bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Characteristics and Self-Harm in Forensic Psychiatric Patients
Authors: Laporte Natalie , Ozolins Andrejs , Westling Sofie , Westrin Åsa , Wallinius Märta
Published: August 2021

Self-harm, comprising non-suicidal self-injury, and suicide attempts, is a serious and potentially life-threatening behavior that has been associated with poor life quality and an increased risk of suicide. In forensic populations, increased rates of self-harm have been reported, and suicide is one of the leading causes of death. Aside from associations between self-harm and mental disorders, knowledge on self-harm in forensic psychiatric populations is limited. The purpose of this study was to characterize the clinical needs of a cohort of forensic psychiatric patients, including self-harm and possible risk factors thereof. Participants (N = 98) were consecutively recruited from a cohort of forensic psychiatric patients in Sweden from 2016 to 2020. Data were collected through file information, self-reports, and complemented with semi-structured interviews. Results showed that self-harm was common among the participants, more than half (68.4%) of whom had at some point engaged in self-harm. The most common methods of non-suicidal self-injury were banging one's head or fist against a wall or other solid surface and cutting, and the most common method of suicide attempt was hanging. The most prominent functions of non-suicidal self-injury among the participants were intrapersonal functions such as affect regulation, self-punishment, and marking distress. Self-harm in general was associated to neurodevelopmental disorders (p = 0.014, CI = 1.23–8.02, OR = 3.14) and disruptive impulse-control and conduct disorders (p = 0.012, CI = 1.19–74.6, OR = 9.41), with reservation to very wide confidence intervals. Conclusions drawn from this study are that self-harm was highly prevalent in this sample and seems to have similar function in this group of individuals as in other studied clinical and non-clinical groups.
Increasing Mental Health Literacy in Law Enforcement to Improve Best Practices in Policing—Introduction of an Empirically Derived, Modular, Differentiated, and End-User Driven Training Design
Authors: Lorey Katharina , Fegert Jörg M.
Published: August 2021

Objective: Law enforcement officers often have contact to persons who show symptoms of mental disorders. Adequately designed training is necessary for developing the best possible practices in policing when coming into contact with mentally ill people, and may help to expand their general knowledge on mental disorders. To achieve a sustainable implementation of training content in daily policing work, the acceptance and proactive integration of methods by the training participants is essential.

Method: This study investigates an exemplary modular training curriculum based on a survey with 2,228 German police officers (28.2% female, 71.8% male) concerning their needs and challenges when coming into contact with persons with mental disorders. This empirical end-user driven approach was used to adapt existing training concepts to the current needs and interests of law enforcement personnel in order to maximize compliance.

Results: The training program draft includes basic modules which are intended to be of direct interest to all police officers, such as mental disorders with high policing relevance, encountering suicidal patients, (non-directive) communication and de-escalation skills, and mental hygiene in policing. They are arranged in more specialized modules that address specific target group audiences within police forces and the training curriculum provides information about genuine risks and self-protection, trauma sensitivity, and interaction with children and victims among other contents. The self-selectable, modular, and empirically-based continued training program also includes an introduction to local mental health service professionals and networks, trialogue sequences, and situational role play scenarios.

Conclusion: Due to frequent contact law enforcement officers have to mentally ill people, improved training designed to maximize knowledge and the integration of trained methods is necessary. Gaining acceptance and proactive support by trainees is ensured through end-user driven implementation of specialized and differentiated up-to-date training programs. Our results showcase how police officers' perspectives on persons with mental illnesses is a main aspect that can and should be used to encourage training course designs.
Lessons Learnt From the COVID-19 Pandemic
Authors: Stenseth Nils Chr. , Dharmarajan Guha , Li Ruiyun , Shi Zheng-Li , Yang Ruifu , Gao George F.
Published: August 2021

The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has been characterized by unprecedented rates of spatio-temporal spread. Here, we summarize the main events in the pandemic's timeline and evaluate what has been learnt by the public health community. We also discuss the implications for future public health policy and, specifically, the practice of epidemic control. We critically analyze this ongoing pandemic's timeline and contrast it with the 2002–2003 SARS outbreak. We identify specific areas (e.g., pathogen identification and initial reporting) wherein the international community learnt valuable lessons from the SARS outbreak. However, we also identify the key areas where international public health policy failed leading to the exponential spread of the pandemic. We outline a clear agenda for improved pandemic control in the future.
The Relationship Between “Protect People's Livelihood” and “Promote the Economy:” Provincial Evidence From China
Authors: Zhou Baicheng , Wang Shu , Qiao Zhi
Published: August 2021

This study focused on medical care in a single country (China) and in regions with different economic backgrounds and different economic development levels to determine the effect of healthcare expenditure on short- and long-term economic growth. The study supported some interesting conclusions: (1) For most areas of China, increasing healthcare expenditure has a negative impact on economic growth in the short term but promotes growth in the long run; (2) Under different levels of economic development within China, there is significant heterogeneity in the interaction between healthcare expenditure and economic growth; (3) The negative effects of healthcare expenditure on short-term economic growth are greater during periods of economic turbulence than during times of stability; and (4) Healthcare expenditure has a negative effect on underdeveloped areas through the accumulation of material capital, while in economically developed areas, this channel has the opposite effect. To improve the quality of medical and health protection and the quality of life and welfare, China needs to consider the development characteristics of different economic zones and establish a multilevel, systematic and diversified medical and health protection system.
Learners Demographics Classification on MOOCs During the COVID-19: Author Profiling via Deep Learning Based on Semantic and Syntactic Representations
Authors: Aljohani Tahani , Cristea Alexandra I.
Published: August 2021

Massive Open Online Courses (MOOCs) have become universal learning resources, and the COVID-19 pandemic is rendering these platforms even more necessary. In this paper, we seek to improve Learner Profiling (LP), i.e. estimating the demographic characteristics of learners in MOOC platforms. We have focused on examining models which show promise elsewhere, but were never examined in the LP area (deep learning models) based on effective textual representations. As LP characteristics, we predict here theemployment statusof learners. We compare sequential and parallel ensemble deep learning architectures based on Convolutional Neural Networks and Recurrent Neural Networks, obtaining an average high accuracy of 96.3% for our best method. Next, we predict thegenderof learners based on syntactic knowledge from the text. We compare different tree-structured Long-Short-Term Memory models (as state-of-the-art candidates) and provide our novel version of aBi-directional composition functionfor existing architectures. In addition, we evaluate 18 different combinations of word-level encoding and sentence-level encoding functions. Based on these results, we show that our Bi-directional model outperforms all other models and the highest accuracy result among our models is the one based on the combination of FeedForward Neural Network and the Stack-augmented Parser-Interpreter Neural Network (82.60% prediction accuracy). We argue that our prediction models recommended for both demographics characteristics examined in this study can achieve high accuracy. This is additionally also the first time a sound methodological approach toward improving accuracy for learner demographics classification on MOOCs was proposed.
Creativity in Generative Musical Networks: Evidence From Two Case Studies
Authors: Cádiz Rodrigo F. , Macaya Agustín , Cartagena Manuel , Parra Denis
Published: August 2021

Deep learning, one of the fastest-growing branches of artificial intelligence, has become one of the most relevant research and development areas of the last years, especially since 2012, when a neural network surpassed the most advanced image classification techniques of the time. This spectacular development has not been alien to the world of the arts, as recent advances in generative networks have made possible the artificial creation of high-quality content such as images, movies or music. We believe that these novel generative models propose a great challenge to our current understanding of computational creativity. If a robot can now create music that an expert cannot distinguish from music composed by a human, or create novel musical entities that were not known at training time, or exhibit conceptual leaps, does it mean that the machine is then creative? We believe that the emergence of these generative models clearly signals that much more research needs to be done in this area. We would like to contribute to this debate with two case studies of our own: TimbreNet, a variational auto-encoder network trained to generate audio-based musical chords, and StyleGAN Pianorolls, a generative adversarial network capable of creating short musical excerpts, despite the fact that it was trained with images and not musical data. We discuss and assess these generative models in terms of their creativity and we show that they are in practice capable of learning musical concepts that are not obvious based on the training data, and we hypothesize that these deep models, based on our current understanding of creativity in robots and machines, can be considered, in fact, creative.
Inherent Serum Inhibition of Influenza Virus Neuraminidases
Authors: Skarlupka Amanda L. , Ross Ted M.
Published: August 2021

Influenza virus vaccines have been designed for human and veterinary medicine. The development for broadly protective influenza virus vaccines has propelled the vaccine field to investigate and include neuraminidase (NA) components into new vaccine formulations. The antibody-mediated protection induced by NA vaccines is quantified by inhibition of sialic acid cleavage. Non-immune inhibitors against influenza viruses naturally occur in varying proportions in sera from different species. In this brief report, the inherent ability of raw animal sera to inhibit a panel of influenza virus NA was determined. Raw sera from the same species inhibited more than 50% of influenza viruses tested from four different subtypes, but the breadth of inhibiting NA activity depended on the source of sera. Furthermore, different influenza viruses were inhibited by different sources of sera. Overall, additional studies are needed to ensure that scientific methods are consistent across studies in order to compare NA inhibition results. Through future investigation into the differences between sera from different animal species and how they influence NA inhibition assays, there can be effective development of a broadly protective influenza virus vaccines for veterinary and human use.
The Potential of Shortening the Adaptation of Nellore Cattle to High-Concentrate Diets Using Only Virginiamycin as Sole Feed Additive
Authors: Rigueiro André L. N. , Squizatti Mariana M. , Silvestre Antonio M. , Pinto Ana C. J. , Estevam Daniela D. , Felizari Luana D. , Dias Evandro F. F. , Demartini Breno L. , Nunes Ana B. P. C. , Costa Victor C. M. , Caixeta Eduardo L. , Santi Pedro F. , Soares Carlos H. G. , Arrigoni Mario D. B. , Millen Danilo D.
Published: August 2021

Feedlot cattle are usually adapted to high-concentrate diets containing sodium monensin (MON) in more than 14 days. However, for finishing diets with lower energy content, the use of MON during adaptation may hold dry matter intake (DMI), and virginiamycin (VM) may be an alternative. This study was designed to determine the potential of shortening the adaptation of Nellore cattle to high-concentrate diets using only VM as a sole feed additive relative to feedlot performance, feeding behavior, and ruminal and cecum morphometrics. The experiment was designed as a completely randomized block replicated six times (four animals/pen) in which 120 Nellore bulls (390.4 ± 19.0 kg) were fed in 30 pens for 111 days according to the following treatments: (1) MON and adaptation for 14 days (MON14), (2) MON + VM and adaptation for 14 days (MONVM14), (3) VM and adaptation for 14 days (VM14), (4) VM and adaptation for 9 days (VM9), and (5) VM and adaptation for 6 days (VM6). At the end of the adaptation, 30 animals (n = 1 per pen) were randomly slaughtered for rumen and cecum evaluations. The remaining 90 bulls were harvested at the end of the study. No effects of treatments were observed (P < 0.10) for final body weight, average daily gain (ADG), and hot carcass weight (HCW). Cattle fed VM14 presented a greater (P ≤ 0.03) DMI, expressed as percent of body weight (BW), than animals fed either MON14 or MONVM14; however, cattle fed either MON14 or MONVM14 improved (P ≤ 0.02) the gain-to-feed ratio (G/F) by 10.4 or 8.1%, respectively, when compared to bulls fed VM14. Bulls fed VM14 had smaller (P < 0.05) papillae area (0.34 vs. 0.42 cm2) and rumen absorptive surface area (28.9 vs. 33.8 cm2) than those fed MON14. The shortening of the adaptation period linearly decreased the 12th rib fat (P = 0.02) and biceps femoris fat daily gain (P = 0.02) of Nellore bulls fed only VM, which linearly decreased the final biceps femoris fat thickness (P < 0.01). Feedlot cattle fed VM as a sole feed additive should not be adapted to high-concentrate diets in less than 14 days. Regardless of either adaptation length or feed additive, feedlot cattle need at least 14 days to adapt to finishing diets.
Modeling of Processes in Plasma of Radio-Frequency Ion Injector with an Antenna Placed inside the Volume of Discharge Chamber
Authors: Gordeev Svyatoslav , Kanev Stepan , Melnikov Andrey , Nazarenko Igor , Khartov Sergey
Published: August 2021

The work is devoted to the theoretical assessment of the efficiency increase possibility for the radio-frequency ion injector, which is designed for the contactless removal of space debris from near-earth orbit by using an antenna located inside the discharge chamber. Four internal antenna configurations and two external ones—end and side—are considered. Expected characteristics were estimated using an engineering mathematical model built in COMSOL Multiphysics using an approximate magnetohydrodynamic description of the charged particle behavior. According to the simulation results, the best characteristics can be obtained with an internal antenna with a conical arrangement of turns. Calculations showed that in some operating modes, such an antenna configuration makes it possible to halve the radio-frequency power consumption compared to the classical antenna located on the discharge chamber side surface. The performed theoretical study showed that the internal antenna can significantly increase the ion injector efficiency. In the future, verification of the obtained results by test is planned.
Effects of Fencing on Vegetation and Soil Nutrients of the Temperate Steppe Grasslands in Inner Mongolia
Authors: Cong Shan , Zhou Daowei , Li Qiang , Huang Yingxin
Published: August 2021

Grazing exclusion has been widely implemented in degraded grassland. However, the changes of plant communities and soil nutrients in response to fencing are still controversial. Thus, the effects of free grazing, 17 and 36 years of fencing on the plant biomass and litter biomass, carbon (C), nitrogen (N) and phosphorus (P) concentrations and stocks of plant, litter and soil were investigated in the temperate steppe grasslands of northern China. The results indicated that fencing increased the aboveground live biomass and litter biomass. In addition, fencing increased C, N and P stocks of aboveground live biomass, litter biomass and soil. Although root biomass and its nutrient stocks were also significantly increased by 17 years of fencing, they were decreased with fencing extending from 17 to 36 years. Moreover, there were no significant differences in aboveground live biomass and soil N and P stocks between 17 and 36 years of fencing. Litter biomass and its C, N and P stocks were positively correlated with soil C, N and P stocks. Our results demonstrated that 17 years of fencing is an effective way to restore vegetation and soil nutrients in the temperate steppe of Inner Mongolia, but a longer fencing duration has no further positive effects on biomass production and soil nutrients accumulation.
The Quality, Intake, and Digestibility of Virginia Fanpetals (Sida hermaphrodita L. Rusby) Silage Produced under Different Technologies and Its Effect on the Performance of Young Cattle
Authors: Purwin Cezary , Starczewski Maciej , Borsuk Marta , Nogalski Zenon , Opyd Paulina M. , Mazur-Kuśnirek Magdalena , Białobrzewski Ireneusz
Published: August 2021

Different harvesting and preservation methods of Virginia fanpetals herbage were evaluated, based on the chemical composition and digestible organic matter (OM) content (D-value) of silage fed to adult sheep, the intake and digestibility of silage, and the performance of young cattle. The following harvesting methods were compared: direct-cut harvesting with a precision-cut forage harvester (DC), harvesting after field wilting with a precision-cut forage harvester (WC) or a round baler (WRB). The silage was fed for 81 days to 24 Polish Holstein Friesian (HF) bulls, as the sole forage supplemented with 3.0 kg of concentrate/head/day. Harvesting methods affected the density (p < 0.001) and water-soluble carbohydrate (WSC) content (p = 0.047). Differences were found among the groups in the digestibility coefficients of OM (DC-73.7, WC-78.9, WRB-79.9%) (p = 0.007), and crude protein (CP) (69.8%, 77.1%, 78.5%, respectively) (p < 0.001). Dry matter intake (DMI) reached 8.38 kg (DC), 8.74 kg (WC) and 7.21 kg (WRB). Live weight gain (LWG) differed (p < 0.001) among groups (0.939, 1.033, 0.813 kg/day, respectively). The feed conversion ratio (FCR) tended to improve in WC (8.66 kg DMI/kg LWG) (p = 0.08). The highest-quality silage was produced in group WC, and it could be successfully fed to growing bulls as the sole forage.
Comprehensive Air Quality Assessment of the Tobacco Heating System 2.2 under Simulated Indoor Environments
Authors: Mitova Maya I. , Cluse Camille , Correia Daniela , Goujon-Ginglinger Catherine G. , Kleinhans Samuel , Poget Laurent , Sendyk Sandra S.
Published: August 2021

Despite the growing popularity of heated tobacco products, there are few comprehensive studies on their environmental aerosols. Therefore, the impact of the Tobacco Heating System 2.2 (THS 2.2) on indoor air quality was evaluated on the basis of a comprehensive list of 31 airborne constituents along with targeted screening of the gas–vapor and particulate phases of the environmental aerosol. The assessments were conducted at three ventilation rates. Indoor use of THS 2.2 increased the levels of nicotine, acetaldehyde, glycerin, and (if mentholated products were used) menthol relative to background levels, with a corresponding increase in total volatile organic compounds (TVOC) values. Moreover, a temporary increase in ultrafine particles was observed when two or more tobacco sticks were used simultaneously or with a short time lapse between usages, but the concentrations returned to close to background levels almost immediately. This is because THS 2.2 generates an aerosol of liquid droplets, which evaporate quickly. Nicotine, acetaldehyde, glycerin, and TVOC levels were measured in the low μg/m3 range and were below the existing guideline limits. A comparison of airborne constituent levels during indoor THS 2.2 use with emissions from combustion products and common everyday activities revealed a substantially lower impact of THS 2.2 on the indoor environment.
Observation and Inversion of Aerosol Particle Size Distribution over Yinchuan Area
Authors: Mao Jiandong , Ren Yali , Li Juan , Wang Qiang , Zhang Yi
Published: August 2021

Particle size distribution is one of the important microphysical parameters to characterize the aerosol properties. The aerosol optical depth is used as the function of wavelength to study the particle size distribution of whole atmospheric column. However, the inversion equation of the particle size distribution from the aerosol optical depth belongs to the Fredholm integral equation of the first kind, which is usually ill-conditioned. To overcome this drawback, the integral equation is first discretized directly by using the complex trapezoid formula. Then, the corresponding parameters are selected by the L curve method. Finally the truncated singular value decomposition regularization method is employed to regularize the discrete equation and retrieve the particle size distribution. To verify the feasibility of the algorithm, the aerosol optical depths taken by a sun photometer CE318 over Yinchuan area in four seasons, as well as hazy, sunny, floating dusty and blowing dusty days, were used to retrieve the particle size distribution. In order to verify the effect of truncated singular value decomposition algorithm, the Tikhonov regularization algorithm was also adopted to retrieve the aerosol PSD. By comparing the errors of the two regularizations, the truncated singular value decomposition regularization algorithm has a better retrieval effect. Moreover, to understand intuitively the sources of aerosol particles, the backward trajectory was used to track the source. The experiment results show that the truncated singular value decomposition regularization method is an effective method to retrieve the particle size distribution from aerosol optical depth.
Space-Time Assessment of Extreme Precipitation in Cuba between 1980 and 2019 from Multi-Source Weighted-Ensemble Precipitation Dataset
Authors: Alvarez-Socorro Gleisis , Fernández-Alvarez José Carlos , Sorí Rogert , Pérez-Alarcón Albenis , Nieto Raquel , Gimeno Luis
Published: August 2021

Precipitation extremes such as heavy rainfall and floods are of great interest for climate scientists, particularly for small islands vulnerable to weather phenomena such as hurricanes. In this study, we investigated the spatio-temporal evolution of extreme rainfall over Cuba from 1980 to 2019, separating the dry and rainy periods. In addition, a ranking of extreme precipitation events was performed, which provides the number of events, the area affected, and a ranking of their magnitude by considering the magnitude of anomalies. The analysis was conducted using daily data from the multi-source weighted-ensemble precipitation (MSWEPv2). In determining the extreme precipitation ranking, the daily extreme precipitation anomaly was calculated with respect to the 95th percentile climatological distribution, giving a measure of the rarity of the event for each day and each grid point. For a more detailed analysis regarding the ranking, a separation was made by regions applying the K-mean methodology. The months belonging to the rainy period of the year presented the highest amount of precipitation above the 95th percentile compared to results obtained for the dry period. Of the six months belonging to the cyclonic season, in five of them Cuba was affected, directly or indirectly, by a tropical cyclone. The years 1982–83 and 1998 presented the highest-ranking value for the dry and rainy periods, respectively. Moreover, a trend analysis revealed an increase in the trend of occurrence of extreme events and a decrease in the percentage of the area affected. The analysis by regions showed a similar behavior to that carried out for all of Cuba. It was found that the warm phase of the ENSO events influenced approximately ~22% of the occurrence of extreme events for both periods.
Environmental Factors Controlling the Precipitation in California
Authors: Hu Feng , Zhang Leying , Liu Qiao , Chyi Dorina
Published: August 2021

Using observational data covering 1948–2020, the environmental factors controlling the winter precipitation in California were investigated. Empirical orthogonal function (EOF) analysis was applied to identify the dominant climate regimes contributing to the precipitation. The first EOF mode described a consistent change, with 70.1% variance contribution, and the second mode exhibited a south–east dipole change, with 11.7% contribution. For EOF1, the relationship was positive between PC1(principal component) and SST (sea surface temperature) in the central Pacific Ocean, while it was negative with SST in the southeast Indian Ocean. The Pacific–North America mode, induced by the positive SST and precipitation in the central Pacific Ocean, leads to California being occupied by southwesterlies, which would transport warm and wet flow from the ocean, beneficial for precipitation. As for the negative relationship, California is controlled by biotrophically high pressure, representing part of the Rossby wave train induced by the positive SST in the Indian ocean, which is unfavorable for the precipitation. For EOF2, California is controlled by positive vorticity at the upper level, whereas at the lower level, there is positive vorticity to the south and negative vorticity to the north, the combination of which leads to the dipole mode change in the precipitation.
Towards B-Spline Atomic Structure Calculations
Authors: Fischer Charlotte Froese
Published: August 2021

The paper reviews the history of B-spline methods for atomic structure calculations for bound states. It highlights various aspects of the variational method, particularly with regard to the orthogonality requirements, the iterative self-consistent method, the eigenvalue problem, and the related sphf, dbsr-hf, and spmchf programs. B-splines facilitate the mapping of solutions from one grid to another. The following paper describes a two-stage approach where the goal of the first stage is to determine parameters of the problem, such as the range and approximate values of the orbitals, after which the level of accuracy is raised. Once convergence has been achieved the Virial Theorem, which is evaluated as a check for accuracy. For exact solutions, the V/T ratio for a non-relativistic calculation is −2.
Combining the Distribution of Relaxation Times from EIS and Time-Domain Data for Parameterizing Equivalent Circuit Models of Lithium-Ion Batteries
Authors: Wildfeuer Leo , Gieler Philipp , Karger Alexander
Published: August 2021

Equivalent circuit models (ECMs) are a widely used modeling approach for lithium-ion batteries in engineering applications. The RC elements, which display the dynamic loss processes of the cell, are usually parameterized by fitting the ECM to experimental data in either the time-domain or the frequency-domain. However, both types of data have limitations with regard to the observable time constants of electrochemical processes. This work proposes a method to combine time-domain and frequency-domain measurement data for parameterization of RC elements by exploiting the full potential of the distribution of relaxation times (DRT). Instead of using only partial information from the DRT to supplement a conventional fitting algorithm, we determine the parameters of an arbitrary number of RC elements directly from the DRT. The difficulties of automated deconvolution of the DRT, including regularization and the choice of an optimal regularization factor, is tackled by using the L-curve criterion for optimized calculation of the DRT via Tikhonov regularization. Three different approaches to merge time- and frequency-domain data are presented, including a novel approach where the DRT is simultaneously calculated from electrochemical impedance spectoscropy (EIS) and pulse relaxation measurements. The parameterized model for a commercial 18650 NCA cell was validated during a validation cycle consisting of constant current and real-world automotive cycling and yields a relative improvement of over 40% compared to a conventional EIS-fitting algorithm.
Nanomaterial-Based Fluorescence Resonance Energy Transfer (FRET) and Metal-Enhanced Fluorescence (MEF) to Detect Nucleic Acid in Cancer Diagnosis
Authors: Choi Jin-Ha , Ha Taehyeong , Shin Minkyu , Lee Sang-Nam , Choi Jeong-Woo
Published: August 2021

Nucleic acids, including DNA and RNA, have received prodigious attention as potential biomarkers for precise and early diagnosis of cancers. However, due to their small quantity and instability in body fluids, precise and sensitive detection is highly important. Taking advantage of the ease-to-functionality and plasmonic effect of nanomaterials, fluorescence resonance energy transfer (FRET) and metal-enhanced fluorescence (MEF)-based biosensors have been developed for accurate and sensitive quantitation of cancer-related nucleic acids. This review summarizes the recent strategies and advances in recently developed nanomaterial-based FRET and MEF for biosensors for the detection of nucleic acids in cancer diagnosis. Challenges and opportunities in this field are also discussed. We anticipate that the FRET and MEF-based biosensors discussed in this review will provide valuable information for the sensitive detection of nucleic acids and early diagnosis of cancers.
The Landscape of Regulatory Noncoding RNAs in Ewing’s Sarcoma
Authors: Barrett Connor , Budhiraja Anuj , Parashar Vijay , Batish Mona
Published: August 2021

Ewing’s sarcoma (ES) is a pediatric sarcoma caused by a chromosomal translocation. Unlike in most cancers, the genomes of ES patients are very stable. The translocation product of the EWS-FLI1 fusion is most often the predominant genetic driver of oncogenesis, and it is pertinent to explore the role of epigenetic alterations in the onset and progression of ES. Several types of noncoding RNAs, primarily microRNAs and long noncoding RNAs, are key epigenetic regulators that have been shown to play critical roles in various cancers. The functions of these epigenetic regulators are just beginning to be appreciated in ES. Here, we performed a comprehensive literature review to identify these noncoding RNAs. We identified clinically relevant tumor suppressor microRNAs, tumor promoter microRNAs and long noncoding RNAs. We then explored the known interplay between different classes of noncoding RNAs and described the currently unmet need for expanding the noncoding RNA repertoire of ES. We concluded the review with a discussion of epigenetic regulation of ES via regulatory noncoding RNAs. These noncoding RNAs provide new avenues of exploration to develop better therapeutics and identify novel biomarkers.
Colorectal Cancer after Kidney Transplantation: A Screening Colonoscopy Case-Control Study
Authors: Privitera Francesca , Gioco Rossella , Civit Alba Ilari , Corona Daniela , Cremona Simone , Puzzo Lidia , Costa Salvatore , Trama Giuseppe , Mauceri Flavia , Cardella Aurelio , Sangiorgio Giuseppe , Nania Riccardo , Veroux Pierfrancesco , Veroux Massimiliano
Published: August 2021

The incidence of colorectal cancer in kidney transplant recipients has been previously reported with conflicting results. In this study, we investigated if the incidence of colorectal advanced neoplasms in kidney transplant recipients, evaluated with screening colonoscopy, was higher than in healthy individuals. One-hundred sixty kidney transplant recipients undergoing screening colonoscopy were compared with 594 age- and sex-matched healthy individuals. Advanced colorectal neoplasia was found in 22 patients (13.7%), including four patients (2.5%) with colorectal cancer. Compared with the healthy population, kidney transplant recipients did not have an increased risk of developing a colorectal cancer (OR 0.69; 95% CI 0.236–2.063, p = 0.688) although it developed at a younger age. In contrast, kidney transplant recipients had a higher risk of developing an advanced adenoma compared with the control group (OR 1.65; 95% CI 0.930–2.981, p = 0.04). In conclusion, kidney transplant recipients did not have an increased incidence of colorectal cancer compared with healthy population. However, transplant patients displayed a higher incidence of colorectal adenomas, suggesting that screening colonoscopy in kidney transplant recipients should be expanded to include even younger recipients (<50 years old).
Electrochemotherapy with Mitomycin C Potentiates Apoptosis Death by Inhibiting Autophagy in Squamous Carcinoma Cells
Authors: Condello Maria , D’Avack Gloria , Vona Rosa , Spugnini Enrico Pierluigi , Scacco Licia , Meschini Stefania
Published: August 2021

We investigated the chemosensitizing effect of electroporation (EP), which, using electrical pulses, permeabilizes cancer cells to drugs. The study involved two human hypopharyngeal and tongue carcinoma cell lines. The surface and intracytoplasmic expression of P-gp were evaluated by flow cytometry, demonstrating that both lines were intrinsically resistant. After establishing the optimal dose of mitomycin C (MMC) to be used, in combination with EP, we showed, by both MTT assay and optical and electron scanning microscopy, the potentiating cytotoxic effect of EP with MMC compared to single treatments. Flow cytometry showed that the cytotoxicity of EP + MMC was due to the induction of apoptosis. In addition to verifying the release of cytochrome C in EP + MMC samples, we performed an expression analysis of caspase-3, caspase-9, Akt, pAkt, HMGB1, LC3I, LC3II, p62, Beclin1, and associated proteins with both apoptotic and autophagic phenomena. Our results were confirmed by two veterinary patients in whom the EP + MMC combination was used to control margins after the resection of corneal squamous carcinoma. In conclusion, we affirmed that the effect for which EP enhances MMC treatment is due to the inhibition of the autophagic process induced by the drug in favor of apoptosis.
Emerging Insights into Keratin 16 Expression during Metastatic Progression of Breast Cancer
Authors: Elazezy Maha , Schwentesius Sandra , Stegat Luisa , Wikman Harriet , Werner Stefan , Mansour Wael Y. , Failla Antonio Virgilio , Peine Sven , Müller Volkmar , Thiery Jean Paul , Ebrahimi Warkiani Majid , Pantel Klaus , Joosse Simon A.
Published: August 2021

Keratins are the main identification markers of circulating tumor cells (CTCs); however, whether their deregulation is associated with the metastatic process is largely unknown. Previously we have shown by in silico analysis that keratin 16 (KRT16) mRNA upregulation might be associated with more aggressive cancer. Therefore, in this study, we investigated the biological role and the clinical relevance of K16 in metastatic breast cancer. By performing RT-qPCR, western blot, and immunocytochemistry, we investigated the expression patterns of K16 in metastatic breast cancer cell lines and evaluated the clinical relevance of K16 expression in CTCs of 20 metastatic breast cancer patients. High K16 protein expression was associated with an intermediate mesenchymal phenotype. Functional studies showed that K16 has a regulatory effect on EMT and overexpression of K16 significantly enhanced cell motility (p < 0.001). In metastatic breast cancer patients, 64.7% of the detected CTCs expressed K16, which was associated with shorter relapse-free survival (p = 0.0042). Our findings imply that K16 is a metastasis-associated protein that promotes EMT and acts as a positive regulator of cellular motility. Furthermore, determining K16 status in CTCs provides prognostic information that helps to identify patients whose tumors are more prone to metastasize.
Substance P Antagonism as a Novel Therapeutic Option to Enhance Efficacy of Cisplatin in Triple Negative Breast Cancer and Protect PC12 Cells against Cisplatin-Induced Oxidative Stress and Apoptosis
Authors: Rodriguez Emma , Pei Guangsheng , Zhao Zhongming , Kim Sang , German Alexis , Robinson Prema
Published: August 2021

Although cisplatin is very effective as a treatment strategy in triple-negative breast cancer (TNBC), it has unwarranted outcomes owing to recurrence, chemoresistance and neurotoxicity. There is critically important to find new, effective and safe therapeutics for TNBC. We determined if SP-receptor antagonism in combination with cisplatin may serve as a novel, more efficacious and safer therapeutic option than existing therapies for TNBC. We used a neuronal cell line (PC12) and two TNBC cell lines (Sum 185 and Sum 159) for these studies. We determined that the levels of cells expressing the high-affinity SP-receptor (neurokinin 1 receptor (NK1R)), as determined by flow-cytometry was significantly elevated in response to cisplatin in all three cells. We determined that treatment with aprepitant, an SP-receptor antagonist decreased cisplatin-induced, loss of viability (studied by MTT assay), production of reactive oxygen species (by DCFDA assay) and apoptosis (by flow-cytometry) in PC12 cells while it was increased in the two TNBC cells. Furthermore, we demonstrated that important genes associated with metastases, inflammation, chemoresistance and cell cycle progression are attenuated by SP-receptor antagonism in the TNBC cell line, Sum 185. These studies implicate that SP-receptor antagonism in combination with cisplatin may possibly serve as a novel, more efficacious and safer therapeutic option than existing therapies for TNBC.
Results of a Primary Skin-Cancer-Prevention Campaign in Early Childhood on Sun-Related Knowledge and Attitudes in Southern Hungary
Authors: Horváth Zsuzsanna , Evelin Csernus A. , Oláh Péter , Gyulai Rolland , Lengyel Zsuzsanna
Published: August 2021

Avoidance of ultraviolet (UV) exposure in early childhood is important for reducing the lifetime risk of developing skin cancer. The goal of the present prospective, multicenter pilot study was to assess the sun-protection practices in kindergartens and daycare centers and to evaluate sun protection knowledge and behavior among caregivers employed in the surveyed facilities. The study consisted of two parts. A baseline questionnaire was completed by the caregivers in relation to knowledge regarding basic sun protection and sun protection practices of the participating facilities. Afterward, a thirty-minute presentation was hosted in reference to this topic. Six months following the presentation, a follow-up questionnaire was distributed among the caregivers, evaluating the attitude-related and behavioral changes towards children. A total of 153 caregivers from five daycare centers (children between 6 months and 3 years of age) and sixteen kindergartens (children between 3 and 7 years of age) willfully participated in our study. According to our results, the main source of information regarding sun protection originated from different types of media. We found that staying in shaded areas and the use of protective clothing were not frequent in the facilities. Following our presentation regarding skin types and sunscreen use, protective measures improved, but not significantly (p = 0.222). The majority (92.31%) of caregivers distributed the information throughout their environment and also to parents. Sun protection knowledge is necessary; however, motivation among caregivers and parents and involvement of children is also relevant. Hence, a continuous, repetitive educational program regarding sun-smart behavior is deemed essential.
A Molecular Signature of Circulating MicroRNA Can Predict Osteolytic Bone Disease in Multiple Myeloma
Authors: Papanota Aristea-Maria , Tsiakanikas Panagiotis , Kontos Christos K. , Malandrakis Panagiotis , Liacos Christine-Ivy , Ntanasis-Stathopoulos Ioannis , Kanellias Nikolaos , Gavriatopoulou Maria , Kastritis Efstathios , Avgeris Margaritis , Dimopoulos Meletios-Athanasios , Scorilas Andreas , Terpos Evangelos
Published: August 2021

Background: Multiple myeloma bone disease (MMBD) constitutes a common and severe complication of multiple myeloma (MM), impacting the quality of life and survival. We evaluated the clinical value of a panel of 19 miRNAs associated with osteoporosis in MMBD. Methods: miRNAs were isolated from the plasma of 62 newly diagnosed MM patients with or without MMBD. First-strand cDNA was synthesized, and relative quantification was performed using qPCR. Lastly, we carried out extensive biostatistical analysis. Results: Circulating levels of let-7b-5p, miR-143-3p, miR-17-5p, miR-214-3p, and miR-335-5p were significantly higher in the blood plasma of MM patients with MMBD compared to those without. Receiver operating characteristic curve and logistic regression analyses showed that these miRNAs could accurately predict MMBD. Furthermore, a standalone multi-miRNA–based logistic regression model exhibited the best predictive potential regarding MMBD. Two of those miRNAs also have a prognostic role in MM since survival analysis indicated that lower circulating levels of both let-7b-5p and miR-335-5p were associated with significantly worse progression-free survival, independently of the established prognostic factors. Conclusions: Our study proposes a miRNA signature to facilitate MMBD diagnosis, especially in ambiguous cases. Moreover, we provide evidence of the prognostic role of let-7b-5p and miR-335-5p as non-invasive prognostic biomarkers in MM.
Genome-Wide Characterization of R2R3-MYB Transcription Factors in Pitaya Reveals a R2R3-MYB Repressor HuMYB1 Involved in Fruit Ripening through Regulation of Betalain Biosynthesis by Repressing Betalain Biosynthesis-Related Genes
Authors: Xie Fangfang , Hua Qingzhu , Chen Canbin , Zhang Zhike , Zhang Rong , Zhao Jietang , Hu Guibing , Chen Jianye , Qin Yonghua
Published: August 2021

The MYB (myeloblastosis) superfamily constitutes one of the most abundant transcription factors (TFs) regulating various biological processes in plants. However, the molecular characteristics and functions of MYB TFs in pitaya remain unclear. To date, no genome-wide characterization analysis of this gene family has been conducted in the Cactaceae species. In this study, 105 R2R3-MYB members were identified from the genome data of Hylocereus undatus and their conserved motifs, physiological and biochemical characteristics, chromosome locations, synteny relationship, gene structure and phylogeny were further analyzed. Expression analyses suggested that three up-regulated HuMYBs and twenty-two down-regulated HuMYBs were probably involved in fruit ripening of pitaya. Phylogenetic analyses of R2R3-MYB repressors showed that seven HuMYBs (HuMYB1, HuMYB21, HuMYB48, HuMYB49, HuMYB72, HuMYB78 and HuMYB101) were in clades containing R2R3-MYB repressors. HuMYB1 and HuMYB21 were significantly down-regulated with the betalain accumulation during fruit ripening of ‘Guanhuahong’ pitaya (H. monacanthus). However, only HuMYB1 had R2 and R3 repeats with C1, C2, C3 and C4 motifs. HuMYB1 was localized exclusively to the nucleus and exhibited transcriptional inhibition capacities. Dual luciferase reporter assay demonstrated that HuMYB1 inhibited the expression of betalain-related genes: HuADH1, HuCYP76AD1-1 and HuDODA1. These results suggested that HuMYB1 is a potential repressor of betalain biosynthesis during pitaya fruit ripening. Our results provide the first genome-wide analyses of the R2R3-MYB subfamily involved in pitaya betalain biosynthesis and will facilitate functional analysis of this gene family in the future.
Enzymatic Spermine Metabolites Induce Apoptosis Associated with Increase of p53, caspase-3 and miR-34a in Both Neuroblastoma Cells, SJNKP and the N-Myc-Amplified Form IMR5
Authors: Kanamori Yuta , Finotti Alessia , Di Magno Laura , Canettieri Gianluca , Tahara Tomoaki , Timeus Fabio , Greco Antonio , Tirassa Paola , Gasparello Jessica , Fino Pasquale , Di Liegro Carlo , Proia Patrizia , Schiera Gabriella , Di Liegro Italia , Gambari Roberto , Agostinelli Enzo
Published: August 2021

Neuroblastoma (NB) is a common malignant solid tumor in children and accounts for 15% of childhood cancer mortality. Amplification of the N-Myc oncogene is a well-established poor prognostic marker in NB patients and strongly correlates with higher tumor aggression and resistance to treatment. New therapies for patients with N-Myc-amplified NB need to be developed. After treating NB cells with BSAO/SPM, the detection of apoptosis was determined after annexin V-FITC labeling and DNA staining with propidium iodide. The mitochondrial membrane potential activity was checked, labeling cells with the probe JC-1 dye. We analyzed, by real-time RT-PCR, the transcript of genes involved in the apoptotic process, to determine possible down- or upregulation of mRNAs after the treatment on SJNKP and the N-Myc-amplified IMR5 cell lines with BSAO/SPM. The experiments were carried out considering the proapoptotic genes Tp53 and caspase-3. After treatment with BSAO/SPM, both cell lines displayed increased mRNA levels for all these proapoptotic genes. Western blotting analysis with PARP and caspase-3 antibody support that BSAO/SPM treatment induces high levels of apoptosis in cells. The major conclusion is that BSAO/SPM treatment leads to antiproliferative and cytotoxic activity of both NB cell lines, associated with activation of apoptosis.
Bend, Push, Stretch: Remarkable Structure and Mechanics of Single Intermediate Filaments and Meshworks
Authors: Sapra K. Tanuj , Medalia Ohad
Published: August 2021

The cytoskeleton of the eukaryotic cell provides a structural and functional scaffold enabling biochemical and cellular functions. While actin and microtubules form the main framework of the cell, intermediate filament networks provide unique mechanical properties that increase the resilience of both the cytoplasm and the nucleus, thereby maintaining cellular function while under mechanical pressure. Intermediate filaments (IFs) are imperative to a plethora of regulatory and signaling functions in mechanotransduction. Mutations in all types of IF proteins are known to affect the architectural integrity and function of cellular processes, leading to debilitating diseases. The basic building block of all IFs are elongated α-helical coiled-coils that assemble hierarchically into complex meshworks. A remarkable mechanical feature of IFs is the capability of coiled-coils to metamorphize into β-sheets under stress, making them one of the strongest and most resilient mechanical entities in nature. Here, we discuss structural and mechanical aspects of IFs with a focus on nuclear lamins and vimentin.