bluuebunny/crossref_metadata_2025 huggingface dataset:
EXPLORING THE URGENCY OF TEACHING CAMPUS QUALITY FOR STUDENTS OF IKIP MUHAMMADIYAH MAUMERE
Authors: Busa Eman Nataliano , Nuwa Gisela
Published: August 2023

The Teaching Campus is a part of the Merdeka Campus program, which presents students from various universities to encourage the teaching and learning process in schools, especially for the elementary school education level, and provide opportunities for students to learn and develop themselves through activities outside the lecture class. IKIP Muhammadiyah Maumere also takes an important role in the teaching campus program by involving the students as pioneers in the teaching campus program. The research purpose of this paper is to find out the urgency of teaching campus quality to IKIP Muhammadiyah Maumere students and the programs participated by students of IKIP Muhammadiyah Maumere in Campus Teaching Activities. The research uses a descriptive qualitative method. The informants of the research involved campus teaching coordinators, field supervisors, and students of the campus teaching at IKIP Muhammadiyah Maumere. Data collection techniques used were observation, interviews, and documentation. Data analysis techniques include data reduction, data display, and data verification. The research results indicate that the urgency of the quality of teaching campus participants is measured by additional skills in the form of certificates of organizational/teaching, academic and non-academic achievements, and parental consent. Campus teaching participants must be able to manage classes and be able to manage time. Campus teaching participants receive financial assistance and recognition for 20 credits of courses that were obtained from the Ministry of Education. Teaching campus participants must be able to make a positive impact by helping the learning activities in schools, assisting school technology, and assisting technology-based school administration. Students participating in teaching campuses must have creativity and innovation that can create a generation of good workers. Campus teaching participants must have a good attitude and behavior. The programs run by Campus Teaching Participants IKIP Muhammadiyah Maumere are the Literacy and Numeracy Learning program, technology adaptation program, and School Administration Assisting program.
EFFORTS TO INCREASE STUDENTS’ LEARNING OUTCOMES THROUGH PROBLEM BASED LEARNING MODEL ON THE MATERIAL OF THE EFFECTS OF HEAT ON CHANGES IN THE FORM OF OBJECTS IN CLASS V AT SDN 112 PALEMBANG
Authors: Latifah Anisa Resti , Indralin Vinencia Ika , Maharani Siti Dewi
Published: August 2023

This research is a class action research (CAR) conducted in class V SDN 112 Palembang. This research was conducted in class V A with a total of 25 students consisting of 12 boys and 13 girls. This study aims to improve  the learning outcomes of students on the science content of the material  of the effect of heat on changes in the forn of objects by using the problem based learning model in class V A SDN 112 Palembang. Data collection techniques in this research used test and nontest. I the form of observation and documentation. Pre-cycle results with KKM 70, the acquisition of scores obtained by students is still a lot below KKM, <70 there are 21 students and there are 4 completed students. Based on the results of this research, the action on cycle 1 using the model problem based learning has reached  the KKM score of 64% of all student with an average of 70.8. Aplication of cycle 2 increased to 96% with an average of 90.8. This suggest that the application of the problem based learning model in the science content of the material of the effect of calor on changes in the form of objects in the class V A at SDN 112 Palembang can improve the learning outcomes.
INCREASING EDUCATIONAL AWARENESS OF PARENTING STYLES AND FAMILY SOCIAL SUPPORT ON ADOLESCENT MENTAL HEALTH
Authors: Kasingku Juwinner Dedy , Warouw Winda Novita , Lumingkewas Edwin Melky
Published: August 2023

Good mental health requires the ability to manage emotions, thoughts, and actions in a healthy and adaptive manner. Parental upbringing and family support are crucial in maintaining the mental health of adolescents, as they are the closest individuals within the family. Emotional support from the family and access to mental health resources like psychologists or mental health clinics can assist adolescents in overcoming stress and pressures in their lives. This paper uses a literature review methodology to explore the family’s role in adolescent mental health. The findings based on the literature review indicate that the family has a significant influence on adolescent mental health. Parenting styles demonstrated by parents have a significant impact on the mental development of adolescents. The social support provided by parents to their children is likewise crucial. With strong social support from the family and the surrounding environment, adolescents can build positive relationships with others, effectively overcome challenges, and achieve desired life goals.
THE IMPROVEMENT OF SCHOOL PRINCIPAL’S SOCIAL COMPETENCE THROUGH GIVING REWARDS AT PUBLIC ELEMENTARY SCHOOLS OF KAMPAR KIRI TENGAH IN KAMPAR
Authors: Wismardi Wismardi
Published: August 2023

The background of the research in this paper is the low social competence of School Principals at the Public Elementary Schools of Kampar Kiri Tengah sub-districts in Kampar. It can be seen from the initial survey conducted by the researchers. Most teachers, apparently, had not made collaboration either individually or in groups in improving schools. The type of research is School Action Research. Based on the results of the data presentation and discussion, it can be concluded that giving rewards can improve the social competence of School Principals at the Public Elementary Schools of Kampar Kiri Tengah sub-districts in Kampar. In terms of the aspect of giving rewards delivered by tutors, it is seen that from cycle I the score increased in cycle II. If in cycle I the percentage score was 74% and in cycle II it was subsequently higher by getting a percentage score of 86%. In the aspect of the School Principal’s social competence, the percentage score in the first cycle was 58.1% with the sufficient category and in the second cycle, it increased to 82.4% with the good category. It means that the improvement of the School Principal’s social competence through giving rewards at public elementary schools of Kampar Kiri Tengah sub-districts in Kampar is considered to be successful.
E-LKS OF POLYHEDRON MATERIAL BASED ON GUIDED DISCOVERY APPROACH TO FACILITATE MATHEMATICAL PROBLEM-SOLVING ABILITY OF JUNIOR HIGH SCHOOL
Authors: Qodriyani Ukhti , Heleni Susda
Published: August 2023

This study aims to produce Electronic-based Student Worksheets (E-LKS) using a Guided Discovery approach on f polyhedron material based that are valid, practical, and potentially affect the Mathematical Problem-Solving Ability (KPMM) of junior high school. The research method used in this research is Research and Development using a 4-D development model consisting of four stages: Define, Design, Development, and Disseminate. Data collection techniques used include validation questionnaires, student response questionnaires, and documentation. This research involved students of class VIII MTs YASMI and IX MTs YASMI. The results showed that E-LKS has been valid from the quality of presentation, technical requirements, didactic requirements, construction requirements, and KPMM aspects with very valid criteria based on expert comments at the Expert Review and One-to-One stages. Next, the implementation of E-LKS at the Small Group and Field Test stage shows the practicality of E-LKS with very practical criteria. This can be seen from E-LKS, which is easy to read and use, and E-LKS can add enthusiasm to learning. The conclusion is that E-LKS uses a Guided Discovery approach to polyhedron material based to facilitate KPMM for junior high school students and has been valid and practically used in the learning process.
What to Do When Chimeric Antigen Receptor T Cells Are Not the Most Appropriate Option in Second-Line Diffuse Large B Cell Lymphoma: Current Treatment Options for Transplant-Ineligible Patients
Authors: Humphry Nicola
Published: August 2023

This symposium was held on the first day of the 2023 International Conference on Malignant Lymphoma (ICML) Congress in Lugano, Switzerland. Björn Chapuy, a Haematologist in the department of Oncology and Tumour Immunology at Benjamin Franklin Campus, Charité – Universitätsmedizin Berlin, Germany, described the rapid pace of development of new treatment options for patients with diffuse large B cell lymphoma (DLBCL) who relapse after their first-line (1L) of therapy, and introduced an expert panel of speakers including both haematologists and a patient representative from the Lymphoma Coalition, Europe.

Philipp Staber, Programme Director for Lymphoma and Chronic Lymphocytic Leukaemia at the Medical University of Vienna, Austria, discussed the importance of tumour boards, and how they are structured, while Natacha Bolaños, Head of membership and alliances for the Lymphoma Coalition Europe, shared insights from a global survey of patients living with DLBCL or relapsed/refractory (R/R) DLBCL. Eva González-Barca, Co-ordinator of the Lymphoma Unit at the Catalan Institute of Oncology, Barcelona, Spain, and Gabriel Brisou, a Haematologist at the Institut Paoli-Calmettes, Marseille, France, presented case studies of patients with R/R DLBCL treated with different therapies at second-line (2L). The panellists also described the supporting data for some of the options for 2L therapy.

The overarching message from the symposium was that involvement of the patient, and potentially their caregiver, in treatment decisions is vital, and that recommendations for treatment should come from a multidisciplinary tumour board composed of pathologists, radiologists, and haemato-oncologists, rather than an individual clinician. Though there is currently no simple answer to which treatment approach should be chosen for each patient, the panel hopes that the next few years will bring a greater understanding of the best choices for individualised therapy.
Acquired PTEN Loss May Mediate Dabrafenib and Trametinib Resistance in BRAF V600E-Mutated Epithelioid Glioblastoma: A Case Report and Literature Review
Authors: Ahmed Abrar , Nobre Liana , Mason Warren , Bennett Julie , Tabori Uri , Hawkins Cynthia , Climans Seth
Published: August 2023

Epithelioid glioblastoma is a rare and aggressive variant of glioblastoma that is common in children and young adults. This variant frequently has a BRAF V600E mutation, and in recent years, this is often treated with BRAF and mitogen-activated protein kinase kinase inhibitors. An 18-year-old female initially presented with headaches and vomiting. They were diagnosed with an epithelioid glioblastoma and treated with temozolomide chemoradiotherapy. Upon progression, they had to redo surgery and then received dabrafenib and trametinib. They had one last surgery shortly before fatal tumour progression. Retrospective molecular analysis of three tumour specimens showed a PTEN mutation that arose upon first progression, but was not there initially. There were no new tumour mutations after initiation of dabrafenib and trametinib. The acquired PTEN mutation may have conferred resistance to dabrafenib and trametinib. This case highlights the potential importance of early treatment with BRAF and mitogen-activated protein kinase kinase inhibitors in high-grade BRAF V600E-mutated gliomas, ideally before the tumour develops resistance to targeted therapy.
Motivasi Kerja Berhubungan Dengan Produktivitas Kerja Tenaga Kesehatan
Authors: Agata Annisa , Sari Nova Nurwinda , Rianda Rianda , Yuliani Eka
Published: August 2023

Semakin meningkatnya mutu pelayanan kesehatan akan berdampak terhadap kepercayaan masyarakat terhadap pelayanan kesehatan yang diberikan oleh tenaga kesehatan. Upaya untuk terciptanya kualitas pelayanan yang bermutu adalah dengan meningkatkan produktivitas kerja yang baik. Salah satu factor yang mempengaruhi produktivitas kerja adalah motivasi kerja. Tujuan penelitian ini adalah untuk Mengetahui hubungan motivasi kerja dengan produktivitas kerja tenaga kesehatan di Puskesmas Bengkunat Belimbing Kecamatan Bengkunat Belimbing Kabupaten Pesisir Barat. Jenis penelitian kuantitatif, desain penelitian deskriptif analitik dengan menggunakan pendekatan cross sectional. Populasi dalam penelitian ini adalah seluruh tenaga kesehatan Di Puskesmas Bengkunat Belimbing Kecamatan Bengkunat Belimbing Kabupaten Pesisir Barat terhitung sejak Mei Tahun 2022 yang berjumlah 82 orang. Teknik sampling yang digunakan adalah total populasi. Uji statistik dalam penelitian ini menggunakan Uji Chi-Square. Hasil penelitian didapatkan ada hubungan motivasi kerja dengan Produktivitas Kerja tenaga kesehatan. Motivasi merupakan salah satu faktor penyebab, penyalur dan pendukung perilaku manusia agar seseorang mau bekerja dengan giat dan antusias dalam mencapai hasil yang optimal. Semakin tinggi motivasi seseorang untuk melakukan pekerjaan, maka akan semakin tinggi juga tingkat produktivitasnya.
TOTAL ASET, SISTEM PENGENDALIAN INTERNAL, LEVERAGE, ROA DAN AUDIT DELAY PADA PERUSAHAAN GO PUBLIC
Authors: Ardi Bagus Kusuma , Sutopo Sutopo , Harjanto Sri
Published: August 2023

Tema penelitian ini adalah Audit Delay, bertujuan menganalisis pengaruh total aset, sistem pengendalian intern, leverage  dan return on asset terhadap audit delay pada perusahaan yang terdaftar di Bursa Efek Indonesia pada tahun 2020. Populasi meliputi  semua perusahaan go public yang terdaftar di BEI, berjumlah 786 perusahaan dan diambil sebagai sampel sebanyak  87 perusahaan yang dipilih secara random. Analisis menggunakan metode regresi linier berganda, yang hasilnya menunjukkan total aset tidak berpengaruh signifikan terhadap audit delay,  leverage berpengaruh positif signifikan terhadap audit delay, sedangkan system pengendalian intern dan return on asset berpengaruh negatif signifikan terhadap audit delay.
Banking regulation in the United States after the world economic crisis of 2007/2008: economic immunity or false hopes
Authors: Freddo Daniela , Nofal Sulafa , Vargas Juliano
Published: August 2023

Based on the Post-Keynesian approach, we argue that commercial banks, through the financial reforms of 1980 and 1999, which made financial institutions more flexible, increased their capacity to operate in the capital market by becoming Banking Financial Holding Companies. The 2007/2008 crisis is understood as a consequence of financial deregulation and financial innovation process that weakened the Federal Reserve's capacity to restrain banking activity. Initially, we discuss the new institutional context that emerged from these changes in the financial regulatory framework between 1980 and 1999. Then, we focus on how financial deregulation allowed banking business to advance in financial markets, how this process contributed to the economic crisis of 2007, characterized both as a liquidity crisis and a solvency crisis, safeguarded by the National States. Finally, we analyze the Dodd-Frank Law (2010), which is interpreted as the reaffirmation of this endogenous process of financial domination.
As transfigurações de um mestre: comentários sobre a trajetória intelectual de Keynes
Authors: Mazzucchelli Frederico
Published: August 2023

Embora o título acima possa parecer pretensioso, o presente texto, de fato, não o é. Percorrer os meandros da trajetória intelectual de Keynes exigiria um enorme esforço de imersão nos 30 volumes dos Collected Writings of John Maynard Keynes [CWJMK], o que está fora de nosso propósito. Entretanto, ao se apoiar nos ombros de pesquisadores de envergadura, a tarefa fica mais fácil. Lendo as primorosas contribuições de Skidelsky, Dostaler, Carter e Belluzzo, é possível identificar os pontos centrais e as inflexões do pensamento de Keynes. Nada, por suposto, é definitivo, sobretudo em se tratando da interpretação da obra de grandes mestres. As sugestões que aqui se apresentam têm o objetivo de proporcionar uma visão geral dos caminhos percorridos por Keynes até a publicação da Teoria Geral, em 1936. Não se trata de uma discussão técnica que pretenda esmiuçar em detalhes os conceitos criados ou utilizados por Keynes, mas sim fornecer uma base para a compreensão da lógica de seu raciocínio. O ponto de partida é a contextualização histórica de seu ambiente de vida.
A LIFE-CYCLE INTERGENERATIONAL MODEL CONSIDERING SOCIAL SECURITY
Authors: Estulano Vieira Beatriz , De Araujo Oliveira João Gabriel , Nozaki Sugahara Renato
Published: August 2023

The central objective of this paper is to deliver an intergenerational Life Cycle model considering the retirement process based on the pay-as-you-go system (PAYG). Our model is inspired by Baranzinis’ approach, where the optimal consumption analysis is made in a two-class type and restricted by the capital variation of each one. Our main results observe the equilibrium solution of the consumption and capital stock to both classes and conclude that the PAYG system does interfere with the results, as well as the time preference to leave or not inheritance. The methodology approached here is the Pontryagins’ Maximum Principle. We also applied a numerical simulation to ensure the robustness of our approach.
ECONOMIA BRASILEIRA: QUATRO DÉCADAS DE “QUASE” ESTAGNAÇÃO
Authors: Marchetti Adalmir , Donadio Miebach Alessandro
Published: August 2023

O presente artigo discute as quatro décadas de quase estagnação e as possibilidades de retomada do crescimento econômico da economia brasileira. Enquanto nos países centrais há indicações do abandono de muitos elementos centrais do neoliberalismo, no Brasil houve a adoção de um neoliberalismo tardio após 2016. A condição necessária para a retomada do crescimento é a superação do neoliberalismo tardio na economia brasileira com a construção de um novo consenso social.
POST-KEYNESIAN INSTITUTIONALISM: CONTOURS AND FRONTIERS
Authors: Whalen Charles
Published: August 2023

Post-Keynesian institutionalism (PKI)—a branch of the (original) institutionalist school that builds on common ground with post-Keynesianism—constitutes a robust tradition with secure foundations and broad methodological, analytical, and policy contours. Since its emergence in the 1980s, that tradition has consistently been ahead of the economic mainstream in shedding light on real-world problems. Drawing on the work of various heterodox economists—including John Kenneth Galbraith, Joan Robinson, Alfred Eichner, and Hyman Minsky—this article sketches the contours of today’s PKI, including its attention to institutional characteristics of labor and product markets, features of industrial organization, interrelations of finance and macroeconomics, and long-term trends in capitalist development. The article also discusses how PKI relates to the post-Keynesian economics of Fernando Cardim de Carvalho and surveys the frontiers of PKI. The discussion of frontiers and the article’s brief conclusion underscore post-Keynesian institutionalists’ commitment to an ever-evolving body of theory and policy research.
Molecular allergology and its application in prevention, diagnosis and therapy
Authors: Podzhilkova Aleksandra , Nagl Christoph , Hoffmann-Sommergruber Karin
Published: August 2023

Allergic diseases represent a relevant global health problem, affecting adults and children and posing a significant burden for health care systems. In addition, the disease is still under-recognized and harmonized diagnostic tools and management plans for patients are still lacking. In this review the most important aspects of the diagnosis of allergic diseases are summarized and the contribution of Molecular allergology to this area is highlighted.
Cerebral autoregulation and cerebral blood flow response to mean arterial pressure challenge following induction of general anaesthesia for neuroradiology procedure
Authors: Manquat Elsa , Ravaux Hugues , Souilamas Jihane , Chamoux Thibaut , Joaquim Jona , Gayat Etienne , Vallée Fabrice , Cartailler Jérôme
Published: August 2023

Introduction

Intraoperative hypotension is common following general anaesthesia induction with propofol, but its impact on cerebral autoregulation (CA) remains unclear. We investigate the incidence and risk factors of impaired CApost-propofol induction and its recovery after a mean arterial pressure (mAP) challenge.

Methods

We included 40 non-emergency neuroradiology surgery patients [58 (47, 58)years old., 57% women]. We recorded mAP, mean blood flow velocity in the mean cerebral artery (MCAvmean), and regional cerebral oxygen saturation (rSO2). We computed the mean flow index (Mxa) pre and post mAP challenge. Mxa > 0.3 defined poor CA.

Results

After anaesthesia induction, 21 (53%) had impaired CBF autoregulation (CA−, Mxa > 0.3). The average mAP was 66 ± 9 mmHg, average MCAv was 39 ± 12 cm.s−1, and rSO2 was 63 ± 7%. We found no significant difference in age, norepinephrine infusion rate, and cardiovascular risks factors were similar between CA− and CA+ (Mxa ≤ 0.3) patients. Among the 22 patients (CA−: n = 14; CA+: n = 8) undergoing mAP challenge, there was a significant Mxa improvement and MCAv increase among CA− patients, (CA−: 0.63 ± 0.18 vs. 0.28 ± 0.20, p < 0.001), and [absolute variation: 1 (0.7–1.5) vs. 7 (3–9) cm.sec−1], respectively.

Conclusion

After induction of general anaesthesia for neuroradiology procedure, 53% of the patients had an impaired CA, regardless of age or medical history. Importantly, a mAP challenge effectively restored CA and improved CBF.

Clinical Trial Registration

identifier, NCT04288869
FungalBraid 2.0: expanding the synthetic biology toolbox for the biotechnological exploitation of filamentous fungi
Authors: Moreno-Giménez Elena , Gandía Mónica , Sáez Zara , Manzanares Paloma , Yenush Lynne , Orzáez Diego , Marcos Jose F. , Garrigues Sandra
Published: August 2023

Fungal synthetic biology is a rapidly expanding field that aims to optimize the biotechnological exploitation of fungi through the generation of standard, ready-to-use genetic elements, and universal syntax and rules for contributory use by the fungal research community. Recently, an increasing number of synthetic biology toolkits have been developed and applied to filamentous fungi, which highlights the relevance of these organisms in the biotechnology field. The FungalBraid (FB) modular cloning platform enables interchangeability of DNA parts with the GoldenBraid (GB) platform, which is designed for plants, and other systems that are compatible with the standard Golden Gate cloning and syntax, and uses binary pCAMBIA-derived vectors to allow Agrobacterium tumefaciens-mediated transformation of a wide range of fungal species. In this study, we have expanded the original FB catalog by adding 27 new DNA parts that were functionally validated in vivo. Among these are the resistance selection markers for the antibiotics phleomycin and terbinafine, as well as the uridine-auxotrophic marker pyr4. We also used a normalized luciferase reporter system to validate several promoters, such as PpkiA, P7760, Pef1α, and PafpB constitutive promoters, and PglaA, PamyB, and PxlnA inducible promoters. Additionally, the recently developed dCas9-regulated GB_SynP synthetic promoter collection for orthogonal CRISPR activation (CRISPRa) in plants has been adapted in fungi through the FB system. In general, the expansion of the FB catalog is of great interest to the scientific community since it increases the number of possible modular and interchangeable DNA assemblies, exponentially increasing the possibilities of studying, developing, and exploiting filamentous fungi.
Effects of citrate-stabilized gold and silver nanoparticles on some safety parameters of Porphyridium cruentum biomass
Authors: Rudi Ludmila , Cepoi Liliana , Chiriac Tatiana , Miscu Vera , Valuta Ana , Djur Svetlana
Published: August 2023

Introduction: Our research raises the question of how realistic and safe it is to use gold and silver nanoparticles in biotechnologies to grow microalgae, which will later be used to obtain valuable products. To this purpose, it was necessary to assess the influence of 10 and 20 nm Au and Ag nanoparticles stabilized in citrate on the growth of microalga Porphyridium cruentum in a closed cultivation system, as well as some safety parameters of biomass quality obtained under experimental conditions.

Methods: Two types of experiments were conducted with the addition of nanoparticles on the first day and the fifth day of the cultivation cycle. Changes in productivity, lipid content, malondialdehyde (MDA), as well as antioxidant activity of microalgae biomass have been monitored in dynamics during the life cycle in a closed culture system.

Results: The impact of nanoparticles on the growth curve of microalgae culture was marked by delaying the onset of the exponential growth phase. A significant increase in the content of lipids and MDA in biomass was noted. Excessive accumulation of lipid oxidation products within the first 24 h of cultivation resulted in altered antioxidant activity of red algae extracts.

Discussion: Citrate-stabilized gold and silver nanoparticles proved to be a stress factor for red microalga Porphyridium cruentum, causing significant changes in both biotechnological and biomass safety parameters. Addition of Au and Ag nanoparticles during the exponential growth phase of porphyridium culture led to an enhanced lipid accumulation and reduced MDA values in biomass.
Senescence during early differentiation reduced the chondrogenic differentiation capacity of mesenchymal progenitor cells
Authors: Voskamp Chantal , Koevoet Wendy J. L. M. , Van Osch Gerjo J. V. M. , Narcisi Roberto
Published: August 2023

Introduction: Mesenchymal stromal/progenitor cells (MSCs) are promising for cartilage cell-based therapies due to their chondrogenic differentiation capacity. However, MSCs can become senescent during in vitro expansion, a state characterized by stable cell cycle arrest, metabolic alterations, and substantial changes in the gene expression and secretory profile of the cell. In this study, we aimed to investigate how senescence and the senescence-associated secretory phenotype (SASP) affect chondrogenic differentiation of MSCs.

Methods: To study the effect of senescence, we exposed MSCs to gamma irradiation during expansion or during chondrogenic differentiation (the pellet culture). Western blot analysis was used to evaluate MSCs response to the chondrogenic inductor TGF-β.

Results: When senescence was induced during expansion or at day 7 of chondrogenic differentiation, we observed a significant reduction in the cartilage matrix. Interestingly, when senescence was induced at day 14 of differentiation, chondrogenesis was not significantly altered. Moreover, exposing chondrogenic pellets to the medium conditioned by senescent pellets had no significant effect on the expression of anabolic or catabolic cartilage markers, suggesting a neglectable paracrine effect of senescence on cartilage generation in our model. Finally, we show that senescent MSCs showed lower phosphorylated SMAD2 levels after TGFβ1 stimulation than control MSCs.

Conclusion: Overall, these results suggest that the occurrence of senescence in MSCs during expansion or early differentiation could be detrimental for cartilage tissue engineering.
CRISPR interference to evaluate modifiers of C9ORF72-mediated toxicity in FTD
Authors: Pickles Sarah , Zanetti Alepuz Desiree , Koike Yuka , Yue Mei , Tong Jimei , Liu Pinghu , Zhou Yugui , Jansen-West Karen , Daughrity Lillian M. , Song Yuping , DeTure Michael , Oskarsson Björn , Graff-Radford Neill R. , Boeve Bradley F. , Petersen Ronald C. , Josephs Keith A. , Dickson Dennis W. , Ward Michael E. , Dong Lijin , Prudencio Mercedes , Cook Casey N. , Petrucelli Leonard
Published: August 2023

Treatments for neurodegenerative disease, including Frontotemporal dementia (FTD) and Amyotrophic lateral sclerosis (ALS), remain rather limited, underscoring the need for greater mechanistic insight and disease-relevant models. Our ability to develop novel disease models of genetic risk factors, disease modifiers, and other FTD/ALS-relevant targets is impeded by the significant amount of time and capital required to develop conventional knockout and transgenic mice. To overcome these limitations, we have generated a novel CRISPRi interference (CRISPRi) knockin mouse. CRISPRi uses a catalytically dead form of Cas9, fused to a transcriptional repressor to knockdown protein expression, following the introduction of single guide RNA against the gene of interest. To validate the utility of this model we have selected the TAR DNA binding protein (TDP-43) splicing target, stathmin-2 (STMN2). STMN2 RNA is downregulated in FTD/ALS due to loss of TDP-43 activity and STMN2 loss is suggested to play a role in ALS pathogenesis. The involvement of STMN2 loss of function in FTD has yet to be determined. We find that STMN2 protein levels in familial FTD cases are significantly reduced compared to controls, supporting that STMN2 depletion may be involved in the pathogenesis of FTD. Here, we provide proof-of-concept that we can simultaneously knock down Stmn2 and express the expanded repeat in the Chromosome 9 open reading frame 72 (C9ORF72) gene, successfully replicating features of C9-associated pathology. Of interest, depletion of Stmn2 had no effect on expression or deposition of dipeptide repeat proteins (DPRs), but significantly decreased the number of phosphorylated Tdp-43 (pTdp-43) inclusions. We submit that our novel CRISPRi mouse provides a versatile and rapid method to silence gene expression in vivo and propose this model will be useful to understand gene function in isolation or in the context of other neurodegenerative disease models.
Solubilization of inclusion bodies: insights from explainable machine learning approaches
Authors: Walther Cornelia , Martinetz Michael C. , Friedrich Anja , Tscheließnig Anne-Luise , Voigtmann Martin , Jung Alexander , Brocard Cécile , Bluhmki Erich , Smiatek Jens
Published: August 2023

We present explainable machine learning approaches for gaining deeper insights into the solubilization processes of inclusion bodies. The machine learning model with the highest prediction accuracy for the protein yield is further evaluated with regard to Shapley additive explanation (SHAP) values in terms of feature importance studies. Our results highlight an inverse fractional relationship between the protein yield and total protein concentration. Further correlations can also be observed for the dominant influences of the urea concentration and the underlying pH values. All findings are used to develop an analytical expression that is in reasonable agreement with experimental data. The resulting master curve highlights the benefits of explainable machine learning approaches for the detailed understanding of certain biopharmaceutical manufacturing steps.
Observational study of endoluminal mural thrombotic apposition in popliteal artery aneurysm stenting and its relationship with stent-graft geometrical features
Authors: Spinella Giovanni , Conti Michele , Magliocco Marco , Pisa Fabio Riccardo , Finotello Alice , Pulze Martina , Pratesi Giovanni , Cittadini Giuseppe , Salsano Giancarlo , Pane Bianca
Published: August 2023

Introduction

The development of intrastent thrombosis is one of the mechanisms related to medium- to long-term failure of endovascular treatment of popliteal artery aneurysm. The present study aims to investigate possible links between the development of endoluminal mural thrombotic apposition in the stented zone (EMTS) with both geometrical features of stent-graft(s) and time of follow-up.

Methods

Patients with popliteal artery aneurysm who underwent endovascular treatment were recruited during the follow-up period. Segmentation of computed tomography angiography scan was performed to detect femoropopliteal artery lumen, leg bones, EMTS, and stent-graft(s). The following parameters were assessed: number, diameter, and length of stent-graft(s); and shape, volume, and length of thrombotic apposition within the stent(s). The spiral shape of the thrombotic apposition was evaluated as well.

Results

Eighteen male patients were recruited in the study. EMTS was observed in 13 of them (72%) during the follow-up analysis. An average of 1.8 ± 0.79 stents-grafts were implanted per patient with a median diameter and length of 6.2 (1.9) mm and 125 (50) mm, respectively. The percentage of the stent length where EMTS was present was 42.1 on average (interquartile range: 42.4%) with a mean volume of 206.8 mm3. A positive correlation was found between the length and volume of EMTS (R-squared = 0.71, p < 0.01). Moreover, EMTS had a helical shape in 8/13 patients, with 4/5 with counterclockwise rotation with stent-grafts in the left leg and 3/3 with clockwise direction treated in the right leg. A higher frequency of EMTS was observed in patients with longer follow-up and higher risk factors, as well.

Conclusions

EMTS is observed in most of the patients under analysis, especially in those with medium- to long-term follow-up. The pattern of such EMTS follows a helical shape having a direction that depends on which leg, right or left, is treated. Our results suggest a close surveillance of popliteal aneurysm stenting by follow-up examinations to control the onset and progression of EMTS.
Strategies and outcomes of different methods for treating abdominal aortic stent graft infection
Authors: Zhang Mengqiang , Chen Zhipeng , Tang Chen , Liu Cheng , Li Xiaoqiang , Liu Zhao , Qiao Tong
Published: August 2023

Objective

To report the strategies and short-term results of different treatment methods for abdominal aortic stent graft infection.

Methods

Six consecutive patients (5 males and 1 female; mean age: 64 years; age range: 49–79 years) received surgical treatment for stent graft infection from November 2021 to December 2022. All patients underwent endovascular aortic repair (EVAR) for abdominal aortic and iliac artery disease, subsequently developed graft infection and then received corresponding surgical treatment with different materials (artificial blood vessel, bovine pericardium, autologous great saphenous vein) in our department. The outcomes were analysed.

Results

Immediate technical success was achieved intraoperatively in all six patients. The 30-day mortality rate was 0%. During a mean follow-up of 4 months (range, 3–13 months), one patient underwent a second operation due to vascular anastomotic haemorrhage and underwent bilateral limb amputations due to ischaemia. All patients survived.

Conclusions

In the short term, the different materils and methods used to treat aortic stent graft infection achieved satisfactory results.
Procedural success of transcatheter annuloplasty in ventricular and atrial functional tricuspid regurgitation
Authors: Barbieri Fabian , Mattig Isabel , Beyhoff Niklas , Thevathasan Tharusan , Romero Dorta Elena , Skurk Carsten , Stangl Karl , Landmesser Ulf , Kasner Mario , Dreger Henryk , Reinthaler Markus
Published: August 2023

Background

Transcatheter annuloplasty is meant to target annular dilatation and is therefore mainly applied in functional tricuspid regurgitation (TR). Due to recent recognition of varying disease pathophysiology and differentiation of ventricular and atrial functional TR (VFTR and AFTR), comparative data regarding procedural success for both disease entities are required.

Methods

In this consecutively enrolled observational cohort study, 65 patients undergoing transcatheter annuloplasty with a Cardioband® device were divided into VFTR (n = 35, 53.8%) and AFTR (n = 30, 46.2%). Procedural success was assessed by comparing changes in annulus dilatation, vena contracta (VC) width, effective regurgitation orifice area (EROA), as well as reduction in TR severity.

Results

Overall, improvement of TR by at least two grades was achieved in 59 patients (90.8%), and improvement of TR by at least three grades was realised in 32 patients (49.2%). Residual TR of ≤2 was observed in 52 patients (80.0%). No significant differences in annulus diameter reduction [VFTR: 11 mm (9–13) vs. AFTR: 12 mm (9–16), p = 0.210], VC reduction [12 mm (8–14) vs. 12 mm (7–14), p = 0.868], and EROA reduction [0.62 cm2 (0.45–1.10) vs. 0.54 cm2 (0.40–0.70), p = 0.204] were reported. Improvement by at least two grades [27 (90.0%) vs. 32 (91.4%), p = 1.0] and three grades [14 (46.7%) vs. 18 (51.4%), p = 0.805] was similar in VFTR and AFTR, respectively. No significant difference in the accomplishment of TR grade of ≤2 [21 (70.0%) vs. 31 (88.6%), p = 0.118] was noted.

Conclusion

According to our results from a real-world scenario, transcatheter annuloplasty with the Cardioband® device may be applied in both VFTR and AFTR with evidence of significant procedural TR reduction.
The inter-chamber differences in the contractile function between left and right atrial cardiomyocytes in atrial fibrillation in rats
Authors: Butova Xenia , Myachina Tatiana , Simonova Raisa , Kochurova Anastasia , Mukhlynina Elena , Kopylova Galina , Shchepkin Daniil , Khokhlova Anastasia
Published: August 2023

Introduction

The left and right atria (LA, RA) work under different mechanical and metabolic environments that may cause an intrinsic inter-chamber diversity in structure and functional properties between atrial cardiomyocytes (CM) in norm and provoke their different responsiveness to pathological conditions. In this study, we assessed a LA vs. RA difference in CM contractility in paroxysmal atrial fibrillation (AF) and underlying mechanisms.

Methods

We investigated the contractile function of single isolated CM from LA and RA using a 7-day acetylcholine (ACh)-CaCl2 AF model in rats. We compared auxotonic force, sarcomere length dynamics, cytosolic calcium ([Ca2+]i) transients, intracellular ROS and NO production in LA and RA CM, and analyzed the phosphorylation levels of contractile proteins and actin-myosin interaction using an in vitro motility assay.

Results

AF resulted in more prominent structural and functional changes in LA myocardium, reducing sarcomere shortening amplitude, and velocity of sarcomere relengthening in mechanically non-loaded LA CM, which was associated with the increased ROS production, decreased NO production, reduced myofibrillar content, and decreased phosphorylation of cardiac myosin binding protein C and troponin I. However, in mechanically loaded CM, AF depressed the auxotonic force amplitude and kinetics in RA CM, while force characteristics were preserved in LA CM.

Discussion

Thus, inter-atrial differences are increased in paroxysmal AF and affected by the mechanical load that may contribute to the maintenance and progression of AF.
Managing arrhythmia in cardiac resynchronisation therapy
Authors: de Vere Felicity , Wijesuriya Nadeev , Elliott Mark K. , Mehta Vishal , Howell Sandra , Bishop Martin , Strocchi Marina , Niederer Steven A. , Rinaldi Christopher A.
Published: August 2023

Arrhythmia is an extremely common finding in patients receiving cardiac resynchronisation therapy (CRT). Despite this, in the majority of randomised trials testing CRT efficacy, patients with a recent history of arrhythmia were excluded. Most of our knowledge into the management of arrhythmia in CRT is therefore based on arrhythmia trials in the heart failure (HF) population, rather than from trials dedicated to the CRT population. However, unique to CRT patients is the aim to reach as close to 100% biventricular pacing (BVP) as possible, with HF outcomes greatly influenced by relatively small changes in pacing percentage. Thus, in comparison to the average HF patient, there is an even greater incentive for controlling arrhythmia, to achieve minimal interference with the effective delivery of BVP. In this review, we examine both atrial and ventricular arrhythmias, addressing their impact on CRT, and discuss the available evidence regarding optimal arrhythmia management in this patient group. We review pharmacological and procedural-based approaches, and lastly explore novel ways of harnessing device data to guide treatment of arrhythmia in CRT.
The therapeutic potential of sphingolipids for cardiovascular diseases
Authors: Ya'ar Bar Sapir , Pintel Noam , Abd Alghne Hesen , Khattib Hamdan , Avni Dorit
Published: August 2023

Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide and Inflammation plays a critical role in the development of CVD. Despite considerable progress in understanding the underlying mechanisms and various treatment options available, significant gaps in therapy necessitate the identification of novel therapeutic targets. Sphingolipids are a family of lipids that have gained attention in recent years as important players in CVDs and the inflammatory processes that underlie their development. As preclinical studies have shown that targeting sphingolipids can modulate inflammation and ameliorate CVDs, targeting sphingolipids has emerged as a promising therapeutic strategy. This review discusses the current understanding of sphingolipids’ involvement in inflammation and cardiovascular diseases, the existing therapeutic approaches and gaps in therapy, and explores the potential of sphingolipids-based drugs as a future avenue for CVD treatment.
In-situ testing for characterizing the landslide deposit in Jiuzhaigou cultural heritage site after the 2017 earthquake
Authors: Pei Xiangjun , Jiang Tao , Cui Shenghua , Guo Bin , Liang Jing
Published: August 2023

The 2017 Jiuzhaigou earthquake caused numerous landslide masses in the Jiuzhaigou cultural heritage site, leading to frequent surface mass movements and affecting the hydrological landscape. This was the first time a strong earthquake hit the heritage site in China, making it an important area for ecological geological environment protection and restoration research. To understand the influence of slope runoff erosion on the activation of landslide accumulations, this study examined remote sensing images from 2017 to 2020 to investigate the geological disaster, while field scour tests were conducted to study the rainfall seepage, mass erosion, and migration.The results indicated that the steep-sloped landslide deposits in the heritage site contain a high content of fine grains and good permeability.
Mentoring as prevention of early school leaving: a qualitative systematic literature review
Authors: Fehérvári Anikó , Varga Aranka
Published: August 2023

One of the biggest challenges facing education systems is preventing early school leaving. Not completing secondary education has serious long-term negative consequences for both individuals and society. There is currently a wide body of empirical literature that reviews the causes of and risk factors for school dropout and the prevention of student attrition. With new reviews emerging over time, our analysis updates previous systematic analyses, and we therefore review empirical studies from seven databases between 2013 and 2021 that use mentoring to prevent early school leaving. We focus on mentoring because personal support is a crucial type of prevention program. We identified 25 studies from this period through a systematic search. The aim of our research was to identify the target groups, the mentoring roles, and the goals and outcomes of the mentoring programs in the interventions undertaken in the studies we identified. The studies present both school-based and community-based mentoring practices primarily in North American and European countries. The results show that the focus of the studies was mainly on secondary school target groups as there were few studies addressing younger age groups. Most of the studies focused on a 1-year period or shorter durations, and several studies found that mentoring had positive effects on students. However, not all the factors identified as development objectives have changed. It should also be stressed that the success of mentoring depends on the quality of the mentors and the quality of their relationship with the mentees, as well as on the implementation of the mentoring programs and the school contexts in which they operate. The importance of the latter has perhaps received less attention in previous reviews and analyses.
Health risk assessment following exposure of operators to backpack-sprayed prothioconazole and its major metabolite in wheat fields in China
Authors: Li Shuang , Mei Chenghan , Wu Xuemin , Li Xuefeng , Pang Sen
Published: August 2023

Introduction: Prothioconazole is a triazolinthione fungicide widely used to control diseases on various crops caused by Ascomycetes, Basidiomycetes, and Imperfecti fungi. However, in view of the rapid transformation of parent prothioconazole to its major metabolite prothioconazole-desthio during application and the fact that the latter is of higher toxicity, prothioconazole poses a potential threat to the health of operators in direct contact with it. Currently, very few studies have been carried out regarding prothioconazole and prothioconazole-desthio exposure.

Methods: Therefore, a typical exposure scenario from wheat-planting provinces in China was chosen, and a motorized backpack-type sprayer was used as the application equipment. The actual exposure doses of prothioconazole and prothioconazole-desthio for mixers/loaders and applicators under different exposure routes were determined, and a tiered risk assessment was conducted considering different conditions.

Results: The results of this study indicated that the exposure risk to operators after spraying with 30% prothioconazole oil dispersion was unacceptable in the primary risk assessment, while the risk was acceptable with integrated risk quotients less than 1 at a better level of protection. Moreover, the upper legs and hands were regarded as the most contaminated sections during the mixing/loading process, and legs were the most contaminated sections during spraying. Good protection equipment, such as hats, long-sleeve shirts, long pants, socks, shoes, and rubber or nitrile gloves, was effective at alleviating prothioconazole and prothioconazole-desthio exposure. This study aims to provide important references for the safe use and risk management of prothioconazole.
Immune cell type signature discovery and random forest classification for analysis of single cell gene expression datasets
Authors: Aybey Bogac , Zhao Sheng , Brors Benedikt , Staub Eike
Published: August 2023

Background

Robust immune cell gene expression signatures are central to the analysis of single cell studies. Nearly all known sets of immune cell signatures have been derived by making use of only single gene expression datasets. Utilizing the power of multiple integrated datasets could lead to high-quality immune cell signatures which could be used as superior inputs to machine learning-based cell type classification approaches.

Results

We established a novel workflow for the discovery of immune cell type signatures based primarily on gene-versus-gene expression similarity. It leverages multiple datasets, here seven single cell expression datasets from six different cancer types and resulted in eleven immune cell type-specific gene expression signatures. We used these to train random forest classifiers for immune cell type assignment for single-cell RNA-seq datasets. We obtained similar or better prediction results compared to commonly used methods for cell type assignment in independent benchmarking datasets. Our gene signature set yields higher prediction scores than other published immune cell type gene sets in random forest-based cell type classification. We further demonstrate how our approach helps to avoid bias in downstream statistical analyses by re-analysis of a published IFN stimulation experiment.

Discussion and conclusion

We demonstrated the quality of our immune cell signatures and their strong performance in a random forest-based cell typing approach. We argue that classifying cells based on our comparably slim sets of genes accompanied by a random forest-based approach not only matches or outperforms widely used published approaches. It also facilitates unbiased downstream statistical analyses of differential gene expression between cell types for significantly more genes compared to previous cell classification algorithms.