bluuebunny/crossref_metadata_2025 huggingface dataset:
Nerve Growth Factor Neutralization Promotes Oligodendrogenesis by Increasing miR-219a-5p Levels
Authors: Brandi Rossella , Fabiano Marietta , Giorgi Corinna , Arisi Ivan , La Regina Federico , Malerba Francesca , Turturro Sabrina , Storti Andrea Ennio , Ricevuti Flavia , Amadio Susanna , Volontè Cinzia , Capsoni Simona , Scardigli Raffaella , D’Onofrio Mara , Cattaneo Antonino
Published: February 2021

In the brain, the neurotrophin Nerve growth factor (NGF) regulates not only neuronal survival and differentiation, but also glial and microglial functions and neuroinflammation. NGF is known to regulate oligodendrogenesis, reducing myelination in the central nervous system (CNS). In this study, we found that NGF controls oligodendrogenesis by modulating the levels of miR-219a-5p, a well-known positive regulator of oligodendrocyte differentiation. We exploited an NGF-deprivation mouse model, the AD11 mice, in which the postnatal expression of an anti-NGF antibody leads to NGF neutralization and progressive neurodegeneration. Notably, we found that these mice also display increased myelination. A microRNA profiling of AD11 brain samples and qRT-PCR analyses revealed that NGF deprivation leads to an increase of miR-219a-5p levels in hippocampus and cortex and a corresponding down-regulation of its predicted targets. Neurospheres isolated from the hippocampus of AD11 mice give rise to more oligodendrocytes and this process is dependent on miR-219a-5p, as shown by decoy-mediated inhibition of this microRNA. Moreover, treatment of AD11 neurospheres with NGF inhibits miR-219a-5p up-regulation and, consequently, oligodendrocyte differentiation, while anti-NGF treatment of wild type (WT) oligodendrocyte progenitors increases miR-219a-5p expression and the number of mature cells. Overall, this study indicates that NGF inhibits oligodendrogenesis and myelination by down-regulating miR-219a-5p levels, suggesting a novel molecular circuitry that can be exploited for the discovery of new effectors for remyelination in human demyelinating diseases, such as Multiple Sclerosis.
CRISPR Genome Editing: How to Make a Fantastic Method Even Better
Authors: Brakebusch Cord
Published: February 2021

CRISPR genome editing describes targeted mutagenesis involving a programmable DNA scissor consisting of a protein (Cas9) bound to a short RNA [...]
“Selected Papers from the 2nd Ellisras Longitudinal Study and Other Non-Communicable Diseases Studies International Conference” Special Issue Editorial
Authors: Monyeki Kotsedi Daniel
Published: February 2021

Epidemics of non-communicable diseases (NCDs) are presently emerging and on the increase in South Africa. It is increasingly recognized that the occurrence of adult chronic disease are influenced by factors operating from childhood, which are sustained throughout the individual’s life course. Increased risk may start in infancy or even before birth and will continue to be influenced by health related behavior during adulthood. The academic level of people in the community influence the level of their health status. Commitment to the promotion of health through prevention, education, and suitable management is the building block for creating a healthy society. The community must make strides to shift from traditional knowledge and medication, and seek new innovative ways of addressing issues facing the population with regard to obesity, overweight, hypertension health, smoking cessation, alcohol abuse, and low physical activity in line with a healthy living lifestyle. The NCDs pose health problems in South Africa and deserve more attention. Poor control of obesity, hypertension, and diabetes, to name just a few, only adds to the current problems. The South African government and the business sector of South Africa should provide safe walking/riding trails in the cities and in rural area to combat emerging NCDs that are killing our community members indiscriminately without considering race, gender, age, and place of residence. Compulsory introduction of physical education lessons to all public schools cannot be over emphasized in the current escalating NCD situation in South Africa.
Cocrystals Based on 4,4’-bipyridine: Influence of Crystal Packing on Melting Point
Authors: Ejarque Daniel , Calvet Teresa , Font-Bardia Mercè , Pons Josefina
Published: February 2021

The reactions of piperonylic acid (HPip) and cinnamic acid (HCinn) with 4,4’-bipyridine (4,4’-bipy) have been assayed using the same synthetic methodology, yielding two binary cocrystals with different acid:4,4’-bipy molar ratios, (HPip)(4,4’-bipy) (1) and (HCinn)2(4,4’-bipy) (2). The melting point (m.p.) of these cocrystals have been measured and a remarkable difference (ΔT ≈ 78 °C) between them was observed. Moreover, the two cocrystals have been characterized by powder X-ray diffraction (PXRD), elemental analysis (EA), FTIR-ATR, 1H NMR spectroscopies, and single-crystal X-ray diffraction. The study of their structural packings via Hirshfeld surface analysis and energy frameworks revealed the important contribution of the π···π and C-H···π interactions to the formation of different structural packing motifs, this being the main reason for the difference of m.p. between them. Moreover, it has been observed that 1 and 2 presented the same packing motifs as the crystal structure of their corresponding carboxylic acids, but 1 and 2 showed lower m.p. than those of the carboxylic acids, which could be related to the lower strength of the acid-pyridine heterosynthons respect to the acid-acid homosynthons in the crystal structures.
Numerical Analysis of the Energy Consumption of Ventilation Processes in the School Swimming Pool
Authors: Ciuman Piotr , Kaczmarczyk Jan
Published: February 2021

Ventilation of an indoor swimming pool is a very energy consuming process. This is a result of, among other things the required high value of the ventilation air volume flow rate, calculated on the basis of the moisture gains in the facility. The total energy consumption consists of the heat required to heat this air and the electricity needed to transport it. It is possible to reduce the ventilation air volume flow rate by assuming the correct value of specific humidity of the supply and indoor air, but then a deterioration of thermal-moisture conditions in the building can be expected. The aim of this paper was to examine how the reduction of the supply air volume flow rate affects the energy consumption for indoor swimming pool ventilation. It was also checked how this consumption can be reduced by using two-stage heat recovery in the air handling unit. Multi-variant simulations of energy consumption for indoor swimming pool ventilation were carried out using the IDA ICE software for day and night operation of the swimming pool throughout the year. The results of the research proved that reduction of the supply air volume flow rate resulted in the lower energy expenditure on ventilation. The variant with additional local air supply to the lifeguard zone was also analysed, which caused only a slight increase in energy demand for ventilation.
Controllable-Dual Bridge Fault Current Limiter for Interconnection Micro-Grids
Authors: Kartijkolaie Hossein Shahbabaei , Hsia Kuo-Hsien , Mobayen Saleh , Firouzi Mehdi , Shafiee Mohammadreza
Published: February 2021

Different types of fault current limiters (FCLs) have been developed and designed based on non-superconducting DC reactors (NSDRs). This paper proposes a controllable dual-bridge FCL (CDBFCL) based on the NSDR for use in an AC-type micro-grid. It includes a NSDR and two series and shunt bridge circuits. The series bridge is based on diode semiconductor switches and is coupled in series with the line via a transformer. The shunt bridge is based on thyristor semiconductor switches and is coupled in parallel with the line. The shunt bridge provides a variable voltage source. It compensates for the DC side voltage drop due to NSDR resistance and semiconductor switches during normal operating condition. In addition, by controlling the shunt bridge firing angle, it produces a controllable DC voltage, which can control the fault current amplitude during a fault. The structure, principle operating work, and control system of the proposed CDBFCL are presented. The CDBFCL performance is studied analytically and through simulation by the PSCAD/EMTDC software. In addition, the simulation results are compared with those obtained experimentally from a prototype CDBFCL and show a close correlation.
Clustering Techniques for Secondary Substations Siting
Authors: Corigliano Silvia , Rosato Federico , Ortiz Dominguez Carla , Merlo Marco
Published: February 2021

The scientific community is active in developing new models and methods to help reach the ambitious target set by UN SDGs7: universal access to electricity by 2030. Efficient planning of distribution networks is a complex and multivariate task, which is usually split into multiple subproblems to reduce the number of variables. The present work addresses the problem of optimal secondary substation siting, by means of different clustering techniques. In contrast with the majority of approaches found in the literature, which are devoted to the planning of MV grids in already electrified urban areas, this work focuses on greenfield planning in rural areas. K-means algorithm, hierarchical agglomerative clustering, and a method based on optimal weighted tree partitioning are adapted to the problem and run on two real case studies, with different population densities. The algorithms are compared in terms of different indicators useful to assess the feasibility of the solutions found. The algorithms have proven to be effective in addressing some of the crucial aspects of substations siting and to constitute relevant improvements to the classic K-means approach found in the literature. However, it is found that it is very challenging to conjugate an acceptable geographical span of the area served by a single substation with a substation power high enough to justify the installation when the load density is very low. In other words, well known standards adopted in industrialized countries do not fit with developing countries’ requirements.
Prediction of Extreme Wind Speed for Offshore Wind Farms Considering Parametrization of Surface Roughness
Authors: Ma Xinwen , Chen Yan , Yi Wenwu , Wang Zedong
Published: February 2021

Large-scale offshore wind farms (OWF) are under construction along the southeastern coast of China, an area with a high typhoon incidence. Measured data and typhoon simulation model are used to improve the reliability of extreme wind speed (EWS) forecasts for OWF affected by typhoons in this paper. Firstly, a 70-year historical typhoon record database is statistically analyzed to fit the typhoon parameters probability distribution functions, which is used to sample key parameters when employing Monte Carlo Simulation (MCS). The sampled typhoon parameters are put into the Yan Meng (YM) wind field to generate massive virtual typhoon in the MCS. Secondly, when typhoon simulation carried out, the change in wind field roughness caused by the wind-wave coupling is studied. A simplified calculation method for realizing this phenomenon is applied by exchanging roughness length in the parametric wind field and wave model. Finally, the extreme value theory is adopted to analyze the simulated typhoon wind data, and results are verified using measured data and relevant standards codes. The EWS with 50-year recurrence of six representative OWF is predicted as application examples. The results show that the offshore EWS is generally stronger than onshore; the reason is sea surface roughness will not keep growing accordingly as the wind speed increases. The traditional prediction method does not consider this phenomenon, causing it to overestimate the sea surface roughness, and as a result, underestimate the EWS for OWF affected by typhoons. This paper’s methods make the prediction of EWS for OWF more precise, and results suggest the planer should choose stronger wind turbine in typhoon prone areas.
Evaluation of Early Bark Beetle Infestation Localization by Drone-Based Monoterpene Detection
Authors: Paczkowski Sebastian , Datta Pawan , Irion Heidrun , Paczkowska Marta , Habert Thilo , Pelz Stefan , Jaeger Dirk
Published: February 2021

The project PROTECTFOREST deals with improvements in early bark beetle (e.g., Ips typographus and Pityogenes chalcographus) detection to allow for fast and effective response to initial infestation. The removal of trees in the early infestation stage can prohibit bark beetle population gradation and successive timber price decrease. A semiconductor gas sensor array was tested in the lab and attached to a drone under artificial and real-life field conditions. The sensor array was able to differentiate between α-pinene amounts and between different temperatures under lab conditions. In the field, the sensor responded to a strong artificial α-pinene source. The real-life field trial above a spruce forest showed preliminary results, as technical and environmental conditions compromised a proof of principle. Further research will evaluate the detection rate of infested trees for the new proposed sensor concept.
Pesticide Residues and Risk Assessment from Monitoring Programs in the Largest Production Area of Leafy Vegetables in South Korea: A 15-Year Study
Authors: Park Duck Woong , Yang Yong Shik , Lee Yeong-Un , Han Sue Ji , Kim Hye Jin , Kim Sun-Hee , Kim Jong Pil , Cho Sun Ju , Lee Davin , Song Nanju , Han Yujin , Hee Kim Hyo , Cho Bae-Sik , Chung Jae Keun , Kim Ae Gyeong
Published: February 2021

Leafy vegetables are widely consumed in South Korea, especially in the form of kimchi and namul (seasoned vegetables) and are used for wrapping meat. Therefore, the management of pesticide residues in leafy vegetables is very important. A total of 17,977 samples (49 leafy vegetables) were mainly collected in the largest production area of leafy vegetables (Gwangju Metropolitan City and Chonnam Province) in South Korea. They were analyzed within the government’s monitoring programs (Gwangju Metropolitan City) of pesticide residues between 2005 and 2019. Pesticide residues were found in 2815 samples (15.7%), and 426 samples (2.4%) from among these exceeded the specified maximum residue limits (MRLs). Samples exceeding the MRLs were mostly detected in spinach, ssamchoo (brassica lee ssp. namai), crown daisy, lettuce, and perilla leaves. Azoxystrobin, dimethomorph, and procymidone were the most frequently detected pesticides. However, procymidone, diniconazole, and lufenuron were found to most frequently exceed the MRLs. The rate of MRLs exceeding has been managed below the average (2.4%) more recently than in the past in this area. Further, leafy vegetables with the most violations of the MRLs in our study in South Korea were not harmful to health by a risk assessment (the range of the hazard index was 0.001–7.6%).
Characterisation of Muffins with Upcycled Sunflower Flour
Authors: Grasso Simona , Pintado Tatiana , Pérez-Jiménez Jara , Ruiz-Capillas Claudia , Herrero Ana Maria
Published: February 2021

There is an increased interest and need to make our economy more circular and our diets healthier and more sustainable. One way to achieve this is to develop upcycled foods that contain food industry by-products in their formulation. In this context, the aim of this study was to develop muffins containing upcycled sunflower flour (a by-product from the sunflower oil industry) and assess the effects of sunflower flour addition on the fibre, protein, amino acid, mineral content, and antioxidant activity measured by a Ferric Reducing Antioxidant Power (FRAP) assay and Photo chemiluminescence (PCL) assay. Results show that the sunflower flour inclusion significantly improved all the parameters analysed as part of this study. A more balanced muffin amino acid profile was achieved, thanks to the increased levels of lysine, threonine, and methionine, the limiting essential amino acids of wheat flour. We can conclude that upcycled ingredients, such as sunflower flour, could be used for the nutritional improvement of baked goods, such as muffins. Their addition can result in several nutritional advantages that could be communicated on packaging through the use of the appropriate EU nutrition claims, such as those on protein, fibre, and mineral content.
Genome-Edited Plants: Opportunities and Challenges for an Anticipatory Detection and Identification Framework
Authors: Ribarits Alexandra , Eckerstorfer Michael , Simon Samson , Stepanek Walter
Published: February 2021

It is difficult to trace and identify genome-edited food and feed products if relevant information is not made available to competent authorities. This results in major challenges, as genetically modified organism (GMO) regulatory frameworks for food and feed that apply to countries such as the member states of the European Union (EU) require enforcement based on detection. An international anticipatory detection and identification framework for voluntary collaboration and collation of disclosed information on genome-edited plants could be a valuable tool to address these challenges caused by data gaps. Scrutinizing different information sources and establishing a level of information that is sufficient to unambiguously conclude on the application of genome editing in the plant breeding process can support the identification of genome-edited products by complementing the results of analytical detection. International coordination to set up an appropriate state-of-the-art database is recommended to overcome the difficulty caused by the non-harmonized bio-safety regulation requirements of genome-edited food and feed products in various countries. This approach helps to avoid trade disruptions and to facilitate GMO/non-GMO labeling schemes. Implementation of the legal requirements for genome-edited food and feed products in the EU and elsewhere would substantially benefit from such an anticipatory framework.
Construction of a Predictive Model for MLB Matches
Authors: Chang Chia-Hao
Published: February 2021

The main purpose of this article was to define a model that could defeat the online bookmakers’ odds, where the betting item considered was the first five innings of major league baseball (MLB) matches. The betting odds of online bookmakers have two purposes: first, they are used to quantify the amount of profit made by the bettors; second, they are regarded as a market equilibrium point between multiple bookmakers and bettors. If the bettors have a more accurate prediction model than the system used to produce betting odds, it will create a positive expected return for the bettors. In this article, we used the Markov process method and the runner advancement model to estimate the expected runs in an MLB match for the teams based on the batting lineup and the pitcher.
A Comparative Analysis of Hippo Signaling Pathway Components during Murine and Bovine Early Mammalian Embryogenesis
Authors: Sharma Jyoti , Antenos Monica , Madan Pavneesh
Published: February 2021

The time required for successful blastocyst formation varies among multiple species. The formation of a blastocyst is governed by numerous molecular cell signaling pathways, such as the Hippo signaling pathway. The Hippo signaling pathway is initiated by increased cell–cell contact and via apical polarity proteins (AMOT, PARD6, and NF2) during the period of preimplantation embryogenesis. Cell–cell contact and cell polarity activate (phosphorylates) the core cascade components of the pathway (mammalian sterile twenty like 1 and 2 (MST1/2) and large tumor suppressor 1 and 2 (LATS1/2)), which in turn phosphorylate the downstream effectors of the pathway (YAP1/TAZ). The Hippo pathway remains inactive with YAP1 (Yes Associated protein 1) present inside the nucleus in the trophectoderm (TE) cells (polar blastomeres) of the mouse blastocyst. In the inner cell mass (ICM) cells (apolar blastomeres), the pathway is activated with p-YAP1 present in the cytoplasm. On the contrary, during bovine embryogenesis, p-YAP1 is exclusively present in the nucleus in both TE and ICM cells. Contrary to mouse embryos, transcription co activator with PDZ-binding motif (TAZ) (also known as WWTR1) is also predominantly present in the cytoplasm in all the blastomeres during bovine embryogenesis. This review outlines the major differences in the localization and function of Hippo signaling pathway components of murine and bovine preimplantation embryos, suggesting significant differences in the regulation of this pathway in between the two species. The variance observed in the Hippo signaling pathway between murine and bovine embryos confirms that both of these early embryonic models are quite distinct. Moreover, based on the similarity of the Hippo signaling pathway between bovine and human early embryo development, bovine embryos could be an alternate model for understanding the regulation of the Hippo signaling pathway in human embryos.
Probabilistic Tsunami Hazard Analysis of Inundated Buildings Following a Subaqueous Volcanic Explosion Based on the 1716 Tsunami Scenario in Taal Lake, Philippines
Authors: Pakoksung Kwanchai , Suppasri Anawat , Imamura Fumihiko
Published: February 2021

A probabilistic hazard analysis of a tsunami generated by a subaqueous volcanic explosion was performed for Taal Lake in the Philippines. The Taal volcano at Taal Lake is an active volcano on Luzon Island in the Philippines, and its eruption would potentially generate tsunamis in the lake. This study aimed to analyze a probabilistic tsunami hazard of inundated buildings for tsunami mitigation in future scenarios. To determine the probabilistic tsunami hazard, different explosion diameters were used to generate tsunamis of different magnitudes in the TUNAMI-N2 model. The initial water level in the tsunami model was estimated based on the explosion energy. The tsunami-induced inundation from the TUNAMI-N2 model was overlaid on the distribution of buildings. The tsunami hazard analysis of inundated buildings was performed by using the maximum inundation depth in each explosion case. These products were used to calculate the probability of the inundated building given the occurrence of a subaqueous explosion. The results from this study can be used for future tsunami mitigation if a tsunami is generated by a subaqueous volcanic explosion.
Cost-Effectiveness Analysis of Type 2 Diabetes Mellitus (T2DM) Treatment in Patients with Complications of Kidney and Peripheral Vascular Diseases in Indonesia
Authors: Priyadi Akhmad , Permana Hikmat , Muhtadi Ahmad , Sumiwi Sri A. , Sinuraya Rano K. , Suwantika Auliya A.
Published: February 2021

Type 2 diabetes mellitus (T2DM) is a chronic disease with high-cost treatment. This study aimed to analyze the cost-effectiveness of T2DM treatment in hospitalized patients with complications of kidney and peripheral vascular disease (PVD) in Indonesia by focusing on patients of Health Social Security Agency (BPJS Kesehatan). An observational study was applied by collecting data retrospectively from patients’ medical record at the biggest public hospital in West Java Province, Indonesia. Two perspectives of payer and healthcare provider were applied to estimate the treatment cost. We considered following inclusion criteria: (i) Hospitalized T2DM patients without complication, with complications of kidney and PVD during 2014–2017; (ii) member of BPJS Kesehatan; (iii) >18 years old patients; and (iv) patients with complete medical record data. The results showed that the majority patients were female (56.72%), 45–64 years old (69.40%), and had a length of stay at 4–10 days (54.48%). The greatest contributions in the total treatment cost were found to be hospital room, medical services and medicines for the treatment of T2DM without complications, with complications of kidney and PVD, respectively. From the perspective of payer, the incremental cost-effectiveness ratios (ICERs) of T2DM treatment with complications of kidney and PVD would be IDR 215,723 and IDR 234,591 per 1 mg/dL blood glucose reduction, respectively. From the perspective of healthcare provider, the ICERs of T2DM treatment with complications of kidney and PVD would be IDR 166,289 and IDR 681,853 per 1 mg/dL blood glucose reduction in both perspectives (1 US$ = IDR 13,451). In a comparison with T2DM without complication, reducing 1 mg/dL blood glucose in T2DM treatment with complication of PVD would require higher cost than in T2DM treatment with complication of kidney from both perspectives.
Advances in Biomarkers and Diagnostics in Periodontitis and Oral Diseases
Authors: Isola Gaetano
Published: February 2021

Oral health is essential to general health and well-being at every stage of life [...]
Dietary Quality in Vegetarian and Omnivorous Female Students in Germany: A Retrospective Study
Authors: Blaurock Julia , Kaiser Birgit , Stelzl Tamara , Weech Michelle , Fallaize Rosalind , Franco Rodrigo Zenun , Hwang Faustina , Lovegrove Julie , Finglas Paul M. , Gedrich Kurt
Published: February 2021

Vegetarian diets have gained in popularity, especially among highly educated women, and are considered beneficial to health. Comparative studies assessing the diet of vegetarians against omnivores are rather limited and often provide ambivalent results. Therefore, this study examined the nutrient intake and nutritional quality of vegetarian and omnivorous diets in a group of 61 female students in Germany. Habitual dietary intake was evaluated using a validated graphical online food frequency questionnaire (FFQ). Differences in nutrient intakes were analyzed by Mann–Whitney-U-Tests. Odds Ratios (OR) were calculated for vegetarians exceeding dietary reference values (DRV) compared to omnivores. The overall nutritional quality was assessed using the Healthy-Eating-Index-2015 (HEI-2015). In omnivores, intakes of total energy from saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), long-chain omega-3 polyunsaturated fatty acids (LC-n3-PUFA), cholesterol, sucrose, lactose, retinol, and cobalamin were significantly higher than in vegetarians. Significantly lower intakes were observed for fiber, magnesium, and beta-carotene. Significant OR were detected for total fat (OR = 0.29), SFA (OR = 0.04), beta-carotene (OR = 4.55), and cobalamin (OR = 0.32). HEI-2015 scores were higher for vegetarians than for omnivores (79 points versus 74 points) and significant differences were recorded for the HEI-2015 components dairy, seafood & plant proteins, fatty acids, added sugars, and saturated fatty acids.
Prevalence and Medical Resource of Patients with Diabetic Foot Ulcer: A Nationwide Population-Based Retrospective Cohort Study for 2001–2015 in Taiwan
Authors: Tai Chia-Hui , Hsieh Tsung-Cheng , Lee Ru-Ping , Lo Shu-Fen
Published: February 2021

Diabetic foot ulcer (DFU) is one of the common complications of diabetes. DFU can cause a huge medical and financial burden due to infections, compromise the quality of life, and increase the mortality rate in patients. However, the consumption of medical resources for DFU is rarely mentioned. A retrospective cohort study was performed. Data were obtained from the National Health Insurance Research Database of Taiwan, and the prevalence and medical utilization data for DFU in 2001–2015 were extracted, followed by the analysis for high-risk populations. Between 2001 and 2015, there were 7511 new DFU patients. A higher proportion in these patients was male, elderly with a low education level, and low income. Between 2001 and 2015, the prevalence of DFU was 0.5–0.8%, and the number of DFU patients showed stable growth. Every year, 12.6–19.3% and 1.2–7.0% of patients underwent debridement and amputation, respectively. The hospitalization fees increased year on year. Our study showed that the DFU prevalence increased year on year, and the DFU medical expenditure increased. DFU tends to occur in males, patients with low socioeconomic status, low education level, those with multiple comorbidities, and old age. Therefore, DFU care and prevention require the entire healthcare system to jointly formulate a prevention plan.
Plasma Xanthine Oxidoreductase Activity Is Associated with a High Risk of Cardiovascular Disease in a General Japanese Population
Authors: Kotozaki Yuka , Satoh Mamoru , Tanno Kozo , Ohmomo Hideki , Otomo Ryo , Tanaka Fumitaka , Nasu Takahito , Taguchi Satoru , Kikuchi Hiroto , Kobayashi Takamasa , Shimizu Atsushi , Sakata Kiyomi , Hitomi Jiro , Sobue Kenji , Sasaki Makoto
Published: February 2021

The purpose of this study was to investigate the association between xanthine oxidoreductase (XOR) activity and a high risk of cardiovascular disease (CVD) in a general Japanese population. The Iwate Tohoku Medical Megabank Organization pooled individual participant data from a general population-based cohort study in Iwate prefecture. The cardiovascular risk was calculated using the Framingham Risk Score (FRS). A total of 1605 of the 1631 participants (98.4%) had detectable XOR activity. Multiple regression analysis demonstrated that XOR activity was independently associated with body mass index (β = 0.26, p < 0.001), diabetes (β = 0.09, p < 0.001), dyslipidemia (β = 0.08, p = 0.001), and uric acid (β = 0.13, p < 0.001). Multivariate analysis showed that the highest quartile of XOR activity was associated with a high risk for CVD (FRS ≥ 15) after adjustment for baseline characteristics (OR 2.93, 95% CI 1.16–7.40). The area under the receiver operating characteristic curves of the FRS with XOR activity was 0.81 (p = 0.008). XOR activity is associated with a high risk for CVD, suggesting that high XOR activity may indicate cardiovascular risk in a general Japanese population.
Predictors of Lung Cancer Risk: An Ecological Study Using Mortality and Environmental Data by Municipalities in Italy
Authors: Gariazzo Claudio , Binazzi Alessandra , Alfò Marco , Massari Stefania , Stafoggia Massimo , Marinaccio Alessandro
Published: February 2021

Lung cancer (LC) mortality remains a consistent part of the total deaths occurring worldwide. Its etiology is complex as it involves multifactorial components. This work aims in providing an epidemiological assessment on occupational and environmental factors associated to LC risk by means of an ecological study involving the 8092 Italian municipalities for the period 2006–2015. We consider mortality data from mesothelioma as proxy of asbestos exposure, as well as PM2.5 and radon levels as a proxy of environmental origin. The compensated cases for occupational respiratory diseases, urbanization and deprivation were included as predictors. We used a negative binomial distribution for the response, with analysis stratified by gender. We estimated that asbestos is responsible for about 1.1% (95% CI: 0.8, 1.4) and 0.5% (95% CI: 0.2, 0.8) of LC mortality in males and females, respectively. The corresponding figures are 14.0% (95% CI: 12.5, 15.7) and 16.3% (95% CI: 16.2, 16.3) for PM2.5 exposure, and 3.9% (95% CI: 3.5, 4.2) and 1.6% (95% CI: 1.4, 1.7) for radon exposure. The assessment of determinants contribution to observed LC deaths is crucial for improving awareness of its origin, leading to increase the equity of the welfare system.
Privacy-Preserving Trajectory Data Publishing by Dynamic Anonymization with Bounded Distortion
Authors: Li Songyuan , Tian Hui , Shen Hong , Sang Yingpeng
Published: February 2021

Publication of trajectory data that contain rich information of vehicles in the dimensions of time and space (location) enables online monitoring and supervision of vehicles in motion and offline traffic analysis for various management tasks. However, it also provides security holes for privacy breaches as exposing individual’s privacy information to public may results in attacks threatening individual’s safety. Therefore, increased attention has been made recently on the privacy protection of trajectory data publishing. However, existing methods, such as generalization via anonymization and suppression via randomization, achieve protection by modifying the original trajectory to form a publishable trajectory, which results in significant data distortion and hence a low data utility. In this work, we propose a trajectory privacy-preserving method called dynamic anonymization with bounded distortion. In our method, individual trajectories in the original trajectory set are mixed in a localized manner to form synthetic trajectory data set with a bounded distortion for publishing, which can protect the privacy of location information associated with individuals in the trajectory data set and ensure a guaranteed utility of the published data both individually and collectively. Through experiments conducted on real trajectory data of Guangzhou City Taxi statistics, we evaluate the performance of our proposed method and compare it with the existing mainstream methods in terms of privacy preservation against attacks and trajectory data utilization. The results show that our proposed method achieves better performance on data utilization than the existing methods using globally static anonymization, without trading off the data security against attacks.
Guide Cells Support Muscle Regeneration and Affect Neuro-Muscular Junction Organization
Authors: Ronzoni Flavio L. , Giarratana Nefele , Crippa Stefania , Quattrocelli Mattia , Cassano Marco , Ceccarelli Gabriele , Benedetti Laura , Van Herck Jens , Cusella De Angelis Maria G. , Vitale Marco , Galli Daniela , Sampaolesi Maurilio
Published: February 2021

Muscular regeneration is a complex biological process that occurs during acute injury and chronic degeneration, implicating several cell types. One of the earliest events of muscle regeneration is the inflammatory response, followed by the activation and differentiation of muscle progenitor cells. However, the process of novel neuromuscular junction formation during muscle regeneration is still largely unexplored. Here, we identify by single-cell RNA sequencing and isolate a subset of vessel-associated cells able to improve myogenic differentiation. We termed them ‘guide’ cells because of their remarkable ability to improve myogenesis without fusing with the newly formed fibers. In vitro, these cells showed a marked mobility and ability to contact the forming myotubes. We found that these cells are characterized by CD44 and CD34 surface markers and the expression of Ng2 and Ncam2. In addition, in a murine model of acute muscle injury and regeneration, injection of guide cells correlated with increased numbers of newly formed neuromuscular junctions. Thus, we propose that guide cells modulate de novo generation of neuromuscular junctions in regenerating myofibers. Further studies are necessary to investigate the origin of those cells and the extent to which they are required for terminal specification of regenerating myofibers.
The Multi-Targeting Ligand ST-2223 with Histamine H3 Receptor and Dopamine D2/D3 Receptor Antagonist Properties Mitigates Autism-Like Repetitive Behaviors and Brain Oxidative Stress in Mice
Authors: Eissa Nermin , Venkatachalam Karthikkumar , Jayaprakash Petrilla , Falkenstein Markus , Dubiel Mariam , Frank Annika , Reiner-Link David , Stark Holger , Sadek Bassem
Published: February 2021

Autism spectrum disorder (ASD) is a complex heterogeneous neurodevelopmental disorder characterized by social and communicative impairments, as well as repetitive and restricted behaviors (RRBs). With the limited effectiveness of current pharmacotherapies in treating repetitive behaviors, the present study determined the effects of acute systemic treatment of the novel multi-targeting ligand ST-2223, with incorporated histamine H3 receptor (H3R) and dopamine D2/D3 receptor affinity properties, on ASD-related RRBs in a male Black and Tan BRachyury (BTBR) mouse model of ASD. ST-2223 (2.5, 5, and 10 mg/kg, i.p.) significantly mitigated the increase in marble burying and self-grooming, and improved reduced spontaneous alternation in BTBR mice (all p < 0.05). Similarly, reference drugs memantine (MEM, 5 mg/kg, i.p.) and aripiprazole (ARP, 1 mg/kg, i.p.), reversed abnormally high levels of several RRBs in BTBR (p < 0.05). Moreover, ST-2223 palliated the disturbed anxiety levels observed in an open field test (all p < 0.05), but did not restore the hyperactivity parameters, whereas MEM failed to restore mouse anxiety and hyperactivity. In addition, ST-2223 (5 mg/kg, i.p.) mitigated oxidative stress status by decreasing the elevated levels of malondialdehyde (MDA), and increasing the levels of decreased glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) in different brain parts of treated BTBR mice (all p < 0.05). These preliminary in vivo findings demonstrate the ameliorative effects of ST-2223 on RRBs in a mouse model of ASD, suggesting its pharmacological prospective to rescue core ASD-related behaviors. Further confirmatory investigations on its effects on various brain neurotransmitters, e.g., dopamine and histamine, in different brain regions are still warranted to corroborate and expand these initial data.
Thyroid Carcinoma: Phenotypic Features, Underlying Biology and Potential Relevance for Targeting Therapy
Authors: Hu Jinwei , Yuan Isabella J. , Mirshahidi Saied , Simental Alfred , Lee Steve C. , Yuan Xiangpeng
Published: February 2021

Thyroid carcinoma consists a group of phenotypically heterogeneous cancers. Recent advances in biological technologies have been advancing the delineation of genetic, epigenetic, and non-genetic factors that contribute to the heterogeneities of these cancers. In this review article, we discuss new findings that are greatly improving the understanding of thyroid cancer biology and facilitating the identification of novel targets for therapeutic intervention. We review the phenotypic features of different subtypes of thyroid cancers and their underlying biology. We discuss recent discoveries in thyroid cancer heterogeneities and the critical mechanisms contributing to the heterogeneity with emphases on genetic and epigenetic factors, cancer stemness traits, and tumor microenvironments. We also discuss the potential relevance of the intratumor heterogeneity in understanding therapeutic resistance and how new findings in tumor biology can facilitate designing novel targeting therapies for thyroid cancer.
The Role of Bcl-xL Protein in Viral Infections
Authors: Wyżewski Zbigniew , Świtlik Weronika , Mielcarska Matylda Barbara , Gregorczyk-Zboroch Karolina Paulina
Published: February 2021

Bcl-xL represents a family of proteins responsible for the regulation of the intrinsic apoptosis pathway. Due to its anti-apoptotic activity, Bcl-xL co-determines the viability of various virally infected cells. Their survival may determine the effectiveness of viral replication and spread, dynamics of systemic infection, and viral pathogenesis. In this paper, we have reviewed the role of Bcl-xL in the context of host infection by eight different RNA and DNA viruses: hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), influenza A virus (IAV), Epstein-Barr virus (EBV), human T-lymphotropic virus type-1 (HTLV-1), Maraba virus (MRBV), Schmallenberg virus (SBV) and coronavirus (CoV). We have described an influence of viral infection on the intracellular level of Bcl-xL and discussed the impact of Bcl-xL-dependent cell survival control on infection-accompanying pathogenic events such as tissue damage or oncogenesis. We have also presented anti-viral treatment strategies based on the pharmacological regulation of Bcl-xL expression or activity.
Immune Profile Analysis in Peripheral Blood and Tumor in Patients with Malignant Melanoma
Authors: Saito Ryuichi , Sawada Yu , Nakamura Motonobu
Published: February 2021

Melanoma is a severe and life-threatening malignancy derived from melanocytes. The traditional treatment for melanoma could not sustain satisfactory outcomes long term; however, the recent immune checkpoint treatment has made a breakthrough in these problems. Nivolumab is a representative immune checkpoint treatment, and this PD-1-targeted therapy has evolutionally developed and improved the clinical outcome in a recent decade. On the other hand, the clinical application of immune checkpoint treatment presents clinicians with novel questions, especially how to obtain additional efficacy and overcome the disadvantage by using this treatment. To answer these problems, we first investigated the distribution of PD-L1 in various organs to clarify the organs most affected by anti-PD-1 antibody treatment. Among various organs, lung, placenta, spleen, heart, and thyroid highly expressed PD-L1, while skin, thalamus, hippocampus, ovary, stomach, testis, and prostate showed lower expressions of PD-L1. Furthermore, the immune profiles were also examined in tumors and peripheral blood in patients with melanoma. PD-1 was highly expressed in CD8 and CD4 cells, and B cells also highly expressed PD-1 compared with NK cells. However, there was no significant difference in Th1/Th2/Th17 cytokines and inhibitory cytokine IL-10. Although nevus showed a low expression of PD-L1 compared with healthy skin, PD-L1 expression was increased in growth-phase melanoma. Finally, we analyzed the peripheral blood profiles in patients treated with nivolumab. PD-1-bearing dendritic cells (DCs) were increased during nivolumab treatment and Lin-CD11c+HLA-DR+ cells were highly increased during nivolumab treatment. These findings indicate a clue to answering the problems during nivolumab treatment and suggest to us the importance of multiple aspect observation during immune checkpoint treatment.
Immunotherapy with 4-1BBL-Expressing iPS Cell‐Derived Myeloid Lines Amplifies Antigen-Specific T Cell Infiltration in Advanced Melanoma
Authors: Kuriyama Haruka , Fukushima Satoshi , Kimura Toshihiro , Kanemaru Hisashi , Miyashita Azusa , Okada Etsuko , Kubo Yosuke , Nakahara Satoshi , Tokuzumi Aki , Nishimura Yuki , Kajihara Ikko , Makino Katsunari , Aoi Jun , Masuguchi Shinichi , Tsukamoto Hirotake , Inozume Takashi , Zhang Rong , Nakatsura Tetsuya , Uemura Yasushi , Senju Satoru , Ihn Hironobu
Published: February 2021

We have established an immune cell therapy with immortalized induced pluripotent stem-cell–derived myeloid lines (iPS-ML). The benefits of using iPS-ML are the infinite proliferative capacity and ease of genetic modification. In this study, we introduced 4-1BBL gene to iPS-ML (iPS-ML-41BBL). The analysis of the cell-surface molecules showed that the expression of CD86 was upregulated in iPS-ML-41BBL more than that in control iPS-ML. Cytokine array analysis was performed using supernatants of the spleen cells that were cocultured with iPS-ML or iPS-ML-41BBL. Multiple cytokines that are beneficial to cancer immunotherapy were upregulated. Peritoneal injections of iPS-ML-41BBL inhibited tumor growth of peritoneally disseminated mouse melanoma and prolonged survival of mice compared to that of iPS-ML. Furthermore, the numbers of antigen-specific CD8+ T cells were significantly increased in the spleen and tumor tissues treated with epitope peptide-pulsed iPS-ML-41BBL compared to those treated with control iPS-ML. The number of CXCR6-positive T cells were increased in the tumor tissues after treatment with iPS-ML-41BBL compared to that with control iPS-ML. These results suggest that iPS-ML-41BBL could activate antigen-specific T cells and promote their infiltration into the tumor tissues. Thus, iPS-ML-41BBL may be a candidate for future immune cell therapy aiming to change immunological “cold tumor” to “hot tumor”.
Computational Techniques for Investigating Information Theoretic Limits of Information Systems
Authors: Tian Chao , Plank James S. , Hurst Brent , Zhou Ruida
Published: February 2021

Computer-aided methods, based on the entropic linear program framework, have been shown to be effective in assisting the study of information theoretic fundamental limits of information systems. One key element that significantly impacts their computation efficiency and applicability is the reduction of variables, based on problem-specific symmetry and dependence relations. In this work, we propose using the disjoint-set data structure to algorithmically identify the reduction mapping, instead of relying on exhaustive enumeration in the equivalence classification. Based on this reduced linear program, we consider four techniques to investigate the fundamental limits of information systems: (1) computing an outer bound for a given linear combination of information measures and providing the values of information measures at the optimal solution; (2) efficiently computing a polytope tradeoff outer bound between two information quantities; (3) producing a proof (as a weighted sum of known information inequalities) for a computed outer bound; and (4) providing the range for information quantities between which the optimal value does not change, i.e., sensitivity analysis. A toolbox, with an efficient JSON format input frontend, and either Gurobi or Cplex as the linear program solving engine, is implemented and open-sourced.
A Linkage-Based Genome Assembly for the Mosquito Aedes albopictus and Identification of Chromosomal Regions Affecting Diapause
Authors: Boyle John H. , Rastas Pasi M. A. , Huang Xin , Garner Austin G. , Vythilingam Indra , Armbruster Peter A.
Published: February 2021

The Asian tiger mosquito, Aedes albopictus, is an invasive vector mosquito of substantial public health concern. The large genome size (~1.19–1.28 Gb by cytofluorometric estimates), comprised of ~68% repetitive DNA sequences, has made it difficult to produce a high-quality genome assembly for this species. We constructed a high-density linkage map for Ae. albopictus based on 111,328 informative SNPs obtained by RNAseq. We then performed a linkage-map anchored reassembly of AalbF2, the genome assembly produced by Palatini et al. (2020). Our reassembled genome sequence, AalbF3, represents several improvements relative to AalbF2. First, the size of the AalbF3 assembly is 1.45 Gb, almost half the size of AalbF2. Furthermore, relative to AalbF2, AalbF3 contains a higher proportion of complete and single-copy BUSCO genes (84.3%) and a higher proportion of aligned RNAseq reads that map concordantly to a single location of the genome (46%). We demonstrate the utility of AalbF3 by using it as a reference for a bulk-segregant-based comparative genomics analysis that identifies chromosomal regions with clusters of candidate SNPs putatively associated with photoperiodic diapause, a crucial ecological adaptation underpinning the rapid range expansion and climatic adaptation of A. albopictus.
Models Applied to Grapevine Pests: A Review
Authors: Lessio Federico , Alma Alberto
Published: February 2021

This paper reviews the existing predictive models concerning insects and mites harmful to grapevine. A brief conceptual description is given on the definition of a model and about different types of models: deterministic vs. stochastics, continuous vs. discrete, analytical vs. computer-based, and descriptive vs. data-driven. The main biological aspects of grapevine pests covered by different types of models are phenology, population growth and dynamics, species distribution, and invasion risk. A particular emphasis is put on forecasting epidemics of plant disease agents transmitted by insects with sucking-piercing mouthparts. The most investigated species or groups are the glassy-winged sharpshooter Homalodisca vitripennis (Germar) and other vectors of Xylella fastidiosa subsp. fastidiosa, a bacterium agent of Pierce’s disease; the European grape berry moth, Lobesia botrana (Denis and Schiffermuller); and the leafhopper Scaphoideus titanus Ball, the main vector of phytoplasmas agents of Flavescence dorée. Finally, the present and future of decision-support systems (DSS) in viticulture is discussed.