bluuebunny/crossref_metadata_2025 huggingface dataset:
HOW TO MAKE LEARNING IN STEM MEANIGFUL FOR THE MILLENNIUM GENERATION
Authors:   University of Latvia, Latvia, Cedere Dagnija , Birzina Rita ,   University of Latvia, Latvia, Pigozne Tamara ,   University of Latvia, Latvia, Vasilevskaya Elena ,   Belarusian State University, Republic of Belarus
Published: September 2021

The education of today more and more encounters the teaching and learning problems of young adults therefore it is topical to find out how to make the teaching/learning of the Millennium generation meaningful. This issue is especially important in STEM education. The survey involved Grade 10-12 students of Latvia, in total 256 students. Spearman’s correlations and Kruskal-Wallis test were used in the data analysis. The obtained results showed that students- millennials as regards the learning of STEM subjects can be described as real-life oriented, digitally educated who want to participate actively in the teaching/learning process and who want to receive the feedback. Keywords: meaningful learning, Millennium generation, teaching and learning principles, STEM learning.
MEASURING KNOWLEDGE GROWTH FOR INDIVIDUAL BACHELOR STUDENTS AT SCIENCE COURSES OF UNIVERSITY OF LATVIA
Authors:   University of Latvia, Latvia, Cinite Ilva , Barinovs Girts ,   University of Latvia, Latvia
Published: September 2021

The purpose of this study is to measure the development of students’ conceptual understanding of basic physics concepts at introductory physics courses at the University of Latvia. The authors of the research have translated, tested and verified the Force Concept Inventory and other Concept Inventories in the context of Latvian education system. The results demonstrated a low improvement of physics understanding using present lecturing approach, which suggests the need for an active learning environment and student-centred learning approach in physics courses at University of Latvia. Due to the very small number of physics graduates from physics faculties in Latvia and especially small number of physics teachers, it becomes increasingly important that these students acquire good conceptual understanding of physics. Keywords: STEM education, conceptual understanding, evidence-based approaches.
LESSON STUDY AS A PROCESS FOR DEVELOPING THE PEDAGOGICAL CONTENT KNOWLEDGE OF PRE-SERVICE PHYSICS AND CHEMISTRY TEACHERS
Authors:   University of Lisbon, Portugal, Conceição Teresa , Baptista Mónica ,   University of Lisbon, Portugal, Pedro da Ponte , João ,   University of Lisbon, Portugal
Published: September 2021

This research aimed to understand what physics and chemistry pre-service teachers learn within pedagogical content knowledge in a lesson study with the topic speed of sound, 8th grade. Participants were three pre-service teachers. This was a qualitative and interpretative study. Data were collected from participant observation, individual interviews and individual written reflections. Results showed that the participants developed their pedagogical content knowledge, when they identified the students’ prior knowledge and when they discussed strategies to help students overcome their difficulties. Keywords: initial teacher education, lesson study, pre-service teachers, professional development, science education.
ANALYSIS OF SOME SELECTED FORCE CONCEPT INVENTORY TASKS USING EYE-TRACKING AND CORRELATION WITH SCIENTIFIC REASONING SKILLS
Authors:   Palacký University Olomouc, Czech Republic, Holubová Renata , Krčmářová Anna ,   Palacký University Olomouc, Czech Republic, Richterek Lukáš ,   Palacký University Olomouc, Czech Republic, Říha Jan ,   Palacký University Olomouc, Czech Republic
Published: September 2021

The aim of the research was the analysis of the problem dealing with solving of six Force concept inventory tasks by first-year university students using obtained eye-tracking data. Some characteristics like attention maps and sequences of fixations provide a deeper insight into the students’ approaches to the tasks verifying their conceptual understanding to Newtonian mechanics. It can be confirmed the correctly answering students found the correct solutions more straightforwardly making their decision between fewer options. This is also supported by the analysis of fixation numbers and fixation times. The results show differences in the way novices and experts process questions and enable to identify some persistent misconceptions. Keywords: eye-tracking, introductory physics course, scientific reasoning, solving tasks.
DATA MINING IN EDUCATION: ONLINE TESTING IN LATVIAN SCHOOLS
Authors:   Riga Technical University (RTU) Riga, Latvia, Juškaite Loreta
Published: September 2021

The new research results on the online- testing method in the Latvian education system for a learning process assessment are presented. Data mining is a very important field in education because it helps to analyse the data gathered in various researches and to implement the changes in the education system according to the learning methods of students. The aim of the research was to analyze how much time students devote to each task depending on the task type and the cognitive activity level in the online national test. Research methods: 1) analysis of scientific literature; 2) descriptive statistics and dependency analysis for processing the data. Research results showed that the time spent on tasks depends not on the complexity of the task but on the form and formulation of it. Keywords: online test, data mining, cognitive actitity level.
Analysis of Community and Local Politics The Challenge of the Horizontal Conflict (A Case Study in Kampar Riau, A Constructive Critical Thinking from the Perspective of Political Anthropology)
Authors: Syafrizal
Published: September 2021

This paper wants to critically explain constructively from the perspective of political anthropology, namely one thought on one of the social realities that develop in society Kampar Riau. Society is a group of people who live in one area for a certain period of time, who have emotional attachments and have a common goal. In that context, it is not uncommon for people to incarnate themselves into various situations, including in terms of politics and society. The phenomenon of folklore and local politics is a form of democratic life that is guaranteed by the laws of the Indonesian state. Everyone has their own life history. Talking about humans would be tantamount to talking about who is the owner and creator of all cultures. Humans create their experiences since childhood in the environment in which they were born. Community phenomenon is one of the oldest that characterizes a person's attitude, behavior pattern, which consciously or unconsciously will be incarnated in the long process of his life wherever that person takes part as an adult, such as taking part in an organization, company, or in a certain political party.
Salgın Sürecinde ve Sonrasında Öğretmenlerin Mesleki Gelişimi İçin Karma Bir Program Önerisi
Authors: Doğan Selçuk , Yurtseven Nihal
Published: September 2021

COVID-19 salgını her sektör ve iş alanında olduğu gibi, eğitim sektöründe de önemli etkiler bırakmıştır. Salgının ilk başladığı tarihin üzerinden uzunca bir zaman geçmiş olmasına rağmen, Türkiye’de öğretmenlere uygun yüz yüze ve çevrim içi bileşenlerin olduğu mesleki gelişim programlarının azlığı dikkat çekmekte ve var olanların da beklentileri ve ihtiyaçları karşılayacak düzeyde olmadığı görülmektedir. Mevcut araştırma, var olan boşluklara ve ihtiyaçlara yönelik bir öneride bulunma, bu alanda bakış açısı geliştirmeye katkıda bulunma ve yüz yüze ile çevrim içi bileşenlerin birbirini desteklediği bir mesleki gelişim programı sunma amacı taşımaktadır. Bu program hem fiziksel olarak yüz yüze hem eş zamanlı (senkron) hem de eş zamanlı olmayan (asenkron) etkinlikleri içinde barındırabilen, kaliteli ve etkili mesleki gelişim programlarının kuramsal temellerini içeren karma bir yapıdadır. Araştırma, salgın sürecinde ve sonrasında öğretmenlerin mesleki gelişim sürecinin nasıl şekillendirildiğinin ve bu programdan öğretmenlerin mesleki gelişimleri için gelecekte nasıl yararlanılabileceğinin betimlenmesi açısından önem arz etmektedir. Araştırmada, salgın süreci boyunca bu programın kullanılmasıyla ilgili detaylar ve örnekler verilmiş, programın uzaktan eğitim araç ve gereçleri kullanılarak nasıl uyarlanılacağına değinilmiştir.
Öğretmen Adaylarının Örnek Olaylara Ait Çözüm Stratejilerinin Çok yüzeyli Rasch Model ile İncelenmesi
Authors: Demir Süleyman
Published: September 2021

Bu çalışmanın amacı mezun durumunda olan sınıf öğretmen adaylarının mesleki hayatlarına başladıklarında karşılaşmaları muhtemel sorunlar karşısında geliştirecekleri çözüm stratejilerinin incelenmesidir. Bu amaç doğrultusunda öncelikle sınıf öğretmeni olarak görev yapan öğretmenlerden görüş alınmış ve çözümünde zorlanılan iki örnek olay (alt ıslatma ve hırsızlık) belirlenmiştir. Mezun aşamasına gelmiş 38 öğretmen adayına oluşturulan örnek olaylar yazılı metin olarak verilmiş ve geliştirmiş oldukları çözüm stratejileri yine yazılı metin olarak toplanmıştır. Elde edilen çözüm stratejileri Sınıf öğretmenliği ve Rehberlik ve Psikolojik Danışmanlık alanlarında uzman ikişer akademisyen tarafından Çözüm Stratejileri Değerlendirme Rubriği kullanılarak puanlanmıştır. Verilerin çözümlenmesinde dört-yüzeyli Rasch model kullanılmış ve örnek olaylar, puanlayıcı, madde ve birey birer yüzey olarak belirlenmiştir. Analizler sonucunda örnek olaylar arasında bir farklılığın olmadığı, puanlayıcıların katılık ve cömertlik açısından birbirlerine çok yakın olduğu ve 1 numaralı maddenin (Öğretmen adayı kriz anında soğukkanlı davranabilmiştir) en kolay karşılandığı, 5 numaralı maddenin ise (Yapılan müdahalenin gerekçesi öğrenciye anlatılmıştır) en zor karşılandığı görülmüştür.
Intercultural Communicative Competence: Why Is It Significant and How Can It Be Enhanced in EFL Settings?
Authors: Tümen Akyıldız Seçil , Çelik Vildan , Ahmed Kwestan Hussein
Published: September 2021

In the current literature on foreign language teaching, it has become clear that having the requisite ability of intercultural communicative competence (ICC) to be aware of different cultures, respect them, and interact with people from different cultures is crucial. Language is connected to culture and societies, in which people need to communicate with one another. English as a lingua franca provides a means of communication among different cultures. Thus, English as a foreign language (EFL) teaching classes offer perfect situations to foster ICC. From this viewpoint, this article gives an account to raise awareness of ICC in EFL settings by explaining ICC and its relationship with language, describing the significance of ICC, and illustrating some suggestions in the literature for the enhancement of ICC in EFL classes. This paper seeks to improve EFL teachers’ understanding of intercultural communication and to help them with their classroom practices.
ANALISIS MANAJEMEN RISIKO KESEHATAN DAN KESELAMATAN KERJA (K3) PADA PEKERJAAN UPPER STRUCTURE GEDUNG BERTINGKAT (STUDI KASUS PROYEK SKYLAND CITY – JATINANGOR)
Authors: Anwar Fahmi Nurul , Farida Ida , Ismail Agus
Published: September 2021

Proyek apartemen dapat dikatakan sebagai proyek yang berisiko sangat tinggi karena besarnya bobot pekerjaan dan tingginya struktur yang akan dibangun. Risiko pada proyek konstruksi sangatlah banyak dan bervariasi, diantaranya risiko biaya proyek, produktivitas pekerja, mutu dan waktu pelaksanaan. Risiko yang harus lebih diperhatikan adalah risiko kesehatan dan keselamatan kerja (K3). Dengan adanya manajemen risiko ini diharapkan kecelakaan kerja yang terjadi dapat dikurangi, sehingga jika terjadi kecelakaan kerja maka dampak dari kecelakaan tersebut tidak akan berpengaruh banyak dan menghambat pekerjaan yang lainnya. Pada penelitian ini akan diidentifikasi bahaya K3, penilaian risiko K3 serta bagaimana cara mengendalikan terhadap risiko K3 yang ada pada pekrejaan upper structure dengan metode penilaian risiko berdasarkan dari NHS Highland yang diadopsi dari AS/NZS 4360:2004 Risk Management. Analisis risiko dilakukan dengan melakukan identifikasi risiko dengan cara review data, interview dan kuisioner. Setelah melakukan identifikasi, nilai dampak dan frekuensi dikalikan untuk mendapatkan nilai tingkat risiko pada tiap faktor risiko. Evaluasi risiko adalah hal selanjutnya yang dilakukan dengan mengurutkan nilai risiko mulai dari yang terbesar sampai terkecil, kemudian melakukan penangan/pengendalian risiko agar tidak berpengaruh besar pada tujuan proyek. Dari hasil penilaian risiko ditemukan risiko yang paling besar adalah potensi risiko beton keropos dalam pekerjaan pengecoran dengan indeks nilai risiko sebesar 10,55.
“Extensive” T4 breast tumors: Considerations regarding local management.
Authors: Charilaos Ioannidis
Published: September 2021

“Extensive” T4 malignant breast tumors are not uncommon and can be either primary or recurrent. Theycan present without or be accompanied by distant metastases at the time of initial presentation. They share one or more of the following symptoms: mass effect, pain, malodor, esthetic distress, exudation, pruritus, bleeding, and crusting. The aim of their treatment is therapeutic, when possible, or palliative, which is quite often the case. A small case series of three female patients with “extensive” T4 breast cancer is presented. The various surgical options for excision of the tumor and reconstruction of the resulting defect are discussed. Methods of management of odor, infection control, and pain, especially when surgery or radiotherapy is contraindicated, is also discussed.
Post Partum Hemorrhage – Mini Review
Authors: Voros Charalampos , Pappa Kalliopi
Published: September 2021

Background: Postpartum hemorrhage (PPH) remains a common cause of maternal mortality worldwide, mainly caused by uterine atony. Medical intervention plays an important part in prevention and therapies of PPH. Prophylactic interventions include the use of uterotonic drugs. We elaborated the consistency of national and international guidelines on those medical approaches. Materials and methods: Medical approaches in PPH were extracted from recent publications. Furthermore, the current guidelines of the World Health Organization, the FIGO and of the American, British,and Canadian of Obstetricians and Gynecologists on PPH were analyzed. Results: Use of oxytocin after delivery of the anterior shoulder is the most important and effective component of this practice. However, the examined guidelines fail to give unequivocal recommendations on further uterotonics in PPH, which may partially be attributed to differing publication dates of the guidelines. Conclusion: Appropriate management of postpartum hemorrhage requires prompt diagnosis and treatment . International guidelines on PPH are characterized by differing recommendations. However, recent publications suggest that adhering to local guidelines significantly reduces the prevalence of severe PPH.
Revealing the enigma of coagulation in endometriosis: the risk of thrombosis and the role of antithrombotic treatment
Authors: Kanellopoulou Theoni
Published: September 2021

Endometriosis is a chronic inflammatory disease of women of reproductive age that is defined by the presence of ectopic endometrium. The pathophysiology of the disease is poorly understood, however platelet activation play a crucial role in initiation of inflammation and fibrinogenesis, which in term further activate the coagulation cascade. The relationship between inflammation and coagulation motivated researchers to study whether patients are in a hypercoagulable state and if endometriosis represent an independent risk factor for venous thromboembolism or cardiovascular risk. This review article focuses on the role of coagulation, the risk of thrombosis and a possible beneficial effect of antithrombotic-treatment.
Poland syndrome: Chest wall and breast repair
Authors: Ioannidis Charilaos
Published: September 2021

Introduction: Poland syndrome is a rare congenital disorder. Its main characteristics are deficiency of the sternocostal portion of the pectoralis major muscle and symbrachydactyly. However, it encompasses a wide spectrum of other chest, breast and upper extremity anomalies. Patients and Methods: The author’s personal experience with a small series of patients with Poland syndrome is retrospectively reviewed. Only chest and breast anomalies were surgically corrected. A bilateral augmentation mammoplasty using different size implants was performed in order to restore chest and breast asymmetry in female patients. The latissimus dorsi muscle was transferred in order to replace the absent pectoralis major in male patients. Results: Eleven adult patients were found. There were 8 female and 3 male patients (age 21-29, mean 23,5y). Two patients refused any kind of treatment. Nine patients (six females, three males) underwent surgical correction (right side n=8, left side n=1). The follow-up period ranged from 6 months to 14 years. There were no major complications. There was a minor complication (seroma) in a male patient after latissimus dorsi transfer, which resolved spontaneously. No capsular contracture has been detected to date and no revision or implant change has been necessary in any of the female patients. All patients were satisfied with the final outcome. Conclusions: The pedicled latissimus dorsi muscle is still the “golden standard” for replacement of the totally absent pectoralis major muscle especially in males. Breast implants are highly successful in correcting chest/ breast asymmetry (size and shape anomalies) in females. Remaining nipple/areola deformities can be easily tackled at a later stage.
A case of meconium peritonitis due to bowel perforation diagnosed at anomaly scan at 20 weeks.
Authors: Sinha Prabha , Sibtain Shabnum , Aoun Hakmi
Published: September 2021

Meconium peritonitis is a rare condition in a fetus which occurs due to perforation of the bowel in the antenatal period. It has serious neonatal consequences resulting in death if the diagnosis is delayed soon after delivery. However, its detection is difficult as the presentation is very variable. A case of meconium peritonitis and pseudocyst detected in a fetus at 33 weeks and 2 days of gestation is discussed regarding its diagnosis and management. Final diagnosis was made only after delivery and managed by surgery (bowel resection). The outcome after treatment was favourable because of the timely intervention.
The Dynamic Role of Religious Figures in The Diffusion of Community Forest Development: A Study of Phenomenology on Madurese Community in Probolinggo Regecny
Authors: Tirmidi Tirmidi , Kanto Sanggar , Hidayat Kliwon , Luth Thohir
Published: September 2021

One of the causes of the successful development of community forests in Probolinggo Regency was the participation of religious leaders. This study explored the dynamics of the role of religious leaders in the development of community forests. Through a qualitative research design with a phenomenological approach and a Naturalistic paradigm, it was found that religious leaders carried out dynamic roles from the pioneering period to the period of obtaining international ecolabel certificates. From this discovery, three propositions were drawn to which after inter-relation between the concepts, two substantive theories were drawn, namely (1) Followers’ Need-Based Visionary Leader Theory, dan (2) Theory of Change-and-Innovation Enabling Leader Quality (Attributes of Change-and-innovation Enabling Leader).
A SCIENTIFIC APPROACH FOR NAHWU LEARNING
Authors: Zaenab Siti
Published: September 2021

The purpose of this study was to determine the development of scientific-based Nahwu learning modules at SMA Darul Ulum 3 Jombang. This research uses the research and development method of the Plomp model. The research targets consisted of the experimental class and the control class. The experimental class is class X IPS2 SMA Darul Ulum 3 Jombang in the 2017/2018 academic year, while the control class is class X MIPA 1 SMA Darul Ulum 3 Jombang in the 2017/2018 academic year. The results of the feasibility test show that the instrument is valid for research. with very good achievement scores, namely: material experts 82.5%, and expert practitioners 83.7%. The results showed that the Nahwu learning module using a scientific approach obtained a significance value = 0.200 and 0.062 > 0.05 during the normality test between the control class and the treatment class. As for the results of the homogeneity test, the significance value = 0.752 and 0.569 > 0.05, and the t-test found that the Sig. (2-tailed) for the posttest of 0.030. Sig. (2-tailed) 0.030 < 5% then the result of t test is H0 is rejected. So, there are differences in student learning outcomes using the nahwu learning module using a scientific approach with student learning outcomes using textbooks..

 Keywords: module, Nahwu learning, Scientific.

PENDEKATAN SAINTIFIK DALAM PEMBELAJARAN NAHWU

Abstrak

Tujuan penelitian ini adalah untuk mengetahui pengembangan modul pembelajaran Nahwu berbasis saintifik di SMA Darul Ulum 3 Jombang. Penelitian ini menggunakan metode penelitian dan pengembangan model Plomp. Sasaran penelitian terdiri atas sasaran kelas eksperimen dan kelas kontrol. Adapun kelas eksperimen adalah siswa kelas X IPS2 SMA Darul Ulum 3 Jombang Tahun Pelajaran 2017/ 2018, sedangkan kelas control adalah siswa kelas X MIPA 1 SMA Darul Ulum 3 Jombang Tahun Pelajaran 2017/ 2018.  Hasil uji coba kelayakan menunjukan bahwa instrumen valid digunakan untuk penelitian dengan nilai pencapaian sangat baik yakni: ahli materi 82, 5 %, dan ahli praktisi 83,7 %. Hasil penelitian menunjukan bahwa modul pembelajaran Nahwu dengan menggunakan pendekatan saintifik didapat nilai signifikansi = 0,200 dan 0,062 > 0,05 pada saat uji normalitas antara kelas kontrol dan kelas perlakuan. Sedangkan untuk hasil dari uji homogenitas didapat nilai signifikansi = 0,752 dan 0,569 > 0,05, dan pada uji-t didapatkan bahwa nilai Sig. (2-tailed) untuk pascates sebesar 0,030. Sig. (2-tailed) 0,030 < 5% maka hasil uji t adalah H0 ditolak. Jadi, terdapat perbedaan hasil belajar siswa yang menggunakan modul pembelajaran nahwu dengan menggunakan Pendekatan saintifik dengan  hasil belajar siswa yang menggunakan buku teks.

Kata kunci: modul, pembelajaran Nahwu, Saintifik
RETRACTED: Liposomes: Structure, Biomedical Applications, and Stability Parameters With Emphasis on Cholesterol
Authors: Nakhaei Pooria , Margiana Ria , Bokov Dmitry O. , Abdelbasset Walid Kamal , Jadidi Kouhbanani Mohammad Amin , Varma Rajender S. , Marofi Faroogh , Jarahian Mostafa , Beheshtkhoo Nasrin
Published: September 2021

Liposomes are essentially a subtype of nanoparticles comprising a hydrophobic tail and a hydrophilic head constituting a phospholipid membrane. The spherical or multilayered spherical structures of liposomes are highly rich in lipid contents with numerous criteria for their classification, including structural features, structural parameters, and size, synthesis methods, preparation, and drug loading. Despite various liposomal applications, such as drug, vaccine/gene delivery, biosensors fabrication, diagnosis, and food products applications, their use encounters many limitations due to physico-chemical instability as their stability is vigorously affected by the constituting ingredients wherein cholesterol performs a vital role in the stability of the liposomal membrane. It has well established that cholesterol exerts its impact by controlling fluidity, permeability, membrane strength, elasticity and stiffness, transition temperature (Tm), drug retention, phospholipid packing, and plasma stability. Although the undetermined optimum amount of cholesterol for preparing a stable and controlled release vehicle has been the downside, but researchers are still focused on cholesterol as a promising material for the stability of liposomes necessitating explanation for the stability promotion of liposomes. Herein, the prior art pertaining to the liposomal appliances, especially for drug delivery in cancer therapy, and their stability emphasizing the roles of cholesterol.
Reconstruction of the Swine Pulmonary Artery Using a Graft Engineered With Syngeneic Cardiac Pericytes
Authors: Alvino Valeria Vincenza , Thomas Anita C. , Ghorbel Mohamed T. , Rapetto Filippo , Narayan Srinivas A. , Kilcooley Michael , Iacobazzi Dominga , Carrabba Michele , Fagnano Marco , Cathery William , Avolio Elisa , Caputo Massimo , Madeddu Paolo
Published: September 2021

The neonatal heart represents an attractive source of regenerative cells. Here, we report the results of a randomized, controlled, investigator-blinded preclinical study, which assessed the safety and effectiveness of a matrix graft cellularized with cardiac pericytes (CPs) in a piglet model of pulmonary artery (PA) reconstruction. Within each of five trios formed by 4-week-old female littermate piglets, one element (the donor) was sacrificed to provide a source of CPs, while the other two elements (the graft recipients) were allowed to reach the age of 10 weeks. During this time interval, culture-expanded donor CPs were seeded onto swine small intestinal submucosa (SIS) grafts, which were then shaped into conduits and conditioned in a flow bioreactor. Control unseeded SIS conduits were subjected to the same procedure. Then, recipient piglets were randomized to surgical reconstruction of the left PA (LPA) with unseeded or CP-seeded SIS conduits. Doppler echocardiography and cardiac magnetic resonance imaging (CMRI) were performed at baseline and 4-months post-implantation. Vascular explants were examined using histology and immunohistochemistry. All animals completed the scheduled follow-up. No group difference was observed in baseline imaging data. The final Doppler assessment showed that the LPA’s blood flow velocity was similar in the treatment groups. CMRI revealed a mismatch in the average growth of the grafted LPA and contralateral branch in both treatment groups. Histology of explanted arteries demonstrated that the CP-seeded grafts had a thicker luminal cell layer, more intraparietal arterioles, and a higher expression of endothelial nitric oxide synthase (eNOS) compared with unseeded grafts. Moreover, the LPA stump adjacent to the seeded graft contained more elastin and less collagen than the unseeded control. Syngeneic CP engineering did not accomplish the primary goal of supporting the graft’s growth but was able to improve secondary outcomes, such as the luminal cellularization and intraparietal vascularization of the graft, and elastic remodeling of the recipient artery. The beneficial properties of neonatal CPs may be considered in future bioengineering applications aiming to reproduce the cellular composition of native arteries.
The Role of Pancreatic Alpha Cells and Endothelial Cells in the Reduction of Oxidative Stress in Pseudoislets
Authors: Wieland Fredrik C. , Sthijns Mireille M.J.P.E. , Geuens Thomas , van Blitterswijk Clemens A. , LaPointe Vanessa L.S.
Published: September 2021

Pancreatic beta cells have inadequate levels of antioxidant enzymes, and the damage induced by oxidative stress poses a challenge for their use in a therapy for patients with type 1 diabetes. It is known that the interaction of the pancreatic endocrine cells with support cells can improve their survival and lead to less vulnerability to oxidative stress. Here we investigated alpha (alpha TC-1), beta (INS1E) and endothelial (HUVEC) cells assembled into aggregates known as pseudoislets as a model of the pancreatic islets of Langerhans. We hypothesised that the coculture of alpha, beta and endothelial cells would be protective against oxidative stress. First, we showed that adding endothelial cells decreased the percentage of oxidative stress-positive cells. We then asked if the number of endothelial cells or the size (number of cells) of the pseudoislet could increase the protection against oxidative stress. However, no additional benefit was observed by those changes. On the other hand, we identified a potential supportive effect of the alpha cells in reducing oxidative stress in beta and endothelial cells. We were able to link this to the incretin glucagon-like peptide-1 (GLP-1) by showing that the absence of alpha cells in the pseudoislet caused increased oxidative stress, but the addition of GLP-1 could restore this. Together, these results provide important insights into the roles of alpha and endothelial cells in protecting against oxidative stress.
RNA-Binding Proteins CLK1 and POP7 as Biomarkers for Diagnosis and Prognosis of Esophageal Squamous Cell Carcinoma
Authors: Yang Xiuping , Han Baoai , He Zuhong , Zhang Ya , Lin Kun , Su Hongguo , Hosseini Davood K. , Sun Haiying , Yang Minlan , Chen Xiong
Published: September 2021

The abnormality of RNA-binding proteins (RBPs) is closely related to the tumorigenesis and development of esophageal squamous cell carcinoma (ESCC), and has been an area of interest for research recently. In this study, 162 tumors and 11 normal samples are obtained from The Cancer Genome Atlas database, among which 218 differentially expressed RBPs are screened. Finally, a prognostic model including seven RBPs (CLK1, DDX39A, EEF2, ELAC1, NKRF, POP7, and SMN1) is established. Further analysis reveals that the overall survival (OS) rate of the high-risk group is lower than that of the low-risk group. The area under the receiver operating characteristic (ROC) curve (AUC) of the training group and testing group is significant (AUCs of 3 years are 0.815 and 0.694, respectively, AUCs of 5 years are 0.737 and 0.725, respectively). In addition, a comprehensive analysis of seven identified RBPs shows that most RBPs are related to OS in patients with ESCC, among which EEF2 and ELCA1 are differentially expressed at the protein level of ESCC and control tissues. CLK1 and POP7 expressions in esophageal cancer tumor samples are undertaken using the tissue microarray, and show that CLK1 mRNA levels are relatively lower, and POP7 mRNA levels are higher compared with non-cancerous esophageal tissues. Survival analysis reveals that a higher expression of CLK1 predicts a significant worse prognosis, and a lower expression of POP7 predicts a worse prognosis in esophageal cancer. These results suggest that CLK1 may promote tumor progression, and POP7 may hinder the development of esophageal cancer. In addition, gene set enrichment analysis reveals that abnormal biological processes related to ribosomes and abnormalities in classic tumor signaling pathways such as TGF-β are important driving forces for the occurrence and development of ESCC. Our results provide new insights into the pathogenesis of ESCC, and seven RBPs have potential application value in the clinical prognosis prediction of ESCC.
WW, PH and C-Terminal Domains Cooperate to Direct the Subcellular Localizations of PLEKHA5, PLEKHA6 and PLEKHA7
Authors: Sluysmans Sophie , Méan Isabelle , Jond Lionel , Citi Sandra
Published: September 2021

PLEKHA5, PLEKHA6, and PLEKHA7 (WW-PLEKHAs) are members of the PLEKHA family of proteins that interact with PDZD11 through their tandem WW domains. WW-PLEKHAs contribute to the trafficking and retention of transmembrane proteins, including nectins, Tspan33, and the copper pump ATP7A, at cell-cell junctions and lateral membranes. However, the structural basis for the distinct subcellular localizations of PLEKHA5, PLEKHA6, and PLEKHA7 is not clear. Here we expressed mutant and chimeric proteins of WW-PLEKHAs in cultured cells to clarify the role of their structural domains in their localization. We found that the WW-mediated interaction between PLEKHA5 and PDZD11 is required for their respective association with cytoplasmic microtubules. The PH domain of PLEKHA5 is required for its localization along the lateral plasma membrane and promotes the lateral localization of PLEKHA7 in a chimeric molecule. Although the PH domain of PLEKHA7 is not required for its localization at the adherens junctions (AJ), it promotes a AJ localization of chimeric proteins. The C-terminal region of PLEKHA6 and PLEKHA7 and the coiled-coil region of PLEKHA7 promote their localization at AJ of epithelial cells. These observations indicate that the localizations of WW-PLEKHAs at specific subcellular sites, where they recruit PDZD11, are the result of multiple cooperative protein-lipid and protein-protein interactions and provide a rational basis for the identification of additional proteins involved in trafficking and sorting of WW-PLEKHAs.
Cytoskeletal Remodeling Mimics Endothelial Response to Microgravity
Authors: Locatelli Laura , Maier Jeanette A. M.
Published: September 2021

Mechanical cues contribute to the maintenance of a healthy endothelium, which is essential for vascular integrity. Indeed endothelial cells are mechanosensors that integrate the forces in the form of biochemical signals. The cytoskeleton is fundamental in sensing mechanical stimuli and activating specific signaling pathways. Because the cytoskeleton is very rapidly remodeled in endothelial cells exposed to microgravity, we investigated whether the disruption of actin polymerization by cytochalasin D in 1g condition triggers and orchestrates responses similar to those occurring in micro- and macro-vascular endothelial cells upon gravitational unloading. We focused our attention on the effect of simulated microgravity on stress proteins and transient receptor potential melastatin 7 (TRPM7), a cation channel that acts as a mechanosensor and modulates endothelial cell proliferation and stress response. Simulated microgravity downregulates TRPM7 in both cell types. However, 24 h of treatment with cytochalasin D decreases the amounts of TRPM7 only in macrovascular endothelial cells, suggesting that the regulation and the role of TRPM7 in microvascular cells are more complex than expected. The 24 h culture in the presence of cytochalasin D mimics the effect of simulated microgravity in modulating stress response in micro- and macro-vascular endothelial cells. We conclude that cytoskeletal disruption might mediate some effects of microgravity in endothelial cells.
Analysis of miRNAs Profiles in Serum of Patients With Steatosis and Steatohepatitis
Authors: Vulf Maria , Shunkina Daria , Komar Aleksandra , Bograya Maria , Zatolokin Pavel , Kirienkova Elena , Gazatova Natalia , Kozlov Ivan , Litvinova Larisa
Published: September 2021

Non-alcoholic fatty liver disease (NAFLD) is emerging as one of the most common chronic liver diseases worldwide, affecting 25% of the world population. In recent years, there has been increasing evidence for the involvement of microRNAs in the epigenetic regulation of genes taking part in the development of steatosis and steatohepatitis—two main stages of NAFLD pathogenesis. In the present study, miRNA profiles were studied in groups of patients with steatosis and steatohepatitis to compare the characteristics of RNA-dependent epigenetic regulation of the stages of NAFLD development. According to the results of miRNA screening, 23 miRNAs were differentially expressed serum in a group of patients with steatohepatitis and 2 in a group of patients with steatosis. MiR-195-5p and miR-16-5p are common differentially expressed miRNAs for both steatosis and steatohepatitis. We analyzed the obtained results: the search for target genes for the differentially expressed miRNAs in our study and the subsequent gene set enrichment analysis performed on KEGG and REACTOME databases revealed which metabolic pathways undergo changes in RNA-dependent epigenetic regulation in steatosis and steatohepatitis. New findings within the framework of this study are the dysregulation of neurohumoral pathways in the pathogenesis of NAFLD as an object of changes in RNA-dependent epigenetic regulation. The miRNAs differentially expressed in our study were found to target 7% of genes in the classic pathogenesis of NAFLD in the group of patients with steatosis and 50% in the group of patients with steatohepatitis. The effects of these microRNAs on genes for the pathogenesis of NAFLD were analyzed in detail. MiR-374a-5p, miR-1-3p and miR-23a-3p do not target genes directly involved in the pathogenesis of NAFLD. The differentially expressed miRNAs found in this study target genes largely responsible for mitochondrial function. The role of miR-423-5p, miR-143-5p and miR-200c-3 in regulating apoptotic processes in the liver and hepatocarcinogenesis is of interest for future experimental studies. These miR-374a, miR-143, miR-1, miR-23a, and miR-423 have potential for steatohepatitis diagnosis and are poorly studied in the context of NAFLD. Thus, this work opens up prospects for further studies of microRNAs as diagnostic and therapeutic biomarkers for NAFLD.
Disease-Associated Gut Microbiota Reduces the Profile of Secondary Bile Acids in Pediatric Nonalcoholic Fatty Liver Disease
Authors: Yu Jiake , Zhang Hu , Chen Liya , Ruan Yufei , Chen Yiping , Liu Qi
Published: September 2021

Children with nonalcoholic fatty liver disease (NAFLD) display an altered gut microbiota compared with healthy children. However, little is known about the fecal bile acid profiles and their association with gut microbiota dysbiosis in pediatric NAFLD. A total of 68 children were enrolled in this study, including 32 NAFLD patients and 36 healthy children. Fecal samples were collected and analyzed by metagenomic sequencing to determine the changes in the gut microbiota of children with NAFLD, and an ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) system was used to quantify the concentrations of primary and secondary bile acids. The associations between the gut microbiota and concentrations of primary and secondary bile acids in the fecal samples were then analyzed. We found that children with NAFLD exhibited reduced levels of secondary bile acids and alterations in bile acid biotransforming-related bacteria in the feces. Notably, the decrease in Eubacterium and Ruminococcaceae bacteria, which express bile salt hydrolase and 7α-dehydroxylase, was significantly positively correlated with the level of fecal lithocholic acid (LCA). However, the level of fecal LCA was negatively associated with the abundance of the potential pathogen Escherichia coli that was enriched in children with NAFLD. Pediatric NAFLD is characterized by an altered profile of gut microbiota and fecal bile acids. This study demonstrates that the disease-associated gut microbiota is linked with decreased concentrations of secondary bile acids in the feces. The disease-associated gut microbiota likely inhibits the conversion of primary to secondary bile acids.
Long Non-Coding RNA FGD5-AS1 Induced by Chlamydia trachomatis Infection Inhibits Apoptosis via Wnt/β-Catenin Signaling Pathway
Authors: Wen Yating , Luo Fangzhen , Zhao Lanhua , Su Shengmei , Lei Wenbo , Liu Yi , Shi Keliang , Li Zhongyu
Published: September 2021

Background

Chlamydia trachomatis (Ct) is one of the most common bacterial sexually transmitted infection (STI) pathogens in the world, but the exact pathogenic mechanism still needs to be further elucidated. Long non-coding RNAs (lncRNAs) have become vital regulators in many biological processes. Their role in the interaction between Ct and host cells has not been reported.

Methods

Microarrays were used to study the expression profiles of lncRNAs and mRNAs in HeLa cells at 12, 24, and 40 h post-infection (hpi). Differentially expressed lncRNAs and mRNAs were verified by RT-qPCR. Coding-non-coding (CNC) network analysis showed co-expression molecules of selected lncRNA. Western blot, flow cytometry, and indirect immunofluorescence were used to detect the effect of lncRNA FGD5-AS1 on apoptosis during Ct infection.

Results

Compared with the uninfected group, the number of differential lncRNAs were 2,130, 1,081, and 1,101 at 12, 24, and 40 hpi, and the number of differential mRNAs was 1,998, 1,129, and 1,330, respectively. Ct induced differential expression of large amounts of lncRNAs and mRNAs in HeLa cells, indicating that lncRNAs may play roles in the pathogenesis of Ct. RT-qPCR verified six differential lncRNAs and six differential mRNAs, confirming the reliability of the microarray. Among these molecules, lncRNA FGD5-AS1 was found to be upregulated at 12 and 24 hpi. Coding-non-coding (CNC) network analysis showed that co-expressed differential molecules of FGD5-AS1 at 12 and 24 hpi were enriched in the DNA replication and Wnt signaling pathway. The downregulation of FGD5-AS1 decreased the expression of β-catenin and inhibited the translocation of β-catenin and the DNA replication, while it promoted apoptosis of the host cells.

Conclusions

DNA replication and apoptosis of host cells were affected by upregulating FGD5-AS1 via Wnt/β-catenin pathway during Ct infection. This study provides evidence that lncRNAs are involved in the coaction between Ct and hosts, and provides new insights into the study of lncRNAs that regulate chlamydial infection.
Acquisition of the Conjugative Virulence Plasmid From a CG23 Hypervirulent Klebsiella pneumoniae Strain Enhances Bacterial Virulence
Authors: Tian Dongxing , Wang Weiwen , Li Meng , Chen Wenjie , Zhou Ying , Huang Yunkun , Sheng Zike , Jiang Xiaofei
Published: September 2021

The emergence of hypervirulent and carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) has become a hot topic and confounding problem for clinicians and researchers alike. Conjugative virulence plasmids have the potential to cause more threatening dissemination of hv-CRKP strains. We previously identified K2606, a CG23 clinical hypervirulent strain of Klebsiella pneumoniae harboring a conjugative virulence plasmid designated pK2606. In this study we examined hypervirulence levels using assays of biofilm formation, serum resistance, and wax larvae and mouse in vivo infection models. Moreover, to define the transfer ability of pK2606 and whether this confers hypervirulence to other strains we performed plasmid transconjugation experiments between K2606 and the ST11 CRKP strain HS11286 along with E. coli J53. We found that although biofilm formation and serum resistance were not significantly increased, the transconjugants acquired the ability of produce high level of siderophores and also caused high mortality of wax larvae and mice. Furthermore, we identified pK2606-like conjugative virulence plasmids in GenBank, providing evidence that such plasmids may have begun to spread throughout China. These findings provide an evidence base for the possible mechanisms of the emergence of hv-CRKP strains and highlight the potential of pK2606-like conjugative virulence plasmids to spread worldwide.
γ' Fibrinogen as a Predictor of Survival in Amyotrophic Lateral Sclerosis
Authors: Pronto-Laborinho Ana Catarina , Lopes Catarina S. , Conceição Vasco A. , Gromicho Marta , Santos Nuno C. , de Carvalho Mamede , Carvalho Filomena A.
Published: September 2021

Amyotrophic lateral sclerosis (ALS) is an aggressive neurodegenerative disorder related to neuroinflammation that is associated with increased risk of thrombosis. We aimed to evaluate γ' fibrinogen plasma level (an in vivo variant of fibrinogen) as a biomarker in ALS, and to test its role as a predictor of disease progression and survival. Sixty-seven consecutive patients with ALS were followed and the results were compared with those from 82 healthy blood donors. Patients were clinically evaluated at the time of blood sampling and on follow-up (every 3 months for the beginning of the follow-up until death) by applying the revised ALS Functional Rating Scale. Human plasma γ' fibrinogen concentration was quantified using a specific two-site sandwich kit enzyme-linked immunosorbent assay. We found, for the first time, a positive association between γ' fibrinogen concentration and survival in ALS patients: patients with higher γ' fibrinogen plasma levels survived longer, and this finding was not influenced by confounders such as age, gender, respiratory impairment, or functionality (ALSFRS-R score). Since increased levels have a positive impact on outcome, this novel biomarker should be further investigated in ALS.
Automated Thrombin Generation Assay for Rivaroxaban, Apixaban, and Edoxaban Measurements
Authors: Meihandoest Tamana , Studt Jan-Dirk , Mendez Adriana , Alberio Lorenzo , Fontana Pierre , Wuillemin Walter A. , Schmidt Adrian , Graf Lukas , Gerber Bernhard , Maeder Gabriela Monika , Bovet Cédric , Sauter Thomas C. , Nagler Michael
Published: September 2021

Background: The thrombin generation assay (TG) is a promising approach to measure the degree of anticoagulation in patients treated with direct oral anticoagulants (DOAC). A strong association with plasma drug concentrations would be a meaningful argument for the potential use to monitor DOAC.

Objectives: We aimed to study the correlation of TG with rivaroxaban, apixaban, and edoxaban drug concentrations in a large, prospective multicenter cross-sectional study.

Methods: Five-hundred and fifty-nine patients were included in nine tertiary hospitals. The Technothrombin® TG was conducted in addition to an anti-Xa assay; LC-MS/MS was performed as the reference standard.

Results: Correlation (rs) between thrombin generation measurements and drug concentrations was −0.72 for peak thrombin generation (95% confidence interval, CI, −0.77, −0.66), −0.55 for area under the curve (AUC; 95% CI −0.61, −0.48), and 0.80 for lag time (95% CI 0.75, 0.84). In contrast, rs was 0.96 with results of the anti-Xa activity (95% CI 0.95–0.97). Sensitivity with regard to the clinically relevant cut-off value of 50 μgL−1 was 49% in case of peak thrombin generation (95% CI, 44, 55), 29% in case of AUC (95% CI, 24, 34), and 64% in case of lag time (95% CI, 58, 69). Sensitivity of the anti-Xa assay was 95% (95% CI, 92, 97).

Conclusions: The correlation of thrombin generation measurements with DOAC drug concentrations was weak, and clinically relevant drug levels were not predicted correctly. Our results do not support an application of TG in the monitoring of DOAC.
Endo-Aortic vs. Trans-Thoracic Clamping in Right Mini-Thoracotomy Mitral Valve Surgery: Outcome on Myocardial Protection
Authors: Barbero Cristina , Rinaldi Mauro , Pocar Marco , Cura Stura Erik , Calia Claudia , Sebastiano Viviana , Marchetto Giovanni , Filippini Claudia , Boffini Massimo , Ricci Davide
Published: September 2021

Background:Perfusion strategies and aortic clamping techniques for right mini-thoracotomy mitral valve (MV) surgery have evolved over time and remarkable short- and long-term results have been reported. However, some concerns have raised about the adequacy of myocardial protection during the minimally invasive approach, particularly with the endo-aortic clamp (EAC). Aim of this study was to compare the efficacy, in terms of myocardial preservation, of the EAC with the trans-thoracic aortic clamp (TTC) in patients undergoing right mini-thoracotomy MV surgery.

Methods:A single center, prospective observational study was performed on patients undergoing right mini-thoracotomy MV surgery with retrograde arterial perfusion and EAC or TTC. A propensity matched analysis was performed to compare the two groups. Primary outcome was the comparison between cardiac troponin T levels measured at different time-points after surgery.

Results:Eighty EAC patients were compared with 37 TTC patients. No cases of myocardial infarction or low cardiac-output syndrome were overall reported. No differences were recorded in terms of stroke, peri-operative mortality, and in the release of myocardial markers, lactates levels and need for inotropic support at different time-points after surgery. CK-MB peak levels were significantly lower in the EAC group.

Conclusion:Despite concerns arising about the EAC, this prospective study shows equivalence in terms of myocardial preservation of the EAC compared with the TTC in patients undergoing right mini-thoracotomy MV surgery.