNASEH2A correlates with cancer progression and cell cycle related genes in Cancer Cell Line Encyclopedia (CCLE) and The Cancer Genome Atlas (TCGA) Pan Cancer datasets and supported our mass spectrometry findings.
Post-Translational Protein Deimination Signatures in Plasma and Plasma EVs of Reindeer (Rangifer tarandus)
Authors: D’Alessio Stefania , Thorgeirsdóttir Stefanía , Kraev Igor , Skírnisson Karl , Lange Sigrun
Published: March 2021

The reindeer (caribou) Rangifer tarandus is a Cervidae in the order Artiodactyla. Reindeer are sedentary and migratory populations with circumpolar distribution in the Arctic, Northern Europe, Siberia and North America. Reindeer are an important wild and domesticated species, and have developed various adaptive strategies to extreme environments. Importantly, deer have also been identified to be putative zoonotic carriers, including for parasites, prions and coronavirus. Therefore, novel insights into immune-related markers are of considerable interest. Peptidylarginine deiminases (PADs) are a phylogenetically conserved enzyme family which causes post-translational protein deimination by converting arginine into citrulline in target proteins. This affects protein function in health and disease. Extracellular vesicles (EVs) participate in cellular communication, in physiological and pathological processes, via transfer of cargo material, and their release is partly regulated by PADs. This study assessed deiminated protein and EV profile signatures in plasma from sixteen healthy wild female reindeer, collected in Iceland during screening for parasites and chronic wasting disease. Reindeer plasma EV profiles showed a poly-dispersed distribution from 30 to 400 nm and were positive for phylogenetically conserved EV-specific markers. Deiminated proteins were isolated from whole plasma and plasma EVs, identified by proteomic analysis and protein interaction networks assessed by KEGG and GO analysis. This revealed a large number of deimination-enriched pathways for immunity and metabolism, with some differences between whole plasma and EVs. While shared KEGG pathways for whole plasma and plasma EVs included complement and coagulation pathways, KEGG pathways specific for EVs were for protein digestion and absorption, platelet activation, amoebiasis, the AGE–RAGE signaling pathway in diabetic complications, ECM receptor interaction, the relaxin signaling pathway and the estrogen signaling pathway. KEGG pathways specific for whole plasma were pertussis, ferroptosis, SLE, thyroid hormone synthesis, phagosome, Staphylococcus aureus infection, vitamin digestion and absorption, and prion disease. Further differences were also found between molecular function and biological processes GO pathways when comparing functional STRING networks for deiminated proteins in EVs, compared with deiminated proteins in whole plasma. This study highlights deiminated proteins and EVs as candidate biomarkers for reindeer health and may provide information on regulation of immune pathways in physiological and pathological processes, including neurodegenerative (prion) disease and zoonosis.
Intraperitoneal Chemotherapy for Peritoneal Metastases: Technical Innovations, Preclinical and Clinical Advances and Future Perspectives
Authors: Christou Niki , Auger Clément , Battu Serge , Lalloué Fabrice , Jauberteau-Marchan Marie-Odile , Hervieu Céline , Verdier Mireille , Mathonnet Muriel
Published: March 2021

(1) Background: Tumors of the peritoneal serosa are called peritoneal carcinosis. Their origin may be primary by primitive involvement of the peritoneum (peritoneal pseudomyxoma, peritoneal mesothelioma, etc.). This damage to the peritoneum can also be a consequence of the dissipation of cancers—in particular, digestive (stomach, pancreas, colorectal, appendix) and gynecological (ovaries) ones in the form of metastases. The aim of the treatment is a maximal reduction of the macroscopic disease called “cytoreduction” in combination with hyperthermic intra-abdominal chemotherapy to treat residual microscopic lesions. (2) Methods: In this narrative review, we fundamentally synthetize the evolution of this process over time and its impact on clinical applications. (3) Results: Over the last past decade, different evolutions concerning both delivery modes and conditions concerning hyperthermic intra-abdominal chemotherapy have been realized. (4) Conclusion: The final objective of these evolutions is the improvement of the global and recurrence-free survival of primary and secondary malignant peritoneal pathologies. However, more large randomized controlled trials are needed to demonstrate the efficacy of such treatments with the help of molecular biology and genetics.
History and Current Status of Phytoplasma Diseases in the Middle East
Authors: Hemmati Chamran , Nikooei Mehrnoosh , Al-Subhi Ali M. , Al-Sadi Abdullah M.
Published: March 2021

Phytoplasmas that are associated with fruit crops, vegetables, cereal and oilseed crops, trees, ornamental, and weeds are increasing at an alarming rate in the Middle East. Up to now, fourteen 16Sr groups of phytoplasma have been identified in association with more than 164 plant species in this region. Peanut witches’ broom phytoplasma strains (16SrII) are the prevalent group, especially in the south of Iran and Gulf states, and have been found to be associated with 81 host plant species. In addition, phytoplasmas belonging to the 16SrVI, 16SrIX, and 16SrXII groups have been frequently reported from a wide range of crops. On the other hand, phytoplasmas belonging to 16SrIV, 16SrV, 16SrX, 16SrXI, 16SrXIV, and 16SrXXIX groups have limited geographical distribution and host range. Twenty-two insect vectors have been reported as putative phytoplasma vectors in the Middle East, of which Orosius albicinctus can transmit diverse phytoplasma strains. Almond witches’ broom, tomato big bud, lime witches’ broom, and alfalfa witches’ broom are known as the most destructive diseases. The review summarizes phytoplasma diseases in the Middle East, with specific emphasis on the occurrence, host range, and transmission of the most common phytoplasma groups.
COVID-19 Rapid Antigen Test as Screening Strategy at Points of Entry: Experience in Lazio Region, Central Italy, August–October 2020
Authors: Colavita Francesca , Vairo Francesco , Meschi Silvia , Valli Maria Beatrice , Lalle Eleonora , Castilletti Concetta , Fusco Danilo , Spiga Giuseppe , Bartoletti Pierluigi , Ursino Simona , Sanguinetti Maurizio , Di Caro Antonino , Vaia Francesco , Ippolito Giuseppe , Capobianchi Maria Rosaria
Published: March 2021

COVID-19 pandemic is a dramatic health, social and economic global challenge. There is urgent need to maximize testing capacity. Rapid Antigen Tests (RAT) represent good candidates for point-of-care and mass surveillance testing to rapidly identify SARS-CoV-2-infected people, counterbalancing lower sensitivity vs. gold standard molecular tests with fast results and possible recurrent testing. We describe the results obtained with the testing algorithm implemented at points of entry (airports and ports) in the Lazio Region (Italy), using the STANDARD F COVID-19 Antigen Fluorescence ImmunoAssay (FIA), followed by molecular confirmation of FIA-positive samples. From mid-August to mid-October 2020, 73,643 RAT were reported to the Regional Surveillance Information System for travelers at points of entry in Lazio Region. Of these, 1176 (1.6%) were FIA-positive, and the proportion of RT-PCR-confirmed samples was 40.5%. Our data show that the probability of confirmation was directly dependent from the semi-quantitative FIA results. In addition, the molecularly confirmed samples were those with high levels of virus and that were actually harboring infectious virus. These results support public health strategies based on early mass screening campaigns by RAT in settings where molecular testing is not feasible or easily accessible, such as points of entry. This approach would contribute to promptly controlling viral spread through travel, which is now of particular concern due to the spread of SARS-CoV-2 variants.
New Triterpene Glycosides from the Far Eastern Starfish Solaster pacificus and Their Biological Activity
Authors: Malyarenko Timofey V. , Kicha Alla A. , Kalinovsky Anatoly I. , Dmitrenok Pavel S. , Malyarenko Olesya S. , Kuzmich Alexandra S. , Stonik Valentin A. , Ivanchina Natalia V.
Published: March 2021

Three new triterpene glycosides, pacificusosides A–C (1–3), and three previously known triterpene glycosides, cucumariosides C1 (4), C2 (5), and A10 (6), were isolated from the alcoholic extract of the Far Eastern starfish Solaster pacificus. The structures of 1–3 were elucidated by extensive NMR and ESIMS techniques and chemical transformations. Compound 1 has a novel, unique structure, containing an aldehyde group of side chains in its triterpene aglycon. This structural fragment has not previously been found in the sea cucumber triterpene glycosides or starfish steroidal glycosides. Probably, pacificusoside A (1) is a product of the metabolism of the glycoside obtained through dietary means from a sea cucumber in the starfish. Another two new triterpene glycosides (2, 3) have closely related characteristics to sea cucumber glycosides. The cytotoxicity of compounds 1–6 was tested against human embryonic kidney HEK 293 cells, colorectal carcinoma HT-29 cells, melanoma RPMI-7951 cells, and breast cancer MDA-MB-231 cells using MTS assay. Compounds 4–6 revealed the highest cytotoxic activity against the tested cell lines, while the other investigated compounds had moderate or slight cytotoxicity. The cytotoxic effects of 2–6 were reduced by cholesterol like the similar effects of the previously investigated individual triterpene glycosides. Compounds 3, 4, and 5 almost completely suppressed the colony formation of the HT-29, RPMI-7951, and MDA-MB-231 cells at a nontoxic concentration of 0.5 µM.
Blood Levels of Galectin-9, an Immuno-Regulating Molecule, Reflect the Severity for the Acute and Chronic Infectious Diseases
Authors: Iwasaki-Hozumi Hiroko , Chagan-Yasutan Haorile , Ashino Yugo , Hattori Toshio
Published: March 2021

Galectin-9 (Gal-9) is a β-galactoside-binding lectin capable of promoting or suppressing the progression of infectious diseases. This protein is susceptible to cleavage of its linker-peptides by several proteases, and the resulting cleaved forms, N-terminal carbohydrate recognition domain (CRD) and C-terminal CRD, bind to various glycans. It has been suggested that full-length (FL)-Gal-9 and the truncated (Tr)-Gal-9s could exert different functions from one another via their different glycan-binding activities. We propose that FL-Gal-9 regulates the pathogenesis of infectious diseases, including human immunodeficiency virus (HIV) infection, HIV co-infected with opportunistic infection (HIV/OI), dengue, malaria, leptospirosis, and tuberculosis (TB). We also suggest that the blood levels of FL-Gal-9 reflect the severity of dengue, malaria, and HIV/OI, and those of Tr-Gal-9 markedly reflect the severity of HIV/OI. Recently, matrix metallopeptidase-9 (MMP-9) was suggested to be an indicator of respiratory failure from coronavirus disease 2019 (COVID-19) as well as useful for differentiating pulmonary from extrapulmonary TB. The protease cleavage of FL-Gal-9 may lead to uncontrolled hyper-immune activation, including a cytokine storm. In summary, Gal-9 has potential to reflect the disease severity for the acute and chronic infectious diseases.
Leptin Is Associated with Poor Clinical Outcomes and Promotes Clear Cell Renal Cell Carcinoma Progression
Authors: Fan Wen-Lang , Yeh Yuan-Ming , Liu Tsung-Ta , Lin Wei-Ming , Yang Tse-Yen , Lee Chao-Wei , Lin Tsung-Chieh
Published: March 2021

Emerging evidence has shown the oncogenic roles of leptin in modulating cancer progression in addition to its original roles. Analyses of transcriptomic data and patients’ clinical information have revealed leptin’s prognostic significance in renal cell carcinoma (RCC). However, its biological effects on RCC progression have not yet been explored. Clinical and transcriptomic data of a RCC cohort of 603 patients were retrieved from The Cancer Genome Atlas (TCGA) and analyzed to reveal the correlation of leptin with clinical outcomes and the hierarchical clustering of gene signatures based on leptin levels. In addition, cox univariate and multivariate regression analyses, cell migration upon leptin treatment, identification of putative leptin-regulated canonical pathways via ingenuity pathway analysis (IPA), and the investigation of induction of Wnt5a, ROR2, and Jun N-terminal Kinases (JNK) phosphorylation activation were performed. We first observed a correlation of high leptin levels and poor outcomes in RCC patients. Knowledge-based analysis by IPA indicated the induction of cancer cell migration by leptin, which was manifested via direct leptin treatment in the RCC cell lines. In RCC patients with high leptin levels, the planar cell polarity (PCP)/JNK signaling pathway was shown to be activated, and genes in the axis, including CTHRC1, FZD2, FZD10, ROR2, WNT2, WNT4, WNT10B, WNT5A, WNT5B, and WNT7B, were upregulated. All of these genes were associated with unfavorable clinical outcomes. WNT5A and ROR2 are pivotal upstream regulators of PCP/JNK signaling, and their correlations with leptin expression levels were displayed by a Pearson correlation analysis. The inhibition of signal transduction by SP600125 reversed leptin-mediated cell migration properties in RCC cell lines. The results indicate the prognostic impact of leptin on RCC patients and uncover its ability to promote cell migration via PCP/JNK signaling.
Evaluation of In Vitro Capsaicin Release and Antimicrobial Properties of Topical Pharmaceutical Formulation
Authors: Goci Enkelejda , Haloci Entela , Di Stefano Antonio , Chiavaroli Annalisa , Angelini Paola , Miha Ajkuna , Cacciatore Ivana , Marinelli Lisa
Published: March 2021

(1) Background: Capsaicin is the main capsaicinoid of the Capsicum genus and it is responsible for the pungent taste. Medical uses of the fruits of chili peppers date from the ancient time until nowadays. Most of all, they are used topically as analgesic in anti-inflammatory diseases as rheumatism, arthritis and in diabetic neuropathy. Reports state that the Capsicum genus, among other plant genera, is a good source of antimicrobial and antifungal compounds. The aim of this study was the preparation of a pharmaceutical Carbopol-based formulation containing capsaicin and the evaluation of its in vitro release and antimicrobial and antifungal properties. (2) Methods: It was first stabilized with an extraction method from the Capsicum annuum fruits with 98% ethanol and then the identification and determination of Capsaicin in this extract was realized by HPLC. (3) Results and Conclusions: Rheological analyses revealed that the selected formulation exhibited a pseudo-plastic behavior. In vitro release studies of capsaicin from a Carbopol-based formulation reported that approximately 50% of capsaicin was release within 52 h. Additionally, the Carbopol-based formulation significantly increased the antimicrobial effects of capsaicin towards all tested bacteria and fungi strains.
New Avenues for Parkinson’s Disease Therapeutics: Disease-Modifying Strategies Based on the Gut Microbiota
Authors: Lorente-Picón Marina , Laguna Ariadna
Published: March 2021

Parkinson’s disease (PD) is a multifactorial neurodegenerative disorder that currently affects 1% of the population over the age of 60 years, and for which no disease-modifying treatments exist. Neurodegeneration and neuropathology in different brain areas are manifested as both motor and non-motor symptoms in patients. Recent interest in the gut–brain axis has led to increasing research into the gut microbiota changes in PD patients and their impact on disease pathophysiology. As evidence is piling up on the effects of gut microbiota in disease development and progression, another front of action has opened up in relation to the potential usage of microbiota-based therapeutic strategies in treating gastrointestinal alterations and possibly also motor symptoms in PD. This review provides status on the different strategies that are in the front line (i.e., antibiotics; probiotics; prebiotics; synbiotics; dietary interventions; fecal microbiota transplantation, live biotherapeutic products), and discusses the opportunities and challenges the field of microbiome research in PD is facing.
Valine-279 Deletion–Mutation on Arginine Vasopressin Receptor 2 Causes Obstruction in G-Protein Binding Site: A Clinical Nephrogenic Diabetes Insipidus Case and Its Sub-Molecular Pathogenic Analysis
Authors: Chen Ming-Chun , Hsiao Yu-Chao , Chang Chun-Chun , Pan Sheng-Feng , Peng Chih-Wen , Li Ya-Tzu , Liu Cheng-Der , Liou Je-Wen , Hsu Hao-Jen
Published: March 2021

Congenital nephrogenic diabetes insipidus (CNDI) is a genetic disorder caused by mutations in arginine vasopressin receptor 2 (AVPR2) or aquaporin 2 genes, rendering collecting duct cells insensitive to the peptide hormone arginine vasopressin stimulation for water reabsorption. This study reports a first identified AVPR2 mutation in Taiwan and demonstrates our effort to understand the pathogenesis caused by applying computational structural analysis tools. The CNDI condition of an 8-month-old male patient was confirmed according to symptoms, family history, and DNA sequence analysis. The patient was identified to have a valine 279 deletion–mutation in the AVPR2 gene. Cellular experiments using mutant protein transfected cells revealed that mutated AVPR2 is expressed successfully in cells and localized on cell surfaces. We further analyzed the pathogenesis of the mutation at sub-molecular levels via long-term molecular dynamics (MD) simulations and structural analysis. The MD simulations showed while the structure of the extracellular ligand-binding domain remains unchanged, the mutation alters the direction of dynamic motion of AVPR2 transmembrane helix 6 toward the center of the G-protein binding site, obstructing the binding of G-protein, thus likely disabling downstream signaling. This study demonstrated that the computational approaches can be powerful tools for obtaining valuable information on the pathogenesis induced by mutations in G-protein-coupled receptors. These methods can also be helpful in providing clues on potential therapeutic strategies for CNDI.
Macrophage Plasticity and Function in the Lung Tumour Microenvironment Revealed in 3D Heterotypic Spheroid and Explant Models
Authors: Evans Lauren , Milward Kate , Attanoos Richard , Clayton Aled , Errington Rachel , Tabi Zsuzsanna
Published: March 2021

In non-small cell lung cancer (NSCLC), stroma-resident and tumour-infiltrating macrophages may facilitate an immunosuppressive tumour microenvironment (TME) and hamper immunotherapeutic responses. Analysis of tumour-associated macrophage (TAM) plasticity in NSCLC is largely lacking. We established a novel, multi-marker, dual analysis approach for assessing monocyte-derived macrophage (Mφ) polarisation and M1/M2 phenotypic plasticity. We developed a flow cytometry-based, two-marker analysis (CD64 and CD206) of CD14+ cells. The phenotype and immune function of in vitro-induced TAMs was studied in a heterotypic spheroid and tumour-derived explant model of NSCLC. Heterotypic spheroids and NSCLC explants skewed Mφs from an M1- (CD206loCD64hi) to M2-like (CD206hiCD64lo) phenotype. Lipopolysaccharide (LPS) and IFNγ treatment reversed M2-like Mφ polarisation, indicating the plasticity of Mφs. Importantly, antigen-specific CD8+ T cell responses were reduced in the presence of tumour explant-conditioned Mφs, but not spheroid-conditioned Mφs, suggesting explants are likely a more relevant model of the immune TME than cell line-derived spheroids. Our data indicates the importance of multi-marker, functional analyses within Mφ subsets and the advantages of the ex vivo NSCLC explant model in immunomodulation studies. We highlight the plasticity of the M1/M2 phenotype using the explant model and provide a tool for studying therapeutic interventions designed to reprogram M2-like Mφ-induced immunosuppression.
Effect of Electrolyte Concentration on Cell Sensing by Measuring Ionic Current Waveform through Micropores
Authors: Yokota Kazumichi , Hashimoto Muneaki , Kajimoto Kazuaki , Tanaka Masato , Murayama Sanae , Tsutsui Makusu , Nakajima Yoshihiro , Taniguchi Masateru , Kataoka Masatoshi
Published: March 2021

Immunostaining has been widely used in cancer prognosis for the quantitative detection of cancer cells present in the bloodstream. However, conventional detection methods based on the target membrane protein expression exhibit the risk of missing cancer cells owing to variable protein expressions. In this study, the resistive pulse method (RPM) was employed to discriminate between cultured cancer cells (NCI-H1650) and T lymphoblastoid leukemia cells (CCRF-CEM) by measuring the ionic current response of cells flowing through a micro-space. The height and shape of a pulse signal were used for the simultaneous measurement of size, deformability, and surface charge of individual cells. An accurate discrimination of cancer cells could not be obtained using 1.0 × phosphate-buffered saline (PBS) as an electrolyte solution to compare the size measurements by a microscopic observation. However, an accurate discrimination of cancer cells with a discrimination error rate of 4.5 ± 0.5% was achieved using 0.5 × PBS containing 2.77% glucose as the electrolyte solution. The potential application of RPM for the accurate discrimination of cancer cells from leukocytes was demonstrated through the measurement of the individual cell size, deformability, and surface charge in a solution with a low electrolyte concentration.