bluuebunny/crossref_metadata_2025 huggingface dataset:
PENGEMBANGAN MEDIA PAPAN EKO (KEGIATAN EKONOMI) PADA MATERI KEGIATAN EKONOMI UNTUK MENINGKATKAN AKTIVITAS BELAJAR KELOMPOK SISWA KELAS IV SEKOLAH DASAR
Authors: Pratama Sindy Muthia Putri , Yanti Yulia Eka
Published: April 2021

Pengembangan media Papan EKO (Kegiatan Ekonomi) ini dilakukan karena siswa masih kesulitan dalam mengurutkan proses terjadinya kegiatan ekonomi dan masih kurangnya media yang digunakan dalam pembelajaran yang menyebabkan aktivitas belajar kelompok siswa pada kelas IV SD masih cukup rendah. Penelitian ini bertujuan untuk menghasilkan media pembelajaran Papan EKO (Kegiatan Ekonomi) yang layak dan valid digunakan dalam pembelajaran materi IPS, serta untuk meningkatkan aktivitas belajar kelompok siswa melalui implementasi media pembelajaran Papan EKO (Kegiatan Ekonomi). Pada penelitian dan pengembangan ini, peneliti menggunakan jenis penelitian RnD (Research and Development) yang dikembangkan oleh Borg and Gall. Aktifitas belajar kelompok siswa diukur dengan angket aktivitas  belajar kelompok siswa, sedangkan kevalidan produk diukur dengan lembar validasi produk ahli materi dan ahli media. Hasil penelitian menunjukkan bahwa media pembelajaran Papan EKO (Kegiatan Ekonomi) layak dan valid digunakan dengan dengan perolehan tingkat kevalidan dari ahli media sebesar 94%, dari ahli materi sebesar 85%. Aktivitas belajar kelompok siswa juga meningkat, hal ini dapat dilihat dari hasil angket aktivitas belajar kelompok siswa pada uji lapangan utama sebelum menggunakan media diperoleh 52%, sesudah menggunakan media Papan EKO (Kegiatan Ekonomi) siswa memperoleh 89%. Hal ini dikatakan bahwa aktivitas belajar kelompok siswa tinggi dan meningkat sebesar 37% setelah diberikan media Papan EKO (Kegiatan Ekonomi). Berdasarkan hasil penelitian ini dapat disarankan bagi pihak sekolah dan guru untuk mengoptimalkan penggunaan media agar siswa semakin meningkat aktivitas belajar kelompok dalam belajar.
THE STRUGGLE OF THE SOVIET REPRESSIVE-PUNITIVE BODIES AGAINST UNITS TV 22 «CHORNYI LIS» (THE BLACK FOREST) (1946–1947)
Authors: ILNYTSKYI Vasyl , BATIUK Taras
Published: April 2021

Three documents are published in the article: the first one is the special report on the case No. 322 «Chornolisnyky» (Black Foresters) (November 22, 1946) (Sectoral State Archive of the State Security Service of Ukraine, f. 2: department of the struggle against banditry of the Ministry of Internal Affairs, 2-N department, the fourth department of Ministry of State Security-KGB of the USSR, Description 107 (1954), Case 2, p. 118–122; the second document was the special report on the agency-operative and military operation to eliminate the kurin «Dzvony» (December 13, 1946) (SSA of the SSS of Ukraine, f. 2, d. 107 (1954), case 2, p. 144–149).; the third one is the certificate on the agent case No. 322 «Chornolisnyky (Black Foresters)» (February 13, 1947) (SSA of the SSS, f. 2, d. 90 (1951), case 66, p. 103–108). The published documents are an important source both for the history of the battle way of TV 22 «Chornyi lis» (Black Forest) and for the characterization of the forms and methods of struggle of the repressive-punitive bodies against the Ukrainian Insurgent Army (UIA). The information potential of the published documents is quite large. They show how the Soviet security forces were in possession of the information about the UIA combat units, their structural transformation, size, the territory of activity, management. It was found that, in addition to conducting military-Chekist operations to eliminate the Organization of Ukrainian Nationalists (OUN), the repressive-punitive authorities actively used the agency. In the struggle against the Ukrainian Liberation Movement, it was considered appropriate to file an agency case for each group of more than 10 people (both in the Ministry of State Security and in the Ministry of Internal Affairs) with its full characterization and mandatory presence in the group of agents who developed it. That is why there were agent cases on all OUN units (rayon, district) and UIA divisions, and after the liquidation of the people, who were on file, they were closed and new ones were discovered (mainly with new titles). Soviet law enforcement bodies were careful about the seized documents. Each document was carefully studied and analyzed, and if it was encrypted, efforts were made to decrypt it. Therefore, the contents of the document were used in agent-operative, investigative and judicial practices. From the seized documents, the security forces made comprehensive, consolidated collections that were used as evidence in the conviction of nationalists (in the 1940s – 1950s and even in the 1960s – 1980s), and they also served as training material for future chekists.

Keywords: Organization of Ukrainian Nationalists (OUN), Ukrainian Insurgent Army (UIA), TV 22 «Chornyi lis» (Black Forest), kurin «Dzvony», «Smertonostsi».
An Assessment of the Effectiveness of Central Bank Sterilization on Capital Inflows in Nigeria
Authors: M. Jume Tijjani
Published: April 2021

This paper assesses the monetary policy response of the Central Bank of Nigeria (CBN) to increases in capital inflows into Nigeria using monthly time series data from January 2009 to December 2017. It presents an econometric assessment of the degree to which the CBN sterilizes net foreign assets (NFA) in response to the capital flows, using Autoregressive Distributed Lag (ARDL) bounds testing approach. The long run sterilization coefficient obtained suggests that the CBN successfully offset 95per cent of capital inflows in the period of analysis. Against the background of rising financial instability in Nigeria, the study illustrates how sterilization has not adequately tackled the major risks of capital inflows which resulted in asset price bubbles and bursts, equity capital inflows reversal, banking crisis, and currency depreciation which contributed, partly, to the economic recession in 2016. The paper argues that effective policy response to capital inflows must adequately address the major downside risks of capital inflows in the short and medium terms through some clearly defined capital flows management and macro-prudential measures.
SISTEMA WEB RESPONSABLE, PARA LA INSCRIPCIÓN Y MATRICULACIÓN EN LÍNEA , DE ESTUDIANTES EN EL DEPARTAMENTO DE POSGRADO DE LA UNIVERSIDAD ESTATAL DE BOLÍVAR.
Authors:   Universidad Estatal de Bolívar, Veloz Elizabeth , Veloz Verónica ,   Universidad Estatal de Bolívar
Published: April 2021

The enrollment and enrollment of students in the different programs offered by the Postgraduate Department of the Bolívar State University are requirements to begin with professional training in the fourth level academic offers; The present investigation identified that the information is kept manually which causes difficulties in its processes, for which it seeks to improve the administrative and academic processes that will allow the progress of functions associated with strategic tasks and decision-making, allowing to store and organize the information in such a way that efficient searches and specific reports can be carried out according to the needs within the aforementioned department, through the migration of manual processes to an automated online system - responsive web system, using Open Source tools according to to the needs of the Department (PHP Programming Language, MySql Database Manager, Netbeans Framework 11.0, JavaScript, Buml 7.9, additional tools and technologies.), in addition, Software Engineering techniques were applied to obtain a reliable and quality system , an adequate collection of information to capture the requirements Functional and non-functional requirements of the web system, reducing development, operation and maintenance time, the aforementioned web system was subjected to different types of tests such as white box, which resulted in a reduction in the number of errors in the software and A black box that focused on the inputs and outputs of the system based on the functional requirements and specifications of the system, will offer a license plate in an interactive and dynamic way with an easy-to-use interface.
Flexibility Effects of a Flapping Mechanism Inspired by Insect Musculoskeletal System on Flight Performance
Authors: Koizumi Sakito , Nakata Toshiyuki , Liu Hao
Published: April 2021

Flying animals such as insects display great flight performances with high stability and maneuverability even under unpredictable disturbances in natural and man-made environments. Unlike man-made mechanical systems like a drone, insects can achieve various flapping motions through their flexible musculoskeletal systems. However, it remains poorly understood whether flexibility affects flight performances or not. Here, we conducted an experimental study on the effects of the flexibility associated with the flapping mechanisms on aerodynamic performance with a flexible flapping mechanism (FFM) inspired by the flexible musculoskeletal system of insects. Based on wing kinematic and force measurements, we found an appropriate combination of the flexible components could improve the aerodynamic efficiency by increasing the wingbeat amplitude. Results of the wind tunnel experiments suggested that, through some passive adjustment of the wing kinematics in concert with the flexible mechanism, the disturbance-induced effects could be suppressed. Therefore, the flight stability under the disturbances is improved. While the FFM with the most rigid spring was least efficient in the static experiments, the model was most robust against the wind within the range of the study. Our results, particularly regarding the trade-off between the efficiency and the robustness, point out the importance of the passive response of the flapping mechanisms, which may provide a functional biomimetic design for the flapping micro air vehicles (MAVs) capable of achieving high efficiency and stability.
The Current Dilemma and Breakthrough of Stem Cell Therapy in Ischemic Heart Disease
Authors: Liu Chuanbin , Han Dong , Liang Ping , Li Yang , Cao Feng
Published: April 2021

Ischemic heart disease (IHD) is the leading cause of mortality worldwide. Stem cell transplantation has become a promising approach for the treatment of IHD in recent decades. It is generally recognized that preclinical cell-based therapy is effective and have yielded encouraging results, which involves preventing or reducing myocardial cell death, inhibiting scar formation, promoting angiogenesis, and improving cardiac function. However, clinical studies have not yet achieved a desired outcome, even multiple clinical studies showing paradoxical results. Besides, many fundamental puzzles remain to be resolved, for example, what is the optimal delivery timing and approach? Additionally, limited cell engraftment and survival, challenging cell fate monitoring, and not fully understood functional mechanisms are defined hurdles to clinical translation. Here we review some of the current dilemmas in stem cell-based therapy for IHD, along with our efforts and opinions on these key issues.
The Role of Notch, Hedgehog, and Wnt Signaling Pathways in the Resistance of Tumors to Anticancer Therapies
Authors: Kumar Vivek , Vashishta Mohit , Kong Lin , Wu Xiaodong , Lu Jiade J. , Guha Chandan , Dwarakanath B. S.
Published: April 2021

Resistance to therapy is the major hurdle in the current cancer management. Cancer cells often rewire their cellular process to alternate mechanisms to resist the deleterious effect mounted by different therapeutic approaches. The major signaling pathways involved in the developmental process, such as Notch, Hedgehog, and Wnt, play a vital role in development, tumorigenesis, and also in the resistance to the various anticancer therapies. Understanding how cancer utilizes these developmental pathways in acquiring the resistance to the multi-therapeutic approach cancer can give rise to a new insight of the anti-therapy resistance mechanisms, which can be explored for the development of a novel therapeutic approach. We present a brief overview of Notch, Hedgehog, and Wnt signaling pathways in cancer and its role in providing resistance to various cancer treatment modalities such as chemotherapy, radiotherapy, molecular targeted therapy, and immunotherapy. Understanding the importance of these molecular networks will provide a rational basis for novel and safer combined anticancer therapeutic approaches for the improvement of cancer treatment by overcoming drug resistance.
New Insights Into Sperm Ultrastructure Through Enhanced Scanning Electron Microscopy
Authors: Korneev Denis , Merriner D. Jo , Gervinskas Gediminas , de Marco Alex , O’Bryan Moira K.
Published: April 2021

The analysis of spermatozoa morphology is fundamental to understand male fertility and the etiology of infertility. Traditionally scanning electron microscopy (SEM) has been used to define surface topology. Recently, however, it has become a critical tool for three-dimensional analysis of internal cellular ultrastructure. Modern SEM provides nanometer-scale resolution, but the meaningfulness of such information is proportional to the quality of the sample preservation. In this study, we demonstrate that sperm quickly and robustly adhere to gold-coated surfaces. Leveraging this property, we developed three step-by-step protocols fulfilling different needs for sperm imaging: chemically fixed monolayers for SEM examination of the external morphology, and two high-pressure freezing-based protocols for fast SEM examination of full cell internal morphology and focused ion-beam SEM tomography. These analyses allow previously unappreciated insights into mouse sperm ultrastructure, including the identification of novel structures within the fibrous sheath and domain-specific interactions between the plasma membrane and exosome-like structures.
Distinct Phenotypes Induced by Different Degrees of Transverse Aortic Constriction in C57BL/6N Mice
Authors: Deng Haiyan , Ma Lei-Lei , Kong Fei-Juan , Qiao Zengyong
Published: April 2021

The transverse aortic constriction (TAC) model surgery is a widely used disease model to study pressure overload–induced cardiac hypertrophy and heart failure in mice. The severity of adverse cardiac remodeling of the TAC model is largely dependent on the degree of constriction around the aorta, and the phenotypes of TAC are also different in different mouse strains. Few studies focus on directly comparing phenotypes of the TAC model with different degrees of constriction around the aorta, and no study compares the difference in C57BL/6N mice. In the present study, C57BL/6N mice aged 10 weeks were subjected to sham, 25G TAC, 26G TAC, and 27G TAC surgery for 4 weeks. We then analyzed the different phenotypes induced by 25G TAC, 26G TAC, and 27G TAC in c57BL/6N mice in terms of pressure gradient, cardiac hypertrophy, cardiac function, heart failure situation, survival condition, and cardiac fibrosis. All C57BL/6N mice subjected to TAC surgery developed significantly hypertrophy. Mice subjected to 27G TAC had severe cardiac dysfunction, severe cardiac fibrosis, and exhibited characteristics of heart failure at 4 weeks post-TAC. Compared with 27G TAC mice, 26G TAC mice showed a much milder response in cardiac dysfunction and cardiac fibrosis compared to 27G TAC, and a very small fraction of the 26G TAC group exhibited characteristics of heart failure. There was no obvious cardiac dysfunction, cardiac fibrosis, and characteristics of heart failure observed in 25G TAC mice. Based on our results, we conclude that the 25G TAC, 26G TAC, and 27G TAC induced distinct phenotypes in C57BL/6N mice.
Changes in Extreme Climate Events in Rice-Growing Regions Under Different Warming Scenarios in China
Authors: Chou Jieming , Zhao Weixing , Li Jiangnan , Xu Yuan , Yang Fan , Sun Mingyang , Li Yuanmeng
Published: April 2021

Scientific prediction of critical time points of the global temperature increases and assessment of the associated changes in extreme climate events can provide essential guidance for agricultural production, regional governance, and disaster mitigation. Using daily temperature and precipitation model outputs from the Coupled Model Intercomparison Project Phase 6 (CMIP6), the time points of the temperature that will increase by 1.5 and 2.0°C were assessed under three different scenarios (SSP126, SSP245, and SSP585). To characterize the change of extreme climate events in the rice-growing regions in China, six indices were designed, and a time slice method was used. An analysis from an ensemble of CMIP6 models showed that under SSP245, the global mean temperature will rise by 1.5°C/2.0°C by approximately 2030/2049. A global warming of 2.0°C does not occur under SSP126. The time for a 1.5°C/2.0°C warming all becomes earlier under SSP585. Under 1.5°C of global warming, the number of warm days (TX90p), rice heat damage index (Ha), consecutive dry days (CDD), 5-day maximum precipitation (Rx5day), and number of annual total extreme precipitation events (R99pTOT) will clearly increase, while the number of cold damage (Cd) events will decrease. All the indices show a strong variability regionally. For example, the CDD increased significantly in the Central China and South China rice-growing regions. The monthly maximum consecutive 5-day precipitation increased by as much as 6.8 mm in the Southwest China rice-growing region.
Non-Alcoholic Fatty Liver Disease and Hypokalemia in Primary Aldosteronism Among Chinese Population
Authors: Chen Yi , Chen Xueyang , Chen Qiang , Yu Chaohui
Published: April 2021

Background

In recent years, evidence that aldosteronism is a risk factor for metabolic disorders has increased. This study was designed to investigate the role of nonalcoholic fatty liver disease (NAFLD) and hypokalemia in primary aldosteronism (PA).

Methods

A total of 222 patients diagnosed with PA and 222 non-PA patients were included in our study. Demographic data, medical histories, clinical evaluations, complete blood counts, serum biochemical analyses, aldosterone and potassium levels were obtained. Data are presented as the means ± standard deviation (SD). To compare the parameters between cases and controls, Student’s t-tests or Mann-Whitney U tests were used for continuous variables, and χ2 tests were used for categorical variables. Pearson correlation analysis was used to define relationships between pairs of parameters. A two-sided P < 0.05 was considered statistically significant. Multivariate logistic regression was performed to assess the independent effects of potassium and other metabolic variables on NAFLD in PA patients.

Results

The diagnosis of NAFLD was more common in PA patients (n=222, 35.1%) than in non-PA subjects (29.7%). PA patients with and without NAFLD had similar metabolic imbalance characteristics. In PA patients with hypokalemia, relatively higher prevalences of NAFLD (44% vs. 27%, P < 0.05) and diabetes mellitus (19.8% vs. 9.9%, P < 0.05) were observed. Hypokalemic PA patients had a worse metabolic status than PA patients without hypokalemia, including higher body mass index (BMI) (25.4 ± 3.4 vs. 24.1 ± 3.9 kg/m2, P < 0.05), more severe dyslipidemia as well as insulin resistance, higher serum uric acid levels (354 ± 95 vs. 319 ± 87 μmol/L, P < 0.01) and aggravated inflammation.

Conclusion

The prevalence of NAFLD was higher in PA patients than in non-PA patients, although the patterns of obesity, dyslipidemia and insulin resistance were similar. Hypokalemic PA patients had a worse metabolic status than normokalemic PA patients. This study provides new insights that can inform further mechanistic studies about metabolic imbalance in patients with aldosteronism.
The Three Domains of Life Within the Discharge Area of a Shallow Subterranean Estuary at a High Energy Beach
Authors: Degenhardt Julius , Khodami Sahar , Milke Felix , Waska Hannelore , Engelen Bert , Martinez Arbizu Pedro
Published: April 2021

Subterranean estuaries (STEs) play an important role in linking nutrient cycling between marine and terrestrial systems. As being the primary drivers of nutrient cycling, the composition of microbial communities and their adaptation toward both, terrestrial and marine conditions are of special interest. While bacterial communities of STEs have received increasing scientific attention, archaeal and meiofaunal diversity was mostly neglected. Previous studies at the investigated sampling site, the STE of a mesotidal beach at the German North Sea island of Spiekeroog, focused on spatial and seasonal patterns of geochemical and bacterial diversity. By additionally investigating the archaeal and meiofaunal diversity and distribution, we now aimed to fill this gap of knowledge to understand the microbial response to submarine groundwater discharge (SGD). The topography of Spiekeroog beach and associated geochemical gradients in porewater displayed a distinct cross-shore zonation, with seawater infiltration on the upper beach at the high water line (HWL), and saline and brackish porewater exfiltration (SGD) at the ridge-runnel structure and the low water line (LWL) on the lower beach. This led to a higher evenness of prokaryotic communities in lower beach areas impacted by SGD compared to unimpacted areas. Archaea contributed 1–4% to the 16S rRNA gene sequence dataset. Those were dominated by Nitrosopumilaceae, corresponding well to higher concentrations of NH4+ in the discharge area of the STE. The unimpacted sites had elevated abundances of Wosearchaeia, which were also detected previously in impacted areas of an STE at Mobile Bay (Gulf of Mexico). While a large proportion of prokaryotes were present in the entire intertidal area, meiofaunal community compositions were site specific and dominated by nematodes. Nematode communities of the high-water line differed distinctively from the other sites. Overall, our data indicates that the three domains of life display distinctly different adaptations when facing the same conditions within the STE. Therefore, distribution patterns of any domain can only be understood if all of them, together with basic environmental information are investigated in an integrated context.
Assessing the Moisture Transports Associated With Nocturnal Low-Level Jets in Continental South America
Authors: Braz Dejanira Ferreira , Ambrizzi Tércio , da Rocha Rosmeri Porfírio , Algarra Iago , Nieto Raquel , Gimeno Luis
Published: April 2021

Given the crucial role of low-level circulation in convective events, this study presents a climatological characterization of the moisture sources and sinks associated with the occurrence of nocturnal low-level jets (NLLJs) in South America. Six selected NLLJ cores are identified according to the jet index that considers a vertical wind speed shear of the lower troposphere at 00:00 local time (LT). The Lagrangian FLEXible PARTicle (FLEXPART) model was used to provide the outputs for tracking atmospheric air masses to determine the moisture sources and sinks for the NLLJ cores (Argentina, Venezuela, and the regions of Brazil: south—Brazil-S, southeast—Brazil-SE, north—Brazil-N, and northeast—Brazil-NE). The analysis is based on 37 years (1980–2016) of the ERA-Interim reanalysis. We found that the NLLJ index is stronger in the warm periods of a year (austral spring and summer) for the six selected regions. The NLLJ frequency is also higher in the warm months of the year, except in Brazil-NE where it is very frequent in all months. In Brazil-NE, the NLLJ also persists for 8 or more days, while the other NLLJs frequently persist for 1–2 days. The NLLJs occupy a broad low-level layer (from 1000 to 700 hPa) and exhibit a mean speed between 7 and 12 ms–1, which peaks mostly at 900 hPa. The moisture transport for each NLLJ shows that in addition to the intense local moisture sources, the NLLJs in Argentina and Brazil-S receive moisture from the tropical-subtropical South Atlantic Ocean and the Amazon basin, while the tropical-subtropical South Atlantic Ocean is the main moisture source for the NLLJ in Brazil-SE. Both moisture sources and sinks are stronger in the austral summer and fall. The NLLJ in Brazil receives moisture from the tropical South Atlantic (TSA) Ocean, which has weak seasonality. The moisture sources for the NLLJs in Brazil-N and Venezuela come from the tropical North Atlantic (TNA) Ocean in the austral summer and fall, while the TSA Ocean appears as an additional moisture source in the austral winter. This research contributes to improving our understanding of the NLLJs and their role in transporting moisture and controlling precipitation over the continent according to the seasons of a year, helping to improve seasonal climate forecasting.
Temporal Patterns of N2O Fluxes From a Rainfed Maize Field in Northeast China
Authors: Su Chenxia , Kang Ronghua , Huang Wentao , Fang Yunting
Published: April 2021

Rainfed agriculture is one of the most common farming practices in the world and is vulnerable to global climate change. However, only limited studies have been conducted on rainfed agriculture, mainly using low-frequency manual techniques, which caused large uncertainties in estimating annual N2O emissions. In this study, we used a fully automated system to continuously measure soil N2O emissions for two years (April 2017 to March 2019) in a typical rainfed maize field in Northeast China. The annual N2O emissions were 2.8 kg N ha−1 in year 1 (April 2017 to March 2018) and 1.8 kg N ha−1 in year 2 (April 2018 to March 2019), accounting for 1.9 and 1.2% of the nitrogen fertilizer applied, respectively. The inter-annual variability was mainly due to different weather conditions encountered in years 1 and 2. A severe drought in year 1 reduced plant N uptake, leaving high mineral N in the soil, and the following moderate rainfalls promoted a large amount of N2O emissions. The seasonal pattern of N2O fluxes was mainly controlled by soil temperature and soil nitrate concentration. Both soil moisture and the molar ratio of NO/N2O indicate that N2O and NO were mainly derived from nitrification, resulting in a significant positive correlation between N2O and NO flux in the intra-rows (where nitrogen fertilizer was applied). Moreover, we observed that the N2O emissions during the freeze–thaw periods were negligible in this region for rainfed agriculture. Our long-term and high-resolution measurements of soil N2O emissions suggest that sampling between LST 9:00 and 10:00 is the best empirical sampling time for the intermittent manual measurements.
OCT Hyperreflective Retinal Foci in Diabetic Retinopathy: A Semi-Automatic Detection Comparative Study
Authors: Midena Edoardo , Torresin Tommaso , Velotta Erika , Pilotto Elisabetta , Parrozzani Raffaele , Frizziero Luisa
Published: April 2021

Optical coherence tomography (OCT) allows us to identify, into retinal layers, new morphological entities, which can be considered clinical biomarkers of retinal diseases. According to the literature, solitary, small (<30 µm), medium level hyperreflective (similar to retinal fiber layer) retinal foci (HRF) may represent aggregates of activated microglial cells and an in vivo biomarker of retinal inflammation. The identification and quantification of this imaging biomarker allows for estimating the level and possibly the amount of intraretinal inflammation in major degenerative retinal disorders, whose inflammatory component has already been demonstrated (diabetic retinopathy, age-related macular degeneration, radiation retinopathy). Currently, diabetic retinopathy (DR) probably represents the best clinical model to apply this analysis in the definition of this clinical biomarker. However, the main limitation to the clinical use of HRF is related to the technical difficulty of counting them: a time-consuming methodology, which also needs trained examiners. To contribute to solve this limitation, we developed and validated a new method for the semi-automatic detection of HRF in OCT scans. OCT scans of patients affected by DR, were analyzed. HRF were manually counted in High Resolution spectral domain OCT images. Then, the same OCT scans underwent semi-automatic HRF counting, using an ImageJ software with four different settings profiles. Statistical analysis showed an excellent intraclass correlation coefficient (ICC) between the manual count and each of the four semi-automated methods. The use of the second setting profile allows to obtain at the Bland–Altman graph a bias of −0.2 foci and a limit of agreement of ±16.3 foci. This validation approach opens the way not only to the reliable and daily clinical applicable quantification of HRF, but also to a better knowledge of the inflammatory component—including its progression and regression changes—of diabetic retinopathy.
Developing an Environmental Impact Assessment for Floating Island Applications
Authors: Tamis Jacqueline E. , Jongbloed Ruud H. , Piet Gerjan J. , Jak Robbert G.
Published: April 2021

In the Space@Sea project a conceptual study is performed to develop standardized cost efficient floating modular islands with low environmental impact. As these floating modular islands are introduced for a purpose which is likely to determine the environmental impact, possible applications were considered: living, aquaculture, ports and logistics, and energy hub. The aim of this study is to develop a structured approach for Environmental Impact Assessments (EIAs) of floating modular islands and their applications as these are considered within the Space@Sea project. To contribute to the efficiency and sustainability of future floating island developments, early awareness of the likely environmental consequences is important and requires a solid knowledge base. To that end we recommend a screening approach to identify the main threats to the marine ecosystem and their potential impacts at the earliest (conceptual) stage of development. For each Space@Sea type of application, this screening approach should identify the main threats through an EIA that links critical pressures with sensitive ecosystem components. While conventional impact assessments only consider negative impacts, we also consider potential environmental benefits of floating islands. This not only to enhance more environmental-friendly designs but also to provide a balanced perspective which considers not only threats but also opportunities in future developments and implementation of floating islands and their applications.
Wire and Arc Additive Manufacturing of High-Strength Al–Zn–Mg Aluminum Alloy
Authors: Fang Xuewei , Chen Guopeng , Yang Jiannan , Xie Yang , Huang Ke , Lu Bingheng
Published: April 2021

High-strength 7xxx series aluminum alloys are of great importance for the aerospace industries. However, this type of aluminum alloys has poor processability for most additive manufacturing techniques. In this paper, a newly designed Al–Zn–Mg alloy was used as a feeding wire to fabricate thin wall-shaped samples using the wire and arc additive manufacturing (WAAM) technique. These samples were fabricated based on the cold metal transfer (CMT) process with four different types of arc modes, that is, CMT, CMT-incorporated pulse (CMT + P), CMT-incorporated polarity (CMT + A), CMT-incorporated pulse and polarity (CMT + PA). The optical microscopy, x-ray computed tomography, and scanning electron microscopy equipped with energy-dispersive x-ray spectroscopy (EDS) and electron backscatter diffraction (EBSD) were employed to characterize the microstructure and phase constitution. The results clearly reveal that the porosity varies with the arc modes, and the densest sample with porosity of 0.97% was obtained using the CMT + P mode. The mechanical properties of the fabricated samples are also dependent on the arc modes. The tensile strength and yield strength of the sample manufactured by the CMT + PA arc mode are the highest. In terms of anisotropy, the strength differences in horizontal and vertical direction of the samples made by CMT + PA, CMT + A, and CMT modes are all large, which is mainly ascribed to the pores distributed at the interlayer region.
Prevalence and Prognostic Value of Heart Failure Stages: An Elderly Inpatient Based Cohort Study
Authors: Zheng Pei-Pei , Yao Si-Min , Guo Di , Cui Ling-ling , Miao Guo-Bin , Dong Wei , Wang Hua , Yang Jie-Fu
Published: April 2021

Background: The prevalence and prognostic value of heart failure (HF) stages among elderly hospitalized patients is unclear.

Methods: We conducted a prospective, observational, multi-center, cohort study, including hospitalized patients with the sample size of 1,068; patients were age 65 years or more, able to cooperate with the assessment and to complete the echocardiogram. Two cardiologists classified all participants in various HF stages according to 2013 ACC/AHA HF staging guidelines. The outcome was rate of 1-year major adverse cardiovascular events (MACE). The Kaplan–Meier method and Cox proportional hazards models were used for survival analyses. Survival classification and regression tree analysis were used to determine the optimal cutoff of N-terminal pro-brain natriuretic peptide (NT-proBNP) to predict MACE.

Results: Participants' mean age was 75.3 ± 6.88 years. Of them, 4.7% were healthy and without HF risk factors, 21.0% were stage A, 58.7% were stage B, and 15.6% were stage C/D. HF stages were associated with worsening 1-year survival without MACE (log-rank χ2 = 69.62, P < 0.001). Deterioration from stage B to C/D was related to significant increases in HR (3.636, 95% CI, 2.174–6.098, P < 0.001). Patients with NT-proBNP levels over 280.45 pg/mL in stage B (HR 2; 95% CI 1.112–3.597; P = 0.021) and 11,111.5 pg/ml in stage C/D (HR 2.603, 95% CI 1.014–6.682; P = 0.047) experienced a high incidence of MACE adjusted for age, sex, and glomerular filtration rate.

Conclusions : HF stage B, rather than stage A, was most common in elderly inpatients. NT-proBNP may help predict MACE in stage B.

Trial Registration: ChiCTR1800017204; 07/18/2018.
Molecular Epidemiology of Salmonellosis in Florida, USA, 2017–2018
Authors: Singh Nitya , Li Xiaolong , Beshearse Elizabeth , Blanton Jason L. , DeMent Jamie , Havelaar Arie H.
Published: April 2021

The state of Florida reports a high burden of non-typhoidal Salmonella enterica with approximately two times higher than the national incidence. We retrospectively analyzed the population structure and molecular epidemiology of 1,709 clinical isolates from 2017 and 2018. We found 115 different serotypes. Rarefaction suggested that the serotype richness did not differ between children under 2 years of age and older children and adults and, there are ~22 well-characterized dominant serotypes. There were distinct differences in dominant serotypes between Florida and the USA as a whole, even though S. Enteritidis and S. Newport were the dominant serotypes in Florida and nationally. S. Javiana, S. Sandiego, and S. IV 50:z4, z23:- occurred more frequently in Florida than nationally. Legacy Multi Locus Sequence Typing (MLST) was of limited use for differentiating clinical Salmonella isolates beyond the serotype level. We utilized core genome MLST (cgMLST) hierarchical clusters (HC) to identify potential outbreaks and compared them to outbreaks detected by Pulse Field Gel Electrophoresis (PFGE) surveillance for five dominant serotypes (Enteritidis, Newport, Javiana, Typhimurium, and Bareilly). Single nucleotide polymorphism (SNP) phylogenetic-analysis of cgMLST HC at allelic distance 5 or less (HC5) corroborated PFGE detected outbreaks and generated well-segregated SNP distance-based clades for all studied serotypes. We propose “combination approach” comprising “HC5 clustering,” as efficient tool to trigger Salmonella outbreak investigations, and “SNP-based analysis,” for higher resolution phylogeny to confirm an outbreak. We also applied this approach to identify case clusters, more distant in time and place than traditional outbreaks but may have been infected from a common source, comparing 176 Florida clinical isolates and 1,341 non-clinical isolates across USA, of most prevalent serotype Enteritidis collected during 2017–2018. Several clusters of closely related isolates (0–4 SNP apart) within HC5 clusters were detected and some included isolates from poultry from different states in the US, spanning time periods over 1 year. Two SNP-clusters within the same HC5 cluster included isolates with the same multidrug-resistant profile from both humans and poultry, supporting the epidemiological link. These clusters likely reflect the vertical transmission of Salmonella clones from higher levels in the breeding pyramid to production flocks.
Pharmacological Mechanisms Underlying the Anti-asthmatic Effects of Modified Guomin Decoction Determined by Network Pharmacology and Molecular Docking
Authors: Wang Guishu , Zhou Bo , Wang Zheyi , Meng Yufeng , Liu Yaqian , Yao Xiaoqin , Feng Cuiling
Published: April 2021

Background

Asthma is a chronic inflammatory disease characterized by Th2-predominant inflammation and airway remodeling. Modified Guo Min decoction (MGMD) has been an extensive practical strategy for allergic disorders in China. Although its potential anti-asthmatic activity has been reported, the exact mechanism of action of MGMD in asthma remains unexplored.

Methods

Network pharmacology approach was employed to predict the active components, potential targets, and molecular mechanism of MGMD for asthma treatment, including drug-likeness evaluation, oral bioavailability prediction, protein–protein interaction (PPI) network construction and analysis, Gene Ontology (GO) terms, and Reactome pathway annotation. Molecular docking was carried out to investigate interactions between active compounds and potential targets.

Results

A total of 92 active compounds and 72 anti-asthma targets of MGMD were selected for analysis. The GO enrichment analysis results indicated that the anti-asthmatic targets of MGMD mainly participate in inflammatory and in airway remolding processes. The Reactome pathway analysis showed that MGMD prevents asthma mainly through regulation of the IL-4 and IL-13 signaling and the specialized pro-resolving mediators (SPMs) biosynthesis. Molecular docking results suggest that each bioactive compounds (quercetin, wogonin, luteolin, naringenin, and kaempferol) is capable to bind with STAT3, PTGS2, JUN, VEGFA, EGFR, and ALOX5.

Conclusion

This study revealed the active ingredients and potential molecular mechanism by which MGMD treatment is effective against airway inflammation and remodeling in asthma through regulating IL-4 and IL-13 signaling and SPMs biosynthesis.
Identification of Prognostic Glycolysis-Related lncRNA Signature in Tumor Immune Microenvironment of Hepatocellular Carcinoma
Authors: Bai Yang , Lin Haiping , Chen Jiaqi , Wu Yulian , Yu Shi’an
Published: April 2021

Purpose: The purpose of this study was to construct a novel risk scoring model with prognostic value that could elucidate tumor immune microenvironment of hepatocellular carcinoma (HCC).

Samples and methods: Data were obtained through The Cancer Genome Atlas (TCGA) database. Univariate Cox analysis, least absolute shrinkage and selection operator (LASSO) analysis, and multivariate Cox analysis were carried out to screen for glycolysis-related long noncoding RNAs (lncRNAs) that could provide prognostic value. Finally, we established a risk score model to describe the characteristics of the model and verify its prediction accuracy. The receiver operating characteristic (ROC) curves of 1, 3, and 5 years of overall survival (OS) were depicted with risk score and some clinical features. ESTIMATE algorithm, single-sample gene set enrichment analysis (ssGSEA), and CIBERSORT analysis were employed to reveal the characteristics of tumor immune microenvironment in HCC. The nomogram was drawn by screening indicators with high prognostic accuracy. The correlation of risk signature with immune infiltration and immune checkpoint blockade (ICB) therapy was analyzed. After enrichment of related genes, active behaviors and pathways in high-risk groups were identified and lncRNAs related to poor prognosis were validated in vitro. Finally, the impact of MIR4435-2HG upon ICB treatment was uncovered.

Results: After screening through multiple steps, four glycolysis-related lncRNAs were obtained. The risk score constructed with the four lncRNAs was found to significantly correlate with prognosis of samples. From the ROC curve of samples with 1, 3, and 5 years of OS, two indicators were identified with high prognostic accuracy and were used to draw a nomogram. Besides, the risk score significantly correlated with immune score, immune-related signature, infiltrating immune cells (i.e. B cells, etc.), and ICB key molecules (i.e. CTLA4,etc.). Gene enrichment analysis indicated that multiple biological behaviors and pathways were active in the high-risk group. In vitro validation results showed that MIR4435-2HG was highly expressed in the two cell lines, which had a significant impact on the OS of samples. Finally, we corroborated that MIR4435-2HG had intimate relationship with ICB therapy in hepatocellular carcinoma.

Conclusion: We elucidated the crucial role of risk signature in immune cell infiltration and immunotherapy, which might contribute to clinical strategies and clinical outcome prediction of HCC.
Advances and Insights of APC-Asef Inhibitors for Metastatic Colorectal Cancer Therapy
Authors: Yang Xiuyan , Zhong Jie , Zhang Qiufen , Feng Li , Zheng Zhen , Zhang Jian , Lu Shaoyong
Published: April 2021

In Colorectal cancer (CRC), adenomatous polyposis coli (APC) directly interacts with the Rho guanine nucleotide exchange factor 4 (Asef) and releases its GEF activity. Activated Asef promotes the aberrant migration and invasion of CRC cell through a CDC42-mediated pathway. Knockdown of either APC or Asef significantly decreases the migration of CRC cells. Therefore, disrupting the APC-Asef interaction is a promising strategy for the treatment of invasive CRC. With the growth of structural information, APC-Asef inhibitors have been designed, providing hope for CRC therapy. Here, we will review the APC-Asef interaction in cancer biology, the structural complex of APC-Asef, two generations of peptide inhibitors of APC-Asef, and small molecule inhibitors of APC-Asef, focusing on research articles over the past 30 years. We posit that these advances in the discovery of APC-Asef inhibitors establish the protein-protein interaction (PPI) as targetable and provide a framework for other PPI programs.
Mitochondrial CHCHD2: Disease-Associated Mutations, Physiological Functions, and Current Animal Models
Authors: Kee Teresa R. , Espinoza Gonzalez Pamela , Wehinger Jessica L. , Bukhari Mohammed Zaheen , Ermekbaeva Aizara , Sista Apoorva , Kotsiviras Peter , Liu Tian , Kang David E. , Woo Jung-A. A.
Published: April 2021

Rare mutations in the mitochondrial protein coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) are associated with Parkinson’s disease (PD) and other Lewy body disorders. CHCHD2 is a bi-organellar mediator of oxidative phosphorylation, playing crucial roles in regulating electron flow in the mitochondrial electron transport chain and acting as a nuclear transcription factor for a cytochrome c oxidase subunit (COX4I2) and itself in response to hypoxic stress. CHCHD2 also regulates cell migration and differentiation, mitochondrial cristae structure, and apoptosis. In this review, we summarize the known disease-associated mutations of CHCHD2 in Asian and Caucasian populations, the physiological functions of CHCHD2, how CHCHD2 mutations contribute to α-synuclein pathology, and current animal models of CHCHD2. Further, we discuss the necessity of continued investigation into the divergent functions of CHCHD2 and CHCHD10 to determine how mutations in these similar mitochondrial proteins contribute to different neurodegenerative diseases.
A New Paradigm for Training Hyperactive Dopamine Transporter Knockout Rats: Influence of Novel Stimuli on Object Recognition
Authors: Kurzina Natalia P. , Volnova Anna B. , Aristova Irina Y. , Gainetdinov Raul R.
Published: April 2021

Attention deficit hyperactivity disorder (ADHD) is believed to be connected with a high level of hyperactivity caused by alterations of the control of dopaminergic transmission in the brain. The strain of hyperdopaminergic dopamine transporter knockout (DAT-KO) rats represents an optimal model for investigating ADHD-related pathological mechanisms. The goal of this work was to study the influence of the overactivated dopamine system in the brain on a motor cognitive task fulfillment. The DAT-KO rats were trained to learn an object recognition task and store it in long-term memory. We found that DAT-KO rats can learn to move an object and retrieve food from the rewarded familiar objects and not to move the non-rewarded novel objects. However, we observed that the time of task performance and the distances traveled were significantly increased in DAT-KO rats in comparison with wild-type controls. Both groups of rats explored the novel objects longer than the familiar cubes. However, unlike controls, DAT-KO rats explored novel objects significantly longer and with fewer errors, since they preferred not to move the non-rewarded novel objects. After a 3 months’ interval that followed the training period, they were able to retain the learned skills in memory and to efficiently retrieve them. The data obtained indicate that DAT-KO rats have a deficiency in learning the cognitive task, but their hyperactivity does not prevent the ability to learn a non-spatial cognitive task under the presentation of novel stimuli. The longer exploration of novel objects during training may ensure persistent learning of the task paradigm. These findings may serve as a base for developing new ADHD learning paradigms.
Emergence of Neuronal Synchronisation in Coupled Areas
Authors: Protachevicz Paulo R. , Hansen Matheus , Iarosz Kelly C. , Caldas Iberê L. , Batista Antonio M. , Kurths Jürgen
Published: April 2021

One of the most fundamental questions in the field of neuroscience is the emergence of synchronous behaviour in the brain, such as phase, anti-phase, and shift-phase synchronisation. In this work, we investigate how the connectivity between brain areas can influence the phase angle and the neuronal synchronisation. To do this, we consider brain areas connected by means of excitatory and inhibitory synapses, in which the neuron dynamics is given by the adaptive exponential integrate-and-fire model. Our simulations suggest that excitatory and inhibitory connections from one area to another play a crucial role in the emergence of these types of synchronisation. Thus, in the case of unidirectional interaction, we observe that the phase angles of the neurons in the receiver area depend on the excitatory and inhibitory synapses which arrive from the sender area. Moreover, when the neurons in the sender area are synchronised, the phase angle variability of the receiver area can be reduced for some conductance values between the areas. For bidirectional interactions, we find that phase and anti-phase synchronisation can emerge due to excitatory and inhibitory connections. We also verify, for a strong inhibitory-to-excitatory interaction, the existence of silent neuronal activities, namely a large number of excitatory neurons that remain in silence for a long time.