bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating markers of neutrophil extracellular traps (NETs) in patients with ovarian tumors
Authors: Dobilas Arturas , Thålin Charlotte , Wallén Håkan , Borgfeldt Christer 
Published: July 2021

Abstract
Background
Inflammation is a hallmark of cancer, and emerging light is being shed on the neutrophil release of nuclear chromatin, referred to as neutrophil extracellular traps (NETs) in cancer and cancer associated thrombosis. The NET-specific marker citrullinated histone H3 (H3Cit) has been found to be elevated in plasma from patients with malignancies, suggesting the potential of NET markers, such as H3Cit, as novel cancer biomarkers.
Objective
To determine the levels of plasma H3Cit in blood in women with adnexal masses.
Subjects and Method
s: Peripheral blood samples were obtained preoperatively from 199 patients admitted for primary surgery of adnexal masses 2015–2017. Patients were grouped according to tumor type and stage of cancer. Plasma levels of H3Cit-DNA, cell free DNA (cfDNA) and the clinically implemented tumor marker cancer antigen 125 (CA125) were determined with ELISA.
Results
Plasma levels of H3Cit-DNA and cfDNA were not elevated in women with borderline or malignant ovarian tumors compared with women with benign tumors. Increased plasma levels of CA125 were detected in borderline and ovarian cancer stage I and stage II-IV compared with benign ovarian tumor patients (ptrend<0.001). In Cox regression analysis high levels of Ca 125 dichotomized at 326 IU/ml (median) showed worse overall survival hazard ratio 1.9 (95 % C.I. 1.03–3.36; p = 0.038). No differences were found in the survival analyses in malignant ovarian tumors analyzing the cfDNA and H3Cit-DNA levels.
Conclusion
This study did not find any association nor prognostic association between the plasma levels of the NET marker H3Cit and ovarian cancer patients.
A nomogram based on Psoas muscle index and prognostic nutritional index predicts the prognosis of intrahepatic cholangiocarcinoma after surgery: a multi-center cohort study
Authors: Bao Wenming , Deng Liming , Yu haitao , He bangjie , Lin Zixia , Lin Zhihui , Yang Jinhuan , Zhao Jungang , Zheng Chongming , Yu Zhengping , Jin Bin , Wang Yi , Chen Gang 
Published: July 2021

Abstract
Background

Intrahepatic cholangiocarcinoma (ICC) is a malignant neoplasm with a poor prognosis. Prediction of prognosis is critical for the individualized clinical management of patients with ICC. The purpose of this study is to establish a nomogram based on the psoas muscle index (PMI) and prognostic nutritional index (PNI) to identify the high risk-patient with ICC after curative resection.
Methods

ICC Patients after hepatectomy in multi-hospital from August 2012 to October 2019 were enrolled. The overall survival (OS) and recurrence-free survival (RFS) rates were analyzed by Kaplan-Meier. The independent factors were identified by univariate and multivariate Cox regression analyses. A nomogram based on independent factors was established to predict ICC patient prognosis.
Results

178 ICC patients were included. The OS was worst in the patients with a combination of low PMI combined low PNI (p < 0.01). PMI, PNI, lymph node metastasis and tumor differentiation were the independent prognostic risk factors; these factors were used to establish the nomogram was established by it. The calibration curve revealed that the nomogram survival probability prediction model was in good agreement with the actual observation results. The nomogram has good reliability in predicting ICC patient prognosis (OS C-index = 0.692). The area under the receiver operating characteristic curve (AUC) for the nomogram's 3-year predicted survival was 0.752. Based on the stratified by nomogram, the median survival for low-risk patients was 59.8 months, compared with 16.2 months for high-risk patients (p༜0.001).
Conclusion

The nomogram based on the PMI and PNI can identify patients with the highest risk of poor prognosis after curative hepatectomy. It is a good decision-making tool for individualized treatment.
Enhancing the Effectiveness of Flipped Classroom in Health Science Education: A State-of-the-art Review
Authors: Oudbier Janique , Spaai Gerard , Timmermans Karline , Boerboom Tobias 
Published: July 2021

Abstract
Background. In a flipped classroom, students acquire knowledge before class and deepen and apply this knowledge during class. This way, lower-order learning goals are achieved before class and higher-order skills are reached during class. This study aims to provide an overview of the factors that contribute to the effectiveness of the flipped classroom and how these factors can be stimulated. The effectiveness of the flipped classroom is conceptualized in this study as learning achievement, the achievement of higher learning goals, and student perceptions. Methods. A state-of-the-art review was conducted. The databases MEDLINE, PsycINFO, PubMed, Web of Science, and Scopus were consulted. The timeframe is 2016 till 2020. The studies were qualitatively analyzed according to the grounded theory method. Results. After screening the studies based on the inclusion-and exclusion criteria, 60 studies were included in this review. The qualitative analysis of these studies revealed six main factors that affect the effectiveness of the flipped classroom: student characteristics, teacher characteristics, implementation, task characteristics, out-of-class activities, and in-class activities. Mediating factors are, amongst other factors, the learner’s level of self-regulated learning, teacher’s role and motivation, assessment approach, and guidance during self-study. These factors can be positively stimulated by structuring the learning process and focusing the teacher training on competencies and learning-and teaching approaches that are essential for the flipped classroom. Conclusion. This paper provides insight into the factors that contribute to the effectiveness of the flipped classroom and how these factors could be stimulated. In order to stimulate the effectiveness of the flipped classroom, the positively and negatively affecting factors and mediating factors should be taken into account in the design of the flipped classroom. The interventions mentioned in this paper could also be used to enhance the effectiveness.
Impact of land-use and land-cover change on soil erosion using the RUSLE model and the geographic information system: a case of Temeji watershed, Western Ethiopia
Authors: Moisa Mitiku Badasa , Negash Daniel Assefa , Merga Biratu Bobo , Gemeda Dessalegn Obsi 
Published: July 2021

Abstract
The impact of land-use land-cover (LULC) change on soil resources is getting global attention. Soil erosion is one of the critical environmental problems worldwide with high severity in developing countries. This study integrates the Revised Universal Soil Loss Equation model with a geographic information system to estimate the impacts of LULC conversion on the mean annual soil loss in the Temeji watershed. In this study, LULC change of Temeji watershed was assessed from 2000 to 2020 by using 2000 Landsat ETM+ and 2020 Landsat OLI/TIRS images and classified using supervised maximum likelihood classification algorithms. Results indicate that the majority of the LULC in the study area is vulnerable to soil erosion. High soil loss is observed when grassland and forest land were converted into cultivated land with a mean soil loss of 88.8 and 86.9 t/ha/year in 2020. Results revealed that about 6,608.5 ha (42.8%) and 8,391.8 ha (54.4%) were categorized under severe classes in 2000 and 2020, respectively. Accordingly, the soil loss severity class is directly correlated with the over-exploitation of forest resources and grasslands for agricultural purposes. These results can be useful for advocacy to enhance local people and stakeholder's participation toward soil and water conservation practices.
Quantifying the effects of watershed subdivision scale and spatial density of weather inputs on hydrological simulations in a Norwegian Arctic watershed
Authors: Bui Minh Tuan , Lu Jinmei , Nie Linmei 
Published: July 2021

Abstract
The effects of watershed subdivisions on hydrological simulations have not been evaluated in Arctic conditions yet. This study applied the Soil and Water Assessment Tool and the threshold drainage area (TDA) technique to evaluate the impacts of watershed subdivision on hydrological simulations at a 5,913-km2 Arctic watershed, Målselv. The watershed was discretized according to four TDA scheme scales including 200, 2,000, 5,000, and 10,000 ha. The impacts of different TDA schemes on hydrological simulations in water balance components, snowmelt runoff, and streamflow were investigated. The study revealed that the complexity of terrain and topographic attributes altered significantly in the coarse discretizations: (1) total stream length (−47.2 to −74.6%); (2) average stream slope (−68 to −83%); and (3) drainage density (−24.2 to −51.5%). The spatial density of weather grid integration reduced from −5 to −33.33% in the coarse schemes. The annual mean potential evapotranspiration, evapotranspiration, and lateral flow slightly decreased, while areal rainfall, surface runoff, and water yield slightly increased with the increases of TDAs. It was concluded that the fine TDAs produced finer and higher ranges of snowmelt runoff volume across the watershed. All TDAs had similar capacities to replicate the observed tendency of monthly mean streamflow hydrograph, except overestimated/underestimated peak flows. Spatial variation of streamflow was well analyzed in the fine schemes with high density of stream networks, while the coarse schemes simplified this. Watershed subdivisions affected model performances, in the way of decreasing the accuracy of monthly streamflow simulation, at 60% of investigated hydro-gauging stations (3/5 stations) and in the upstream. Furthermore, watershed subdivisions strongly affected the calibration process regarding the changes in sensitivity ranking of 18 calibrated model parameters and time it took to calibrate.
Potential production of struvite from the anaerobic digestion of food waste: analysis in one-phase and two-phase configurations
Authors: Parra-Orobio Brayan Alexis , Pérez-Vidal Andrea , Torres-Lozada Patricia 
Published: July 2021

Abstract
Anaerobic digestion (AD) of food waste (FW) has been gaining more interest as it has potential for the production of organic amendments with high struvite (NH4MgPO4·6H2O) content, which is a nutrient of great interest in sustainable agriculture. In this study, the influence of AD of FW in one- and two-phase configurations on methane production and the potential for struvite formation using digestate was evaluated. It was found that the two-phase is more efficient as its organic loading rate is 18% higher than that of one-phase configuration. In addition, the two-phase yielded a higher methane content in biogas (&gt;60%) and a higher organic matter transformation in each of the AD stages (&gt;20%); further, the digestate complied with the regulatory requirements for the use of organic amendments, thereby being deemed as a Type-B material with a struvite precipitation potential, exceeding 80%, as opposed to the digestate from one-phase configuration, which may represent a revenue of up to US$ 26,505 per year.
4D-QSAR Models Applied to the Study of TGF- β1 Receptor Inhibitors
Authors: Maria de Assis Tamiris , Ramalho Teodorico Castro , Ferreira da Cunha Elaine Fontes 
Published: July 2021

Background:
The quantitative structure-activity relationship is an analysis method that
can be applied for designing new molecules. In 1997, Hopfinger and coworkers developed the 4DQSAR
methodology aiming to eliminate the question of which conformation to use in a QSAR
study. In this work, the 4D-QSAR methodology was used to quantitatively determine the influence
of structural descriptors on the activity of aryl pyrimidine derivatives as inhibitors of the TGF-β1
receptor. The members of the TGF-β subfamily are interesting molecular targets, since they play
an important function in the growth and development of cell cellular including proliferation, apoptosis,
differentiation, Epithelial-Mesenchymal Transition (EMT), and migration. In late stages,
TGF-β exerts tumor-promoting effects, increasing tumor invasiveness, and metastasis. Therefore,
TGF-β is an attractive target for cancer therapy.

Objective:
The major goal of the current research is to develop 4D-QSAR models aiming to propose
new structures of aryl pyrimidine derivatives.

Materials and Methods:
Molecular dynamics simulation was carried out to generate the conformational
ensemble profile of a data set with aryl pyrimidine derivatives. The conformations were overlaid
into a three-dimensional cubic box, according to the three-ordered atom alignment. The occupation
of the grid cells by the interaction of pharmacophore elements provides the Grid Cell Occupancy
Descriptors (GCOD), the dependent variables used to build the 4D-QSAR models. The best
models were validated (internal and external validation) using several statistical parameters. Docking
molecular studies were performed to better understand the binding mode of pyrimidine derivatives
inside the TGF-β active site.

Results :
The 4D-QSAR model presented seven descriptors and acceptable statistical parameters
(R2 = 0.89, q2 = 0.68, R2
pred = 0.65, r2
m = 0.55, R2
P = 0.68 and R2
rand = 0.21) besides pharmacophores
groups important for the activity of these compounds. The molecular docking studies helped to understand
the pharmacophoric groups and proposed substituents that increase the potency of aryl
pyrimidine derivatives.

Conclusion:
The best QSAR model showed adequate statistical parameters that ensure their fitness,
robustness, and predictivity. Structural modifications were assessed, and five new structures
were proposed as candidates for a drug for cancer treatment.
Larrea tridentata and its Biological Activities
Authors: Reyes-Melo Karen Y. , Galván-Rodrigo Adrián A. , Martínez-Olivo Isaí E. , Núñez-Mojica Guillermo , Ávalos-Alanís Francisco G. , García Abraham , del Rayo Camacho-Corona María 
Published: July 2021

Background:
Larrea tridentata is a dominant shrub in the deserts of North America and
is recognized for its various traditional uses. More than 50 traditional uses have been recorded. Regarding
its chemical composition, the products of the mevalonate, shikimate, and malonate pathways
are predominant. L. tridentata has nordihydroguaiaretic acid (NDGA), one of its most studied
secondary metabolites that exhibited remarkable different biological activities: sequestration of reactive
oxygen species, inhibition of lipoxygenases (LOX) and activation of the endogenous antioxidant
response mediated by nuclear factor erythroid 2-related factor 2 (NRF2).

Objective and Methods:
This review seeks to draw attention to metabolites other than NDGA and
which also contribute to the various biological activities of L. tridentata. Therefore, the present review
includes those reports focused on the pharmacological properties of the organic extracts of L.
tridentata and its natural products with promising values.

Results and Conclusion:
Among the most promising and widely reported metabolites from L. tridentata,
are: 3’-demethoxy-6-O-demethylisoguaiacin, 3’-O-methyldihydroguaiaretic acid, meso-dihydroguaiaretic
acid, and tetra-O-methylnordihydroguaiaretic acid. These have been reported to exhibit
antibacterial, antiprotozoal, anthelmintic, antifungal, antiviral, anticancer, and antioxidant activities.
Synthesis, Molecular Docking and Mosquitocidal Efficacy of Lawsone and
its Derivatives Against the Dengue Vector Aedes aegypti L. (Diptera:
Culicidae)
Authors: Stalin Antony , Dhivya Paul , Lin Ding , Feng Yue , Asharaja Antony Cruz , Gandhi Munusamy Rajiv , Kannan Balakrishnan Senthamarai , Kandhasamy Subramani , Reegan Appadurai Daniel , Chen Yuan 
Published: July 2021

Background:
Aedes aegypti is the primary dengue vector, a significant public health problem in many countries. Controlling the growth of Ae. aegypti is the biggest challenge in the mosquito control program, and there is a need for finding bioactive molecules to control Ae. aegypti in order to prevent dengue virus transmission.

Objective:
To assess the mosquitocidal property of lawsone and its 3-methyl-4H-chromen-3-yl-1-phenylbenzo[6,7]chromeno[2,3,c]pyrazole-dione derivatives (6a-6h) against various life stages of Ae. aegypti. Besides, to study the mode of action of the active compound by molecular docking and histopathological analysis.

Methods:
All derivatives were synthesized from the reaction between 2-hydroxy-1,4-naphthoquinone, chromene-3-carbaldehyde, and 1-phenyl-3-methyl-pyrazol-5-one by using one pot sequential multicomponent reaction. The mosquito life stages were subjected to diverse concentrations ranging from 1.25, 2.5, 5.0, and 10 ppm for lawsone and its derivatives. The structure of all synthesized compounds was characterized by spectroscopic analysis. Docking analysis was performed using autodock tools. Midgut sections of Ae. aegypti larvae were analyzed for histopathological effects.

Results:
Among the nine compounds screened, derivative 6e showed the highest mortality on Ae. aegypti life stages. The analyzed LC50 and LC90 results of derivative 6e were 3.01, 5.87 ppm, and 3.41, 6.28 ppm on larvae and pupae of Ae. aegypti, respectively. In the ovicidal assay, the derivative 6e recorded 47.2% egg mortality after 96-hour post-exposure to 10 ppm concentration. In molecular docking analysis, the derivative 6e confirmed strong binding interaction (-9.09 kcal/mol and -10.17 kcal/mol) with VAL 60 and HIS 62 of acetylcholinesterase 1 (AChE1) model and LYS 255, LYS 263 of kynurenine aminotransferase of Ae. aegypti, respectively. The histopathological results showed that the derivative 6e affected the columnar epithelial cells (CC) and peritrophic membrane (pM).

Conclusion:
The derivative 6e is highly effective in the life stages of Ae. aegypti mosquito and it could be used in the integrated mosquito management programme.
Safety Assessment and Potential Risks of the Glucagon Stimulation Test in
the Diagnosis of Secondary Adrenal Insufficiency
Authors: Ach Taieb , Abdelkrim Asma Ben , Hasni Yosra , Saad Ghada , Kacem Maha , Chaieb Molka , Zaouali Monia , Maaroufi Amel , Ach Koussay 
Published: July 2021

Background:
Although it takes more time, the Glucagon Stimulation Test (GST) is a reliable
measure for assessing growth hormone (GH) and Adrenocorticotropic Hormone (ACTH) secretion.
The GST is considered to be a safe test; however, it still has mild side effects and potential
risks.

Objective :
The objective of this study was to analyze the side effects of the GST while testing
adrenal-insufficient patients.

Methods:
This was a prospective study in which GST was performed in eighty-one patients (44
men, 37 women, mean age: 35.83A9.62 years) with the pituitary disorder. The GST consisted of an
intramuscular injection of 1 mg of glucagon. Blood samples were collected at baseline, and 30, 60,
90, 120, 150, 180, and 210 min after glucagon injection for cortisol measurements. All patients
were asked to report side effects associated with this test.

Results:
The mean peak blood glucose level under GST was 9.01A.03 mmol/L, and the mean
glycemic nadir was 4.34A.75 mmol/L most frequently found during the 30th minute (p <10-3).
During the test, 35 subjects (43.2%) had side effects with a mean age of 42.89 A19.75 years. Frequent
side effects included: nausea (29.62%), vomiting (27.16%), abdominal cramps (18.51%) and
hunger (13.58%). All patients tolerated the test until the end. Adverse effects were significantly
more prevalent in patients older than 50 years (p=0.012).

Conclusions:
The GST is a reliable alternative to assess the hypothalamic pituitary adrenal axis
but should be cautiously used especially in the elderly, despite minor side effects.
Potentially Inappropriate Medication Use in Older People: A Crosssectional Study Using Beers Criteria
Authors: Yüksel Gülsüm Hatice , Ozaydin Fuat Nihat , Ozaydin Ayse Nilufer 
Published: July 2021

Background:The use of Potentially Inappropriate Medications (PIMs) is common and negatively affects elderly health and disease prognosis.Objective:This study aims to analyze the frequency of PIMs in the elderly health records registered to a family health center and to identify risk factors, prescription/nonprescription distribution, distribution by healthcare institutions, number of doctors visits, and health literacy.Methods:In this cross-sectional study, a stratified sampling method was used to select individuals aged ≥ 65 years. The health records of the participants up to the last 12 months were examined, and medicines used by participants were evaluated according to Beers 2019 criteria.Results:Most of the participants (89.7%, n:183) had PIMs in health records. The mean number of PIMs used by the elderly was 2.9±1.9 (min:0, max:8). A positive linear relationship was observed between multimorbidity and the number of PIMs (p=0.001). There was no significant difference in terms of PIMs frequency among healthcare institutions. Prescription and non-prescription PIMs were found to belong to the same drug groups (Pain relievers and stomach medications). A linear and significant correlation was found between the number of PIMs and doctor visits (p=0.047).Conclusion:The doctor should examine prescription and over-the-counter medications used by the elderly during the visit. It will be useful to establish a warning system stating that PIMs are available while registering the medications in the electronic system. So, it will be possible for health authorities to re-evaluate the treatment and replace PIMs with rational drug options.
Multivariate Information Fusion for Identifying Antifungal Peptides with
Hilbert-Schmidt Independence Criterion
Authors: Zhou Haohao , Wang Hao , Ding Yijie , Tang Jijun 
Published: July 2021

Background:
Antifungal Peptides (AFP) have been found to be effective against many fungal
infections.

Objective:
However, it is difficult to identify AFP. Therefore, it is great practical significance to identify
AFP via machine learning methods (with sequence information).

Method:
In this study, a Multi-Kernel Support Vector Machine (MKSVM) with Hilbert-Schmidt Independence
Criterion (HSIC) is proposed. Proteins are encoded with five types of features (188-bit,
AAC, ASDC, CKSAAP, DPC), and then construct kernels using Gaussian kernel function. HSIC are
used to combine kernels and multi-kernel SVM model is built.

Results:
Our model performed well on three AFPs datasets and the performance is better than or comparable
to other state-of-art predictive models.

Conclusion:
Our method will be a useful tool for identifying antifungal peptides.