bluuebunny/crossref_metadata_2025 huggingface dataset:
Emerging and Re-emerging Vector-Borne Infectious Diseases and the Challenges for Control: A Review
Authors: Chala Bayissa , Hamde Feyissa
Published: October 2021

Vector-borne emerging and re-emerging diseases pose considerable public health problem worldwide. Some of these diseases are emerging and/or re-emerging at increasing rates and appeared in new regions in the past two decades. Studies emphasized that the interactions among pathogens, hosts, and the environment play a key role for the emergence or re-emergence of these diseases. Furthermore, social and demographic factors such as human population growth, urbanization, globalization, trade exchange and travel and close interactions with livestock have significantly been linked with the emergence and/or re-emergence of vector-borne diseases. Other studies emphasize the ongoing evolution of pathogens, proliferation of reservoir populations, and antimicrobial drug use to be the principal exacerbating forces for emergence and re-emergence of vector-borne infectious diseases. Still other studies equivocally claim that climate change has been associated with appearance and resurgence of vector-borne infectious diseases. Despite the fact that many important emerging and re-emerging vector-borne infectious diseases are becoming better controlled, our success in stopping the many new appearing and resurging vector-borne infectious diseases that may happen in the future seems to be uncertain. Hence, this paper reviews and synthesizes the existing literature to explore global patterns of emerging and re-emerging vector-borne infections and the challenges for their control. It also attempts to give insights to the epidemiological profile of major vector-borne diseases including Zika fever, dengue, West Nile fever, Crimean-Congo hemorrhagic fever, Chikungunya, Yellow fever, and Rift Valley fever.
Mechanisms of Intergenerational Environmental Stewardship Activated by COVID-19: Gratitude, Fairness, and Legacy Motives
Authors: Syropoulos Stylianos , Markowitz Ezra M.
Published: October 2021

The COVID-19 pandemic has caused an immense loss of human life, increased economic uncertainty, and negatively impacted individuals' mental health and close relationships. At the same time, experts have noted a concurrent improvement in many environmental quality indicators, including significant decreases in both localized air pollution and global greenhouse gas emissions. These positive trends are due to changes in human behavior necessitated by social distancing and self-quarantining measures (e.g., reduced car and air travel). However, there is already evidence that these improvements in environmental quality are only temporary. This suggests that more intentional efforts will be necessary in order to maintain positive environmental benefits and address major environmental issues as the world gets back to some version of pre-pandemic economic and social activity. Still, our collective experience over the course of the pandemic provides clear evidence that such change is possible and on a rapid timetable. Our individual and collective responses to COVID-19 reveal that we do indeed have the ability to respond to novel societal threats in highly coordinated and effective ways, suggesting that confronting the existential threat of climate change may in fact be feasible. Here, we theorize that the COVID-19 pandemic has potentially activated and made more salient some key psychological mechanisms—including norms of fairness and reciprocity, feelings of gratitude, and consideration of personal legacies—that previous empirical work suggests can be harnessed to promote beneficent intergenerational decision-making aimed at solving the environmental challenges we and our descendants will face in the twenty-first century.
Femoral Stem Fracture and Successful Reimplantation Using Femoral Window Technique in Canine Cemented Total Hip Replacement: Case Report
Authors: Degórska Beata , Sterna Jacek , Kalwas-Śliwińska Magdalena
Published: October 2021

A fractured stem is a very rare, late complication in total hip replacement procedure in dogs. Here, we present one case after cemented total hip replacement with successful reimplantation, including clinical signs and radiographic findings.
Estimating Global Prevalence of Metabolic Dysfunction-Associated Fatty Liver Disease in Overweight or Obese Children and Adolescents: Systematic Review and Meta-Analysis
Authors: Liu Jiaye , Mu Chunyang , Li Kewei , Luo Han , Liu Yong , Li Zhihui
Published: October 2021

Objectives: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new terminology updated from non-alcoholic fatty liver disease (NAFLD). We aim to estimate the global prevalence of MAFLD in overweight or obese children and adolescents, by repurposing existing data on fatty liver disease.

Methods: We screened relevant articles published up to December 2020. Pooled prevalence was calculated using Logit transformations.

Results: Our search returned 35,441 records, of which 156 studies fulfilled the inclusion criteria. The overall prevalence of MAFLD was 33.78% in the general population and 44.94% in a special population based on child obesity clinics, regardless of the diagnostic techniques. For subgroup analysis, MAFLD prevalence was significantly higher in boys compared to girls (36.05 vs. 26.84% in the general population; 50.20 vs. 35.34% in the child obesity clinics-based population). Interestingly, based on study source, the pooled prevalence of MAFLD was 1.5-fold higher in other “fatty liver disease” studies compared to the classical “NAFLD” studies in the general population.

Conclusion: MAFLD is highly prevalent in overweight or obese children and adolescents. Raising awareness and urgent actions are warranted to control the MAFLD pandemic across the globe.
RETORYKA EKSPRESYWNEJ EGZEMPLIFIKACJI
W JĘZYKACH TYPOLOGICZNIE ODLEGŁYCH
– NA PRZYKŁADZIE WYBRANYCH WYPOWIEDZI
POLSKICH ORAZ JAPOŃSKICH
Authors: Pietrow Jarosław A.
Published: October 2021

A confrontative analysis of distant natural languages proves fully useful in
terms of cognition when, as a result, formal differences in statement/utterance
structures arising from typological dissimilarities, yet disclosing universal
communication strategies, can be noticed. This refers also to the colloquial
rhetoric, which is illustrated by this attempt at comparing the strategy of
expressive exemplifi cation combined with the mechanism of negation in Polish
and Japanese. Usages of the Polish negative pronoun żaden (no, none) are
compared here based on an extensive corpus of colloquial sentences to the
corresponding Japanese exemplifi cation structure based on the use of the
form nanka, which, in turn, permits the observation of characteristic shifts in
the hierarchy of the exponents of the former and the latter semantic function
mentioned here. The synthetic nature of the Polish structure places the negation
higher in the hierarchy, thus prevailing over the meaning of the exemplifi cation,
while in the Japanese language the analytical separation of both meanings
places the exemplifi cation and the negation at an equal level as part of the
separately shaped thematic-rhematic segmentation of statements/utterances.
Financialization of economy and politics in contemporary capitalism. Selected problems
Authors: Osiński Joachim , Zawiślińska Izabela
Published: October 2021

The authors analyze the essence of the problem of financialization of economy in the national and global perspectives, at the same time pointing out that this process also refers to the sphere of politics. The example of the 2007+ financial and banking crisis indicates the negative features of this process in reference to economy but also to the financial security of the states and their citizens. In the sphere of politics financialization in the external aspect is reflected in transferring public funds to private economic entities, mainly financial corporations, by virtue of political decisions. In the internal aspects financialization means an increasing role of financial instruments and resources in establishing public authorities, including parliaments and presidential offices. This tendency is considered by the authors to be an immanent feature of contemporary capitalism and a threat to democracy.
Carbon Polygons and Carbon Offsets: Current State, Key Challenges and Pedological Aspects
Authors: Abakumov Evgeny , Polyakov Vyacheslav
Published: October 2021

Russia holds the largest store of carbon in soils, forests and permafrost grounds. Carbon, stored in a stabilized form, plays an important role in the balance of the global biogeochemical cycle and greenhouse gases. Thus, recalcitrance of soil organic matter to mineralization results in a decrease in current emissions of carbon dioxide into the atmosphere. At the same time, stabilization of organic matter in the form of humus due to organo–mineral interactions leads to the sequestration of carbon from the atmosphere into soils and biosediments. Thus, global carbon balance is essentially determined by soil cover state and stability. Currently, Russia is faced with a set of problems regarding carbon offsets and the carbon economy. One of the methods used to evaluate carbon stocks in ecosystems and verify offsets rates is carbon polygons, which are currently being organized, or are under organization, in various regions of Russia. This discussion addresses the current issues surrounding the methods and methodology of carbon polygons and their pedological organization and function.
Enterococcus spp. as a Producer and Target of Bacteriocins: A Double-Edged Sword in the Antimicrobial Resistance Crisis Context
Authors: Almeida-Santos Ana C. , Novais Carla , Peixe Luísa , Freitas Ana R.
Published: October 2021

Enterococcus spp. are one of the most frequent producers of bacteriocins (enterocins), which provides them with an advantage to compete in their natural environment, which is the gut of humans and many animals. The enterocins’ activity against microorganisms from different phylogenetic groups has raised interest in Enterococcus spp. in different contexts throughout the last decades, especially in the food industry. Nevertheless, some species can also cause opportunistic life-threatening infections and are frequently multidrug-resistant (MDR). Vancomycin-resistant Enterococcus (VRE), in particular, are an ongoing global challenge given the lack of therapeutic options. In this scenario, bacteriocins can offer a potential solution to this persistent threat, either alone or in combination with other antimicrobials. There are a handful of studies that demonstrate the advantages and applications of bacteriocins, especially against VRE. The purpose of this review is to present a current standpoint about the dual role of Enterococcus spp., from important producers to targets needed to be controlled, and the crucial role that enterocins may have in the expansion of enterococcal populations. Classification and distribution of enterocins, the current knowledge about the bacteriocinome of clinical enterococci, and the challenges of bacteriocin use in the fight against VRE infections are particularly detailed.
Integrating the Human and Animal Sides of Mycoplasmas Resistance to Antimicrobials
Authors: Pereyre Sabine , Tardy Florence
Published: October 2021

Mycoplasma infections are frequent in humans, as well as in a broad range of animals. However, antimicrobial treatment options are limited, partly due to the lack of a cell wall in these peculiar bacteria. Both veterinary and human medicines are facing increasing resistance prevalence for the most commonly used drugs, despite different usage practices. To date, very few reviews have integrated knowledge on resistance to antimicrobials in humans and animals, the latest dating back to 2014. To fill this gap, we examined, in parallel, antimicrobial usage, resistance mechanisms and either phenotype or genotype-based methods for antimicrobial susceptibility testing, as well as epidemiology of resistance of the most clinically relevant human and animal mycoplasma species. This review unveiled common features and differences that need to be taken into consideration in a “One Health” perspective. Lastly, two examples of critical cases of multiple drug resistance are highlighted, namely, the human M. genitalium and the animal M. bovis species, both of which can lead to the threat of untreatable infections.
Development of an Optimized Drying Process for the Recovery of Bioactive Compounds from the Autumn Fruits of Berberis vulgaris L. and Crataegus monogyna Jacq.
Authors: Moldovan Cadmiel , Frumuzachi Oleg , Babotă Mihai , Menghini Luigi , Cesa Stefania , Gavan Alexandru , Sisea Cristian R. , Tanase Corneliu , Dias Maria Inês , Pereira Carla , Ferreira Isabel C.F.R. , Crișan Gianina , Mocan Andrei , Barros Lillian
Published: October 2021

Hot air drying has proven to be an efficient method to preserve specific edible plant materials with medicinal properties. This is a process involving chemical, physical, and biological changes in plant matrices. Understanding these processes will lead to an improvement in the yields of bioactive compounds. This study aims to optimize the drying process of two species’ fruits used in folk medicine, Berberis vulgaris and Crataegus monogyna. The optimized extracts’ antioxidant capacity was assessed using various assays, with the barberry extract showing very good activity (50.85, 30.98, and 302.45 mg TE/g dw for DPPH, TEAC, and FRAP assays, respectively). Both species exerted good fungal α-glucosidase inhibitory activity (IC50 = 0.34 and 0.56 mg/mL, respectively) but no activity on mammalian α-glucosidase. Additionally, this study identified and quantified the main bioactive compounds. The results presented herein are a breakthrough in industrializing this drying process. Additional studies are necessary to mechanistically understand the drying process involved in these plant materials.
Modeling and Spatiotemporal Mapping of Water Quality through Remote Sensing Techniques: A Case Study of the Hassan Addakhil Dam
Authors: El Ouali Anas , El Hafyani Mohammed , Roubil Allal , Lahrach Abderrahim , Essahlaoui Ali , Hamid Fatima Ezzahra , Muzirafuti Anselme , Paraforos Dimitrios S. , Lanza Stefania , Randazzo Giovanni
Published: October 2021

With its high water potential, the Ziz basin is one of the most important basins in Morocco. This paper aims to develop a methodology for spatiotemporal monitoring of the water quality of the Hassan Addakhil dam using remote sensing techniques combined with a modeling approach. Firstly, several models were established for the different water quality parameters (nitrate, dissolved oxygen and chlorophyll a) by combining field and satellite data. In a second step, the calibration and validation of the selected models were performed based on the following statistical parameters: compliance index R2, the root mean square error and p-value. Finally, the satellite data were used to carry out spatiotemporal monitoring of the water quality. The field results show excellent quality for most of the samples. In terms of the modeling approach, the selected models for the three parameters (nitrate, dissolved oxygen and chlorophyll a) have shown a good correlation between the measured and estimated values with compliance index values of 0.62, 0.56 and 0.58 and root mean square error values of 0.16 mg/L, 0.65 mg/L and 0.07 µg/L for nitrate, dissolved oxygen and chlorophyll a, respectively. After the calibration, the validation and the selection of the models, the spatiotemporal variation of water quality was determined thanks to the multitemporal satellite data. The results show that this approach is an effective and valid methodology for the modeling and spatiotemporal mapping of water quality in the reservoir of the Hassan Addakhil dam. It can also provide valuable support for decision-makers in water quality monitoring as it can be applied to other regions with similar conditions.
FLINT: Flows for the Internet of Things
Authors: Moons Bart , Aernouts Michiel , Bracke Vincent , Volckaert Bruno , Hoebeke Jeroen
Published: October 2021

New protocols and technologies are continuously competing in the Internet of Things. This has resulted in a fragmented landscape that complicates the integration of different solutions. Standardization efforts try to avoid this problem, however within a certain ecosystem, multiple standards still require integration to enable trans-sector innovation. Moreover, existing devices require transformations to fit in an ecosystem. In this paper, we discuss several integration problems in the field of Low Power Wide Area Networks in the context of the Port of the Future and propose a new distributed platform architecture, called FLINT. FLINT is a framework to program flexible and configurable flows on a per device basis. A flow is constructed from fine-grained components, called adapters. Due to the modularity of an adapter, users can easily integrate existing software. We evaluated FLINT based on five levels of interoperability and show that FLINT can be used to interconnect non-interoperable systems and protocols on every level. We have also implemented FLINT in a container based environment and demonstrated that a basic configuration has a 99% forwarding rate of 17.500 513-byte packets per second, showing that the architecture can deliver good performance.
An Observational Study of GPS-Derived Integrated Water Vapor over India
Authors: Gopalan Kaushik , Shukla Bipasha Paul , Sharma Som , Kumar Prashant , Shyam Abhineet , Gaur Amita , Sunda Surendra
Published: October 2021

This study describes the process of deriving integrated water vapor (IWV) from (a) a set of 18 GPS receivers that were installed at different airports across India and (b) a pair of GPS receivers located in Ahmedabad situated around 8 km apart. The Zenith Tropospheric Delay was estimated from the GPS observations using the GAMIT software. Further, IWV was estimated from the ZTD values using surface temperature and pressure from ERA-I reanalysis as additional inputs. The IWV estimates for 1 year—March 2013 to February 2014—were compared with ECMWF Reanalysis Interim (ERA-I) reanalysis as well as radiosonde soundings. The Root Mean Squared Error (RMSE) was ≈6 mm or better for most stations. The IWV estimates for July 2013 were assimilated into the WRF model and had a positive impact on model analysis of IWV. The forecasted rain improved by up to 3–4 mm/day in some regions as a result of GPS-derived IWV estimates. For the Ahmedabad receivers, the GPS-derived IWV was compared with IWV from ERA-I reanalysis and was found to have a RMSE of ≈7.7 mm which is <20% of the mean value. The study demonstrates that the observed IWV variation is consistent with rainfall patterns over Ahmedabad. The rise and dips in the IWV correlate well with the active-break cycle in the monsoon rain. The study demonstrates the value of local measurements of IWV with high temporal frequency, as they are more likely to respond to fast-moving weather phenomena such as rainfall. Thus, the GPS-derived IWV measurements are likely to have significant value in the short-term forecasts of precipitation.
Assessment and Calibration of a Low-Cost PM2.5 Sensor Using Machine Learning (HybridLSTM Neural Network): Feasibility Study to Build an Air Quality Monitoring System
Authors: Park Donggeun , Yoo Geon-Woo , Park Seong-Ho , Lee Jong-Hyeon
Published: October 2021

Commercially available low-cost air quality sensors have low accuracy. The improved accuracy of low-cost PM2.5 sensors allows the use of low-cost sensor systems to reasonably investigate PM2.5 emissions from industrial activities or to accurately estimate individual exposure to PM2.5. In this work, we developed a new PM2.5 calibration model (HybridLSTM) by combining a deep neural network (DNN) optimized in calibration problems and a long short-term memory (LSTM) neural network optimized in time-dependent characteristics to improve the performance of conventional calibration algorithms of low-cost PM sensors. The PM2.5 concentrations, temperature and humidity by low-cost sensors and gravimetric-based PM2.5 measuring instrument were sampled for a sufficiently long time. The proposed model was compared with benchmarks (multiple linear regression model (MLR), DNN model) and low-cost sensor results. The gravimetric measurements were used as reference data to evaluate sensor accuracy. For root-mean-square error (RMSE) for PM2.5 concentrations, the proposed model reduced 41–60% of error when compared with the raw data of low-cost sensors, reduced 30–51% of error when compared with the MLR model and reduced 8–40% of error when compared with the MLR model. R2 of HybridLSTM, DNN, MLR and raw data were 93, 90, 80 and 59%, respectively. HybridLSTM showed the state-of-the-art calibration performance for a low-cost PM sensor. In other words, the proposed ML model has state-of-the-art calibration performance among the tested calibration algorithms.
Compositional Spatio-Temporal PM2.5 Modelling in Wildfires
Authors: Sánchez-Balseca Joseph , Pérez-Foguet Agustií
Published: October 2021

Wildfires are natural ecological processes that generate high levels of fine particulate matter (PM2.5) that are dispersed into the atmosphere. PM2.5 could be a potential health problem due to its size. Having adequate numerical models to predict the spatial and temporal distribution of PM2.5 helps to mitigate the impact on human health. The compositional data approach is widely used in the environmental sciences and concentration analyses (parts of a whole). This numerical approach in the modelling process avoids one common statistical problem: the spurious correlation. PM2.5 is a part of the atmospheric composition. In this way, this study developed an hourly spatio-temporal PM2.5 model based on the dynamic linear modelling framework (DLM) with a compositional approach. The results of the model are extended using a Gaussian–Mattern field. The modelling of PM2.5 using a compositional approach presented adequate quality model indices (NSE = 0.82, RMSE = 0.23, and a Pearson correlation coefficient of 0.91); however, the correlation range showed a slightly lower value than the conventional/traditional approach. The proposed method could be used in spatial prediction in places without monitoring stations.
Characteristics of Subseasonal Winter Prediction Skill Assessment of GloSea5 for East Asia
Authors: Ham Suryun , Jeong Yeomin
Published: October 2021

In this study, the characteristics of systematic errors in subseasonal prediction for East Asia are investigated using an ensemble hindcast (1991–2010) produced by the Global Seasonal Forecasting System version 5 (GloSea5). GloSea5 is a global prediction system for the subseasonal-to-seasonal time scale, based on a fully coupled atmosphere, land, ocean, and sea ice model. To examine the fidelity of the system with respect to reproducing and forecasting phenomena, this study assesses the systematic biases in the global prediction model focusing on the prediction skill for the East Asian winter monsoon (EAWM), which is a major driver of weather and climate variability in East Asia. To investigate the error characteristics of GloSea5, the hindcast period is analyzed by dividing it into two periods: 1991–2000 and 2001–2010. The main results show that the prediction skill for the EAWM with a lead time of 3 weeks is significantly decreased in the 2000s compared to the 1990s. To investigate the reason for the reduced EAWM prediction performance in the 2000s, the characteristics of the teleconnections relating to the polar and equatorial regions are examined. It is found that the simulated excessive weakening of the East Asian jet relating to the tropics and a failure in representing the Siberian high pressure relating to the Arctic are mainly responsible for the decreased EAWM prediction skill.
A Missing Puzzle in Dissociative Electron Attachment to Biomolecules: The Detection of Radicals
Authors: Ptasinska Sylwia
Published: October 2021

Ionizing radiation releases a flood of low-energy electrons that often causes the fragmentation of the molecular species it encounters. Special attention has been paid to the electrons’ contribution to DNA damage via the dissociative electron attachment (DEA) process. Although numerous research groups worldwide have probed these processes in the past, and many significant achievements have been made, some technical challenges have hindered researchers from obtaining a complete picture of DEA. Therefore, this research perspective calls urgently for the implementation of advanced techniques to identify non-charged radicals that form from such a decomposition of gas-phase molecules. Having well-described DEA products offers a promise to benefit society by straddling the boundary between physics, chemistry, and biology, and it brings the tools of atomic and molecular physics to bear on relevant issues of radiation research and medicine.
Development of a Spinal Cord Injury Model Permissive to Study the Cardiovascular Effects of Rehabilitation Approaches Designed to Induce Neuroplasticity
Authors: Wainman Liisa , Erskine Erin L. , Ahmadian Mehdi , Hanna Thomas Matthew , West Christopher R.
Published: October 2021

As primary medical care for spinal cord injury (SCI) has improved over the last decades there are more individuals living with neurologically incomplete (vs. complete) cervical injuries. For these individuals, a number of promising therapies are being actively researched in pre-clinical settings that seek to strengthen the remaining spinal pathways with a view to improve motor function. To date, few, if any, of these interventions have been tested for their effectiveness to improve autonomic and cardiovascular (CV) function. As a first step to testing such therapies, we aimed to develop a model that has sufficient sparing of descending sympathetic pathways for these interventions to target yet induces robust CV impairment. Twenty-six Wistar rats were assigned to SCI (n = 13) or naïve (n = 13) groups. Animals were injured at the T3 spinal segment with 300 kdyn of force. Fourteen days post-SCI, left ventricular (LV) and arterial catheterization was performed to assess in vivo cardiac and hemodynamic function. Spinal cord lesion characteristics along with sparing in catecholaminergic and serotonergic projections were determined via immunohistochemistry. SCI produced a decrease in mean arterial pressure of 17 ± 3 mmHg (p < 0.001) and left ventricular contractility (end-systolic elastance) of 0.7 ± 0.1 mmHg/µL (p < 0.001). Our novel SCI model produced significant decreases in cardiac and hemodynamic function while preserving 33 ± 9% of white matter at the injury epicenter, which we believe makes it a useful pre-clinical model of SCI to study rehabilitation approaches designed to induce neuroplasticity.
Deciphering the Molecular Machinery—Influence of sE-Cadherin on Tumorigenic Traits of Prostate Cancer Cells
Authors: Tsaur Igor , Thomas Anita , Juengel Eva , Maxeiner Sebastian , Grein Timothy , Le Quynh Chi , Muschta Veronika , Rutz Jochen , Chun Felix K. H. , Blaheta Roman A.
Published: October 2021

The serum level of soluble (s)E-cadherin is elevated in several malignancies, including prostate cancer (PCa). This study was designed to investigate the effects of sE-cadherin on the behavior of PCa cells in vitro, with the aim of identifying a potential therapeutic target. Growth as well as adhesive and motile behavior were evaluated in PC3, DU-145, and LNCaP cells. Flow cytometry was used to assess cell cycle phases and the surface expression of CD44 variants as well as α and β integrins. Confocal microscopy was utilized to visualize the distribution of CD44 variants within the cells. Western blot was applied to investigate expression of α3 and β1 integrins as well as cytoskeletal and adhesion proteins. Cell growth was significantly inhibited after exposure to 5 µg/mL sE-cadherin and was accompanied by a G0/G1-phase arrest. Adhesion of cells to collagen and fibronectin was mitigated, while motility was augmented. CD44v4, v5, and v7 expression was elevated while α3 and β1 integrins were attenuated. Blocking integrin α3 reduced cell growth and adhesion to collagen but increased motility. sE-cadherin therefore appears to foster invasive tumor cell behavior, and targeting it might serve as a novel and innovative concept to treat advanced PCa.
An OpenCV-Based Approach for Automated Cardiac Rhythm Measurement in Zebrafish from Video Datasets
Authors: Farhan Ali , Kurnia Kevin Adi , Saputra Ferry , Chen Kelvin H.-C. , Huang Jong-Chin , Roldan Marri Jmelou M. , Lai Yu-Heng , Hsiao Chung-Der
Published: October 2021

Cardiac arrhythmia has been defined as one of the abnormal heart rhythm symptoms, which is a common problem dealt with by cardiologists. Zebrafish were established as a powerful animal model with a transparent body that enables optical observation to analyze cardiac morphology and cardiac rhythm regularity. Currently, research has observed heart-related parameters in zebrafish, which used different approaches, such as starting from the use of fluorescent transgenic zebrafish, different software, and different observation methods. In this study, we developed an innovative approach by using the OpenCV library to measure zebrafish larvae heart rate and rhythm. The program is designed in Python, with the feature of multiprocessing for simultaneous region-of-interest (ROI) detection, covering both the atrium and ventricle regions in the video, and was designed to be simple and user-friendly, having utility even for users who are unfamiliar with Python. Results were validated with our previously published method using ImageJ, which observes pixel changes. In summary, the results showed good consistency in heart rate-related parameters. In addition, the established method in this study also can be widely applied to other invertebrates (like Daphnia) for cardiac rhythm measurement.
Cisplatin Mouse Models: Treatment, Toxicity and Translatability
Authors: Perše Martina
Published: October 2021

Cisplatin is one of the most widely used chemotherapeutic drugs in the treatment of a wide range of pediatric and adult malignances. However, it has various side effects which limit its use. Cisplatin mouse models are widely used in studies investigating cisplatin therapeutic and toxic effects. However, despite numerous promising results, no significant improvement in treatment outcome has been achieved in humans. There are many drawbacks in the currently used cisplatin protocols in mice. In the paper, the most characterized cisplatin protocols are summarized together with weaknesses that need to be improved in future studies, including hydration and supportive care. As demonstrated, mice respond to cisplatin treatment in similar ways to humans. The paper thus aims to illustrate the complexity of cisplatin side effects (nephrotoxicity, gastrointestinal toxicity, neurotoxicity, ototoxicity and myelotoxicity) and the interconnectedness and interdependence of pathomechanisms among tissues and organs in a dose- and time-dependent manner. The paper offers knowledge that can help design future studies more efficiently and interpret study outcomes more critically. If we want to understand molecular mechanisms and find therapeutic agents that would have a potential benefit in clinics, we need to change our approach and start to treat animals as patients and not as tools.
Role of Adropin in Cardiometabolic Disorders: From Pathophysiological Mechanisms to Therapeutic Target
Authors: Bozic Josko , Kumric Marko , Ticinovic Kurir Tina , Males Ivan , Borovac Josip A. , Martinovic Dinko , Vilovic Marino
Published: October 2021

Although a large amount of data supports the crucial role of endothelial dysfunction (ED) in cardiovascular diseases (CVDs), there is a large bench-to-bedside chasm between basic and clinical research of ED, limiting the implementation of these findings in everyday clinical settings. Hence, it is important to further investigate the pathophysiological mechanisms underlying ED and find modalities that will alleviate its clinical implementation. Adropin, a highly conserved peptide hormone secreted primarily by the liver, recently emerged as an important regulatory component of the vascular endothelium. Specifically, the vasoprotective role of adropin is achieved mainly by affecting endothelial NO synthesis. Thus, in this review, we aimed to summarize the current knowledge regarding the role of adropin in physiological processes and address the protective role of adropin in endothelium with consequent implications to CV pathologies. We focused on data regarding the role of adropin in the clinical setting, with concurrent implications to future clinical use of adropin. Studies suggest that plasma levels of adropin correlate with indices of ED in various pathologies and enhanced disease progression, implying that adropin may serve as a useful biomarker of ED in the upcoming future. On the other hand, despite notable results with respect to therapeutic potential of adropin in preliminary experiments, further well-designed studies are warranted in order to establish if adropin might be beneficial in this setting.
Design and Analysis of a Single System of Impedimetric Biosensors for the Detection of Mosquito-Borne Viruses
Authors: Nasrin Fahmida , Tsuruga Kenta , Utomo Doddy Irawan Setyo , Chowdhury Ankan Dutta , Park Enoch Y.
Published: October 2021

The treatment for mosquito-borne viral diseases such as dengue virus (DENV), zika virus (ZIKV), and chikungunya virus (CHIKV) has become difficult due to delayed diagnosis processes. In addition, sharing the same transmission media and similar symptoms at the early stage of infection of these diseases has become more critical for early diagnosis. To overcome this, a common platform that can identify the virus with high sensitivity and selectivity, even for the different serotypes, is in high demand. In this study, we have attempted an electrochemical impedimetric method to detect the ZIKV, DENV, and CHIKV using their corresponding antibody-conjugated sensor electrodes. The significance of this method is emphasized on the fabrication of a common matrix of gold–polyaniline and sulfur, nitrogen-doped graphene quantum dot nanocomposites (Au-PAni-N,S-GQDs), which have a strong impedimetric response based only on the conjugated antibody, resulting in minimum cross-reactivity for the detection of various mosquito-borne viruses, separately. As a result, four serotypes of DENV and ZIKV, and CHIKV have been detected successfully with an LOD of femtogram mL−1.
Dealing with Headache: Sex Differences in the Burden of Migraine- and Tension-Type Headache
Authors: Neumeier Maria Susanne , Pohl Heiko , Sandor Peter S. , Gut Hans , Merki-Feld Gabriele S. , Andrée Colette
Published: October 2021

Objective: The aim of this study was to investigate sex differences in the burden of migraine and tension-type headache (TTH). Background: Migraine and TTH are more common in women than in men, with differences in comorbidities, treatment responses, disease-modifying factors, and ictal and interictal burden of disease. Information about sex-related influences on ictal and interictal burden is limited, and an increased understanding is mandatory to provide tailored individual treatment for female and male patients. Methods: Participants answered an online survey based on the EUROLIGHT questionnaire. Inclusion criteria were the consent to participate, complete responses to the diagnostic questions, and information about their sex. Sex differences were investigated using the Mann–Whitney U test or Chi-square test. For detecting factors that influence the burden of disease, we built binary regression models. Results: We included 472 (74.6% female) migraineurs and 161 (59.6% female) participants with TTH. Women with migraine reported significantly more problems in their love lives, more self-concealment, less feelings of being understood by family and friends, more interictal anxiety, a higher pain severity, and more depression and anxiety symptoms than men. For TTH, we did not find significant sex-related differences. A higher headache frequency was the factor that increased the burden of disease in female but not in male migraneurs. Conclusion: The burden of disease was higher in women than men with migraine in many aspects, but not with TTH. Therefore, according to our results, there is a need for sex-specific precision medicine for migraine but not TTH. Controlling the headache frequency with a proper acute or prophylactic treatment and treating comorbid depression and anxiety symptoms is crucial to ease migraine’s burden, especially in women.
Timing-Dependent Effects of Transcranial Direct Current Stimulation on Hand Motor Function in Healthy Individuals: A Randomized Controlled Study
Authors: Jo Nam-Gyu , Kim Gi-Wook , Won Yu Hui , Park Sung-Hee , Seo Jeong-Hwan , Ko Myoung-Hwan
Published: October 2021

The timing of transcranial direct current stimulation (tDCS) is essential for enhancing motor skill learning. Previously, tDCS, before or concurrently, with motor training was evaluated in healthy volunteers or elderly patients, but the optimal timing of stimulation has not been determined. In this study, we aimed to optimize the existing tDCS protocols by exploring the timing-dependent stimulation effects on finger movements in healthy individuals. We conducted a single-center, prospective, randomized controlled trial. The study participants (n = 39) were randomly assigned into three groups: tDCS concurrently with finger tapping training (CON), tDCS prior to finger tapping training (PRI), and SHAM-tDCS simultaneously with finger tapping training (SHAM). In all groups, the subjects participated in five 40-min training sessions for one week. Motor performance was measured before and after treatment using the finger-tapping task (FTT), the grooved pegboard test (GPT), and hand strength tests. tDCS treatment prior to finger tapping training significantly improved motor skill learning, as indicated by the GPT and hand strength measurements. In all groups, the treatment improved the FTT performance. Our results indicate that applying tDCS before training could be optimal for enhancing motor skill learning. Further research is required to confirm these findings.
Is There a Relation between 677C>T Polymorphism in the MTHFR Gene and the Susceptibility to Epilepsy in Young Patients? A Meta-Analysis
Authors: Sarecka-Hujar Beata
Published: October 2021

Background: Numerous data show a role for genetic polymorphisms in the development of epilepsy. Previously, the TT genotype of the MTHFR 677C>T polymorphism was found to be associated with a decreased leucocyte DNA methylation status. Polymorphisms in the MTHFR gene could modify the pharmacodynamics of many drugs. This meta-analysis aimed to assess the relationship between MTHFR 677C>T polymorphism and susceptibility to epilepsy in young patients. Methods: Available databases (PubMed, Embase, Google Scholar, SciELO, and Medline) were searched using specific keywords. Eight studies, published between 1999 and 2019, with 1678 young patients with epilepsy and 1784 controls, met the inclusion criteria. Apart from the total groups, additional analyses in age subgroups (i.e., young adults and children) were conducted. Statistical analyses were conducted using the RevMan 5.4 and MedCalc software. The pooled odds ratio (OR) was estimated with a random- or fixed-effects model depending on the heterogeneity. Analyses were performed for five genetic models, i.e., dominant (CT + TT vs. CC), recessive (TT vs. CC + CT), additive (TT vs. CC), heterozygous (CT vs. CC), and allelic (T vs. C). The publication bias was assessed with the use of Egger’s and Begg’s tests. Results: Both the MTHFR TT genotype (in the additive model) and the T allele (in the allelic model) significantly increased the risk of epilepsy when the total groups were compared (OR = 1.44, p = 0.002, and OR = 1.183, p = 0.001, respectively). The sensitivity analysis for these models indicated the stability of the results. Similarly, significant results were obtained among young adults for all the genetic models (dominant model: OR = 1.28, p = 0.002; recessive model: OR = 1.48, p = 0.003; additive model: OR = 1.63, p < 0.001; heterozygous model: OR = 1.21, p = 0.028; and allelic model: OR = 1.256, p < 0.001). Those results were also stable and reliable. In the group of children, no relation between 677C>T polymorphism and epilepsy was observed; however, the analysis was based only on three studies, and one study also comprised young adults. No publication bias was demonstrated. Conclusions: The meta-analysis revealed that the carrier state for the T allele as well as the TT genotype of the MTHFR 677C>T polymorphism increases the risk of epilepsy in young adults but not in children.
Oligometastatic Disease Detection with 68Ga-PSMA-11 PET/CT in Hormone-Sensitive Prostate Cancer Patients (HSPC) with Biochemical Recurrence after Radical Prostatectomy: Predictive Factors and Clinical Impact
Authors: Artigas Carlos , Diamand Romain , Shagera Qaid Ahmed , Plouznikoff Nicolas , Fokoue Fabrice , Otte François-Xavier , Gil Thierry , Peltier Alexandre , Van Gestel Dirk , Flamen Patrick
Published: October 2021

Metastasis-directed therapy (MDT) in oligometastatic prostate cancer has the potential of delaying the start of androgen deprivation therapy (ADT) and disease progression. We aimed to analyze the efficacy of PSMA-PET/CT in detecting oligometastatic disease (OMD), to look for predictive factors of OMD, and to evaluate the impact of PSMA-PET/CT findings on clinical management. We retrospectively analyzed a homogeneous population of 196 hormone-sensitive prostate cancer patients (HSPC), considered potential candidates for MDT, with a PSMA-PET/CT performed at biochemical recurrence (BCR) after radical prostatectomy (RP). Multivariable logistic regression analysis was performed based on several clinico-pathological factors. Changes in clinical management before and after PSMA-PET/CT were analyzed. The OMD detection rate was 44% for a total positivity rate of 60%. PSMA-PET/CT positivity was independently related to PSA (OR (95% CI), p) (1.7 (1.3–2.3), p < 0.0001) and PSAdt (0.4 (0.2–0.8), p = 0.013), and OMD detection was independently related to PSA (1.6 (1.2–2.2), p = 0.001) and no previous salvage therapy (0.3 (0.1–0.9), p = 0.038). A treatment change was observed in 58% of patients, mostly to perform MDT after OMD detection (60% of changes). This study showed that PSMA-PET/CT is an excellent imaging technique to detect OMD early in HSPC patients with BCR after RP, changing therapeutic management mostly into MDT.
Vimentin Is at the Heart of Epithelial Mesenchymal Transition (EMT) Mediated Metastasis
Authors: Usman Saima , Waseem Naushin H. , Nguyen Thuan Khanh Ngoc , Mohsin Sahar , Jamal Ahmad , Teh Muy-Teck , Waseem Ahmad
Published: October 2021

Epithelial-mesenchymal transition (EMT) is a reversible plethora of molecular events where epithelial cells gain the phenotype of mesenchymal cells to invade the surrounding tissues. EMT is a physiological event during embryogenesis (type I) but also happens during fibrosis (type II) and cancer metastasis (type III). It is a multifaceted phenomenon governed by the activation of genes associated with cell migration, extracellular matrix degradation, DNA repair, and angiogenesis. The cancer cells employ EMT to acquire the ability to migrate, resist therapeutic agents and escape immunity. One of the key biomarkers of EMT is vimentin, a type III intermediate filament that is normally expressed in mesenchymal cells but is upregulated during cancer metastasis. This review highlights the pivotal role of vimentin in the key events during EMT and explains its role as a downstream as well as an upstream regulator in this highly complex process. This review also highlights the areas that require further research in exploring the role of vimentin in EMT. As a cytoskeletal protein, vimentin filaments support mechanical integrity of the migratory machinery, generation of directional force, focal adhesion modulation and extracellular attachment. As a viscoelastic scaffold, it gives stress-bearing ability and flexible support to the cell and its organelles. However, during EMT it modulates genes for EMT inducers such as Snail, Slug, Twist and ZEB1/2, as well as the key epigenetic factors. In addition, it suppresses cellular differentiation and upregulates their pluripotent potential by inducing genes associated with self-renewability, thus increasing the stemness of cancer stem cells, facilitating the tumour spread and making them more resistant to treatments. Several missense and frameshift mutations reported in vimentin in human cancers may also contribute towards the metastatic spread. Therefore, we propose that vimentin should be a therapeutic target using molecular technologies that will curb cancer growth and spread with reduced mortality and morbidity.
Insulin Receptor in Pancreatic Cancer—Crown Witness in Cross Examination
Authors: Heckl Steffen M. , Kercher Lukas , Abdullazade Samir , Schneider Carolin , Krüger Sandra , Behrens Hans-Michael , Sebens Susanne , Schäfer Heiner , Schreiber Stefan , Röcken Christoph
Published: October 2021

Background: The proximity of pancreatic cancer (PDAC) to the physiological source of the growth promoting hormone insulin might be exploited by this highly malignant cancer entity. We investigated if (I) PDACs express the insulin receptor (IR) in cancer cells and cancer vasculature, (II) if IR correlates with clinicopathological patient characteristics, including survival, and hence is involved in PDAC biology, (III) if IR is already expressed in precursor lesions, if (IV) the IGF1 receptor (IGF1R) is associated with clinicopathological patient characteristics and survival and (V) is linked to IR expression. Methods: 160 PDAC samples were examined for IR and IGF1R expression by immunohistochemistry. A modified HistoScore was correlated with clinicopathological characteristics and survival. Results: IR overexpression was already observed in pancreatic intraepithelial neoplasia. Furthermore, it was more frequently observed in advanced disease and associated with distant metastasis, UICC stage, lymphatic invasion and an increased lymph node ratio, but without impacting survival in the end. IGF1R expression was not associated with clinicopathological parameters or survival, in contrast to former paradigms. Conclusions: We hypothesize that the close proximity to the pancreatic islets might be advantageous for cancer growth at first, but it experiences self-limitation due to surgical removal or local destruction following accelerated cancer growth.
Using Organotypic Tissue Slices to Investigate the Microenvironment of Pancreatic Cancer: Pharmacotyping and Beyond
Authors: Weitz Jonathan Robert , Tiriac Herve , Hurtado de Mendoza Tatiana , Wascher Alexis , Lowy Andrew M.
Published: October 2021

Organotypic tissue slices prepared from patient tumors are a semi-intact ex vivo preparation that recapitulates many aspects of the tumor microenvironment (TME). While connections to the vasculature and nervous system are severed, the integral functional elements of the tumor remain intact for many days during the slice culture. During this window of time, the slice platforms offer a suite of molecular, biomechanical and functional tools to investigate PDAC biology. In this review, we first briefly discuss the development of pancreatic tissue slices as a model system. Next, we touch upon using slices as an orthogonal approach to study the TME as compared to other established 3D models, such as organoids. Distinct from most other models, the pancreatic slices contain autologous immune and other stromal cells. Taking advantage of the existing immune cells within the slices, we will discuss the breakthrough studies which investigate the immune compartment in the pancreas slices. These studies will provide an important framework for future investigations seeking to exploit or reprogram the TME for cancer therapy.