bluuebunny/crossref_metadata_2025 huggingface dataset:
COMPARISON OF 4 YEAR AND 5 YEAR PHARMACY DEGREE EDUCATION IN TURKEY
Authors: YILDIZ Büşra , ÇALIKUŞU Muammer , ÖZÇELİKAY Gülbin
Published: September 2022

Objective: In this study, by comparing the views of pharmacists who graduated from 4-year pharmacy degree and 5-year pharmacy degree is discussed whether the 5-year pharmacy degree education achieves its purpose. Material and Method: A mixed method was used in the research. In the quantitative research, 160 pharmacists graduated from different Pharmacy Faculties participated in the questions asked by the questionnaire technique. In the qualitative research, focus group discussions were held with 24 pharmacists in 3 separate sessions Result and Discussion: As a result, it has been shown that nanocrystals can perform similar imaging by using less radiocontrast materials with their unique properties. In this way, it is likely to cause fewer side effects and/or toxic effects due to the lower dosage. In the light of these successful results, it is planned to detail this study with clinical trials in the future. As a result of the research, although statistically positive changes were observed in 5-year education compared to 4-year education, it was seen that there are still areas that need improvement. Such as patient-oriented education has increased, but not enough. In addition to classical teaching methods, it was determined that it would be appropriate to use more catchy and problem-based methods, the importance of continuing internship practices and supervision, and finally, career management was better done in 5-year education. It is recommended to complete the identified deficiencies and increase the research.
Prediksi Penggunaan Listrik Rumah Tangga Menggunakan Metode Decision Tree C4.5 dan CART
Authors: Daamastuti Natalia
Published: September 2022

Saat ini listrik sudah menjadi kebutuhan primer yang tidak bisa lepas dari kegiatan masyarakat sehari-hari. Pada masa pandemi Covid-19 energi listrik sangat diperlukan masyarakat untuk melakukan aktivitas kerja hingga belajar yang banyak dilakukan di rumah. PT. PLN Warujayeng merupakan salah satu cabang PT. PLN yang mengelola sekitar 98.000 pelanggan. Namun dalam penyediaan energi listrik banyak ditemukan pemakaian energi listrik yang melebihi batas dan ketentuan sehingga mengakibatkan listrik otomatis mati. Maka dari itu diperlukannya klasifikasi kebutuhan daya listrik agar dapat menggambarkan kondisi daya yang dibutuhkan pelanggan. pada penelitian ini dilakukan analisis data penggunaan listrik rumah tangga menggunakan algoritma C4.5 dan CART, dimana keduanya merupakan kelompok dari Metode Decision Tree. Pengujian dilakukan menggunakan 500 data pelanggan yang diolah dengan Rapidmaner. Pengujian dilakukan dengan menggunakan split validation dan menghitung keakuratan algoritma dengan Confusion Matrix. Algoritma C4.5 memiliki tingkat akurasi, error rate, recall, dan precision sebesar 99.09%, 0.91%, 99.33% dan 93.33% dan CART sebesar 87.27%, 12.73%, 67.67%, dan 76.62%.
Content Validity of KIP-K Scholarship Instruments at Higher Education Using Aiken's Coefficient Validity Scale
Authors: Sabaruddin Sabaruddin , Nur Muhammad , Fadli M. , Mazlan Mazlan
Published: September 2022

This study aims to analyze the KIP-K Scholarship instrument at PTKIN IAIN Langsa while developing non-test instruments (questionnaires). This instrument is used to obtain information about students who apply for KIP-K scholarships. The instrument of content validity is obtained through a quantitative analysis by nine selected experts and a qualitative approach with an expert review of a set of questionnaires that have been arranged. In determining the content validity and reliability level, the experts analyzed a questionnaire quantitatively consisting of 29 items with three components: economic, household, and academic and non-academic students’ achievements. The data from this expert judgment is calculated using the formula Aiken V. While expert reviews are qualitatively similar to suggestions and feedback, they are used to refine constructed items. The result of these students’ economic condition, household, and academic and non-academic achievements was above 0.72 with a significance level of 5%, namely 0.92, 0.96, and 0.96. All of the 29 items are very valid (V > 0.72, V1 > 0.50) and reliable (α = 0,944). The conclusion that each component is closely related indicates information on the feasibility of distributing KIP-K. The instruments embodied at IAIN Langsa have high validity, and the level of reliability is excellent. This instrument can obtain complete information on prospective students who will become KIP-K scholarship recipients in 2022.
Financial Performance on Improving The Quality of Human Resources in Higher Education
Authors: Syarifuddin Syarifuddin
Published: September 2022

This study aims to analyze and understand financial performance in improving the quality of human resources in high school lecturers. This study uses a qualitative data collection case study type. The data collection technique is done through interviews, observation, and documentation. Meanwhile, the data analysis was carried out circularly, starting with data collection and reduction and concluding. The results showed that financial performance to improve the quality of human resources through the balanced scorecard approach at the University of Muhammadiyah Berau was effective. This is because the university's Balanced scorecard can identify strengths and opportunities for improvement related to leadership, vision, values, and strategy, focusing on finance, customers, internal processes, human resources, and performance excellence.
The Influence of Visionary Leadership and Managerial Accountability towards Competitive Advantage
Authors: Wijayanti Titik , Hidayatullah Hidayatullah , Prasetiya Benny
Published: September 2022

This research is essential to measure the effectiveness of the factors that determine the competitive advantage of educational institutions. This study aims to determine the effect of visionary leadership and accountability toward competitive advantage at an educational institution. The research method used a survey; meanwhile, multiple regression tests were used to examine research hypotheses. The research samples were as many as 42 employees consisting of teachers and staff. The results of this research conclude that there is a significant influence between the visionary leadership of the headmaster and the ability to conduct accountability to competitive advantage. The coefficient score of determination shows that 88, 7 % of competitive advantage is determined by the pattern of visionary leadership and accountability. The competitive advantage of an educational institution is influenced by the principal's visioner, leadership, and accountability. The implication of this study is finding the concept that competitive advantage is influenced by visionary leadership and accountability.
Leading Change at The Faculty of Education in Light of Kotter's Change Model
Authors: Onia Saifaldin Idris
Published: September 2022

The purpose of this study was to examine Kotter's leading change model at the Faculty of Education University of Khartoum with a major purpose of evaluating the contribution of this theory to enhance the importance and understanding of leading change at the University context. In doing so, a survey research design was employed. Among 239 staff members at the Faculty of Education University of Khartoum, data were collected from 106 (44.00%) respondents using questionnaire. Data collected were analyzed using one sample t-test. The result showed that creating a climate for change has been practised in the Faculty of Education University of Khartoum. The Faculty of Education University of Khartoum has engaged and enabled the whole organization in the change process. The findings also indicated that the Faculty of Education University of Khartoum has implemented and sustained change process. Hence, the implication of these findings adds to the understanding of how college officials ought to play a role model in embedding the change in their behaviors.
Madrasah-Based Management: Quality Improvement Strategies in Madrasah
Authors: Susanto Susanto
Published: September 2022

This study explores quality improvement strategies in Madrasahs in the Ponorogo district during the Covid-19 situation. This research is quantitative research with a descriptive method. The population in this study were educators and education staff in Madrasah, Ponorogo Regency, amounting to 15 madrasah. The research analysis was done descriptively. This study found that the madrasa-based quality improvement strategy developed in Ponorogo Regency during the Covid-19 pandemic; First, the planning aspect, namely curriculum adjustments, online-based learning services, administrative services, and adjustments to the rules according to the Covid-19 situation policy. Second is the development of intelligent system innovation. Third, ensure that educators and education personnel carry out their duties according to health protocols and increase capacity according to learning needs in the Covid-19 situation; Fourth, aspects of parental support, provision of parental consultation rooms, and essential skills. The implications of the research findings can be a positive inspiration for improving the quality of madrasah in the Covid-19 pandemic.
English learner corpora and research in Korea
Authors: Kwon Heokseung
Published: September 2022

The interest in the exploitation of corpora in the study of Korean L2 learners’ use of English has risen dramatically over the past two decades, leading to the compilation of learner corpora and to numerous empirical investigations into Korean learners’ use of English. This paper will give an overview of the compilation and characteristics of English learner corpora in Korea and will also provide an analysis of the recent trends in learner corpus research. It was not until the mid-2000s that Korean academics started to compile English learner corpora, such as the snu Korean-speaking English Learner Corpus (skelc), the Yonsei English Learner Corpus (yelc), the Gachon Learner Corpus (glc), the Neungyule Interlanguage Corpus of Korean Learners of English (nickle), the efl Teacher Corpus (etc), the Korean English Learners’ Spoken Corpus (kelsc) and the ets Corpus of Non-native Written English (TOEFL11). There have also been a growing number of learner corpus-based studies that used the existing learner corpora as well as self-compiled corpus data. All the learner corpus-based research articles published in two Korean academic journals ( English Teaching and Korean Journal of Applied Linguistics) will be reviewed and analysed in terms of research topics and areas, data types, analysis methods and corpus compilation practices. Finally, this paper will suggest some future directions for learner corpus compilation and research in Korea.
‘I Became Much Wiser over Time’: Readers’ Use of Innocence and Wisdom as Age Norms in Responses to Children’s Literature
Authors: Duthoy Leander
Published: September 2022

Age norms are the social norms that, within a specific socio-cultural environment, operate as the expectations about the appearance and behaviour of members of various age groups (Radl 758). In addition, age is ‘relational’ (Pickard 203), meaning that age groups are defined in relation to other age groups. In that context, children are often described as ‘innocent and inexperienced’ (Nodelman 157) and adults as wise (Woodward 187). However, scholars have also criticised childhood innocence and adult wisdom as problematic generalisations (Kitzinger 79; Woodward 206).

In this article I discuss how child and adult readers of children’s literature use innocence and wisdom as age norms to reflect both on their own age and the age of characters. Data was gathered through fifty-seven one-on-one interviews and four focus-group conversations with readers aged nine to seventy-five, based on two Dutch language children’s books: Iep! (1996), written by Joke van Leeuwen, and Voor altijd samen, amen (1999), written by Guus Kuijer.

Young readers demonstrated an awareness of adult discourse surrounding child innocence, which some adopted without criticism, while others admitted to ‘performing’ innocence to escape adult ire. Furthermore, these same young readers also used innocence to ‘age’ young characters. For late adolescent and early adult readers, both young and old characters were sometimes deemed innocent. In contrast, older readers emphasised their own wisdom and reflected on the age of characters through that lens. Wisdom therefore emerged as a key age norm older readers used not only to praise older characters, but also to give positive meaning to their own experience of older adulthood. Notably, some characters that were perceived as especially wise by older readers were thought of as naïve and innocent by younger readers. Thus, the complexity of the readers’ responses challenged straightforward age-bound generalisations of wisdom and innocence.
Living Film Histories: Researching at the Bill Douglas Cinema Museum
Authors: Wickham Phil , Hanson Helen
Published: September 2022

The Bill Douglas Cinema Museum at the University of Exeter is both a public museum and a research and teaching resource originally based on the collection put together by film-maker Bill Douglas and his friend Peter Jewell. Augmented constantly with new donations, it now holds over 85,000 items. In this article we will demonstrate how the range and depth of the museum’s collections on moving image history create a ‘people’s history’ of the medium. Despite the variety of the holdings, the museum has a coherence for researchers, allowing scholars to evidence continuities as well as changes across the history which it charts. We will show how this works in three distinct ways. Firstly we will consider how research on the everyday ephemera of cinema, and the optical media that preceded it, which forms much of the collection, such as programmes, publicity material or merchandise, can illuminate our understanding of film history as it is lived: what Raymond Williams saw as ‘the structures of feeling’ underpinning popular culture.

Second, we will draw on examples from the stipend scheme that we operate, whereby awards enable researchers from around the world to explore our holdings in order to discover new paths through this history. How has material found within collections complicated research questions or allowed scholars to make connections between the past and the present? Lastly, we will explore how artefacts gain meanings from the processes of their curation. Here we will analyse the curatorial practices of students at the University of Exeter.
‘The Man Will Shame Me’: Women, Sex and Kirk Discipline during the Cromwellian Occupation
Authors: Brock Michelle D.
Published: September 2022

This article explores the experiences of Scottish women and their interactions with the Kirk during the Cromwellian occupation. Drawing on kirk session records, it demonstrates that amid the heightened anxieties of the 1650s, parish kirks viewed and treated female bodies as potential sources of social and religious disorder. This analysis reveals the strength of the Kirk’s regulatory toolkit in times of crisis as well as the continuity of gendered experiences of discipline. It also offers new insights into civilian experiences of the Cromwellian invasion.
Optimal design and biomechanical analysis of sandwich composite metal locking screws for far cortical locking constructs
Authors: Deng Yuping , Zhao Dongliang , Yang Yang , Ouyang Hanbin , Xu Chujiang , Xiong Liang , Li Yanbin , Tan Wenchang , Huang Gang , Huang Wenhua
Published: September 2022

In the interests of more flexible and less stiff bridge constructs to stimulate bone healing, the technique of far cortical locking has been designed to improve locked plating constructs in terms of stress concentration, stress shielding, and inhibition of issues around fracture healing. However, far cortical locking screws currently lack objective designs and anti-fatigue designs. This study investigates an optimization algorithm to form a special locking screw composed of various metals, which can theoretically achieve the maintenance of the excellent mechanical properties of far cortical locking constructs in terms of fracture internal fixation, while maintaining the biomechanical safety and fatigue resistance of the structure. The numerical results of our study indicate that the maximum von Mises stress of the optimized construct is less than the allowable stress of the material under each working condition while still achieving sufficient parallel interfragmentary motion. Numerical analysis of high cycle fatigue indicates that the optimized construct increases the safety factor to five. A high cycle fatigue test and defect analysis indicates that the sandwich locking constructs have better fatigue resistance. We conclude that the sandwich locking construct theoretically maintains its biomechanical safety and fatigue resistance while also maintaining excellent mechanical properties for fracture internal fixation.
A machine learning regression approach for predicting the bearing capacity of a strip footing on rock mass under inclined and eccentric load
Authors: Lai Van Qui , Sangjinda Kongtawan , Keawsawasvong Suraparb , Eskandarinejad Alireza , Chauhan Vinay Bhushan , Sae-Long Worathep , Limkatanyu Suchart
Published: September 2022

In this study, the Multivariate Adaptive Regression Splines (MARS) model is employed to create a data-driven prediction for the bearing capacity of a strip footing on rock mass subjected to an inclined and eccentric load. The strengths of rock masses are based on the Hoek-Brown failure criterion. To develop the set of training data in MARS, the lower and upper bound finite element limit analysis (FELA) is carried out to obtain the numerical results of the bearing capacity of a strip footing with the width of B. There are six considered dimensionless variables, including the geological strength index (GSI), the rock constant/yield parameter (mi), the dimensionless strength (γB/σci), the adhesion factor (α), load inclined angle from the vertical axis (β), and the eccentricity of load (e/B). A total of 5,120 FELA solutions of the bearing capacity factor (P/σciB) are obtained and used as a training data set. The influences of all dimensionless variables on the bearing capacity factors and the failure mechanisms are investigated and discussed in detail. The sensitivity analysis of these dimensionless variables is also examined.
Ligands modification strategies for mononuclear water splitting catalysts
Authors: Wang Lei , Wang Lijuan
Published: September 2022

Artificial photosynthesis (AP) has been proved to be a promising way of alleviating global climate change and energy crisis. Among various materials for AP, molecular complexes play an important role due to their favorable efficiency, stability, and activity. As a result of its importance, the topic has been extensively reviewed, however, most of them paid attention to the designs and preparations of complexes and their water splitting mechanisms. In fact, ligands design and preparation also play an important role in metal complexes’ properties and catalysis performance. In this review, we focus on the ligands that are suitable for designing mononuclear catalysts for water splitting, providing a coherent discussion at the strategic level because of the availability of various activity studies for the selected complexes. Two main designing strategies for ligands in molecular catalysts, substituents modification and backbone construction, are discussed in detail in terms of their potentials for water splitting catalysts.
Real-time multiple cross displacement amplification assay for rapid and sensitive detection of Haemophilus influenzae
Authors: Sun Chunrong , Jia Nan , Huang Xiaolan , Xiao Fei , Zhou Juan , Zhang Yu , Fu Jin , Xu Zheng , Qu Dong , Cui Xiaodai , Wang Yi
Published: September 2022

Haemophilus influenzae is an opportunistic pathogen usually causing bacteremia, meningitis, and pneumonia in children. Here, we developed a method based on multiple cross displacement amplification (MCDA) method and real-tme fluorescence technique for rapid detection of H. influenzae. A set of 10 primers was designed for the H. influenzae real-time MCDA reaction, and a core primer was modified with a restriction endonuclease recognition sequence, a fluorescent, and a quencher according to the principle of the real-time MCDA assay. The H. influenzae real-time MCDA reactions were performed using a fluorescence instrument at 63°C for 40 min. The H. influenzae real-time MCDA assay can specifically detect H. influenzae without any cross-reaction with other bacteria as our results confirmed. The sensitivity of our assay is as low as 10 CFU per reaction. To validate its feasibility, our assay was applied to 40 DNA extracted from sputum samples. The results obtained from H. influenzae real-time MCDA were compared with that of H. influenzae–loop-mediated isothermal amplification (H. influenzae-LAMP) and MCDA-based lateral flow biosensor (MCDA-LFB). The positive rate of the real-time MCDA assay was 62.5%, which was consistent with the H. influenzae-MCDA-LFB assay, but was more sensitive than H. influenzae-LAMP (57.5%). Furthermore, the H. influenzae real-time MCDA assay takes only 40 min, which was less than that of a traditional PCR test. Taken together, the H. influenzae real-time MCDA assay reported here offers a new and valuable diagnostic tool for the reliable and rapid detection of H. influenzae.
Development of new bioactive molecules to treat breast and lung cancer with natural myricetin and its derivatives: A computational and SAR approach
Authors: Akash Shopnil , Kumer Ajoy , Rahman Md. Mominur , Emran Talha Bin , Sharma Rohit , Singla Rajeev K. , Alhumaydhi Fahad A. , Khandaker Mayeen Uddin , Park Moon Nyeo , Idris Abubakr M. , Wilairatana Polrat , Kim Bonglee
Published: September 2022

Each biopharmaceutical research and new drug development investigation is targeted at discovering novel and potent medications for managing specific ailments. Thus, to discover and develop new potent medications, it should be performed sequentially or step by step. This is because drug development is a lengthy and risky work that requires significant money, resources, and labor. Breast and lung cancer contributes to the death of millions of people throughout the world each year, according to the report of the World Health Organization, and has been a public threat worldwide, although the global medical sector is developed and updated day by day. However, no proper treatment has been found until now. Therefore, this research has been conducted to find a new bioactive molecule to treat breast and lung cancer—such as natural myricetin and its derivatives—by using the latest and most authentic computer-aided drug-design approaches. At the beginning of this study, the biological pass prediction spectrum was calculated to select the target protein. It is noted that the probability of active (Pa) score is better in the antineoplastic (Pa: 0.788–0.938) in comparison with antiviral (Pa: 0.236–0.343), antibacterial (Pa: 0.274–0.421), and antifungal (Pa: 0.226–0.508). Thus, cancerous proteins, such as in breast and lung cancer, were picked up, and the computational investigation was continued. Furthermore, the docking score was found to be -7.3 to -10.4 kcal/mol for breast cancer (standard epirubicin hydrochloride, -8.3 kcal/mol), whereas for lung cancer, the score was -8.2 to -9.6 kcal/mol (standard carboplatin, -5.5 kcal/mol). The docking score is the primary concern, revealing that myricetin derivatives have better docking scores than standard chemotherapeutic agents epirubicin hydrochloride and carboplatin. Finally, drug-likeness, ADME, and toxicity prediction were fulfilled in this investigation, and it is noted that all the derivatives were highly soluble in a water medium, whereas they were totally free from AMES toxicity, hepatotoxicity, and skin sensitization, excluding only ligands 1 and 7. Thus, we proposed that the natural myricetin derivatives could be a better inhibitor for treating breast and lung cancer.
Testosterone induces sexual dimorphism during infection with Plasmodium berghei ANKA
Authors: Aguilar-Castro Jesús , Cervantes-Candelas Luis Antonio , Buendía-González Fidel Orlando , Fernández-Rivera Omar , Nolasco-Pérez Teresita de Jesús , López-Padilla Monserrat Sofía , Chavira-Ramírez David Roberto , Cervantes-Sandoval Armando , Legorreta-Herrera Martha
Published: September 2022

Malaria is the most lethal parasitic disease worldwide; men exhibit higher mortality and more severe symptomatology than women; however, in most studies of immune response in malaria, sex is not considered a variable. Sex hormones 17β-oestradiol and testosterone are responsible for the main physiological differences between sexes. When interacting with their receptors on different immune cells, they modify the expression of genes that modulate cell proliferation, differentiation, and synthesis of cytokines. The immunosuppressive activity of testosterone is well accepted; however, its participation in the sexual dimorphism of the immune response to malaria has not been studied. In this work, we analysed whether altering the concentration of testosterone, through increasing the concentration of this hormone for exogenous administration for three weeks, or gonadectomy before infection withPlasmodium bergheiANKA affects different cells of the immune response necessary for parasite clearance. We also assessed the concentration of pro-and anti-inflammatory cytokines in male and female CBA/Ca mice infected or not with the parasite. Our results show that testosterone changes affect females more than males, resulting in sex-associated patterns. Testosterone administration increased parasitaemia in intact males while reducing it in intact females leading to a dimorphic pattern. In addition, gonadectomy increased parasitaemia in both sexes. Moreover, testosterone administration prevented both weight loss caused by the infection in females and hypothermia in gonadectomized mice of both sexes. Boosting testosterone concentration increased CD3+and CD8+populations but decreased the B220+cells exclusively in females. Additionally, testosterone reduced IFN-γ concentration and increased IL-6 levels only in females, while in males, testosterone increased the number of NK cells. Finally, gonadectomy decreased TNF-α concentration in both sexes. Our results demonstrate that testosterone induces different patterns depending on sex and testosterone concentration. The results of this work contribute to understanding the impact of modifying testosterone concentration on the immune response specific againstPlasmodiumand the participation of this hormone in sexual dimorphism in malaria.
The emerging role of Deubiquitinases (DUBs) in parasites: A foresight review
Authors: Kumar Prakash , Kumar Pawan , Mandal Debabrata , Velayutham Ravichandiran
Published: September 2022

Before the discovery of the proteasome complex, the lysosomes with acidic proteases and caspases in apoptotic pathways were thought to be the only pathways for the degradation of damaged, unfolded, and aged proteins. However, the discovery of 26S and 20S proteasome complexes in eukaryotes and microbes, respectively, established that the degradation of most proteins is a highly regulated ATP-dependent pathway that is significantly conserved across each domain of life. The proteasome is part of the ubiquitin-proteasome system (UPS), where the covalent tagging of a small molecule called ubiquitin (Ub) on the proteins marks its proteasomal degradation. The type and chain length of ubiquitination further determine whether a protein is designated for further roles in multi-cellular processes like DNA repair, trafficking, signal transduction, etc., or whether it will be degraded by the proteasome to recycle the peptides and amino acids. Deubiquitination, on the contrary, is the removal of ubiquitin from its substrate molecule or the conversion of polyubiquitin chains into monoubiquitin as a precursor to ubiquitin. Therefore, deubiquitylating enzymes (DUBs) can maintain the dynamic state of cellular ubiquitination by releasing conjugated ubiquitin from proteins and controlling many cellular pathways that are essential for their survival. Many DUBs are well characterized in the human system with potential drug targets in different cancers. Although, proteasome complex and UPS of parasites, like plasmodium and leishmania, were recently coined as multi-stage drug targets the role of DUBs is completely unexplored even though structural domains and functions of many of these parasite DUBs are conserved having high similarity even with its eukaryotic counterpart. This review summarizes the identification & characterization of different parasite DUBs based on in silico and a few functional studies among different phylogenetic classes of parasites including Metazoan (Schistosoma, Trichinella), Apicomplexan protozoans (Plasmodium, Toxoplasma, Eimeria, Cryptosporidium), Kinetoplastidie (Leishmania, Trypanosoma) and Microsporidia (Nosema). The identification of different homologs of parasite DUBs with structurally similar domains with eukaryotes, and the role of these DUBs alone or in combination with the 20S proteosome complex in regulating the parasite survival/death is further elaborated. We propose that small molecules/inhibitors of human DUBs can be potential antiparasitic agents due to their significant structural conservation.
Cardiac MRI assessment of anthracycline-induced cardiotoxicity
Authors: Mabudian Leila , Jordan Jennifer H. , Bottinor Wendy , Hundley W. Gregory
Published: September 2022

The objective of this review article is to discuss how cardiovascular magnetic resonance (CMR) imaging measures left ventricular (LV) function, characterizes tissue, and identifies myocardial fibrosis in patients receiving anthracycline-based chemotherapy (Anth-bC). Specifically, CMR can measure LV ejection fraction (EF), volumes at end-diastole (LVEDV), and end-systole (LVESV), LV strain, and LV mass. Tissue characterization is accomplished through T1/T2-mapping, late gadolinium enhancement (LGE), and CMR perfusion imaging. Despite CMR’s accuracy and efficiency in collecting data about the myocardium, there are challenges that persist while monitoring a cardio-oncology patient undergoing Anth-bC, such as the presence of other cardiovascular risk factors and utility controversies. Furthermore, CMR can be a useful adjunct during cardiopulmonary exercise testing to pinpoint cardiovascular mediated exercise limitations, as well as to assess myocardial microcirculatory damage in patients undergoing Anth-bC.
A predictive patient-specific computational model of coronary artery bypass grafts for potential use by cardiac surgeons to guide selection of graft configurations
Authors: Chaudhuri Krish , Pletzer Alexander , Smith Nicolas P.
Published: September 2022

Cardiac surgeons face a significant degree of uncertainty when deciding upon coronary artery bypass graft configurations for patients with coronary artery disease. This leads to significant variation in preferred configuration between different surgeons for a particular patient. Additionally, for the majority of cases, there is no consensus regarding the optimal grafting strategy. This situation results in the tendency for individual surgeons to opt for a “one size fits all” approach and use the same grafting configuration for the majority of their patients neglecting the patient-specific nature of the diseased coronary circulation. Quantitative metrics to assess the adequacy of coronary bypass graft flows have recently been advocated for routine intraoperative use by cardiac surgeons. In this work, a novel patient-specific 1D-0D computational model called “COMCAB” is developed to provide the predictive haemodynamic parameters of functional graft performance that can aid surgeons to avoid configurations with grafts that have poor flow and thus poor patency. This model has significant potential for future expanded applications.
Outcomes and occurrence of post-operative pulmonary hypertension crisis after late referral truncus arteriosus repair
Authors: Zhu Yifan , Jiang Qi , Zhang Wen , Hu Renjie , Dong Wei , Zhang Hao , Zhang Haibo
Published: September 2022

Background

Truncus arteriosus (TA) is a rare congenital heart disease with a high rate of early mortality. The occurrence of post-operative pulmonary hypertension crisis (PHC), known to be a common and life-threatening complication, increases due to the irreversible development of pulmonary vascular resistance with age. We sought to figure out the risk factors for PHC and describe the surgical outcomes of TA patients with late referral (repair <1 month excluded).

Materials and methods

We retrospectively reviewed patients after TA repair between 2009 and 2021 at Shanghai Children’s Medical Center. The occurrence of PHC was defined according to post-operative Pp/Ps ≥ 1 and clinical manifestations. Risk factors for PHC and mortality were conducted by multivariable analysis.

Results

A total of 98 patients were treated, including 55 males and 43 females. The median age at repair was 121 (69, 245) days. Post-operative PHC occurred in 22 (22.4%) patients with a median age of 186 (122, 293) days. By multivariable analysis, patients with the sum of Z-score of pre-operative bilateral pulmonary artery (PA) diameters (OR: 1.6, 95% CI: 1.2–2.3, P = 0.01) was more likely to experience PHC. Longer CPB duration contributed to early death (OR: 1.0, 95% CI: 1.0–1.0, P = 0.01). Total survival at 10 years was 81.4%. In 4.5 (2.9, 7.5) years of follow-up, twenty-six patients received 30 reinterventions. Valved reconstruction of RVOT most predicted reinterventions (OR: 4.2, 95% CI: 1.4–13.0, P = 0.01).

Conclusion

Surgical repair of TA patients with late referral has resulted in comparatively favorable early and mid-term outcomes. PHC occurred more commonly in patients with overextended bilateral PA pre-operatively. Meanwhile, valved reconstruction of RVOT would more likely lead to early reintervention.
Study on improving the gas extraction efficiency by deep-hole pre-split blasting in Wulunshan Coal Mine, Guizhou
Authors: Yang Junwei , Zheng Xigui , Liu Chengwei , Zhai Wenjie , Liu Hongyang , Zhang Peng
Published: September 2022

Due to the low permeability of the coal seam and the low gas extraction rate in conventional boreholes in the Wulunshan Coal Mine in Guizhou, in this study, the deep-hole pre-split blasting method is applied to study the improvement of the gas extraction efficiency by increasing the permeability of the coal seam. The study comprehensively expounds the process in which the deep-hole pre-split blasting method is applied to improve the gas extraction efficiency and proposes a numerical simulation method that combines ANSYS/LS-DYNA and COMSOL Multiphysics. Using the method, the initiation of blasting fracture channels and the subsequent influence on the gas extraction range have been comprehensively and directly researched and analyzed. Finally, some theoretical research has been verified by field experiments. According to the recorded simulation of the Wulunshan Coal Mine, the exposed area of the blasting borehole was 42 times the size of the conventional drilling borehole, and the pressure relief space was 1,050 times that of the conventional drilling borehole, which can connect about 32 m3 of coal. Compared with conventional drilling boreholes, in the process of gas extraction, the control range of the controlled pressure reduction was 4–7 times, the range of gas pressure reaching the standard was 25 times, and the peak pressure was reduced by 3–5 times. The average gas concentration was 1.85 times that of conventional boreholes, and the cumulative gas extraction volume of blasting boreholes was 4.48 times that of conventional boreholes. The research results prove that the application of blasting and permeability enhancement in the coal seam with a high gas content and low permeability can effectively improve the gas extraction efficiency in the Wulunshan Coal Mine in Guizhou.
Somatostatin receptors in congenital hyperinsulinism: Biology to bedside
Authors: van Albada Mirjam E. , Mohnike Klaus , Dunne Mark J. , Banerjee Indi , Betz Stephen F.
Published: September 2022

Congenital hyperinsulinism (CHI), although a rare disease, is an important cause of severe hypoglycemia in early infancy and childhood, causing preventable morbidity and mortality. Prompt diagnosis and appropriate treatment is necessary to prevent hypoglycaemia mediated brain damage. At present, the medical treatment of CHI is limited to diazoxide as first line and synthetic somatostatin receptor ligands (SRLs) as second line options; therefore understanding somatostatin biology and treatment perspectives is important. Under healthy conditions, somatostatin secreted from pancreatic islet δ-cells reduces insulin release through somatostatin receptor induced cAMP-mediated downregulation and paracrine inhibition of β- cells. Several SRLs with extended duration of action are now commercially available and are being used off-label in CHI patients. Efficacy remains variable with the present generation of SRLs, with treatment effect often being compromised by loss of initial response and adverse effects such as bowel ischaemia and hepatobiliary dysfunction. In this review we have addressed the biology of the somatostatin system contexualised to CHI. We have discussed the clinical use, limitations, and complications of somatostatin agonists and new and emerging therapies for CHI.
Ontology modeling method applied in simulation modeling of distribution network time series operation
Authors: Luo Fengzhang , Feng Shaoting , Yang Yang , Ao Zhiqi , Li Xueling , Chai Yanxin
Published: September 2022

Aiming at the difficulties in the realization of timing simulation in the digital twin environment, this article proposes an ontology modeling method applied to the simulation modeling of distribution network timing series operation. First, the two-layer ontology modeling architecture is introduced, and the power system domain structure ontology and the business-based application ontology are constructed. Second, based on the dynamic ontology modeling method, combined with the operational simulation business requirements, the sequential operation simulation ontology model is dynamically constructed. Finally, the effects of the modeling method in terms of simulation expression and modeling efficiency are shown through practical application example, and the modeling methods are compared and analyzed. The results provide a reference for the technical realization of power grid modeling in digital twin environments.
In vivo and in vitro genome editing to explore GNE functions
Authors: Ilouz Nili , Harazi Avi , Guttman Miriam , Daya Alon , Ruppo Shmuel , Yakovlev Lena , Mitrani-Rosenbaum Stella
Published: September 2022

GNE myopathy is an adult onset neuromuscular disorder characterized by slowly progressive distal and proximal muscle weakness, caused by missense recessive mutations in the GNE gene. Although the encoded bifunctional enzyme is well known as the limiting factor in the biosynthesis of sialic acid, no clear mechanisms have been recognized to account for the muscle atrophic pathology, and novel functions for GNE have been hypothesized. Two major issues impair studies on this protein. First, the expression of the GNE protein is minimal in human and mice muscles and there is no reliable antibody to follow up endogenous expression. Second, no reliable animal model is available for the disease and cellular models from GNE myopathy patients’ muscle cells (expressing the mutated protein) are less informative than expected. In order to broaden our knowledge on GNE functions in muscle, we have taken advantage of the CRISPR/Cas9 method for genome editing to first, add a tag to the endogenous Gne gene in mouse, allowing the determination of the spatiotemporal expression of the protein in the organism, using well established and reliable antibodies against the specific tag. In addition we have generated a Gne knock out murine muscle cell lineage to identify the events resulting from the total lack of the protein. A thorough multi-omics analysis of both cellular systems including transcriptomics, proteomics, phosphoproteomics and ubiquitination, unraveled novel pathways for Gne, in particular its involvement in cell cycle control and in the DNA damage/repair pathways. The elucidation of fundamental mechanisms of Gne in normal muscle may contribute to the identification of the disrupted functions in GNE myopathy, thus, to the definition of novel biomarkers and possible therapeutic targets for this disease.
Case Report: Progressive central conducting lymphatic abnormalities in the RASopathies. Two case reports, including successful treatment by MEK inhibition
Authors: Gordon Kristiana , Moore Matthew , Van Zanten Malou , Pearce Julian , Itkin Maxim , Madden Brendan , Ratnam Lakshmi , Mortimer Peter S. , Nagaraja Rani , Mansour Sahar
Published: September 2022

The RASopathies are a group of genetic conditions resulting from mutations within the RAS/mitogen-activated protein kinase (RAS-MAPK) pathway. Lymphatic abnormalities are commonly associated with these conditions, however central conducting lymphatic abnormalities (CCLA) have only recently been described. CCLAs may be progressive and can result in devastating systemic sequelae, such as recurrent chylothoraces, chylopericardium and chylous ascites which can cause significant morbidity and even mortality. Improvements in imaging modalities of the central lymphatics have enhanced our understanding of these complex abnormalities. Management is challenging and have mainly consisted of diuretics and invasive mechanical drainages. We describe two adult males with Noonan syndrome with a severe and progressive CCLA. In one patient we report the therapeutic role of targeted molecular therapy with the MEK inhibitor ‘Trametinib’, which has resulted in dramatic, and sustained, clinical improvement. The successful use of MEK inhibition highlights the importance of understanding the molecular cause of lymphatic abnormalities and utilising targeted therapies to improve quality of life and potentially life expectancy.
The role of lncRNA H19 in tumorigenesis and drug resistance of human Cancers
Authors: Zhang Xun , Luo Mingpeng , Zhang Jiahang , Guo Bize , Singh Shreya , Lin Xixi , Xiong Hanchu , Ju Siwei , Wang Linbo , Zhou Yulu , Zhou Jichun
Published: September 2022

Systemic therapy is one of the most significant cancer treatments. However, drug resistance often appears and has become the primary cause of cancer therapy failure. Regulation of drug target, drug metabolism and drug efflux, cell death escape (apoptosis, autophagy, et al.), epigenetic changes, and many other variables are complicatedly involved in the mechanisms of drug resistance. In various types of cancers, long non-coding RNA H19 (lncRNA H19) has been shown to play critical roles in tumor development, proliferation, metastasis, and multiple drug resistance as well. The efficacy of chemotherapy, endocrine therapy, and targeted therapy are all influenced by the expression of H19, especially in breast cancer, liver cancer, lung cancer and colorectal cancer. Here, we summarize the relationship between lncRNA H19 and tumorigenesis, and illustrate the drug resistance mechanisms caused by lncRNA H19 as well. This review may provide more therapeutic potential targets for future cancer treatments.
Predicting miRNA-disease associations based on multi-view information fusion
Authors: Xie Xuping , Wang Yan , Sheng Nan , Zhang Shuangquan , Cao Yangkun , Fu Yuan
Published: September 2022

MicroRNAs (miRNAs) play an important role in various biological processes and their abnormal expression could lead to the occurrence of diseases. Exploring the potential relationships between miRNAs and diseases can contribute to the diagnosis and treatment of complex diseases. The increasing databases storing miRNA and disease information provide opportunities to develop computational methods for discovering unobserved disease-related miRNAs, but there are still some challenges in how to effectively learn and fuse information from multi-source data. In this study, we propose a multi-view information fusion based method for miRNA-disease association (MDA)prediction, named MVIFMDA. Firstly, multiple heterogeneous networks are constructed by combining the known MDAs and different similarities of miRNAs and diseases based on multi-source information. Secondly, the topology features of miRNAs and diseases are obtained by using the graph convolutional network to each heterogeneous network view, respectively. Moreover, we design the attention strategy at the topology representation level to adaptively fuse representations including different structural information. Meanwhile, we learn the attribute representations of miRNAs and diseases from their similarity attribute views with convolutional neural networks, respectively. Finally, the complicated associations between miRNAs and diseases are reconstructed by applying a bilinear decoder to the combined features, which combine topology and attribute representations. Experimental results on the public dataset demonstrate that our proposed model consistently outperforms baseline methods. The case studies further show the ability of the MVIFMDA model for inferring underlying associations between miRNAs and diseases.
Practical aspects of chimeric antigen receptor T-cell administration: From commercial to point-of-care manufacturing
Authors: Martinez-Cibrian Nuria , Español-Rego Marta , Pascal Mariona , Delgado Julio , Ortiz-Maldonado Valentín
Published: September 2022

Chimeric antigen receptor T-cells targeting the CD19 antigen have achieved impressive results in patients with relapsed/refractory (R/R) B-cell malignancies, leading to their approval in the European Union and other jurisdictions. In Spain, the 100% academic anti-CD19 CART-cell product varnimcabtagene autoleucel (var-cel, ARI-0001 cells) has been extraordinarily approved under the Hospital Exemption clause for the treatment of patients older than 25 years of age with R/R acute lymphoblastic leukaemia. Var-cel has also been granted PRIority MEdicines designation by the European Medicines Agency for the same indication. In this review we reveal some practical aspects related to the preparation and administration of academic point-of-care CART-cell products, using var-cel as an example, and put them into the context of commercial products.