bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determinants of postnatal care non-utilization among women in Demba Gofa rural district, southern Ethiopia: a community-based unmatched case-control study
Authors: Manote Markos , Gebremedhin Tsegaye 
Published: September 2020

AbstractBackgroundMaternal and neonatal mortality remain a significant problem across much of the developing world, especially in sub-Saharan Africa countries. In Ethiopia, most maternal and neonatal deaths occur during the postpartum period; this is a critical time for monitoring the health of women and newborns, but the most neglected period for care. In rural communities of Ethiopia, the utilization of postnatal care service is very low and evidence on which factors contribute to the non-utilization of postnatal care (PNC) is insufficient. Consequently, this study was designed to identify the determinants of postnatal service non-utilization among women who gave birth in Demba Gofa rural district, Southern Ethiopia.MethodsA community-based unmatched case-control study was conducted among 186 cases (postnatal care non-utilizers) and 186 controls (postnatal care utilizers) in Demba Gofa rural district from March 1 to April 10, 2019. A previously tested interviewer-administered structured questionnaire was used for data collection. Binary logistic regression analysis was performed. In the final multivariable logistic regression analysis model, a p-value of less than 0.05 and an Adjusted Odd Ratio (AOR) with a 95% confidence interval (CI) was used to determine variables for postnatal care non-utilization.ResultsIn this study, women who delivered recently were incorporated within 186 cases and 186 controls. Not knowing the availability of PNC services (AOR: 4.33, 95% CI: 1.71–10.99), having a home delivery (AOR: 7.06, 95% CI: 3.71–13.44), ANC non-attendance (AOR: 6.14, 95% CI: 3.01–12.50), unable to make an independent decision (AOR: 9.31, 95% CI: 3.29–26.35), and not participating in the Women’s Development Army (WDA) (AOR: 5.09, 95% CI: 2.73–9.53) comprised the determinants which were assessed for non-utilization of postnatal care services.ConclusionsEncouraging institutional delivery along with integrated health education about postnatal care and postnatal danger signs, empowering women to execute independent decisions, accessing PNC services and strengthening participation in the Model Families will likely improve postnatal care service utilization in the district of Ethiopia.
Anti-cancer agent 3-bromopyruvate reduces growth of MPNST and inhibits metabolic pathways in a representative in-vitro model
Authors: Linke Christian , Wösle Markus , Harder Anja 
Published: September 2020

Abstract
Background
Anticancer compound 3-bromopyruvate (3-BrPA) suppresses cancer cell growth via targeting glycolytic and mitochondrial metabolism. The malignant peripheral nerve sheath tumor (MPNST), a very aggressive, therapy resistant, and Neurofibromatosis type 1 associated neoplasia, shows a high metabolic activity and affected patients may therefore benefit from 3-BrPA treatment. To elucidate the specific mode of action, we used a controlled cell model overexpressing proteasome activator (PA) 28, subsequently leading to p53 inactivation and oncogenic transformation and therefore reproducing an important pathway in MPNST and overall tumor pathogenesis.

Methods
Viability of MPNST cell lines S462, NSF1, and T265 in response to increasing doses (0–120 μM) of 3-BrPA was analyzed by CellTiter-Blue® assay. Additionally, we investigated viability, reactive oxygen species (ROS) production (dihydroethidium assay), nicotinamide adenine dinucleotide dehydrogenase activity (NADH-TR assay) and lactate production (lactate assay) in mouse B8 fibroblasts overexpressing PA28 in response to 3-BrPA application. For all experiments normal and nutrient deficient conditions were tested. MPNST cell lines were furthermore characterized immunohistochemically for Ki67, p53, bcl2, bcl6, cyclin D1, and p21.

Results
MPNST significantly responded dose dependent to 3-BrPA application, whereby S462 cells were most responsive. Human control cells showed a reduced sensitivity. In PA28 overexpressing cancer cell model 3-BrPA application harmed mitochondrial NADH dehydrogenase activity mildly and significantly failed to inhibit lactate production. PA28 overexpression was associated with a functional glycolysis as well as a partial resistance to stress provoked by nutrient deprivation. 3-BrPA treatment was not associated with an increase of ROS. Starvation sensitized MPNST to treatment.

Conclusions
Aggressive MPNST cells are sensitive to 3-BrPA therapy in-vitro with and without starvation. In a PA28 overexpression cancer cell model leading to p53 inactivation, thereby reflecting a key molecular feature in human NF1 associated MPNST, known functions of 3-BrPA to block mitochondrial activity and glycolysis were reproduced, however oncogenic cells displayed a partial resistance. To conclude, 3-BrPA was sufficient to reduce NF1 associated MPNST viability potentially due inhibition of glycolysis which should lead to the initiation of further studies and promises a potential benefit for NF1 patients.
Influenza A (H1N1)pdm09 outbreak of unknown source in a Ghanaian senior high school
Authors: Ameme Donne Kofi , Dadzie Dora , Asiedu-Bekoe Franklin , Edu-Quansah Elijah Paa , Kaburi Basil Benduri , Wullar Oxygen , Amo-Mensah Patrick , Kenu Ernest 
Published: September 2020

Abstract
Background
Influenza is an acute viral respiratory tract infection caused by influenza virus and transmitted from person to person. Though usually seasonal in temperate climates, influenza occurs throughout the year in the tropics with outbreaks occurring at irregular intervals. On February 6, 2018, a number of students from a Senior High School (SHS) in Accra reported to a district hospital with cough, fever and other respiratory symptoms. An influenza-like illness (ILI) outbreak was suspected. We investigated to determine the magnitude and source of the outbreak and implement control and preventive measures.

Methods
We interviewed health workers, staff and students of the school as well as case-patients and reviewed health records to collect data on demographic characteristics, signs and symptoms, date of illness onset and outcome. We defined ILI case as “any person in the SHS with fever (measured axillary temperature of ≥ 37.5 °C or history of fever) and cough with or without sore throat or runny nose from January 21 to February 26, 2018”. We conducted active case search to identify more cases and took oropharyngeal samples for laboratory testing. We performed descriptive and inferential analysis by calculating attack rate ratios (ARR) and their exact 95% confidence intervals (CI).

Results
Of the 3160 students, 104 case-patients were recorded from January 25, 2018 to February 13, 2018 (overall attack rate of 3.3%). Mean age of case-patients was 16.1 (±2.3) years with males constituting 71.2% (74/104). Sex specific attack rates were 5.6% (74/1331) and 1.6% (30/1829) for males and females respectively. Compared to females, males were 3.4 times as likely to be ill [ARR =3.4, 95%CI = (2.23–5.15)]. Nine oropharyngeal samples from 17 suspected case-patients tested positive for influenza A (H1N1)pdm09.

Conclusion
Outbreak of influenza A (H1N1)pdm09 occurred in a SHS in Accra from January to February, 2018. Even though source of the outbreak could not be determined, prompt case management and health education on hand and personal hygiene as non-pharmacological factors probably contributed to the outbreak control. The outbreak ended with a scheduled mid-term break. This underscores the need for more evidence on the effect of school closure in influenza outbreak control.
The regulatory role of the RANKL/RANK/OPG signaling pathway in the mechanisms of tooth eruption in patients with impacted teeth
Authors: Brodetska Ludmila , Natrus Larysa , Lisakovska Olha , Kaniura Olexandr , Iakovenko Liudmyla , Skrypnyk Irina , Flis Petro 
Published: September 2020

Abstract
Background
Tooth impaction is a common problem in orthodontic practice and in some cases accompanied by pain and pathological changes of surrounding teeth. Understanding the cellular and molecular mechanisms underlying tooth impaction allows finding the most effective orthodontic treatment for patients with impacted teeth (IT). RANK (receptor activator of NF-κB) / RANKL (RANK ligand) / OPG (osteoprotegerin) signaling pathway controls bone resorption and may be involved in the regulation of tooth eruption. The study aimed to evaluate bone remodeling based on the assessment of the RANKL/RANK/OPG status in patients with IT.

Methods
Bone samples from 18 patients (mean age 25.27 ± 3.34) were divided into 3 groups: 1 – bone tissue of healthy persons (control group); 2 – bone tissue, that was taken near the healthy tooth in patients with tooth impaction; 3 – bone tissue, that was collected near the IT. Levels of RANKL, RANK, OPG, osteocalcin (OC), NF-κB p65 subunit, NFATc1, and caspase-3 were determined by western blotting. The difference between groups was assessed using ANOVA followed by Tukey’s post-hoc test. P-value ≤0.05 was considered statistically significant.

Results
We established a 1.73-fold elevation of RANK level in the IT area vs. control, indicating the recruitment of preosteoclasts. An increase in RANKL, OPG, and OC content was demonstrated (1.46-, 1.48-, and 1.42-fold respectively), reflecting the high activity of osteoblasts near the IT. Despite the activation of the RANKL/RANK/OPG system in the impaction area, NF-κB and NFATc1 levels did not change compared vs. control, indicating a blocked/delayed process of osteoclastogenesis. We found a decrease in the content of procaspase-3 (1.28-fold), while the level of its active form p17 increased by 2.26 folds near the healthy tooth in patients with IT compared with control. In the area of ​​IT, we observed an increase in procaspase-3 and p17 levels (1.32 and 1.78 folds). This reflects impairments of caspase-3 activation and accumulation of its inactive form in the IT area that may contribute to the tooth eruption failure.

Conclusions
Tooth impaction may be associated with the disturbances in the caspase-3 cascade activation and the imbalance in the RANKL/RANK/OPG system, and as a result, blocked bone resorption.
Fermented mulberry (Morus alba) leaves suppress high fat diet-induced hepatic steatosis through amelioration of the inflammatory response and autophagy pathway
Authors: Lee Mi Rim , Kim Ji Eun , Park Ji Won , Kang Mi Ju , Choi Hyeon Jun , Bae Su Ji , Choi Young Whan , Kim Kyung Mi , Hong Jin Tae , Hwang Dae Youn 
Published: September 2020

Abstract
Background
A novel extract of mulberry leaves fermented with Cordyceps militaris (EMfC) is reported to exert anti-obesity activity, although their molecular mechanism during hepatic steatosis has not verified.

Methods
To investigate the role of inflammation and autophagy during the anti-hepatic steatosis effects of EMfC, we measured alterations in the key parameters for inflammatory response and autophagy pathway in liver tissues of the high fat diet (HFD) treated C57BL/6N mice after exposure to EMfC for 12 weeks.

Results
Significant anti-hepatic steatosis effects, including decreased number of lipid droplets and expression of Klf2 mRNA, were detected in the liver of the HFD + EMfC treated group. The levels of mast cell infiltration, expression of two inflammatory mediators (iNOS and COX-2), and the MAPK signaling pathway were remarkably decreased in the liver of HFD + EMfC treated group as compared to the HFD + Vehicle treated group. Furthermore, a similar inhibitory effect was measured for the expression levels of pro-inflammatory cytokines, including IL-1β, IL-6, TNF-α and NF-κB. The expression level of members in the AKT/mTOR signaling pathway (a central regulator in autophagy) was recovered after treatment with EMfC, and autophagy-related proteins (Beclin and LC3-II) were remarkably decreased in the HFD + EMfC treated group compared to the HFD + Vehicle treated group. Moreover, the HFD + EMfC treated group showed decreased transcript levels of autophagy-regulated genes including Atg4b, Atg5, Atg7 and Atg12.

Conclusions
Taken together, findings of the present study provide novel evidences that the anti-hepatic steatosis of EMfC is tightly linked to the regulation of the inflammatory response and autophagy pathway in the liver tissue of HFD-induced obesity mice.
A network pharmacology study on analgesic mechanism of Yuanhu-Baizhi herb pair
Authors: Mi Bobin , Li Qiushi , Li Tong , Marshall Jessica , Sai Jiayang 
Published: September 2020

Abstract
Background
Millions of people are suffering from chronic pain conditions, such as headache, arthritis, cancer. Apart from western medicines, traditional Chinese medicines are also well accepted for pain management, especially in Asian countries. Yuanhu-Baizhi herb pair (YB) is a typical herb pair applied to the treatment of stomach pain, hypochondriac pain, headache, and dysmenorrhea, due to its effects on analgesia and sedation. This study is to identify potentially active compounds and the underlying mechanisms of YB in the treatment of pain.

Methods
Compounds in YB were collected from 3 online databases and then screened by bioavailability and drug likeness parameters. Swiss target prediction was applied to obtain targets information of the active compounds. Pain-related genes were conducted for Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Protein-protein interaction (PPI) networks of the genes were constructed using Cytoscape software. In addition, the hub genes were screened using maximal clique centrality (MCC) algorithm.

Results
In total, 31 compounds from Yuanhu were screened out with 35 putative target genes, while 26 compounds in Baizhi with 43 target genes were discovered. Hence, 78 potential target genes of YB were selected for further study. After overlap analysis of the 78 genes of YB and 2408 pain-associated genes, we finally achieved 34 YB-pain target genes, as well as 10 hub genes and 23 core compounds. Go enrichment and KEGG pathway analysis indicated that YB had a strong integration with neuro system, which might significantly contribute to antinociceptive effect.

Conclusion
Our data provide deep understanding of the pharmacological mechanisms of YB in attenuating pain. The discovery shed new light on the development of active compounds of YB for the treatment of pain.
Learning outcomes of a flipped classroom teaching approach in an adult-health nursing course: a quasi-experimental study
Authors: Fan Jun-Yu , Tseng Ying-Jung , Chao Li-Fen , Chen Shiah-Lian , Jane Sui-Whi 
Published: September 2020

Abstract
Background
New teaching strategies must be developed not only to enhance nurse’s competence but also to allow nurses to respond to the complex health care needs of today’s society. The purpose of this study was to explore the learning outcomes of a flipped classroom teaching approach in an adult-health nursing course for students in a two-year Bachelor of Science in Nursing program.

Methods
The study had a quasi-experimental design. An 18-week flipped classroom teaching approach was applied in an adult-health nursing course. In total, 485 nursing students enrolled in the study, with 287 in the experimental group and 198 in the control group. The Self-Evaluated Core Competencies Scale, Metacognitive Inventory for Nursing Students, Self-Directed Learning Readiness Scale, and self-designed learning satisfaction questionnaire were used to evaluate the students’ learning outcomes.

Results
The experimental group showed a statistically significant increase in the overall scores for self-evaluated core competencies, the “self-modification” subscale of the Metacognitive Inventory for Nursing Students, and in overall self-directed learning readiness; further, they also showed high levels of course satisfaction.

Conclusions
A flipped classroom teaching approach had a positive impact on student’s learning motivation and contributed to better learning outcomes in an adult-health nursing course. The flipped classroom combined with hybrid teaching methods is a suitable and effective learning strategy for a registered nurse (RN) to Bachelor of Science in Nursing (BSN) program to tackle today’s complex revolution in nursing curricula, and may enhance nursing students’ abilities to address numerous challenges.
A practical approach to the ethical use of memory modulating technologies
Authors: Tan Shawn Zheng Kai , Lim Lee Wei 
Published: September 2020

Abstract
Background
Recent advancements in neuroscientific techniques have allowed us to make huge progress in our understanding of memories, and in turn has paved the way for new memory modification technologies (MMTs) that can modulate memories with a degree of precision, which was not previously possible. With advancements in such techniques, new and critical ethical questions have emerged. Understanding and framing these ethical questions within the current philosophical theories is crucial in order to systematically examine them as we translate these techniques to the clinic.

Main body
In this paper, we discuss the ethical implications of modern neuroscience techniques that aim to disrupt or enhance memories. We attempt to frame the MMTs in the context of existing ethical philosophical theories to provide a cohesive analysis of the myriad of ethical quagmires that might emerge from such technologies. We argue the application of Aristotle’s Golden Mean and multiple accounts of authenticity are useful in approaching the ethical questions surrounding MMTs. We then propose a framework in which ethical considerations can be systematically examined. Lastly, we provide caveats and considerations for the use of this framework. Overall, we provide a practical approach for the ethical use of MMTs depending on the situation.

Conclusion
While at face value, our model appears to put severe limitations on the application of MMTs, we are not completely opposed to their use, but rather our framework guides the agent to consider the implications before making any decisions. Most importantly, we argue that the use of MMTs does not reduce the responsibility of the initial decision, and the agent must accept the post-MMT self as the new “true self” regardless of the outcome. As the developmental trajectory of MMTs suggests we are getting closer to practical clinical applications, ethical concerns across a wide range of disciplines need to be addressed to develop best strategies and policies when dealing with MMTs. If this can be achieved, we believe the ethical use of MMTs is not only possible but would also be of tremendous benefit to many people suffering from memory-related mental disorders.
Radiation recall pneumonitis induced by PD-1/PD-L1 blockades: mechanisms and therapeutic implications
Authors: Teng Feifei , Li Min , Yu Jinming 
Published: September 2020

Abstract
Background
The synergistic effect of radiotherapy (RT) in combination with immunotherapy has been shown in several clinical trials and case reports. The overlapping pulmonary toxicity induced by thoracic RT and programmed death 1/programmed death ligand-1 (PD-1/PD-L1) blockades is an important issue of clinical investigation in combination treatment. Thus far, the underlying mechanism of this toxicity remains largely unknown.

Main text
In this review, we discuss the unique pattern of radiation recall pneumonitis (RRP) induced by PD-1 blockade. The clinical presentation is different from common radiation pneumonitis (RP) or RRP induced by cytotoxic drugs. The immune checkpoint inhibitors may evoke an inflammatory reaction in patients’ previously irradiated fields, with infiltrating lymphocytes and potential involvement of related cytokines. All RRP patients have showed durable response to anti-PD-1/PD-L1. RRP is manageable; however, interruption of checkpoint blockades is necessary and immunosuppressive treatment should be started immediately. Further analyses of the predictive factors, including RT dosimetric parameters, tumor-infiltrating lymphocytes (TILs), and PD-L1 expression, are needed given the wide use of immune checkpoint inhibitors and high mortality from lung toxicity with the combination treatment.

Conclusion
Immune checkpoint inhibitors may evoke an RRP in the patients’ previously irradiated fields. Interactions between immune checkpoint inhibitors and radiotherapy should be studied further.
Mutation profiling in eight cases of vagal paragangliomas
Authors: Kudryavtseva Anna V. , Kalinin Dmitry V. , Pavlov Vladislav S. , Savvateeva Maria V. , Fedorova Maria S. , Pudova Elena A. , Kobelyatskaya Anastasiya A. , Golovyuk Alexander L. , Guvatova Zulfiya G. , Razmakhaev George S. , Demidova Tatiana B. , Simanovsky Sergey A. , Slavnova Elena N. , Poloznikov Andrey А. , Polyakov Andrey P. , Melnikova Nataliya V. , Dmitriev Alexey A. , Krasnov George S. , Snezhkina Anastasiya V. 
Published: September 2020

Abstract
Background
Vagal paragangliomas (VPGLs) belong to a group of rare head and neck neuroendocrine tumors. VPGLs arise from the vagus nerve and are less common than carotid paragangliomas. Both diagnostics and therapy of the tumors raise significant challenges. Besides, the genetic and molecular mechanisms behind VPGL pathogenesis are poorly understood.

Methods
The collection of VPGLs obtained from 8 patients of Russian population was used in the study. Exome library preparation and high-throughput sequencing of VPGLs were performed using an Illumina technology.

Results
Based on exome analysis, we identified pathogenic/likely pathogenic variants of the SDHx genes, frequently mutated in paragangliomas/pheochromocytomas. SDHB variants were found in three patients, whereas SDHD was mutated in two cases. Moreover, likely pathogenic missense variants were also detected in SDHAF3 and SDHAF4 genes encoding for assembly factors for the succinate dehydrogenase (SDH) complex. In a patient, we found a novel variant of the IDH2 gene that was predicted as pathogenic by a series of algorithms used (such as SIFT, PolyPhen2, FATHMM, MutationTaster, and LRT). Additionally, pathogenic/likely pathogenic variants were determined for several genes, including novel genes and some genes previously reported as associated with different types of tumors.

Conclusions
Results indicate a high heterogeneity among VPGLs, however, it seems that driver events in most cases are associated with mutations in the SDHx genes and SDH assembly factor-coding genes that lead to disruptions in the SDH complex.